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Sample records for gentamicins

  1. A prospective study of gentamicin ototoxicity

    DEFF Research Database (Denmark)

    Winkel, O; Hansen, M M; Kaaber-Bühler, Søren;

    1978-01-01

    Twenty patients were included in a prospective otoneurological study performed to assess the ototoxicity in gentamicin therapy. Gentamicin was administered intravenously, and the serum level was currently determined. Audiographic and electronystagmographic studies were carried out at the institut...

  2. Clinical Pharmacokinetics of Gentamicin in Neonates

    Directory of Open Access Journals (Sweden)

    Gian Maria Pacifici

    2017-03-01

    Full Text Available Gentamicin is a bactericidal aminoglycoside antibiotic, it inhibits the protein synthesis. Gentamicin is active against the majority of aerobic gram-negative bacilli such as Pseudomonas, Klebsiella and Escherichia coli. The gentamicin doses are 3 mg/kg once-daily for preterm newborns 35 weeks of gestation. The monitoring of gentamicin serum concentration is recommended when infants are treated for 48 hours or more. The gentamicin peak concentration must be at least 8 times the minimum inhibitory concentration (MIC to be bactericidal and the gentamicin trough concentration must be < 2 µg/ml to avoid ototoxicity and nephrotoxicity.Once-daily dosing of gentamicin (4 mg/kg, is preferred than twice-daily dose of 2.5 mg/kg gentamicin. A gentamicin loading dose (4 mg/kg, followed by once-daily dosing of 2.5 mg/kg yields safe and target range in neonates. An extended dosing interval of 48-hour (5 mg/kg gentamicin, was compared with twice-daily dose of 2.5 mg/kg gentamicin. Infants in the 48-hour interval and in the twice-daily achieved peak gentamicin concentrations of 9.43 µg/ml and 6.0 µg/ml, respectively, (p

  3. Compound list: gentamicin [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available gentamicin GMC 00147 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/gentamic...in.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/gentamic...at/in_vivo/Liver/Repeat/gentamicin.Rat.in_vivo.Liver.Repeat.zip ftp://ftp.bioscie...ncedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/gentamicin.Rat.in_vivo.Kidney.Single.zip ftp...://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Repeat/gentamicin.Rat.in_vivo.Kidney.Repeat.zip ...

  4. Gentamicin concentrations in human subcutaneous tissue

    DEFF Research Database (Denmark)

    Lorentzen, Hanne; Kallehave, Finn Lasse; Kolmos, Hans Jørn Jepsen

    1996-01-01

    in human subcutaneous adipose tissue by a microdialysis technique. Seven healthy young volunteers each had four microdialysis probes placed in the fat (subcutaneous) layer of the abdominal skin. After the administration of a 240-mg gentamicin intravenous bolus, consecutive measurements of the drug...... of the gentamicin concentration in human subcutaneous tissue. In this adipose tissue, the peak concentrations of gentamicin were approximately seven times the MIC for Pseudomonas aeruginosa and 33 times the MIC for Staphylococcus aureus after the administration of an intravenous bolus of 240 mg, indicating......Wound infections frequently originate from the subcutaneous tissue. The effect of gentamicin in subcutaneous tissue has, however, normally been evaluated from concentrations in blood or wound fluid. The aim of the present study was to investigate the pharmacokinetic properties of gentamicin...

  5. A prospective study of gentamicin ototoxicity

    DEFF Research Database (Denmark)

    Winkel, O; Hansen, M M; Kaaber-Bühler, Søren

    2010-01-01

    Twenty patients were included in a prospective otoneurological study performed to assess the ototoxicity in gentamicin therapy. Gentamicin was administered intravenously, and the serum level was currently determined. Audiographic and electronystagmographic studies were carried out at the institut......Twenty patients were included in a prospective otoneurological study performed to assess the ototoxicity in gentamicin therapy. Gentamicin was administered intravenously, and the serum level was currently determined. Audiographic and electronystagmographic studies were carried out...... at the institution and discontinuation of the treatment and again a few weeks later. Ten patients exhibited ototoxic actions, predominantly cochlear, 4 of the cases being fully reversible. Two patients developed severe hearing loss, associated in one with bilateral extinction of vestibular function. Low serum levels...... of gentamicin did not rule out the possiblity of ototoxicity. These results urge the continuing of prospective studies and indicate that gentamicin should be used only as a link in the primary treatment of severe infection or in cases in which other, less toxic agents have failed....

  6. Depression of vitamin B6 levels due to gentamicin.

    Science.gov (United States)

    Weir, M R; Keniston, R C; Enriquez, J I; McNamee, G A

    1990-06-01

    The renal toxicity of gentamicin is altered by dietary protein modifications, bicarbonate and acetazolamide administration, magnesium supplementation, polyaspartic acid, piperacillin, hypercalcemia and calcium channel blockers. Renal tissue gentamicin levels have an undetermined role. Reduction of renal pyridoxal 5'-phosphate (PLP- by gentamicin has been shown, as has protection from nephrotoxicity by administration of vitamin B6. To explore an interaction between gentamicin and vitamin B6, gentamicin (5 mg/kg) was given to rabbits by ip injection, with either pyridoxine (10 mg) or isovolemic saline for 3 weeks. There was not a difference between gentamicin levels for animals given gentamicin and pyridoxine versus those given gentamicin and saline. Gentamicin administration led to a 47% fall (p = .0001) in plasma PLP levels. Three days after the last gentamicin administration, the animals maintained a 32% decrease from the pre-gentamicin baseline values (p = 0.02). When pyridoxine was administered concurrently with gentamicin, the PLP rise of 49% was significant (p = 0.001). The mean level after the study (6%) was not significantly lower than baseline (p = .6). We believe that gentamicin interfers with vitamin B6 metabolism, but that vitamin B6 status does not affect levels of gentamicin. A number of drugs affect B6 levels, creating the potential for hypovitaminosis B6 to be an important mechanism of drug-drug interaction in seriously ill patients, particularly in sick newborns or the elderly with lower average PLP levels.

  7. 21 CFR 522.1044 - Gentamicin.

    Science.gov (United States)

    2010-04-01

    ... treatment of infections of urinary tract (cystitis, nephritis), respiratory tract (tonsillitis, pneumonia... treatment of infections of urinary tract (cystitis, nephritis), respiratory tract (pneumonitis, pneumonia... food for at least 9 weeks after treatment. (3) Chickens—(i) Amount. 0.2 milligram of gentamicin per 0.2...

  8. Silica-Gentamicin Nanohybrids: Synthesis and Antimicrobial Action

    Directory of Open Access Journals (Sweden)

    Dina Ahmed Mosselhy

    2016-03-01

    Full Text Available Orthopedic applications commonly require the administration of systemic antibiotics. Gentamicin is one of the most commonly used aminoglycosides in the treatment and prophylaxis of infections associated with orthopedic applications, but gentamicin has a short half-life. However, silica nanoparticles (SiO2 NPs can be used as elegant carriers for antibiotics to prolong their release. Our goal is the preparation and characterization of SiO2-gentamicin nanohybrids for their potential antimicrobial administration in orthopedic applications. In vitro gentamicin release profile from the nanohybrids (gentamicin-conjugated SiO2 NPs prepared by the base-catalyzed precipitation exhibited fast release (21.4% during the first 24 h and further extension with 43.9% release during the five-day experiment. Antimicrobial studies of the SiO2-gentamicin nanohybrids versus native SiO2 NPs and free gentamicin were performed against Bacillus subtilis (B. subtilis, Pseudomonas fluorescens (P. fluorescens and Escherichia coli (E. coli. SiO2-gentamicin nanohybrids were most effective against B. subtilis. SiO2 NPs play no antimicrobial role. Parallel antimicrobial studies for the filter-sterilized gentamicin were performed to assess the effect of ultraviolet (UV-irradiation on gentamicin. In summary, the initial fast gentamicin release fits the need for high concentration of antibiotics after orthopedic surgical interventions. Moreover, the extended release justifies the promising antimicrobial administration of the nanohybrids in bone applications.

  9. Gentamicin Nephrotoxicity in Subclinical Renal Disease.

    Science.gov (United States)

    Frazier, Donita L.

    The purpose of the present study was to examine the pharmacokinetic disposition of gentamicin and to define the mechanisms which predispose to nephrotoxicity in subclinical renal disease. Subtotally nephrectomized beagle dogs were used as a model for human beings with compromised renal function secondary to a reduced number of functional nephrons. Using ultrastructural morphometry, light microscopy and clinical chemistry data, the model was defined and the nephrotoxic responses of intact dogs administered recommended doses of drug were compared to the response of subtotally nephrectomized dogs administered reduced doses based on each animal's clearance of drug. Lysosomal and mitochondrial morphometric changes suggested mechanisms for increased sensitivity. To determine if increased sensitivity in this model was dependent on altered serum concentrations, variable rate infusions based on individual pharmacokinetic disposition of drug were administered using computer-driven infusion pumps. Identical serum concentration-time profiles were achieved in normal dogs and subtotally nephrectomized dogs, however, toxicity was significantly greater in nephrectomized dogs. The difference in the nephrotoxic response was characterized by administering supratherapeutic doses of drug to dogs. Nephrectomized dogs given a recommended dose of gentamicin became oliguric during the second week of treatment and increasingly uremic after withdrawal of drug. In contrast, intact dogs administered 2 times the recommended dose of gentamicin become only slightly polyuric during week 4 of treatment. The need to individualize dosage regimens based on drug clearance and not serum creatinine nor creatinine clearance alone was substantiated by describing the pharmacokinetic disposition of gentamicin in spontaneously occurring disease states. Four individualized dosage regimens with differing predicted efficacy were then administered to nephrectomized dogs to determine their relative nephrotoxic

  10. The Rapid Emergence of High Level Gentamicin Resistance in Enterococci

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    Kevin R Forward

    1990-01-01

    Full Text Available The proportion of enterococci isolated from blood and urine cultures that were highly resistant to gentamicin and streptomycin were determined. No blood or urine isolates highly resistant to gentamicin were seen in 1983, whereas by 1986–87 25% of blood and 17% of urine isolates were highly resistant. The rapid emergence of gentamicin resistance has serious implications for patients with life threatening enterococcal disease.

  11. Teratogenic effects of Gentamicin on skeletal system of rat fetuses

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    Marzban H

    1999-09-01

    Full Text Available Gentamicin was evaluated for developmental toxicity in pregnant Sprague-Dawley rat. Gentamicin was administered subcutaneously on days 6-15 gestation at dose of 100 mg/kg. On gestation day 21, all live fetuses were examined for external and skeletal malformations and variations. Increased resorptions and dead fetuses, and reduced fetal body weight were observed at dose of 100 mg/kg. Gentamicin caused severe skeletal anomalies, such as: wavy ribs, incomplete ossification of sternebrae, tail vertebra, metacarpus, metatarsus and calvaria. These results indicate the nature and extent of embryotoxicity and teratogenicity of gentamicin in Sprague-Dawley rats.

  12. Flavocoxid attenuates gentamicin-induced nephrotoxicity in rats.

    Science.gov (United States)

    El-Kashef, Dalia H; El-Kenawi, Asmaa E; Suddek, Ghada M; Salem, Hatem A

    2015-12-01

    Gentamicin is a widely used antibiotic against serious and life-threatening infections; however, its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine whether flavocoxid has a protective effect against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of flavocoxid on gentamicin induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was determined. Twenty-four male Wistar albino rats were randomly divided into three groups, namely control, gentamicin (100 mg/kg, i.p.) and gentamicin plus flavocoxid (20 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood, urine samples and kidneys were collected for further analysis. Gentamicin administration caused a severe nephrotoxicity which was evidenced by an elevated renal somatic index (RSI), serum creatinine, blood urea nitrogen, serum lactate dehydrogenase, and protein in urine with a concomitant reduction in serum albumin and normalized creatinine clearance value as compared with the controls. Moreover, a significant increase in renal contents of malondialdehyde, myeloperoxidase, and tumor necrosis factor-alpha with a significant decrease in renal reduced glutathione and superoxide dismutase activities was detected upon gentamicin administration together with increasing the sensitivity of isolated urinary bladder rings to ACh. Exposure to gentamicin induced necrosis of renal tubular epithelial cells. Flavocoxid protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by gentamicin treatment. In addition, flavocoxid significantly reduced the responses of isolated bladder rings to ACh. The results from our study indicate that flavocoxid supplement attenuates gentamicin-induced renal injury via the amelioration of

  13. Pressure treatment versus gentamicin for Meniere's disease.

    Science.gov (United States)

    Odkvist, L

    2001-01-01

    Ménière's disease may be treated in different ways. After obtaining a case history and performing auditory and vestibular tests the diagnosis should be obvious. In terms of treatment, the first steps are to provide the patient with information, institute a low-salt diet and regulate internal medical disorders. The next step is pharmacological treatment using diuretics, betahistine and other drugs. Local pulsated pressure treatment in the ear canal has been used in a placebo-controlled study and showed significant improvement, primarily of vertigo, but also in terms of tinnitus and hearing. Hence, this form of treatment can be used in some phases of the disease. In more severe cases gentamicin treatment has proved successful; in the present study, vertigo was cured in all but 3 of 35 patients. On average, no extra hearing loss was caused: however, one ear became deaf, some ears showed improvement and some ears showed a certain degree of hearing loss. In cases of escalation of Ménière's disease, pressure treatment should be used initially, followed by gentamicin. These two methods of treatment are not in competition as they are used to treat different stages of the disease.

  14. Patients’ safety: is there a systemic release of gentamicin by gentamicin-coated tibia nails in clinical use?

    Science.gov (United States)

    Moghaddam, Arash; Graeser, Viola; Westhauser, Fabian; Dapunt, Ulrike; Kamradt, Till; Woerner, Stefan M; Schmidmaier, Gerhard

    2016-01-01

    Introduction Osteitis is one of the most serious complications in orthopedic surgery. Expert Tibia Nail (ETN) PROtect™ coated with a biodegradable layer of gentamicin-laden polymer was developed for prophylaxis of osteomyelitis. In systemic administration, gentamicin has only a small therapeutic index and serious side effects; it is potentially nephrotoxic as well as ototoxic. It is not yet known if relevant gentamicin concentrations are released into the systemic circulation after implantation of gentamicin-coated nails. In order to evaluate the patients’ risks profiles and increase patient safety, we measured gentamicin levels in pre- and postoperative serum samples of patients undergoing implantation of ETN PROtect. Methods Twenty-five patients who received ETN PROtect between March 2012 and August 2014 were included in this study. Collection of blood samples occurred before the operation, at weeks 1–4, 3 and 6 months, and up to 1 year after the implantation. Measurement of gentamicin levels in serum samples was performed at the central laboratory of Heidelberg University Hospital. Additionally, laboratory parameters, C-reactive protein, leukocyte number, urea and creatinine concentrations were analyzed in routine controls before and after operating and assessed for systemic side effects. Results Over the course of this prospective observational study, we were able to determine that gentamicin-coated nails do not release gentamicin into the systemic circulation above the lowest detectable level of 0.2 mg/dL. There were slight increases in the mean inflammation and renal retention markers, but no gentamicin-associated side effects could be linked to implantation. Furthermore, no allergic reactions could be detected during our study. Conclusion Our findings suggest that there is no relevant release of gentamicin into the systemic circulation causing a systemic effect, and serious side effects due to gentamicin-coated tibia nails should not be feared

  15. Enzymuria in neonates receiving continuous intravenous infusion of gentamicin

    DEFF Research Database (Denmark)

    Colding, H; Brygge, K; Brendstrup, L;

    1992-01-01

    with non-treatment periods in the same newborn infant (33 infants). The same tendency applied to AAP. Newborn infants receiving continuous intravenous infusion of gentamicin were not found to be at greater risk of nephrotoxicity than those receiving intermittent gentamicin treatment, using NAG and AAP...

  16. Gentamicin Exposure and Sensorineural Hearing Loss in Preterm Infants.

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    Aline Fuchs

    Full Text Available To evaluate the impact of gentamicin exposure on sensorineural hearing loss (SNHL in very low birth weight (VLBW infants.Exposure to gentamicin was determined in infants born between 1993 and 2010 at a gestational age < 32 weeks and/or with a birthweight < 1500 g, who presented with SNHL during the first 5 years of life. For each case, we selected two controls matched for gender, gestational age, birthweight, and year of birth.We identified 25 infants affected by SNHL, leading to an incidence of SNHL of 1.58% in our population of VLBW infants. The proportion of infants treated with gentamicin was 76% in the study group and 70% in controls (p = 0.78. The total cumulated dose of gentamicin administered did not differ between the study group (median 10.2 mg/kg, Q1-Q3 1.6-13.2 and the control group (median 7.9 mg/kg, Q1-Q3 0-12.8, p = 0.47. The median duration of gentamicin treatment was 3 days both in the study group and the control group (p = 0.58. Maximum predicted trough serum levels of gentamicin, cumulative area under the curve and gentamicin clearance were not different between cases and controls.The impact of gentamicin on SNHL can be minimized with treatments of short duration, monitoring of blood levels and dose adjustment.

  17. Hydrogel iontophoresis for gentamicin administration to the rabbit eye

    Science.gov (United States)

    Eljarrat-Binstock, Esther; Raiskup, Frederik; Frucht-Pery, Joseph; Domb, Abraham J.

    2005-04-01

    Iontophoresis (IONT) is a non-invasive technique in which a low electric current is used to enhance the penetration of charged molecules into tissue. This technique has been used in various fields of medicine, mostly in transdermal drug delivery. This study was aimed to evaluate the efficacy and the distribution profile of gentamicin using corneal IONT on infected and healthy rabbit eyes. Corneal iontophoresis of gentamicin sulfate was studied using drug-loaded disposable hydrogel probes mounted on a portable iontophoretic device, applying a low current for 60 seconds. This study confirmed that a triple iontophoretic treatment of gentamicin for only 60 seconds (0.5mA) significantly reduces the count of pseudomonas in the infected cornea to a non-infectious level. Peak gentamicin concentrations at the healthy corneas (363.1 +/- 127.3 μg/g) and at the aqueous humor (29.4 +/- 17.4 μg/ml) were reached immediately and two hours after a single iontophoretic treatment, respectively. The concentration versus time profile of gentamicin following iontophoresis revealed a gentamicin half life of 2.07 h in the anterior chamber, and a clearance of 1.73 μl/min from the anterior chamber to the posterior segments of the eye. This study indicates that a short iontophoretic treatment using gentamicin-loaded hydrogels has a potential clinical value in treating corneal infections, by increasing drug penetration to the eye and maintaining therapeutic levels for more than eight hours.

  18. Effect of Taurine on the antimicrobial efficiency of Gentamicin

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    Islambulchilar Mina

    2011-12-01

    Full Text Available Context: Gentamicin is mainly used in severe infections caused by gram-negatives. However toxicity including nephrotoxicity and ototoxicity is one of the most important complications of its treatment. The production of free radicals seems to be involved in gentamicin toxicity mechanism. Taurine, a major intracellular free β-amino acid, is known to be an endogenous antioxidant. So potentially the co-therapy of taurine and gentamicin would reduce the adverse effects of the antibiotic. Objectives: In this study, we wished to know the effect of taurine on the antibiotic capacity of gentamicin. methods: strains of P. aeruginosa, E. coli, S. aureus and S. epidermidis were used as test organisms. Minimum inhibitory concentrations of gentamicin in the presence and absence of taurine at quantities from 40 to 2 mg/L were determined using macro-dilution method. Results: MICs were determined in the various concentrations of taurine for bacterial indicators. The MIC values of gentamicin for P. aeruginosa, S. aureus and E. coli remained unchanged in the values of 2.5, 5 and 20 μg/ml respectively in the absence and presences of different concentrations of taurine. The bactericidal activity of gentamicin against S. epidermidis was increased by addition of taurine in the concentrations higher than 6 mg/L. Conclusion: According to our study the antibacterial activity of gentamicin against the indicator microorganisms were not interfere with taurine at selected concentrations. Further in vivo studies are needed to establish if a combination of gentamicin and taurine would have the same effect.

  19. Effects of Kangshen Oral Liquid on Gentamicin-induced Acute ...

    African Journals Online (AJOL)

    Purpose: To investigate the effects of Kangshen oral liquid (KSOL) on gentamicin sulfate (GS)-induced acute kidney injury ..... Upon GS administration, several physiological markers are .... Kara A, Bozkurt A. The protective effect of taurine.

  20. Instrumental characterization of the smectite clay–gentamicin hybrids

    Indian Academy of Sciences (India)

    Alicja Rapacz-Kmita; Ewa Stodolak-Zych; Magdalena Ziabka; Agnieszka Rozycka; Magdalena Dudek

    2015-08-01

    This paper focusses on the intercalation of clay mineral with gentamicin (an aminoglycoside antibiotic). The smectite clay–gentamicin hybrids were prepared by a solution intercalation at 60°C and the process was carried out on unmodified smectite clay and on smectite after Na+ ionic activation. The resulting structural/microstructural properties and the potential for introducing gentamicin between smectite clay layers were investigated by means of X-ray diffraction, Fourier transform infrared spectroscopic techniques and transmission electron microscopy and scanning electron microscopy with energy-dispersive spectroscopy X-ray analysis. The results confirm the successful intercalation of gentamicin into the interlayer space of smectite clay, demonstrating that the material thus obtained could potentially be used as a drug carrier.

  1. Once versus twice daily gentamicin dosing for infective endocarditis

    DEFF Research Database (Denmark)

    Buchholtz, Kristine; Larsen, Carsten Toftager; Schaadt, Bente

    2011-01-01

    to half-life, mean CRP and leukocytes. Results: Baseline GFR was similar in the two groups. Both groups displayed a significant fall in GFR from admission to discharge. The mean decrease in GFR was as follows: with once daily gentamicin, 17.0% (95% confidence interval 7.5– 26.5), and with twice daily......Objectives: The aim of this randomized study was to investigate the effects of once versus twice daily gentamicin dosing on renal function and measures of infectious disease in a population with infective endocarditis (IE). Methods: Seventy-one IE patients needing gentamicin treatment according...... to guidelines were randomized to either once (n = 37) or twice daily (n = 34) doses of gentamicin. Kidney function (glomerular filtration rate, GFR) was measured with an isotope method ( 51 Cr-EDTA) at the beginning of treatment and at discharge. Treatment efficacy was assessed by C-reactive protein (CRP) time...

  2. Gentamicin nephrotoxicity: Animal experimental correlate with human pharmacovigilance outcome

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    Olufunsho Awodele

    2015-04-01

    Full Text Available Background: National Agency for Food and Drugs Administration and Control (NAFDAC, which is responsible for pharmacovigilance activity in Nigeria, recently withdrew injection gentamicin 280 mg, used in the management of life-threatening and multidrug-resistant infections from circulation, due to reported toxicity. Thus, this study aimed to investigate the toxicity profile of the commonly used strengths (80 mg and 280 mg of gentamicin on kidney using animal models. Methods: Animals were divided into five groups of 16 rats each. For rats of groups 1 and 2, gentamicin (1.14 mg/kg each group was administered intramuscularly twice daily for 7 and 14 days, respectively, after which eight of them were sacrificed by cervical dislocation. Blood was collected via cardiac puncture and the kidneys were carefully removed and weighed immediately. The remaining eight animals were kept for reversibility study for another 7 and 14 days, respectively. For groups 3 and 4, gentamicin (4 mg/kg each group was administered as a single daily dose for 7 and 14 days, respectively, and eight animals from the groups were subjected to reversibility study for 7 and 14 days, respectively. Group 5, the control group animals, were given 10 ml/kg distilled water for 14 days. Histopathology of the kidneys, serum creatinine levels, and antioxidant enzyme activities were investigated. Results: Significant increase (p ≤ 0.001 in the level of creatinine of rats administered 4.0 mg/kg for 14 days was observed compared with all other groups. Significant (p ≤ 0.001 elevations in the lipid peroxidation in all gentamicin-administered animals and acute tubular necrosis in most of the gentamicin-administered animals were observed. Conclusion: Toxicity profile of gentamicin on the kidneys is dependent on both dose and duration of administration. The findings justify the decision made by NAFDAC to ban the use of high-dose inj. gentamicin 280 mg in Nigeria.

  3. Acoustic trauma increases cochlear and hair cell uptake of gentamicin.

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    Hongzhe Li

    Full Text Available BACKGROUND: Exposure to intense sound or high doses of aminoglycoside antibiotics can increase hearing thresholds, induce cochlear dysfunction, disrupt hair cell morphology and promote hair cell death, leading to permanent hearing loss. When the two insults are combined, synergistic ototoxicity occurs, exacerbating cochlear vulnerability to sound exposure. The underlying mechanism of this synergism remains unknown. In this study, we tested the hypothesis that sound exposure enhances the intra-cochlear trafficking of aminoglycosides, such as gentamicin, leading to increased hair cell uptake of aminoglycosides and subsequent ototoxicity. METHODS: Juvenile C57Bl/6 mice were exposed to moderate or intense sound levels, while fluorescently-conjugated or native gentamicin was administered concurrently or following sound exposure. Drug uptake was then examined in cochlear tissues by confocal microscopy. RESULTS: Prolonged sound exposure that induced temporary threshold shifts increased gentamicin uptake by cochlear hair cells, and increased gentamicin permeation across the strial blood-labyrinth barrier. Enhanced intra-cochlear trafficking and hair cell uptake of gentamicin also occurred when prolonged sound, and subsequent aminoglycoside exposure were temporally separated, confirming previous observations. Acute, concurrent sound exposure did not increase cochlear uptake of aminoglycosides. CONCLUSIONS: Prolonged, moderate sound exposures enhanced intra-cochlear aminoglycoside trafficking into the stria vascularis and hair cells. Changes in strial and/or hair cell physiology and integrity due to acoustic overstimulation could increase hair cell uptake of gentamicin, and may represent one mechanism of synergistic ototoxicity.

  4. Could edaravone prevent gentamicin ototoxicity? An experimental study.

    Science.gov (United States)

    Turan, M; Ciğer, E; Arslanoğlu, S; Börekci, H; Önal, K

    2017-02-01

    Clinical application of gentamicin may cause nephrotoxicity and ototoxicity. Our study is the first study to investigate the protective effects of edaravone against the gentamicin-induced ototoxicity. We investigated the protective effect of intraperitoneal (i.p.) edaravone application against gentamicin-induced ototoxicity in guinea pigs. Fourteen guinea pigs were divided into two equal groups consisting of a control group and a study group. One-hundred sixty milligrams per kilogram subcutaneous gentamicin and 0.3 mL i.p. saline were applied simultaneously once daily to seven guinea pigs in the control group (group 1). One-hundred sixty milligrams per kilogram gentamicin was applied subcutaneously and 3 mg/kg edaravone was applied intraperitoneally once daily for 7 days simultaneously to seven guinea pigs in the study group (group 2). Following the drug application, auditory brainstem response measurements were performed for the left ear on the 3rd and 7th days. Hearing threshold values of the group 1 and group 2 measured in the 3rd day of the study were detected as 57.14 ± 4.88 and 82.86 ± 7.56, respectively. This difference was statistically significant ( p ototoxic effects of gentamicin and the severity of the hearing loss.

  5. Salicylic Acid Attenuates Gentamicin-Induced Nephrotoxicity in Rats

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    Pavle Randjelovic

    2012-01-01

    Full Text Available Gentamicin (GM is a widely used antibiotic against serious and life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine the protective effect of salicylic acid (SA in gentamicin-induced nephrotoxicity in rats. Quantitative evaluation of gentamicin-induced structural alterations and degree of functional alterations in the kidneys were performed by histopathological and biochemical analyses in order to determine potential beneficial effects of SA coadministration with gentamicin. Gentamicin was observed to cause a severe nephrotoxicity which was evidenced by an elevation of serum urea and creatinine levels. The significant increases in malondialdehyde (MDA levels and protein carbonyl groups indicated that GM-induced tissue injury was mediated through oxidative reactions. On the other hand, simultaneous SA administration protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by GM treatment. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules was found to be prevented by SA pretreatment. The results from our study indicate that SA supplement attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation in gentamicin-treated rats.

  6. Salicylic acid attenuates gentamicin-induced nephrotoxicity in rats.

    Science.gov (United States)

    Randjelovic, Pavle; Veljkovic, Slavimir; Stojiljkovic, Nenad; Jankovic-Velickovic, Ljubinka; Sokolovic, Dusan; Stoiljkovic, Milan; Ilic, Ivan

    2012-01-01

    Gentamicin (GM) is a widely used antibiotic against serious and life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine the protective effect of salicylic acid (SA) in gentamicin-induced nephrotoxicity in rats. Quantitative evaluation of gentamicin-induced structural alterations and degree of functional alterations in the kidneys were performed by histopathological and biochemical analyses in order to determine potential beneficial effects of SA coadministration with gentamicin. Gentamicin was observed to cause a severe nephrotoxicity which was evidenced by an elevation of serum urea and creatinine levels. The significant increases in malondialdehyde (MDA) levels and protein carbonyl groups indicated that GM-induced tissue injury was mediated through oxidative reactions. On the other hand, simultaneous SA administration protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by GM treatment. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules was found to be prevented by SA pretreatment. The results from our study indicate that SA supplement attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation in gentamicin-treated rats.

  7. Intermittent exposure to xenon protects against gentamicin-induced nephrotoxicity.

    Directory of Open Access Journals (Sweden)

    Ping Jia

    Full Text Available Aminoglycoside antibiotics, especially gentamicin, are widely used to treat Gram-negative infections due to their efficacy and low cost. Nevertheless the use of gentamicin is limited by its major side effect, nephrotoxicity. Xenon (Xe provided substantial organoprotective effects in acute injury of the brain and the heart and protected against renal ischemic-reperfusion injury. In this study, we investigated whether xenon could protect against gentamicin-induced nephrotoxicity. Male Wistar rats were intermittently exposed to either 70% xenon or 70% nitrogen (N2 balanced with 30% oxygen before and during gentamicin administration at a dose of 100 mg/kg for 7 days to model gentamicin-induced kidney injury. We observed that intermittent exposure to Xe provided morphological and functional renoprotection, which was characterized by attenuation of renal tubular damage, apoptosis, and oxidative stress, but not a reduction in inflammation. We also found that Xe pretreatment upregulated hypoxia-inducible factor 2α (HIF-2α and its downstream effector vascular endothelial growth factor, but not HIF-1α. With regard to the three HIF prolyl hydroxylases, Xe pretreatment upregulated prolyl hydroxylase domain-containing protein-2 (PHD2, suppressed PHD1, and had no influence on PHD3 in the rat kidneys. Pretreatment with Xe also increased the expression of miR-21, a microRNA known to have anti-apoptotic effects. These results support Xe renoprotection against gentamicin-induced nephrotoxicity.

  8. Clinicopathological Studies on Gentamicin Toxicity in White Leghorn Commercial Layers

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    Najam Ul Islam, M. Zargham Khan1, M. Kashif Saleemi*1, Ahrar Khan1, Sheraz Ahmed Bhatti1, Muhammad Yousaf2 and Zahoor-ul-Hassan3

    2011-10-01

    Full Text Available Gentamicin is an effective and economical drug used to control infectious diseases in poultry but is highly toxic and had slow clearance from the body. This study aimed to report three cases of gentamicin toxicity in three White Leghorn (WLH layer flocks in different poultry producing areas of Pakistan. In first case, gentamicin was injected in a 9000 WLH layer flock @ 10 mg/kg body weight (BW for seven times during 9-15 weeks for age. In second case, gentamicin was injected in a flock of 7500 WLH layers @ 25 mg/kg BW for four times during 17-18 weeks of age. In third case, gentamicin was injected in flock of 16000 WLH layers @ 22.22 mg/kg BW three times in 20-21 weeks of age. Flock wise mortality was 8.69, 82.63 and 71.86%, respectively. Birds were dehydrated, emaciated and had prominent keel bone. Clinical signs included dehydration, decreased body weight leading to emaciation, decreased feed intake, increased water intake and watery diarrhea. Necropsy revealed prominent keal bone, shrunken muscles swollen kidneys bulging out from bony sockets. Petechial and echymotic hemorrhages were present on heart and skeletal muscles. Liver was enlarged with hemorrhagic streaks on its surface. Microscopically, hemorrhages and acute tubular necrosis was recorded in kidneys. Liver had hemorrhages, cellular infiltration and vacuolar (fatty degeneration of hepatocytes. From the results, it could be concluded that overdosing and repeated administration of gentamicin was highly toxic to birds.

  9. Some pharmacokinetic and pharmacodynamic interactions between digoxin and gentamicin.

    Science.gov (United States)

    Staneva-Stoytcheva, D; Kristeva, E; Prodanova, K

    1992-01-01

    Some pharmacokinetic and pharmacodynamic interactions between digoxin and gentamicin were studied in experiments on rabbits, guinea-pigs and cats. An increase of digoxin serum levels and changes in some basic pharmacokinetic parameters of digoxin (t1/2 alpha t1/2 beta, AUC, C1) were found in gentamicin-pretreated rabbits, the changes being dependent on the dose and schedule of administration. The most pronounced changes were those in digoxin kinetics during simultaneous 5-day treatment with digoxin (0.035 mg/kg i.v.) and nontoxic (10 and 2 mg/kg) doses of gentamicin. The toxicity of digoxin in guinea-pigs, assessed by administration of lethal doses of digoxin, was increased only after the highest dose of gentamicin (100 mg/kg), while after nontoxic or close to therapeutic doses (10 and 2 mg/kg) of gentamicin, the digoxin toxicity was either unchanged or even decreased. Digoxin decreased the nerve-muscle blocking effect of gentamicin on cat ischiadicus-gastrocnemius preparation. The possible mechanisms involved are discussed.

  10. Correlation between apramycin and gentamicin use in pigs and an increasing reservoir of gentamicin-resistant Escherichia coli

    DEFF Research Database (Denmark)

    Jensen, Vibeke Frøkjær; Jakobsen, Lotte; Emborg, Hanne-Dorthe;

    2006-01-01

    and gentamicin resistance in Escherichia coli strains from pork, healthy pigs and diagnostic submissions from pigs and to investigate potential relationships to the use of apramycin and gentamicin at farm and national levels. Methods: Data on Danish E. coli isolates from healthy pigs (indicator bacteria......-2004). The genetic background for gentamicin resistance was investigated by PCR. Relationships between antimicrobial usage and resistance were analysed by chi(2) test and logistic regression. Results: At the farm level, the occurrence of apramycin/gentamicin cross-resistance was correlated to the use of apramycin (P...... resistance in clinical E. coli 0149 isolates was significantly correlated with the amounts and duration of apramycin use. The aac(3)-IV gene was detected in all tested cross-resistant isolates. Conclusions: Apramycin consumption...

  11. Patients’ safety: is there a systemic release of gentamicin by gentamicin-coated tibia nails in clinical use?

    Directory of Open Access Journals (Sweden)

    Moghaddam A

    2016-09-01

    Full Text Available Arash Moghaddam,1 Viola Graeser,1 Fabian Westhauser,1 Ulrike Dapunt,1 Till Kamradt,1 Stefan M Woerner,2 Gerhard Schmidmaier1 1HTRG – Heidelberg Traume Research Group Center for Orthopedics, Trauma and Spinal Cord Injury, University Hospital Heidelberg, Heidelberg, Germany; 2Department of Internal Medicine and Clinical Chemistry, University Hospital Heidelberg, Heidelberg, Germany Introduction: Osteitis is one of the most serious complications in orthopedic surgery. Expert Tibia Nail (ETN PROtect™ coated with a biodegradable layer of gentamicin-laden polymer was developed for prophylaxis of osteomyelitis. In systemic administration, gentamicin has only a small therapeutic index and serious side effects; it is potentially nephrotoxic as well as ototoxic. It is not yet known if relevant gentamicin concentrations are released into the systemic circulation after implantation of gentamicin-coated nails. In order to evaluate the patients’ risks profiles and increase patient safety, we measured gentamicin levels in pre- and postoperative serum samples of patients undergoing implantation of ETN PROtect.Methods: Twenty-five patients who received ETN PROtect between March 2012 and August 2014 were included in this study. Collection of blood samples occurred before the operation, at weeks 1–4, 3 and 6 months, and up to 1 year after the implantation. Measurement of gentamicin levels in serum samples was performed at the central laboratory of Heidelberg University Hospital. Additionally, laboratory parameters, C-reactive protein, leukocyte number, urea and creatinine concentrations were analyzed in routine controls before and after operating and assessed for systemic side effects.Results: Over the course of this prospective observational study, we were able to determine that gentamicin-coated nails do not release gentamicin into the systemic circulation above the lowest detectable level of 0.2 mg/dL. There were slight increases in the mean

  12. Fagonia olivieri prevented hepatorenal injuries induced with gentamicin in rat.

    Science.gov (United States)

    Rashid, Umbreen; Khan, Muhammad Rashid

    2017-04-01

    Gentamicin is used clinically against Gram negative bacteria because of its efficacy. However, it causes renal injuries and failure at clinical dosages on account of induced oxidative stress. Fagonia olivieri is used in kidneys, liver, alimentary canal and cardiovascular disorders in local system of medicine in Pakistan. This study evaluates the protective abilities of methanol extract of F. olivieri (FOM) against the liver and renal injuries induced with gentamicin in rat. Sprague-Dawley male rats were treated with gentamicin (80mg/kg) alone or with silymarin (50mg/kg) as standard antioxidant drug. The other groups of rats were treated with gentamicin along with FOM (200mg/kg, 400mg/kg) or FOM (400mg/kg) alone. Effect of FOM was investigated on body weight, urine and serum biochemical markers, enzymatic antioxidants of renal and liver along with histopathological alterations. FOM was investigated by GC-MS for the presence of bioactive constituents. Treatment of FOM to rats ameliorated the gentamicin induced toxicity and increased the percent increase in body weight while decreased the absolute and relative weight of hepatic and kidneys. Gentamicin increased the level of specific gravity, count of RBCs and WBCs, and urobilinogen in urine; and AST, ALT, ALP, LDH, total bilirubin, total cholesterol, triglycerides and LDL in serum. Level of lipid peroxides in terms of thiobarbituric acid reactive substances (TBARS) and DNA damages increased while the GSH contents and activity level of CAT, SOD, GSH-Px and GR decreased with gentamicin in liver and kidney samples. Co-treatment of FOM, dose dependently, alleviated the injuries induced with gentamicin. Histopathological studies of liver and kidneys supported the protective abilities of FOM. GC-MS analysis indicated the presence of various compounds including hexadecanoic acid, 2-methoxy-4-vinylphenol, benzoic acid and thalicpureine in the FOM. Results of the present investigation suggested the protective potential of FOM

  13. Gentamicin resistance among Escherichia coli strains isolated in neonatal sepsis.

    Science.gov (United States)

    Hasvold, J; Bradford, L; Nelson, C; Harrison, C; Attar, M; Stillwell, T

    2013-01-01

    Neonatal sepsis is a significant cause of morbidity and mortality among term and preterm infants. Ampicillin and gentamicin are standard empiric therapy for early onset sepsis. Four cases of neonatal sepsis secondary to Escherichia coli (E. coli) found to be gentamicin resistant occurred within a five week period in one neonatal intensive care unit (NICU). To determine whether these cases could be tied to a single vector of transmission, and to more broadly evaluate the incidence of gentamicin resistant strains of E. coli in the neonatal population at our institution compared to other centers, we reviewed the charts of the four neonates (Infants A through D) and their mothers. The E. coli isolates were sent for Pulse Field Gel Electrophoresis (PFGE) to evaluate for genetic similarity between strains. We also reviewed all positive E. coli cultures from one NICU over a two year period. Infants A and B had genetically indistinguishable strains which matched that of urine and placental cultures of Infant B's mother. Infant C had a genetically distinct organism. Infant D, the identical twin of Infant C, did not have typing performed. Review of all cultures positive for E. coli at our institution showed a 12.9 percent incidence of gentamicin-resistance. A review of other studies showed that rates of resistance vary considerably by institution. We conclude that gentamicin-resistant E. coli is a relatively uncommon cause of neonatal sepsis, but should remain a consideration in patients who deteriorate despite initiation of empiric antibiotics.

  14. Effect of platelet activating factor antagonist treatment on gentamicin nephrotoxicity

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    A. Rodriguez-Barbero

    1992-01-01

    Full Text Available To assess whether PAF could be involved in the gentamicin-induced nephrotoxicity, we have studied the effect of PAF antagonist BN-52021 on renal function in rats after gentamicin (GENTA treatment. Experiments were completed in 21 Wistar rats divided into three groups: group GENTA was injected with gentamicin 100 mg kg−1 body wt/day s.c. for 6 days. Group GENTA + BN received gentamicin and BN-52021 i.p. 5 mg kg−1 body wt/day. A third group served as control. Rats were placed in meta-bolic cages and plasma creatinine and creatinine clearance were measured daily. GENTA group showed a progressive increase in plasma creatinine, a drop in creatinine clearance and an increase in urinary excretion of N-acetyl-β-D-glucosaminidase and alkaline phosphatase. GENTA + BN group showed a lesser change in plasma creatinine and a creatinine clearance, but no difference with GENTA group in urinary excretion of NAG and AP were observed. Histological examination revealed a massive cortical tubular necrosis in rats treated with gentamicin, whereas in BN-52021 injected animals tubular damage was markedly attenuated. The present results suggest a role for PAF in the gentamicininduced nephro-toxicity.

  15. Doripenem, Gentamicin, and Colistin, Alone and in Combinations, against Gentamicin-Susceptible, KPC-Producing Klebsiella pneumoniae Strains with Various ompK36 Genotypes

    Science.gov (United States)

    Clancy, Cornelius J.; Hao, Binghua; Shields, Ryan K.; Chen, Liang; Perlin, David S.; Kreiswirth, Barry N.

    2014-01-01

    Gentamicin doses of 2 and 10 μg/ml were bactericidal against 64% and 100%, respectively, of gentamicin-susceptible KPC-2-producing Klebsiella pneumoniae strains. Treatment with the combination of doripenem (8 μg/ml) plus colistin (2 μg/ml) was inferior to treatment with gentamicin (2 μg/ml), doripenem-gentamicin, gentamicin-colistin, and doripenem-gentamicin-colistin against strains with glycine and aspartic acid insertions in OpmK36 porin at amino acid (aa) positions 134 and 135 (n = 9). Doripenem-colistin was comparable to other 2- or 3-drug regimens and superior to single drugs against wild-type/minor ompK36 mutants (n = 5). An algorithm incorporating ompK36 genotypes and susceptibility to gentamicin and doripenem may predict antimicrobial activity against KPC-producing K. pneumoniae. PMID:24566172

  16. Partridge embryo pathology in relation to gentamicin-induced lesions

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    Hadi Tavakkoli

    2016-10-01

    Full Text Available Objective: To determine the macroscopic and microscopic lesions of various dosages of gentamicin in the partridge embryo. Methods: Fertile chukar partridge eggs were allocated into four groups. Group 1: salineinjected group whose individuals were administered by sterile physiological saline solution of 0.2 mL/egg inserted into yolk sac. Groups 2, 3 and 4 whose individuals were similarly administered by gentamicin sulfate at a dosage of 80 mg/kg egg-weight once, twice and three times, respectively. Results: Results showed that the embryos were congested and stunted in the gentamicininjected groups. Defects in feet, wings and feather development were accompanied by microscopic lesions in brain, meninges, heart, lungs, liver and kidneys. Histopathological lesions were noticed as edema, undeveloped tissues, necrosis and degeneration in the affected organs. Conclusions: Based on acquired results, it is concluded that gentamicin at above-described dosages causes toxicopathological effects to the partridge embryo in a dose dependent manner.

  17. Antibiotic disposition in experimental pneumonic pasteurellosis: gentamicin and tylosin.

    Science.gov (United States)

    Burrows, G E; Barto, P B; Martin, B

    1986-01-01

    The effects of severe respiratory disease on the disposition of antibiotics were evaluated using two drugs chosen because of their widely differing solubility characteristics. The experiments were carried out in series, using five calves for each drug. The drugs were given to seven week old calves before and after induction of pneumonia by bilateral intrapulmonary administration of 3 mL of 5 X 10(7) colony forming units of Pasteurella haemolytica. Following inoculation, the calves developed clinical signs of pneumonia and were given gentamicin (5 mg/kg) or tylosin (10 mg/kg) 48, 60 and 72 hours after Pasteurella administration. There was a statistically significant decrease in distribution rate but not elimination rate of gentamicin. For tylosin, there was a significant increase in elimination rate. These results indicate the kinetics of tylosin but not gentamicin are sufficiently altered as to support a need for increased frequency of administration with severe respiratory disease in calves. Images Fig. 2. PMID:3756673

  18. Developmental pharmacokinetics of gentamicin in preterm and term neonates

    DEFF Research Database (Denmark)

    Nielsen, Elisabet I; Sandström, Marie; Honoré, Per Hartvig;

    2009-01-01

    for concentration monitoring. This study was performed to characterize the population pharmacokinetics of gentamicin in preterm and term neonates and to identify and quantify relationships between patient characteristics and IIV. A secondary aim was to evaluate cystatin C as a marker for gentamicin clearance...... was included as the primary covariate according to an allometric power model. Other evaluated covariates were age (postmenstrual age, gestational age [GA], postnatal age [PNA]), markers for renal function (serum creatinine, serum cystatin C) and concomitant medication with cefuroxime, vancomycin or indometacin...... as having a significant influence on the central volume of distribution, with a preterm neonate having a larger central volume of distribution per kilogram of bodyweight than a term neonate. Cystatin C and creatinine were not correlated with gentamicin clearance in this study population. The external...

  19. Cochlear and Vestibular Effects of Combined Intratympanic Gentamicin and Dexamethasone.

    Science.gov (United States)

    Güneri, Enis Alpin; Olgun, Yüksel; Aslıer, Mustafa; Nuti, Daniele; Kırkım, Günay; Mungan, Serpil; Kolatan, Efsun; Aktaş, Safiye; Trabalzini, Franco; Ellidokuz, Hülya; Yılmaz, Osman; Mandala, Marco

    2017-04-01

    The aim of this study is to evaluate the effects of an intratympanic gentamicin-dexamethasone combination on the inner ear. Twenty-six Wistar albino rats were divided into four groups: Group I (Control), group II (Intratympanic dexamethasone; ITD), group III (Intratympanic gentamicin; ITG), and group IV (Intratympanic gentamicin and dexamethasone; ITGD). On the first day after basal auditory brainstem response (ABR) measurements, the ITG group received 0.03 mL of intratympanic gentamicin (26.7 mg/mL). Intratympanic injection of 0.06 mL of a solution containing 13.35 mg/mL gentamicin and 2 mg/mL dexamethasone was performed in the ITGD group. 0.03 mL of physiological intratympanic serum and dexamethasone (4 mg/mL) was applied in control and ITD groups, respectively. On the 7th day, ABR measurements were repeated and vestibular functions were evaluated. On the 21th day, ABR and vestibular tests were repeated, and the animals were sacrificed for histopathological investigation. The ITG group's hearing thresholds deteriorated in all frequencies. The ITGD group's hearing thresholds were significantly better than the ITG group, except at 8 kHz on the 7th day and in all frequencies at the 21th day measurements. The vestibular function scores of the ITG and ITGD groups were higher than the controls. Apoptotic changes were seen in cochlea, spiral ganglion, and vestibule of the ITG group. Cochlear and vestibular structures were well preserved in the ITGD group, similar to the controls. The ITGD combination led to a significant hearing preservation. Although in subjective vestibular tests, it seemed that vestibulotoxicity was present in both ITG and ITGD groups the histopathological investigations revealed no signs of vestibulotoxicity in the ITGD group in contrast to the ITG group. Further studies using a combination of different concentrations of gentamicin and dexamethasone are needed.

  20. Protective effect of quercetin in gentamicin-induced oxidative stress in vitro and in vivo in blood cells. Effect on gentamicin antimicrobial activity.

    Science.gov (United States)

    Bustos, Pamela Soledad; Deza-Ponzio, Romina; Páez, Paulina Laura; Albesa, Ines; Cabrera, José Luis; Virgolini, Miriam Beatriz; Ortega, María Gabriela

    2016-12-01

    We have evaluated the effect of gentamicin and gentamicin plus quercetin on ROS production, endogenous antioxidant defenses (SOD and CAT) and lipid peroxidation in vitro on human leukocytes and in vivo on whole rat blood. Gentamicin generated ROS production in human leukocytes, produced a dual effect on both enzymes dosage-dependent and generated an increase in lipid peroxidation. Quercetin, in leukocytes stimulated by gentamicin, showed more inhibitory capacity in ROS production than the reference inhibitor (vitaminC) in mononuclear cells and a similar protective behavior at this inhibitor in polymorphonuclear cells. Quercetin, in both cellular systems, tend to level SOD and CAT activities, reaching basal values and could prevent lipidic peroxidation induced by gentamicin. The results in Wistar rats confirmed that therapeutic doses of gentamicin can induce oxidative stress in whole blood and that the gentamicin treatment plus quercetin can suppress ROS generation, collaborate with SOD and CAT and diminish lipid peroxidation. Finally, flavonoid and antibiotic association was evaluated on the antimicrobial activity in S. aureus and E. coli, showing that changes were not generated in the antibacterial activity of gentamicin against E. coli strains, while for strains of S. aureus a beneficial effect observes. Therefore, we have demonstrated that gentamicin could induce oxidative stress in human leukocytes and in whole blood of Wistar rats at therapeutic doses and that quercetin may to produce a protective effect on this oxidative stress generated without substantially modifying the antibacterial activity of gentamicin against E. coli strains, and it contributes to this activity against S. aureus strains.

  1. Concepts for increasing gentamicin release from handmade bone cement beads

    NARCIS (Netherlands)

    Rasyid, Hermawan N; van der Mei, Henny C; Frijlink, Henderik W; Soegijoko, Soegijardjo; Van Horn, Jim R; Busscher, Hendrik; Neut, Daniëlle

    2009-01-01

    BACKGROUND AND PURPOSE: Commercial gentamicin-loaded bone cement beads (Septopal) constitute an effective delivery system for local antibiotic therapy. These beads are not available in all parts of the world, and are too expensive for frequent use in others. Thus, orthopedic surgeons worldwide make

  2. Dose-Dependent Amelioration of Gentamicin-Induced ...

    African Journals Online (AJOL)

    Dose-Dependent Amelioration of Gentamicin-Induced Nephrotoxicity in Adult Swiss Albino ... Purpose: To evaluate the effect of vitamin B-complex on the nephrotoxicity of ... increase in serum urea and creatine while 3ml/kg of the same drug ...

  3. Serum concentrations of gentamicin following oral administration to preterm newborns.

    Science.gov (United States)

    Grylack, L; Boehnert, J; Scanlon, J

    1982-01-01

    Serum gentamicin concentration was measured in 31 newborn babies who received oral gentamicin for prophylaxis of necrotizing enterocolitis in order to determine the presence and degree of gastrointestinal absorption and its relationship to birth weight, gestational age, postnatal age and perinatal asphyxia. A dose of 2.5 mg/kg every 6 h by nasogastric tube was administered during a 3-week course after birth. The mean birth weight was 1,269 +/- 489 g; mean gestational age 29.6 +/- 3.7 weeks. The mean serum gentamicin levels were: 0.06 +/- 0.03 microgram/ml at 30 min after the first dose; 0.29 +/- 0.48 microgram/ml at 4 h; 1.62 +/- 1.43 microgram/ml at 24 h, and 0.33 +/- 0.57 microgram/ml at 7 days. The 24-hour and 7-day samples were taken before the next dose. The mean 24-hour level was significantly (p less than 0.001) higher than the other levels. There was no significant (p less than 0.05) relationship between the 24-hour serum gentamicin level and birth weight, gestational age or umbilical venous pH.

  4. Once daily dose gentamicin in neonates - is our dosing correct?

    Science.gov (United States)

    Serane, Tiroumourougane V; Zengeya, Stanley; Penford, Gemma; Cooke, Jane; Khanna, Gitika; McGregor-Colman, Elle

    2009-07-01

    The aim of this paper is to study the safety and efficacy (measured by therapeutic level) of once daily gentamicin in neonates >or=32 weeks of gestation and or=32 weeks of gestation and 2 mg/L. Only 39 (60%) had peak and trough levels within the therapeutic range. All babies who had audiometric evaluation (62 out of 65) had normal hearing. Out of the 65 babies, 60 had paired serum creatinine levels estimated and none had evidence of renal dysfunction. Among term neonates, only 2 out of 50 had the trough serum concentration of >2 mg/L. In 38 (76%) of the 50 neonates, the trough serum gentamicin concentration was <2.0 mg/L and the peak level was <10 mg/L. Forty-eight babies had audiometric evaluation which was normal. A dose of 4 mg/kg/day produces serum gentamicin levels outside the therapeutic range in two-fifths of neonates between 32 and 36 +/- 6 weeks. A single dose of 4 mg/kg/day of gentamicin is appropriate for term babies and probably excessive for 32-36 weeks' neonates.

  5. Alpha-linolenic acid protects against gentamicin induced toxicity

    Directory of Open Access Journals (Sweden)

    Priyadarshini M

    2012-11-01

    Full Text Available Medha Priyadarshini, Mohammad Aatif, Bilqees BanoDepartment of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, IndiaBackground: Recent studies indicate that reactive oxygen species are the major culprits behind the renal damage induced by gentamicin, an aminoglycoside antibiotic used to treat serious and life threatening Gram-negative infections. Experimental evidence suggests a protective role of alpha-linolenic acid supplementation against oxidative stress. The aim of the present study was to investigate the possible beneficial role of alpha-linolenic acid against gentamicin induced renal distress.Methods: Male Wistar rats were divided into three groups of eight rats each, with the first group serving as a control. The other groups were treated intraperitoneally with gentamicin 100 mg/kg body weight per day for 10 days ± alpha-linolenic acid and vitamin E (each given as 250 mg/kg body weight per day. Concentrations of creatinine, urea, cholesterol, inorganic phosphate in serum, malondialdehyde and total sulfhydryl levels, and glutathione-S-transferase, superoxide dismutase, and catalase activity in kidney tissues were determined.Results: Administration of gentamicin to rats induced marked renal failure, characterized by a profound increase in serum creatinine, urea, and cholesterol concentrations, accompanied by significant lowering of renal alkaline phosphatase and acid phosphatase activity, an increase in malondialdehyde, a decline in total sulfhydryl levels, and lowered superoxide dismutase, catalase, and glutathione-S-transferase activity. Cotreatment with alpha-linolenic acid produced amelioration in these biochemical indices of nephrotoxicity in serum as well as in tissue. Further histopathological and human studies are necessary to demonstrate the beneficial effects of alpha-linolenic acid in renal disease.Conclusion: Alpha-linolenic acid may represent a nontoxic and effective intervention strategy in

  6. Antibacterial Efficacy of a New Gentamicin-Coating for Cementless Prostheses Compared to Gentamicin-Loaded Bone Cement

    NARCIS (Netherlands)

    Neut, Danielle; Dijkstra, Rene J. B.; Thompson, Jonathan I.; van der Mei, Henny C.; Busscher, Henk J.

    2011-01-01

    Cementless prostheses are increasingly popular but require alternative prophylactic measures than the use of antibiotic-loaded bone cements. Here, we determine the 24-h growth inhibition of gentamicin-releasing coatings from grit-blasted and porous-coated titanium alloys, and compare their antibacte

  7. Mentha piperita in nephrotoxicity - a possible intervention to ameliorate renal derangements associated with gentamicin

    Directory of Open Access Journals (Sweden)

    Naveed Ullah

    2014-01-01

    Full Text Available Objective: Free radical generation has a strong role in the pathogenesis of renal damage associated with the use of gentamicin. Therefore, the present study was carried out to evaluate the renoprotective effect of Mentha piperita against gentamicin induced nephrotoxicity. Materials and Methods: A total of 24 male rabbits were divided into 4 groups receiving normal saline, gentamicin, M. piperita extract and co-therapy of extract and gentamicin respectively. Gentamicin was provided as 80 mg/kg/day intramuscularly and extract was given 200 mg/kg/day orally for a period of 21 days. Serum and urinary biochemical parameters and histological changes were studied for each group. The impact of the extract on the antibacterial action of gentamicin was also evaluated. Results: Animals treated with gentamicin showed derangements in serum and urinary biochemical parameters. These alterations were reversed by treatment with M. piperita extract. The histological changes showed in gentamicin group were also reverted by treatment with the extract. Further the plant did not influence the efficacy of gentamicin with respect to its antimicrobial properties. Conclusion: Co-therapy of M. piperita with gentamicin successfully attenuated biochemical kidney functioning derangements and morphological changes associated with gentamicin.

  8. Protective potential of Tamarindus indica against gentamicin-induced nephrotoxicity.

    Science.gov (United States)

    Ullah, Naveed; Azam Khan, Mir; Khan, Taous; Ahmad, Waqar

    2014-01-13

    Abstract Context: Gentamicin is an antibiotic that is effective against Gram-negative microorganisms. However, its clinical applications are often limited due to nephrotoxic effects. Objective: This study investigated the protective effects of aqueous-ethanol extract of Tamarindus indica L. (Leguminosae) fruits against gentamicin-induced renal toxicity. Materials and methods: A daily dose of 200 mg/kg of 70% aqueous-ethanol extract derived from T. indica was employed in male rabbits as a co-therapy with gentamicin (80 mg/kg) for a period of three weeks. Serum and urinary renal function parameters and histological assessments were carried out and compared with one way analysis of variance (Graphpad prism version 5.00, Graphpad Software, San Diego, CA). Results: The results showed that gentamicin-treated animals had significantly elevated blood urea nitrogen (54.1 ± 2.6 mg/dl), serum creatinine (4.0 ± 0.1 mg/dl), serum uric acid (2.3 ± 0.1 mg/dl) and urinary protein excretion (3.8 ± 0.3 mg/dl) with a fall in body weight (10 ± 1%), creatinine clearance (0.7 ± 0.09 ml/min), serum potassium (3.4 ± 0.1 mEq/l), serum calcium (7.6 ± 0.2 mg/dl), urinary volume (126 ± 9 ml/24 h) and urinary lactate dehydrogenase secretion (103.1 ± 4.2 U/l). However, animals treated by co-therapy with gentamicin and T. indica had significantly improved renal structure and function. Discussion and conclusion: Co-therapy of 200 mg/kg/d of T. indica for a period of three weeks successfully prevented functional and morphological derangements caused by gentamicin as assessed by different renal function parameters and histological examinations.

  9. Integrated transcriptomic and proteomic evaluation of gentamicin nephrotoxicity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Com, Emmanuelle, E-mail: emmanuelle.com@univ-rennes1.fr [sanofi-aventis R and D, Disposition Safety and Animal Research, Vitry-sur-Seine (France); INSERM U625, Proteomics Core Facility Biogenouest, Rennes (France); Boitier, Eric; Marchandeau, Jean-Pierre [sanofi-aventis R and D, Disposition Safety and Animal Research, Vitry-sur-Seine (France); Brandenburg, Arnd [Genedata AG, Basel (Switzerland); Schroeder, Susanne [Nycomed GmbH, Barsbüttel (Germany); Hoffmann, Dana; Mally, Angela [University of Würzburg, Department of Toxicology, University of Würzburg, Würzburg (Germany); Gautier, Jean-Charles [sanofi-aventis R and D, Disposition Safety and Animal Research, Vitry-sur-Seine (France)

    2012-01-01

    Gentamicin is an aminoglycoside antibiotic, which induces renal tubular necrosis in rats. In the context of the European InnoMed PredTox project, transcriptomic and proteomic studies were performed to provide new insights into the molecular mechanisms of gentamicin-induced nephrotoxicity. Male Wistar rats were treated with 25 and 75 mg/kg/day subcutaneously for 1, 3 and 14 days. Histopathology observations showed mild tubular degeneration/necrosis and regeneration and moderate mononuclear cell infiltrate after long-term treatment. Transcriptomic data indicated a strong treatment-related gene expression modulation in kidney and blood cells at the high dose after 14 days of treatment, with the regulation of 463 and 3241 genes, respectively. Of note, the induction of NF-kappa B pathway via the p38 MAPK cascade in the kidney, together with the activation of T-cell receptor signaling in blood cells were suggestive of inflammatory processes in relation with the recruitment of mononuclear cells in the kidney. Proteomic results showed a regulation of 163 proteins in kidney at the high dose after 14 days of treatment. These protein modulations were suggestive of a mitochondrial dysfunction with impairment of cellular energy production, induction of oxidative stress, an effect on protein biosynthesis and on cellular assembly and organization. Proteomic results also provided clues for potential nephrotoxicity biomarkers such as AGAT and PRBP4 which were strongly modulated in the kidney. Transcriptomic and proteomic data turned out to be complementary and their integration gave a more comprehensive insight into the putative mode of nephrotoxicity of gentamicin which was in accordance with histopathological findings. -- Highlights: ► Gentamicin induces renal tubular necrosis in rats. ► The mechanisms of gentamicin nephrotoxicity remain still elusive. ► Transcriptomic and proteomic analyses were performed to study this toxicity in rats. ► Transcriptomic and proteomic

  10. Toxicity of gentamicin in red-tailed hawks.

    Science.gov (United States)

    Bird, J E; Walser, M M; Duke, G E

    1983-07-01

    Gentamicin sulfate at dosage levels of 10 and 20 mg/kg of body weight was administered twice daily IV to red-tailed hawks. Clinical signs, water consumption, and changes in blood chemical values were monitored. Tissues were examined grossly and ultrastructurally, using light and electron microscopy. Clinical signs of weakness and apnea were attributed to gentamicin-induced neuromuscular blockade in the 20-mg/kg group. Serum values of aspartate transaminase, alanine transaminase, cholesterol, inorganic phosphorus, total protein, albumin, and uric acid increased in some birds. There was a decrease in periodic acid-Schiff staining of proximal tubular brush borders. Increased numbers of cytoplasmic lysosomes, many of which contained myelin figures, in renal epithelial cells were seen at the ultrastructural level. All birds given 20 mg/kg died. Both dosage levels were considered toxic in red-tailed hawks.

  11. A biodegradable gentamicin-hydroxyapatite-coating for infection prophylaxis in cementless hip prostheses

    Directory of Open Access Journals (Sweden)

    D Neut

    2015-01-01

    Full Text Available A degradable, poly (lactic-co-glycolic acid (PLGA, gentamicin-loaded prophylactic coating for hydroxyapatite (HA-coated cementless hip prostheses is developed with similar antibacterial efficacy as offered by gentamicin-loaded cements for fixing traditional, cemented prostheses in bone. We describe the development pathway, from in vitro investigation of antibiotic release and antibacterial properties of this PLGA-gentamicin-HA-coating in different in vitro models to an evaluation of its efficacy in preventing implant-related infection in rabbits. Bone in-growth in the absence and presence of the coating was investigated in a canine model. The PLGA-gentamicin-HA-coating showed high-burst release, with antibacterial efficacy in agar-assays completely disappearing after 4 days, minimising risk of inducing antibiotic resistance. Gentamicin-sensitive and gentamicin-resistant staphylococci were killed by the antibiotic-loaded coating, in a simulated prosthesis-related interfacial gap. PLGA-gentamicin-HA-coatings prevented growth of bioluminescent staphylococci around a miniature-stem mounted in bacterially contaminated agar, as observed using bio-optical imaging. PLGA-gentamicin-HA-coated pins inserted in bacterially contaminated medullary canals in rabbits caused a statistically significant reduction in infection rates compared to HA-coated pins without gentamicin. Bone ingrowth to PLGA-gentamicin-HA-coated pins, in condylar defects of Beagle dogs was not impaired by the presence of the degradable, gentamicin-loaded coating. In conclusion, the PLGA-gentamicin-HA-coating constitutes an effective strategy for infection prophylaxis in cementless prostheses.

  12. Protective effect of alpha-linolenic acid on gentamicin-induced ototoxicity in mice.

    Science.gov (United States)

    Kaplan, Halil Mahir; Şingirik, Ergin; Erdoğan, Kıvılcım Eren; Doran, Figen

    2017-07-31

    Alpha-linolenic acid is one of the fatty acids known as omega 3. Previous studies have shown the antioxidant and anti-inflammatory effects of alpha-linolenic acid, which prevented cell damage by inhibiting apoptotic pathway. Also, it is known that gentamicin activates apoptotic mediators and causes necrosis in the kidney. Due to this reason, we planned a study to evaluate the protective effects of alpha-linolenic acid on gentamicin induced ototoxicity by evaluating inflammation and apoptotic mediators. For this purpose, 100 mg/kg gentamicin (i.p; intraperitoneally) and 200 mg/kg alpha-linolenic acid (gavage) are administered to mice for 9 days. On 9th and 10th days, rotarod performance was assessed to test the effect of gentamicin and alpha-linolenic acid treatment on the motor coordination of mice. Gentamicin treatment decreased fall latency of mice and gentamicin treatment together with alpha-linolenic acid increased fall latency of mice. Gentamicin treatment also increased expression of phospholipase A2(plA2), cyclooxygenase-2(COX-2) and inducible nitric oxide syntheses (iNOS). Furthermore, it increased Bax and caspase-3, which are proapoptotic proteins and decreased bcl-2 that is an antiapoptotic protein. Gentamicin treatment together alpha-linolenic acid recovered the change of expression of these enzymes. In conclusion, this study showed that alpha-linolenic acid will be useful to prevent gentamicin-induced ototoxicity by inhibiting apoptosis and inflammation.

  13. Microsomal protein synthesis inhibition: an early manifestation of gentamicin nephrotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, W.M.; Mela-Riker, L.M.; Houghton, D.C.; Gilbert, D.N.; Buss, W.C.

    1988-08-01

    Aminoglycoside antibiotics achieve bacterial killing by binding to bacterial ribosomes and inhibiting protein synthesis. To examine whether similar mechanisms could be present in renal tubular cells prior to the onset of overt proximal tubular necrosis due to these drugs, we isolated microsomes from Fischer rats given 20 mg/kg gentamicin every 12 h subcutaneously for 2 days and from vehicle-injected controls. Concomitant studies of renal structure, function, and mitochondrial respiration were carried out. (3H)leucine incorporation into renal microsomes of treated animals was reduced by 21.9% (P less than 0.01), whereas brain and liver microsomes from the same animals were unaffected. Gentamicin concentration in the renal microsomal preparation was 56 micrograms/ml, a value 7- to 10-fold above concentrations necessary to inhibit bacterial growth. Conventional renal function studies were normal (blood urea, serum creatinine, creatinine clearance). Treated animals showed only a mild reduction of inulin clearance, 0.71 compared with 0.93 ml.min-1.100 g-1 in controls (P less than 0.05), and an increase in urinary excretion of N-acetylglucosaminidase of 20 compared with 14.8 units/l (P less than 0.05). Renal slice transport of p-aminohippuric acid, tetraethylammonium, and the fractional excretion of sodium were well preserved. There was no evidence, as seen by light microscopy, of proximal tubular necrosis. Mitochondrial cytochrome concentrations were normal and respiratory activities only slightly reduced. Processes similar to those responsible for bacterial killing could be involved in experimental gentamicin nephrotoxicity before overt cellular necrosis.

  14. Gentamicin-mediated ototoxicity and nephrotoxicity: A clinical trial study

    Directory of Open Access Journals (Sweden)

    Parviz Saleh

    2016-01-01

    Full Text Available Background: Aminoglycosides and mainly gentamicin are the most important antimicrobial agents. Two different methods of administration exist: Single and multiple doses. There has always been a controversy about the less harmful administration method, to minimize adverse effects of gentamicin - deafness and renal insufficiency. In this study, it was aimed to compare two different methods of administration to figure out the least harmful treatment method. Materials and Methods: In a clinical study, eighty patients aged 12-55 years who were admitted with sepsis syndrome were included in the study; they were divided into two groups: The first group received single-dose treatment (5 mg/kg whereas the second group was treated with multiple doses (1.7 mg/kg three times a day of gentamicin. Results: The results show that blood urea nitrogen (BUN and creatinine (CR levels were decreased in the first group. Both blood urea nitrogen and creatinine and also mean glomerular filtration rate was increased in the same group. In the second group, mean BUN and CR levels were increased while the GFR was decreased in the same group. There was also a gradual increase in GFR in the first group. GFR <80 was decreased from 20% to 5.1% in the first group while increased from 5% to 27.5% in the second group. Results of audiometric studies show 6.1% hearing problem in the first group and 12.8% in the second one. Conclusions: Results of the present study showed that nephrotoxicity and ototoxicity are minimized in single-dose administration compared to multiples doses.

  15. Controlled Delivery of Gentamicin Using Poly(3-hydroxybutyrate Microspheres

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    Ipsita Roy

    2011-07-01

    Full Text Available Poly(3-hydroxybutyrate, P(3HB, produced from Bacillus cereus SPV using a simple glucose feeding strategy was used to fabricate P(3HB microspheres using a solid-in-oil-water (s/o/w technique. For this study, several parameters such as polymer concentration, surfactant and stirring rates were varied in order to determine their effect on microsphere characteristics. The average size of the microspheres was in the range of 2 µm to 1.54 µm with specific surface areas varying between 9.60 m2/g and 6.05 m2/g. Low stirring speed of 300 rpm produced slightly larger microspheres when compared to the smaller microspheres produced when the stirring velocity was increased to 800 rpm. The surface morphology of the microspheres after solvent evaporation appeared smooth when observed under SEM. Gentamicin was encapsulated within these P(3HB microspheres and the release kinetics from the microspheres exhibiting the highest encapsulation efficiency, which was 48%, was investigated. The in vitro release of gentamicin was bimodal, an initial burst release was observed followed by a diffusion mediated sustained release. Biodegradable P(3HB microspheres developed in this research has shown high potential to be used in various biomedical applications.

  16. 21 CFR 524.1044b - Gentamicin sulfate, betamethasone valerate otic solution.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate, betamethasone valerate otic solution. 524.1044b Section 524.1044b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1044b Gentamicin sulfate, betamethasone valerate otic solution....

  17. The release of gentamicin from acrylic bone cements in a simulated prosthesis-related interfacial gap

    NARCIS (Netherlands)

    Hendriks, JGE; Neut, D; van Horn, [No Value; van der Mei, HC; Busscher, HJ

    2003-01-01

    Gentamicin is added to polymethylmethacrylate bone cements in orthopedics as a measure against infection in total joint arthroplasties. Numerous studies have been published on gentamicin release from bone cements, but none have been able to estimate the local concentrations in the prosthesis-related

  18. Gentamicin Binds to Megalin as a Competitive Inhibitor Using the Common Ligand Binding Motif of Complement Type Repeats

    DEFF Research Database (Denmark)

    Dagil, Robert; O'Shea, Charlotte; Nykjaer, Anders

    2012-01-01

    Gentamicin is an aminoglycoside widely used in treatments of, in particular, enterococcal, mycobacterial, and severe Gram-negative bacterial infections. Large doses of gentamicin cause nephrotoxicity and ototoxicity, entering the cell via the receptor megalin. Until now, no structural information...

  19. Gentamicin in vitro activity and tentative gentamicin interpretation criteria for the CLSI and calibrated dichotomous sensitivity disc diffusion methods for Neisseria gonorrhoeae.

    Science.gov (United States)

    Bala, Manju; Singh, Vikram; Philipova, Ivva; Bhargava, Aradhana; Chandra Joshi, Naveen; Unemo, Magnus

    2016-07-01

    XDR Neisseria gonorrhoeae imposes the threat of untreatable gonorrhoea. Gentamicin is considered for future treatment; however, no interpretation criteria for the CLSI and calibrated dichotomous sensitivity (CDS) disc diffusion (DD) techniques are available for N. gonorrhoeae. We investigated the in vitro gentamicin activity by MIC and DD methods, proposed DD breakpoints and determined DD ranges for 10 international quality control (QC) strains. Gentamicin susceptibility of 333 N. gonorrhoeae isolates, including 323 clinical isolates and 10 QC strains, was determined. MIC determination (Etest) and DD methods (CLSI and CDS) were performed. The relationship between MIC, inhibition zone diameter and annular radius was determined by linear regression analysis and the correlation coefficient (r) was calculated. Gentamicin MICs for the QC strains were within published ranges. Of the 323 clinical isolates, according to published breakpoints 75.9%, 23.5% and 0.6% were susceptible, intermediately susceptible and resistant, respectively. Based on error minimization with MICs of ≤4, 8-16 and ≥32 mg/L, breakpoints proposed are susceptible ≥16 mm, intermediately susceptible 13-15 mm and resistant ≤12 mm for the CLSI method and susceptible ≥6 mm, less susceptible 3-5 mm and resistant ≤2 mm for the CDS technique. Low resistance to gentamicin was identified and gentamicin might be a future treatment option for gonorrhoea. Tentative gentamicin zone breakpoints were defined for two DD methods and QC ranges for 10 international reference strains were established. Our findings suggest that in resource-poor settings where MIC testing is not a feasible option, the DD methods can be used to indicate gentamicin resistance. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Effects of gentamicin on the recovery of renal function after unilateral hydronephrosis

    Energy Technology Data Exchange (ETDEWEB)

    Seki, Nobumitsu [Ehime Univ., Shigenobu (Japan). School of Medicine

    2002-06-01

    Urinary tract infection is one of complications in hydronephrosis, and antibiotics such as gentamicin are indicated for the treatment. However, gentamicin is known to cause drug-induced nephropathy. Using a rat kidney model, we investigated the effects of gentamicin treatment on the functional recovery from unilateral hydronephrosis. Quantitative separate renal function study by means of Technetium-99m DMSA renoscintigraphy revealed that contralateral kidney was affected by the treatment right after the release of complete ureteral obstruction. Moreover, in the case of incomplete ureteral obstruction, bilateral kidneys were affected by the treatment. Morphological studies using in situ DNA3' -end labeling and immunohistochemical methods showed that regeneration in the bilateral kidney followed gentamicin treatment right after the release. These results suggest that we should take account of separate renal function failure after gentamicin administration in the perihydronephrotic periods. (author)

  1. Direct laser light enhancement of susceptibility of bacteria to gentamicin antibiotic

    Science.gov (United States)

    Reznick, Yana; Banin, Ehud; Lipovsky, Anat; Lubart, Rachel; Zalevsky, Zeev

    2011-11-01

    ObjectivesTo test the effect of pulsed (Q-switched) and continuous wave (CW) laser light at wavelength of 532 nm on the viability of free-living stationary phase bacteria with and without gentamicin (an antibiotic) treatment. MethodsFree living stationary phase gram negative bacteria ( Pseudomonas aeruginosa strain PAO1) was immersed in Luria Broth (LB) solution and exposed to Q-switched and CW lasers with and without the addition of the antibiotic gentamicin. Cell viability was determined at different time points. ResultsLaser treatment alone did not reduce cell viability compared to untreated control and the gentamicin treatment alone only resulted in a 0.5 log reduction in the viable count for P. aeruginosa. The combined laser and gentamicin treatment, however, resulted in a synergistic effect and viability was reduced by 8 logs for P. aeruginosa PAO1. ConclusionsCombination of laser light with gentamicin shows an improved efficacy against P. aeruginosa.

  2. Cost evaluation of therapeutic drug monitoring of gentamicin at a teaching hospital in Malaysia

    Directory of Open Access Journals (Sweden)

    Ibrahim MI

    2014-03-01

    Full Text Available Background: Therapeutic drug monitoring (TDM makes use of serum drug concentrations as an adjunct to decision-making. Preliminary data in our hospital showed that approximately one-fifth of all drugs monitored by TDM service were gentamicin. Objective: In this study, we evaluated the costs associated with providing the service in patients with bronchopneumonia and treated with gentamicin. Methods: We retrospectively collected data from medical records of patients admitted to the Hospital Universiti Sains Malaysia over a 5-year period. These patients were diagnosed with bronchopneumonia and were on gentamicin as part of their treatment. Five hospitalisation costs were calculated; (i cost of laboratory and clinical investigations, (ii cost associated with each gentamicin dose, (iii fixed and operating costs of TDM service, (iv cost of providing medical care, and (v cost of hospital stay during gentamicin treatment. Results: There were 1920 patients admitted with bronchopneumonia of which 67 (3.5% had TDM service for gentamicin. Seventy-three percent (49/67 patients were eligible for final analysis. The duration of gentamicin therapy ranged from 3 to 15 days. The cost of providing one gentamicin assay was MYR25, and the average cost of TDM service for each patient was MYR104. The average total hospitalisation cost during gentamicin treatment for each patient was MYR442 (1EUR approx. MYR4.02. Conclusion: Based on the hospital perspective, in patients with bronchopneumonia and treated with gentamicin, the provision of TDM service contributes to less than 25% of the total cost of hospitalization.

  3. [A clinical study on gentamicin in the field of surgery].

    Science.gov (United States)

    Fujimoto, M; Ueda, T; Hirao, S; Sakai, K

    1976-03-01

    Gentamicin (GM), one of the amino-glucosides, was administered intramuscularly to 27 patients with Pseudomonas and/or other antibiotics resistant infections. The clinical evaluation of the results obtained was classified excellent in 1 case good 6, fair 8, none 11 and indeterminate 1, the effectiveness accounting for 57.7 percent. Satisfactory results were noted in wound infections, peritonitis and urinary tract infections. Among untoward side effects, an elevation in GOT and GPT values was observed in 6 cases, an elevation of BUN value in 1, proteinuria in 1 and hematuria in 1. However, it is difficult to conclude that those side effects were attributable to GM itself because blood transfusion or combined therapy with anti-cancer agents was conducted in these cases during the GM therapy.

  4. Protective effect of naringenin against gentamicin-induced nephrotoxicity in rats.

    Science.gov (United States)

    Fouad, Amr A; Albuali, Waleed H; Zahran, Ahmed; Gomaa, Wafaey

    2014-09-01

    The protective effect of naringenin, a flavonoid compound isolated from citrus fruits, was investigated against nephrotoxicity induced by gentamicin (80mgkg(-1)/day, i.p., for eight days) in rats. Naringenin treatment (50mgkg(-1)/day, p.o.) was administered for eight days, starting on the same day of gentamicin administration. Gentamicin caused significant elevations of serum creatinine, and kidney tissue levels of malondialdehyde, nitric oxide, and interleukin-8, and a significant decrease in renal glutathione peroxidase activity. Naringenin treatment significantly ameliorated the changes in the measured biochemical parameters resulted from gentamicin administration. Also, naringenin markedly attenuated the histopathological renal tissue injury observed with gentamicin. Immunohistochemical examinations showed that naringenin significantly reduced the gentamicin-induced expression of kidney injury molecule-1, vascular endothelial growth factor, inducible nitric oxide synthase, and caspase-9, and increased survivin expression in the kidney tissue. It was concluded that naringenin, through its antioxidant and anti-inflammatory effects, may represent a therapeutic option to protect against gentamicin nephrotoxicity.

  5. Agmatine improves renal function in gentamicin-induced nephrotoxicity in rats.

    Science.gov (United States)

    El-Kashef, Dalia H; El-Kenawi, Asmaa E; Abdel Rahim, Mona; Suddek, Ghada M; Salem, Hatem A

    2016-03-01

    The present study was designed to explore the possible protective effects of agmatine, a known nitric oxide (NO) synthase inhibitor, against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of agmatine on gentamicin-induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was evaluated. Twenty-four male Wistar albino rats were randomly divided into 3 groups, namely control, gentamicin (100 mg/kg, i.p.), and gentamicin plus agmatine (40 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood and urine samples and kidneys were taken. Administration of agmatine significantly decreased kidney/body mass ratio, serum creatinine, lactate dehydrogenase (LDH), renal malondialdehyde (MDA), myeloperoxidase (MPO), NO, and tumor necrosis factor-alpha (TNF-α) while it significantly increased creatinine clearance and renal superoxide dismutase (SOD) activity when compared with the gentamicin-treated group. Additionally, agmatine ameliorated tissue morphology as evidenced by histological evaluation and reduced the responses of isolated bladder rings to ACh. Our study indicates that agmatine administration with gentamicin attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation, restoring NO level and inhibiting inflammatory mediators such as TNF-α.

  6. Evaluating synergy between marbofloxacin and gentamicin in Pseudomonas aeruginosa strains isolated from dogs with otitis externa.

    Science.gov (United States)

    Jerzsele, Ákos; Pásztiné-Gere, Erzsébet

    2015-03-01

    The aim of this study was to determine antimicrobial susceptibility of Pseudomonas aeruginosa strains to marbofloxacin and gentamicin, and investigate the possible synergistic, additive, indifferent or antagonistic effects between the two agents. P. aeruginosa strains can develop resistance quickly against certain antibiotics if used alone, thus the need emerges to find synergistic combinations. A total of 68 P. aeruginosa strains isolated from dogs were examined. In order to describe interactions between marbofloxacin and gentamicin the checkerboard microdilution method was utilized. The MICs (minimum inhibitory concentrations) for marbofloxacin and gentamicin were in the range 0.25-64 mg/L and 0.25-32 mg/L, respectively. The combination of marbofloxacin and gentamicin was more effective with a MIC range of 0.031-8 mg/L and a MIC90 of 1 mg/L, compared to 16 mg/L for marbofloxacin alone and 8 mg/L for gentamicin alone. The FIC (fractional inhibitory concentration) indices ranged from 0.0945 (pronounced synergy) to 1.0625 (indifference). Synergy between marbofloxacin and gentamicin was found in 33 isolates. The mean FIC index is 0.546, which represents a partial synergistic/additive effect close to the full synergy threshold. In vitro results indicate that marbofloxacin and gentamicin as partially synergistic agents may prove clinically useful in combination therapy against P. aeruginosa infections. Although marbofloxacin is not used in the human practice, the interactions between fluoroquinolones and aminoglycosides may have importance outside the veterinary field.

  7. Gentamicin removal in submerged fermentation using the novel fungal strain Aspergillus terreus FZC3

    Science.gov (United States)

    Liu, Yuanwang; Chang, Huiqing; Li, Zhaojun; Zhang, Cheng; Feng, Yao; Cheng, Dengmiao

    2016-10-01

    Social concern and awareness of the potential risk posed by environmental residues of antibiotics such as gentamicin in the development of antibiotic resistance genes have increased. The present study used laboratory-scale experiments to develop methods for gentamicin removal from the environment. A fungus, strain FZC3, which could remove gentamicin in submerged fermentation, was isolated from solid waste and sewage water from a gentamicin production factory. The fungus was identified as Aspergillus terreus by sequencing the PCR-amplified ITS fragments of its rRNA-coding genes and by its morphology. The gentamicin removal efficiency exceeded 95% by day 7 under optimized culture conditions. The results showed that both biosorption and biodegradation were involved. We speculated that Aspergillus terreus FZC3 absorbed gentamicin and subsequently degraded it. We also found that Aspergillus terreus FZC3 survived and maintained a high bioremediation efficiency over a wide pH range, indicating its potential for future use in the large-scale bioremediation of gentamicin.

  8. Is Penicillin plus Gentamicin Synergistic against Clinical Group B Streptococcus isolates?: A in-vitro Study.

    Directory of Open Access Journals (Sweden)

    Corinne Ruppen

    2016-10-01

    Full Text Available Group B Streptococcus (GBS is increasingly causing invasive infections in nonpregnant adults. Elderly patients and those with comorbidities are at increased risk. On the basis of previous studies focusing on neonatal infections, penicillin plus gentamicin is recommended for infective endocarditis (IE and periprosthetic joint infections (PJI in adults. The purpose of this study was to investigate whether a synergism with penicillin and gentamicin is present in GBS isolates that caused IE and PJI. We used 5 GBS isolates, two clinical strains and three control strains, including one displaying high-level gentamicin resistance (HLGR. The results from the checkerboard and time-kill assays (TKAs were compared. For TKAs, antibiotic concentrations for penicillin were 0.048 and 0.2 mg/L, and for gentamicin 4 mg/L or 12.5 mg/L. In the checkerboard assay, the median fractional inhibitory concentration indices (FICIs of all isolates indicated indifference. TKAs for all isolates failed to demonstrate synergism with penicillin 0.048 or 0.2 mg/L, irrespective of gentamicin concentrations used. Rapid killing was seen with penicillin 0.048 mg/L plus either 4 mg/L or 12.5 mg/L gentamicin, from 2 h up to 8 h hours after antibiotic exposure. TKAs with penicillin 0.2 mg/L decreased the starting inoculum below the limit of quantification within 4 h to 6 h, irrespective of the addition of gentamicin. Fast killing was seen with penicillin 0.2 mg/L plus 12.5 mg/L gentamicin within the first 2 h. Our in vitro results indicate that the addition of gentamicin to penicillin contributes to faster killing at low penicillin concentrations, but only within the first few hours. Twenty-four hours after antibiotic exposure, PEN alone was bactericidal and synergism was not seen.

  9. Is Penicillin Plus Gentamicin Synergistic against Clinical Group B Streptococcus isolates?: An In vitro Study.

    Science.gov (United States)

    Ruppen, Corinne; Lupo, Agnese; Decosterd, Laurent; Sendi, Parham

    2016-01-01

    Group B Streptococcus (GBS) is increasingly causing invasive infections in non-pregnant adults. Elderly patients and those with comorbidities are at increased risk. On the basis of previous studies focusing on neonatal infections, penicillin plus gentamicin is recommended for infective endocarditis (IE) and periprosthetic joint infections (PJI) in adults. The purpose of this study was to investigate whether a synergism with penicillin and gentamicin is present in GBS isolates that caused IE and PJI. We used 5 GBS isolates, two clinical strains and three control strains, including one displaying high-level gentamicin resistance (HLGR). The results from the checkerboard and time-kill assays (TKAs) were compared. For TKAs, antibiotic concentrations for penicillin were 0.048 and 0.2 mg/L, and for gentamicin 4 mg/L or 12.5 mg/L. In the checkerboard assay, the median fractional inhibitory concentration indices (FICIs) of all isolates indicated indifference. TKAs for all isolates failed to demonstrate synergism with penicillin 0.048 or 0.2 mg/L, irrespective of gentamicin concentrations used. Rapid killing was seen with penicillin 0.048 mg/L plus either 4 mg/L or 12.5 mg/L gentamicin, from 2 h up to 8 h hours after antibiotic exposure. TKAs with penicillin 0.2 mg/L decreased the starting inoculum below the limit of quantification within 4-6 h, irrespective of the addition of gentamicin. Fast killing was seen with penicillin 0.2 mg/L plus 12.5 mg/L gentamicin within the first 2 h. Our in vitro results indicate that the addition of gentamicin to penicillin contributes to faster killing at low penicillin concentrations, but only within the first few hours. Twenty-four hours after antibiotic exposure, PEN alone was bactericidal and synergism was not seen.

  10. Effect of nettle (Urtica dioica) extract on gentamicin induced nephrotoxicity in male rabbits

    Institute of Scientific and Technical Information of China (English)

    Nadia Abdulkarim Salih

    2015-01-01

    To investigate the antioxidant effect of an orally administered ethanol extract of nettle (Urtica dioica) and its protective role in preventing or ameliorating oxidative stress as a major factor in gentamicin-induced nephrotoxicity in male rabbits. Methods: Twenty rabbits were divided into 4 equal groups: (G1) control group, (G2) gentamicin treated group (100 mg/kg), (G3) nettle treated group (100 mg/kg), (G4) combination treated group with both gentamicin (100 mg/kg) and nettle (100 mg/kg) for 10 days. The antioxidant properties of nettle were evaluated using different antioxidant tests, such as determination of glutathione and malondialdehyde levels and total phenolic content analysis. Results: Biochemical and histopathological study revealed that gentamicin caused nephrotoxicity observed clearly in the histopathological section of the kidney in the gentamicin treated group. Serum creatinine and blood urea nitrogen were biochemical indicators for nephrotoxicity which increased significantly in gentamicin treated group; other groups have no significant change in these two parameters. Nettle extract protected the rabbits from alteration in the level of blood urea nitrogen and serum creatinine when given after inducing of gentamicin nephrotoxicity. The nettle treated group showed a great effect as an antioxidant factor by increasing the glutathione level and reducing malondialdehyde level. No significant changes in biochemical parameters and no renal histopathological changes observed in the groups treated with nettle extract, which meant nettle had powerful antioxidant activity. Conclusions: Therefore, it can be assumed that the nephroprotective effect shown by nettle in gentamicin-induced nephrotoxicity can reserve intracellular levels of biological pathways and supportively enhance excretion of toxic levels of gentamicin.

  11. Protective effect of allicin against gentamicin-induced nephrotoxicity in rats.

    Science.gov (United States)

    El-Kashef, Dalia H; El-Kenawi, Asmaa E; Suddek, Ghada M; Salem, Hatem A

    2015-12-01

    In this study, the modulator effect of allicin on the oxidative nephrotoxicity of gentamicin in the kidneys of rats was investigated by determining indices of lipid peroxidation and the activities of antioxidant enzymes, as well as by histological analyses. Furthermore, the effect of allicin on gentamicin induced hypersensitivity of urinary bladder rings to ACh was estimated. Twenty-four male Wistar albino rats were randomly divided into three groups, control, gentamicin (100mg/kg, i.p.) and gentamicin+allicin (50mg/kg, orally). At the end of the study, all rats were sacrificed and then urine, blood samples and kidneys were taken. Gentamicin administration caused a severe nephrotoxicity as evidenced by an elevated kidney/body weight ratio, serum creatinine, blood urea nitrogen (BUN), serum lactate dehydrogenase (LDH) and proteinuria with a reduction in serum albumin and creatinine clearance as compared with control group. In addition, a significant increase in renal contents of malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NOx) and tumor necrosis factor-alpha (TNF-α) concomitantly with a significant decrease in renal reduced glutathione (GSH) and superoxide dismutase (SOD) activities was detected upon gentamicin injection. Exposure to gentamicin increased the sensitivity of isolated urinary bladder rings to ACh and induced acute renal tubular epithelial cells necrosis. Administration of allicin significantly decreased kidney/body weight ratio, serum creatinine, LDH, renal MDA, MPO, NOx and TNF-α while it significantly increased creatinine clearance, renal GSH content and renal SOD activity when compared to gentamicin-treated group. Additionally, allicin significantly reduced the responses of isolated bladder rings to ACh and ameliorated tissue morphology as evidenced by histological evaluation. Our study indicates that allicin exerted protection against structural and functional damage induced by gentamicin possibly due to its antioxidant, anti

  12. Effect of nettle(Urtica dioica) extract on gentamicin induced nephrotoxicity in male rabbits

    Institute of Scientific and Technical Information of China (English)

    Nadia; Abdulkarim; Salih

    2015-01-01

    Objective:To investigate the antioxidant ef ect of an orally administered ethanol extract of nettle(Urtica dioica) and its protective role in preventing or ameliorating oxidative stress as a major factor in gentamicin-induced nephrotoxicity in male rabbits. Methods: Twenty rabbits were divided into 4 equal groups:(G1) control group,(G2) gentamicin treated group(100 mg/kg),(G3) nettle treated group(100 mg/kg),(G4) combination treated group with both gentamicin(100 mg/kg) and nettle(100 mg/kg) for 10 days. The antioxidant properties of nettle were evaluated using dif erent antioxidant tests, such as determination of glutathione and malondialdehyde levels and total phenolic content analysis. Results: Biochemical and histopathological study revealed that gentamicin caused nephrotoxicity observed clearly in the histopathological section of the kidney in the gentamicin treated group. Serum creatinine and blood urea nitrogen were biochemical indicators for nephrotoxicity which increased signii cantly in gentamicin treated group; other groups have no signii cant change in these two parameters. Nettle extract protected the rabbits from alteration in the level of blood urea nitrogen and serum creatinine when given after inducing of gentamicin nephrotoxicity. The nettle treated group showed a great ef ect as an antioxidant factor by increasing the glutathione level and reducing malondialdehyde level. No signii cant changes in biochemical parameters and no renal histopathological changes observed in the groups treated with nettle extract, which meant nettle had powerful antioxidant activity. Conclusions: Therefore, it can be assumed that the nephroprotective ef ect shown by nettle in gentamicin-induced nephrotoxicity can reserve intracellular levels of biological pathways and supportively enhance excretion of toxic levels of gentamicin.

  13. Functional and anatomic alterations in the gentamicin-damaged vestibular system in the guinea pig

    NARCIS (Netherlands)

    Oei, MLYM; Segenhout, HM; Dijk, T; Stokroos, [No Value; van der Want, TJL; Albers, FWJ

    2004-01-01

    Hypothesis: The purpose of this study was to investigate the expected functional and morphologic effect of gentamicin on the vestibular system simultaneously by measurement of vestibular evoked potentials and electron microscopic evaluation. Background: Vestibular short-latency evoked potentials to

  14. Gentamicin modified chitosan film with improved antibacterial property and cell biocompatibility.

    Science.gov (United States)

    Liu, Yang; Ji, Peihong; Lv, Huilin; Qin, Yong; Deng, Linhong

    2017-05-01

    Gentamicin modified chitosan film (CS-GT) was produced using a three-step procedure comprising: (i) the chitosan solution was air-dried to form a chitosan (CS) film, (ii) using citric acid to generate the amide and carboxyl groups on the surface of CS, (iii) the CS with surface carboxyl groups was modified by grafting of gentamicin. After modification, this CS-GT film has excellent hydrophilicity and biocompatibility. It is very evident that the gentamicin grafting treatment significantly improves the antibacterial properties of the CS film. Our preliminary results suggest that this novel gentamicin modified chitosan film, which can be prepared in large quantities and at low cost, should have potential application in biomedical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Simultaneous immobilization of heparin and gentamicin on polypropylene textiles: a dual therapeutic activity.

    Science.gov (United States)

    Degoutin, Stéphanie; Jimenez, Maude; Chai, Feng; Pinalie, Thibaut; Bellayer, Severine; Vandenbossche, Marianne; Neut, Christel; Blanchemain, Nicolas; Martel, Bernard

    2014-11-01

    The aim of this work was to prepare a nonwoven polypropylene (PP) textile functionalized with bioactive molecules in order to improve simultaneously anticoagulation and antibacterial properties. The immobilization of either heparin (anticoagulation agent) or gentamicin (aminoglycoside class antibiotic) alone has already been proven to be effective on PP nonwoven textiles. In this work, we managed to go further, by immobilizing both heparin and gentamicin at the same time on one unique textile. A successive immersion in different heparin and gentamicin bathes successfully led to a dual drug coated textile, as confirmed by several characterization techniques (Fourier transform infrared-attenuated total reflectance, X-ray photoelectron spectroscopy, and scanning electron microscopy). The immobilization times were varied in order to determine the best compromise between cytocompatibility, anticoagulant effect, and antimicrobial activity. Short immersion times in gentamicin solutions confer very good antimicrobial activity to the textile and avoid cytotoxicity, whereas long immersion times in heparin solution were necessary to observe a significant anticoagulant effect.

  16. Pharmacokinetics and clinical evaluations of gentamicin-induced nephrotoxicity in puppies

    Directory of Open Access Journals (Sweden)

    Fidelis A. Gberindyer

    2015-08-01

    Conclusion: These suggest the risk of nephrotoxicity following treatment with gentamicin beyond 5 consecutive days irrespective of the dosing interval in puppies. [Int J Basic Clin Pharmacol 2015; 4(4.000: 691-696

  17. Protective effect of lycopene on gentamicin-induced oxidative stress and nephrotoxicity in rats.

    Science.gov (United States)

    Karahan, I; Ateşşahin, A; Yilmaz, S; Ceribaşi, A O; Sakin, F

    2005-11-15

    A potential therapeutic approach to protect or reverse gentamicin-induced oxidative stress and nephrotoxicity would have more importance for clinical consequences. Therefore, the present study was designed to investigate the possible protective effects of lycopene against gentamicin-induced renal damage in rats. Male Sprague-Dawley rats were divided into four groups of six rats in each one; first group served as control. The other groups were treated intraperitoneally with gentamicin alone (100 mg kg(-1) per day) for six successive days, gentamicin for 6 days following 10 days of orally lycopene (4 mg kg(-1) per day) pre-treatment and 6-days of simultaneous lycopene and gentamicin. Biochemical and histopathological examinations were utilized for evaluation of the oxidative stress and renal nephrotoxicity. Creatinine, urea, Na(+) and K(+) levels in plasma and malondialdehyde (MDA), reduced glutathione (GSH) levels and glutathione peroxidase (GSH-Px) and catalase (CAT) activities were determined in kidney tissue. Administration of gentamicin to rats induced a marked renal failure, characterized by a significant increase in plasma creatinine and urea concentrations. The animals treated with gentamicin alone showed a significantly higher kidney MDA and lower GSH-Px and CAT activities but unaffected GSH concentrations when compared with the control group. Pre-treatment with lycopene produced amelioration in biochemical indices of nephrotoxicity in plasma. However, little changes were observed in the kidney MDA and GSH levels and GSH-Px and CAT activities when compared with the gentamicin treated group. The histological structures of the renal proximal tubules showed similar patterns. On the other hand, administration of simultaneous lycopene to rats produced amelioration in MDA and GSH levels and GSH-Px and CAT activities when compared with gentamicin group. In addition, simultaneous lycopene was found to reduce the degree of kidney tissue damage in histopathological

  18. Effect of cyclooxygenase inhibitors on gentamicin-induced nephrotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Hosaka E.M.

    2004-01-01

    Full Text Available The frequent use of nonsteroidal anti-inflammatory drugs (NSAID in combination with gentamicin poses the additional risk of nephrotoxic renal failure. Cyclooxygenase-1 (COX-1 is the main enzyme responsible for the synthesis of renal vasodilator prostaglandins, while COX-2 participates predominantly in the inflammatory process. Both are inhibited by non-selective NSAID such as indomethacin. Selective COX-2 inhibitors such as rofecoxib seem to have fewer renal side effects than non-selective inhibitors. The objective of the present study was to determine whether the combined use of rofecoxib and gentamicin can prevent the increased renal injury caused by gentamicin and indomethacin. Male Wistar rats (250-300 g were treated with gentamicin (100 mg/kg body weight, ip, N = 7, indomethacin (5 mg/kg, orally, N = 7, rofecoxib (1.4 mg/kg, orally, N = 7, gentamicin + rofecoxib (100 and 1.4 mg/kg, respectively or gentamicin + indomethacin (100 and 5 mg/kg, respectively, N = 8 for 5 days. Creatinine clearance and alpha-glutathione-S-transferase concentrations were used as markers of renal injury. Animals were anesthetized with ether and sacrificed for blood collection. The use of gentamicin plus indomethacin led to worsened renal function (0.199 ± 0.019 ml/min, as opposed to the absence of a nephrotoxic effect of rofecoxib when gentamicin plus rofexicob was used (0.242 ± 0.011 ml/min. These results indicate that COX-2-selective inhibitors can be used as an alternative treatment to conventional NSAID, especially in situations in which risk factors for nephrotoxicity are present.

  19. Protective Effects of Houttuynia cordata Thunb. on Gentamicin-induced Oxidative Stress and Nephrotoxicity in Rats

    OpenAIRE

    Kang, Changgeun; Lee, Hyungkyoung; Hah, Do-Yun; Heo, Jung Ho; Kim, Chung Hui; Kim, Euikyung; Kim, Jong Shu

    2013-01-01

    Development of a therapy providing protection from, or reversing gentamicin-sulfate (GS)-induced oxidative stress and nephrotoxicity would be of great clinical significance. The present study was designed to investigate the protective effects of Houttuynia cordata Thunb. (HC) against gentamicin sulfate-induced renal damage in rats. Twenty-eight Sprague-Dawley rats were divided into 4 equal groups as follows: group 1, control; group 2, GS 100 mg/kg/d, intraperitoneal (i.p.) injection; group 3,...

  20. Comparative effect of olive oil and fish oil supplementation in combating gentamicin induced nephrotoxicity in rats

    OpenAIRE

    Rashid, Fouzia; M. Kaleem; Sheema; Bano, B.

    2005-01-01

    The present study is related to the comparative effects of fish oil and olive oil supplementation on gentamicin induced nephrotoxicity in rats. Three treatment groups (Pretrement, Co-treatment and post treatment) were chosen for the study. Nephrotoxicity in rats was induced by intraperitonial administration of gentamicin (80 mg/kg/d) for 3,5,7,10,& 12 consecutive days. The animals were sacrificed 12 hrs after last treatment in each group. The maximum nephrotoxicity was developed on 10 days tr...

  1. Gentamicin susceptibility in Escherichia coli related to the genetic background: problems with breakpoints

    DEFF Research Database (Denmark)

    Jakobsen, L.; Sandvang, D.; Jensen, Vibeke Frøkjær

    2007-01-01

    In total, 120 Escherichia coli isolates positive for one of the gentamicin resistance (GEN(R)) genes aac(3)-II, aac(3)-IV or ant(2 '')-I were tested for gentamicin susceptibility by the agar dilution method. Isolates positive for aac(3)-IV or ant(2 '')-I had an MIC distribution of 8-64 mg/L, wher...... by EUCAST and questions the breakpoint recommended by the CLSI (>= 16 mg/L)....

  2. Protective Effects of Acupuncture Against Gentamicin-Induced Ototoxicity in Rats: Possible Role of Neurotrophin-3

    Science.gov (United States)

    Zhou, Ping; Ma, Weijun; Sheng, Ying; Duan, Maoli; Zhang, Xiaotong

    2017-01-01

    Background The aim of this study was to investigate the protective effects of acupuncture against gentamicin-induced ototoxicity and explore the possible protective role of neurotrophin-3 (NT-3). Material/Methods Twenty-four rats were divided randomly into 4 groups: control group, gentamicin group, neitinggong group, and tinggong group. Rats in the gentamicin, neitinggong, and tinggong groups received intraperitoneal injection of gentamicin (100 mg/kg) for 14 consecutive days. Rats in the neitinggong and tinggong groups further received acupuncture at neitinggong or tinggong acupoints once every 2 days for 20 days. Rats in the control group received intraperitoneal injection of saline. Auditory brainstem response (ABR) was tested in all rats on the day before treatment (day 0), and again on day 14 and day 20 to determine the average threshold value of ABR for each treatment group. The expression of NT-3 in the cochlear nucleus and the inferior colliculus nucleus were detected by immunohistochemical staining. Results The average threshold value of ABR was significantly higher in the gentamicin group as compared with that of the control group on day 14 (P0.05). However, the expression of NT-3 in the inferior colliculus nucleus in both the neitinggong and tinggong groups was significantly higher than that of the gentamicin group (P<0.01). Conclusions A decrease in NT-3 expression in the inferior colliculus nucleus may contribute to gentamicin-induced ototoxicity in rats. Acupuncture at neitinggong or tinggong acupoints effectively improved hearing, which was attributed partially to the rescue of NT-3 expression in the inferior colliculus nucleus. Therefore, preserving NT-3 expression in the auditory system may be a viable strategy to counteract gentamicin-induced ototoxicity. PMID:28121979

  3. Nigella sativa Infusion as an Antioxidant Agent Against Gentamicin-Induced Kidney Damaged in Mice

    Directory of Open Access Journals (Sweden)

    Hamsiah binti Halim

    2014-08-01

    Full Text Available Background: Gentamicin is one of the most common antibiotics related to nephrotoxicity. It has been proposed that the nephrotoxicity is associated with the generation of the reactive oxygen species. Thymoquinone, an active compound of Nigella sativa, shows to have an antioxidant property. The study aims to identify the possible nephroprotective action of Nigella sativa infusion against gentamicin-induced kidney damaged in mice. Methods:This experimental study was carried out in the Department of Cell Biology Laboratory, Universitas Padjadjaran, Bandung from 10th November 2012 to 14th December 2012. There were four groups, each consisting of 6 mice. Group I (control negative, group II (gentamicin 100 mg/kg, group III (3.9 mg Nigella sativa infusion+gentamicin 100mg/kg and group IV (7.8 mg Nigella sativa infusion+gentamicin 100mg/kg. The kidneys were evaluated histopathologically by light microscope. The percentage average number of normal proximal tubules in group I and the percentage average number of proximal tubules damaged in group II, III and IV were measured. Results: The results showed the percentage average number of the proximal tubules damaged in group II, III and IV were 14.53%, 7.49% and 3.94% respectively. Significant differences were observed between group II and III, group II and IV, and group III and IV. Conclusion:Nigella sativa infusion protects against gentamicin-induced kidney damage in mice.

  4. K88 Fimbrial Adhesin Targeting of Microspheres Containing Gentamicin Made with Albumin Glycated with Lactose

    Directory of Open Access Journals (Sweden)

    Andre-i Sarabia-Sainz

    2015-09-01

    Full Text Available The formulation and characterization of gentamicin-loaded microspheres as a delivery system targeting enterotoxigenic Escherichia coli K88 (E. coli K88 was investigated. Glycated albumin with lactose (BSA-glucose-β (4-1 galactose was used as the microsphere matrix (MS-Lac and gentamicin included as the transported antibiotic. The proposed target strategy was that exposed galactoses of MS-Lac could be specifically recognized by E. coli K88 adhesins, and the delivery of gentamicin would inhibit bacterial growth. Lactosylated microspheres (MS-Lac1, MS-Lac2 and MS-Lac3 were obtained using a water-in-oil emulsion, containing gentamicin, followed by crosslinking with different concentrations of glutaraldehyde. Electron microscopy displayed spherical particles with a mean size of 10–17 µm. In vitro release of gentamicin from MS-Lac was best fitted to a first order model, and the antibacterial activity of encapsulated and free gentamicin was comparable. MS-Lac treatments were recognized by plant galactose-specific lectins from Ricinus communis and Sophora japonica and by E. coli K88 adhesins. Results indicate MS-Lac1, produced with 4.2 mg/mL of crosslinker, as the best treatment and that lactosylated microsphere are promising platforms to obtain an active, targeted system against E. coli K88 infections.

  5. Persistence of gentamicin residues in milk after the intramammary treatment of lactating cows for mastitis

    Institute of Scientific and Technical Information of China (English)

    Xun TAN; Ye-wen JIANG; Yi-jun HUANG; Song-hua HU

    2009-01-01

    This study was designed to investigate persistence of gentamicin residues in milk after the intramammary treatment of lactating cows for mastitis. Milk samples were collected at a 1-d interval after the last administration from 34 individual cows that had received intramammary infusions of gentamicin. The doses and treatment times evaluated in this study represented those that have been applied by veterinarians in practice. The tetrazolium chloride assay was used to determine whether there were sig-nificant residues of the antibiotic in the samples. Persistence of detectable drug residues in milk from 33 cows (28 cows, <6 infusions at≤0.7 g gentamicin; and 5 cows, 2 infusions at 0.8 g gentamicin) did not exceed 5 d; but 1 cow (5 infusions at 0.8 g gentamicin) had detectable residues in its milk for 9 d. Our results suggest that a 5-d milk withdrawal period might be insufficient to secure the clearance of the contamination of gentamicin, because treatment times and dosages contribute to the antibiotic clearance. A larger scale of samples are needed for further investigations.

  6. K88 Fimbrial Adhesin Targeting of Microspheres Containing Gentamicin Made with Albumin Glycated with Lactose

    Science.gov (United States)

    Sarabia-Sainz, Andre-i; Sarabia-Sainz, Hector Manuel; Ramos-Clamont Montfort, Gabriela; Mata-Haro, Veronica; Guzman-Partida, Ana María; Guzman, Roberto; Garcia-Soto, Mariano; Vazquez-Moreno, Luz

    2015-01-01

    The formulation and characterization of gentamicin-loaded microspheres as a delivery system targeting enterotoxigenic Escherichia coli K88 (E. coli K88) was investigated. Glycated albumin with lactose (BSA-glucose-β (4-1) galactose) was used as the microsphere matrix (MS-Lac) and gentamicin included as the transported antibiotic. The proposed target strategy was that exposed galactoses of MS-Lac could be specifically recognized by E. coli K88 adhesins, and the delivery of gentamicin would inhibit bacterial growth. Lactosylated microspheres (MS-Lac1, MS-Lac2 and MS-Lac3) were obtained using a water-in-oil emulsion, containing gentamicin, followed by crosslinking with different concentrations of glutaraldehyde. Electron microscopy displayed spherical particles with a mean size of 10–17 µm. In vitro release of gentamicin from MS-Lac was best fitted to a first order model, and the antibacterial activity of encapsulated and free gentamicin was comparable. MS-Lac treatments were recognized by plant galactose-specific lectins from Ricinus communis and Sophora japonica and by E. coli K88 adhesins. Results indicate MS-Lac1, produced with 4.2 mg/mL of crosslinker, as the best treatment and that lactosylated microsphere are promising platforms to obtain an active, targeted system against E. coli K88 infections. PMID:26389896

  7. The Role of Monitoring Gentamicin Levels in Patients with Gram-Negative Peritoneal Dialysis-Associated Peritonitis

    Science.gov (United States)

    Tang, Wen; Cho, Yeoungjee; Hawley, Carmel M.; Badve, Sunil V.; Johnson, David W.

    2014-01-01

    ♦ Background: There is limited available evidence regarding the role of monitoring serum gentamicin concentrations in peritoneal dialysis (PD) patients receiving this antimicrobial agent in gram-negative PD-associated peritonitis. ♦ Methods: Using data collected in all patients receiving PD at a single center who experienced a gram-negative peritonitis episode between 1 January 2005 and 31 December 2011, we investigated the relationship between measured serum gentamicin levels on day 2 following initial empiric antibiotic therapy and subsequent clinical outcomes of confirmed gram-negative peritonitis. ♦ Results: Serum gentamicin levels were performed on day 2 in 51 (77%) of 66 first gram-negative peritonitis episodes. Average serum gentamicin levels on day 2 were 1.83 ± 0.84 mg/L with levels exceeding 2 mg/L in 22 (43%) cases. The overall cure rate was 64%. No cases of ototoxicity were observed. Day-2 gentamicin levels were not significantly different between patients who did and did not have a complication or cure. Using multivariable logistic regression analysis, failure to cure peritonitis was not associated with either day-2 gentamicin level (adjusted odds ratio (OR) 0.96, 95% confidence interval (CI) 0.25 - 3.73) or continuation of gentamicin therapy beyond day 2 (OR 0.28, 0.02 - 3.56). The only exception was polymicrobial peritonitis, where day-2 gentamicin levels were significantly higher in episodes that were cured (2.06 ± 0.41 vs 1.29 ± 0.71, p = 0.01). In 17 (26%) patients receiving extended gentamicin therapy, day-5 gentamicin levels were not significantly related to peritonitis cure. ♦ Conclusion: Day-2 gentamicin levels did not predict gentamicin-related harm or efficacy during short-course gentamicin therapy for gram-negative PD-related peritonitis, except in cases of polymicrobial peritonitis, where higher levels were associated with cure. PMID:24385334

  8. Gentamicin coated iron oxide nanoparticles as novel antibacterial agents

    Science.gov (United States)

    Bhattacharya, Proma; Neogi, Sudarsan

    2017-09-01

    Applications of different types of magnetic nanoparticles for biomedical purposes started a long time back. The concept of surface functionalization of the iron oxide nanoparticles with antibiotics is a novel technique which paves the path for further application of these nanoparticles by virtue of their property of superparamagnetism. In this paper, we have synthesized novel iron oxide nanoparticles surface functionalized with Gentamicin. The average size of the particles, concluded from the HR-TEM images, came to be around 14 nm and 10 nm for unmodified and modified nanoparticles, respectively. The magnetization curve M(H) obtained for these nanoparticles are typical of superparamagnetic nature and having almost zero values of coercivity and remanance. The release properties of the drug coated nanoparticles were studied; obtaining an S shaped profile, indicating the initial burst effect followed by gradual sustained release. In vitro investigations against various gram positive and gram negative strains viz Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Bacillus subtilis indicated significant antibacterial efficiency of the drug-nanoparticle conjugate. The MIC values indicated that a small amount like 0.2 mg ml‑1 of drug capped particles induce about 98% bacterial death. The novelty of the work lies in the drug capping of the nanoparticles, which retains the superparamagnetic nature of the iron oxide nanoparticles and the medical properties of the drug simultaneously, which is found to extremely blood compatible.

  9. Sulforaphane Attenuates Gentamicin-Induced Nephrotoxicity: Role of Mitochondrial Protection

    Science.gov (United States)

    Huerta-Yepez, Sara; Medina-Campos, Omar Noel; Zatarain-Barrón, Zyanya Lucía; Hernández-Pando, Rogelio; Torres, Ismael; Tapia, Edilia; Pedraza-Chaverri, José

    2013-01-01

    Sulforaphane (SFN), an isothiocyanate naturally occurring in Cruciferae, induces cytoprotection in several tissues. Its protective effect has been associated with its ability to induce cytoprotective enzymes through an Nrf2-dependent pathway. Gentamicin (GM) is a widely used antibiotic; nephrotoxicity is the main side effect of this compound. In this study, it was investigated if SFN is able to induce protection against GM-induced nephropathy both in renal epithelial LLC-PK1 cells in culture and in rats. SFN prevented GM-induced death and loss of mitochondrial membrane potential in LLC-PK1 cells. In addition, it attenuated GM-induced renal injury (proteinuria, increases in serum creatinine, in blood urea nitrogen, and in urinary excretion on N-acetyl-β-D-glucosaminidase, and decrease in creatinine clearance and in plasma glutathione peroxidase activity) and necrosis and apoptosis in rats. The apoptotic death was associated with enhanced active caspase-9. Caspase-8 was unchanged in all the studied groups. In addition, SFN was able to prevent GM-induced protein nitration and decrease in the activity of antioxidant enzymes catalase and glutathione peroxidase in renal cortex. In conclusion, the protective effect of SFN against GM-induced acute kidney injury could be associated with the preservation in mitochondrial function that would prevent the intrinsic apoptosis and nitrosative stress. PMID:23662110

  10. Sulforaphane Attenuates Gentamicin-Induced Nephrotoxicity: Role of Mitochondrial Protection

    Directory of Open Access Journals (Sweden)

    Mario Negrette-Guzmán

    2013-01-01

    Full Text Available Sulforaphane (SFN, an isothiocyanate naturally occurring in Cruciferae, induces cytoprotection in several tissues. Its protective effect has been associated with its ability to induce cytoprotective enzymes through an Nrf2-dependent pathway. Gentamicin (GM is a widely used antibiotic; nephrotoxicity is the main side effect of this compound. In this study, it was investigated if SFN is able to induce protection against GM-induced nephropathy both in renal epithelial LLC-PK1 cells in culture and in rats. SFN prevented GM-induced death and loss of mitochondrial membrane potential in LLC-PK1 cells. In addition, it attenuated GM-induced renal injury (proteinuria, increases in serum creatinine, in blood urea nitrogen, and in urinary excretion on N-acetyl-β-D-glucosaminidase, and decrease in creatinine clearance and in plasma glutathione peroxidase activity and necrosis and apoptosis in rats. The apoptotic death was associated with enhanced active caspase-9. Caspase-8 was unchanged in all the studied groups. In addition, SFN was able to prevent GM-induced protein nitration and decrease in the activity of antioxidant enzymes catalase and glutathione peroxidase in renal cortex. In conclusion, the protective effect of SFN against GM-induced acute kidney injury could be associated with the preservation in mitochondrial function that would prevent the intrinsic apoptosis and nitrosative stress.

  11. Therapeutic efficacy of liposome-encapsulated gentamicin in rat Klebsiella pneumoniae pneumonia in relation to impaired host defense and low bacterial susceptibility to gentamicin.

    NARCIS (Netherlands)

    R.M. Schiffelers (Raymond); G. Storm (Gert); M.T. ten Kate (Marian); I.A.J.M. Bakker-Woudenberg (Irma)

    2001-01-01

    textabstractLong-circulating liposomes (LCL) may be used as targeted antimicrobial drug carriers as they localize at sites of infection. As a result, LCL-encapsulated gentamicin (LE-GEN) has demonstrated superior antibacterial activity over the free drug in a single-dos

  12. Activity of daptomycin alone and in combination with rifampin and gentamicin against Staphylococcus aureus assessed by time-kill methodology.

    Science.gov (United States)

    Credito, Kim; Lin, Gengrong; Appelbaum, Peter C

    2007-04-01

    The synergistic effects of daptomycin plus gentamicin or rifampin were tested against 50 Staphylococcus aureus strains, with daptomycin MICs ranging between 0.25 and 8 microg/ml. Daptomycin sub-MICs combined with gentamicin concentrations lower than the MIC yielded synergy in 34 (68%) of the 50 strains. Daptomycin combined with rifampin yielded synergy in one vancomycin-intermediate S. aureus strain only, and virtually all synergy occurred between daptomycin and gentamicin.

  13. Protective effect of quercetin against gentamicin-induced nephrotoxicity in rats.

    Science.gov (United States)

    Abdel-Raheem, Ihab Talat; Abdel-Ghany, Ahmed Ali; Mohamed, Gamal Abdallah

    2009-01-01

    Gentamicin (GM) is an antibiotic widely used in treating severe gram-negative infections. However, its clinical use is limited by its nephrotoxicity. Several lines of evidence indicate that free radicals are important mediators of gentamicin nephrotoxicity. Therefore, the aim of this work was to investigate the possible protective effect of the flavonoid quercetin, an antioxidant, on gentamicin-induced nephrotoxicity. For this purpose, rats were divided into four groups. First group served as a control and injected with the normal saline, second group was injected with quercetin (50 mg/kg/d, per os) for 7 d, third group was injected with gentamicin (80 mg/kg/d, intraperitoneally) for 7 d and the fourth group of animals was injected with quercetin plus gentamicin simultaneously for 7 d. Total protein levels were estimated in 24-h urine samples to assess kidney dysfunction. The rats were sacrificed on the seventh day and kidneys were collected for histopathological studies. Blood urea nitrogen (BUN) and creatinine levels were measured in the blood. Moreover, glutathione (GSH), lipid peroxide (TBARS) levels, superoxide dismutase (SOD) and catalase (CAT) activities were determined in renal tissues. GM-treated rats showed early kidney dysfunction as urinary total protein, BUN and serum creatinine levels were significantly increased. The significant decrease in GSH levels, SOD, CAT activities and increase in TBARS levels, indicated that GM-induced nephrotoxicity was mediated through oxidative stress reactions. Histopathological examination of GM-treated rats revealed degenerative changes in glomeruli and tubules. On the other hand, simultaneous administration of quercetin plus gentamicin protected kidney tissues against nephrotoxic effects of gentamicin as evidenced from amelioration of histopathological changes and normalization of kidney biochemical parameters.

  14. In vitro release and antibacterial activity of poly(oleic/linoleic acid dimer:sebacic acid)-gentamicin

    Institute of Scientific and Technical Information of China (English)

    YANGXiu-Fen; ZHOUZhi-Bin; 等

    2003-01-01

    AIM:To investigate whether poly(oleic/linoleic acid dimer:sebacic acid)-getamicin[Poly(OAD/LOAD:SA)-gentamicin]delivery system was useful to treat chronic osteomyelitis.METHODS:Drug delivery system consisted of gentamicin sufate dispersed in a copolymer containing oleic/linoleic acid dimer(OAD/LOAD)and sebacic acid(SA)in a 1:1 weight ration.The gentamicin releast from[Poly(OAD/LOAD:SA)-gentamicin]was tested in water 0.9% saline,and phosphate buffer 0.1mol/L,RESULTS:The gentamicin concentration peak was found on d2,then slowly decreased.considerable amout of gentamicin was still released on d 50.From d 2 o d 50,the gentamicin concentration in the releasing fluids was from 59 to 42128-fold and 1.8 to 1314-fold of the MIC for Staphylococcus aureus and Escherichia coli,respectively.Staphylococcus aureus and Escherichia coli were strongly inhibited by the releasing fluids for 50d.The gentamicin release and anti-bacterial activity in the three media were similar.only in 0.1mol/L phosphate buffer,from d 2 to 14 it was lower.CONCLUSION:Poly(OAD/LOAD:SA)-gentamicin was useful to treat chronic osteomyelitis.

  15. Teicoplanin plus ciprofloxacin versus gentamicin plus piperacillin in the treatment of febrile neutropenic patients.

    Science.gov (United States)

    Kelsey, S M; Weinhardt, B; Collins, P W; Newland, A C

    1992-06-01

    Teicoplanin plus ciprofloxacin was compared with gentamicin plus piperacillin for the empirical treatment of fever in 80 neutropenic patients. A favourable response was seen in 78% of patients receiving teicoplanin plus ciprofloxacin and in 49% receiving gentamicin plus piperacillin (p less than 0.05). When microbiologically documented episodes were analysed separately, the response to teicoplanin plus ciprofloxacin was favourable in 81% of patients whereas only 35% responded favourably to gentamicin plus piperacillin (p = 0.034). Gram-positive organisms accounted for 76% of bacterial isolates, Staphylococcus epidermidis being the most common pathogen. Ten of 12 (83%) Staphylococcus epidermidis infections resolved when treated with teicoplanin plus ciprofloxacin as compared with 2 of 8 (25%) treated with gentamicin plus piperacillin. Teicoplanin is at least as effective as gentamicin plus piperacillin in the empirical treatment of febrile neutropenic patients and may be more effective in situations where gram-positive organisms are prevalent. The high incidence of gram-positive infections in our unit justifies the use of an agent with specific activity against gram-positive organisms in the first-line antibiotic regimen.

  16. Optimising intraperitoneal gentamicin dosing in peritoneal dialysis patients with peritonitis (GIPD study

    Directory of Open Access Journals (Sweden)

    Lipman Jeffrey

    2009-12-01

    Full Text Available Abstract Background Antibiotics are preferentially delivered via the peritoneal route to treat peritonitis, a major complication of peritoneal dialysis (PD, so that maximal concentrations are delivered at the site of infection. However, drugs administered intraperitoneally can be absorbed into the systemic circulation. Drugs excreted by the kidneys accumulate in PD patients, increasing the risk of toxicity. The aim of this study is to examine a model of gentamicin pharmacokinetics and to develop an intraperitoneal drug dosing regime that maximises bacterial killing and minimises toxicity. Methods/Design This is an observational pharmacokinetic study of consecutive PD patients presenting to the Royal Brisbane and Women's Hospital with PD peritonitis and who meet the inclusion criteria. Participants will be allocated to either group 1, if anuric as defined by urine output less than 100 ml/day, or group 2: if non-anuric, as defined by urine output more than 100 ml/day. Recruitment will be limited to 15 participants in each group. Gentamicin dosing will be based on the present Royal Brisbane & Women's Hospital guidelines, which reflect the current International Society for Peritoneal Dialysis Peritonitis Treatment Recommendations. The primary endpoint is to describe the pharmacokinetics of gentamicin administered intraperitoneally in PD patients with peritonitis based on serial blood and dialysate drug levels. Discussion The study will develop improved dosing recommendations for intraperitoneally administered gentamicin in PD patients with peritonitis. This will guide clinicians and pharmacists in selecting the most appropriate dosing regime of intraperitoneal gentamicin to treat peritonitis. Trial Registration ACTRN12609000446268

  17. Grape seed extract prevents gentamicin-induced nephrotoxicity and genotoxicity in bone marrow cells of mice.

    Science.gov (United States)

    El-Ashmawy, Ibrahim M; El-Nahas, Abeer F; Salama, Osama M

    2006-09-01

    The protection conferred by grape seed extract against gentamicin-induced nephrotoxicity and bone marrow chromosomal aberrations have been evaluated in adult Swiss albino mice. The activity of reduced glutathione peroxidase (GSH peroxidase), the levels of glutathione (GSH) and lipid peroxidation as malondialdehyde (MDA) in the kidneys homogenates, serum urea and creatinine were measured, and in addition the changes in kidney histology and bone marrow chromosomes were investigated. Gentamicin (80 mg/kg b.wt. intraperitoneally for 2 weeks) induced kidney damage as indicated from a pronounced changes in kidney histology, a significant increase in serum urea and creatinine and MDA content in the kidney homogenate. While the activity of the antioxidant enzyme GSH peroxidase and the level of GSH were significantly decreased. Gentamicin induced genotoxicity indicated by increased the number of aberrant cells and different types of structural chromosomal aberrations (fragment, deletion and ring chromosome) and showed no effect on mitotic activity of the cell. Pretreatment with grape seed extract (7 days) and simultaneously (14 days) with gentamicin significantly protected the kidney tissue by ameliorating its antioxidant activity. Moreover, grape seed extract significantly protected bone marrow chromosomes from gentamicin induced genotoxicity by reducing the total number of aberrant cells, and different types of structural chromosomal aberrations. It could be concluded that grape seed extract acts as a potent antioxidant prevented kidney damage and genotoxicity of bone marrow cells.

  18. Intramammary treatment with gentamicin in lactating cows with clinical and subclinical mastitis

    Directory of Open Access Journals (Sweden)

    Thamires Martins

    2016-04-01

    Full Text Available Abstract The study evaluated the microbiological profile of milk samples collected before and after mastitis treatment with gentamicin and investigated biofilms production and antimicrobial susceptibility of Staphylococcus spp. isolated. The presence of gentamicin residues in milk after the recommended withdrawal period was also evaluated. Antimicrobial residues were analyzed by Delvotest® SP NT over a period of 12 days beginning after 24 hours the last gentamicin application. Some of Staphylococcus spp. isolates were biofilm producers (19.05%. Staphylococcus spp. showed high levels of resistance to neomycin (16.95%, penicillin G (10.17%, and ampicillin (10.17%. Multidrug resistance to all antibiotics tested was observed in 1.69% of the Staphylococcus spp. isolates. Among 1440 mammary quarter milk samples 24.95% presented gentamicin residues after the withdrawal period. Gentamicin residues were also detected in 3.8% of samples from calibrated glass recorder jar (n=383 4.1 days after treatment. The indiscriminate use of antibiotics may lead to the emergence of multidrug-resistant strains as well as increasing the risk of presence of residues of these drugs in milk. These problems affect the milk quality and may become a public health problem.

  19. Bactericidal Effect of Pterostilbene Alone and in Combination with Gentamicin against Human Pathogenic Bacteria

    Directory of Open Access Journals (Sweden)

    Wee Xian Lee

    2017-03-01

    Full Text Available The antibacterial activity of pterostilbene in combination with gentamicin against six strains of Gram-positive and Gram-negative bacteria were investigated. The minimum inhibitory concentration and minimum bactericidal concentration of pterostilbene were determined using microdilution technique whereas the synergistic antibacterial activities of pterostilbene in combination with gentamicin were assessed using checkerboard assay and time-kill kinetic study. Results of the present study showed that the combination effects of pterostilbene with gentamicin were synergistic (FIC index < 0.5 against three susceptible bacteria strains: Staphylococcus aureus ATCC 25923, Escherichia coli O157 and Pseudomonas aeruginosa 15442. However, the time-kill study showed that the interaction was indifference which did not significantly differ from the gentamicin treatment. Furthermore, time-kill study showed that the growth of the tested bacteria was completely attenuated with 2 to 8 h treatment with 0.5 × MIC of pterostilbene and gentamicin. The identified combinations could be of effective therapeutic value against bacterial infections. These findings have potential implications in delaying the development of bacterial resistance as the antibacterial effect was achieved with the lower concentrations of antibacterial agents.

  20. Bactericidal Effect of Pterostilbene Alone and in Combination with Gentamicin against Human Pathogenic Bacteria.

    Science.gov (United States)

    Lee, Wee Xian; Basri, Dayang Fredalina; Ghazali, Ahmad Rohi

    2017-03-17

    The antibacterial activity of pterostilbene in combination with gentamicin against six strains of Gram-positive and Gram-negative bacteria were investigated. The minimum inhibitory concentration and minimum bactericidal concentration of pterostilbene were determined using microdilution technique whereas the synergistic antibacterial activities of pterostilbene in combination with gentamicin were assessed using checkerboard assay and time-kill kinetic study. Results of the present study showed that the combination effects of pterostilbene with gentamicin were synergistic (FIC index < 0.5) against three susceptible bacteria strains: Staphylococcus aureus ATCC 25923, Escherichia coli O157 and Pseudomonas aeruginosa 15442. However, the time-kill study showed that the interaction was indifference which did not significantly differ from the gentamicin treatment. Furthermore, time-kill study showed that the growth of the tested bacteria was completely attenuated with 2 to 8 h treatment with 0.5 × MIC of pterostilbene and gentamicin. The identified combinations could be of effective therapeutic value against bacterial infections. These findings have potential implications in delaying the development of bacterial resistance as the antibacterial effect was achieved with the lower concentrations of antibacterial agents.

  1. Chitosan improves anti-biofilm efficacy of gentamicin through facilitating antibiotic penetration.

    Science.gov (United States)

    Mu, Haibo; Guo, Fan; Niu, Hong; Liu, Qianjin; Wang, Shunchun; Duan, Jinyou

    2014-12-03

    Antibiotic overuse is one of the major drivers in the generation of antibiotic resistant "super bugs" that can potentially cause serious effects on health. In this study, we reported that the polycationic polysaccharide, chitosan could improve the efficacy of a given antibiotic (gentamicin) to combat bacterial biofilms, the universal lifestyle of microbes in the world. Short- or long-term treatment with the mixture of chitosan and gentamicin resulted in the dispersal of Listeria monocytogenes (L. monocytogenes) biofilms. In this combination, chitosan with a moderate molecular mass (~13 kDa) and high N-deacetylation degree (~88% DD) elicited an optimal anti-biofilm and bactericidal activity. Mechanistic insights indicated that chitosan facilitated the entry of gentamicin into the architecture of L. monocytogenes biofilms. Finally, we showed that this combination was also effective in the eradication of biofilms built by two other Listeria species, Listeria welshimeri and Listeria innocua. Thus, our findings pointed out that chitosan supplementation might overcome the resistance of Listeria biofilms to gentamicin, which might be helpful in prevention of gentamicin overuse in case of combating Listeria biofilms when this specific antibiotic was recommended.

  2. Chitosan Improves Anti-Biofilm Efficacy of Gentamicin through Facilitating Antibiotic Penetration

    Directory of Open Access Journals (Sweden)

    Haibo Mu

    2014-12-01

    Full Text Available Antibiotic overuse is one of the major drivers in the generation of antibiotic resistant “super bugs” that can potentially cause serious effects on health. In this study, we reported that the polycationic polysaccharide, chitosan could improve the efficacy of a given antibiotic (gentamicin to combat bacterial biofilms, the universal lifestyle of microbes in the world. Short- or long-term treatment with the mixture of chitosan and gentamicin resulted in the dispersal of Listeria monocytogenes (L. monocytogenes biofilms. In this combination, chitosan with a moderate molecular mass (~13 kDa and high N-deacetylation degree (~88% DD elicited an optimal anti-biofilm and bactericidal activity. Mechanistic insights indicated that chitosan facilitated the entry of gentamicin into the architecture of L. monocytogenes biofilms. Finally, we showed that this combination was also effective in the eradication of biofilms built by two other Listeria species, Listeria welshimeri and Listeria innocua. Thus, our findings pointed out that chitosan supplementation might overcome the resistance of Listeria biofilms to gentamicin, which might be helpful in prevention of gentamicin overuse in case of combating Listeria biofilms when this specific antibiotic was recommended.

  3. Gentamicin binds to the megalin receptor as a competitive inhibitor using the common ligand binding motif of complement type repeats: insight from the nmr structure of the 10th complement type repeat domain alone and in complex with gentamicin

    NARCIS (Netherlands)

    Dagil, R.; O'Shea, C.; Nykjaer, A.; Bonvin, A.M.J.J.; Kragelund, B.B.

    2013-01-01

    Gentamicin is an aminoglycoside widely used in treatments of, in particular, enterococcal, mycobacterial, and severe Gram-negative bacterial infections. Large doses of gentamicin cause nephrotoxicity and ototoxicity, entering the cell via the receptor megalin. Until now, no structural information ha

  4. The development of an injection-molding process for a polyanhydride implant containing gentamicin sulfate.

    Science.gov (United States)

    Deng, Jone-Shin; Meisters, Marts; Li, Luk; Setesak, Jeff; Claycomb, Lee; Tian, Youqin; Stephens, Dennis; Widman, Matt

    2002-01-01

    A production-scale manufacturing process has been developed for polyanhydride/gentamicin sulfate implants for the treatment of osteomyelitis. Gentamicin sulfate was first dried to an acceptable moisture level by using a tumble vacuum dryer. Dried gentamicin sulfate powder and polyanhydride granules were separately fed into the twin-screw extruder at a pre-determined metering rate using a gravimetric feeding device. The extruded molten mixture was solidified to form strands which were subsequently cut into pellets by using a pelletizer. The pellets were characterized with respect to copolymer molecular weight and drug content uniformity. The pellets were later fed into production-scale injection-molding equipment for implant fabrication. The injection-molding cycle was developed and evaluated in terms of cycle reproducibility. Implants were tested and shown to yield an oriented skin-core structure exhibiting a desirable in-vitro drug release profile.

  5. Development of a Multicommutated Flow System with Chemiluminometric Detection for Quantification of Gentamicin in Pharmaceuticals

    Science.gov (United States)

    Santos, Lúcia H. M. L. M.; Araújo, A. N.; Reis, Boaventura; Montenegro, M. C. B. S. M.

    2010-01-01

    A new flow procedure based on multicommutation with chemiluminometric detection was developed to quantify gentamicin sulphate in pharmaceutical formulations. This approach is based on gentamicin's ability to inhibit the chemiluminometric reaction between luminol and hypochlorite in alkaline medium, causing a decrease in the analytical signal. The inhibition of the analytical signal is proportional to the concentration of gentamicin sulphate, within a linear range of 1 to 4 μg mL−1 with a coefficient variation <3%. A sample throughput of 55 samples h−1 was obtained. The developed method is sensitive, simple, with low reagent consumption, reproducible, and inexpensive, and when applied to the analysis of pharmaceutical formulations (eye drops and injections) it gave results with RSD between 1.10 and 4.40%. PMID:20981343

  6. Gentamicin tissue concentration in various avian species following recommended dosage therapy

    Science.gov (United States)

    Bush, M.; Locke, D.; Neal, L.A.; Carpenter, J.W.

    1981-01-01

    Plasma and tissue drug concentrations were compared in eastern bobwhite quail (Colinus virginianus virginianus) and pigeons (Columba livia) given gentamicin by IM administration at the dosage of 10 mg/kg, and in greater sandhill cranes (Grus canadensis tabida) and hybrid rosybill ducks (Netta sp) given the same antibiotic at a dosage of 5 mg/kg. Quail and cranes had significantly higher liver concentrations of gentamicin at 6 hours after injection than did pigeons and ducks. Cranes had significantly higher plasma concentrations than did ducks at 6 hours after injection. Compared with plasma values, gentamicin concentrations were significantly higher in the liver of cranes at 12 hours after injection, and in the kidneys at 18 hours.

  7. Toxic Anterior Segment Syndrome following Phacoemulsification Secondary to Overdose of Intracameral Gentamicin

    Directory of Open Access Journals (Sweden)

    Yaran Koban

    2014-01-01

    Full Text Available Objective. To report a case of toxic anterior segment syndrome (TASS that was caused by inadvertent anterior chamber and cornea stromal injection with high dose gentamicin following cataract surgery. Methods. Case report. Results. We report a 72-year-old female patient who developed TASS that was caused by high dose gentamicin (20 mg/0.5 mL, which was inadvertently used during the formation of the anterior chamber and hydration of the corneal incision. Unlike previous cases, hyphema and hemorrhagic fibrinous reaction were seen in the anterior chamber. Despite treatment, bullous keratopathy developed and penetrating keratoplasty was performed. The excised corneal button was sent for histopathological examination. Conclusions. Subconjunctival gentamicin is highly toxic to the corneal endothelium and anterior chamber structures. Including it on the surgical table carries a potentially serious risk for contamination of the anterior chamber.

  8. Toxic Anterior Segment Syndrome following Phacoemulsification Secondary to Overdose of Intracameral Gentamicin

    Science.gov (United States)

    Koban, Yaran; Genc, Selim; Cagatay, Halil Huseyin; Ekinci, Metin; Gecer, Melin; Yazar, Zeliha

    2014-01-01

    Objective. To report a case of toxic anterior segment syndrome (TASS) that was caused by inadvertent anterior chamber and cornea stromal injection with high dose gentamicin following cataract surgery. Methods. Case report. Results. We report a 72-year-old female patient who developed TASS that was caused by high dose gentamicin (20 mg/0.5 mL), which was inadvertently used during the formation of the anterior chamber and hydration of the corneal incision. Unlike previous cases, hyphema and hemorrhagic fibrinous reaction were seen in the anterior chamber. Despite treatment, bullous keratopathy developed and penetrating keratoplasty was performed. The excised corneal button was sent for histopathological examination. Conclusions. Subconjunctival gentamicin is highly toxic to the corneal endothelium and anterior chamber structures. Including it on the surgical table carries a potentially serious risk for contamination of the anterior chamber. PMID:25574173

  9. Production of biocompatible and antimicrobial bacterial cellulose polymers functionalized by RGDC grafting groups and gentamicin.

    Science.gov (United States)

    Rouabhia, Mahmoud; Asselin, Jérémie; Tazi, Neftaha; Messaddeq, Younès; Levinson, Dennis; Zhang, Ze

    2014-02-12

    Bacterial cellulose (BC), a three-dimensional fibril, is a natural polymer that can be used for many applications. BC effectiveness may be improved by enhancing surface characteristics contributing to a better physiologic interaction with human and animal cells and to intrinsically present antimicrobial agents. In the present study, gentamicin-activated BC membranes were obtained by chemically grafting RGDC peptides (R: arginine; G: glycine; D: aspartic acid; C: cysteine) using coupling agent 3-aminopropyltriethoxysilane (APTES) followed by covalent attachment of gentamicin onto the surface of the BC membrane network. X-ray photoelectron spectroscopy (XPS) analyses showed that the BC-APTES contained 0.7% of silicon in terms of elemental composition, corresponding to a grafting ratio of 1:12. The presence of silicon and nitrogen in the BC-APTES confirmed the surface functionalization of the BC membrane. Fourier-transform infrared (FTIR) analyses show the formation of the secondary amide as supported by the valence bond C═O (ν(C═O)), a characteristic vibrational transition at 1650 cm(-1) which is particularly intense with the BC-RGDC-gentamicin membrane. Energy-dispersive X-ray (EDX) analyses showed a low level of carbon and nitrogen (C + N) in pure BC but a high level of (C + N) in BC-RGDC-gentamicin confirming the surface modification of the BC membrane by RGDC and gentamicin enrichment. Of great interest, the gentamicin-RGDC-grafted BC membranes are bactericidal against Streptococcus mutans but nontoxic to human dermal fibroblasts and thus may be useful for multiple applications such as improved wound healing and drug delivery systems.

  10. Efficacies of gentamicin-loaded magnetite block ionomer complexes against chronic Brucella melitensis infection

    Science.gov (United States)

    Jain-Gupta, Neeta; Pothayee, Nipon; Pothayee, Nikorn; Tyler, Ronald; Caudell, David L.; Balasubramaniam, Sharavanan; Hu, Nan; Davis, Richey M.; Riffle, Judy S.; Sriranganathan, Nammalwar

    2013-11-01

    Anionic copolymers can enable intracellular delivery of cationic drugs which otherwise cannot cross cell membrane barriers. We tested the efficacy of gentamicin-loaded magnetite block ionomer complexes (MBICs) against intracellular Brucella melitensis. Anionic block copolymers were used to coat nanomagnetite through adsorption of a portion of anions on the particle surfaces, then the remaining anions were complexed with 30-32 weight percentage of gentamicin. The zeta potential changed from -39 to -13 mV after encapsulation of the drug with complementary charge. The gentamicin-loaded MBICs had intensity average hydrodynamic diameters of 62 nm, while the polymer-coated nanomagnetite particles without drug were 34 nm in size. No toxicity as measured by a MTS assay was observed upon incubation of the MBICs with J774A.1 murine macrophage-like cells. Confocal microscopic images showed that the MBICs were taken up by the macrophages and distributed in the cell cytoplasm and endosomal/lysosomal compartments. Upon treatment with gentamicin-loaded MBICs (3.5 Log10), B. melitensis-infected macrophages showed significantly higher clearance of Brucella compared to the treatment with free g (0.9 Log10). Compared to doxycycline alone, a combination of doxycycline and gentamicin (either free or encapsulated in MBICs) showed significantly higher clearance of B. melitensis from chronically infected mice. Histopathological examination of kidneys from the MBICs-treated mice revealed multifocal infiltration of macrophages containing intracytoplasmic iron (MBICs) in peri-renal adipose. Although MBICs showed similar efficacy as free gentamicin against Brucella in mice, our strategy presents an effective way to deliver higher loads of drugs intracellularly and ability to study the bio-distribution of drug carriers.

  11. Efficacies of gentamicin-loaded magnetite block ionomer complexes against chronic Brucella melitensis infection

    Energy Technology Data Exchange (ETDEWEB)

    Jain-Gupta, Neeta [Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Department of Biomedical Sciences and Pathobiology (United States); Pothayee, Nipon; Pothayee, Nikorn [Virginia Polytechnic Institute and State University, Macromolecules and Interfaces Institute (United States); Tyler, Ronald; Caudell, David L. [Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Department of Biomedical Sciences and Pathobiology (United States); Balasubramaniam, Sharavanan; Hu, Nan; Davis, Richey M.; Riffle, Judy S. [Virginia Polytechnic Institute and State University, Macromolecules and Interfaces Institute (United States); Sriranganathan, Nammalwar, E-mail: nathans@vt.edu [Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Department of Biomedical Sciences and Pathobiology (United States)

    2013-11-15

    Anionic copolymers can enable intracellular delivery of cationic drugs which otherwise cannot cross cell membrane barriers. We tested the efficacy of gentamicin-loaded magnetite block ionomer complexes (MBICs) against intracellular Brucella melitensis. Anionic block copolymers were used to coat nanomagnetite through adsorption of a portion of anions on the particle surfaces, then the remaining anions were complexed with 30–32 weight percentage of gentamicin. The zeta potential changed from −39 to −13 mV after encapsulation of the drug with complementary charge. The gentamicin-loaded MBICs had intensity average hydrodynamic diameters of 62 nm, while the polymer-coated nanomagnetite particles without drug were 34 nm in size. No toxicity as measured by a MTS assay was observed upon incubation of the MBICs with J774A.1 murine macrophage-like cells. Confocal microscopic images showed that the MBICs were taken up by the macrophages and distributed in the cell cytoplasm and endosomal/lysosomal compartments. Upon treatment with gentamicin-loaded MBICs (3.5 Log{sub 10}), B. melitensis-infected macrophages showed significantly higher clearance of Brucella compared to the treatment with free g (0.9 Log{sub 10}). Compared to doxycycline alone, a combination of doxycycline and gentamicin (either free or encapsulated in MBICs) showed significantly higher clearance of B.melitensis from chronically infected mice. Histopathological examination of kidneys from the MBICs-treated mice revealed multifocal infiltration of macrophages containing intracytoplasmic iron (MBICs) in peri-renal adipose. Although MBICs showed similar efficacy as free gentamicin against Brucella in mice, our strategy presents an effective way to deliver higher loads of drugs intracellularly and ability to study the bio-distribution of drug carriers.

  12. Gentamicin coating of plasma chemical oxidized titanium alloy prevents implant-related osteomyelitis in rats.

    Science.gov (United States)

    Diefenbeck, M; Schrader, C; Gras, F; Mückley, T; Schmidt, J; Zankovych, S; Bossert, J; Jandt, K D; Völpel, A; Sigusch, B W; Schubert, H; Bischoff, S; Pfister, W; Edel, B; Faucon, M; Finger, U

    2016-09-01

    Implant related infection is one of the most feared and devastating complication associated with the use of orthopaedic implant devices. Development of anti-infective surfaces is the main strategy to prevent implant contamination, biofilm formation and implant related osteomyelitis. A second concern in orthopaedics is insufficient osseointegration of uncemented implant devices. Recently, we reported on a macroporous titanium-oxide surface (bioactive TiOB) which increases osseointegration and implant fixation. To combine enhanced osseointegration and antibacterial function, the TiOB surfaces were, in addition, modified with a gentamicin coating. A rat osteomyelitis model with bilateral placement of titanium alloy implants was employed to analyse the prophylactic effect of gentamicin-sodiumdodecylsulfate (SDS) and gentamicin-tannic acid coatings in vivo. 20 rats were randomly assigned to four groups: (A) titanium alloy; PBS inoculum (negative control), (B) titanium alloy, Staphylococcus aureus inoculum (positive control), (C) bioactive TiOB with gentamicin-SDS and (D) bioactive TiOB plus gentamicin-tannic acid coating. Contamination of implants, bacterial load of bone powder and radiographic as well as histological signs of implant-related osteomyelitis were evaluated after four weeks. Gentamicin-SDS coating prevented implant contamination in 10 of 10 tibiae and gentamicin-tannic acid coating in 9 of 10 tibiae (infection prophylaxis rate 100% and 90% of cases, respectively). In Group (D) one implant showed colonisation of bacteria (swab of entry point and roll-out test positive for S. aureus). The interobserver reliability showed no difference in the histologic and radiographic osteomyelitis scores. In both gentamicin coated groups, a significant reduction of the histological osteomyelitis score (geometric mean values: C = 0.111 ± 0.023; D = 0.056 ± 0.006) compared to the positive control group (B: 0.244 ± 0.015; p < 0.05) was observed. The

  13. Floral extract ofTecoma stans:A potent inhibitor of gentamicin-induced nephrotoxicityin vivo

    Institute of Scientific and Technical Information of China (English)

    Raju S; Kavimani S; Uma Maheshwara rao V; Sreeramulu Reddy K; Vasanth Kumar G

    2011-01-01

    Objective:To highlight the nephroprotective activity of ethyl acetate extract of dried flowers ofTecoma stans for its protective effects on gentamicin-induced nephrotoxicity in albino rats. Methods:For studying acute toxicity study, single oral dose of5 000 mg ethyl acetate floral extract/kg body weight was administered to albino rats (five females, five males). Nephrotoxicity was induced in albino rats by intraperitoneal administration of gentamicin80 mg/kg/day for eight days. Effect of concurrent administration of ethyl acetate floral extract of Tecoma stans at a dose of 100, 200 and 300 mg/kg/day given by oral route was determined using serumcreatinine, serum uric acid, blood urea nitrogen and serum urea as indicators of kidney damage. The study groups contained six rats in each group. As nephrotoxicity of gentamicin is known to involve induction of oxidative stress,in vitro antioxidant activity and free radical-scavenging activity of this extract was also evaluated.Results:For acute toxicity testing both female and male rats administered with the extract at a dose of5 000mg/kg. The results showed no toxicity in terms of general behavior change, mortality, or change in gross appearance of internal organs (LD50 > 5 000 mg/kg). It was observed that the ethyl acetate floral extract ofTecoma stans significantly protected rat kidneys from gentamicin-induced histopathological changes. Gentamicin-induced glomerular congestion, peritubular and blood vessel congestion, epithelial desquamation, accumulation of inflammatory cells and necrosis of the kidney cells were found to be reduced in the groups receiving the ethyl acetate floral extract ofTecoma stans along with gentamicin in a dose dependent manner. The floral extract also reduced the gentamicin-induced increase in serum creatinine, serum uric acid, blood urea nitrogen and serum urea levels (P>0.01).Conclusions:The present study indicates a very important role of reactive oxygen species (ROS)and the relation to

  14. An Antioxidant Screen Identifies Candidates for Protection of Cochlear Hair Cells from Gentamicin Toxicity

    Directory of Open Access Journals (Sweden)

    Volker Noack

    2017-08-01

    Full Text Available Reactive oxygen species are important elements in ototoxic damage to hair cells (HCs, appearing early in the damage process. Higher levels of natural antioxidants are positively correlated with resistance to ototoxins and many studies have shown that exogenous antioxidants can protect HCs from damage. While a very wide variety of antioxidants with different characteristics and intracellular targets exist, most ototoxicity studies have focused upon one or a few well-characterized compounds. Relatively little research has attempted to determine the comparative efficacy of large variety of different antioxidants. This has been in part due to the lack of translation between cell culture and in vivo measures of efficacy. To circumvent this limitation, we used an in vitro assay based on micro-explants from the basal and middle turns of the neonatal mouse organ of Corti to screen a commercial redox library of diverse antioxidant compounds for their ability to protect mammalian HCs from a high dose of the ototoxic antibiotic gentamicin. The library included several antioxidants that have previously been studied as potential treatments for HC damage, as well as many antioxidants that have never been applied to ototoxicity. The micro-explants were treated with 200 μM gentamicin alone, gentamicin plus one of three dosages of a redox compound, the highest dosage of compound alone, or were untreated. HC counts were determined before the gentamicin insult and at 1, 2, and 3 days afterward to evaluate the HC survival. From a total of 81 antioxidant compounds, 13 exhibited significant protection of HCs. These included members of a variety of antioxidant classes with several novel antioxidants, not previously tested on HCs, appearing to alleviate the damaging gentamicin effect. Some compounds previously shown to be protective of HCs were correspondingly protective in this in vitro screen, while others were not. Finally, one of the three pro-oxidant compounds

  15. Auditory function after continuous infusion of gentamicin to high-risk newborns

    DEFF Research Database (Denmark)

    Colding, H; Andersen, E A; Prytz, S;

    1989-01-01

    Audiometry was performed at four years of age in 69 of 105 surviving children who had received continuous intravenous infusion of gentamicin during neonatal intensive care. A hearing loss of 20 dB was found in 2 of them (3%), corresponding to that shown in other studies of survivors following...... neonatal intensive care. Free field audiometry performed in another 7 children and questionnaires returned from 13 of the remaining 29 gave no suspicion of hearing loss. Thus there is no indication that continuous 24 hours intravenous infusion of gentamicin causes more hearing impairment than intermittent...

  16. Effect of sepsis and systemic inflammatory response syndrome on neonatal hearing screening outcomes following gentamicin exposure.

    Science.gov (United States)

    Cross, Campbell P; Liao, Selena; Urdang, Zachary D; Srikanth, Priya; Garinis, Angela C; Steyger, Peter S

    2015-11-01

    Hearing loss in neonatal intensive care unit (NICU) graduates range from 2% to 15% compared to 0.3% in full-term births, and the etiology of this discrepancy remains unknown. The majority of NICU admissions receive potentially ototoxic aminoglycoside therapy, such as gentamicin, for presumed sepsis. Endotoxemia and inflammation are associated with increased cochlear uptake of aminoglycosides and potentiated ototoxicity in mice. We tested the hypothesis that sepsis or systemic inflammatory response syndrome (SIRS) and intravenous gentamicin exposure increases the risk of hearing loss in NICU admissions. The Institutional Review Board at Oregon Health & Science University (OHSU) approved this study design. Two hundred and eight infants met initial criteria, and written, informed consent were obtained from parents or guardians of 103 subjects ultimately enrolled in this study. Prospective data from 91 of the enrolled subjects at OHSU Doernbecher Children's Hospital Neonatal Care Center were processed. Distortion product otoacoustic emissions (DPOAEs; f2 frequency range: 2063-10,031 Hz) were obtained prior to discharge to assess auditory performance. To pass the DPOAE screen, normal responses in >6 of 10 frequencies in both ears were required; otherwise the subject was considered a "referral" for a diagnostic hearing evaluation after discharge. Cumulative dosing data and diagnosis of neonatal sepsis or SIRS were obtained from OHSU's electronic health record system, and the data processed to obtain risk ratios. Using these DPOAE screening criteria, 36 (39.5%) subjects would be referred. Seventy-four (81%) subjects had intravenous gentamicin exposure. Twenty (22%) had ≥4 days of gentamicin, and 71 (78%) had sepsis or met neonatal SIRS criteria, 9 of whom had ≥5 days of gentamicin and a DPOAE referral risk ratio of 2.12 (p=0.02) compared to all other subjects. Combining subjects with either vancomycin or furosemide overlap with gentamicin treatment yielded an almost

  17. Community Acquisition of Gentamicin-Sensitive Methicillin-Resistant Staphylococcus aureus in Southeast Queensland, Australia

    OpenAIRE

    Nimmo, Graeme R.; Schooneveldt, Jacqueline; O'Kane, Gabrielle; McCall, Brad; Vickery, Alison

    2000-01-01

    Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) susceptible to gentamicin has been reported in a number of countries in the 1990s. To study the acquisition of gentamicin-sensitive MRSA (GS-MRSA) in southeast Queensland and the relatedness of GS-MRSA to other strains of MRSA, 35 cases of infection due to GS-MRSA from October 1997 through September 1998 were examined retrospectively to determine the mode of acquisition and risk factors for MRSA acquisition. Thirty-one isol...

  18. Effects of gentamicin on choline acetyltransferase expression in paraolivary nucleus neurons of guinea pigs

    Institute of Scientific and Technical Information of China (English)

    Mingguang Zhao; Xiaochen Wang; Yong Liang; Peng Xie; Xuejun Guo; Jinjiang Li; Wei Wang

    2008-01-01

    BACKGROUND: It is generally accepted that gentamicin can damage the cochlear nerve and acoustic nerve. In recent years, scholars have focused on neuronal changes and neurochemical information in the brainstem primary auditory center. OBJECTIVE: To explore morphological changes of choline acetyltransferase (ChAT)-positive neurons in the paraolivary nucleus (PON) of guinea pigs, and the effect on hearing following gentamicin injection. DESIGN, TIME AND SETTING: Randomized grouping and morphological observational study was performed at Animal Experimental Center of General Hospital of Shenyang Military Area Command of Chinese PLA from January to August 2007. MATERIALS: A total of 48 healthy guinea pigs were randomly divided into model (n = 40) and control (n = 8) groups. The model group was divided into five subgroups at five time points of I and 3 days, 1, 2, and 3 weeks. METHODS: Guinea pigs in the model group were intraperitoneally injected with gentamicin, and those in the control group were intraperitoneally injected with the same volume of saline. MAIN OUTCOME MEASURES: Auditory brainstem-evoked potential was used to record auditory threshold; distribution and morphological changes of ChAT-positive neurons in the PON were observed with immunohistochemistry; section area and gray value of ChAT-positive neurons were measured with Quantimet 570 image-analyzing system. RESULTS: ChAT-positive neurons were diffusedly distributed in the PON. The majority was composed of large, round cells, with positive neurites that could be clearly observed. Following gentamicin injection, the positive neurons displayed an irregular outline, and their neurites began to shorten and disappear. The gray value increased with prolonged gentamicin administration (P < 0.05). In addition, the somatic cross-sectional area was enlarged in the model group at 1 and 3 days after injection (P < 0.05), whereas cell number significantly decreased at three weeks after injection (P < 0.05). Starting

  19. Effect of Tephrosia purpurea (L.) Pers. Leaves on Gentamicin-Induced Nephrotoxicity in Rats

    OpenAIRE

    JAIN, Avijeet; NAHATA, Alok; SINGHAI, Abhay

    2013-01-01

    The aim of the study was to evaluate the nephroprotective and nephrocurative effects of Tephrosia purpurea (L.) Pers. leaves against gentamicin-induced acute renal injury in albino rats. The maximum free radical scavenging activity of the ethanolic extract was the basis for the selection of this extract for the in vivo study. Gentamicin (40 mg/kg, s.c.) was administered to induce toxicity in the toxic group and the ethanolic extract (200 mg/kg p.o.) was administered in all treated groups. Blo...

  20. Chemopreventive role of Coriandrum sativum against gentamicin-induced renal histopathological damage in rats

    Directory of Open Access Journals (Sweden)

    Lakhera Abhijeet

    2015-06-01

    Full Text Available Drug induced nephrotoxicity is one of the most common causes of renal failure. Gentamicin belongs to aminoglycosides, which elicit nephrotoxic potential. Natural antioxidants from plants demonstrate a number of biotherapeutic activities. Coriander is an important medicinal plant known for its hepatoprotective, diuretic, carminative, digestive and antihelminthic potential. This study was designed to investigate whether the extract of Coriandrum sativum ameliorates the nephrotoxicity induced by gentamicin in rats. Dried coriander powder was coarsely grinded and subjected to defatting by petroleum ether and further with ethyl acetate. The extract was filtered and subjected to phytochemical and phytoanalytical studies.

  1. Kinetics and dose calculations of ampicillin and gentamicin given as continuous intravenous infusion during parenteral nutrition in 88 newborn infants

    DEFF Research Database (Denmark)

    Colding, H; Møller, S; Bentzon, M W

    1983-01-01

    Ampicillin and gentamicin were administered continuously intravenously to 88 newborn infants using individually calculated dosages. For infants with a mean value of plasma clearance of the antibiotics, it was calculated that the serum ampicillin and gentamicin concentrations would be between 35...

  2. Kinetics and dose calculations of ampicillin and gentamicin given as continuous intravenous infusion during parenteral nutrition in 88 newborn infants

    DEFF Research Database (Denmark)

    Colding, H; Møller, S; Bentzon, M W

    1983-01-01

    Ampicillin and gentamicin were administered continuously intravenously to 88 newborn infants using individually calculated dosages. For infants with a mean value of plasma clearance of the antibiotics, it was calculated that the serum ampicillin and gentamicin concentrations would be between 35-5...

  3. Carissa carandas Linn. fruit extract ameliorates gentamicin-induced nephrotoxicity in rats via attenuation of oxidative stress

    Institute of Scientific and Technical Information of China (English)

    Jayesh B. Dhodi; Deepavali R. Thanekar; Snehal N. Mestry; Archana R. Juvekar

    2015-01-01

    Objective: To elucidate the mechanism of action of methanolic extract of Carissa carandas fruits (MCCF) in attenuation of diabetic nephropathy using gentamicin induced nephrotoxicity model.Methods:Extract was daily administered to Sprague Dawley rats at doses of 100, 200 and 400 mg/kg for 8 days along with intramuscular injection of gentamicin (80 mg/kg). After completion of the study, serum was analyzed for blood urea nitrogen, albumin and creatinine; urine (24 h) was analyzed for albumin and creatinine. Kidney was evaluated for its biochemical and morphological changes. Results: Extract at doses of 200 and 400 mg/kg significantly normalized the nephrotoxic biomarkers in serum and urine and increased the kidney antioxidant activities which were altered due to gentamicin toxicity. The histological findings reveal that MCCF was capable of protecting the kidney against gentamicin toxicity. Conclusions: Extract ameliorated oxidative stress generated by gentamicin administration, which is one of the mechanisms for its preventive action against diabetic nephropathy.

  4. Severity of gentamicin's nephrotoxic effect on patients with infective endocarditis: a prospective observational cohort study of 373 patients

    DEFF Research Database (Denmark)

    Buchholtz, Kristine; Larsen, Carsten T; Hassager, Christian;

    2009-01-01

    and mortality in patients with IE. METHODS: A prospective observational cohort study was performed at 2 tertiary university hospitals in Copenhagen from October 2002 through October 2007; 373 consecutive patients with IE were included. A total of 287 (77%) of the patients received gentamicin treatment (median...... duration, 14 days); dosage was adjusted according to daily serum creatinine and trough serum gentamicin levels. Kidney function was determined by estimated endogenous creatinine clearance (EECC). Statistical correlation between gentamicin and EECC change was analyzed, and the association between mortality...... and nephrotoxicity was investigated. RESULTS: The primary bacteriological etiologies were as follows: Streptococcus species (37.1%), Staphylococcus aureus (18.2%), and Enterococcus species (16.1%). In the gentamicin group, the mean EECC change was an 8.6% decrease, but in the no-gentamicin group, the mean change...

  5. Oral Gentamicin Gut Decontamination for Prevention of KPC-Producing Klebsiella pneumoniae Infections: Relevance of Concomitant Systemic Antibiotic Therapy

    Science.gov (United States)

    Tascini, Carlo; Sbrana, Francesco; Flammini, Sarah; Tagliaferri, Enrico; Arena, Fabio; Leonildi, Alessandro; Ciullo, Ilaria; Amadori, Francesco; Di Paolo, Antonello; Ripoli, Andrea; Lewis, Russell; Rossolini, Gian Maria

    2014-01-01

    Gut colonization represents the main source for KPC-producing Klebsiella pneumoniae (KPC-Kp) epidemic dissemination. Oral gentamicin, 80 mg four times daily, was administered to 50 consecutive patients with gut colonization by gentamicin-susceptible KPC-Kp in cases of planned surgery, major medical intervention, or need for patient transfer. The overall decontamination rate was 68% (34/50). The median duration of gentamicin treatment was 9 days (interquartile range, 7 to 15 days) in decontaminated patients compared to 24 days (interquartile range, 20 to 30 days) in those with persistent colonization (P < 0.001). In the six-month period of follow-up, KPC-Kp infections were documented in 5/34 (15%) successfully decontaminated patients compared to 12/16 (73%) persistent carriers (P < 0.001). The decontamination rate was 96% (22/23) in patients receiving oral gentamicin only, compared to 44% (12/27) of those treated with oral gentamicin and concomitant systemic antibiotic therapy (CSAT) (P < 0.001). The multivariate analysis confirmed CSAT and KPC-Kp infection as the variables associated with gut decontamination. In the follow-up period, KPC-Kp infections were documented in 2/23 (9%) of patients treated with oral gentamicin only and in 15/27 (56%) of those also receiving CSAT (P = 0.003). No difference in overall death rate between different groups was documented. Gentamicin-resistant KPC-Kp strains were isolated from stools of 4/16 persistent carriers. Peak gentamicin blood levels were below 1 mg/liter in 12/14 tested patients. Oral gentamicin was shown to be potentially useful for gut decontamination and prevention of infection due to KPC-Kp, especially in patients not receiving CSAT. The risk of emergence of gentamicin-resistant KPC-Kp should be considered. PMID:24419337

  6. Population pharmacokinetics and relationship between demographic and clinical variables and pharmacokinetics of gentamicin in neonates

    NARCIS (Netherlands)

    Stolk, L M L; Degraeuwe, P L J; Nieman, F H M; de Wolf, M C; de Boer, A

    2002-01-01

    Population pharmacokinetic parameter estimates were calculated from 725 routine plasma gentamicin concentrations obtained in 177 neonates of 24 to 42 weeks' gestational age in their first week of life. Kel increases and V/W decreases with increasing gestational age. Almost identical results were obt

  7. Effects of intratympanic gentamicin on vestibular afferents and hair cells in the chinchilla.

    Science.gov (United States)

    Hirvonen, Timo P; Minor, Lloyd B; Hullar, Timothy E; Carey, John P

    2005-02-01

    Gentamicin is toxic to vestibular hair cells, but its effects on vestibular afferents have not been defined. We treated anesthetized chinchillas with one injection of gentamicin (26.7 mg/ml) into the middle ear and made extracellular recordings from afferents after 5-25 (early) or 90-115 days (late). The relative proportions of regular, intermediate, and irregular afferents did not change after treatment. The spontaneous firing rate of regular afferents was lower (P galvanic currents was unaffected for all afferents. Intratympanic gentamicin treatment reduced the histological density of all hair cells by 57% (P = 0.04). The density of hair cells with calyx endings was reduced by 99% (P = 0.03), although some remaining hair cells had other features suggestive of type I morphology. Type II hair cell density was not significantly reduced. These findings suggest that a single intratympanic gentamicin injection causes partial damage and loss of vestibular hair cells, particularly type I hair cells or their calyceal afferent endings, does not damage the afferent spike initiation zones, and preserves enough hair cell synaptic activity to drive the spontaneous activity of vestibular afferents.

  8. Leishmanicidal Activity of Films Containing Paromomycin and Gentamicin Sulfate both In Vitro and In Vivo.

    Science.gov (United States)

    Tolouei, S; Hasheminia, Sj; Narimani, M; Khamesipour, A; Shatalebi, Ma; Hejazi, Sh

    2011-08-01

    Based on the efficacy of paromomycin ointment and recent ongoing clinical trials of combination of paromomycin and gentamicin, a new physical form of films of the paromomycin and gentamicin was prepared and anti-Leishmania activities of the prepared films were assessed in vitro and in vivo. Paromomycin 15% and gentamicin 0.5% was incorporated in a film using ethyl cellulose and HPMC (Hydroxyl Propyl Methyl Cellulose). In order to assess the drug release and anti-Leishmania activities of the preparation, a clone L. major parasite was established using a set of modified NNN medium without overlay liquid layer. Therapeutic effects of the films were evaluated using Balb/c mice model. The mice were inoculated with 2×10(6)L. major promastigotes (MRHO/IR/75/ER) and then when the lesions developed the mice were randomly divided in 3 groups, 10 mice per group, and treated with either perpetrated films or placebo for 28 days or left untreated. Growth inhibition of cloned promastigotes showed that the films have enough releasing capacity and in vivo system, the films containing paromomycin and gentamicin was able to reduce the lesion size and induced complete cure in 80% of the mice but relapse was seen in 60% of the cured mice and overall 50% cure rate was seen during 20 weeks period of the study. It seems that the prepared films might be further used in human clinical trials.

  9. Gentamicin induced nitric oxide-related oxidative damages on vestibular afferents in the guinea pig.

    Science.gov (United States)

    Hong, Sung Hwa; Park, Sook Kyung; Cho, Yang-Sun; Lee, Hyun-Seok; Kim, Ki Ryung; Kim, Myung Gu; Chung, Won-Ho

    2006-01-01

    Gentamicin is a well-known ototoxic aminoglycoside. However, the mechanism underlying this ototoxicity remains unclear. One of the mechanisms which may be responsible for this ototoxicity is excitotoxic damage to hair cells. The overstimulation of the N-methyl-d-aspartate (NMDA) receptors increases the production of nitric oxide (NO), which induces oxidative stress on hair cells. In order to determine the mechanism underlying this excitotoxicity, we treated guinea pigs with gentamicin by placing gentamicin (0.5 mg) pellets into a round window niche. After the sacrifice of the animals, which occurred at 3, 7 and 14 days after the treatment, the numbers of hair cells in the animals were counted with a scanning electron microscope. We then performed immunostaining using neuronal nitric oxide synthase (nNOS), inducible NOS (iNOS) and nitrotyrosine antibodies. The number of hair cells in the animals was found to decrease significantly after 7 days. nNOS and iNOS expression levels were observed to have increased 3 days after treatment. Nitrotyrosine was expressed primarily at the calyceal afferents of the type I hair cells 3 days after treatment. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining revealed positive hair cells 3 days after treatment. Our results suggest that inner ear treatment with gentamicin may upregulate nNOS and iNOS to induce oxidative stress in the calyceal afferents of type I hair cells, via nitric oxide overproduction.

  10. Novel model-based dosing guidelines for gentamicin and tobramycin in preterm and term neonates

    NARCIS (Netherlands)

    P.A.J. Välitalo (Pyry A. J.); J.N. van den Anker (John); K. Allegaert (Karel); R.F.W. de Cock (Roosmarijn); M. de Hoog (Matthijs); S.H. Simons (Sinno); J.W. Mouton (Johan); C.A.J. Knibbe (Catherijne)

    2015-01-01

    textabstractObjectives: In the heterogeneous group of preterm and term neonates, gentamicin and tobramycin are mainly dosed according to empirical guidelines, after which therapeutic drug monitoring and subsequent dose adaptation are applied. In view of the variety of neonatal guidelines available,

  11. Preparation, characterization, and in vitro release of gentamicin from coralline hydroxyapatite-alginate composite microspheres.

    Science.gov (United States)

    Sivakumar, M; Rao, K Panduranga

    2003-05-01

    In this work, composite microspheres were prepared from bioactive ceramics such as coralline hydroxyapatite [Ca(10)(PO(4))(6)(OH)(2)] granules, a biodegradable polymer, sodium alginate, and an antibiotic, gentamicin. Previously, we have shown a gentamicin release from coralline hydroxyapatite granules-chitosan composite microspheres. In the present investigation, we attempted to prepare composite microspheres containing coralline hydroxyapatite granules and sodium alginate by the dispersion polymerization technique with gentamicin incorporated by absorption method. The crystal structure of the composite microspheres was analyzed using X-ray powder diffractometer. Fourier transform infrared spectra clearly indicated the presence of per-acid of sodium alginate, phosphate, and hydroxyl groups in the composite microspheres. Scanning electron micrographs and optical micrographs showed that the composite microspheres were spherical in shape and porous in nature. The particle size of composite microspheres was analyzed, and the average size was found to be 15 microns. The thermal behavior of composite microspheres was studied using thermogravimetric analysis and differential scanning calorimetric analysis. The cumulative in vitro release profile of gentamicin from composite microspheres showed near zero order patterns.

  12. Lack of protection against gentamicin ototoxicity by auditory conditioning with noise

    Directory of Open Access Journals (Sweden)

    Alex Strose

    2014-10-01

    Full Text Available INTRODUCTION: Auditory conditioning consists of the pre-exposure to low levels of a potential harmful agent to protect against a subsequent harmful presentation. OBJECTIVE: To confirm if conditioning with an agent different from the used to cause the trauma can also be effective. METHOD: Experimental study with 17 guinea pigs divided as follows: group Som: exposed to 85 dB broadband noise centered at 4 kHz, 30 minutes a day for 10 consecutive days; group Cont: intramuscular administration of gentamicin 160 mg/kg a day for 10 consecutive days; group Expt: conditioned with noise similarly to group Som and, after each noise presentation, received gentamicin similarly to group Cont. The animals were evaluated by distortion product otoacoustic emissions (DPOAEs, brainstem auditory evoked potentials (BAEPs and scanning electron microscopy. RESULTS: The animals that were conditioned with noise did not show any protective effect compared to the ones that received only the ototoxic gentamicin administration. This lack of protection was observed functionally and morphologically. CONCLUSION: Conditioning with 85 dB broadband noise, 30 min a day for 10 consecutive days does not protect against an ototoxic gentamicin administration of 160 mg/kg a day for 10 consecutive days in the guinea pig.

  13. Continuous intravenous infusion of ampicillin and gentamicin during parenteral nutrition in 88 newborn infants

    DEFF Research Database (Denmark)

    Colding, H; Møller, S; Andersen, G E

    1982-01-01

    Ampicillin and gentamicin were dissolved once a day in an L-amino acid solution especially prepared for parenteral nutrition of newborn infants and infused continuously to 88 infants in whom septicaemia was suspected or had been proved. The mean dosages were 162 and 5.3 mg/kg per 24 hours...

  14. Administration of gentamicin and ampicillin by continuous intravenous infusion to newborn infants during parenteral nutrition

    DEFF Research Database (Denmark)

    Colding, H; Andersen, G E

    1982-01-01

    Gentamicin and ampicillin were dissolved in an L-amino acid solution especially prepared for newborn infants and infused intravenously over 24 h in 7 babies with serious neonatal surgical problems. Serum concentrations of the antibiotics were maintained rather constant and well above the minimal ...

  15. N-ACETYLCYSTEINE EFFECT ON GENTAMICIN INDUCED NEPHROTOXICITY IN ANIMAL MODELS

    Directory of Open Access Journals (Sweden)

    Laishram Elizabeth

    2016-05-01

    Full Text Available BACKGROUND Gentamicin exerts a unique pharmacokinetic effect on renal physiology and its use at high dose or prolonged treatment requires monitoring of kidney function test. Antioxidants has been claimed to have nephroprotective potential and hence antioxidant compound, N-acetylcysteine (NAC has been used in renal impairment; however, its efficacy is not very well documented. Therefore, the present study has been undertaken to evaluate the role of antioxidant (NAC in impaired kidney function due to high dose Gentamicin in rat models. Gentamicin at the dose of 80 mg/kg b.w. intramuscularly was given in 18 adult healthy albino rats for 10 days and varying doses of antioxidant NAC (20 and 40 mg/kg were given orally for 3 wks. starting from day 5 of the experiment. Blood urea and creatinine levels were measured on day 5, 10 and after completion of treatment of NAC and histopathology examination conducted. Intramuscular injection of high dose of Gentamicin significantly produced biochemical signs of nephrotoxicity. Serum creatinine levels were significantly lowered in NAC treated group compared to the control group. The group treated with NAC 40 mg/kg for 3 wks. had significantly lowered renal biochemical parameters and histopathological features compared to control.

  16. The pharmacokinetics and tissue levels of polymyxin B, colistin and gentamicin in calves.

    Science.gov (United States)

    Ziv, G; Nouws, J F; van Ginneken, C A

    1982-03-01

    Following a single intravenous injection of polymyxin B, colistin (5 mg/kg, each) and gentamicin (3 mg/kg) to calves, the decline in serum antibiotic concentration generally suggested a three-compartment (open system) pharmacokinetic model. Tissue binding is a dominant factor in the distribution and elimination kinetics of the drugs. Less than 65% of the dose of polymyxin B and colistin was recovered in the urine during 48 h after treatment. Concentrations of nonbound polymyxin B and colistin in the kidney, liver, lung, heart, and skeletal muscles were similar to total (free and bound) serum drug levels, but considerably higher concentrations were found, in bound form, in chloroform-ethanol extracts of these organs. At 24 h after treatment, more than 50% of the doses of polymyxin B and colistin were present bound to the tissues; the largest amount was in the skeletal muscles. Gentamicin was concentrated in the kidney, predominantly in the free form. At 48 h after treatment the amount of gentamicin in the kidney was 6.3% of the administered dose, being more than five times greater than the corresponding amounts of polymyxin B and colistin. The extent of tissue uptake of polymyxin B and colistin limits the usefulness of kinetic values, which are derived from the analysis of serum drug levels, for the purpose of designing dosage schedules. The strong affinity of the polymyxins to the muscle tissue, and gentamicin to the kidney, can result in drug residues persisting in the body for several weeks.

  17. Spherical gold nanoparticles and gold nanorods for the determination of gentamicin

    Science.gov (United States)

    Miranda-Andrades, Jarol R.; Pérez-Gramatges, Aurora; Pandoli, Omar; Romani, Eric C.; Aucélio, Ricardo Q.; da Silva, Andrea R.

    2017-02-01

    Gentamicin is an antibiotic indicated to treat mastitis in dairy cattle and for the treatment of bacterial resistance in the context of hospital infections. The effect caused by gentamicin on the optical properties of gold nanoparticles aqueous dispersions were used to develop quantitative methods to determine this antibiotic. Two different aqueous dispersions, one containing spherical Au nanoparticles (AuNPs) and the other containing Au nanorods (AuNRs), had their conditions adjusted to enable a stable and sensitive response towards gentamicin. The use of AuNPs, with measurement at 681 nm of the rising coupling plasmon band, enabled a limit of detection (LOD) of 0.4 ng mL- 1 (0.02 ng absolute LOD), ten times lower than the one achieved by measuring the decreasing of the longitudinal surface plasmon resonance band (at 662 nm). The linear analytical response of AuNPs measured at 681 nm did not require rationing of signal values to correct for linearity. Stability of the analytical response resulted in intermediary precision below 2%. No significant interference was imposed by excipients traditionally present in injectable solutions for veterinary use. Percent recoveries obtained in such formulations were between 94.5 and 98.2% regardless the existence of any difference in the proportion of the compounds known as gentamicin (C1, C1a and C2) in standard and in the samples. The method requires no derivatization with toxic reagents as usually is required in other spectroscopic approaches.

  18. 21 CFR 524.1044d - Gentamicin sulfate, betamethasone valerate ointment.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate, betamethasone valerate ointment. 524.1044d Section 524.1044d Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... preparation. Administration of recommended doses beyond 7 days may result in delayed wound healing. Animals...

  19. Gentamicin pharmacokinetics in preterm infants with a patent and a closed ductus arteriosus

    NARCIS (Netherlands)

    Touw, D J; Proost, J H; Stevens, R; Lafeber, H N; van Weissenbruch, M M

    2001-01-01

    BACKGROUND AND AIM: A patent ductus arteriosus (PDA) may influence renal and hepatic blood flow and hence pharmacokinetics of drugs in neonates compared to neonates with a closed ductus arteriosus (CDA). A 10-percent difference of gentamicin pharmacokinetic parameters between PDA and CDA has been re

  20. Continuous intravenous infusion of ampicillin and gentamicin during parenteral nutrition in 88 newborn infants

    DEFF Research Database (Denmark)

    Colding, H; Møller, S; Andersen, G E

    1982-01-01

    Ampicillin and gentamicin were dissolved once a day in an L-amino acid solution especially prepared for parenteral nutrition of newborn infants and infused continuously to 88 infants in whom septicaemia was suspected or had been proved. The mean dosages were 162 and 5.3 mg/kg per 24 hours...

  1. Single Daily Dosing of Gentamicin: Pharmacokinetic Comparison of Two Dosing Methodologies for Postpartum Endometritis

    Directory of Open Access Journals (Sweden)

    C. Liu

    1999-01-01

    Full Text Available Objective: We compared the pharmacokinetics of two methods for dosing gentamicin for the treatment of postpartum endometritis with the goal of achieving adequate peak serum concentrations (>12 mg/L and prolonged trough levels below 2 mg/L.

  2. The Effects of Vitamin D on Gentamicin-Induced Acute Kidney Injury in Experimental Rat Model

    Directory of Open Access Journals (Sweden)

    Ender Hur

    2013-01-01

    Full Text Available Introduction. Acute kidney injury (AKI pathogenesis is complex. Findings of gentamicin nephrotoxicity are seen in 30% of the AKI patients. Vitamin D has proven to be effective on renin expression, inflammatory response, oxidative stress, apoptosis, and atherosclerosis. We aimed to investigate the effect of vitamin D in an experimental rat model of gentamicin-induced AKI. Methods. Thirty nonuremic Wistar albino rats were divided into 3 groups: Control group, 1 mL saline intramuscular (im daily; Genta group, gentamicin 100 mg/kg/day (im; Genta + vitamin D, gentamicin 100 mg/kg/day (im in addition to 1α, 25 (OH2D3 0.4 mcg/kg/day subcutaneously for 8 days. Blood pressures and 24-hour urine were measured. Blood urea and creatinine levels and urine tubular injury markers were measured. Renal histology was semiquantitatively assessed. Results. Urea, creatinine and urine neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 were all increased in Genta group indicating AKI model. Systolic blood pressure decreased, but urine volume and glutathione increased in Genta + Vit D group compared to Control group. Histological scores indicating tubular injury increased in Genta and Genta + Vit D groups. Conclusions. Vitamin D does not seem to be effective on histological findings although it has some beneficial effects via RAS system and a promising effect on antioxidant system.

  3. Microbubble-Mediated Ultrasound Enhances the Lethal Effect of Gentamicin on Planktonic Escherichia coli

    Directory of Open Access Journals (Sweden)

    Han-Xiao Zhu

    2014-01-01

    Full Text Available Previous research has found that low-intensity ultrasound enhanced the lethal effect of gentamicin on planktonic E. coli. We aimed to further investigate whether microbubble-mediated low-intensity ultrasound could further enhance the antimicrobial efficacy of gentamicin. The planktonic E. coli (ATCC 25922 was distributed to four different interventions: control (GCON, microbubble only (GMB, ultrasound only (GUS, and microbubble-mediated ultrasound (GMUS. Ultrasound was applied with 100 mW/cm2 (average intensity and 46.5 KHz, which presented no bactericidal activity. After 12 h, plate counting was used to estimate the number of bacteria, and bacterial micromorphology was observed with transmission electron microscope. The results showed that the viable counts of E. coli in GMUS were decreased by 1.01 to 1.42 log10 CFU/mL compared with GUS (P<0.01. The minimal inhibitory concentration (MIC of gentamicin against E. coli was 1 μg/mL in the GMUS and GUS groups, lower than that in the GCON and GMB groups (2 μg/mL. Transmission electron microscopy (TEM images exhibited more destruction and higher thickness of bacterial cell membranes in the GMUS than those in other groups. The reason might be the increased permeability of cell membranes for gentamicin caused by acoustic cavitation.

  4. A new dosing schedule for gentamicin in blood pythons (Python curtus): a pharmacokinetic study.

    Science.gov (United States)

    Hilf, M; Swanson, D; Wagner, R; Yu, V L

    1991-03-01

    Gentamicin is frequently used in the treatment of aerobic Gram-negative infections in reptiles. Pharmacokinetic data to ensure proper dosing are scant, especially for large snakes. A pharmacokinetic study of gentamicin was therefore conducted in four blood pythons. Snakes were given intramuscular injections of either 2.5 mg kg-1 or 3.0 mg kg-1 loading dose followed by 1.5 mg kg-1 at 72 and 96 hours. A linear pharmacokinetic relationship between gentamicin serum concentrations and time was demonstrated in each of the four snakes studied. Peak serum concentrations occurred six to 10 hours after injection and ranged from 4.6 to 8.9 micrograms ml-1. Half-life was variable and ranged from 32 to 110 hours. Total body clearance and apparent volume of distribution varied little between the individual snakes studied. There was no evidence of renal toxicity. For blood pythons a loading dose of 2.5 mg kg-1 followed by 1.5 mg kg-1 at 96 hour intervals is recommended. If higher concentrations are desired, a loading dose of 3.0 mg kg-1 followed by 1.5 mg kg-1 at 96 hours can be given. These dosing schedules will provide serum concentrations in excess of the minimum inhibitory concentrations for most aerobic Gram-negative bacilli that are pathogenic in snakes; gentamicin accumulation with subsequent renal dysfunction should not occur.

  5. In-vitro analysis of the effect of gentamicin and polyhexanide on bone tissue.

    Science.gov (United States)

    Kock, Hans-Jürgen; Ernst, Dirk; Jethon, Frank; Fabry, Werner

    2013-04-01

    Though anti-infectives have been used for a long time in surgical procedures, the effect on bone tissue has not been determined for most antibiotics and antiseptics. In our in vitro study, 4x4x8 mm(3) blocks of rabbit cancellous bone tissue were incubated with Ringer's solution, gentamicin and Lavasorb(®) each for time intervals of 15 minutes, 30 minutes, one hour, four hours and eight hours. Samples were examined double blinded through optical and electron microscopy. Tissue degeneration was observed in all samples. It was low in Ringer's solution. Samples with Lavasorb showed a moderate degeneration after 15 and 30 minutes, which was accelerated after one hour. Gentamicin led to a moderate degeneration of bone tissue after 15 and 30 minutes and to a more accelerated degeneration after one hour. The effect of gentamicin on bone tissue was more pronounced than the effect of Lavasorb. This investigation showed that local application of Lavasorb or gentamicin on bone tissue should be restricted to 30 minutes, while Lavasorb showed a better tissue tolerability. This finding could have clinical implications for the management of wounds with open osseous tissue and should be further investigated by in vivo studies.

  6. Effect of two cleaning processes for bone allografts on gentamicin impregnation and in vitro antibiotic release.

    Science.gov (United States)

    Coraça-Huber, D C; Hausdorfer, J; Fille, M; Steidl, M; Nogler, M

    2013-06-01

    Bone allografts are a useful and sometimes indispensable tool for the surgeon to repair bone defects. Microbial contamination is a major reason for discarding allografts from bone banks. To improve the number of safe allografts, we suggest chemical cleaning of the grafts followed by antibiotic impregnation. Comparison of two chemical cleaning processes for bone allografts aiming for antibiotic impregnation and consequently delivery rates in vitro. Bone chips of 5-10 mm were prepared from human femoral heads. Two cleaning methods (cleaning A and cleaning B) based on solutions containing hydrogen peroxide, paracetic acid, ethanol and biological detergent were carried out and compared. After the cleaning processes, the bone chips were impregnated with gentamicin. Bacillus subtilis bioassay was used to determine the gentamicin release after intervals of 1-7 days. Differences were compared with non-parametric Mann-Whitney U tests. The zones of inhibition obtained from the bone grafts cleaned with both cleaning processes were similar between the groups. The concentration of the released antibiotic was decreasing gradually over time, following a similar pattern for both groups. The cleaning procedure A as well as the cleaning procedure B for bone allografts allowed the impregnation with gentamicin powder in the same concentrations in both groups. The delivery of gentamicin was similar for both groups. Both cleaning procedures were easy to be carried out, making them suitable for routine use at the bone banks.

  7. Chemopreventive role of Coriandrum sativum against gentamicin-induced renal histopathological damage in rats.

    Science.gov (United States)

    Lakhera, Abhijeet; Ganeshpurkar, Aditya; Bansal, Divya; Dubey, Nazneen

    2015-06-01

    Drug induced nephrotoxicity is one of the most common causes of renal failure. Gentamicin belongs to aminoglycosides, which elicit nephrotoxic potential. Natural antioxidants from plants demonstrate a number of biotherapeutic activities. Coriander is an important medicinal plant known for its hepatoprotective, diuretic, carminative, digestive and antihelminthic potential. This study was designed to investigate whether the extract of Coriandrum sativum ameliorates the nephrotoxicity induced by gentamicin in rats. Dried coriander powder was coarsely grinded and subjected to defatting by petroleum ether and further with ethyl acetate. The extract was filtered and subjected to phytochemical and phytoanalytical studies. Acute toxicity in Wistar rats was determined by the OECD Guideline (423). Animals were divided into four groups. The first group served as positive control, while the second group was toxic control (gentamicin treated). The third and fourth group were treated with the extract (200 and 400 mg/kg gentamicin). After 8 days, the animals were sacrificed and biochemical and histopathological studies were carried out. Phytochemical screening of the extract demonstrated Coriandrum sativum to be rich in flavonoids, polyphenolics and alkaloids. Results of acute toxicity suggested the use of 200 mg/kg and 400 mg/kg for Coriandrum sativum in the study. Coriandrum sativum extract at the dose of 400 mg/kg significantly (pCoriandrum sativum extract ameliorated renal histological lesions. It is concluded that Coriandrum sativum is a potential source of nephroprotective phytochemical activity, with flavonoids and polyphenols as the major components.

  8. Staphylococcus aureus biofilm formation on different gentamicin-loaded polymethylmethacrylate bone cements

    NARCIS (Netherlands)

    van de Belt, H; Neut, D; Schenk, W; van Horn, [No Value; van der Mei, HC; Busscher, HJ

    In this in vitro study, the formation of a Staphylococcus aureus biofilm on six gentamicin-loaded bone cements (CMW1, CMW3, CMW Endurance, CMW2000, Palacos. and Palamed) was determined in a modified Robbins device over a 3 days time span and related with previously (Van de Belt et al., Biomaterials

  9. Staphylococcus aureus biofilm formation on different gentamicin-loaded polymethylmethacrylate bone cements

    NARCIS (Netherlands)

    van de Belt, H; Neut, D; Schenk, W; van Horn, [No Value; van der Mei, HC; Busscher, HJ

    2001-01-01

    In this in vitro study, the formation of a Staphylococcus aureus biofilm on six gentamicin-loaded bone cements (CMW1, CMW3, CMW Endurance, CMW2000, Palacos. and Palamed) was determined in a modified Robbins device over a 3 days time span and related with previously (Van de Belt et al., Biomaterials

  10. Changes in renal enzyme activities following the administration of gentamicin to unilateral nephrectomized rats.

    Science.gov (United States)

    Avidan, G; Aladjem, M; Israeli, B A; Bogin, E

    1986-02-28

    The effects of unilateral nephrectomy and the impact of gentamicin administration on renal tissue enzyme activities in adult Wistar rats were investigated. Gentamicin 200 mg/kg body wt. or an equivalent volume of saline to control rats was administered subcutaneously on three consecutive days, followed by unilateral nephrectomy. Rats were killed on day 3, 7 or 14 following nephrectomy. Alkaline phosphatase, predominantly a proximal tubular brush border enzyme, rose in both the experimental and control groups, however, significantly less in the gentamicin treated rats. Aspartate aminotransferase activity, an enzyme participating in renal glucogenesis, increased transiently in the control but remained unchanged in the experimental group. No difference in glucose-6-phosphate dehydrogenase activity between the two groups was observed, probably reflecting the localization of this enzyme to distal tubular segments, a site unaffected by gentamicin. Significant and similar increases in Mg2+ and Na+ K+ ATPase were observed on day 14 in both groups. The administration of the drug resulted in a marked reduction in oxygen consumption, with a higher oxidation to phosphorylation ratio (P/O). Serum creatinine concentration was significantly higher on days 3 and 7 in the experimental group reverting to control values on the 14th day. Urea concentration increased significantly on days 3 and 7, decreasing on the 14th day to values slightly, but significantly, higher than those of the controls.

  11. Nephroprotective effect of ethanolic extract of abutilon indicum root in gentamicin induced acute renal failure

    Directory of Open Access Journals (Sweden)

    Jacob Jesurun RS

    2016-06-01

    Conclusions: The ethanolic extract of abutilon indicum root has nephron protective effect in gentamicin induced acute renal failure. Nephro protective action in this study could be due to the antioxidant and other phytochemical of abutilon indicum root. [Int J Basic Clin Pharmacol 2016; 5(3.000: 841-845

  12. Effect of endogenous hydrogen sulfide inhibition on structural and functional renal disturbances induced by gentamicin

    Energy Technology Data Exchange (ETDEWEB)

    Francescato, H.D.C.; Chierice, J.R.A.; Marin, E.C.S. [Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Cunha, F.Q. [Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Costa, R.S. [Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Silva, C.G.A.; Coimbra, T.M. [Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2012-02-17

    Animal models of gentamicin nephrotoxicity present acute tubular necrosis associated with inflammation, which can contribute to intensify the renal damage. Hydrogen sulfide (H{sub 2}S) is a signaling molecule involved in inflammation. We evaluated the effect of DL-propargylglycine (PAG), an inhibitor of endogenous H{sub 2}S formation, on the renal damage induced by gentamicin. Male Wistar rats (N = 8) were injected with 40 mg/kg gentamicin (im) twice a day for 9 days, some of them also received PAG (N = 8, 10 mg·kg{sup −1}·day{sup −1}, ip). Control rats (N = 6) were treated with saline or PAG only (N = 4). Twenty-four-hour urine samples were collected one day after the end of these treatments, blood samples were collected, the animals were sacrificed, and the kidneys were removed for quantification of H{sub 2}S formation and histological and immunohistochemical studies. Gentamicin-treated rats presented higher sodium and potassium fractional excretion, increased plasma creatinine [4.06 (3.00; 5.87) mg%] and urea levels, a greater number of macrophages/monocytes, and a higher score for tubular interstitial lesions [3.50 (3.00; 4.00)] in the renal cortex. These changes were associated with increased H{sub 2}S formation in the kidneys from gentamicin-treated rats (230.60 ± 38.62 µg·mg protein{sup −1}·h{sup −1}) compared to control (21.12 ± 1.63) and PAG (11.44 ± 3.08). Treatment with PAG reduced this increase (171.60 ± 18.34), the disturbances in plasma creatinine levels [2.20 (1.92; 4.60) mg%], macrophage infiltration, and score for tubular interstitial lesions [2.00 (2.00; 3.00)]. However, PAG did not interfere with the increase in fractional sodium excretion provoked by gentamicin. The protective effect of PAG on gentamicin nephrotoxicity was related, at least in part, to decreased H{sub 2}S formation.

  13. Effect of endogenous hydrogen sulfide inhibition on structural and functional renal disturbances induced by gentamicin

    Directory of Open Access Journals (Sweden)

    H.D.C. Francescato

    2012-03-01

    Full Text Available Animal models of gentamicin nephrotoxicity present acute tubular necrosis associated with inflammation, which can contribute to intensify the renal damage. Hydrogen sulfide (H2S is a signaling molecule involved in inflammation. We evaluated the effect of DL-propargylglycine (PAG, an inhibitor of endogenous H2S formation, on the renal damage induced by gentamicin. Male Wistar rats (N = 8 were injected with 40 mg/kg gentamicin (im twice a day for 9 days, some of them also received PAG (N = 8, 10 mg·kg-1·day-1, ip. Control rats (N = 6 were treated with saline or PAG only (N = 4. Twenty-four-hour urine samples were collected one day after the end of these treatments, blood samples were collected, the animals were sacrificed, and the kidneys were removed for quantification of H2S formation and histological and immunohistochemical studies. Gentamicin-treated rats presented higher sodium and potassium fractional excretion, increased plasma creatinine [4.06 (3.00; 5.87 mg%] and urea levels, a greater number of macrophages/monocytes, and a higher score for tubular interstitial lesions [3.50 (3.00; 4.00] in the renal cortex. These changes were associated with increased H2S formation in the kidneys from gentamicin-treated rats (230.60 ± 38.62 µg·mg protein-1·h-1 compared to control (21.12 ± 1.63 and PAG (11.44 ± 3.08. Treatment with PAG reduced this increase (171.60 ± 18.34, the disturbances in plasma creatinine levels [2.20 (1.92; 4.60 mg%], macrophage infiltration, and score for tubular interstitial lesions [2.00 (2.00; 3.00]. However, PAG did not interfere with the increase in fractional sodium excretion provoked by gentamicin. The protective effect of PAG on gentamicin nephrotoxicity was related, at least in part, to decreased H2S formation.

  14. Effects of gentamicin on guinea pig vestibular ganglion function and on substance P and neuropeptide Y.

    Science.gov (United States)

    Lin, Chi-Te; Young, Yi-Ho; Cheng, Po-Wen; Lue, June-Horng

    2010-12-01

    Previous studies have demonstrated that following intratympanic gentamicin application in the guinea pigs, vestibular evoked myogenic potentials (VEMPs) were absent regardless of stimulation mode using either air-conducted sound (ACS) stimuli or galvanic vestibular stimulation (GVS). Ultrastructurally, both type I hair cells and their calyx terminals were distorted in the saccular macula. However, little is known about the toxic effects of gentamicin on the vestibular ganglion (VG). In this study, absent ACS- and GVS-VEMPs were noted in all the gentamicin-treated ears (100%), which were confirmed by the substantial loss of sensory hair cells in the saccular macula. Moreover, dramatic up-regulation of growth associated protein-43 (GAP-43) expression was detected in the ipsilateral VG neurons. The mean percentage of substance P-like immunoreactive (SP-LI) neurons in the treated VG (81.8±1.9%) was significantly higher than that in the control VG (68.6±3.3%). Conversely, the mean percentage of neuropeptide Y-like immunoreactive (NPY-LI) neurons in the treated VG (13.7±3.8%) was dramatically lower than that in the control VG (49.0±3.8%). Double labeling results shown 82% of SP-LI and 16% of NPY-LI neurons coexpressed with GAP-43, suggested that SP accumulating coincided with NPY decreasing in regenerating VG neurons after gentamicin treatment. Overall, the changes in SP and NPY expression in VG neurons after gentamicin treatment were like to those in the superior cervical ganglion following sympathectomy.

  15. Gentamicin induces efaA expression and biofilm formation in Enterococcus faecalis.

    Science.gov (United States)

    Kafil, Hossein Samadi; Mobarez, Ashraf Mohabati; Moghadam, Mehdi Forouzandeh; Hashemi, Zahra Sadat; Yousefi, Mehdi

    2016-03-01

    Enterococci have been ranked among the leading causes of nosocomial bacteremia and urinary tract infection. This study aimed to investigate the effect of ampicillin, vancomycin, gentamicin and ceftizoxime on biofilm formation and gene expression of colonization factors on Enterococcus faecalis. Twelve clinical isolates of E. faecalis were used to investigate the effect of antibiotics on biofilm formation and gene expression of efaA, asa1, ebpA, esp and ace. Flow system assay and Microtiter plates were used for biofilm assay. Two hundred clinical isolates were used for confirming the effect of antibiotics on biofilm formation. Ampicillin, vancomycin and ceftizoxime did not have any significant effect on biofilm formation, but gentamicin induced biofilm formation in 89% of isolates. In twelve selected isolate gentamicin increased expression of esp (+50.9%) and efaA (+33.9%) genes and reduced or maintained expression of others (asa1:-47.4%, ebpA: 0, ace:-19.2%). Vancomycin increased expression of esp (+89.1%) but reduced the others (asa1: -34.9%, ebpA:-11%, ace:-30%, efaA:-60%). Ceftizoxime increased slightly ebpA (+19.7%) and reduced others (asa1:-66.2%, esp:-35%, ace:-28.1%, efaA:-38.4%). and ampicillin strongly increased expression of ace (+231%), esp (+131%) and ebpA (+83%) but reduced others (asa1:-85.5%, efaA:-47.4%). The findings of the present study showed that antibiotics may have a role in biofilm formation and sustainability of enterococci, especially in case of gentamicin. efaA gene may have an important role, especially in antibiotic induced biofilm formation by gentamicin. Experiments with efaA mutants are needed to investigate the exact effect of efaA on biofilm formation with antibiotic induced cells.

  16. Pharmacokinetic profile that reduces nephrotoxicity of gentamicin in a perfused kidney-on-a-chip.

    Science.gov (United States)

    Kim, Sejoong; LesherPerez, Sasha Cai; Kim, Byoung Choul C; Yamanishi, Cameron; Labuz, Joseph M; Leung, Brendan; Takayama, Shuichi

    2016-03-24

    Nephrotoxicity is often underestimated because renal clearance in animals is higher compared to in humans. This paper aims to illustrate the potential to fill in such pharmacokinetic gaps between animals and humans using a microfluidic kidney model. As an initial demonstration, we compare nephrotoxicity of a drug, administered at the same total dosage, but using different pharmacokinetic regimens. Kidney epithelial cell, cultured under physiological shear stress conditions, are exposed to gentamicin using regimens that mimic the pharmacokinetics of bolus injection or continuous infusion in humans. The perfusion culture utilized is important both for controlling drug exposure and for providing cells with physiological shear stress (1.0 dyn cm(-2)). Compared to static cultures, perfusion culture improves epithelial barrier function. We tested two drug treatment regimens that give the same gentamycin dose over a 24 h period. In one regimen, we mimicked drug clearance profiles for human bolus injection by starting cell exposure at 19.2 mM of gentamicin and reducing the dosage level by half every 2 h over a 24 h period. In the other regimen, we continuously infused gentamicin (3 mM for 24 h). Although junctional protein immunoreactivity was decreased with both regimens, ZO-1 and occludin fluorescence decreased less with the bolus injection mimicking regimen. The bolus injection mimicking regimen also led to less cytotoxicity and allowed the epithelium to maintain low permeability, while continuous infusion led to an increase in cytotoxicity and permeability. These data show that gentamicin disrupts cell-cell junctions, increases membrane permeability, and decreases cell viability particularly with prolonged low-level exposure. Importantly a bolus injection mimicking regimen alleviates much of the nephrotoxicity compared to the continuous infused regimen. In addition to potential relevance to clinical gentamicin administration regimens, the results are important in

  17. Renal oxidative stress status and histology in gentamicin nephrotoxicity: The effects of antioxidant vitamins

    Directory of Open Access Journals (Sweden)

    R. Ghaznavi

    2006-07-01

    Full Text Available Background: In recent publications, several mechanisms have been implicated in gentamicin (GM nephrotoxicity. Reactive oxygen species have been proposed as one of the causative factors of the drug renal side effects. This study was designed to evaluate the protective effects of the antioxidant vitamins against GM-mediated nephropathy in insitu isolated rat kidneys. Methods: Male Sprague-Dawley rats were randomly assigned to one of the following groups of seven rats: Group 1 (control was tyrode perfused kidneys. Group 2 (GM, 200µg/ml gentamicin was added to the perfusate. Group 3 (GM + Vit C, the same as group 2 but vitamin C (200 mg/L was added to the drinking water for 3 days and 100 mg/L to the perfusate. Group 4 (GM + Vit E, the same as group 2 but vitamin E (100 mg/100 g BW, ip was injected 12 h before experiments. Group 5 (GM + Vit C + Vit E the same as group 2 but Vit E and C were co-administered (same as Group 3 & 4. Urinary N-acetyle-B-D-glucosaminidas (NAG and renal cortex superoxide dismutase (SOD levels were measured and tissue histological evaluations were performed. Results: Gentamicin caused a significant nephrotoxicity demonstrated by increase in urinary NAG. Decline in SOD contents were observed comparing to controls. Vit C or Vit E inhibited the gentamicin-induced increased releases of NAG into urine but did not show a significant effect on the SOD levels. Conclusion: Co-administration of VitC&E significantly prevented the GM nephrotoxicity demonstrating by preservation of SOD levels and prevention of increase in urinary enzyme activities. Histological studies of renal tissues provided additional evidences for protective effects of antioxidant vitamins. We concluded that moderate doses of Vit C & E have protective effects in gentamicin nephrotoxicity and co-administration of these vitamins have additional beneficial effects.

  18. Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: Possible mechanism of nephroprotection

    Energy Technology Data Exchange (ETDEWEB)

    Sahu, Bidya Dhar [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Tatireddy, Srujana [National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037 (India); Koneru, Meghana [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Borkar, Roshan M. [National Centre for Mass Spectrometry, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Kumar, Jerald Mahesh [CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad 500 007 (India); Kuncha, Madhusudana [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Srinivas, R. [National Centre for Mass Spectrometry, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Shyam Sunder, R. [Faculty of Pharmacy, Osmania University, Hyderabad 500 007 (India); Sistla, Ramakrishna, E-mail: sistla@iict.res.in [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India)

    2014-05-15

    Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrial NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100 mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and apoptosis in

  19. Efficacy of liposomal gentamicin against Rhodococcus equi in a mouse infection model and colocalization with R. equi in equine alveolar macrophages.

    Science.gov (United States)

    Burton, Alexandra J; Giguère, Steeve; Berghaus, Londa J; Hondalus, Mary K; Arnold, Robert D

    2015-04-17

    Rhodococcus equi, a facultative intracellular pathogen and an important cause of pneumonia in foals, is highly susceptible to killing by gentamicin in vitro. However, gentamicin is not effective in vivo, due to its poor cellular penetration. Encapsulation of drugs in liposomes enhances cellular uptake. The objectives of this study were to compare liposomal gentamicin and free gentamicin with respect to their uptake by equine macrophages and intracellular colocalization with R. equi and to compare the efficacies of liposomal gentamicin, free gentamicin and clarithromycin with rifampin for the reduction of R. equi CFU in a mouse model of infection. After ex vivo exposure, a significantly higher mean (±SD) percentage of equine alveolar macrophages contained liposomal gentamicin (91.9±7.6%) as opposed to free gentamicin (16.8±12.5%). Intracellular colocalization of drug and R. equi, as assessed by confocal microscopy, occurred in a significantly higher proportion of cells exposed to liposomal gentamicin (81.2±17.8%) compared to those exposed to free gentamicin (10.4±8.7%). The number of R. equi CFU in the spleen was significantly lower in mice treated with liposomal gentamicin compared to that of mice treated with free gentamicin or to untreated control mice. Treatment with liposomal gentamicin also resulted in a significantly greater reduction in the number of R. equi CFU in the liver compared to treatment with clarithromycin in combination with rifampin. These results support further investigation of liposomal gentamicin as a new treatment for infections caused by R. equi. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Tritium Labeled Gentamicin C: II.- Bioradiactive Degradation Products of Gentamicin by Catalytic H2O-3H Exchange Reaction; Getamicina C Tritiada: II.- Productos de Degradacion Radiactivos y Bioactivos en el Intercambio Catalitico con H2O-3H

    Energy Technology Data Exchange (ETDEWEB)

    Suarez, C.; Diaz, A.; Paz, D.; Jimeno, M. L.

    1992-07-01

    The main bio radioactive degradation products from catalytic hydrogen exchange of gentamicin C, (C1 + C2 + Cla) in basic form, are generated by N-demethylation in 3{sup -}N and 6-N positions. Their structures were confirmed by 1HNMR and 13CNMR. These derivatives were fractionated by chromatography on silica gel. Antibacterial activities were similar to those of the parent antibiotics. Tritium exchange, under vacuum or nitrogen, is highly increased (4:1) when gentamicin are in basic form. In contrast with gentamicin sulfate, hydrolytic sub products as gramine, genta mines, garosamine and purpurosamines are practically absent. To properly optimize the exchange process, the composition of the gentamicin C complex must be taken into account. The exchange decreases in the order C2 > C1> Cla. Because of 6'-N-demethyl gentamicin C1 is C2, the radiochemical yield of C2 appears enhanced in the H2O-3H exchange of a mixture of them. Radioactivity distribution among the components and subunits of these three gentamicin were studied by strong and mild hydrolysis, and by methanolysis. (Author) 18 refs.

  1. Nephro-protective effect of vitamin C and Nigella sativa oil on gentamicin associated nephrotoxicity in rabbits

    National Research Council Canada - National Science Library

    Saleem, Uzma; Ahmad, Bashir; Rehman, Kanwal; Mahmood, Saeed; Alam, Maqsood; Erum, Alia

    2012-01-01

    .... An aminoglycoside, gentamicin, has pronounced nephrotoxic effect in humans and animals and this study was planned to observe the nephro-protective effect of antioxidants, vitamin C and Nigella sativa oil...

  2. Impact of clinical decision support guidelines on therapeutic drug monitoring of gentamicin in newborns.

    Science.gov (United States)

    Fonzo-Christe, Caroline; Guignard, Bertrand; Zaugg, Claudia; Coehlo, Ana; Posfay-Barbe, Klara M; Gervaix, Alain; Desmeules, Jules; Rollason, Victoria; Combescure, Christophe; Corbelli, Regula; Rimensberger, Peter; Pfister, Riccardo; Bonnabry, Pascal

    2014-10-01

    Our institution's gentamicin dosing and therapeutic drug monitoring (TDM) practices for newborns were suspected to be very heterogeneous. Once-daily dosing (ODD) or extended-interval dosing (EID) and trough concentration measurement were recommended. Clinical decision support guidelines were developed and implemented as clinical decision support in the computerized prescriber order entry system. Impact on dosing, TDM practices, and blood sampling were evaluated. A 1-year retrospective historically controlled study before (April 2008-March 2009) and after the implementation of guidelines (January 2010-December 2010) for newborns ( 0.05). After implementation of the guidelines, an ODD/EID regimen was almost exclusively used (97.7% versus 61.6%, P Guideline implementation generated a sharp reduction in blood sampling. Clinical benefits of better gentamicin dosing and TDM practices were evident. Cost-effectiveness and clinical benefit of reduced blood sampling should be evaluated.

  3. Nitric oxide in guinea pig vestibular sensory cells following gentamicin exposure in vitro.

    Science.gov (United States)

    Takumida, M; Anniko, M

    2001-04-01

    Gentamicin-induced production of nitric oxide (NO) in the vestibular end organs of the guinea pig was investigated using the new fluorescence indicator 4,5-diaminofluorescein diacetate for direct detection of NO. Utricular maculae and isolated vestibular sensory cells were examined to locate NO production sites. The fluorescence intensity of the sensory cells was augmented by stimulation with gentamicin. This increase in fluorescence was inhibited by the presence of the non-specific inhibitor for nitric oxide synthase, L-N(G)-nitroarginine methylester, and by the non-specific N-methyl-D-aspartic acid antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate. These findings indicate that NO may play an important role in the ototoxicity of aminoglycoside.

  4. Novel pathways for ameliorating the fitness cost of gentamicin resistant small colony variants

    DEFF Research Database (Denmark)

    Vestergaard, Martin; Paulander, Wilhelm Erik Axel; Leng, Bingfeng

    2016-01-01

    mutations in the menaquinone and hemin biosynthesis pathways, which caused a significant reduction in exponential growth rates relative to wild type (WT; 0.59-0.72) and reduced membrane potentials. Fifty independent lineages of the low-fitness, resistant mutants were serially passaged for up to 500......Small colony variants (SCVs) of the human pathogen Staphylococcus aureus are associated with persistent infections. Phenotypically, SCVs are characterized by slow growth and they can arise upon interruption of the electron transport chain that consequently reduce membrane potential and thereby...... in the absence of gentamicin, 12 out of 15 lineages derived from SCVs with point mutations acquired intra-codonic suppressor mutations restoring membrane potential, growth rate, gentamicin susceptibility and colony size to WT levels. For the SCVs carrying deletions, all lineages enhanced fitness independent...

  5. Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: possible mechanism of nephroprotection.

    Science.gov (United States)

    Sahu, Bidya Dhar; Tatireddy, Srujana; Koneru, Meghana; Borkar, Roshan M; Kumar, Jerald Mahesh; Kuncha, Madhusudana; Srinivas, R; Shyam Sunder, R; Sistla, Ramakrishna

    2014-05-15

    Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrial NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and apoptosis in

  6. Effect of uric acid on gentamicin-induced nephrotoxicity in rats - role of matrix metalloproteinases 2 and 9.

    Science.gov (United States)

    Romero, Freddy; Pérez, Mariela; Chávez, Maribel; Parra, Gustavo; Durante, Paula

    2009-12-01

    In this work, we aimed to study the effect of uric acid on gentamicin-induced nephrotoxicity. Male Sprague-Dawley rats were assigned to one of six groups (six rats each) which received intraperitoneal injections for 9 days: (S) saline; (UA) Uric acid alone; (G) Gentamicin alone; (G + UA) Gentamicin + uric acid; (G rec) Gentamicin recovery and (G + UA rec) Gentamicin + uric acid recovery. In (G rec) and (G + UA rec), rats recovered for 7 days after the last injection. Urine and blood samples were taken on day 0 and at the end of every stage. Kidneys were harvested for histological scoring, determination of renal malondialdehyde (MDA), zymography and western blots for matrix metalloprotease (MMP)-2 and MMP-9. Uric acid alone did not provoke changes in biochemical and histological parameters when compared to controls. Gentamicin alone increased significantly plasma creatinine and blood urea nitrogen and caused a moderate histological damage. When combined with uric acid, these conditions worsened. MMP-9 activity and expression was decreased in rats from group G + UA as compared with rats from group G, while activity of MMP-2 was similarly increased in both groups when compared to controls. The increase in renal MDA induced by gentamicin was not altered when it was combined with uric acid. During the recovery stage, all biochemical parameters returned to normal levels, though a trend for delay of tubular damage recovery was observed in group G + UA rec when compared with group G rec. The results indicate that uric acid worsens gentamicin-induced nephrotoxicity. The mechanism is likely to implicate down-regulation of MMP-9.

  7. Histological Evidence of Nephroprotective Effect of Ashwagandha (Withania somnifera Root Extract against Gentamicin Induced Nephrotoxicity in Rats

    Directory of Open Access Journals (Sweden)

    Sadia Choudhury Shimmi

    2014-01-01

    Full Text Available Background: Kidney damage can occur due to exposure to nephrotoxic drugs, chemicals, toxins and infectious agents, ultimately leading to renal failure, management of which is a great challenge. So, efforts have been focused on traditional and herbal medicines for the treatment of renal failure. Ashwagandha (Withania somnifera may have free radical scavenging activity and can be used for the prevention and treatment of kidney damage. Objective: To observe the histological evidence of nephroprotective effect of Ashwagandha root against gentamicin induced nephrotoxicity in rats. Materials and Methods: This study was done in the department of Physiology, Sir Salimullah Medical College, Dhaka. A total number of 31 male Wistar albino rats were acclimatized for 14 days. Then, these were divided into two groups, control group consisted of 18 rats (Group A and Ashwagandha pretreated and gentamicin-treated group consisted of 13 rats (Group B. Control group was again subdivided into baseline control and gentamicin-treated control groups (A1 and A2 ─ each group contained 9 rats. All the animals received basal diet for 22 consecutive days. In addition to this, animals of Group A2 received gentamicin subcutaneously (100 mg/kg body weight/day from 15th to 22nd day and animals of Group B received Ashwagandha root extract (500 mg/kg body weight/day orally for 22 consecutive days and gentamicin subcutaneously (100 mg/kg body weight/day from 15th to 22nd day. All the animals were sacrificed on 23rd day. Then kidney samples were collected and histology was done by using standard laboratory procedure. Results: Histological examination of kidney revealed abnormal histological findings in 100% of gentamicin-treated rats. But 92.31% of rats in Ashwagandha pretreated and gentamicin-treated group showed almost normal structure and 7.69% showed mild histological changes. Conclusion: Ashwagandha root may have some nephroprotective effect against gentamicin induced

  8. Leishmanicidal Activity of Films Containing Paromomycin and Gentamicin Sulfate both In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    SH Hejazi

    2011-09-01

    Full Text Available Background: Based on the efficacy of paromomycin ointment and recent ongoing clinical trials of combination of paromomycin and gentamicin, a new physical form of films of the paromomy­cin and gentamicin was prepared and anti-Leishmania activities of the prepared films were as­sessed in vitro and in vivo.Methods: Paromomycin 15% and gentamicin 0.5% was incorporated in a film using ethyl cellu­lose and HPMC (Hydroxyl Propyl Methyl Cellulose. In order to assess the drug release and anti-Leishmania activities of the preparation, a clone L. major parasite was established using a set of modified NNN medium without overlay liquid layer. Therapeutic effects of the films were evalu­ated using Balb/c mice model. The mice were inoculated with 2×106 L. major promastigotes (MRHO/IR/75/ER and then when the lesions developed the mice were randomly divided in 3 groups, 10 mice per group, and treated with either perpetrated films or placebo for 28 days or left untreated.Results: Growth inhibition of cloned promastigotes showed that the films have enough releasing capacity and in vivo system, the films containing paromomycin and gentamicin was able to re­duce the lesion size and induced complete cure in 80% of the mice but relapse was seen in 60% of the cured mice and overall 50% cure rate was seen during 20 weeks period of the study.Conclusion: It seems that the prepared films might be further used in human clinical trials.

  9. Controlled gentamicin release from multi-layered electrospun nanofibrous structures of various thicknesses

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    Sirc J

    2012-10-01

    Full Text Available Jakub Sirc,1 Sarka Kubinova,2 Radka Hobzova,1 Denisa Stranska,3 Petr Kozlik,4 Zuzana Bosakova,4 Dana Marekova,2 Vladimir Holan,5 Eva Sykova,2 Jiri Michalek11Department of Polymer Gels, Institute of Macromolecular Chemistry, Academy of Science of the Czech Republic, Prague, Czech Republic; 2Department of Neuroscience, Institute of Experimental Medicine, Academy of Science of the Czech Republic, Prague, Czech Republic; 3Elmarco Ltd, Liberec, Czech Republic; 4Department of Analytical Chemistry, Faculty of Science, Charles University in Prague, Prague, Czech Republic; 5Department of Transplant Immunology, Institute of Molecular Genetics, Academy of Science of the Czech Republic, Prague, Czech RepublicAbstract: Polyvinyl alcohol nanofibers incorporating the wide spectrum antibiotic gentamicin were prepared by Nanospider™ needleless technology. A polyvinyl alcohol layer, serving as a drug reservoir, was covered from both sides by polyurethane layers of various thicknesses. The multilayered structure of the nanofibers was observed using scanning electron microscopy, the porosity was characterized by mercury porosimetry, and nitrogen adsorption/desorption measurements were used to determine specific surface areas. The stability of the gentamicin released from the electrospun layers was proved by high-performance liquid chromatography (HPLC and inhibition of bacterial growth. Drug release was investigated using in vitro experiments with HPLC/MS quantification, while the antimicrobial efficacy was evaluated on Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa. Both experiments proved that the released gentamicin retained its activity and showed that the retention of the drug in the nanofibers was prolonged with the increasing thickness of the covering layers.Keywords: nanofibers, electrospinning, multilayered structure, morphology, gentamicin, drug release

  10. Effect of caraway on gentamicin-induced oxidative stress, inflammation and nephrotoxicity in rats

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    Hoda Erjaee

    2015-07-01

    Full Text Available Different potentially therapeutic approaches to prevent or attenuate gentamicin (GEM induced nephrotoxicity have been proposed. The aim of the present study was to investigate the possible protective effects of caraway seed oil against GEM-induced nephrotoxicity in rats. Rats (24 were randomly assigned into four equal groups: i normal control group, ii treated with GEM, iii pretreated with orally caraway seed oil 10 (mg kg−1 plus GEM and iv treated with GEM and caraway seed oil 10 mg kg−1. Biochemical examinations were utilized for evaluation of the oxidative stress and renal nephrotoxicity. Creatinine, blood urea nitrogen (BUN, plasma malondialdehyde (MDA levels, catalase (CAT, superoxide dismutase (SOD and glutathione peroxidase (GSH-Px activities were determined. Administration of gentamicin to rats induced a marked renal failure, characterized by a significant increase in plasma creatinine and BUN concentrations. The animals treated with gentamicin alone showed a significantly higher plasma MDA level andlower SOD, GSH-Px and CAT activities when compared with the control group. Treatment and simultaneous treatment with caraway seed oil produced amelioration in MDA and increased the activity of antioxidant enzymes SOD, GSH-Px and CAT when compared with the gentamicin treated group. In addition, GEM nephrotoxicity increased renal inflammatory cytokines (TNF-α, IL-6 and IFN-γ. Pro-inflammatory cytokines were significantly decreased (P<0.05 in the test groups administered caraway seed oil. These findings suggest that caraway seed oil treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress and inflammation in rats.

  11. Vestibular results after intratympanic gentamicin therapy in disabling Menière's disease.

    Science.gov (United States)

    Junet, Philippe; Karkas, Alexandre; Dumas, Georges; Quesada, Jean Louis; Schmerber, Sébastien

    2016-10-01

    Intratympanic injection of gentamicin is increasingly used in the treatment of unilateral disabling Menière's disease (MD). Several objective functional and subjective tests have been developed to assess the control of vertigo after gentamicin treatment. The aim of this study was to show that subjective results require a vestibular deafferentation as profound as possible, evidenced with multifrequency vestibular assessment. Sixty four patients with intractable MD in situation of medical treatment failure longer than 6 months were included between 1998 and 2013 in this case control study. A 2-year follow-up was performed after the last intratympanic gentamicin performed with the titration technique. A vestibular assessment was applied before and after 2 years of treatment with a functional level score using the AAOHNS vertigo scale and multifrequency vestibular assessment: skull vibration-induced nystagmus test (SVINT), head-shaking test (HST) and caloric test (CaTe). The correlation between the results of the questionnaire and the level of the deafferentation as evaluated by the tests was analyzed with the Spearman test. Among the 64 included patients, 56 (87.5 %) described vertigo control. There was a correlation (=-0.33 [-0.53; -0.09], p = 0.008) between subjective improvement (AAO -HNS 1 or 2) and the degree of vestibular deafferentation as evidenced by a destructive nystagmus (beating toward the safe side) with the HST and the SVINT, as well as a caloric hypofunction >90 % with the CaTe. The present study demonstrates that a profound vestibular deafferentation confirmed with multifrequency test evaluation is needed to have a subjective improvement in the treatment of unilateral disabling MD with intratympanic gentamicin.

  12. Amylase-creatinine clearance ratio. A simple test to predict gentamicin nephrotoxicity.

    Science.gov (United States)

    Aderka, D; Tene, M; Graff, E; Levo, Y

    1988-05-01

    The initial target of aminoglycoside nephrotoxicity is the proximal tubule. Yet, no simple test is available to predict such toxicity. Taking advantage of the fact that amylase is filtered in the glomerulus and reabsorbed by the proximal tubules, we prospectively examined in 23 patients if changes in renal amylase creatinine clearance ratio (ACCR) can predict gentamicin nephrotoxicity. Eighteen of these patients had an initial creatinine clearance (rCcr) above 30 mL/min. Eleven of them (group A) had an ACCR above 3.5% (control 3% +/- 1.03%) and all exhibited an average reduction of 32.2% +/- 11.6% in rCcr following one week of gentamicin therapy. In contrast, only one of seven patients (group B) with an initial ACCR below 3.5% had a reduction, albeit transient, in rCcr. During gentamicin therapy, group A patients had a further increase in ACCR which was proportional to the reduction observed in rCcr (r = -.54). Our preliminary data suggest that ACCR may prove a simple and possibly a reliable predictor of kidney function deterioration during gentamicin therapy in patients with rCcr above 30 mL/min: patients with pretherapy ACCR above 3.5% may exhibit a deterioration in the creatinine clearance during the first week of therapy. For patients with pretherapy renal failure (rCcr less than 30 mL/min) the creatinine levels (but not the ACCR) seem to retain their significance in predicting and monitoring further renal function deterioration during aminoglycoside therapy.

  13. Effect of Tephrosia purpurea (L.) Pers. Leaves on Gentamicin-Induced Nephrotoxicity in Rats.

    Science.gov (United States)

    Jain, Avijeet; Nahata, Alok; Singhai, Abhay Kumar

    2013-01-01

    The aim of the study was to evaluate the nephroprotective and nephrocurative effects of Tephrosia purpurea (L.) Pers. leaves against gentamicin-induced acute renal injury in albino rats. The maximum free radical scavenging activity of the ethanolic extract was the basis for the selection of this extract for the in vivo study. Gentamicin (40 mg/kg, s.c.) was administered to induce toxicity in the toxic group and the ethanolic extract (200 mg/kg p.o.) was administered in all treated groups. Blood urea and serum creatinine levels were monitored to assess the effects. The antioxidant potential was also evaluated by the estimation of reduced glutathione (GSH) and malondialdehyde (MDA). Gentamicin intoxication caused significant increases in blood urea and serum creatinine levels as compared to the normal control. In the preventive regimen, the extract (200 mg/kg, p.o.) showed significant reductions in the elevated blood urea and serum creatinine. Histopathological changes were in accordance with the biochemical findings. Also in the curative regimen, the blood urea and serum creatinine levels revealed significant curative effects. In our in vivo antioxidant activity, the GSH level was significantly (PTephrosia purpurea leaves possesses marked nephroprotective and curative activities without any toxicity. The proposed mechanisms for the claimed activity are antioxidant activity and the inhibition of an overproduction of NO and Cox-2 expression. These activities may be attributed to the presence of phenolics and flavonoidal compounds like rutin and quercetin. Thus, it can be said that Tephrosia purpurea could offer a promising role in the treatment of acute renal injury caused by nephrotoxins like gentamicin.

  14. Collagen implant with gentamicin sulphate reduces surgical site infection in vascular surgery: a prospective cohort study.

    Science.gov (United States)

    Costa Almeida, Carlos Eduardo Perdigão; Reis, Luis; Carvalho, Luis; Costa Almeida, Carlos Manuel

    2014-10-01

    Surgical site infection (SSI) is a common complication after vascular surgery. It may cause exposure of the underlying prosthesis causing graft infection, which may require the removal of the vascular graft, increasing amputation and mortality risks. Graft contamination usually occurs during operative procedure or by direct spread from an infected wound. It is therefore advisable to a strong effort in reducing SSI. Topic antibiotics have not been fully studied in vascular surgery, but collagen implant with gentamicin sulphate has shown to reduce SSI in cardiac surgery, orthopaedics, and general surgery procedures. Sixty (60) non-diabetic and non-obese patients with lower limb ischaemia with indication for femoropopliteal PTFE prosthetic bypass were allocated into 2 groups of 30 patients. A collagen implant impregnated with gentamicin sulphate (Collatamp(®)) was applied in the groin incision adjacent to the prosthesis in one group, and the other was a control group. The same surgical team operated all patients. Szilagyi classification was used. There was no SSI (0% - 0/30) in the collagen implant with gentamicin sulphate group, contrasting with 6 cases (20% - 6/30) of SSI (grade I and II) in the control group (p = 0.024). In-hospital day's data shows a significant difference between the two groups (p = 0.004) with a mean of 5.66 days for implant group and 8.10 days for control group. There was no SSI grade III. Collagen implant with gentamicin sulphate (Collatamp(®)) reduces SSI in the groin incision in ischaemic patients submitted to femoropopliteal PTFE prosthetic bypass. Days of hospitalization are also reduced. Decreasing SSI rate and in-hospital days, this implant may also reduce health care costs. Because this is a small pilot study, a multicentre RCT is necessary for validation. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  15. Protective effect of pomegranate flower extract against gentamicin-induced renal toxicity in male rats

    OpenAIRE

    Sadeghi, Ferdos; Nematbakhsh, Mehdi; Noori-Diziche, Ali; Eshraghi-Jazi, Fatemeh; Talebi, Ardeshir; Nasri, Hamid; Mansouri, Azam; Dehghani, Aghdas; Saberi, Shadan; Shirdavani, Soheila; Ashrafi, Farzaneh

    2015-01-01

    Introduction: Gentamicin (GM) as an antibiotic is used in clinic. However, its administration is limited by side effects such as nephrotoxicity. Herbal extracts could be used in therapeutic approaches. Objectives: The present study was planned to investigate whether pomegranate flower extract (PFE) could ameliorate GM-induced renal toxicity in male rats. Materials and Methods: Twenty eight male Wistar rats were divided into 5 groups. Groups 1 and 2 respectively received PFE 25 and 50 mg/kg fo...

  16. Sensitive immunochemical approaches for quantitative (FPIA) and qualitative (lateral flow tests) determination of gentamicin in milk.

    Science.gov (United States)

    Beloglazova, N V; Shmelin, P S; Eremin, S A

    2016-01-01

    Three kinds of immunoassays for the determination of gentamicin in milk samples were developed and validated. First, a fast and easily-performed fluorescence polarization immunoassay was used for characterization of the employed polyclonal antibody. The calculated Kaff were (1.9±0.4)×10(9)М(-1) and (6.0±0.2)×10(6)М(-1) for the high- and low-affinity fractions respectively. The assay was characterized with a good sensitivity, the limit of detection being 5μgkg(-1). Two different kinds of detection labels, i.e. colloidal gold (CG) and quantum dots (QDs), were evaluated for use in lateral-flow format with respect to rapid visual on-site testing. The cut-off levels for both qualitative formats were selected based on the maximum level for gentamicin in milk established by the European Commission, 100μgkg(-1), resulting in a 10μgkg(-1) cut-off considering sample dilution. The intra-laboratory validation was performed with sterilized milk samples artificially spiked with gentamicin at concentrations less than, equal to, and greater than the cut-off level. It was shown that milk products could be analyzed without any sample preparation, except for dilution with the buffer solution. The rates of false-positive and false-negative results were below 5% for both labels. The different developed immunoassays were tested towards gentamicin determination in artificially-spiked and naturally contaminated milk samples. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Refractory episodic vertigo: role of intratympanic gentamicin and vestibular evoked myogenic potentials.

    Science.gov (United States)

    Celis-Aguilar, Erika; Hinojosa-González, Ramon; Vales-Hidalgo, Olivia; Coutinho-Toledo, Heloisa

    Even today, the treatment of intractable vertigo remains a challenge. Vestibular ablation with intratympanic gentamicin stands as a good alternative in the management of refractory vertigo patients. To control intractable vertigo through complete saccular and horizontal canal vestibular ablation with intratympanic gentamicin treatment. Patients with refractory episodic vertigo were included. The inclusion criteria were: unilateral ear disease, moderate to profound sensorineural hearing loss, and failure to other treatments. Included patients underwent 0.5-0.8mL of gentamicin intratympanic application at a 30mg/mL concentration. Vestibular ablation was confirmed by the absence of response on cervical vestibular evoked myogenic potentials and no response on caloric tests. Audiometry, electronystagmography with iced water, and vestibular evoked myogenic potentials were performed in all patients. Ten patients were included; nine patients with Meniere's disease and one patient with (late onset) delayed hydrops. Nine patients showed an absent response on vestibular evoked myogenic potentials and no response on caloric tests. The only patient with low amplitude on cervical vestibular evoked myogenic potentials had vertigo recurrence. Vertigo control was achieved in 90% of the patients. One patient developed hearing loss >30dB. Cervical vestibular evoked myogenic potentials confirmed vestibular ablation in patients treated with intratympanic gentamicin. High-grade vertigo control was due to complete saccular and horizontal canal ablation (no response to iced water in electronystagmography and no response on cervical vestibular evoked myogenic potentials). Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  18. Subcutaneous gentamicin injection around the cuff in treatment of resistant exit site infection in peritoneal dialysis patients: a pilot study.

    Science.gov (United States)

    Dizdar, Oguzhan Sıtkı; Ozer, Ozerhan; Erdem, Selahattin; Gunal, Ali Ihsan

    2017-01-01

    One of the most common complications of the peritoneal dialysis (PD) is the infection of the exit site of the peritoneal catheter. The aim of the present study was to evaluate the efficacy of the subcutaneous gentamicin injection around the cuff as a part of routine treatment of the resistant exit site infection (ESI). If the exit site remains infected after a 2-week systemic antibiotics treatment, it is defined as resistant ESI. In these cases, systemic antibiotics were discontinued and a subcutaneous 40-mg gentamicin injection was administered around the external cuff of the PD catheter every 3 days. A total of three or four injections were given to each patient. A subcutaneous gentamicin injection was administered around the cuff in thirteen patients for the treatment of resistant ESI over a 2-year period. The median follow-up time in cured patients was 12 months. Eleven of the thirteen patients had been apparently cured of their resistant ESI, with no recurrence. None of the patients had a gentamicin-resistant species. Subcutaneous gentamicin-related adverse effect was not observed in any patient. Subcutaneous gentamicin injection around the cuff is a well-tolerated and effective strategy for treating resistant ESI. To gain widespread approval of this therapy and reach a consensus about ESI management, additional studies are needed.

  19. Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS

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    Mohamed A. Morsy

    2014-01-01

    Full Text Available Gentamicin, an aminoglycoside antibiotic, is used for the treatment of serious Gram-negative infections. However, its usefulness is limited by its nephrotoxicity. Sildenafil, a selective phosphodiesterase-5 inhibitor, was reported to prevent or decrease tissue injury. The aim of this study is to evaluate the potential protective effects of sildenafil on gentamicin-induced nephrotoxicity in rats. Male Wistar rats were injected with gentamicin (100 mg/kg/day, i.p. for 6 days with and without sildenafil. Sildenafil administration resulted in nephroprotective effect in gentamicin-intoxicated rats as it significantly decreased serum creatinine and urea, urinary albumin, and renal malondialdehyde and nitrite/nitrate levels, with a concomitant increase in renal catalase and superoxide dismutase activities compared to gentamicin-treated rats. Moreover, immunohistochemical examination revealed that sildenafil treatment markedly reduced inducible nitric oxide synthase (iNOS expression, while expression of endothelial nitric oxide synthase (eNOS was markedly enhanced. The protective effects of sildenafil were verified histopathologically. In conclusion, sildenafil protects rats against gentamicin-induced nephrotoxicity possibly, in part, through its antioxidant activity, inhibition of iNOS expression, and induction of eNOS production.

  20. [Amoxicillin and clavulanic acid versus amoxicillin plus gentamicin in the empirical initial treatment of urinary tract infections in hospitalized patients].

    Science.gov (United States)

    Verzasconi, R; Rodoni, P; Monotti, R; Marone, C; Mombelli, G

    1995-08-19

    We compared the fixed combination amoxicillin plus clavulanic acid with that of amoxicillin plus gentamicin in the empirical initial treatment of severe urinary tract infections. The study included 87 hospitalized patients (51 women and 36 men, mean age 58 +/- 22 years) with acute uncomplicated pyelonephritis (n = 48) or with complicated urinary tract infections (n = 39). 80 patients (92%) had fever and 31 patients (36%) positive blood cultures. 45 patients were randomly assigned to amoxicillin plus clavulanic acid and 42 to amoxicillin plus gentamicin. Overall, 18 patients (21%) were infected with organisms resistant in vitro to amoxicillin plus clavulanic acid, whereas no pathogen was isolated with resistance to amoxicillin plus gentamicin (p amoxicillin plus gentamicin (p amoxicillin plus gentamicin group. Although the in-vitro resistance did not result in a lower clinical efficacy of amoxicillin plus clavulanic acid compared to amoxicillin plus gentamicin in our relatively small sample of patients, the data indicate that the antimicrobial activity of amoxicillin plus clavulanic acid is inadequate to cover the spectrum of causative agents in hospitalized patients with pyelonephritis or complicated urinary tract infections. Amoxicillin plus clavulanic acid should therefore not be used in the initial empirical treatment of these infections.

  1. Gentamicin loaded PLGA nanoparticles as local drug delivery system for the osteomyelitis treatment.

    Science.gov (United States)

    Posadowska, Urszula; Brzychczy-Włoch, Monika; Pamuła, Elżbieta

    2015-01-01

    Since there are more and more cases of multiresistance among microorganisms, rational use of antibiotics (especially their systemic vs. local application) is of great importance. Here we propose polymeric nanoparticles as locally applied gentamicin delivery system useful in osteomyelitis therapy. Gentamicin sulphate (GS) was encapsulated in the poly(lactide-co-glycolide) (PLGA 85:15) nanoparticles by double emulsification (water/oil/water, W1/O/W2). The nanoparticles were characterized by dynamic light scattering, laser electrophoresis and atomic force microscopy. UV-vis spectroscopy (O-phthaldialdehyde assay, OPA) and Kirby-Bauer tests were used to evaluate drug release and antimicrobial activity, respectively. Physicochemical characterization showed that size, shape and drug solubilization of the nanoparticles mainly depended on GS content and concentration of surface stabilizer (polyvinyl alcohol, PVA). Laser electrophoresis demonstrated negative value of zeta potential of the nanoparticles attributed to PLGA carboxyl end group presence. Drug release studies showed initial burst release followed by prolonged 35-day sustained gentamicin delivery. Agar-diffusion tests performed with pathogens causing osteomyelitis (Staphylococcus aureus and Staphylococcus epidermidis, both reference strains and clinical isolates) showed antibacterial activity of GS loaded nanoparticles (GS-NPs). It can be concluded that GS-NPs are a promising form of biomaterials useful in osteomyelitis therapy.

  2. Chromosomally and Extrachromosomally Mediated High-Level Gentamicin Resistance in Streptococcus agalactiae.

    Science.gov (United States)

    Sendi, Parham; Furitsch, Martina; Mauerer, Stefanie; Florindo, Carlos; Kahl, Barbara C; Shabayek, Sarah; Berner, Reinhard; Spellerberg, Barbara

    2016-01-04

    Streptococcus agalactiae (group B Streptococcus [GBS]) is a leading cause of sepsis in neonates. The rate of invasive GBS disease in nonpregnant adults also continues to climb. Aminoglycosides alone have little or no effect on GBS, but synergistic killing with penicillin has been shown in vitro. High-level gentamicin resistance (HLGR) in GBS isolates, however, leads to the loss of a synergistic effect. We therefore performed a multicenter study to determine the frequency of HLGR GBS isolates and to elucidate the molecular mechanisms leading to gentamicin resistance. From eight centers in four countries, 1,128 invasive and colonizing GBS isolates were pooled and investigated for the presence of HLGR. We identified two strains that displayed HLGR (BSU1203 and BSU452), both of which carried the aacA-aphD gene, typically conferring HLGR. However, only one strain (BSU1203) also carried the previously described chromosomal gentamicin resistance transposon designated Tn3706. For the other strain (BSU452), plasmid purification and subsequent DNA sequencing resulted in the detection of plasmid pIP501 carrying a remnant of a Tn3 family transposon. Its ability to confer HLGR was proven by transfer into an Enterococcus faecalis isolate. Conversely, loss of HLGR was documented after curing both GBS BSU452 and the transformed E. faecalis strain from the plasmid. This is the first report showing plasmid-mediated HLGR in GBS. Thus, in our clinical GBS isolates, HLGR is mediated both chromosomally and extrachromosomally.

  3. A New Type of Biphasic Calcium Phosphate Cement as a Gentamicin Carrier for Osteomyelitis

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    Wen-Yu Su

    2013-01-01

    Full Text Available Osteomyelitis therapy is a long-term and inconvenient procedure for a patient. Antibiotic-loaded bone cements are both a complementary and alternative treatment option to intravenous antibiotic therapy for the treatment of osteomyelitis. In the current study, the biphasic calcium phosphate cement (CPC, called α-TCP/HAP (α-tricalcium phosphate/hydroxyapatite biphasic cement, was prepared as an antibiotics carrier for osteomyelitis. The developed biphasic cement with a microstructure of α-TCP surrounding the HAP has a fast setting time which will fulfill the clinical demand. The X-ray diffraction and Fourier transform infrared spectrometry analyses showed the final phase to be HAP, the basic bone mineral, after setting for a period of time. Scanning electron microscopy revealed a porous structure with particle sizes of a few micrometers. The addition of gentamicin in α-TCP/HAP would delay the transition of α-TCP but would not change the final-phase HAP. The gentamicin-loaded α-TCP/HAP supplies high doses of the antibiotic during the initial 24 hours when they are soaked in phosphate buffer solution (PBS. Thereafter, a slower drug release is produced, supplying minimum inhibitory concentration until the end of the experiment (30 days. Studies of growth inhibition of Staphylococcus aureus and Pseudomonas aeruginosa in culture indicated that gentamicin released after 30 days from α-TCP/HAP biphasic cement retained antibacterial activity.

  4. Application of a neural network for gentamicin concentration prediction in a general hospital population.

    Science.gov (United States)

    Corrigan, B W; Mayo, P R; Jamali, F

    1997-02-01

    Neural network (NN) computation is computer modeling based in part on simulation of the structure and function of the brain. These modeling techniques have been found useful as pattern recognition tools. In the present study, data including age, sex, height, weight, serum creatinine concentration, dose, dosing interval, and time of measurement were collected from 240 patients with various diseases being treated with gentamicin in a general hospital setting. The patient records were randomly divided into two sets: a training set of 220 patients used to develop relationships between input and output variables (peak and trough plasma concentrations) and a testing set (blinded from the NN) of 20 to test the NN. The network model was the back-propagation, feed-forward model. Various networks were tested, and the most accurate networks for peak and trough (calculated as mean percent error, root mean squared error of the testing group, and tau value between observed and predicted values) were reported. The results indicate that NNs can predict gentamicin serum concentrations accurately from various input data over a range of patient ages and renal function and may offer advantages over traditional dose prediction methods for gentamicin.

  5. Effect of Momordica dioica Roxb on gentamicin model of acute renal failure.

    Science.gov (United States)

    Jain, Avijeet; Singhai, A K

    2010-09-01

    The ethanolic extract of the fruits of Momordica dioica was studied for its protective and curative effect against gentamicin-induced acute renal injury in albino rats of both sexes. Gentamicin intoxicated group showed significant increase in blood urea (69.48 +/- 4.34) and serum creatinine (3.017 +/- 0.208) from normal levels 33.72 +/- 1.92 and 0.818 +/- 0.073, respectively, in control group. In the preventive regimen, the extract at dose levels of 200 mg kg(-1) showed significant reduction in the elevated blood urea (47.93 +/- 2.46) and serum creatinine (2.067 +/- 0.1745), respectively. This treatment normalised the histopathological changes compared to the intoxicated group. In the curative regimen at 200 mg kg(-1) blood urea was found to be 48.21 +/- 2.36 and serum creatinine level was 2.050 +/- 0.183, which revealed significant curative effect. In vivo antioxidant and free radial scavenging activities were also determined. The maximum free radical scavenging activity with ethanolic extract was the basis of selection of this extract for in vivo study. Reduced glutathione (GSH) level was significantly (p Momordica dioica seeds possesses marked nephroprotective and curative activities without any toxicity due to its antioxidant activity and could offer a promising role in the treatment of acute renal injury caused by nephrotoxin-like gentamicin.

  6. Activity of Daptomycin Alone and in Combination with Rifampin and Gentamicin against Staphylococcus aureus Assessed by Time-Kill Methodology▿ †

    Science.gov (United States)

    Credito, Kim; Lin, Gengrong; Appelbaum, Peter C.

    2007-01-01

    The synergistic effects of daptomycin plus gentamicin or rifampin were tested against 50 Staphylococcus aureus strains, with daptomycin MICs ranging between 0.25 and 8 μg/ml. Daptomycin sub-MICs combined with gentamicin concentrations lower than the MIC yielded synergy in 34 (68%) of the 50 strains. Daptomycin combined with rifampin yielded synergy in one vancomycin-intermediate S. aureus strain only, and virtually all synergy occurred between daptomycin and gentamicin. PMID:17220402

  7. Extracellular gentamicin reduces the activity of connexin hemichannels and interferes with purinergic Ca2+ signaling in HeLa cells

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    Vania A Figueroa

    2014-09-01

    Full Text Available Gap junction channels (GJCs and hemichannels (HCs are composed of protein subunits termed connexins (Cxs and are permeable to ions and small molecules. In most organs, GJCs communicate the cytoplasm of adjacent cells, while HCs communicate the intra and extracellular compartments. In this way, both channel types coordinate physiological responses of cell communities. Cx mutations explain several genetic diseases, including about 50% of autosomal recessive nonsyndromic hearing loss. However, the possible involvement of Cxs in the etiology of acquired hearing loss remains virtually unknown. Factors that induce post-lingual hearing loss are diverse, exposure to gentamicin an aminoglycoside antibiotic, being the most common. Gentamicin has been proposed to block GJCs, but its effect on HCs remains unknown. In this work, the effect of gentamicin on the functional state of HCs was studied and its effect on GJCs was reevaluated in HeLa cells stably transfected with Cxs. We focused on Cx26 because it is the main Cx expressed in the cochlea of mammals where it participates in purinergic signaling pathways. We found that gentamicin applied extracellularly reduces the activity of HCs, while dye transfer across GJCs was not affected. HCs were also blocked by streptomycin, another aminoglycoside antibiotic. Gentamicin also reduced the ATP release and the HC-dependent oscillations of cytosolic free-Ca2+ signal. Moreover, gentamicin drastically reduced the Cx26 HC-mediated membrane currents in Xenopus laevis oocytes. Therefore, the extracellular gentamicin-induced inhibition of Cx HCs may adversely affect autocrine and paracrine signaling, including the purinergic one, which might partially explain its ototoxic effects.

  8. Extracellular gentamicin reduces the activity of connexin hemichannels and interferes with purinergic Ca2+ signaling in HeLa cells

    Science.gov (United States)

    Figueroa, Vania A.; Retamal, Mauricio A.; Cea, Luis A.; Salas, José D.; Vargas, Aníbal A.; Verdugo, Christian A.; Jara, Oscar; Martínez, Agustín D.; Sáez, Juan C.

    2014-01-01

    Gap junction channels (GJCs) and hemichannels (HCs) are composed of protein subunits termed connexins (Cxs) and are permeable to ions and small molecules. In most organs, GJCs communicate the cytoplasm of adjacent cells, while HCs communicate the intra and extracellular compartments. In this way, both channel types coordinate physiological responses of cell communities. Cx mutations explain several genetic diseases, including about 50% of autosomal recessive non-syndromic hearing loss. However, the possible involvement of Cxs in the etiology of acquired hearing loss remains virtually unknown. Factors that induce post-lingual hearing loss are diverse, exposure to gentamicin an aminoglycoside antibiotic, being the most common. Gentamicin has been proposed to block GJCs, but its effect on HCs remains unknown. In this work, the effect of gentamicin on the functional state of HCs was studied and its effect on GJCs was reevaluated in HeLa cells stably transfected with Cxs. We focused on Cx26 because it is the main Cx expressed in the cochlea of mammals where it participates in purinergic signaling pathways. We found that gentamicin applied extracellularly reduces the activity of HCs, while dye transfer across GJCs was not affected. HCs were also blocked by streptomycin, another aminoglycoside antibiotic. Gentamicin also reduced the adenosine triphosphate release and the HC-dependent oscillations of cytosolic free-Ca2+ signal. Moreover, gentamicin drastically reduced the Cx26 HC-mediated membrane currents in Xenopus laevis oocytes. Therefore, the extracellular gentamicin-induced inhibition of Cx HCs may adversely affect autocrine and paracrine signaling, including the purinergic one, which might partially explain its ototoxic effects. PMID:25237294

  9. Gentamicin-induced ototoxicity and nephrotoxicity vary with circadian time of treatment and entail separate mechanisms.

    Science.gov (United States)

    Blunston, Mary A; Yonovitz, Al; Woodahl, Erica L; Smolensky, Michael H

    2015-01-01

    The aminoglycoside antibiotic gentamicin can cause both ototoxicity and nephrotoxicity, the severity of which varies with circadian time of daily treatment. However, it is not yet resolved if such drug-induced adverse effects are independent or interdependent phenomena. Two groups of 9 female Sprague-Dawley rats (200-250 g), each housed separately and entrained to a 12 h light (06:00-18:00 h) - 12 h dark cycle, received a daily subcutaneous injection of 100 mg/kg gentamicin. One group was treated at the beginning of the activity span, 2 Hours After Lights On (HALO), and the other at the beginning of the rest span, 14 HALO. Global toxicity was gauged by both body weight loss relative to the pre-treatment baseline and number of deaths. Ototoxicity, i.e., hearing loss, was assessed by changes in auditory brainstem response (ABR) for pure tone stimuli of 8, 16, 24, and 32 kHz before and after 2 and 4 weeks of gentamicin treatment. Renal toxicity was evaluated by changes in urinary N-acetyl-β-glucosaminidase (NAG)/creatinine (CR) concentration ratio before and after each week of treatment. In a complementary substudy of separate but comparable 2 and 14 HALO groups of rats, blood samples were obtained before and 30, 60, 120, and 240 min post-subcutaneous injection of 100 mg/kg gentamicin. Number of animal deaths was greater in the 2 (4 deaths) than 14 HALO (1 death) group, mirroring more severe initial (first two weeks of treatment) body weight losses from baseline, being more than 2-fold greater in animals of the 2 than 14 HALO group. Ototoxicity progressively worsened during the treatment; although, the extent of hearing loss varied according to circadian time of treatment across all frequencies (p ototoxicity. The mean urinary NAG/CR ratio peaked after the first week of treatment, averaging 13.64-fold greater than baseline for the 2 HALO-treated animals compared to 7.38-fold greater than baseline for the 14 HALO-treated ones. Ratio values declined

  10. Mesenchymal stem cell-conditioned medium accelerates regeneration of human renal proximal tubule epithelial cells after gentamicin toxicity.

    Science.gov (United States)

    Moghadasali, Reza; Mutsaers, Henricus A M; Azarnia, Mahnaz; Aghdami, Nasser; Baharvand, Hossein; Torensma, Ruurd; Wilmer, Martijn J G; Masereeuw, Rosalinde

    2013-07-01

    Bone marrow-derived mesenchymal stem cells (MSCs) have the capacity to regenerate renal tubule epithelia and repair renal function without fusing with resident tubular cells. The goal of the present project was to investigate the role of MSCs secreted cytokines on tubule cell viability and regeneration after a toxic insult, using a conditionally immortalized human proximal tubule epithelial cell (ciPTEC) line. Gentamicin was used to induce nephrotoxicity, and cell viability and migration were studied in absence and presence of human MSC-conditioned medium (hMSC-CM) i.e. medium containing soluble factors produced and secreted by MSCs. Exposure of ciPTEC to 0-3000 μg/ml gentamicin for 24 h caused a significant dose-dependent increase in cell death. We further demonstrated that the nephrotoxic effect of 2000 μg/ml gentamicin was recovered partially by exposing cells to hMSC-CM. Moreover, exposure of ciPTEC to gentamicin (1500-3000 μg/ml) for 7 days completely attenuated the migratory capacity of the cells. In addition, following scrape-wounding, cell migration of both untreated and gentamicin-exposed cells was increased in the presence of hMSC-CM, as compared to exposures to normal medium, indicating improved cell recovery. Our data suggest that cytokines secreted by MSCs stimulate renal tubule cell regeneration after nephrotoxicity. Copyright © 2012 Elsevier GmbH. All rights reserved.

  11. Neurotrophic and antioxidant effects of silymarin comparable to 4-methylcatechol in protection against gentamicin-induced ototoxicity in guinea pigs.

    Science.gov (United States)

    Draz, Eman I; Abdin, Amany A; Sarhan, Naglaa I; Gabr, Takwa A

    2015-04-01

    Despite that gentamicin is a very effective aminoglycoside, its potential ototoxicity which is of irreversible nature makes a challenge and limitation for its use. This study was designed to investigate possible neurotrophic and antioxidant effects of silymarin comparable to 4-methylcatechol in protection against gentamicin-induced ototoxicity. Twenty pigmented guinea pigs were divided into four equal groups, where group I served as normal control group. The other groups received gentamicin (120 mg/kg/day, ip) for 19 days where group II given vehicle of 1% CMC, group III and group IV were pre-treated 2h before gentamicin by 4-methylcatechol (10 μg/kg, ip) and silymarin (100mg/kg, oral gavage), respectively. The main findings indicated that silymarin exhibited restoration of nerve growth factor (NGF) levels and increased tropomyosin-related kinase receptors-A (Trk-A) m-RNA expression in cochlear tissue and preservation of hair cells of organ of Corti by scanning electron microscopy (SEM) with significant decrease in auditory brainstem response (ABR) threshold compared to 4-methylcatechol. Only silymarin caused significant amelioration in oxidative stress state by reducing malondialdehyde (MDA) levels and increasing catalase activity. Silymarin exerts superiority over 4-methylcatechol when recommended as protective agent against gentamicin ototoxicity based on its efficient neurotrophic and antioxidant activities. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  12. Gentamicin-loaded wound dressing with polyvinyl alcohol/dextran hydrogel: gel characterization and in vivo healing evaluation.

    Science.gov (United States)

    Hwang, Ma-Ro; Kim, Jong Oh; Lee, Jeong Hoon; Kim, Yong Il; Kim, Jeong Hoon; Chang, Sun Woo; Jin, Sung Gju; Kim, Jung Ae; Lyoo, Won Seok; Han, Sung Soo; Ku, Sae Kwang; Yong, Chul Soon; Choi, Han-Gon

    2010-09-01

    To develop a gentamicin-loaded wound dressing, cross-linked hydrogel films were prepared with polyvinyl alcohol (PVA) and dextran using the freezing-thawing method. Their gel properties such as gel fraction, swelling, water vapor transmission test, morphology, tensile strength, and thermal property were investigated. In vitro protein adsorption test, in vivo wound healing test, and histopathology were performed. Dextran decreased the gel fraction, maximum strength, and thermal stability of hydrogels. However, it increased the swelling ability, water vapor transmission rate, elasticity, porosity, and protein adsorption. The drug gave a little positive effect on the gel properties of hydrogels. The gentamicin-loaded wound dressing composed of 2.5% PVA, 1.13% dextran, and 0.1% drug was more swellable, flexible, and elastic than that with only PVA because of its cross-linking interaction with PVA. In particular, it could provide an adequate level of moisture and build up the exudates on the wound area. From the in vivo wound healing and histological results, this gentamicin-loaded wound dressing enhanced the healing effect more compared to conventional product because of the potential healing effect of gentamicin. Thus, this gentamicin-loaded wound dressing would be used as a potential wound dressing with excellent forming and improved healing effect in wound care.

  13. Co-delivery of ibuprofen and gentamicin from nanoporous anodic titanium dioxide layers.

    Science.gov (United States)

    Pawlik, Anna; Jarosz, Magdalena; Syrek, Karolina; Sulka, Grzegorz D

    2017-04-01

    Although single-drug therapy may prove insufficient in treating bacterial infections or inflammation after orthopaedic surgeries, complex therapy (using both an antibiotic and an anti-inflammatory drug) is thought to address the problem. Among drug delivery systems (DDSs) with prolonged drug release profiles, nanoporous anodic titanium dioxide (ATO) layers on Ti foil are very promising. In the discussed research, ATO samples were synthesized via a three-step anodization process in an ethylene glycol-based electrolyte with fluoride ions. The third step lasted 2, 5 and 10min in order to obtain different thicknesses of nanoporous layers. Annealing the as-prepared amorphous layers at the temperature of 400°C led to obtaining the anatase phase. In this study, water-insoluble ibuprofen and water-soluble gentamicin were used as model drugs. Three different drug loading procedures were applied. The desorption-desorption-diffusion (DDD) model of the drug release was fitted to the experimental data. The effects of crystalline structure, depth of TiO2 nanopores and loading procedure on the drug release profiles were examined. The duration of the drug release process can be easily altered by changing the drug loading sequence. Water-soluble gentamicin is released for a long period of time if gentamicin is loaded in ATO as the first drug. Additionally, deeper nanopores and anatase phase suppress the initial burst release of drugs. These results confirm that factors such as morphological and crystalline structure of ATO layers, and the procedure of drug loading inside nanopores, allow to alter the drug release performance of nanoporous ATO layers.

  14. Electrochemical detection of tobramycin or gentamicin according to the European Pharmacopoeia analytical method.

    Science.gov (United States)

    Ghinami, C; Giuliani, V; Menarini, A; Abballe, F; Travaini, S; Ladisa, T

    2007-01-12

    Tobramycin and gentamicin are two aminoglycosidic antibiotics used in lung infection, ophthalmic treatments as well as in skin infections. Pharmaceutical companies which produce remedies containing tobramycin and gentamicin need an analytical method for their internal quality control. For several years a simple chromatographic method based on anion exchange separation coupled with amperometric detection was proposed for aminoglycosides. This analytical approach was partially used in the last edition of the European Pharmacopoeia (EP) for tobramycin and gentamicin analysis. In fact they use integrated pulsed amperometric detection (IPAD) on a gold electrode while the separation is obtained on a polymeric wide pore reversed phase instead of anion exchange in alkaline conditions. Such coupling seems to be cumbersome and not so easy to realize and to reproduce from one laboratory to another. Besides, the described method lacks some of the details as important as the waveform steps duration. Unfortunately the quality control (QC) laboratories have to use exactly the method described in the EP, so they complained about the troubles. Therefore, the EP authors published recently a paper regarding the guidelines for good practice in the method application, but the suggestion was not yet resolutive. In our work we evaluated the eluent composition and the kind of amperometric cell, work electrode diameter and cell volume. Mainly we optimized the amperometric waveform. In addition, for tobramycin analysis another chromatographic phase was explored in order to achieve better efficiency and to separate all the impurities confirming the effectiveness of the detection. The conditions described in the paper seem to allow the analyst to operate in conformity with the EP method.

  15. Using Six Sigma to improve once daily gentamicin dosing and therapeutic drug monitoring performance.

    LENUS (Irish Health Repository)

    Egan, Sean

    2012-08-07

    BACKGROUND: Safe, effective therapy with the antimicrobial gentamicin requires good practice in dose selection and monitoring of serum levels. Suboptimal therapy occurs with breakdown in the process of drug dosing, serum blood sampling, laboratory processing and level interpretation. Unintentional underdosing may result. This improvement effort aimed to optimise this process in an academic teaching hospital using Six Sigma process improvement methodology. METHODS: A multidisciplinary project team was formed. Process measures considered critical to quality were defined, and baseline practice was examined through process mapping and audit. Root cause analysis informed improvement measures. These included a new dosing and monitoring schedule, and standardised assay sampling and drug administration timing which maximised local capabilities. Three iterations of the improvement cycle were conducted over a 24-month period. RESULTS: The attainment of serum level sampling in the required time window improved by 85% (p≤0.0001). A 66% improvement in accuracy of dosing was observed (p≤0.0001). Unnecessary dose omission while awaiting level results and inadvertent disruption to therapy due to dosing and monitoring process breakdown were eliminated. Average daily dose administered increased from 3.39 mg\\/kg to 4.78 mg\\/kg\\/day. CONCLUSIONS: Using Six Sigma methodology enhanced gentamicin usage process performance. Local process related factors may adversely affect adherence to practice guidelines for gentamicin, a drug which is complex to use. It is vital to adapt dosing guidance and monitoring requirements so that they are capable of being implemented in the clinical environment as a matter of routine. Improvement may be achieved through a structured localised approach with multidisciplinary stakeholder involvement.

  16. Inhibition of K+ currents in type I vestibular hair cells by gentamicin and neomycin.

    Science.gov (United States)

    Mann, Scott E; Johnson, Matthew; Meredith, Frances L; Rennie, Katherine J

    2013-01-01

    Significant ototoxicity limits the use of aminoglycoside (AG) antibiotics. Several mechanisms may contribute to the death of both auditory and vestibular hair cells. In this study the effects of gentamicin and neomycin on K(+) currents in mature and early postnatal type I vestibular hair cells (HCI) were tested directly. The whole-cell patch clamp technique was used to assess the effects of AG and KCNQ channel modulators on K(+) currents (IK) in HCI acutely isolated from gerbil semicircular canals. Extracellular neomycin (1 mM) rapidly reduced peak outward IK by 16 ± 4% (n = 9) in mature HCI (postnatal days, P, 25-66). Gentamicin (5 mM) reduced outward IK by 16 ± 3% (n = 8). A similar reduction in outward current was seen in immature HCI (P5-9) that lacked the low-voltage-activated component of IK observed in mature cells. Intracellular application of gentamicin and neomycin also reduced IK in mature HCI. Modulators of KCNQ channels were used to probe KCNQ channel involvement. The selective KCNQ antagonist XE991 did not reduce IK and the neomycin-induced reduction in IK was not reversed by the KCNQ agonist flupirtine. Application of intracellular poly-D-lysine to sequester PIP2 did not reduce IK. Application of the K(+) channel blocker 4-aminopyridine (4-AP) strongly reduced IK, and extracellular AG in the presence of 4-AP gave no further inhibition of IK. In summary, AG significantly reduce the 4-AP-sensitive IK in early postnatal and mature HCI. K(+) current inhibition differs from that seen in outer hair cells, since it does not appear to involve PIP2 sequestration or KCNQ channels.

  17. Use of Liposomal Gentamicin for Treatment of 5 Foals with Experimentally Induced Rhodococcus equi Pneumonia.

    Science.gov (United States)

    Cohen, N D; Giguère, S; Burton, A J; Rocha, J N; Berghaus, L J; Brake, C N; Bordin, A I; Coleman, M C

    2016-01-01

    Adverse effects of, and bacterial resistance to, macrolides used to treat Rhodococcus equi infections have prompted search for clinically effective alternative antimicrobials. Liposomal gentamicin (LG) is effective against R. equi in vitro and decreases tissue concentrations of R. equi in experimentally infected mice. Effectiveness of LG treatment of foals with R. equi pneumonia, however, has not been described. Liposomal gentamicin is safe and effective for treating foals with R. equi pneumonia. Ten foals with experimentally induced R. equi pneumonia. Pilot treatment trial. Foals with pneumonia induced by intrabronchial instillation of R. equi were randomly allocated to receive either clarithromycin combined with rifampin (CLR + RIF) PO or LG IV, and followed by daily physical examinations and weekly thoracic ultrasonography and serum creatinine concentration determinations until the resolution of clinical signs. Treatment success was defined as the resolution of clinical signs and ultrasonographically identified pulmonary abscesses. All 10 foals were successfully treated. Two of 5 foals treated with LG developed azotemia within 1 week; LG was discontinued and treatment switched to CLR + RIF for these foals. None of the CLR + RIF treated foals developed azotemia. Liposomal gentamicin IV can be effective for treatment of R. equi pneumonia, but nephrotoxicity indicates that an alternative dosing interval or route (such as nebulization) will be needed before LG is adequately safe for clinical use. Larger comparative trials will be needed to evaluate the relative efficacy of a safer LG dosage regimen. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  18. Pharmacokinetic modeling of gentamicin in treatment of infective endocarditis: Model development and validation of existing models

    Science.gov (United States)

    van der Wijk, Lars; Proost, Johannes H.; Sinha, Bhanu; Touw, Daan J.

    2017-01-01

    Gentamicin shows large variations in half-life and volume of distribution (Vd) within and between individuals. Thus, monitoring and accurately predicting serum levels are required to optimize effectiveness and minimize toxicity. Currently, two population pharmacokinetic models are applied for predicting gentamicin doses in adults. For endocarditis patients the optimal model is unknown. We aimed at: 1) creating an optimal model for endocarditis patients; and 2) assessing whether the endocarditis and existing models can accurately predict serum levels. We performed a retrospective observational two-cohort study: one cohort to parameterize the endocarditis model by iterative two-stage Bayesian analysis, and a second cohort to validate and compare all three models. The Akaike Information Criterion and the weighted sum of squares of the residuals divided by the degrees of freedom were used to select the endocarditis model. Median Prediction Error (MDPE) and Median Absolute Prediction Error (MDAPE) were used to test all models with the validation dataset. We built the endocarditis model based on data from the modeling cohort (65 patients) with a fixed 0.277 L/h/70kg metabolic clearance, 0.698 (±0.358) renal clearance as fraction of creatinine clearance, and Vd 0.312 (±0.076) L/kg corrected lean body mass. External validation with data from 14 validation cohort patients showed a similar predictive power of the endocarditis model (MDPE -1.77%, MDAPE 4.68%) as compared to the intensive-care (MDPE -1.33%, MDAPE 4.37%) and standard (MDPE -0.90%, MDAPE 4.82%) models. All models acceptably predicted pharmacokinetic parameters for gentamicin in endocarditis patients. However, these patients appear to have an increased Vd, similar to intensive care patients. Vd mainly determines the height of peak serum levels, which in turn correlate with bactericidal activity. In order to maintain simplicity, we advise to use the existing intensive-care model in clinical practice to avoid

  19. Synergy effects of the antibiotics gentamicin and the essential oil of Croton zehntneri.

    Science.gov (United States)

    Rodrigues, Fabíola F G; Costa, José G M; Coutinho, Henrique D M

    2009-11-01

    The leaves of Croton zehntneri Pax et Hoffm (Euphorbiaceae) were subjected to hydrodistillation, and the essential oil extracted was examined with respect to antibacterial and antibiotic modifying activity by gaseous contact. The gaseous component of the oil inhibited the bacterial growth of Staphylococcus aureus and Pseudomonas aeruginosa with a MID of 0.5 and<1mg/l air, respectively. The activity of the antibiotic gentamicin was increased by 42,8% against P. aeruginosa after contact with the gaseous component, showing that this oil influences the activity of the antibiotic and may be used as an adjuvant in the antibiotic therapy of respiratory tract bacterial pathogens.

  20. Combined action of carbenicillin and gentamicin on Pseudomonas aeruginosa in vitro.

    Science.gov (United States)

    Sonne, M; Jawetz, E

    1969-06-01

    The minimal inhibitory and minimal bactericidal concentrations of carbenicillin and gentamicin were determined for 10 strains of Pseudomonas aeruginosa isolated from the urinary tract. Combinations of the two drugs were tested for possible enhanced activity. Such enhancement was demonstrated in the inhibitory activity of combinations for eight strains. Striking bactericidal activity against five strains was achieved by the combination, whereas neither drug alone in low dosage was capable of bactericidal action. The possible mode of action and the possible merit of pursuing these preliminary findings are discussed.

  1. Detection of the esp gene in high-level gentamicin resistant Enterococcus faecalis strains from pet animals in Japan.

    Science.gov (United States)

    Harada, Tetsuya; Tsuji, Noboru; Otsuki, Koichi; Murase, Toshiyuki

    2005-03-20

    We investigated the prevalence of the esp gene and the susceptibility to gentamicin in Enterococcus faecalis and E. faecium strains obtained from pet animals. Nine of 30 E. faecalis and 2 of 38 E. faecium strains from the pet animals had the esp gene. Three esp-positive E. faecalis strains, which were isolated from two dogs and a cat, showed gentamicin MICs of > or =256 microg/ml and harbored the high-level gentamicin resistance (HLGR) gene, aac(6')-Ie-aph(2'')-Ia. Of the nine esp-positive E. faecalis strains, five, including the three strains with the HLGR gene, were closely related by numerical analysis of PFGE patterns. Longitudinal investigation needs to elucidate whether the HLGR gene was incorporated into a subpopulation of the esp-positive E. faecalis.

  2. The Protective Effects of Carrot Seed Extract on Spermatogenesis and Cauda Epididymal Sperm Reserves in Gentamicin Treated Rats

    Directory of Open Access Journals (Sweden)

    Mohammad Nouri

    2009-01-01

    Full Text Available Objective: Carrot (Daucus carota L. is known to possess antifertility properties in female.However, according to Iranian traditional medicine, it can increase the potency in men. Theaim of this study was to investigate the influence of carrot seed extract (CSE on spermatogenesis,number and motility of sperms in cauda epididyme in male rats.Materials and Methods: Forty adult male rats were randomly divided into 5 groups: controlgroup, groups receiving low- and high doses of CSE, animals that received high-dose of CSEwith gentamicin, and a gentamicin only group. After 4 weeks treatment, fasting serum sampleswere obtained for the sex hormone analysis. Under anesthesia, testis, cauda epididymidesand sperm ducts were dissected and sperm count, motility and cauda epididymis spermreserves (CESR were determined. Histopathological changes of testis were also studied toassess spermatogenesis. Data analysis was performed using one-way ANOVA followed byTukey HSD tests.Results: Administration of CSE caused a significant increase in CESR compared with thecontrol (28.2 ± 1.8 vs. 45.1 ± 2.0, ×106. The extract could also protect testis from the gentamicin-induced necrosis. The CSE administration caused about 3.5-times increase in theLH levels even in spite of receiving 5 mg/kg/day gentamicin with no significant effect on FSHlevels. The testosterone concentrations in the group received 400 mg/kg CSE were 30% and83% higher than its levels in the control and the gentamicin treated group, respectively.Conclusion: CSE can overcome reproductive toxicity of gentamicin and induces spermatogenesisprobably mainly through the elevation of testosterone levels.

  3. Antibacterial efficacy of core-shell nanostructures encapsulating gentamicin against an in vivo intracellular  Salmonella model

    Directory of Open Access Journals (Sweden)

    Ashish Ranjan

    2009-12-01

    Full Text Available Ashish Ranjan1, Nikorn Pothayee2,3, Mohammed N Seleem2, Ronald D Tyler Jr4, Bonnie Brenseke4, Nammalwar Sriranganathan2,4, Judy S Riffle2,3, Ramanathan Kasimanickam11Department of Large Animal Clinical Sciences, 2Institute for Critical Technology and Applied Science, 3Macromolecules and Interfaces Institute, 4Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, VAAbstract: Pluronic based core-shell nanostructures encapsulating gentamicin were designed in this study. Block copolymers of (PAA–+Na-b-(PEO-b-PPO-b-PEO-b-PAA– +Na were blended with PAA– Na+ and complexed with the polycationic antibiotic gentamicin to form nanostructures. Synthesized nanostructures had a hydrodynamic diameter of 210 nm, zeta potentials of –0.7 (±0.2, and incorporated ~20% by weight of gentamicin. Nanostructures upon co-incubation with J774A.1 macrophage cells showed no adverse toxicity in vitro. Nanostructures administered in vivo either at multiple dosage of 5 µg g–1 or single dosage of 15 µg g–1 in AJ-646 mice infected with Salmonella resulted in significant reduction of viable bacteria in the liver and spleen. Histopathological evaluation for concentration-dependent toxicity at a dosage of 15 µg g–1 revealed mineralized deposits in 50% kidney tissues of free gentamicin-treated mice which in contrast was absent in nanostructure-treated mice. Thus, encapsulation of gentamicin in nanostructures may reduce toxicity and improve in vivo bacterial clearance.Keywords: gentamicin, core-shell nanostructures, Salmonella

  4. Attenuation of Pseudomonas aeruginosa biofilm formation by Vitexin: A combinatorial study with azithromycin and gentamicin

    Science.gov (United States)

    Das, Manash C.; Sandhu, Padmani; Gupta, Priya; Rudrapaul, Prasenjit; de, Utpal C.; Tribedi, Prosun; Akhter, Yusuf; Bhattacharjee, Surajit

    2016-03-01

    Microbial biofilm are communities of surface-adhered cells enclosed in a matrix of extracellular polymeric substances. Extensive use of antibiotics to treat biofilm associated infections has led to the emergence of multiple drug resistant strains. Pseudomonas aeruginosa is recognised as a model biofilm forming pathogenic bacterium. Vitexin, a polyphenolic group of phytochemical with antimicrobial property, has been studied for its antibiofilm potential against Pseudomonas aeruginosa in combination with azithromycin and gentamicin. Vitexin shows minimum inhibitory concentration (MIC) at 260 μg/ml. It’s antibiofilm activity was evaluated by safranin staining, protein extraction, microscopy methods, quantification of EPS and in vivo models using several sub-MIC doses. Various quorum sensing (QS) mediated phenomenon such as swarming motility, azocasein degrading protease activity, pyoverdin and pyocyanin production, LasA and LasB activity of the bacteria were also evaluated. Results showed marked attenuation in biofilm formation and QS mediated phenotype of Pseudomonas aeruginosa in presence of 110 μg/ml vitexin in combination with azithromycin and gentamicin separately. Molecular docking of vitexin with QS associated LuxR, LasA, LasI and motility related proteins showed high and reasonable binding affinity respectively. The study explores the antibiofilm potential of vitexin against P. aeruginosa which can be used as a new antibiofilm agent against microbial biofilm associated pathogenesis.

  5. Tebal Struktur Histologis Duodenum Ayam Pedaging yang Diberi Kombinasi Tylosin dan Gentamicin

    Directory of Open Access Journals (Sweden)

    I Gede Gilang Ikra Raditya

    2013-12-01

    Usaha ternak broiler, sejak tahun 1998 semakin menonjol perannya dalam mempersempit kesenjangan terhadap meningkatnya kebutuhan akan daging. Daging ayam broiler dipilih sebagai salah satu alternatif, karena kita tahu bahwa ayam broiler sangat efisen diproduksi. Tujuan dilakukan penelitian ini adalah untuk mengetahui tebal struktur histologis duodenum ayam yang diberi kombinasi tylosin dan gentamicin. Metode yang dipakai pada penelitian ini menggunakan 32 ayam pedaging yang di bagi dalam 4 kelompok yang di mana masing masing kelompok terbagi atas 8 ayam. Hasil penelitian ini sendiri adalah ketebalan struktur histologis duodenum pada kontrol (P0 rata-rata 7,2 ?m, perlakuan P1 rata-rata 7,2 ?m, perlakuan P2 rata-rata adalah 7,6 ?m, dan perlakuan P3 rata-rata adalah 7,9 ?m. P3 lebih tebal dari P2 dan P2 lebih besar dari P1 dan P0. Kesimpulan dari penelitian ini adalah kombinasi tylosin dan gentamicin ini efektif untuk menyeimbangkan flora normal yang ada di dalam duodenum sehingga membuat pertumbuhan ayam menjadi sempurna.

  6. Impairment of membrane phosphoinositide metabolism by aminoglycoside antibiotics: streptomycin, amikacin, kanamycin, dibekacin, gentamicin and neomycin.

    Science.gov (United States)

    Marche, P; Koutouzov, S; Girard, A

    1983-11-01

    Like many amphiphilic cationic drugs, aminoglycosides are able to produce phospholipidosis, mainly by inhibiting enzymes involved in phospholipid metabolism. Phosphoinositides have been suggested to function as receptors for aminoglycosides. Therefore, we investigated the influence of these drugs upon phosphoinositide metabolism by measuring the 32P-incorporation into the polyphosphoinositides, using the rat erythrocyte membrane as a model. Depending upon the experimental conditions, neomycin induced a decrease and/or an increase in the 32P-labeling of triphosphoinositides (TPI) and of diphosphoinositides (DPI), respectively. These variations were rapid and depended upon the drug concentration. At 0.3 mM, neomycin reversed the distribution of radioactivities associated with DPI and TPI without modifying the total radioactivity incorporated. This drug concentration altered neither the Mg++-activated TPI-specific phosphomonoesterase activity nor the Ca++-activated polyphosphoinositide phosphodiesterase activity. It appears likely that the drug inhibits the DPI-kinase activity, by interacting with DPI and thereby lowering the substrate availability. Over the range of concentrations studied (up to 1-2 mM), gentamicin, kanamycin and dibekacin behave as neomycin. However, their effects could be observed only at drug concentrations higher than those of neomycin. By contrast, streptomycin and amikacin did not alter the 32P-labeling of TPI and of DPI. The order of potency of aminoglycosides for the impairment of the phosphoinositide interconversion was neomycin, gentamicin, dibekacin, kanamycin. A possible relationship between the toxicity of aminoglycosides and their capacity to impair the phosphoinositide metabolism is discussed.

  7. Effect of n-Hexane extract of Nigella sativa on gentamicin-induced nephrotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Nasim A Begum

    2006-03-01

    Full Text Available The present study investigated whether the administration of the n-hexane extract of the Nigella sativa Linn. (kalajira ameliorates gentamicin-induced nephrotoxicity in rats. Gentamicin (100 mg/kg/day for 7 days was administered and nephrotoxicity was evaluated biochemically (significantly decreased reduced glutathione in renal cortex and significantly increased serum creatinine and serum urea and histologically (moderate degree of proximal tubular damage. The n-hexane extract of N. sativa (5 ml/kg/day was administered as pre-, post- and concomitant treatment for 7 days in the nephrotoxic rats. Statistically significant amelioration in all the biochemical parameters supported by significantly improved renal cortical histology was observed in the n-hexane extract of N. sativa treated nephrotoxic rats, which was more evident in the post-treatment group than the pre- treatment and the concomitantly-treated group. It is suggested that some ingredients contained in the n-hexane extract of N. sativa effected in ameliorating the signs of nephrotoxicity and that the specific active principle of the n-hexane extract of N. sativa responsible for this amelioration if obtained, would be more useful.

  8. Protective Effects of Houttuynia cordata Thunb. on Gentamicin-induced Oxidative Stress and Nephrotoxicity in Rats.

    Science.gov (United States)

    Kang, Changgeun; Lee, Hyungkyoung; Hah, Do-Yun; Heo, Jung Ho; Kim, Chung Hui; Kim, Euikyung; Kim, Jong Shu

    2013-03-01

    Development of a therapy providing protection from, or reversing gentamicin-sulfate (GS)-induced oxidative stress and nephrotoxicity would be of great clinical significance. The present study was designed to investigate the protective effects of Houttuynia cordata Thunb. (HC) against gentamicin sulfate-induced renal damage in rats. Twenty-eight Sprague-Dawley rats were divided into 4 equal groups as follows: group 1, control; group 2, GS 100 mg/kg/d, intraperitoneal (i.p.) injection; group 3, GS 100 mg/kg/d, i.p. + HC 500 mg/kg/d, oral; and group 4, GS 100 mg/kg/d i.p. + HC 1000 mg/kg/d, oral administration). Treatments were administered once daily for 12 d. After 12 d, biochemical and histopathological analyses were conducted to evaluate oxidative stress and renal nephrotoxicity. Serum levels of creatinine, malondialdehyde (MDA), and blood urea nitrogen (BUN), together with renal levels of MDA, glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were quantified to evaluate antioxidant activity. Animals treated with GS alone showed a significant increase in serum levels of creatinine, BUN, and MDA, with decreased renal levels of GSH, SOD, and CAT. Treatment of rats with HC showed significant improvement in renal function, presumably as a result of decreased biochemical indices and oxidative stress parameters associated with GS-induced nephrotoxicity. Histopathological examination of the rat kidneys confirmed these observations. Therefore, the novel natural antioxidant HC may protect against GSinduced nephrotoxicity and oxidative stress in rats.

  9. In vitro antibacterial activity of seven Indian spices against high level gentamicin resistant strains of enterococci

    Science.gov (United States)

    Bipin, Chapagain; Chitra, Pai (Bhat); Minakshi, Bhattacharjee

    2015-01-01

    Introduction The aim of the study was to explore the in vitro antibacterial activity of seven ethanolic extracts of spices against high level gentamicin resistant (HLGR) enterococci isolated from human clinical samples. Material and methods Two hundred and fifteen enterococcal strains were isolated from clinical samples. High level gentamicin resistance in ethanolic extracts of cumin (Cuminum cyminum), cinnamon (Cinnamomum zeylanicum), ginger (Zingiber officinale), fenugreek (Trigonella foenum-graecum), cloves (Syzygium aromaticum), cardamom (Elettaria cardamomum Maton) and black pepper (Piper nigrum) were prepared using Soxhlet apparatus. The antibacterial effect of the extracts was studied using the well diffusion method. Statistical analysis was carried out by χ2 test using SPSS 17 software. Results Only cinnamon and ginger were found to have activity against all the isolates, whereas cumin and cloves had a variable effect on the strains. Fenugreek, black pepper and cardamom did not show any effect on the isolates. The zone diameter of inhibition obtained for cinnamon, ginger, cloves and cumin was in the range 31–34 mm, 27–30 mm, 25–26 mm and 19–20 mm respectively. Conclusions Cinnamomum zeylanicum and Z. officinale showed the maximum antibacterial activity against the enterococcal isolates followed by S. aromaticum and C. cyminum. The findings of the study show that spices used in the study can contribute to the development of potential antimicrobial agents for inclusion in the anti-enterococcal treatment regimen. PMID:26322099

  10. Application of Box-Behnken design to prepare gentamicin-loaded calcium carbonate nanoparticles.

    Science.gov (United States)

    Maleki Dizaj, Solmaz; Lotfipour, Farzaneh; Barzegar-Jalali, Mohammad; Zarrintan, Mohammad-Hossein; Adibkia, Khosro

    2016-09-01

    The aim of this research was to prepare and optimize calcium carbonate (CaCO3) nanoparticles as carriers for gentamicin sulfate. A chemical precipitation method was used to prepare the gentamicin sulfate-loaded CaCO3 nanoparticles. A 3-factor, 3-level Box-Behnken design was used for the optimization procedure, with the molar ratio of CaCl2: Na2CO3 (X1), the concentration of drug (X2), and the speed of homogenization (X3) as the independent variables. The particle size and entrapment efficiency were considered as response variables. Mathematical equations and response surface plots were used, along with the counter plots, to relate the dependent and independent variables. The results indicated that the speed of homogenization was the main variable contributing to particle size and entrapment efficiency. The combined effect of all three independent variables was also evaluated. Using the response optimization design, the optimized Xl-X3 levels were predicted. An optimized formulation was then prepared according to these levels, resulting in a particle size of 80.23 nm and an entrapment efficiency of 30.80%. It was concluded that the chemical precipitation technique, together with the Box-Behnken experimental design methodology, could be successfully used to optimize the formulation of drug-incorporated calcium carbonate nanoparticles.

  11. PROTECTIVE EFFECT OF AQUEOUS AND METHANOLIC EXTRACTS OF LAGENARIA SICERARIA SEEDS IN GENTAMICIN INDUCED NEPHROTOXICITY

    Directory of Open Access Journals (Sweden)

    Mahurkar N.

    2012-06-01

    Full Text Available The aim of present study was to carry out the preliminary phytochemical studies and nephroprotective activity of metahanolic and aqueous extracts of Lagenaria siceraria seeds, family cucurbitaceae. These studies revealed the presence of flavonoids, tannins (ellagitannins, saponins, polyphenols, triterpenes, lagenin (protein in the extracts. The extract was found to be potent diuretic which causes excretion of sodium and potassium. Gentamicin is an extensively used aminolgycoside antibiotic. It has been reported to produce nephrotoxicity even at normal therapeutic dose level. Gentamicin was administrated intraperitonealy at a dose of 80mg/kg body weight for 9 days. The biochemical parameters viz. serum createnine, blood urea nitrogen (BUN and serum uric acid was found to be significantly increased whereas serum total protein was decreased. Histopathological sections showed marked glomerular, peritubular and blood vessel congestion. These increased levels of biochemical parameters and extent of renal damage were decreased by the methanolic and aqueous extracts of Lagenaria siceraria seeds at a dose of 250mg/kg, Cystone tab. (500mg/kg was used as reference standard to compare with the toxicant and test group animals.

  12. Increased expression of p38 mitogen- activated protein kinase is related to the acute renal lesions induced by gentamicin

    Directory of Open Access Journals (Sweden)

    Volpini R.A.

    2006-01-01

    Full Text Available Mitogen-activated protein kinases (MAPK may be involved in the pathogenesis of acute renal failure. This study investigated the expression of p-p38 MAPK and nuclear factor kappa B (NF-kappaB in the renal cortex of rats treated with gentamicin. Twenty rats were injected with gentamicin, 40 mg/kg, im, twice a day for 9 days, 20 with gentamicin + pyrrolidine dithiocarbamate (PDTC, an NF-kappaB inhibitor, 14 with 0.15 M NaCl, im, twice a day for 9 days, and 14 with 0.15 M NaCl , im, twice a day for 9 days and PDTC, 50 mg kg-1 day-1, ip, twice a day for 15 days. The animals were killed 5 and 30 days after the last of the injections and the kidneys were removed for histological, immunohistochemical and Western blot analysis and for nitrate determination. The results of the immunohistochemical study were evaluated by counting the p-p38 MAPK-positive cells per area of renal cortex measuring 0.05 mm². Creatinine was measured by the Jaffé method in blood samples collected 5 and 30 days after the end of the treatments. Gentamicin-treated rats presented a transitory increase in plasma creatinine levels. In addition, animals killed 5 days after the end of gentamicin treatment presented acute tubular necrosis and increased nitrate levels in the renal cortex. Increased expression of p-p38 MAPK and NF-kappaB was also observed in the kidneys from these animals. The animals killed 30 days after gentamicin treatment showed residual areas of interstitial fibrosis in the renal cortex, although the expression of p-p38 MAPK in their kidneys did not differ from control. Treatment with PDTC reduced the functional and structural changes induced by gentamicin as well as the expression of p-p38 MAPK and NF-kappaB. The increased expression of p-p38 MAPK and NF-kappaB observed in these rats suggests that these signaling molecules may be involved in the pathogenesis of tubulointerstitial nephritis induced by gentamicin.

  13. Intratympanic gentamicin treatment for Ménière's disease: A randomized, double-blind, placebo-controlled trial on dose efficacy - results of a prematurely ended study

    NARCIS (Netherlands)

    H.G. Bremer (Hendrik G.); I. van Rooy (Ingrid); B. Pullens (Bas); C. Colijn (Carla); I. Stegeman; H.J. van der Zaag-Loonen (Hester); P.P. van Benthem (Peter P.); S.F.L. Klis (Sjaak F L.); W. Grolman (Wilko); Tj.D. Bruintjes

    2014-01-01

    textabstractBackground: Gentamicin is used as a therapeutic agent for Ménière's disease because of its vestibulotoxicity causing chemo-ablation of the vestibular sensory epithelia. Its use has increased in recent years. However, there is still no consensus about the dose regimen of gentamicin in the

  14. Tissue reactions to bacteria-inoculated rat lead samples .2. Effect of local gentamicin release through surface-modified polyurethane tubing

    NARCIS (Netherlands)

    vanWachem, PB; vanLuyn, MJA; deWit, AW; Raatjes, D; Hendriks, M; Verhoeven, MLPM; Cahalan, PT

    1997-01-01

    A surface modification technique was developed to achieve controlled release of gentamicin from implanted polyurethane (PU) rat lead samples. PU tubing first was provided with an acrylic acid/acrylamide copolymer surface graft and then loaded with gentamicin. This surface modification technique resu

  15. Role of somatostatin receptor-2 in gentamicin-induced auditory hair cell loss in the Mammalian inner ear.

    Directory of Open Access Journals (Sweden)

    Yves Brand

    Full Text Available Hair cells and spiral ganglion neurons of the mammalian auditory system do not regenerate, and their loss leads to irreversible hearing loss. Aminoglycosides induce auditory hair cell death in vitro, and evidence suggests that phosphatidylinositol-3-kinase/Akt signaling opposes gentamicin toxicity via its downstream target, the protein kinase Akt. We previously demonstrated that somatostatin-a peptide with hormone/neurotransmitter properties-can protect hair cells from gentamicin-induced hair cell death in vitro, and that somatostatin receptors are expressed in the mammalian inner ear. However, it remains unknown how this protective effect is mediated. In the present study, we show a highly significant protective effect of octreotide (a drug that mimics and is more potent than somatostatin on gentamicin-induced hair cell death, and increased Akt phosphorylation in octreotide-treated organ of Corti explants in vitro. Moreover, we demonstrate that somatostatin receptor-1 knockout mice overexpress somatostatin receptor-2 in the organ of Corti, and are less susceptible to gentamicin-induced hair cell loss than wild-type or somatostatin-1/somatostatin-2 double-knockout mice. Finally, we show that octreotide affects auditory hair cells, enhances spiral ganglion neurite number, and decreases spiral ganglion neurite length.

  16. Development of a standardized susceptibility test for Campylobacter with quality control ranges for ciprofloxacin, doxycycline, erythromycin, gentamicin, and meropenem

    DEFF Research Database (Denmark)

    McDermott, P. F.; Bodeis, S. M.; Aarestrup, Frank Møller

    2004-01-01

    -control (QC) strain. Minimal inhibitory concentration (MIC) QC ranges were determined for two incubation time/temperature combinations: 36degreesC for 48 hr and 42degreesC for 24 hr. Quality-control ranges were determined for ciprofloxacin, doxycycline, erythromycin, gentamicin, and meropenem. For all...

  17. Neamin as an immunogen for the development of a generic ELISA detecting gentamicin, kanamycin and neomycin in milk

    NARCIS (Netherlands)

    Loomans, E.E.M.G.; Wiltenburg, van J.; Koets, M.; Amerongen, van A.

    2003-01-01

    A broad-specific ELISA using one antibody preparation for the detection of gentamicin, kanamycin, and neomycin in milk is reported for the first time. For the immunization of rabbits, neamin was used as the generic hapten on the basis of the facts that it is a two-ring fragment of neomycin and, in s

  18. Continuous intravenous infusion of ampicillin and gentamicin during parenteral nutrition to 36 newborn infants using a dosage schedule

    DEFF Research Database (Denmark)

    Colding, H; Møller, S; Andersen, G E

    1984-01-01

    Ampicillin and gentamicin were given continuously i.v. to 36 newborn infants using a dosage schedule and the results were compared with those obtained in an earlier study including 88 infants who received individually calculated dosages. With the dosage schedule the variation in the serum concent...

  19. Beetroot (Beta vulgaris L. Extract Ameliorates Gentamicin-Induced Nephrotoxicity Associated Oxidative Stress, Inflammation, and Apoptosis in Rodent Model

    Directory of Open Access Journals (Sweden)

    Ali A. El Gamal

    2014-01-01

    Full Text Available The present investigation was designed to investigate the protective effect of (Beta vulgaris L. beat root ethanolic extract (BVEE on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific kidney function parameters (urea, uric acid, total protein, creatinine, and histopathology of kidney tissue were evaluated to access gentamicin-induced nephrotoxicity. The oxidative/nitrosative stress (Lipid peroxidation, MDA, NP-SH, Catalase, and nitric oxide levels was assessed. The inflammatory response (TNF-α, IL-6, MPO, NF-κB (p65, and NF-κB (p65 DNA binding and apoptotic marker (Caspase-3, Bax, and Bcl-2 were also evaluated. BVEE (250 and 500 mg/kg treatment along with gentamicin restored/increased the renal endogenous antioxidant status. Gentamicin-induced increased renal inflammatory cytokines (TNF-α and IL-6, nuclear protein expression of NF-κB (p65, NF-κB-DNA binding activity, myeloperoxidase (MPO activity, and nitric oxide level were significantly down regulated upon BVEE treatment. In addition, BVEE treatment significantly reduced the amount of cleaved caspase 3 and Bax, protein expression and increased the Bcl-2 protein expression. BVEE treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. These findings suggest that BVEE treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, inflammation, and apoptosis in the kidney.

  20. Biochemical assessment of nephroprotective and nephrocurative activity of Withania somnifera on gentamicin induced nephrotoxicity in experimental rats

    Directory of Open Access Journals (Sweden)

    Vimlesh Kushwaha

    2016-01-01

    Results: BUN and serum creatinine values were significantly low as compared to GT group in all test duration in phase-1. In phase two there was no significant difference of these markers in two groups. Conclusions: Withania Somnifera root extract have nephroprotective activity against gentamicin induced nephrotoxicity. [Int J Res Med Sci 2016; 4(1.000: 298-302

  1. Neamin as an immunogen for the development of a generic ELISA detecting gentamicin, kanamycin and neomycin in milk

    NARCIS (Netherlands)

    Loomans, E.E.M.G.; Wiltenburg, van J.; Koets, M.; Amerongen, van A.

    2003-01-01

    A broad-specific ELISA using one antibody preparation for the detection of gentamicin, kanamycin, and neomycin in milk is reported for the first time. For the immunization of rabbits, neamin was used as the generic hapten on the basis of the facts that it is a two-ring fragment of neomycin and, in s

  2. Synthesis and characterization of a novel controlled release zinc oxide/gentamicin-chitosan composite with potential applications in wounds care.

    Science.gov (United States)

    Vasile, Bogdan Stefan; Oprea, Ovidiu; Voicu, Georgeta; Ficai, Anton; Andronescu, Ecaterina; Teodorescu, Andrei; Holban, Alina

    2014-03-25

    Freshly prepared ZnO nanoparticles were incorporated into a chitosan solution in weight ratios ranging from 1:1 to 12:1. Starting from the ratio of 3:1 the chitosan solution was transformed into a gel with a high consistency, which incorporates 15mL water for only 0.1g solid substance. The powders obtained after drying the gel were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM) and thermal analysis (TG-DSC). The electronic (UV-vis), infrared (FTIR) and photoluminescence (PL) spectra were also recorded. ZnO particles were coated with gentamicin and incorporated into the chitosan matrix, to yield a ZnO/gentamicin-chitosan gel. The release rate of gentamicin was monitored photometrically. This ZnO/gentamicin-chitosan gel proved great antimicrobial properties, inhibiting Staphylococcus aureus and Pseudomonas aeruginosa growth in both planktonic and surface-attached conditions. The results indicate that the obtained composite can be used in cutaneous healing for developing improved wound dressings, which combine the antibacterial activity of all three components with the controlled release of the antibiotic. This wound dressing maintains a moist environment at the wound interface, providing a cooling sensation and soothing effect, while slowly releasing the antibiotic. The system is fully scalable to any other soluble drug, as the entire solution remains trapped in the ZnO-chitosan gel.

  3. Continuous intravenous infusion of ampicillin and gentamicin during parenteral nutrition to 36 newborn infants using a dosage schedule

    DEFF Research Database (Denmark)

    Colding, H; Møller, S; Andersen, G E

    1984-01-01

    Ampicillin and gentamicin were given continuously i.v. to 36 newborn infants using a dosage schedule and the results were compared with those obtained in an earlier study including 88 infants who received individually calculated dosages. With the dosage schedule the variation in the serum concent...

  4. Effects of the sol-gel route on the structural characteristics and antibacterial activity of silica-encapsulated gentamicin.

    Science.gov (United States)

    Corrêa, G G; Morais, E C; Brambilla, R; Bernardes, A A; Radtke, C; Dezen, D; Júnior, A V; Fronza, N; Santos, J H Z Dos

    2014-04-01

    The effects of sol-gel processes, i.e., acid-catalyzed gelation, base-catalyzed gelation and base-catalyzed precipitation routes, on the encapsulation of gentamicin were investigated. The resulting xerogels were characterized using a series of complementary instrumental techniques, i.e., the adsorption/desorption of nitrogen, small-angle X-ray scattering, Fourier transform infrared spectroscopy, diffuse reflectance spectroscopy, X-ray photoelectron spectroscopy, atomic force microscopy and scanning electron microscopy. The encapsulated gentamicin samples were tested against a series of Gram-positive and Gram-negative bacterial strains. The best antimicrobial activity was observed with the encapsulated gentamicin that was prepared via the precipitation route, even in comparison with the neat antibiotic, especially in the case of the Gram-positive strain Staphylococcus aureus. The gentamicin concentration on the outermost surface and the zeta potential were identified as factors that affected the highest efficiency, as observed in the case of encapsulation via the base-catalyzed process.

  5. Local Application of Gentamicin in the Prophylaxis of Perineal Wound Infection after Abdominoperineal Resection: A Systematic Review

    NARCIS (Netherlands)

    G.D. Musters (Gijsbert D.); J.W.A. Burger (Jacobus); C.J. Buskens (Christianne); W.A. Bemelman; P.J. Tanis (Pieter)

    2015-01-01

    textabstractBackground: Use of topical antibiotics to improve perineal wound healing after abdominoperineal resection (APR) is controversial. The aim of this systematic review was to determine the impact of local application of gentamicin on perineal wound healing after APR. Methods: The electronic

  6. Protective effects of the aqueous leaf extract of Aloe barbadensis on gentamicin and cisplatin-induced nephrotoxic rats

    Institute of Scientific and Technical Information of China (English)

    Paoulomi Chatterjee﹡; Aniruddha Mukherjee; Subhangkar Nandy

    2012-01-01

    Objective: To study the protective effects of the aqueous leaf extract of Aloe barbadensis (AEAB) on gentamicin and Cisplatin-induced nephrotoxic Wistar rats. Methods: In each model of nephrotoxicity, thirty adult male Wistar rats were evenly divided into 5 groups. Groups I and II served as untreated and model controls, respectively while groups III-V were the treatment groups which were pretreated with 100-200 mg/kg bodyweight per day of AEAB 1 h before each dose of the nephrotoxicants. On the 8th day(in case of gentamicin) and on 6th day(in case of Cisplatin), blood samples for serum urea, total protein and creatinine as well as some ions like sodium, potassium, chloride and uric acid while the rat kidneys for histology were obtained under inhaled diethyl ether anesthesia. Results: In the gentamicin nephrotoxic rats, 100-200 mg/kg bodyweight per day significantly attenuated elevations in the serum creatinine, total protein and blood urea nitrogen levels in dose related fashion and no treatment related effect on uric acid and ions, and attenuated the gentamicin-induced tubulonephrosis. Similar effects were also recorded in the Cisplatin model of acute renal injury. Conclusions:The nephroprotective effect of AEAB could be due to the inherent antioxidant and free-radical-scavenging principle(s) contained in the extract.In the near future, AEAB could constitute a lead to discovery of a novel drug for the treatment of drug-induced nephrotoxicity.

  7. Extended-Interval Dosing of Gentamicin Aiming for a Drug-Free Period in Neonates: A Prospective Cohort Study.

    NARCIS (Netherlands)

    van Maarseveen, Erik M; Sprij, Arwen; Touw, Daniel J

    2016-01-01

    BACKGROUND Current gentamicin dosing algorithms in adult populations target a high peak concentration (Cmax) assuring efficacy and a drug-free period (concentration 8 mg·L and estimated trough concentrations 8 mg·L with a Cmin value

  8. Extended-Interval Dosing of Gentamicin Aiming for a Drug-Free Period in Neonates : A Prospective Cohort Study

    NARCIS (Netherlands)

    van Maarseveen, Erik M.; Sprij, Arwen; Touw, Daniel J.

    2016-01-01

    Background:Current gentamicin dosing algorithms in adult populations target a high peak concentration (C-max) assuring efficacy and a drug-free period (concentration 8 mgL(-1) and estimated trough concentrations 8 mgL(-1) with a C-min value

  9. Novel Glycoconjugate of 8-Fluoro Norfloxacin Derivatives as Gentamicin-resistant Staphylococcus aureus Inhibitors: Synthesis and Molecular Modelling Studies.

    Science.gov (United States)

    Azad, Chandra S; Bhunia, Shome S; Krishna, Atul; Shukla, Praveen K; Saxena, Anil K

    2015-10-01

    Antibiotic resistance has been the subject of interest in clinical practice due to high prevalence of antibiotic-resistant pathogenic organisms. In view of the prevalence of lesser resistance in antibiotics belonging to aminoglycoside class of compounds viz. Food and Drug Administration-approved gentamicin for the treatment of Staphylococcus infections, which also has instances of resistance in the clinical isolates of Staphylococcus aureus, a series of novel glycoconjugates of 8-fluoro norfloxacin analogues with high regio-selectivity by employing copper (I)-catalyzed 1, 3-dipolar cycloaddition of 1-O-propargyl monosaccharides has been synthesized and evaluated for the antibacterial activity against gentamicin resistance Staphylococcus aureus. Among these compounds, the compound 10g showed better antibacterial activity (MIC = 3.12 μg/ml) than gentamicin (Escherichia coli (12.5 μg/ml), Staphylococcus aureus (6.25 μg/ml) and Klebsiella pneumonia (6.25 μg/ml), including gentamicin resistant (>50 μg/ml) strain in vitro). The docking studies suggest DNA gyrase of Staphylococcus aureus as a probable target for the antibacterial action of compound 10g. © 2014 John Wiley & Sons A/S.

  10. An experimental design approach to the preparation of pegylated polylactide-co-glicolide gentamicin loaded microparticles for local antibiotic delivery

    Energy Technology Data Exchange (ETDEWEB)

    Dorati, Rossella; DeTrizio, Antonella; Genta, Ida; Grisoli, Pietro; Merelli, Alessia [Department of Drug Sciences, Viale Taramelli 12, University of Pavia, 27100, Pavia (Italy); Tomasi, Corrado [IENI CNR Lecco Unit, Via Promessi Sposi 29, 23900, Lecco (Italy); Conti, Bice, E-mail: bice.conti@unipv.it [Department of Drug Sciences, Viale Taramelli 12, University of Pavia, 27100, Pavia (Italy)

    2016-01-01

    The present paper takes into account the DOE application to the preparation process of biodegradable microspheres for osteomyelitis local therapy. With this goal gentamicin loaded polylactide-co-glycolide-co-polyethyleneglycol (PLGA-PEG) microspheres were prepared and investigated. Two preparation protocols (o/w and w/o/w) with different process conditions, and three PLGA-PEG block copolymers with different compositions of lactic and glycolic acids and PEG, were tested. A Design Of Experiment (DOE) screening design was applied as an approach to scale up manufacturing step. The results of DOE screening design confirmed that w/o/w technique, the presence of salt and the 15%w/v polymer concentration positively affected the EE% (72.1–97.5%), and span values of particle size distribution (1.03–1.23), while salt addition alone negatively affected the yield process. Process scale up resulted in a decrease of gentamicin EE% that can be attributed to the high volume of water used to remove PVA and NaCl residues. The results of in vitro gentamicin release study show prolonged gentamicin release up to three months from the microspheres prepared with salt addition in the dispersing phase; the behavior being consistent with their highly compact structure highlighted by scanning electron microscopy analysis. The prolonged release of gentamicin is maintained even after embedding the biodegradable microspheres into a thermosetting composite gel made of chitosan and acellular bovine bone matrix (Orthoss® granules), and the microbiologic evaluation demonstrated the efficacy of the gentamicin loaded microspheres on Escherichia coli. The collected results confirm the feasibility of the scale up of microsphere manufacturing process and the high potential of the microparticulate drug delivery system to be used for the local antibiotic delivery to bone. - Highlights: • To get a more effective therapy for the prevention and treatment of osteomyelitis. • To exploit the local

  11. Effects of neuroactive steroids on cochlear hair cell death induced by gentamicin.

    Science.gov (United States)

    Nakamagoe, Mariko; Tabuchi, Keiji; Nishimura, Bungo; Hara, Akira

    2011-12-11

    As neuroactive steroids, sex steroid hormones have non-reproductive effects. We previously reported that 17β-estradiol (βE2) had protective effects against gentamicin (GM) ototoxicity in the cochlea. In the present study, we examined whether the protective action of βE2 on GM ototoxicity is mediated by the estrogen receptor (ER) and whether other estrogens (17α-estradiol (αE2), estrone (E1), and estriol (E3)) and other neuroactive steroids, dehydroepiandrosterone (DHEA) and progesterone (P), have similar protective effects. The basal turn of the organ of Corti was dissected from Sprague-Dawley rats and cultured in a medium containing 100 μM GM for 48h. The effects of βE2 and ICI 182,780, a selective ER antagonist, were examined. In addition, the effects of other estrogens, DHEA and P were tested using this culture system. Loss of outer hair cells induced by GM exposure was compared among groups. βE2 exhibited a protective effect against GM ototoxicity, but its protective effect was antagonized by ICI 182,780. αE2, E1, and E3 also protected hair cells against gentamicin ototoxicity. DHEA showed a protective effect; however, the addition of ICI 182,780 did not affect hair cell loss. P did not have any effect on GM-induced outer hair cell death. The present findings suggest that estrogens and DHEA are protective agents against GM ototoxicity. The results of the ER antagonist study also suggest that the protective action of βE2 is mediated via ER but that of DHEA is not related to its conversion to estrogen and binding to ER. Further studies on neuroactive steroids may lead to new insights regarding cochlear protection.

  12. Protective effect of selenium on gentamicin-induced oxidative stress and nephrotoxicity in rats.

    Science.gov (United States)

    Randjelovic, Pavle; Veljkovic, Slavimir; Stojiljkovic, Nenad; Velickovic, Ljubinka; Sokolovic, Dusan; Stoiljkovic, Milan; Ilic, Ivan

    2012-04-01

    Gentamicin (GM) is a widely used antibiotic against serious, life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine the protective effect of selenium (Se) in GM-induced nephrotoxicity in rats. Experiments were done on 32 adult Wistar rats divided into four groups of 8 animals each. The GM group received gentamicin (100 mg/kg), whereas the GM+Se group received the same dose of GM and selenium (1 mg/kg) by intraperitoneal (i.p.) injections on a daily basis. Animals in the Se group, serving as a positive control, received only selenium (1 mg/kg) and the control group received saline (1 mL/day), both given i.p. All groups were treated during 8 consecutive days. Quantitative evaluation of GM-induced structural alterations and degree of functional alterations in the kidneys were performed by histopathological and biochemical analyses in order to determine potential beneficial effects of selenium coadministration with GM. GM was observed to cause a severe nephrotoxicity, which was evidenced by an elevation of serum urea and creatinine levels. The significant increases in malondialdehyde levels and protein carbonyl groups indicated that GM-induced tissue injury was mediated through oxidative reactions. On the other hand, simultaneous selenium administration protected kidney tissue against oxidative damage and the nephrotoxic effect caused by GM treatment. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules was found to be prevented by selenium pretreatment. The results from our study indicate that selenium supplementation attenuates oxidative-stress-associated renal injury by reducing oxygen free radicals and lipid peroxidation in GM-treated rats.

  13. Synergistic action of gentamicin and bacteriophage in a continuous culture population of Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    Amy E Kirby

    Full Text Available With the increasing frequency of antibiotic resistance and the decreasing frequency of new antibiotics entering the market, interest has returned to developing bacteriophage as a therapeutic agent. Acceptance of phage therapy, however, is limited by the unknown pharmacodynamics of a replicating agent, as well as the potential for the evolution of resistant bacteria. One way to overcome some of these limitations is to incorporate phage and antibiotics into a dual therapy regimen; however, this increases the complexity of the pharmacodynamics. The aim of this study is to develop an experimental system to evaluate the pharmacodynamics of dual phage-drug therapy. A continuous culture system for Staphylococcus aureus is used to simulate the pharmacokinetics of periodic antibiotic dosing alone and in combination with lytic phage. A computer model representation of the system allows further evaluation of the conditions governing the observed pharmacodynamics. The results of this experimental/modeling approach suggest that dual therapy can be more efficacious than single therapies, particularly if there is an overlap in the physiological pathways targeted by the individual agents. In this case, treatment with gentamicin induces a population of cells with a strong aggregation phenotype. These aggregators also have an increased ability to form biofilm, which is a well-known, non-genetic mechanism of drug resistance. However, the aggregators are also more susceptible than the parental strain to the action of the phage. Thus, dual treatment with gentamicin and phage resulted in lower final cell densities than either treatment alone. Unlike in the phage-only treatment, phage-resistant isolates were not detected in the dual treatment.

  14. Ampicillin and gentamicin are a useful first-line combination for the management of sepsis in under-five children at an urban hospital in Bangladesh.

    Science.gov (United States)

    Bibi, Samira; Chisti, Mohammod Jobayer; Akram, Farhana; Pietroni, Mark A C

    2012-12-01

    The study evaluated the commonly-used drugs for the management of sepsis and their outcome among under-five children. We evaluated the hospital-records of all paediatric sepsis patients (n = 183) in the intensive care unit (ICU) and longer-stay unit (LSU) of the Dhaka Hospital of icddr,b. These records were collected from the hospital management system (SHEBA) during November 2009 to October 2010. A total of 183 under-five children with clinical sepsis were found during the study period, and 14 (8%) of them were neonates. One hundred and eighty-one patients had received a combination of injection ampicilin and injection gentamicin, and two patients had received the combination of injection ceftriaxone and injection gentamicin. Only 46 (25%) patients required a change of antibiotics to the combination of intravenous ceftriaxone plus gentamicin after non-response of injection ampicilin and injection gentamicin combination; 7/181 (4%) patients died who received injection ampicilin and injection gentamicin whereas none died among the other two patients who received injection ceftriaxone and injection gentamicin (p = 1.00). The combination of injection ampicilin and injection gentamicin as the first-line antibiotics for the management of sepsis in children even beyond the neonatal age is very effective, resulting in lower mortality.

  15. In vitro gentamicin release from commercially available calcium-phosphate bone substitutes influence of carrier type on duration of the release profile

    Directory of Open Access Journals (Sweden)

    Bronckers Antonius LJJ

    2006-02-01

    Full Text Available Abstract Background Polymethyl-methacrylate (PMMA beads releasing antibiotics are used extensively to treat osteomyelitis, but require surgical removal afterwards because they do not degrade. Methods As an alternative option, this report compares the in vitro gentamicin release profile from clinically used, biodegradable carrier-materials: six injectable cements and six granule-types. Cement cylinders and coated granules containing 3% gentamicin were submerged in dH2O and placed in a 48-sample parallel drug-release system. At regular intervals (30, 90, 180 min. and then every 24 h, for 21 days, the release fluid was exchanged and the gentamicin concentration was measured. The activity of released gentamicin was tested on Staphylococcus aureus. Results All combinations showed initial burst-release of active gentamicin, two cements had continuous-release (17 days. The relative release of all cements (36–85% and granules (30–62% was higher than previously reported for injectable PMMA-cements (up to 17% and comparable to other biodegradable carriers. From the cements residual gentamicin could be extracted, whereas the granules released all gentamicin that had adhered to the surface. Conclusion The high release achieved shows great promise for clinical application of these biodegradable drug-carriers. Using the appropriate combination, the required release profile (burst or sustained may be achieved.

  16. Effect of Catechins, Green tea Extract and Methylxanthines in Combination with Gentamicin Against Staphylococcus aureus and Pseudomonas aeruginosa - Combination therapy against resistant bacteria -

    Directory of Open Access Journals (Sweden)

    Bibi Sedigheh Fazly Bazzaz

    2016-12-01

    Full Text Available Objectives: Bacterial resistant infections have become a global health challenge and threaten the society’s health. Thus, an urgent need exists to find ways to combat resistant pathogens. One promising approach to overcoming bacterial resistance is the use of herbal products. Green tea catechins, the major green tea polyphenols, show antimicrobial activity against resistant pathogens. The present study aimed to investigate the effect of catechins, green tea extract, and methylxanthines in combination with gentamicin against standard and clinical isolates of Staphylococcus aureus (S. aureus and the standard strain of Pseudomonas aeruginosa (P. aeruginosa. Methods: The minimum inhibitory concentration (MIC and the minimum bactericidal concentration (MBC values of different agents against bacterial strains were determined. The interactions of green tea extract, epigallate catechin, epigallocatechin gallate, two types of methylxanthine, caffeine, and theophylline with gentamicin were studied in vitro by using a checkerboard method and calculating the fraction inhibitory concentration index (FICI. Results: The MICs of gentamicin against bacterial strains were in the range of 0.312 - 320 μg/mL. The MIC values of both types of catechins were 62.5 - 250 μg/ mL. Green tea extract showed insufficient antibacterial activity when used alone. Methylxanthines had no intrinsic inhibitory activity against any of the bacterial strains tested. When green tea extract and catechins were combined with gentamicin, the MIC values of gentamicin against the standard strains and a clinical isolate were reduced, and synergistic activities were observed (FICI < 1. A combination of caffeine with gentamicin did not alter the MIC values of gentamicin. Conclusion: The results of the present study revealed that green tea extract and catechins potentiated the antimicrobial action of gentamicin against some clinical isolates of S. aureus and standard P. aeruginosa strains

  17. Intratympanic gentamicin therapy for control of vertigo in unilateral Meniere's disease : a prospective, double-blind, randomized, placebo-controlled trial

    NARCIS (Netherlands)

    Postema, Rolf J.; Kingma, Charlotte M.; Wit, Hero P.; Albers, Frans W. J.; Van Der Laan, Bernard F. A. M.

    2008-01-01

    Conclusions. Intratympanic application of gentamicin is a relatively safe and efficient treatment for the reduction of complaints of vertigo attacks associated with Meniere's disease. The treatment also reduces the severity of the perceived aural fullness. Objective. To investigate the effectiveness

  18. Protective Effect of Hexane and Ethanol Extract of Piper Longum L. on Gentamicin-Induced Hair Cell Loss in Neonatal Cultures

    National Research Council Canada - National Science Library

    Yadav, Mukesh Kumar; Choi, June; Song, Jae-Jun

    2014-01-01

    Gentamicin (GM) is a commonly used aminoglycoside antibiotic that generates free oxygen radicals within the inner ear, which can cause vestibulo-cochlear toxicity and permanent damage to the sensory hair cells and neurons. L. (PL...

  19. Preliminary study on synergistic combinations of raw honey with gentamicin against Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa of veterinary origin

    Institute of Scientific and Technical Information of China (English)

    MoussaAhmed; Baghdad Khiati; SaadAissat; Noureddine Djebli

    2015-01-01

    Objective: To search for further synergistic combinations of gentamicin and raw honey that might have potential in treating wounds. Methods: The antibacterial activity and synergistic interaction of raw honey and gentamicin was assessed by using agar well diffusion method. Two Gram-negative (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 2154) bacteria were selected for antibacterial activity assay. The cultures of bacteria were maintained in their appropriate agar slants at 4 °C throughout the study and used as stock cultures. Results: Raw honey and gentamicin interacted synergistically to inhibit Escherichia coli and Pseudomonas aeruginosa. Conclusions: These results suggest that combinations of raw honey and gentamicin have therapeutic benefits in prophylaxis of infections caused by multidrug-resistant Gram-negative bacilli.

  20. Evaluation of gentamicin and lidocaine release profile from gum acacia-crosslinked-poly(2-hydroxyethylmethacrylate)-carbopol based hydrogels.

    Science.gov (United States)

    Singh, Baljit; Dhiman, Abhishek

    2017-01-27

    In this manuscript an attempt has been made to incorporate both, antibiotic agent 'gentamicin' and pain relieving agent 'lidocaine' into the gum acacia-poly(2-hydroxyethylmethacrylate)-carbopol based hydrogel for wound dressing application. Drug release, gel strength, network parameter, antimicrobial activity and biodegradation properties of hydrogel have been evaluated. Porous microstructure of the hydrogel was observed in cryo-SEM images. The hydrogel showed mesh size 37.29 nm, cross-link density 2.19× 10-5 mol/cm3, molecular weight between two cross-links 60.25× 10-3 g/mol and gel strength 0.625±0.112 N in simulated wound fluid. The hydrogels were evaluated as a drug carrier for model drugs gentamicin and lidocaine. The release of these drugs occurred through Fickian diffusion mechanism and release profile of the drugs was best fitted in first order kinetic model.

  1. Nephro-protective effect of vitamin C and Nigella sativa oil on gentamicin associated nephrotoxicity in rabbits.

    Science.gov (United States)

    Saleem, Uzma; Ahmad, Bashir; Rehman, Kanwal; Mahmood, Saeed; Alam, Maqsood; Erum, Alia

    2012-10-01

    Oxidative stress causes the generation of reactive oxygen species (ROS) that lead to nephrotoxicity. An aminoglycoside, gentamicin, has pronounced nephrotoxic effect in humans and animals and this study was planned to observe the nephro-protective effect of antioxidants, vitamin C and Nigella sativa oil. Serum creatinine, blood urea nitrogen, and antioxidant activity were measured as indicators of nephrotoxicity for all the groups of rabbits. Results showed that vitamin C and Nigella sativa oil both had nephro-protective effect as they lowered the values of nephrotoxicity indicators (serum creatinine, blood urea nitrogen, and antioxidant activity) as compared to gentamicin control group values. When these two antioxidants were given as combination, they proved to have synergistic nephro-protective effect.

  2. Effects of gentamicin monotherapy for the initial treatment of community-onset complicated non-obstructive acute pyelonephritis due to Enterobacteriaceae in elderly and non-elderly women.

    Science.gov (United States)

    Wie, S-H; Kim, H W; Chang, U-I

    2014-11-01

    Aminoglycosides may serve as fluoroquinolone-sparing or cephalosporin-sparing agents if the clinical effectiveness of aminoglycoside monotherapy is demonstrated. The purposes of this study were to investigate the clinical efficacy of gentamicin as an initial empirical antimicrobial agent and to evaluate the effects of gentamicin resistance on clinical outcomes in women with complicated non-obstructive acute pyelonephritis (APN). Medical records of 1066 women with a diagnosis of APN were reviewed retrospectively. We enrolled 275 women with community-onset complicated non-obstructive APN due to Enterobacteriaceae who received gentamicin as their initial antibiotic. Of these 275 patients, 43 had gentamicin-resistant (GM-R) Enterobacteriaceae APN, and 232 had gentamicin-susceptible (GM-S) Enterobacteriaceae APN. The early clinical success rates were 67.4% (29/43) versus 89.7% (208/232) at 72 h in the GM-R versus the GM-S groups (p 0.001). The overall clinical cure rate was 100% (43/43) and 98.7% (229/232) in the GM-R and GM-S groups, respectively. The duration of hospital stay was significantly longer in the elderly, although there were no significant differences in the rates of early clinical success, final clinical cure, mortality, and time to fever clearance between the elderly and non-elderly groups. Resistance of Enterobacteriaceae to gentamicin, haematuria and serum C-reactive protein level≥20 mg/dL were independently associated with early clinical failure. Gentamicin can be an effective initial antibiotic option for empirical therapy in women with community-onset complicated APN who do not need urological interventional procedures. The use of gentamicin may contribute to a reduction of fluoroquinolone or broad-spectrum cephalosporin use in the treatment of complicated APN.

  3. RELEASE OF GENTAMICIN FROM CEMENT SPACERS IN TWO-STAGE PROCEDURES FOR HIP AND KNEE PROSTHETIC INFECTION: AN IN VIVO PHARMACOKINETIC STUDY WITH CLINICAL FOLLOW-UP.

    Science.gov (United States)

    Balato, G; Ascione, T; Rosa, D; Pagliano, P; Solarino, G; Moretti, B; Mariconda, M

    2015-01-01

    Eighteen patients undergoing two-stage exchange arthroplasty for infected total hip or knee arthroplasty using gentamicin-loaded bone cement spacers (80g bone cement, 2 g gentamicin and 2 g clindamycin) were studied. The concentration of gentamicin eluted from the spacers was assessed on samples of blood, urine, and drainage fluid that were collected from each patient at set intervals during the 48 hours following the first-stage surgery. The hip and knee cement spacers showed similar curve of release over the first postoperative hours (early peak followed by slow release), but the mean gentamicin concentration in the drainage fluid was higher in patients with hip spacers compared to patients with knee spacers (30.61±19.47 mg/L vs 17.43±13,63 mg/L, p less than 0.05). In patients with hip spacers, the mean, maximum, and minimum concentration of gentamicin was higher with respect to the minimum inhibitory concentration (MIC) break point for Staphylococcus spp, Pseudomonas Aeruginosa and Enterobacteriaceae throughout the first postoperative 48 h. Conversely, in 25% of patients with a knee spacer a drug concentration below the MIC break point for Gram negative bacteria was found in the drainage fluid after 12 h. Gentamicin levels in the blood samples were negligible over the entire time interval and were steadily well below the renal toxicity reference. The highest urinary concentration of gentamicin was observed between 4 and 9 h postoperatively. Subsequently, it gradually declined until 48 h. Clinically, the rate of cure was 100% at a mean follow-up of 113 weeks (range 90-182). Gentamicin-loaded cement spacers offer the advantage of achieving early high concentrations of the antibiotic directly at the site of infection but especially in the knee a systemic antibiotic therapy must be given as a complement to the spacer implantation to eradicate periprosthetic joint infection (PJI).

  4. Light-microscopic immunocytochemistry for Gentamicin and its use for studying uptake of the drug in kidney

    DEFF Research Database (Denmark)

    Fujiwara, Kunio; Shin, Masashi; Matsunaga, Hayato

    2009-01-01

    Gentamicin (GM) is a widely used antibiotic but shows renal toxicity. We produced a serum against GM (anti-GM) conjugated to bovine serum albumin with N-(gamma-maleimidobutyryloxy)succinimide. The antiserum was monospecific for GM and did not cross-react with the analog streptomycin, tobramycin...... compartments. This approach should be useful for accurately detecting the uptake and toxicity of the antibiotic in different tissues....

  5. Kinetics of kill of bacterial conjunctivitis isolates with moxifloxacin, a fluoroquinolone, compared with the aminoglycosides tobramycin and gentamicin

    Directory of Open Access Journals (Sweden)

    Rudolph S Wagner

    2010-01-01

    Full Text Available Rudolph S Wagner1, David B Granet2, Steven J Lichtenstein3, Tiffany Jamison4, Joseph J Dajcs4, Robert D Gross5, Paul Cockrum41New Jersey Medical School, Newark, NJ, USA; 2Ratner Children’s Eye Center, University of California – San Diego, La Jolla, CA, USA; 3University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA; 4Alcon Research, Ltd, Fort Worth, TX, USA; 5Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, USAPurpose: To compare the kinetics and speed of kill of Streptococcus pneumoniae and Haemophilus influenzae on exposure to three topical ophthalmic antibiotic solutions.Materials and methods: Bacterial conjunctivitis isolates of S. pneumoniae and H. influenzae were exposed to 1:1000 dilutions of moxifloxacin 0.5%, tobramycin 0.3%, gentamicin 0.3%, and water (control. At 15, 30, 60, 120, and 180 minutes after exposure, aliquots were collected, cells were cultured, and viable cell counts were determined using standard microbiological methods.Results: Moxifloxacin achieved 99.9% kill (3-log reduction at approximately 2 hours for S. pneumoniae and at 15 minutes for H. influenzae. Tobramycin and gentamicin did not achieve 3-log reduction of S. pneumoniae during the 180-minute study period. An increase in bacterial growth was noted for these isolates. Gentamicin took more than 120 minutes to achieve the 3-log reduction of H. influenzae and tobramycin did not reach the 3-log reduction of this pathogen during the 180-minute study period.Conclusion: Moxifloxacin killed S. pneumoniae and H. influenzae in vitro faster than tobramycin and gentamicin, suggesting its potential clinical benefit as a first-line treatment for bacterial conjunctivitis to minimize patient symptoms and to limit the contagiousness of the disease.Keywords: kinetics of kill, bacterial conjunctivitis, in vitro, Streptococcus pneumoniae, Haemophilus influenzae, fluoroquinolones, aminoglycosides

  6. Evaluation of biochemical effects of Casuarina equisetifolia extract on gentamicin-induced nephrotoxicity and oxidative stress in rats. Phytochemical analysis

    OpenAIRE

    El-Tantawy, Walid Hamdy; Mohamed, Shaza Abdel-Halim; Abd Al Haleem, Ekram Nemr

    2013-01-01

    Nephrotoxicity is defined as renal dysfunction that arises as result of exposure to external agents such as drugs and environmental chemicals. The present work was undertaken to carry out the phytochemical study and nephroprotective activity of methanolic extract of Casuarina equisetifolia leaves in gentamicin-induced nephrotoxicity in Wistar rats. Flavonoids and phenolic acids were identified and quantified using high performance liquid chromatography. Subcutaneous injection of rats with gen...

  7. Contaminated fistula following J-pouch ileoanal reservoir. Treatment with a collagen sponge containing gentamicin and metronidazole. Case report

    DEFF Research Database (Denmark)

    Nielsen, R; Bülow, Steffen; Moesgaard, F

    1991-01-01

    In a 55-year-old woman, a 1 x 5 cm fistula developed in the ileoanal anastomosis after restorative proctocolectomy with J-pouch ileoanal reservoir and temporary ileostomy for intractable ulcerative colitis. The fistula extended between the pouch and the sacral bone. Lasting closure was achieved b...... by intrafistular placement of a collagen sponge containing gentamicin and soaked in metronidazole solution and pouch drainage through a transanal Foley catheter....

  8. Contaminated fistula following J-pouch ileoanal reservoir. Treatment with a collagen sponge containing gentamicin and metronidazole. Case report

    DEFF Research Database (Denmark)

    Nielsen, R; Bülow, Steffen; Moesgaard, F

    1991-01-01

    In a 55-year-old woman, a 1 x 5 cm fistula developed in the ileoanal anastomosis after restorative proctocolectomy with J-pouch ileoanal reservoir and temporary ileostomy for intractable ulcerative colitis. The fistula extended between the pouch and the sacral bone. Lasting closure was achieved b...... by intrafistular placement of a collagen sponge containing gentamicin and soaked in metronidazole solution and pouch drainage through a transanal Foley catheter....

  9. Influence of osmotic and oncotic factors on gentamicin and insulin transport across the peritoneal membrane in vitro.

    Science.gov (United States)

    Grzelak, Teresa; Wojciechowska, Katarzyna; Szary, Beata; Czyzewska, Krystyna

    2011-01-01

    Glucose or its polymer is usually added to dialysis solution for the development of sufficient ultrafiltration during peritoneal dialysis. The aim of the present study was to determine the influence of glucose and icodextrin on the transport of gentamicin and insulin from the mesothelial to the interstitial side of the peritoneal membrane. Transfer values are expressed as a coefficient of diffusive permeability, P, in centimeters per second. Each of the molecules was tested in 3 series of experiments using rabbit parietal peritoneum, a modified Ussing chamber, and a mathematical model of mass transport. First, transperitoneal transfers of gentamicin (0.040 g/dL) and insulin (0.1 g/dL) were analyzed in control conditions for 120 minutes. Then, transport parameters for gentamicin and insulin were separately determined before (15-60 minutes) and after (75-120 minutes or 75-130 minutes) the application of glucose (1.8 g/dL) or icodextrin (2 g/ dL) on the mesothelial side of the peritoneal membrane. Insulin transport was observed to be stable in the control series. Gentamicin transfer was not stable; its passage declined by 52% (p insulin, the mean P (+ standard error of the mean) was 0.15 +/- 0.02 cm/s (x0.0001) at the first hour of transfer and 0.14 - 0.02 cm/s (x0.0001) at the second. Glucose induced a nonsignificant intensification of insulin transport. Icodextrin increased insulin passage by 107% (p insulin transport from the mesothelial to the interstitial side of the peritoneum. Similar modifications might be observed in vivo during peritoneal dialysis or continuous intraperitoneal administration of insulin, influencing the efficiency of those treatments.

  10. Electrochemical oxidation of drug residues in water by the example of tetracycline, gentamicin and Aspirin {sup trademark}

    Energy Technology Data Exchange (ETDEWEB)

    Weichgrebe, D.; Danilova, E.; Rosenwinkel, K.H. [Inst. of Water Quality and Waste Management, Univ. of Hannover, Hannover (Germany); Vedenjapin, A.; Baturova, M. [Inst. of Organic Chemistry, Russian Academy of Science, Moscow (Russian Federation)

    2003-07-01

    The electrochemical oxidation as a method to destroy drug residues like Aspirin {sup trademark}, tetracycline or gentamicin in water was investigated with C-Anode (modified by manganese oxides) and Pt Anode. The mechanism of Aspirin {sup trademark} and tetracycline oxidation and the influence of the biocide effect was observed using GC-MS and three different microbiological tests. In general the biological availability increases with progressive oxidation of the antibiotics. (orig.)

  11. NaHS Protects Cochlear Hair Cells from Gentamicin-Induced Ototoxicity by Inhibiting the Mitochondrial Apoptosis Pathway.

    Directory of Open Access Journals (Sweden)

    Yaodong Dong

    Full Text Available Aminoglycoside antibiotics such as gentamicin could cause ototoxicity in mammalians, by inducing oxidative stress and apoptosis in sensory hair cells of the cochlea. Sodium hydrosulfide (NaHS is reported to alleviate oxidative stress and apoptosis, but its role in protecting aminoglycoside-induced hearing loss is unclear. In this study, we investigated the anti-oxidant and anti-apoptosis effect of NaHS in in vitro cultured House Ear Institute-Organ of Corti 1 (HEI-OC1 cells and isolated mouse cochlea. Results from cultured HEI-OC1 cells and cochlea consistently indicated that NaHS exhibited protective effects from gentamicin-induced ototoxicity, evident by maintained cell viability, hair cell number and cochlear morphology, reduced reactive oxygen species production and mitochondrial depolarization, as well as apoptosis activation of the intrinsic pathway. Moreover, in the isolated cochlear culture, NaHS was also demonstrated to protect the explant from gentamicin-induced mechanotransduction loss. Our study using multiple in vitro models revealed for the first time, the potential of NaHS as a therapeutic agent in protecting against aminoglycoside-induced hearing loss.

  12. NaHS Protects Cochlear Hair Cells from Gentamicin-Induced Ototoxicity by Inhibiting the Mitochondrial Apoptosis Pathway

    Science.gov (United States)

    Dong, Yaodong; Liu, Dongliang; Hu, Yue; Ma, Xiulan

    2015-01-01

    Aminoglycoside antibiotics such as gentamicin could cause ototoxicity in mammalians, by inducing oxidative stress and apoptosis in sensory hair cells of the cochlea. Sodium hydrosulfide (NaHS) is reported to alleviate oxidative stress and apoptosis, but its role in protecting aminoglycoside-induced hearing loss is unclear. In this study, we investigated the anti-oxidant and anti-apoptosis effect of NaHS in in vitro cultured House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and isolated mouse cochlea. Results from cultured HEI-OC1 cells and cochlea consistently indicated that NaHS exhibited protective effects from gentamicin-induced ototoxicity, evident by maintained cell viability, hair cell number and cochlear morphology, reduced reactive oxygen species production and mitochondrial depolarization, as well as apoptosis activation of the intrinsic pathway. Moreover, in the isolated cochlear culture, NaHS was also demonstrated to protect the explant from gentamicin-induced mechanotransduction loss. Our study using multiple in vitro models revealed for the first time, the potential of NaHS as a therapeutic agent in protecting against aminoglycoside-induced hearing loss. PMID:26295804

  13. Protective Effect of Carvacrol on Renal Functional and Histopathological Changes in Gentamicin-Induced-Nephrotoxicity in Rats

    Directory of Open Access Journals (Sweden)

    Hassan Ahmadvand

    2016-04-01

    Full Text Available Background Nephrotoxicity is one of the most important side effects of the use of gentamicin sulphate (GS resulted in reactive oxygen species generation. Antioxidant compounds played effective roles in reduction of renal injuries caused by using of gentamicin. Carvacrol is a strong antioxidant compound. Objectives The aim of this study is to explore the effect of carvacrol inhibition in lesions of gentamicin-induced nephrotoxicity. Materials and Methods In this experimental study, 32 male mature Sprague-Dawley rats were divided into 4 groups of 8; group1: control, group 2 sham received daily carvacrol injection (74 mg/kg for 12 days, group 3 received daily GS injection (100 mg/kg for 12 days, group 4 received daily GS (100 mg/kg and carvacrol (74 mg/kg for 12 days. After 12 days, rats were anaesthetized, blood sample were obtained and kidneys were removed then stained with hematoxylin and eosin method and then were studied histophatologically. Serum creatinine and urea were measured. Results Flow treatment of nephrotoxic animals with carvacrol could significantly inhibit leukocyte infiltration (9.42% and tubular necrosis (38.18% in comparison with the nephrotoxic untreated group. Carvacrol significantly decreased the levels of urea and creatinine in treated group compared with the nephrotoxic untreated group. Conclusions The findings showed that carvacrol alleviates loss of leukocyte infiltration (9.42% and tubular necrosis and exerts beneficial effects on kidney function test in nephrotoxic group.

  14. In vitro activity of RPR 106972 alone and in combination with vancomycin, ampicillin, and gentamicin against multidrug-resistant enterococci.

    Science.gov (United States)

    Messick, C R; Woodward, J; Pendland, S L

    1998-10-01

    This investigation used checkerboard and time-kill assays to evaluate the in vitro activity of RPR 106972 (45% pristinamycin IB and 55% pristinamycin IIB) alone and in combination with vancomycin or ampicillin +/- gentamicin against multidrug-resistant enterococci. The checkerboard procedure resulted in synergistic or additive effects in 91% of the isolates with the combination of RPR 106972 plus vancomycin versus 68% with RPR 106972 plus ampicillin. The addition of gentamicin to either combination resulted in synergistic or additive results in 100% of the isolates. Inhibitory activity was observed with the time-kill assay with mean change in log10 CFU/mL at 24 h of -0.31 for RPR 106972, 3.3 for vancomycin, -0.46 for RPR 106972 plus vancomycin, and -0.35 for RPR 106972 plus vancomycin and gentamicin. No antagonism was noted with any of the combinations. RPR 106972 demonstrates good inhibitory activity against Enterococcus faecium and may prove useful in the treatment of enterococcal infections.

  15. Evaluation of biochemical effects of Casuarina equisetifolia extract on gentamicin-induced nephrotoxicity and oxidative stress in rats. Phytochemical analysis.

    Science.gov (United States)

    El-Tantawy, Walid Hamdy; Mohamed, Shaza Abdel-Halim; Abd Al Haleem, Ekram Nemr

    2013-11-01

    Nephrotoxicity is defined as renal dysfunction that arises as result of exposure to external agents such as drugs and environmental chemicals. The present work was undertaken to carry out the phytochemical study and nephroprotective activity of methanolic extract of Casuarina equisetifolia leaves in gentamicin-induced nephrotoxicity in Wistar rats. Flavonoids and phenolic acids were identified and quantified using high performance liquid chromatography. Subcutaneous injection of rats with gentamicin (80 mg/kg body weight/day) for six consecutive days induced marked acute renal toxicity, manifested by a significant increase in serum urea, creatinine and uric acid levels, along with a significant depletion of serum potassium level, compared to normal controls. Also oxidative stress was noticed in renal tissue as evidenced by a significant decrease in glutathione level, superoxide dismutase, glutathione-S-transferase activities, also a significant increase in malondialdehyde and nitric oxide levels when compared to control group. Administration of plant extract at a dose of 300 mg/kg once daily for 4 weeks restored normal renal functions and attenuated oxidative stress. In conclusion, Casuarina equisetifolia leaves extract ameliorates gentamicin-induced nephrotoxicity and oxidative damage by scavenging oxygen free radicals, decreasing lipid peroxidation and improving intracellular antioxidant defense, thus extract may be used as nephroprotective agent.

  16. Determination of gentamicin sulfate and related compounds by high-performance liquid chromatography with evaporative light scattering detection.

    Science.gov (United States)

    Clarot, I; Chaimbault, P; Hasdenteufel, F; Netter, P; Nicolas, A

    2004-03-26

    A rapid and simple method for the separation and quantitation of gentamicin sulfate by HPLC coupled with evaporative light scattering detection (ELSD) has been developed. Detection of the different components of gentamicin is problematic because of the lack of UV absorbing chromophore. The use of the universal ELSD avoids the need for sample derivatization or use of specific detector such as pulsed amperometry. Separation was performed on a highpurity C18 125 mm x 4 mm i.d., 3 microm, reversed phase column with 48.5 mM trifluoroacetic acid-methanol (97:3, v/v), as mobile phase at a flow rate of 0.7 ml/min. The influence of the gas nature, gas pressure and temperature of the drift tube of the detector on the detection response was investigated. Optimization was performed with the help of a specific experimental design software. This method allows the determination of the composition in components C1, C1a, C2, C2a and C2b of gentamicin sulfate samples. Mass spectrometry was employed to confirm the ELSD chromatographic profile. The method was validated using methodology described by the International Conference of Harmonization in the field of Medicinal Substances. Commercial samples of different sources were analyzed and results were in good agreement with specifications of both European and United States Pharmacopoeia.

  17. In vitro gentamicin release from bioactive Bhagelena implant against Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Aniek Setiya Budiatin

    2014-05-01

    Full Text Available Osteomyelitis is a bone-related infectious desease which is difficult to treat, because the antibiotic reaches the target is lower than the MIC and bacteria can €™t be eradicated. This condition can cause the bacteria become resistant. To solve this problem, we can use local antibiotics as BHAG(ELENA pellets implant, which can release gentamicin (GEN continuously for more than a day with a concentration greater than MIC. BHAG(ELENA pellet that have made contain BHA : GEL = 20 : 2 (dry state; GEN 10% and cross-linking with glutaraldehyde (GA 0,5%, cylindrical weigh 100 mg; 4 mm in diameter and 3.2 mm thick. The release of GEN from BHAG(ELENA pellet were tested in vitro, by soaking the pellet in phosphate buffer saline pH 7.4 at temperature 370C. The sample were sampled every day until 28 days. Then, the sample were tested by agar diffusion method that contain Staphylococcus aureus. Results showed that inhibition zone diameter greater than MIC GEN to S. aureus. Within 28 days, the release of GEN provide a total activity 99,24%, it showed that after 28 days, the pellets are still actively inhibit the bacterial growth. Furthermore, required to be tested in animal study (in vivo with a defect in the femoral bone then filled with BHAG(ELENA pellets as drug delivery system of GEN and bone fillers

  18. Sida rhomboidea.Roxb leaf extract ameliorates gentamicin induced nephrotoxicity and renal dysfunction in rats.

    Science.gov (United States)

    Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Devkar, Ranjitsinh V; Ramachandran, A V

    2010-10-28

    Sida rhomboidea.Roxb (SR) known as "Mahabala" in Ayurveda and marketed as "Shahadeyi" is used in ethnomedicine to treat ailments such as dysuria and urinary disorders. To evaluate nephroprotective potential of SR against gentamicin (GM) induced nephrotoxicity and renal dysfunction. Nephrotoxicity was induced in rats with GM (100 mg/kg bodyweight (i.p.) for 8 days) and were treated with SR extract (200 and 400 mg/kg bodyweight (p.o.) for 8 days) or 0.5% carboxymethyl cellulose (vehicle). Plasma and urine urea and creatinine, renal enzymatic and non-enzymatic antioxidants along with lipid peroxidation were evaluated in various experimental groups. GM treatment induced significant elevation (p<0.05) in plasma and urine urea, creatinine, renal lipid peroxidation along with significant decrement (p<0.05) in renal enzymatic and non-enzymatic antioxidants. SR treatment to GM treated rats (GM+SR) recorded significant decrement (p<0.05) in plasma and urine urea and creatinine, renal lipid peroxidation along with significant increment (p<0.05) in renal enzymatic and non-enzymatic antioxidants. SR leaf extract ameliorates GM induced nephrotoxicity and renal dysfunction and thus validates its ethnomedicinal use. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  19. Gentamicin sulfate-loaded porous natural rubber films for wound dressing.

    Science.gov (United States)

    Phaechamud, Thawatchai; Issarayungyuen, Pongsathorn; Pichayakorn, Wiwat

    2016-04-01

    Antimicrobial wound dressings have been developed for effectiveness of wound therapy. In this study, gentamicin sulfate was loaded into modified porous natural rubber films. The hydrophilic porous structure in natural rubber films was formed when the polar liquid such as glycerin or triethyl citrate and hydrophilic xanthan gum were blended. Film properties including morphology, drug release, water sorption and erosion, mechanical property, adhesive property, surface free energy, water vapor transmission rate, oxygen permeation, and antimicrobial activity were determined. The angiogenesis activity of films was investigated using chick chorio-allantoic membrane assay. For the system containing triethyl citrate, bi-layers comprising of a dense-top layer and a high porous-bottom layer were observed. Xanthan gum enhanced the water sorption capacity and modified to obtain the optimum rate of the drug release from the film. The developed film topography with dense-top layer induced the low adhesive property, water vapor and oxygen permeability whereas demonstrated good antimicrobial activities against Staphylococcus aureus and Pseudomonas aeruginosa with angiogenic activity. Therefore it had the potential use for medicated wound dressing.

  20. Melatonin prevents gentamicin-induced testicular toxicity and oxidative stress in rats.

    Science.gov (United States)

    Kim, S-H; Lee, I-C; Baek, H-S; Shin, I-S; Moon, C; Kim, S-H; Yun, W-K; Nam, K-H; Kim, H-C; Kim, J-C

    2014-01-01

    This study investigated the protective effects of melatonin (MT) against gentamicin (GM)-induced testicular toxicity and oxidative damage in rats. GM (100 mg kg(-1) ) was injected intraperitoneally (i.p.) to rats for 6 days. MT (15 mg kg(-1) ) was administered i.p. to rats for 6 days at 1 hr after the GM treatment. GM caused a decrease in prostate and seminal vesicle weights, sperm count and sperm motility. Histopathological examination showed various morphological alterations in the testis, characterised by degeneration of spermatogonia/spermatocytes, decrease in the number of early spermatogenic cells and vacuolisation. In addition, an increased malondialdehyde concentration and decreased glutathione content and glutathione reductase, catalase and glutathione-S-transferase activities were found in the testis. In contrast, MT treatment significantly attenuated the testicular toxicity of GM, including decreased reproductive organ weights, sperm count, and sperm motility and increased histopathological alterations. MT also had an antioxidant benefit by decreasing the lipid peroxidative product malondialdehyde and increasing the level of the antioxidant glutathione and the activities of antioxidant enzymes in the testis. These results indicate that MT prevents testicular toxicity induced by GM in rats, presumably due to its potent antioxidant activity, and its ability to inhibit lipid peroxidation, and restore antioxidant enzyme activity.

  1. Gentamicin rapidly inhibits mitochondrial metabolism in high-frequency cochlear outer hair cells.

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    Heather C Jensen-Smith

    Full Text Available Aminoglycosides (AG, including gentamicin (GM, are the most frequently used antibiotics in the world and are proposed to cause irreversible cochlear damage and hearing loss (HL in 1/4 of the patients receiving these life-saving drugs. Akin to the results of AG ototoxicity studies, high-frequency, basal turn outer hair cells (OHCs preferentially succumb to multiple HL pathologies while inner hair cells (IHCs are much more resilient. To determine if endogenous differences in IHC and OHC mitochondrial metabolism dictate differential sensitivities to AG-induced HL, IHC- and OHC-specific changes in mitochondrial reduced nicotinamide adenine dinucleotide (NADH fluorescence during acute (1 h GM treatment were compared. GM-mediated decreases in NADH fluorescence and succinate dehydrogenase activity were observed shortly after GM application. High-frequency basal turn OHCs were found to be metabolically biased to rapidly respond to alterations in their microenvironment including GM and elevated glucose exposures. These metabolic biases may predispose high-frequency OHCs to preferentially produce cell-damaging reactive oxygen species during traumatic challenge. Noise-induced and age-related HL pathologies share key characteristics with AG ototoxicity, including preferential OHC loss and reactive oxygen species production. Data from this report highlight the need to address the role of mitochondrial metabolism in regulating AG ototoxicity and the need to illuminate how fundamental differences in IHC and OHC metabolism may dictate differences in HC fate during multiple HL pathologies.

  2. Autophagic flux, a possible mechanism for delayed gentamicin-induced ototoxicity

    Science.gov (United States)

    Kim, Yeon Ju; Tian, Chunjie; Kim, Jangho; Shin, Beomyong; Choo, Oak-Sung; Kim, You-Sun; Choung, Yun-Hoon

    2017-01-01

    Aminoglycoside antibiotics including gentamicin (GM) induce delayed ototoxic effects such as hearing loss after long-term use, unlike the early-onset ototoxicity caused by cisplatin. The purpose of the study was to identify the mechanism of the delayed GM-induced ototoxicity by exploring the role of autophagy in vitro and in vivo. Treating HEI-OC1 auditory cells with GM led to a time-dependent increase of the autophagosome marker LC3-II, which was accompanied by cell death. In contrast, cisplatin and penicillin caused a rapid increase and had no effect on LC3-II levels, respectively. LC3-II-expressing autophagosomes co-localized with the labeled GM. GM-treated autophagosomes expressed reduced levels of Rab7, which is necessary for the fusion of autophagosomes with lysosomes. When the autophagic flux enhancer rapamycin was applied to GM-treated cells, Rab7 and the lysosomal enzyme cathepsin D were upregulated, and increased cell survival was observed. In animal studies, the intraperitoneal injection of GM worsened hearing thresholds and induced the accumulation of LC3 in the organ of Corti. This hearing impairment was attenuated by rapamycin. These findings suggest that the delayed onset-ototoxicity of GM may be closely related to the accumulation of autophagosomes via impaired autophagy. This GM-induced auditory cell death could be inhibited by enhancing autophagic flux. PMID:28145495

  3. Transient ischemia/hypoxia enhances gentamicin ototoxicity via caspase-dependent cell death pathway.

    Science.gov (United States)

    Lin, Chia-Der; Kao, Ming-Ching; Tsai, Ming-Hsui; Lai, Chih-Ho; Wei, I-Hua; Tsai, Mang-Hung; Tang, Chih-Hsin; Lin, Cheng-Wen; Hsu, Chuan-Jen; Lin, Ching-Yuang

    2011-07-01

    Aminoglycoside ototoxicity is a common cause of drug-induced hearing loss. Toxicity is dose related, but some patients may still develop hearing loss even under safe dosage. Apart for genetic idiosyncrasy, indirect evidences imply that ischemia may increase the aminoglycoside ototoxic sensitivity because common clinical situations associated with cochlear ischemia such as noise, sepsis, and shock are known to augment the development of aminoglycoside ototoxicity. At present, a direct interaction of cochlear ischemia and aminoglycoside ototoxicity is still lacking. This study demonstrated a direct evidence of increased gentamicin (GM) ototoxic sensitivity in chronic guinea pig models of transient cochlear ischemia. No permanent auditory changes were observed after a single dose of GM (125 mg/kg) or after transient cochlear ischemia for 30 min. Persistent and significant auditory threshold shift was detected when GM was given after transient cochlear ischemia. Cochlear hair cells and spiral ganglion neurons are the major regions affected. Apoptosis contributes to hair cell death during acute interaction of ischemia and GM ototoxicity. Increased apoptotic cell death was also depicted when GM crossreacted with hypoxia in vitro, using cochlear cell lines. Generation of reactive oxygen species, loss of mitochondrial membrane potential, calcium release, and caspase-dependent apoptotic cell death were shown during the interaction of hypoxia and GM ototoxicity in vitro. This synergistic ototoxicity may be critical to aminoglycoside-induced hearing loss in clinical scenarios. The results should improve our understanding of the interacting mechanism and potential preventive strategy to aminoglycoside ototoxicity.

  4. Administration of BMSCs with muscone in rats with gentamicin-induced AKI improves their therapeutic efficacy.

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    Pengfei Liu

    Full Text Available The therapeutic action of bone marrow-derived mesenchymal stem cells (BMSCs in acute kidney injury (AKI has been reported by several groups. However, recent studies indicated that BMSCs homed to kidney tissues at very low levels after transplantation. The lack of specific homing of exogenously infused cells limited the effective implementation of BMSC-based therapies. In this study, we provided evidence that the administration of BMSCs combined with muscone in rats with gentamicin-induced AKI intravenously, was a feasible strategy to drive BMSCs to damaged tissues and improve the BMSC-based therapeutic effect. The effect of muscone on BMSC bioactivity was analyzed in vitro and in vivo. The results indicated that muscone could promote BMSC migration and proliferation. Some secretory capacity of BMSC still could be improved in some degree. The BMSC-based therapeutic action was ameliorated by promoting the recovery of biochemical variables in urine or blood, as well as the inhibition of cell apoptosis and inflammation. In addition, the up-regulation of CXCR4 and CXCR7 expression in BMSCs could be the possible mechanism of muscone amelioration. Thus, our study indicated that enhancement of BMSCs bioactivities with muscone could increase the BMSC therapeutic potential and further developed a new therapeutic strategy for the treatment of AKI.

  5. Temperature-dependent gentamicin resistance of Francisella tularensis is mediated by uptake modulation

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    Kathleen eLoughman

    2016-01-01

    Full Text Available Gentamicin (Gm is an aminoglycoside commonly used to treat bacterial infections such as tularemia – the disease caused by Francisella tularensis. In addition to being pathogenic, F. tularensis is found in environmental niches such as soil where this bacterium likely encounters Gm producers (Micromonospora sp.. Here we show that F. tularensis exhibits increased resistance to Gm at ambient temperature (26°C compared to mammalian body temperature (37°C. To evaluate whether F. tularensis was less permeable to Gm at 26°C, a fluorescent marker [Texas Red (Tr] was conjugated with Gm, yielding Tr-Gm. Bacteria incubated at 26°C showed reduced fluorescence compared to those at 37°C when exposed to Tr-Gm suggesting that uptake of Gm was reduced at 26°C. Unconjugated Gm competitively inhibited uptake of Tr-Gm, demonstrating that this fluorescent compound was taken up similarly to unconjugated Gm. Lysates of F. tularensis bacteria incubated with Gm at 37°C inhibited the growth of Escherichia coli significantly more than lysates from bacteria incubated at 26°C, further indicating reduced uptake at this lower temperature. Other facultative pathogens (Listeria monocytogenes and Klebsiella pneumoniae exhibited increased resistance to Gm at 26°C suggesting that the results generated using F. tularensis may be generalizable to diverse bacteria. Regulation of the uptake of antibiotics provides a mechanism by which facultative pathogens survive alongside antibiotic-producing microbes in nature.

  6. Curcumin Attenuates Gentamicin-Induced Kidney Mitochondrial Alterations: Possible Role of a Mitochondrial Biogenesis Mechanism

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    Mario Negrette-Guzmán

    2015-01-01

    Full Text Available It has been shown that curcumin (CUR, a polyphenol derived from Curcuma longa, exerts a protective effect against gentamicin- (GM- induced nephrotoxicity in rats, associated with a preservation of the antioxidant status. Although mitochondrial dysfunction is a hallmark in the GM-induced renal injury, the role of CUR in mitochondrial protection has not been studied. In this work, LLC-PK1 cells were preincubated 24 h with CUR and then coincubated 48 h with CUR and 8 mM GM. Treatment with CUR attenuated GM-induced drop in cell viability and led to an increase in nuclear factor (erythroid-2-related factor 2 (Nrf2 nuclear accumulation and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α cell expression attenuating GM-induced losses in these proteins. In vivo, Wistar rats were injected subcutaneously with GM (75 mg/Kg/12 h during 7 days to develop kidney mitochondrial alterations. CUR (400 mg/Kg/day was administered orally 5 days before and during the GM exposure. The GM-induced mitochondrial alterations in ultrastructure and bioenergetics as well as decrease in activities of respiratory complexes I and IV and induction of calcium-dependent permeability transition were mostly attenuated by CUR. Protection of CUR against GM-induced nephrotoxicity could be in part mediated by maintenance of mitochondrial functions and biogenesis with some participation of the nuclear factor Nrf2.

  7. Curcumin Attenuates Gentamicin-Induced Kidney Mitochondrial Alterations: Possible Role of a Mitochondrial Biogenesis Mechanism.

    Science.gov (United States)

    Negrette-Guzmán, Mario; García-Niño, Wylly Ramsés; Tapia, Edilia; Zazueta, Cecilia; Huerta-Yepez, Sara; León-Contreras, Juan Carlos; Hernández-Pando, Rogelio; Aparicio-Trejo, Omar Emiliano; Madero, Magdalena; Pedraza-Chaverri, José

    2015-01-01

    It has been shown that curcumin (CUR), a polyphenol derived from Curcuma longa, exerts a protective effect against gentamicin- (GM-) induced nephrotoxicity in rats, associated with a preservation of the antioxidant status. Although mitochondrial dysfunction is a hallmark in the GM-induced renal injury, the role of CUR in mitochondrial protection has not been studied. In this work, LLC-PK1 cells were preincubated 24 h with CUR and then coincubated 48 h with CUR and 8 mM GM. Treatment with CUR attenuated GM-induced drop in cell viability and led to an increase in nuclear factor (erythroid-2)-related factor 2 (Nrf2) nuclear accumulation and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) cell expression attenuating GM-induced losses in these proteins. In vivo, Wistar rats were injected subcutaneously with GM (75 mg/Kg/12 h) during 7 days to develop kidney mitochondrial alterations. CUR (400 mg/Kg/day) was administered orally 5 days before and during the GM exposure. The GM-induced mitochondrial alterations in ultrastructure and bioenergetics as well as decrease in activities of respiratory complexes I and IV and induction of calcium-dependent permeability transition were mostly attenuated by CUR. Protection of CUR against GM-induced nephrotoxicity could be in part mediated by maintenance of mitochondrial functions and biogenesis with some participation of the nuclear factor Nrf2.

  8. Gentamicin-loaded poly(lactic-co-glycolic acid) microparticles for the prevention of maxillofacial and orthopedic implant infections

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    Flores, Claudia [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Degoutin, Stephanie [Univ. Lille, 59000 Lille (France); UMET, Ingénierie des Systèmes Polymères, Université de Lille 1, 59655 Villeneuve d' Ascq (France); Chai, Feng [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Raoul, Gwenael [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Service Chirurgie Maxillo-Faciale, CHRU de Lille, 59000 Lille (France); Hornez, Jean-Chritophe [Laboratoire des Matériaux Céramiques et Procédés Associés (LMCPA), Université de Valenciennes, 59300 Valenciennes (France); Martel, Bernard [Univ. Lille, 59000 Lille (France); UMET, Ingénierie des Systèmes Polymères, Université de Lille 1, 59655 Villeneuve d' Ascq (France); Siepmann, Juergen [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Ferri, Joel [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Service Chirurgie Maxillo-Faciale, CHRU de Lille, 59000 Lille (France); Blanchemain, Nicolas, E-mail: nicolas.blanchemain@univ-lille2.fr [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France)

    2016-07-01

    Trauma and orthopedic surgery can cause infections as any open surgical procedures. Such complications occur in only1 to 5% of the cases, but the treatment is rather complicated due to bacterial biofilm formation and limited drug access to the site of infection upon systemic administration. An interesting strategy to overcome this type of complications is to prevent bacterial proliferation and biofilm formation via the local and controlled release of antibiotic drugs from the implant itself. Obviously, the incorporation of the drug into the implant should not affect the latter's biological and mechanical properties. In this context, we optimized the preparation process for gentamicin-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles, which can be incorporated in the macropores of calcium phosphate-based bone substitutes. Microparticles were prepared using a double emulsion solvent extraction/evaporation technique. The processing parameters were optimized in order to provide an average microparticle size of about 60 μm, allowing for incorporation inside the macropores (100 μm) of the hydroxyapatite scaffold. Gentamicin-loaded PLGA microparticles showed a sustained release for 25–30 days and a rapid antibacterial activity due to a burst effect, the extent of which was controlled by the initial loading of the microparticles. SEM pictures revealed a highly porous microparticle structure, which can help to reduce the micro environmental pH drop and autocatalytic effects. The biological evaluation showed the cytocompatibility and non-hemolytic property of the microparticles, and the antibacterial activity against Staphylococcus aureus under the given conditions. - Highlights: • The optimization of microparticle preparation parameters allows to obtain a size compatible with the bone substitute porosity • PDL% has a direct impact on the burst effect, a control release of gentamicin was obtained • The incorporation of microparticles into the

  9. Sensitive fluorimetric determination of gentamicin sulfate in biological matrices using solid-phase extraction, pre-column derivatization with 9-fluorenylmethyl chloroformate and reversed-phase high-performance liquid chromatography.

    Science.gov (United States)

    Stead, D A; Richards, R M

    1996-01-26

    A high-performance liquid chromatographic method is described for the determination of gentamicin in bacterial culture medium or plasma with increased sensitivity and improved separation of the C1 component. Gentamicin was extracted from the biological matrix with high efficiency using carboxypropyl (CBA)-bonded silica. Derivatization with 9-fluorenylmethyl chloroformate (FMOC-Cl) followed by C18 reversed-phase chromatography allowed the fluorimetric detection of gentamicins C1, C1a and C2. A fourth component, considered to be gentamicin C2a, was partially resolved from the C2 peak. Optimal conditions for the extraction and derivatization of gentamicin are described. The detection limit was below 50 micrograms/l, the assay was linear to 5 mg/l and showed good reproducibility. It is concluded that pre-column derivatization with FMOC-Cl substantially improves the analysis of gentamicin compared with present methods based on reaction with o-phthaldialdehyde.

  10. Gentamicin-induced preconditioning of proximal tubular LLC-PK1 cells stimulates nitric oxide production but not the synthesis of heat shock protein

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    E.A. Pessoa

    2009-07-01

    Full Text Available Nephrotoxicity is the main side effect of antibiotics such as gentamicin. Preconditioning has been reported to protect against injuries as ischemia/reperfusion. The objective of the present study was to determine the effect of preconditioning with gentamicin on LLC-PK1 cells. Preconditioning was induced in LLC-PK1 cells by 24-h exposure to 2.0 mM gentamicin (G/IU. After 4 or 15 days of preconditioning, cells were again exposed to gentamicin (2.0 mM and compared to untreated control or G/IU cells. Necrosis and apoptosis were assessed by acridine orange and HOESCHT 33346. Nitric oxide (NO and endothelin-1 were assessed by the Griess method and available kit. Heat shock proteins were analyzed by Western blotting. After 15 days of preconditioning, LLC-PK1 cells exhibited a significant decrease in necrosis (23.5 ± 4.3 to 6.5 ± 0.3% and apoptosis (23.5 ± 4.3 to 6.5 ± 2.1% and an increase in cell proliferation compared to G/IU. NO (0.177 ± 0.05 to 0.368 ± 0.073 µg/mg protein and endothelin-1 (1.88 ± 0.47 to 2.75 ± 0.53 pg/mL production significantly increased after 15 days of preconditioning compared to G/IU. No difference in inducible HSP 70, constitutive HSC 70 or HSP 90 synthesis in tubular cells was observed after preconditioning with gentamicin. The present data suggest that preconditioning with gentamicin has protective effects on proximal tubular cells, that involved NO synthesis but not reduction of endothelin-1 or production of HSP 70, HSC 70, or HSP 90. We conclude that preconditioning could be a useful tool to prevent the nephrotoxicity induced by gentamicin.

  11. Evaluation of protective effect of hydroalcoholic extract of Crocus sativus petals on preventing of gentamicin induced peliosis hepatis and hepatic telangiectasis in rats: short communication

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    Arash Omidi

    2013-02-01

    Full Text Available Peliosis hepatis is a rare liver disease characterized by blood-filled cavities scattered irregularly throughout the liver. Risk factors for peliosis include chronic illness such as AIDS, tuberculosis, cancer also use of some drugs such as anabolic steroids and azathioprine. The aim of the present study was to evaluate the curative properties of crocus sativus petals on induced peliosis hepatis in rats. Thirty two male Wistar rats (weight: 180-220 g were randomly divided into four equal groups: group 1 (healthy group received only IP normal saline, group2 received IP 80mg/kg.bw gentamicin, group3 IP 80mg/kg.bw gentamicin+ 40mg/kg crocus sativus petal extract, and group 4 was given IP 80mg/kg.bw gentamicin+ 40mg/kg crocus sativus petal extract. At the end of the experiment, the rats were anesthetized and their blood samples were collected through cardiac puncture for AST and ALT measurement.Then, the livers of the subjects were excised and fixed in formalin. It was found that AST significantly increased in gentamicin group (P<0.05 compared to the healthy group and groups treated by means of crocus sativus petal extract .Moreover, there was no significant differences between the groups administered the extract and those given gentamicin. Histologically,heterogeneous multiple blood-filled cavities were observed in gentamicin group (2 and the treatment groups (3 and 4. The results of the present study show that doses of hydroalcoholic extract of crocus sativus do not effect on peliosis hepatic and telangiectasis due to gentamicin sulfate in rats

  12. Chitosan Prevents Gentamicin-Induced Nephrotoxicity via a Carbonyl Stress-Dependent Pathway

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    Chu-Kung Chou

    2015-01-01

    Full Text Available Aminoglycosides are widely used to treat infections; however, their applications are limited by nephrotoxicity. With the increase of antibiotic resistance, the use of aminoglycosides is inevitable. Low-molecular-weight chitosan (LMWC has shown renal protective effects in dialysis patients. However, no study has evaluated LMWC for preventing aminoglycoside-induced nephrotoxicity or determined the mechanisms underlying the renal protective effects. In this study, LMWC (165 or 825 mg/kg/day or metformin (100 mg/kg/day was orally administered for 13 days to rats with nephropathy induced by gentamicin (GM, a kind of aminoglycoside (150 mg/kg/day i.p. for 6 days. Both LMCW doses improved renal function. Serum creatinine levels improved in rats treated with 165 and 825 mg/kg/day LMWC (from 2.14 ± 0.74 mg/dL to 1.26 ± 0.46 mg/dL and 0.69 ± 0.12 mg/dL, resp., P < 0.05. Blood urea nitrogen levels were also improved in these rats (from 73.73 ± 21.13 mg/dL to 58.70 ± 22.71 mg/dL and 28.82 ± 3.84 mg/dL, resp., P < 0.05. Additionally, renal tissue morphology improved after LMWC treatment, and accumulation of renal methylglyoxal, a damage factor associated with carbonyl stress, was reversed. These results show that LMWC prevents GM-induced renal toxicity via a carbonyl stress-dependent pathway.

  13. Efficacy of ciprofloxacin-gentamicin combination therapy in murine bubonic plague.

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    Nadine Lemaître

    Full Text Available Potential benefits of combination antibiotic therapy for the treatment of plague have never been evaluated. We compared the efficacy of a ciprofloxacin (CIN and gentamicin (GEN combination therapy with that of each antibiotic administered alone (i against Yersinia pestis in vitro and (ii in a mouse model of bubonic plague in which animals were intravenously injected with antibiotics for five days, starting at two different times after infection (44 h and 56 h. In vitro, the CIN+GEN combination was synergistic at 0.5x the individual drugs' MICs and indifferent at 1x- or 2x MIC. In vivo, the survival rate for mice treated with CIN+GEN was similar to that observed with CIN alone and slightly higher than that observed for GEN alone 100, 100 and 85%, respectively when treatment was started 44 h post challenge. 100% of survivors were recorded in the CIN+GEN group vs 86 and 83% in the CIN and GEN groups, respectively when treatment was delayed to 56 h post-challenge. However, these differences were not statistically significant. Five days after the end of treatment, Y. pestis were observed in lymph nodes draining the inoculation site (but not in the spleen in surviving mice in each of the three groups. The median lymph node log(10 CFU recovered from persistently infected lymph nodes was significantly higher with GEN than with CIN (5.8 vs. 3.2, p = 0.04 or CIN+GEN (5.8 vs. 2.8, p = 0.01. Taken as the whole, our data show that CIN+GEN combination is as effective as CIN alone but, regimens containing CIN are more effective to eradicate Y. pestis from the draining lymph node than the recommended GEN monotherapy. Moreover, draining lymph nodes may serve as a reservoir for the continued release of Y. pestis into the blood - even after five days of intravenous antibiotic treatment.

  14. Efficacy of ciprofloxacin-gentamicin combination therapy in murine bubonic plague.

    Science.gov (United States)

    Lemaître, Nadine; Ricard, Isabelle; Pradel, Elizabeth; Foligné, Benoît; Courcol, René; Simonet, Michel; Sebbane, Florent

    2012-01-01

    Potential benefits of combination antibiotic therapy for the treatment of plague have never been evaluated. We compared the efficacy of a ciprofloxacin (CIN) and gentamicin (GEN) combination therapy with that of each antibiotic administered alone (i) against Yersinia pestis in vitro and (ii) in a mouse model of bubonic plague in which animals were intravenously injected with antibiotics for five days, starting at two different times after infection (44 h and 56 h). In vitro, the CIN+GEN combination was synergistic at 0.5x the individual drugs' MICs and indifferent at 1x- or 2x MIC. In vivo, the survival rate for mice treated with CIN+GEN was similar to that observed with CIN alone and slightly higher than that observed for GEN alone 100, 100 and 85%, respectively when treatment was started 44 h post challenge. 100% of survivors were recorded in the CIN+GEN group vs 86 and 83% in the CIN and GEN groups, respectively when treatment was delayed to 56 h post-challenge. However, these differences were not statistically significant. Five days after the end of treatment, Y. pestis were observed in lymph nodes draining the inoculation site (but not in the spleen) in surviving mice in each of the three groups. The median lymph node log(10) CFU recovered from persistently infected lymph nodes was significantly higher with GEN than with CIN (5.8 vs. 3.2, p = 0.04) or CIN+GEN (5.8 vs. 2.8, p = 0.01). Taken as the whole, our data show that CIN+GEN combination is as effective as CIN alone but, regimens containing CIN are more effective to eradicate Y. pestis from the draining lymph node than the recommended GEN monotherapy. Moreover, draining lymph nodes may serve as a reservoir for the continued release of Y. pestis into the blood - even after five days of intravenous antibiotic treatment.

  15. Beneficial effects of calcium oral coadministration in gentamicin-induced nephrotoxicity in rats.

    Science.gov (United States)

    Stojiljkovic, Nenad; Stoiljkovic, Milan; Mihailovic, Dragan; Randjelovic, Pavle; Ilic, Sonja; Gocmanac-Ignjatovic, Marija; Veljkovic, Milica

    2012-01-01

    Frequent therapeutical use of an aminoglycoside antibiotic gentamicin (GM) is limited by its nephrotoxic effects often characterized by both morphological and functional alterations of kidney leading to acute renal failure. The aim of this study was to examine the effect of dietary calcium supplementation on GM-induced nephrotoxicity in rats. Experiments were performed on 30 adult male Wistar rats divided into three groups of 10 animals each. G-group received GM intraperitoneally at a dose of 100 mg/kg; GCa-group received the same dose of GM concomitantly with 1 g/kg calcium carbonate given orally; and C-group, serving as control, received 1 mL/day of normal saline. All groups were treated during 8 consecutive days. Quantitative evaluation of GM-induced structural and functional changes of kidney was performed by histopathological, morphometrical, and biochemical analyses. Compared with control, G-group of rats were found to have diffusely and unequally thickened glomerular basement membrane with neutrophil cells infiltration. In addition, vacuolization of cytoplasm of proximal tubule cells with coagulation-type necrosis was observed. These GM-induced pathological lesions were significantly reduced in the rats of GCa-group. Morphometric analysis revealed statistically significant differences in the size of glomeruli (area, major and minor axes, perimeter), optical density, and roundness of glomeruli (p Biochemical analysis showed significant elevation in blood urea and serum creatinine concentrations, whereas potassium concentration was lowered in G-group compared with the other groups (p < 0.01). It is concluded that oral supplementation of calcium during treatment with GM resulted in significant reduction of morphological and functional kidney alterations.

  16. Evaluation of various gentamicin dosage regimens in geriatric patients: a simulation study.

    Science.gov (United States)

    Bourguignon, Laurent; Goutelle, Sylvain; De Saint-Martin, Julie Burdin; Maire, Pascal; Ducher, Michel

    2010-02-01

    The aim of this simulation study was to evaluate the ability of three regimens proposed in official French recommendations for gentamicin to hit defined pharmacokinetic (PK) and pharmacodynamic targets in a population of elderly patients. The first drug regimen tested consisted of a loading dose of 1 mg/kg and a maintenance dose weighted by creatininemia, every 8 h. The second regimen consisted of a fixed dose of 1 mg/kg at various intervals of time, calculated from creatinine clearance. The last regimen was a fixed dose of 3 mg/kg once a day. All regimens were for 5 days. We used a bicompartmental PK model and implemented a Monte Carlo simulation to generate a large sample of geriatric subjects. The analysis examined three ranges of creatinine clearance. Simulations showed that for the two regimens using multiple doses per day, neither was able to reach an efficacy level without significant toxicity after 5 days of treatment, regardless of the level of renal function. The use of creatininemia or creatinine clearance to adjust the drug dose did not alter these findings. The once-a-day dosing regimen gave better results both in efficacy and toxicity, except for patients with creatinine clearance lower than 60 mL/min, where the incidence of potential toxicity was above 25%. These results strongly suggest that official French recommendations about aminoglycoside dosage regimens in elderly patients with renal impairment should be updated, and that the frequent need for therapeutic drug monitoring and dosage individualization should be clearly stated.

  17. Cefazolin-Gentamicin versus Vancomycin-Ceftazidime Eye Drops for Bacterial Corneal Ulcers; a Randomized Clinical Trial

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    Ali-Reza Dehghani

    2009-01-01

    Full Text Available

    PURPOSE: To compare the efficacy of topical cefazolin-gentamicin versus vancomycin-ceftazidime for treatment of bacterial corneal ulcers. METHODS: This randomized double-masked clinical trial was performed on consecutive patients with bacterial corneal ulcers referred to Feiz Hospital, Isfahan, Iran from 2004 to 2005. Patients were randomly assigned to cefazolin-gentamicin or vancomycin-ceftazidime eye drops in a masked fashion. Outcome measures included time for resolution of stromal infiltration, re-epithelization of the epithelial defect, and clearance of anterior chamber inflammation as well as culture results and complications. RESULTS: The study included 89 eyes of 89 patients with bacterial corneal ulcers consisting of 57 (64% male and 32 (36% female subjects. Specimens were culture-negative in 46% of cases. Forty-one eyes received cefazolin-gentamicin and 48 eyes were treated with vancomycin-ceftazidime. Time for resolution of stromal infiltration was 17.7±4.3 days versus 13.8±3.6 days (P=0.04, time to complete re-epithelization was 13.2±3.1 days versus 9.6±2.7 days (P=0.01 and time for clearing of the anterior chamber was 11.6±2.9 days versus 8.1±2.3 days (P

  18. Molecular screening of virulence genes in high-level gentamicin-resistant Enterococcus faecalis and Enterococcus faecium isolated from clinical specimens in Northwest Iran

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    A Hasani

    2012-01-01

    Full Text Available Purpose: The present study screened clinical isolates of Enterococcus faecalis and Enterococcus faecium to determine the prevalence of high-level gentamicin-resistant enterococci and the potential virulence genes among them. Materials and Methods: Clinical enterococcal isolates were obtained from three university teaching hospitals in Northwest Iran. Isolated enterococci were identified phenotypically followed by antibiotic susceptibility testing. Multiplex PCR was performed for the detection of genus, species-specific targets, gentamicin resistance, and potential virulence genes. Results: Of 220 enterococcal isolates, 133 (60.45% isolates were identified as high-level gentamicin-resistant. Of these isolates, 79 (59.4% and 54 (40.6% were E. faecalis and E. faecium, respectively. All high-level gentamicin-resistant strains carried aac(6′Ie-aph(2″Ia. Of 220 isolates, 65.9% were positive for gelE, and 55%, 53.6%, 51.8%, and 49.5% of isolates were positive for cpd, asa1, ace, and esp, respectively. Phenotypically detected β-haemolytic strains (19.54% were found to possess cylL ls MAB. Conclusion: The study revealed that high-level gentamicin-resistance was related to the presence of aac(6′Ie-aph(2″Ia. Isolated enterococci harboured potential virulence determinants, which were more common among E. faecalis than among E. faecium strains.

  19. In vitro protection of auditory hair cells by salicylate from the gentamicin-induced but not neomycin-induced cell loss.

    Science.gov (United States)

    Mazurek, Birgit; Lou, Xiangxin; Olze, Heidi; Haupt, Heidemarie; Szczepek, Agnieszka J

    2012-01-01

    Salicylate has been shown to protect animals and people from the gentamicin-induced hearing loss. The objective of our study was to determine if salicylate is otoprotective in vitro. In this fashion, we wanted to validate the use of explant culture system for future studies on the ototoxicity prevention. In addition, we wanted to find out if salicylate protects from the ototoxicity of other aminoglycosides. As a model, we used the membranous cochlear tissues containing the organ of Corti, spiral limbus and spiral ganglion neurons dissected from the cochleas of p3-p5 Wistar pups. The explants were divided into apical, medial and basal parts and cultured in presence or absence of 100μM gentamicin, 100μM neomycin and 5mM salicylate. Following the tissue fixation and staining with phalloidin-TRITC, the number of inner and outer hair cells (IHCs, OHCs) was scored under the fluorescent microscope. Presence of 5mM salicylate in explants cultures exposed to 100μM gentamicin significantly reduced the loss of IHCs and OHCs, as compared to explants exposed to gentamicin alone. In contrast, neomycin-induced auditory hair cell loss remained unaffected by the presence of salicylate. Our results corroborate earlier in vivo findings and validate the use of cochlear explants for future studies on ototoxicity and its prevention. Moreover, the inability of salicylate to prevent neomycin-induced ototoxicity implies possible differences between the mechanisms of auditory hair cell loss induced by gentamicin and neomycin.

  20. Effect of a novel mucoadhesive polysaccharide obtained from tamarind seeds on the intraocular penetration of gentamicin and ofloxacin in rabbits.

    Science.gov (United States)

    Ghelardi, E; Tavanti, A; Celandroni, F; Lupetti, A; Blandizzi, C; Boldrini, E; Campa, M; Senesi, S

    2000-11-01

    This report describes the efficacy of a novel mucoadhesive polymer, the tamarind seed polysaccharide, as a delivery system for the ocular administration of hydrophilic and hydrophobic antibiotics. Healthy rabbits were subjected to repeated ocular instillations with either conventional gentamicin or ofloxacin or these agents viscosified with the tamarind seed polysaccharide. Administration of viscosified preparations produced antibiotic concentrations both in the aqueous humour and cornea that were significantly higher than those achieved with the drugs alone. The increased drug absorption and the prolonged drug elimination phase obtained with the viscosified formulations indicate the usefulness of the tamarind seed polysaccharide as an ophthalmic delivery system for topical administration of antibiotics.

  1. Use of gentamicin-loaded collagen sponge in internal fixation of open fractures

    Institute of Scientific and Technical Information of China (English)

    Chaudhary Susheel; Sen Ramesh; Saini Uttam Chand; Soni Ashwani; Gahlot Nitesh; Singh Daljit

    2011-01-01

    Objective: To assess the outcome of immediate plate osteosynthesis via application of antibiotic impregnated collagen fleeces (gentamicin-collagen and antibiotic sponge) which gradually release antibiotic locally in the surgical treatment of open fractures presented to us 6 hours after injury. Methods: All cases were treated in our tertiary level trauma center and teaching hospital including 35 patients with open fractures who were treated by immediate open reduction and plate fixation from January 2008 to August 2010. Among them, 31 patients were available for adequate follow-up and assessment. All fractures were treated by irrigation and debridement, immediate open reduction and plate fixation along with placement of antibiotic-releasing collagen fleeces around the plate just before closure of wound. Patients were assessed to determine postoperative infection, delayed union or nonunion and development of other postoperative complications. It was hypothesized that immediate plate osteosynthesis after thorough debridement and local antibiotics would give safe and acceptable clinical results in treatment of open fractures. Results: The 31 patients with adequate final follow-up were assessed at a mean time of 40 weeks (15-160 weeks). Most fractures united primarily in an acceptable time period according to area of involvement. Local wound complications (superficial infection and skin loss) were found in 3 patients (9.67%). Deep infection was noted in 2 patients (6.45%). None of these patients needed implant removal and both fractures united in due time. Delayed union was noted in 5 patients (16.13%). No patient progressed to nonunion or implant failure in long term follow-up. Excessive scarring was developed in 2 patients (6.45%). Conclusions: Immediate plate osteosynthesis after adequate debridement and placement of collagen film eluting antibiotics locally produces excellent results regarding bone union and absence of deep infections and is a safe technique in the

  2. Update on new medicinal applications of gentamicin: Evidence-based review

    Directory of Open Access Journals (Sweden)

    Changhua Chen

    2014-02-01

    Full Text Available Gentamicin (GM was discovered in 1963 and was introduced into parenteral usage in 1971. Since then, GM has been widely used in medicinal applications. The Food and Drug Administration of the United States approved the routine prescription of GM to treat the following infectious disorders: infection due to Klebsiella pneumoniae, Escherichia coli, Serratia marcescens, Citrobacter spp., Enterobacteriaceae spp., Pseudomonas spp.; Staphylococcus infectious disease; bacterial meningitis; bacterial sepsis of newborns; bacterial septicemia; infection of the eye, bone, skin and/or subcutaneous tissue; infective endocarditis; peritoneal dialysis–associated peritonitis due to Pseudomonas and other gram-negative organisms; peritonitis due to gastrointestinal tract infections; respiratory tract infections; and urinary tract infectious disease. GM is an old antibiotic and is used widely beyond its FDA-labeled indications as follows: actinomycotic infection; Staphylococcus saprophyticus bacteremia with pyelonephritis; appendicitis; cystic fibrosis; diverticulitis; adjunct regimen for febrile neutropenia; female genital infection; uterine infection; postnatal infection; necrotizing enterocolitis in fetus or newborn; osteomyelitis; pelvic inflammatory disease; plague; gonorrhea; tularemia; prophylaxis of post-cholecystectomy infection, transrectal prostate biopsy, and post–tympanostomy-related infection; malignant otitis externa; and intratympanically or transtympanically for Ménière's disease. GM is also used in combination regimens, such as with beta-lactam antibiotics to treat mixed infection and with bacteriophage to treat Staphylococcus aureus infections. It is also added to medical materials, such as GM-loaded cement spacers for osteomyelitis and prosthetic joint–associated infections. Overall, there are many medicinal applications for GM. To reduce the development of GM-resistant bacteria and to maintain its effectiveness, GM should be used

  3. General Tritium Labelling of Gentamicin C by catalytic hydrogen exchange Reaction with Tritiated Water; Marcado general con tritio de la Gentamicina C por intercambio catalitico con agua triatiada

    Energy Technology Data Exchange (ETDEWEB)

    Suarez, C.; Diaz, D.; Paz, D.

    1991-07-01

    Gentamicin C was labelled with tritium by means of a PtO2 catalyzed hydrogen exchange reaction. Under the conditions of the exchange (100 mg of gentamicin, basic form, 0,3 ml H2O-3H, and 50 mg of prereduced PtO2) the radiochemical yield was 0,24, 0,38 and 0,48 % at 120 degree celsius, for 8, 16 and 24 hours respectively. Chemical yield for purified gentamicin was about 60 %. Purification was accomplished with a cellulose column eluted with the lower phase of chloroform-methanol 17 % ammonium hydroxide (2:1:1, v/v) . Chemical purity, determined by HPLC, was 96,5 % and radiochemical one was 95. Main exchange degradation products show biological activity. (Author) 12 refs.

  4. Urine profiles and kidney histology following intravenous diatrizoate and iohexol in the degeneration phase of gentamicin nephropathy in rats. Effects on urine and serum profiles.

    Science.gov (United States)

    Thomsen, H S; Golman, K; Larsen, S; Hemmingsen, L; Skaarup, P

    1991-11-01

    Urine chemical profiles were followed for three or nine days after intravenous injection of diatrizoate, iohexol, or saline in 30 rats, where a tubulointerstitial nephropathy was induced by gentamicin given over an eight-day period. Another ten rats injected with saline served as controls. Compared to injection of saline, both iohexol and diatrizoate induced dysfunction. The excretion of the cytoplasmic enzyme lactate dehydrogenase was significantly greater following iohexol than following diatrizoate. No significant differences between the two media were shown by the various serum components examined. Among the gentamicin-treated rats, light microscopy showed prolonged occurrence of tubular necrosis and a more intensive round cell infiltration following iohexol than following diatrizoate and saline. Both contrast media induced further temporary renal dysfunction in rats with gentamicin nephropathy; iohexol induced more morphologic changes than diatrizoate.

  5. The in vitro antibacterial effect of S53P4 bioactive glass and gentamicin impregnated polymethylmethacrylate beads.

    Science.gov (United States)

    Gergely, István; Zazgyva, Ancuta; Man, Adrian; Zuh, Sándor György; Pop, Tudor Sorin

    2014-06-01

    Osteomyelitis is a disease that is still difficult to treat, with considerable morbidity and associated costs. The current "gold standard" in treatment - debridement and implantation of antibiotic impregnated polymethylmethacrylate (PMMA) beads - presents the disadvantage of a second surgical intervention required for the removal of the beads. We comparatively investigated the in vitro antibacterial effect of S53P4 bioactive glass (BAG) and gentamicin impregnated PMMA beads. Bacterial viability was assessed hourly by Standard Plate Count during 24 hours of incubation, by determining the number of colony forming units (CFU) of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Klebsiella pneumoniae. Both tested materials showed an antibacterial effect on all studied bacteria. In case of S. aureus, BAG granules were almost as effective as gentamicin impregnated PMMA beads, with no statistically significant differences. In contrast, PMMA beads had a superior antibacterial effect on S. epidermidis and K. pneumoniae. The antibacterial effect of BAG was greatly influenced by granule size and contact time. There was a statistically significant correlation between pH values and the number of CFU in the case of S53P4 BAG granules. As a biocompatible and biodegradable bone substitute, S53P4 bioactive glass can be a good alternative in the local management of osteomyelitis.

  6. Comparative study of the effects of gentamicin, neomycin, streptomycin and ofloxacin antibiotics on sperm parameters and testis apoptosis in rats.

    Science.gov (United States)

    Khaki, Arash; Novin, Marefat Ghaffari; Khaki, Amir Afshin; Nouri, Mohammad; Sanati, Ehsan; Nikmanesh, Mahdad

    2008-07-01

    The aim of this study was to investigate the comparative effects of aminoglycosides and fluoroquinolones on testis apoptosis and sperm parameters in rats. Fifty male Wistar rats were randomly divided into control (n = 10) and experimental (n = 40) groups. The experimental groups subdivided into four groups often. Each received 5 mg kg(-1) (IP) gentamicin, 50 mg kg(-1) (IP) neomycin, 40 mg kg(-1) (IP) streptomycin and 72 mg kg(-1) (IP) ofloxacin daily for 14 days, respectively; however, the control group just received vehicle (IP). In the fourteenth day, rats were killed and sperm analyzed for sperm parameters. Testis tissues were also prepared for TUNEL assay for detection of apoptosis. There was a significant decrease in sperm count, viability and motility in all of experimental groups when compared with control group. Although in streptomycin group these parameters were less decreased than in the other experimental groups. The apoptotic cells were significantly increased in all experimental groups when compared with those seen in the controlled group. Gentamicin, neomycin and streptomycin and ofloxacin have negative effects on sperm parameters and testis apoptosis in rats. However, these side effects are less seen in the streptomycin group. Therefore, it is recommended that usage of this drug have fewer side effects on male fertility.

  7. INTERACTIVE EFFECTS OF DIFFERENT DURATION OF LITHIUM PRETREATMENT WITH AMIKACIN AND GENTAMICIN ONAPOMORPHINE-INDUCED LICKING IN RATS

    Directory of Open Access Journals (Sweden)

    MOHAMMAD SHARIFZADEH

    2000-07-01

    Full Text Available In this study the hypothesis that aminoglycoside antibiotics and lithium may influence apomorphine-induced licking via their effects on phosphoinositide pathways and calcium stores were investigated in male rats. Subcutaneous administration of apomorphine (0.1,0.25 and 0.5 mg/kg to rats induced licking in a dose-dependent manner and the maximum response was obtained by the dose of 0.5 mg/kg of the drug. Intracerebroventricular injections of amikacin (5, 25 and 50 ug/rat and gentamicin (10, 20 and 40 ug/rat decreased the apomorphine-induced licking significantly. Pretreatment of animals with lithium (600 mg/1 for 7,14 and 21 days increased licking induced by apomorphine. The inhibitory effects of amikacin and high dose of gentamicin were not affected by lithium pretreatment for 14 and 28 days. These findings indicate the possible involvement of phosphoinositide cascade in alterations of apomorphine-induced licking by aminoglycoside antibiotics and lithium in the brain. Also it is suggested that type and dose of aminoglycoside antibiotics and duration of lithium administration probably have different effects on responses mediated by phosphoinositide hydrolysis.

  8. In vitro bactericidal activity of amoxicillin, gentamicin, rifampicin, ciprofloxacin and trimethoprim-sulfamethoxazole alone or in combination against Listeria monocytogenes.

    Science.gov (United States)

    Boisivon, A; Guiomar, C; Carbon, C

    1990-03-01

    The in vitro bactericidal activity of amoxicillin, gentamicin, rifampicin, ciprofloxacin and trimethoprim-sulfamethoxazole alone or in combination was determined against seven strains of Listeria monocytogenes by the killing curve method. Amoxicillin plus gentamicin was the most rapidly bactericidal combination, whereas trimethoprim-sulfamethoxazole was less bactericidal at 6 h but as bactericidal at 24 h. The combination of trimethoprim-sulfamethoxazole with either amoxicillin, ciprofloxacin or rifampicin did not result in antagonism, but the combinations were no more active than trimethoprim-sulfamethoxazole alone. The interaction of amoxicillin with rifampin was fairly antagonistic (1 log10 difference). The combination of amoxicillin and ciprofloxacin, although producing antagonism during the first 6 h, was more active at 24 h than amoxicillin alone and prevented the regrowth observed with ciprofloxacin alone. Ciprofloxacin and rifampicin interacted antagonistically during the first 6 h, and the combination was not very bactericidal (3 log10) but prevented the emergence of mutants, as observed with each drug alone, when used at concentrations greater than the MICs for the strain tested. These regimens merit evaluation in in vivo models of Listeria monocytogenes meningitis.

  9. Evaluation of efficacy of vitamin E and N-acetyl cysteine in gentamicin-induced nephrotoxicity in rats.

    Science.gov (United States)

    Patel Manali, Bhalchandra; Deshpande, Shrikalp; Shah, Gaurang

    2011-01-01

    Gentamicin (GM), an aminoglycoside, is widely employed in clinical practice for the treatment of serious gram-negative infections. The clinical utility of GM is limited by the frequent incidence of acute renal failure. This study was designed to investigate treatment and posttreatment renoprotective potential of vitamin E and N-acetyl cysteine (NAC) against GM-induced oxidative stress and renal dysfunction. Male Sprague-Dawley rats were divided into six groups: first group is the control group that received olive oil (0.1 mL/100 g B.W.), second is the one that was treated with GM (80 mg/kg/i.p./8 days), third is the one that was treated with GM (80 mg/kg/i.p./8 days) and vitamin E (50 mg/kg/i.p./8 days), fourth is the one that was treated with GM (80 mg/kg/i.p./8 days) and NAC (50 mg/kg/i.p./8 days), fifth is the one that was treated with GM (80 mg/kg/i.p./8 days), vitamin E (50 mg/kg/i.p./8 days), and NAC (50 mg/kg/i.p./8 days), and sixth is the one that was treated with GM initially for 8 days (at 80 mg/kg/i.p.) after which vitamin E (at 50 mg/kg/i.p.) and NAC (at 50 mg/kg/i.p.) were administered for 8 days. Serum creatinine, blood urea nitrogen, serum glucose, renal malondialdehyde, renal reduced glutathione, urine sodium, fractional excretion of sodium, and histopathological examination of kidney were performed after treatment. Gentamicin treatment caused nephrotoxicity as evidenced by marked elevation in serum creatinine, blood urea nitrogen, renal malondialdehyde, urine sodium, and fractional excretion of sodium. Study of renal morphology showed marked loss of epithelium in proximal convoluted tubule, inflammatory infiltrate in the form of lymphocytes, mainly in interstitium. Treatment and posttreatment with vitamin E and NAC significantly restored renal functions, reduced lipid peroxidation, enhanced reduced glutathione level, and restored the biochemical parameters. The results of this study demonstrate the therapeutic potential of vitamin E and NAC in

  10. Nephro-protective effect of a novel formulation of unopened coconut inflorescence sap powder on gentamicin induced renal damage by modulating oxidative stress and inflammatory markers.

    Science.gov (United States)

    Jose, Svenia P; S, Asha; Im, Krishnakumar; M, Ratheesh; Santhosh, Savitha; S, Sandya; B, Girish Kumar; C, Pramod

    2017-01-01

    Fresh oyster white translucent sap obtained from the tender unopened inflorescence of coconut trees (Cocos nucifera) is identified to have great health benefits. Drug induced Nephrotoxicity is one of the major causes of renal damage in present generation. As a therapeutic agent, gentamicin imparts direct toxicity to kidney, resulting in acute tubular necrosis, glomerular and tubulointerstitial injury, haemodynamically mediated damage and obstructive nephropathy.There exists an increasing demand for safe and natural agents for the treatment and/or preventionofchronic nephrotoxicity and pathogenesis of kidney diseases. Our study shows the nephro protective/curing effect of a novel powder formulation of micronutrient enriched, unfermented coconut flower sap (CSP). The study was performed on adult male Wistar rats. The animals were grouped into three and treated separately with vehicle, gentamicin and gentamicin+CSP for 16days. Initially, gentamicin treatment significantly (pcoconut flower sap powder showed significant (p<0.05) reversal of all these biochemical parameters indicating an effective inhibition of the pathogenesis of nephrotoxicity and kidney disease.

  11. The prevalence and clonal expansion of high-level gentamicin-resistant enterococci isolated from blood cultures in a Dutch university hospital

    NARCIS (Netherlands)

    N.P.W.C.J. van den Braak (Nicole); A.F. van Belkum (Alex); D. Kreft; R. te Witt (René); H.A. Verbrugh (Henri); H.P. Endtz (Hubert)

    1999-01-01

    textabstractWe studied the prevalence and clonality of high-level gentamicin-resistant enterococci (HLGRE) in a Dutch university hospital. Of 238 enterococcal strains isolated from blood cultures between 1991 and 1997, 57 were HLGRE. Genomic analysis of these strains re

  12. Effects of ampicillin, gentamicin, and cefotaxime on the release of Shiga toxins from Shiga toxin-producing Escherichia coli isolated during a diarrhea episode in Faisalabad, Pakistan.

    Science.gov (United States)

    Mohsin, Mashkoor; Haque, Abdul; Ali, Aamir; Sarwar, Yasra; Bashir, Saira; Tariq, Ayesha; Afzal, Amna; Iftikhar, Tayyaba; Saeed, Muhammad Azeem

    2010-01-01

    The Shiga toxin-producing Escherichia coli (STEC) is an emerging foodborne pathogen. The proportion of cases attributed to STEC in an episode of diarrhea in the Faisalabad region of Pakistan was investigated. In addition, as increase in Shiga toxin (Stx) release after exposure to various antimicrobial agents is widely reported, we also elucidated the in vitro effects of three commonly used antibiotics (ampicillin, gentamicin, and cefotaxime) on Stx release. Isolation and detection of STEC was done using enzyme-linked immunosorbent assay and polymerase chain reaction, followed by phenotypic characterization. In vitro Stx release from isolated STEC was determined using enzyme-linked immunosorbent assay, and Stx-induced verocytotoxicity was quantified using cytotoxicity detection assay. STEC was detected in 5 (21.7%) of 23 patients. Exposure to minimum inhibitory concentration (MIC) of ampicillin, gentamicin, and cefotaxime resulted in a considerable decrease in toxin release and level of cytotoxicity in most of the STEC isolates when compared with control (without antibiotic exposure). Exposure to sub-MIC of ampicillin resulted in a relative increase in Stx release and cytotoxicity (p cefotaxime. Sub-MIC of gentamicin resulted in largest decrease in Stx release and a similar trend was observed with cefotaxime to a lesser extent. In conclusion, these in vitro observations suggested that sub-MIC of ampicillin may stimulate Stx release and level of cytotoxicity and therefore should be avoided. Gentamicin did not show such effects and therefore may be considered for STEC antimicrobial therapy.

  13. Effect of gentamicin and levels of ambient sound on hearing screening outcomes in the neonatal intensive care unit: A pilot study.

    Science.gov (United States)

    Garinis, Angela C; Liao, Selena; Cross, Campbell P; Galati, Johnathan; Middaugh, Jessica L; Mace, Jess C; Wood, Anna-Marie; McEvoy, Lindsey; Moneta, Lauren; Lubianski, Troy; Coopersmith, Noe; Vigo, Nicholas; Hart, Christopher; Riddle, Artur; Ettinger, Olivia; Nold, Casey; Durham, Heather; MacArthur, Carol; McEvoy, Cynthia; Steyger, Peter S

    2017-06-01

    Hearing loss rates in infants admitted to neonatal intensive care units (NICU) run at 2-15%, compared to 0.3% in full-term births. The etiology of this difference remains poorly understood. We examined whether the level of ambient sound and/or cumulative gentamicin (an aminoglycoside) exposure affect NICU hearing screening results, as either exposure can cause acquired, permanent hearing loss. We hypothesized that higher levels of ambient sound in the NICU, and/or gentamicin dosing, increase the risk of referral on the distortion product otoacoustic emission (DPOAE) assessments and/or automated auditory brainstem response (AABR) screens. This was a prospective pilot outcomes study of 82 infants (sound pressure level dosimeter was used to collect daily sound exposure in the NICU for each neonate. Gentamicin dosing was also calculated for each infant, including the total daily dose based on body mass (mg/kg/day), as well as the total number of treatment days. DPOAE and AABR assessments were conducted prior to discharge to evaluate hearing status. Exclusion criteria included congenital infections associated with hearing loss, and congenital craniofacial or otologic abnormalities. The mean level of ambient sound was 62.9 dBA (range 51.8-70.6 dBA), greatly exceeding American Academy of Pediatrics (AAP) recommendation of 4172 Hz) was 44%. DPOAE referrals were significantly greater for infants receiving >2 days of gentamicin dosing compared to fewer doses (p = 0.004). The effect of sound exposure and gentamicin treatment on hearing could not be determined due to the low number of NICU infants without gentamicin exposure (for control comparisons). All infants were exposed to higher levels of ambient sound that substantially exceed AAP guidelines. More referrals were generated by DPOAE assessments than with AABR screens, with significantly more DPOAE referrals with a high-frequency F2 range, consistent with sound- and/or gentamicin-induced cochlear dysfunction. Adding

  14. Characterisation, dissemination and persistence of gentamicin resistant Escherichia coli from a Danish university hospital to the waste water environment

    DEFF Research Database (Denmark)

    Jakobsen, Lotte; Sandvang, Dorthe; Hansen, Lars H

    2008-01-01

    in waste water from the residential area. PFGE profiling revealed no spread of specific patient isolates to the waste water. The aac(3)-II gene was detected both in patient and waste water isolates. Furthermore horizontal transfer of the aac(3)-II gene of patient origin to a recipient was shown in vitro......, indicating a potential spread of the gene from patient isolates to waste water isolates. Regardless of origin, most isolates exhibited multi-resistance and contained several virulence genes. In conclusion, our study showed a possible spread of aac(3)-II from the hospital to the waste water. Most of the GEN......The aim of the study was to investigate the potential spread of gentamicin resistant (GEN(R)) Escherichia coli isolates or GEN(R) determinants from a Danish university hospital to the waste water environment. Waste water samples were collected monthly from the outlets of the hospital bed wards...

  15. Impact of Gentamicin Coadministration along with High Fructose Feeding on Progression of Renal Failure and Metabolic Syndrome in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Zaid O. Ibraheem

    2014-01-01

    Full Text Available The current study evaluates the impact of high fructose feeding in rat model of gentamicin induced nephrotoxicity. Sprague-Dawley rats weighing 180–200 g were randomized into four groups; (C received standard rodents chow with free access to ad libitum drinking water for 8 weeks and was considered as control, (F received standard rodents chow with free access to drinking water supplemented with 20% (W/V fructose for the same abovementioned period, (FG was fed as group F and was given 80 mg/kg (body weight/day gentamicin sulphate intraperitoneally during the last 20 days of the feeding period, and (G was given gentamicin as above and fed as group C. Renal function was assessed at the end of the treatment period through measuring serum creatinine, uric acid and albumin, creatinine clearance, absolute and fractional excretion of both sodium and potassium, twenty-four-hour urinary excretion of albumin, and renal histology. For metabolic syndrome assessment, fasting plasma glucose and insulin were measured and oral glucose tolerance test was performed throughout the treatment period. Results showed that gentamicin enhances progression of fructose induced metabolic syndrome. On the other hand, fructose pretreatment before gentamicin injection produced a comparable degree of renal dysfunction to those which were given fructose-free water but the picture of nephrotoxicity was somewhat altered as it was characterized by higher extent of glomerular congestion and protein urea. Overall, more vigilance is required when nephrotoxic drugs are prescribed for patients with fructose induced metabolic syndrome.

  16. Gentamicin-loaded poly(lactic-co-glycolic acid) microparticles for the prevention of maxillofacial and orthopedic implant infections.

    Science.gov (United States)

    Flores, Claudia; Degoutin, Stephanie; Chai, Feng; Raoul, Gwenael; Hornez, Jean-Chritophe; Martel, Bernard; Siepmann, Juergen; Ferri, Joel; Blanchemain, Nicolas

    2016-07-01

    Trauma and orthopedic surgery can cause infections as any open surgical procedures. Such complications occur in only1 to 5% of the cases, but the treatment is rather complicated due to bacterial biofilm formation and limited drug access to the site of infection upon systemic administration. An interesting strategy to overcome this type of complications is to prevent bacterial proliferation and biofilm formation via the local and controlled release of antibiotic drugs from the implant itself. Obviously, the incorporation of the drug into the implant should not affect the latter's biological and mechanical properties. In this context, we optimized the preparation process for gentamicin-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles, which can be incorporated in the macropores of calcium phosphate-based bone substitutes. Microparticles were prepared using a double emulsion solvent extraction/evaporation technique. The processing parameters were optimized in order to provide an average microparticle size of about 60μm, allowing for incorporation inside the macropores (100μm) of the hydroxyapatite scaffold. Gentamicin-loaded PLGA microparticles showed a sustained release for 25-30days and a rapid antibacterial activity due to a burst effect, the extent of which was controlled by the initial loading of the microparticles. SEM pictures revealed a highly porous microparticle structure, which can help to reduce the micro environmental pH drop and autocatalytic effects. The biological evaluation showed the cytocompatibility and non-hemolytic property of the microparticles, and the antibacterial activity against Staphylococcus aureus under the given conditions.

  17. High-Dose, Extended-Interval Gentamicin and Tobramycin for Pediatric Inpatients: A Survey of Canadian Hospital Pharmacists.

    Science.gov (United States)

    Roy, Caitlin; Gray, Carolyn; Ruda, Lisa; Bell, Ali; Bolt, Jennifer

    2016-01-01

    The use of high-dose, extended-interval aminoglycosides, a common practice in adult populations, is less well established for pediatric patients. In younger populations, these drugs are often administered according to a multiple daily dosing method. To characterize prescribing practices for aminoglycosides in pediatric inpatients across Canada, with a focus on high-dose, extended-interval regimens. This study was based on an electronic survey of pharmacists representing Canadian health care delivery organizations that provided pediatric inpatient services, which was distributed in March 2015. Questions focused on demographic characteristics; indications for high-dose, extended-interval tobramycin or gentamicin; use of these regimens in patients with particular comorbidities; empiric dosing; monitoring parameters; and the extent of pharmacists' authority to independently prescribe doses and order monitoring parameters for aminoglycosides at their respective institutions. Forty-five (48%) of the 94 prospective participants responded to the survey. Of these 45 respondents, 35 (78%) indicated that their respective health regions used high-dose, extended-interval tobramycin or gentamicin in pediatric inpatients. The patient characteristics for use of such regimens were varied. The median reported doses were 10 mg/kg for pulmonary exacerbation in cystic fibrosis, 7 mg/kg for urinary tract infection, and 8 mg/kg for febrile neutropenia. Thirty-one (89%) of the 35 respondents using these regimens reported that they monitored serum levels, and 27 (77%) reported monitoring for nephrotoxicity. With regard to prescriptive authority, 7 (16%) of the 45 respondents indicated that pharmacists were authorized to independently adjust dosing at their institutions, and pharmacists at 14 (31%) of 45 sites were authorized to order monitoring parameters. High-dose, extended-interval aminoglycoside therapy was frequently used for pediatric patients across Canada, although the dosages and

  18. Development of a modified gentamicin protection assay to investigate the interaction between Campylobacter jejuni and Acanthamoeba castellanii ATCC 30010.

    Science.gov (United States)

    Dirks, Brian P; Quinlan, Jennifer J

    2014-05-01

    Campylobacter jejuni is one of the leading causes of diarrheal illness worldwide. It is persistent in the environment and on poultry despite its microaerophilic nature and sensitivity to dessication and pH. Studies have demonstrated that C. jejuni co-incubated with Acanthamoeba spp. may be protected from harmful environmental factors. Research in this area, however has included a range of different methodologies for co-incubation, recovery of bacteria and amoebae, and verification of internalization. In this study a modified gentamicin protection assay (mGPA) was developed with a standardized co-incubation procedure. The mGPA addresses limitations of the traditional GPA by providing quantification of the rate of internalization, or lack of internalization, of C. jejuni by Acanthamoeba castellanii. The mGPA described here utilizes tubes instead of cell culture plates allowing for determination of exact numbers of A. castellanii and C. jejuni to be co-incubated prior to addition to tubes. Additionally, the mGPA allows for the incorporation of C. jejuni-only controls to determine the fate of C. jejuni throughout the assay in the absence of A. castellanii. Using the mGPA it was determined that on average 1.6×10(5) C. jejuni (or 0.006% of initial 1×10(9) inoculum) survive the assay in the absence of A. castellanii. Additionally, results obtained with the mGPA demonstrated that while co-incubation with amoebae sometimes (56% of co-incubations) provided a protective effect for C. jejuni, in other cases it did not provide any protective effect (39% of co-incubations), and in at least one case there was a statistically significant higher recovery of C. jejuni in controls when compared to C. jejuni co-incubated with amoebae. The modified gentamicin protection assay described here allows better quantification of the rate and incidence of internalization of bacteria by amoebae. Use of the standardized mGPA developed here with varying environmental parameters and/or strains

  19. Macrophage-stimulating protein attenuates gentamicin-induced inflammation and apoptosis in human renal proximal tubular epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ko Eun [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Eun Young [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Chang Seong; Choi, Joon Seok; Bae, Eun Hui; Ma, Seong Kwon [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Kyung Keun [Department of Pharmacology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Lee, Jong Un [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Soo Wan, E-mail: skimw@chonnam.ac.kr [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of)

    2013-05-10

    Highlights: •MSP/RON system is activated in rat kidney damaged by gentamicin. •MSP inhibits GM-induced cellular apoptosis and inflammation in HK-2 cells. •MSP attenuates GM-induced activation of MAPKs and NF-κB pathways in HK-2 cells. -- Abstract: The present study aimed to investigate whether macrophage-stimulating protein (MSP) treatment attenuates renal apoptosis and inflammation in gentamicin (GM)-induced tubule injury and its underlying molecular mechanisms. To examine changes in MSP and its receptor, recepteur d’origine nantais (RON) in GM-induced nephropathy, rats were injected with GM for 7 days. Human renal proximal tubular epithelial (HK-2) cells were incubated with GM for 24 h in the presence of different concentrations of MSP and cell viability was measured by MTT assay. Apoptosis was determined by flow cytometry of cells stained with fluorescein isothiocyanate-conjugated annexin V protein and propidium iodide. Expression of Bcl-2, Bax, caspase-3, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB), IκB-α, and mitogen-activated protein kinases (MAPKs) was analyzed by semiquantitative immunoblotting. MSP and RON expression was significantly greater in GM-treated rats, than in untreated controls. GM-treatment reduced HK-2 cell viability, an effect that was counteracted by MSP. Flow cytometry and DAPI staining revealed GM-induced apoptosis was prevented by MSP. GM reduced expression of anti-apoptotic protein Bcl-2 and induced expression of Bax and cleaved caspase 3; these effects and GM-induced expression of COX-2 and iNOS were also attenuated by MSP. GM caused MSP-reversible induction of phospho-ERK, phospho-JNK, and phospho-p38. GM induced NF-κB activation and degradation of IκB-α; the increase in nuclear NF-κB was blocked by inhibitors of ERK, JNK, p-38, or MSP pretreatment. These findings suggest that MSP attenuates GM-induced inflammation and apoptosis by inhibition of the MAPKs

  20. Effect of low level laser therapy on hair cell regeneration following gentamicin induced ototoxicity in postnatal organotypic culture of rat cochlea

    Science.gov (United States)

    Rhee, Chung-Ku; Kim, Young Hoon; Kim, Se Hyung; He, Peijie; Ahn, Jin Chul

    2010-02-01

    Aim: To investigate effects of low level laser therapy (LLLT) on hair cell regeneration following gentamicin ototoxicity in organotypic culture of rat cochlea. Methods: Organotypic cultures of cochlea in culture medium were allowed to grow for 17 days (C group). The organotypic cultures were irradiated daily with 808 nm LD laser, at 28.8 J/ cm2(L group). The organotypic culture were exposed to 1 mM of gentamicin for 48 hr and allowed to recover (G group) or allowed to recover in the culture medium with daily LLLT at 28.8 J/ cm2 (GL group) for 17 days. The cochleae were stained with FM1-43. The number of hair cells was counted in each group serially for 17 days. Results: While the C group kept on losing hair cells in vitro culture, the hair cells remained rather stationary in the L group. The number of hair cells revealed significantly larger number of hair cells in the L group compared to the C group (p=0.05). And the group × time interaction was also significant (p=0.04). That is, the number of hair cells in the C group showed decreasing tendency which was significantly different from the L group. In G group, the initial number of hair cells decreased to 37.2% of that of the gentamicin non-exposed groups. While the G group kept on losing hair cells, the number of hair cells increased in the GL group. The number of hair cells revealed significantly larger in the GL group (p=0.01) compared to G group. And the group × time interaction was also significant (p=0.01). Also, the number of hair cells in the GL group showed increasing tendency which was significantly different from the G group. Conclusion: These results suggest that LLLT promotes hair cell regeneration following gentamicin damage in cochlear explants.

  1. JBP485 improves gentamicin-induced acute renal failure by regulating the expression and function of Oat1 and Oat3 in rats

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Xinjin [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian (China); Meng, Qiang; Liu, Qi; Wang, Changyuan; Sun, Huijun; Peng, Jinyong; Ma, Xiaochi [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Dalian Medical University, Liaoning (China); Kaku, Taiichi [Japan Bioproducts Industry Co. Ltd., Tomigaya, Shibuya-ku, Tokyo (Japan); Liu, Kexin, E-mail: kexinliu@dlmedu.edu.cn [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Dalian Medical University, Liaoning (China)

    2013-09-01

    We investigated the effects of JBP485 (an anti-inflammatory dipeptide and a substrate of OAT) on regulation of the expression and function of renal Oat1 and Oat3, which can accelerate the excretion of accumulated uremic toxins (e.g. indoxyl sulfate) in the kidney to improve gentamicin-induced ARF in rats. JBP485 caused a significant decrease in the accumulation of endogenous substances (creatinine, blood urea nitrogen and indoxyl sulfate) in vivo, an increase in the excretion of exogenous compounds (lisinopril and inulin) into urine, and up-regulation of the expressions of renal Oat1 and Oat3 in the kidney tissues and slices via substrate induction. To determine the effect of JBP485 on the accelerated excretion of uremic toxins mediated by Oat1 and Oat3, the mRNA and protein expression levels of renal basolateral Oats were assessed by quantitative real-time PCR, western blot, immunohistochemical analysis and an immunofluorescence method. Gentamicin down-regulated the expression of Oats mRNA and protein in rat kidney, and these effects were reversed after administration of JBP485. In addition, JBP485 caused a significant decrease in MPO and MDA levels in the kidney, and improved the pathological condition of rat kidney. These results indicated that JBP485 improved acute renal failure by increasing the expression and function of Oat1 and Oat3, and by decreasing overoxidation of the kidney in gentamicin-induced ARF rats. - Highlights: • JBP485 could up-regulate function and expression of Oat1 and Oat3 in kidney. • Effects of JBP485 on ARF are mediated by stimulating excretion of uremic toxins. • JBP485 protected against gentamicin-induced ARF by decreasing MPO and MDA.

  2. Bax, Bcl2, and p53 differentially regulate neomycin- and gentamicin-induced hair cell death in the zebrafish lateral line.

    Science.gov (United States)

    Coffin, Allison B; Rubel, Edwin W; Raible, David W

    2013-10-01

    Sensorineural hearing loss is a normal consequence of aging and results from a variety of extrinsic challenges such as excessive noise exposure and certain therapeutic drugs, including the aminoglycoside antibiotics. The proximal cause of hearing loss is often death of inner ear hair cells. The signaling pathways necessary for hair cell death are not fully understood and may be specific for each type of insult. In the lateral line, the closely related aminoglycoside antibiotics neomycin and gentamicin appear to kill hair cells by activating a partially overlapping suite of cell death pathways. The lateral line is a system of hair cell-containing sense organs found on the head and body of aquatic vertebrates. In the present study, we use a combination of pharmacologic and genetic manipulations to assess the contributions of p53, Bax, and Bcl2 in the death of zebrafish lateral line hair cells. Bax inhibition significantly protects hair cells from neomycin but not from gentamicin toxicity. Conversely, transgenic overexpression of Bcl2 attenuates hair cell death due to gentamicin but not neomycin, suggesting a complex interplay of pro-death and pro-survival proteins in drug-treated hair cells. p53 inhibition protects hair cells from damage due to either aminoglycoside, with more robust protection seen against gentamicin. Further experiments evaluating p53 suggest that inhibition of mitochondrial-specific p53 activity confers significant hair cell protection from either aminoglycoside. These results suggest a role for mitochondrial p53 activity in promoting hair cell death due to aminoglycosides, likely upstream of Bax and Bcl2.

  3. Effect of moxifloxacin combined with cefotaxime compared to cefotaxime-gentamicin combination on prevention of white matter damage associated with Escherichia coli sepsis in neonatal rats.

    Science.gov (United States)

    Le Saché, Nolwenn; Baud, Olivier; Pansiot, Julien; Pham, Hoa; Biran, Valérie; Brunel-Meunier, Nadège; Bidet, Philippe; Kitzis, Marie-Dominique; Gressens, Pierre; Bingen, Edouard; Charriaut-Marlangue, Christiane; Bonacorsi, Stéphane

    2011-07-01

    Relative to the cefotaxime-gentamicin combination, the moxifloxacin-cefotaxime combination significantly reduced microglial activation and immature oligodendrocyte cell death and delayed myelination in the developing white matter of neonatal rats with experimental Escherichia coli sepsis. These neuroprotective effects were not due to differences in in vivo bactericidal activities or in the systemic inflammatory responses and could be related to the intrinsic immunomodulatory properties of moxifloxacin. Molecular mechanisms underlying the neuroprotective effect of moxifloxacin remain to be elucidated.

  4. Deposition of antibacterial of poly(1,3-bis-(p-carboxyphenoxy propane)-co-(sebacic anhydride)) 20:80/gentamicin sulfate composite coatings by MAPLE

    Energy Technology Data Exchange (ETDEWEB)

    Cristescu, R., E-mail: rodica.cristescu@inflpr.ro [National Institute for Lasers, Plasma and Radiation Physics, Lasers Department, Atomistilor 409, P.O. Box MG-36, RO-077125 Bucharest-Magurele (Romania); Popescu, C.; Socol, G.; Visan, A.; Mihailescu, I.N. [National Institute for Lasers, Plasma and Radiation Physics, Lasers Department, Atomistilor 409, P.O. Box MG-36, RO-077125 Bucharest-Magurele (Romania); Gittard, S.D.; Miller, P.R. [Joint Department of Biomedical Engineering, North Carolina State University, Raleigh, NC 27695 (United States); Joint Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC 27514 (United States); Martin, T.N. [Joint Department of Biomedical Engineering, North Carolina State University, Raleigh, NC 27695 (United States); Narayan, R.J. [Joint Department of Biomedical Engineering, North Carolina State University, Raleigh, NC 27695 (United States); Joint Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC 27514 (United States); Andronie, A.; Stamatin, I. [University of Bucharest, 3 Nano-SAE Research Center, P.O. Box MG-38, Bucharest-Magurele (Romania); Chrisey, D.B. [Rensselaer Polytechnic Institute, Department of Materials Science and Engineering, Troy, 12180-3590 NY (United States)

    2011-04-01

    We report on thin film deposition of poly(1,3-bis-(p-carboxyphenoxy propane)-co-sebacic anhydride)) 20:80 thin films containing several gentamicin concentrations by matrix assisted pulsed laser evaporation (MAPLE). A pulsed KrF* excimer laser was used to deposit the polymer-drug composite thin films. Release of gentamicin from these MAPLE-deposited polymer conjugate structures was assessed. Fourier transform infrared spectroscopy was used to demonstrate that the functional groups of the MAPLE-transferred materials were not changed by the deposition process nor were new functional groups formed. Scanning electron microscopy confirmed that MAPLE may be used to fabricate thin films of good morphological quality. The activity of gentamicin-doped films against Escherichia coli and Staphylococcus aureus bacteria was demonstrated using disk diffusion and antibacterial drop test. Our studies indicate that deposition of polymer-drug composite thin films prepared by MAPLE is a suitable technique for performing controlled drug delivery. Antimicrobial thin film coatings have several medical applications, including use for indwelling catheters and implanted medical devices.

  5. Geldanamycin induces production of heat shock protein 70 and partially attenuates ototoxicity caused by gentamicin in the organ of Corti explants

    Directory of Open Access Journals (Sweden)

    Haupt Heidemarie

    2009-09-01

    Full Text Available Abstract Background Heat shock protein 70 (HSP70 protects inner ear cells from damage and death induced by e.g. heat or toxins. Benzoquinone ansamycin antibiotic geldanamycin (GA was demonstrated to induce the expression of HSP70 in various animal cell types. The aim of our study was to investigate whether GA induces HSP70 in the organ of Corti (OC, which contains the auditory sensory cells, and whether GA can protect these cells from toxicity caused by a common aminoglycoside antibiotic gentamicin. Methods To address these questions, we used the OC explants isolated from p3-p5 rats. As a read-out, we used RT-PCR, ELISA and immunofluorescence. Results We found that GA at the concentration of 2 μM efficiently induced HSP70 expression on mRNA and protein level in the OC explants. Confocal microscopy revealed that HSP70 induced by GA is expressed by hair cells and interdental cells of spiral limbus. Preincubation of explants with 2 μM GA prior to adding gentamicin (500 μM significantly reduced the loss of outer but not inner hair cells, suggesting different mechanisms of otoprotection needed for these two cell types. Conclusion GA induced HSP70 in the auditory sensory cells and partially protected them from toxicity of gentamicin. Understanding the molecular mechanisms of GA otoprotection may provide insights for preventative therapy of the hearing loss caused by aminoglycoside antibiotics.

  6. Comparison of single doses of amoxicillin or of amoxicillin-gentamicin for the prevention of endocarditis caused by Streptococcus faecalis and by viridans streptococci.

    Science.gov (United States)

    Francioli, P; Moreillon, P; Glauser, M P

    1985-07-01

    Recent recommendations for the prophylaxis of endocarditis in humans have advocated single doses or short courses of antibiotic combinations (beta-lactam plus aminoglycoside) for susceptible patients in whom enterococcal bacteremia might develop or for patients at especially high risk of developing endocarditis (e.g., patients with prosthetic cardiac valves). We tested the prophylactic efficacy (in rats with catheter-induced aortic vegetations) of single doses of amoxicillin plus gentamicin against challenge with various streptococcal strains (two strains of Streptococcus faecalis, one of Streptococcus bovis, and three of viridans streptococci); we then compared this efficacy with that of single doses of amoxicillin alone. Successful prophylaxis against all six strains was achieved with single doses of both amoxicillin alone and amoxicillin plus gentamicin. This protection, however, was limited, for both regimens, to the lowest bacterial-inoculum size producing endocarditis in 90% of control rats and was not extended to higher inocula by using the combination of antibiotics. We concluded that a single dose of amoxicillin alone was protective against enterococcal and nonenterococcal endocarditis in the rat, but that its efficacy was limited and could not be improved by the simultaneous administration of gentamicin.

  7. In vitro activity of daptomycin in combination with β-lactams, gentamicin, rifampin, and tigecycline against daptomycin-nonsusceptible enterococci.

    Science.gov (United States)

    Hindler, Janet A; Wong-Beringer, Annie; Charlton, Carmen L; Miller, Shelley A; Kelesidis, Theodoros; Carvalho, Marissa; Sakoulas, George; Nonejuie, Poochit; Pogliano, Joseph; Nizet, Victor; Humphries, Romney

    2015-07-01

    Enterococci that are nonsusceptible (NS; MIC > 4 μg/ml) to daptomycin are an emerging clinical concern. The synergistic combination of daptomycin plus beta-lactams has been shown to be effective against vancomycin-resistant Enterococcus (VRE) species in vitro. This study systematically evaluated by in vitro time-kill studies the effect of daptomycin in combination with ampicillin, cefazolin, ceftriaxone, ceftaroline, ertapenem, gentamicin, tigecycline, and rifampin, for a collection of 9 daptomycin-NS enterococci that exhibited a broad range of MICs and different resistance-conferring mutations. We found that ampicillin plus daptomycin yielded the most consistent synergy but did so only for isolates with mutations to the liaFSR system. Daptomycin binding was found to be enhanced by ampicillin in a representative isolate with such mutations but not for an isolate with mutation to the yycFGHIJ system. In contrast, ampicillin enhanced the killing of the LL-37 human antimicrobial peptide against daptomycin-NS E. faecium with either the liaFSR or yycFGHIJ mutation. Antagonism was noted only for rifampin and tigecycline and only for 2 or 3 isolates. These data add support to the growing body of evidence indicating that therapy combining daptomycin and ampicillin may be helpful in eradicating refractory VRE infections. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  8. Comparative Study of Bacteremias Caused by Enterococcus spp. with and without High-Level Resistance to Gentamicin

    Science.gov (United States)

    Caballero-Granado, Francisco Javier; Cisneros, J. M.; Luque, R.; Torres-Tortosa, M.; Gamboa, F.; Díez, F.; Villanueva, J. L.; Pérez-Cano, R.; Pasquau, J.; Merino, D.; Menchero, A.; Mora, D.; López-Ruz, M. A.; Vergara, A.; Infecciosas, for the Grupo Andaluz Para El Estudio De Las Enfermedades

    1998-01-01

    A prospective, multicenter study was carried out over a period of 10 months. All patients with clinically significant bacteremia caused by Enterococcus spp. were included. The epidemiological, microbiological, clinical, and prognostic features and the relationship of these features to the presence of high-level resistance to gentamicin (HLRG) were studied. Ninety-three patients with enterococcal bacteremia were included, and 31 of these cases were caused by HLRG (33%). The multivariate analysis selected chronic renal failure, intensive care unit stay, previous use of antimicrobial agents, and Enterococcus faecalis species as the independent risk factors that influenced the development of HLRG. The strains with HLRG showed lower levels of susceptibility to penicillin and ciprofloxacin. Clinical features (except for chronic renal failure) were similar in both groups of patients. HLRG did not influence the prognosis for patients with enterococcal bacteremia in terms of either the crude mortality rate (29% for patients with bacteremia caused by enterococci with HLRG and 28% for patients not infected with strains with HLRG) or the hospital stay after the acquisition of enterococcal bacteremia. Hemodynamic compromise, inappropriate antimicrobial therapy, and mechanical ventilation were revealed in the multivariate analysis to be the independent risk factors for mortality. Prolonged hospitalization was associated with the nosocomial acquisition of bacteremia and polymicrobial infections. PMID:9466769

  9. Design and production of gentamicin/dextrans microparticles by supercritical assisted atomisation for the treatment of wound bacterial infections.

    Science.gov (United States)

    Aquino, Rita P; Auriemma, Giulia; Mencherini, Teresa; Russo, Paola; Porta, Amalia; Adami, Renata; Liparoti, Sara; Della Porta, Giovanna; Reverchon, Ernesto; Del Gaudio, Pasquale

    2013-01-20

    In this work, the supercritical assisted atomisation (SAA) is proposed, for the first time, for the production of topical carrier microsystems based on alginate-pectin blend. Gentamicin sulphate (GS) was loaded as high soluble and hygroscopic antibiotic model with poor flowability. Particularly, different water solutions of GS/alginate/pectin were processed by SAA to produce spherical microparticles (GAP) of narrow size (about 2 μm). GS loading was varied between 20% and 33% (w/w) with an encapsulation efficiency reaching about 100%. The micronised powders also showed high flow properties, good stability and constant water content after 90 days in accelerated storage conditions. The release profiles of the encapsulated drug were monitored using vertical diffusion Franz cells to evaluate the application of GAP microsystems as self-consistent powder formulation or in specific fibres or gels for wound dressing. All formulations showed an initial burst effect in the first 6h of application (40-65% of GS loaded), and in particular GAP4 produced with a GS/alginate/pectin ratio of 1:3:1, exhibited the ability to release GS continuously over 6 days. Antimicrobial tests against Staphylococcus aureus indicated that GS antibiotic activity was preserved at 6 days and higher than pure GS at 12 and 24 days for all SAA formulations, especially for GAP1.

  10. Intoxicação experimental por gentamicina em cães Experimental gentamicin toxicosis in dogs

    Directory of Open Access Journals (Sweden)

    Antônio Flávio Medeiros Dantas

    1997-08-01

    Full Text Available A toxicose experimental por gentamicina foi estudada em 11 cães. Dez cães receberam 10mg/kg de gentamicina por via intramuscular, 3 vezes ao dia, durante 14 dias. Outro cão recebeu a mesma dose por 10 dias. Os cães foram submetidos à eutanásia e necropsiados no 11°, 15°-19°, 21°, 27° e 37° dias do experimento. Os principais sinais clínicos foram anorexia, apatia, poliuria, polidipsia, diarréia, vômito e oligúria. Os achados laboratoriais foram enzimúria, cilindrúria, azotemia e isostenúria. As lesões macroscópicas eram restritas aos rins, que estavam acentuadamente pálidos, tumefeitos e macios. Dois cães desenvolveram edema perirrenal discreto. Ao exame histológico do rim, dez cães tinham necrose tóxica aguda restrita aos túbulos contorcidos proximais. Regeneração das células epiteliais desses túbulos foi observada nos rins de todos os cães, principalmente na cortical externa, variando de mínima a acentuada e associada a dilatação acentuada da luz tubular. Aos 37 dias os rins apresentavam-se morfologicamente recuperados. Não foram observadas lesões glomerulares, nem lesões extra-renais de uremia. Concluiu-se que a gentamicina, na dose e frequência administradas, foi tóxica para todos os cães, causando necrose tubular renal aguda com subsequentes graus variados de regeneração tubular.An experiment on gentamicin toxicosis was carried out in 11 dogs. Ten dogs received 10 mg/kg intramuscularly 3 times a day for 14 days and another dog the same dosage for 10 days. All dogs were euthanatized and necropsied at the 11th, 15th-19th, 21th, 27th, and 37th day of the experiment. Main clinical signs were: loss of appetite, apathy, polyuria, polydpsia, diarrhea, vomit and oliguria. Laboratory findings included enzymuria, cylindruria, azotemia and isosthenuria. Gross lesions were restricted to the kidneys, these were pallid, swollen and soft. Two dogs developed mild perirenal edema. Histologically, tubular necrosis

  11. Fenofibrate exerts protective effects against gentamicin-induced toxicity in cochlear hair cells by activating antioxidant enzymes

    Science.gov (United States)

    Park, Channy; Ji, Hye-Min; Kim, Se-Jin; Kil, Sung-Hee; Lee, Joon No; Kwak, Seongae; Choe, Seong-Kyu; Park, Raekil

    2017-01-01

    Fenofibrate, an activator of peroxisome proliferator-activated receptors (PPARs), has been shown to protect the kidneys and brain cells from oxidative stress; however, its role in preventing hearing loss has not been reported to date, at least to the best of our knowledge. In this study, we demonstrated the protective effects of fenofibrate against gentamicin (GM)-induced ototoxicity. We found that the auditory brainstem response threshold which was increased by GM was significantly reduced by pre-treatment with fenofibrate in rats. In cochlear explants, the disruption of hair cell layers by GM was also markedly attenuated by pre-treatment with fenofibrate. In addition, fenofibrate almost completely abolished GM-induced reactive oxygen species generation, which seemed to be mediated at least in part by the restoration of the expression of PPAR-α-dependent antioxidant enzymes, including catalase and superoxide dismutase (SOD)-1. Of note, fenofibrate markedly increased the expression of heme oxygenase-1 (HO-1) which was also induced to a certain degree by GM alone. The induced expression of HO-1 by fenofibrate appeared to be essential for mediating the protective effects of fenofibrate, as the inhibition of HO-1 activity significantly diminished the protective effects of fenofibrate against the GM-mediated death of sensory hair cells in cochlea explant culture, as well as in zebrafish neuromasts. These results suggest that fenofibrate protects sensory hair cells from GM-induced toxicity by upregulating PPAR-α-dependent antioxidant enzymes, including HO-1. Our results provide insight into the preventive therapy for hearing loss caused by aminoglycoside antibiotics. PMID:28290603

  12. Nephroprotective activity ofSolanum xanthocarpum fruit extract against gentamicin-induced nephrotoxicity and renal dysfunction in experimental rodents

    Institute of Scientific and Technical Information of China (English)

    Talib Hussain; Ramesh K Gupta; K Sweety; Bavani Eswaran; M Vijayakumar; Chandana Venkateswara Rao

    2012-01-01

    Objective:To evaluate nephroprotective potential ofSolanum xanthocarpum(S. xanthocarpum) fruit extract(SXE) against gentamicin(GM) induced nephrotoxicity and renal dysfunction. Methods:Twenty-fourWistar rats were divided into four groups(n=6).Control rats that received normal saline(i.p.) and0.5% carboxymethyl cellulose(p.o.) per day for8 d.Nephrotoxicity was induced in rats by intraperitoneal administration ofGM(100 mg/kg/d for8 d) and were treated withSXE(200 and400 mg/kg/d(p.o.) for8 d).Plasma and urine urea and creatinine, kidney weight, urine output, blood urea nitrogen, renal enzymatic and non-enzymatic antioxidants and lipid peroxidation was evaluated along with histopathological investigation in various experimental groupsof rats.Results:It was observed that theGM treatment induced significant elevation(P<0.001) in plasma and urine urea, creatinine, kidney weight, blood urea nitrogen, renal lipid peroxidation along with significant decrement(P<0.001) in urine output, renal enzymatic and non-enzymatic antioxidants.SXE200 and400 mg/kg treatment toGM treated rats recorded significant decrement(up toP<0.001) in plasma and urine urea and creatinine, renal lipid peroxidation along with significant increment(up toP<0.001) in renal enzymatic and non-enzymatic antioxidants.Histological observations of kidney tissues too correlated with the biochemical observations.Conclusions:These finding powerfully supports thatS. xanthocarpum fruit extract acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects ofGM both in the biochemical and histopathological parameters and thus validates its ethnomedicinal use.

  13. Bacterial Contamination of Boar Semen and its Relationship to Sperm Quality Preserved in Commercial Extender Containing Gentamicin Sulfate.

    Science.gov (United States)

    Gączarzewicz, D; Udała, J; Piasecka, M; Błaszczyk, B; Stankiewicz, T

    2016-09-01

    This study was designed to determine the degree and type of bacterial contamination in boar semen (79 ejaculates from Large White and Landrace boars) and its consequences for sperm quality during storage (27 extended semen samples, 16°C for five days) under practical conditions of artificial insemination (AI). The results revealed the presence of aerobic bacteria in 99% of the ejaculates (from 80 to 370 ×106 colony-forming units/mL). Most of the ejaculates contained two or three bacterial contaminants, while the Staphylococcus, Streptococcus, and Pseudomonas bacterial genera were most frequently isolated. Also detected were Enterobacter spp., Bacillus spp., Proteus spp., Escherichia coli, P. fluorescens, and P. aeruginosa. In general, the growth of certain bacterial types isolated prior to semen processing (Enterobacter spp., E. coli, P. fluorescens, and P. aeruginosa) was not discovered on different days of storage, but fluctuations (with a tendency towards increases) were found in the frequencies of Bacillus spp., Pseudomonas spp., and Staphylococcus spp. isolates up to the end of storage. Semen preserved for five days exhibited decreases in sperm motility and increases in the average number of total aerobic bacteria; this was associated with sperm agglutination, plasma membrane disruption, and acrosome damage. We inferred that, due to the different degrees and types of bacterial contaminants in the boar ejaculates, the inhibitory activity of some antimicrobial agents used in swine extenders (such as gentamicin sulfate) may be limited. Because such agents can contribute to the overgrowth of certain aerobic bacteria and a reduction in the quality of stored semen, procedures with high standards of hygiene and microbiological control should be used when processing boar semen.

  14. Rapid emergence of secondary resistance to gentamicin and colistin following selective digestive decontamination in patients with KPC-2-producing Klebsiella pneumoniae: a single-centre experience.

    Science.gov (United States)

    Lübbert, Christoph; Faucheux, Sarah; Becker-Rux, Diana; Laudi, Sven; Dürrbeck, Axel; Busch, Thilo; Gastmeier, Petra; Eckmanns, Tim; Rodloff, Arne C; Kaisers, Udo X

    2013-12-01

    After a single patient was transferred to Leipzig University Hospital from a hospital in Rhodes, Greece, the hospital experienced the largest outbreak due to a KPC-2-producing Klebsiella pneumoniae (KPC-2-KP) strain thus far observed in Germany. Ninety patients hospitalised between July 2010 and October 2012 were affected. In an attempt to eliminate KPC-2-KP from their digestive tracts, 14 consecutive patients (16%) were treated with a short course (7 days) of selective digestive decontamination (SDD), employing colistin (1 million units q.i.d.) and gentamicin (80 mg q.i.d.) as oral solutions, and applying colistin/gentamicin gel (0.5 g) to the oral cavity. In a retrospective analysis, these 14 SDD patients were compared with the remaining 76 patients harbouring KPC-2-KP. KPC-2-KP carrier status was followed in all 14 SDD patients by submitting stool samples to KPC-specific PCR. The mean follow-up period was 48 days (range 12-103 days). Successful elimination of KPC-2-KP was defined as a minimum of three consecutive negative PCR test results separated by ≥48 h each. Decolonisation of KPC-2-KP was achieved in 6/14 patients (43%) after a mean of 21 days (range 12-40 days), but was also observed in 23/76 (30%) of the non-SDD controls (P = 0.102). SDD treatment resulted in the development of secondary resistance to colistin (19% increase in resistance rate) and gentamicin (45% increase) in post-treatment isolates. In the control group, no secondary resistance occurred. We conclude that the SDD protocol applied in this study was not sufficiently effective for decolonisation and was associated with resistance development.

  15. Effect of local hemostatics on bone induction in rats: a comparative study of bone wax, fibrin-collagen paste, and bioerodible polyorthoester with and without gentamicin

    DEFF Research Database (Denmark)

    Solheim, E; Pinholt, E M; Bang, G

    1992-01-01

    evaluated by light microscopy and 85Sr uptake analyses. Non-absorbable bone wax of 88% beeswax and absorbable bovine fibrin-collagen paste both significantly inhibited osteoinduction, whereas a bioerodible polyorthoester drug delivery system with or without 4% gentamicin did not. Bone wax was not absorbed...... and induced a chronic foreign body reaction. Fibrin-collagen paste induced less inflammation with numerous monocytes and macrophages with engulfed material. Bioerodible polyorthoester caused a very moderate tissue reaction and was mostly resorbed at week 4....

  16. In vivo antimicrobial activity of gentamicin polybutylcyanoacrylate nanoparticles%庆大霉素毫微球的体内抗菌活性研究

    Institute of Scientific and Technical Information of China (English)

    张强; 廖工铁; 张淑华

    1998-01-01

    To observe whether the in vivo antimicrobial activity of gentamicin (specially in the intracellular infected animals) could be improved after associting with polybutylcyanoacrylate nanoparticles. METHOD: S. typhimurium infected C57BL/6j mice were chosen as the animal model of the intracellular infection, then the antimicrobial activity of gentamicin polycyano-eacrylate nanoparticles (GM-NP) was evaluated by the mouse survival and the bacterial counts. RESULTS: By comparison with gentamicin solution (GM-Sol), the therapeutic index of GM-NP based on mouse mortality was incrased by 10 fold, and the bacterial counts on liver, spleen and kidney could be as low as 1/426, 1/141 and 1/30 of GM-Sol treated groups respectively. CONCLUSION: By comparison with GM-Sol, in vivo antimicrobial activity of gentamicin over S. typhimurium infected C57BL/6j mice improved significantly after associting with polybutylcyanoacrylate nanoparticles.%目的:观察庆大霉素与聚氰基丙烯酸正丁酯毫微球结合以后,其体内抗菌活性(特别是对细胞内感染)是否有所增加。方法:以鼠伤寒沙门杆菌感染的C57BL/6j小鼠为细胞内感染的动物模型,以小鼠存活率和器官组织中的活菌计数为指标,对庆大霉素聚氰基丙烯酸正丁酯毫微球的体内抗菌活性进行评价。结果:从存活率评价其治疗指数提高了10倍。肝、脾、肾中活菌计数最低可降至庆大霉素溶液组的1/426,1/141和1/30。结论:与庆大霉素溶液相比,庆大霉素毫微球明显提高了对伤寒沙门杆菌感染小鼠的治疗效果。

  17. Nucleotide sequence of the aacC2 gene, a gentamicin resistance determinant involved in a hospital epidemic of multiply resistant members of the family Enterobacteriaceae.

    OpenAIRE

    Vliegenthart, J S; Ketelaar-van Gaalen, P A; Van de Klundert, J A

    1989-01-01

    A gentamicin resistance determinant of a conjugative plasmid from Enterobacter cloacae was cloned on a 3.2-kilobase fragment in the PstI site of pBR322. Substrate profiles for eight aminoglycosides at three concentrations showed that the resistance was due to aminoglycoside-(3)-N-acetyltransferase isoenzyme II. Insertion mapping by the gamma-delta transposon revealed that the size of the gene was approximately 1 kilobase. Nucleotide sequencing of the aacC2 gene identified an open reading fram...

  18. Pattern of hair cell loss and delayed peripheral neuron degeneration in inner ear by a high-dose intratympanic gentamicin

    Institute of Scientific and Technical Information of China (English)

    Jintao Yu; Dalian Ding; Fengjun Wang; Haiyan Jiang; Hong Sun; Richard Salvi

    2014-01-01

    To gain insights into the ototoxic effects of aminoglycoside antibiotics (AmAn) and delayed peripheral ganglion neuron death in the inner ear, experimental animal models were widely used with several different approaches including AmAn systemic injections, combination treat-ment of AmAn and diuretics, or local application of AmAn. In these approaches, systemic AmAn treatment alone usually causes incomplete damage to hair cells in the inner ear. Co-administration of diuretic and AmAn can completely destroy the cochlear hair cells, but it is impossible to damage the vestibular system. Only the approach of AmAn local application can selectively eliminate most sensory hair cells in the inner ear. Therefore, AmAn local application is more suitable for studies for complete hair cell destructions in cochlear and vestibular system and the following delayed peripheral ganglion neuron death. In current studies, guinea pigs were unilaterally treated with a high concentration of gentamicin (GM, 40 mg/ml) through the tympanic membrane into the middle ear cavity. Auditory functions and vestibular functions were measured before and after GM treatment. The loss of hair cells and delayed degeneration of ganglion neurons in both cochlear and vestibular system were quantified 30 days or 60 days after treatment. The results showed that both auditory and vestibular functions were completely abolished after GM treatment. The sensory hair cells were totally missing in the cochlea, and severely destroyed in vestibular end-organs. The delayed spiral ganglion neuron death 60 days after the deafening procedure was over 50%. However, no obvious pathological changes were observed in vestibular ganglion neurons 60 days post-treatment. These results indicated that a high concentration of gentamycin delivered to the middle ear cavity can destroy most sensory hair cells in the inner ear that subsequently causes the delayed spiral ganglion neuron degeneration. This model might be useful for studies

  19. Decrease in Shiga toxin expression using a minimal inhibitory concentration of rifampicin followed by bactericidal gentamicin treatment enhances survival of Escherichia coli O157:H7-infected BALB/c mice

    Directory of Open Access Journals (Sweden)

    Abdelnoor Alexander M

    2011-09-01

    Full Text Available Abstract Background Treatment of Escherichia coli O157:H7 infections with antimicrobial agents is controversial due to an association with potentially fatal sequelae. The production of Shiga toxins is believed to be central to the pathogenesis of this organism. Therefore, decreasing the expression of these toxins prior to bacterial eradication may provide a safer course of therapy. Methods The utility of decreasing Shiga toxin gene expression in E. coli O157:H7 with rifampicin prior to bacterial eradication with gentamicin was evaluated in vitro using real-time reverse-transcription polymerase chain reaction. Toxin release from treated bacterial cells was assayed for with reverse passive latex agglutination. The effect of this treatment on the survival of E. coli O157:H7-infected BALB/c mice was also monitored. Results Transcription of Shiga toxin-encoding genes was considerably decreased as an effect of treating E. coli O157:H7 in vitro with the minimum inhibitory concentration (MIC of rifampicin followed by the minimum bactericidal concentration (MBC of gentamicin (> 99% decrease compared to treatment with gentamicin alone (50-75% decrease. The release of Shiga toxins from E. coli O157:H7 incubated with the MIC of rifampicin followed by addition of the MBC of gentamicin was decreased as well. On the other hand, the highest survival rate in BALB/c mice infected with E. coli O157:H7 was observed in those treated with the in vivo MIC equivalent dose of rifampicin followed by the in vivo MBC equivalent dose of gentamicin compared to mice treated with gentamicin or rifampicin alone. Conclusions The use of non-lethal expression-inhibitory doses of antimicrobial agents prior to bactericidal ones in treating E. coli O157:H7 infection is effective and may be potentially useful in human infections with this agent in addition to other Shiga toxin producing E. coli strains.

  20. [Development of a gentamicin producer under different culture conditions studied by a method of differential centrifugation of the mycelium in a saccharose density gradient].

    Science.gov (United States)

    Losev, V V; Laznikova, T N; Dmitrieva, S V

    1981-05-01

    The method of differential centrifugation in the sucrose density gradient (SDG) enabled one to trace the changes in the development of the seed and fermentation mycelium of the gentamicin-producing organism. Correlation between gentamicin distribution in the SDG and the culture productivity was found. It was shown that the culture grown under the optimal aeration and agitation conditions was characterized by formation of higher amounts of the mycelium in the 5th and 6th layers of the SDG. Such mycelium was more productive than that from the other SDG layers. The most productive 48-hour seed culture had the more significant part of the mycelium in the 3rd layer of the SDG. When such a culture had the more significant part of the mycelium in the 3rd layer of the SDG. When such a culture was used as the seed material, the activity of the fermentation broth was the highest. The method of differential centrifugation in the SDG provides determination of the culture productivity by the volumes of the fermentation mycelium in the 5th and 6th layers or the seed mycelium in the 3rd layer of the SDG.

  1. Gentamicin treatment in exercised mdx mice: Identification of dystrophin-sensitive pathways and evaluation of efficacy in work-loaded dystrophic muscle.

    Science.gov (United States)

    De Luca, Annamaria; Nico, Beatrice; Rolland, Jean-François; Cozzoli, Anna; Burdi, Rosa; Mangieri, Domenica; Giannuzzi, Viviana; Liantonio, Antonella; Cippone, Valentina; De Bellis, Michela; Nicchia, Grazia Paola; Camerino, Giulia Maria; Frigeri, Antonio; Svelto, Maria; Camerino, Diana Conte

    2008-11-01

    Aminoglycosides force read through of premature stop codon mutations and introduce new mutation-specific gene-corrective strategies in Duchenne muscular dystrophy. A chronic treatment with gentamicin (32 mg/kg/daily i.p., 8-12 weeks) was performed in exercised mdx mice with the dual aim to clarify the dependence on dystrophin of the functional, biochemical and histological alterations present in dystrophic muscle and to verify the long term efficiency of small molecule gene-corrective strategies in work-loaded dystrophic muscle. The treatment counteracted the exercise-induced impairment of in vivo forelimb strength after 6-8 weeks. We observed an increase in dystrophin expression level in all the fibers, although lower than that observed in normal fibers, and found a concomitant recovery of aquaporin-4 at sarcolemma. A significant reduction in centronucleated fibers, in the area of necrosis and in the percentage of nuclear factor-kB-positive nuclei was observed in gastrocnemious muscle of treated animals. Plasma creatine kinase was reduced by 70%. Ex vivo, gentamicin restored membrane ionic conductance in mdx diaphragm and limb muscle fibers. No effects were observed on the altered calcium homeostasis and sarcolemmal calcium permeability, detected by electrophysiological and microspectrofluorimetric approaches. Thus, the maintenance of a partial level of dystrophin is sufficient to reinforce sarcolemmal stability, reducing leakiness, inflammation and fiber damage, while correction of altered calcium homeostasis needs greater expression of dystrophin or direct interventions on the channels involved.

  2. Listeria monocytogenes Strains Selected on Ciprofloxacin or the Disinfectant Benzalkonium Chloride Exhibit Reduced Susceptibility to Ciprofloxacin, Gentamicin, Benzalkonium Chloride, and Other Toxic Compounds▿

    Science.gov (United States)

    Rakic-Martinez, Mira; Drevets, Douglas A.; Dutta, Vikrant; Katic, Vera; Kathariou, Sophia

    2011-01-01

    Listeria monocytogenes is a leading agent for severe food-borne illness and death in the United States and other nations. Even though drug resistance has not yet threatened therapeutic interventions for listeriosis, selective pressure associated with exposure to antibiotics and disinfectants may result in reduced susceptibility to these agents. In this study, selection of several L. monocytogenes strains on either ciprofloxacin (2 μg/ml) or the quaternary ammonium disinfectant benzalkonium chloride (BC; 10 μg/ml) led to derivatives with increased MICs not only to these agents but also to several other toxic compounds, including gentamicin, the dye ethidium bromide, and the chemotherapeutic drug tetraphenylphosphonium chloride. The spectrum of compounds to which these derivatives exhibited reduced susceptibility was the same regardless of whether they were selected on ciprofloxacin or on BC. Inclusion of strains harboring the large plasmid pLM80 revealed that MICs to ciprofloxacin and gentamicin did not differ between the parental and plasmid-cured strains. However, ciprofloxacin-selected derivatives of pLM80-harboring strains had higher MICs than those derived from the plasmid-cured strains. Susceptibility to the antimicrobials was partially restored in the presence of the potent efflux inhibitor reserpine. Taken together, these data suggest that mutations in efflux systems are responsible for the multidrug resistance phenotype of strains selected on ciprofloxacin or BC. PMID:22003016

  3. In vitro Antimicrobial Activity of Chlorquinaldol against Microorganisms Responsible for Skin and Soft Tissue Infections: Comparative Evaluation with Gentamicin and Fusidic Acid

    Directory of Open Access Journals (Sweden)

    Monica Bortolin

    2017-06-01

    Full Text Available Skin and soft tissue infections (SSTIs are a major therapeutic challenge for clinicians. The emergence of pathogens with decreased susceptibility to available therapies has become an emerging problem often associated with treatment failure. Hence, there is an urgent need for novel broad-spectrum antimicrobial agents. The purpose of this study was to assess the feasibility of chlorquinaldol as an alternative approach to currently used topical antibiotics for the treatment of skin and soft tissue infections. The activity of chlorquinaldol was investigated against a collection of bacterial isolates responsible for skin infections, including strains resistant to fusidic acid and gentamicin. After determination of MIC and MBC, time-kill experiments were carried out by counting colonies grown after 0, 3, 6, 9, 24, and 48 h of incubation with concentrations equal to ¼×, ½×, 1×, 2×, and 4× MIC of chlorquinaldol, gentamicin, or fusidic acid. Staphylococci resulted the Gram-positives most sensitive to chlorquinaldol, with MIC-values ranging from 0.016 to 0.5 mg/L. A lower activity was observed against Gram-negative bacteria, with 77% of the isolates being inhibited at concentrations ranging from 128 to 512 mg/L. Generally, in time-kill studies, chlorquinaldol showed a bactericidal activity at the higher concentrations (2×, 4× MIC after 24–48 h of incubation. In conclusion, chlorquinaldol may represent a valuable alternative to conventional topical antibiotics for the treatment of skin and soft tissue infections.

  4. Comparison of antibacterial activity of Ag nanoparticles synthesized from leaf extract of Parthenium hystrophorus L in aqueous media and Gentamicin sulphate: in-vitro.

    Science.gov (United States)

    Anwar, Mohammad F; Yadav, Deepak; Kapoor, Sumeet; Chander, Jagdish; Samim, Mohd

    2015-01-01

    Monodisperse silver (Ag) nanoparticles were synthesized by using Parthenium hystrophorus L leaf extract in aqueous media. The synthesized nanoparticles were characterized by using UV-vis spectrophotometer, X-ray diffracto-meter (XRD), transmission electron microscope (TEM), and dynamics light scattering (DLS). Size-dependent antibacterial activities of Ag nanoparticles were tested against Gram negative Pseudomonas aeruginosa and Gram positive Staphylococcus aureus. Ag nanoparticles having 20 ± 2 nm size in diameter show maximum zone of inhibition (23 ± 2.2 mm) in comparison to 40 nm and 70 nm diameter nanoparticles for Pseudomonas aeruginosa. The zone of inhibition against Staphylococcus aureus were 19 ± 1.8 mm, 15 ± 1.5 mm and 11 ± 1 mm for 20 nm, 40 nm, and 70 nm, respectively. In addition, affect of concentration of 20 nm size Ag nanoparticles on Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus species were also reported and results were compared with 10 µg/ml dose of Gentamicin sulphate. The Parthenium hystrophorus L leaf extract capped 20 ± 2 nm Ag nanoparticles (7.5 µg/ml) shows statistically significant antibacterial activity than Gentamicin sulphate (10 µg/ml) against Staphylococcus aureus.

  5. Beneficial Effects of Green Tea Extract in Gentamicin-Induced Acute Renal Failure in Rats / Povoljni efekti ekstrakta zelenog čaja na akutnu bubrežnu insuficijenciju uzrokovanu gentamicinom kod pacova

    Directory of Open Access Journals (Sweden)

    Veljković Milica

    2015-03-01

    Full Text Available Cilj našeg istraživanja bio je da ispitamo efekat zelenog čaja na akutnu bubrežnu insuficijenciju uzrokovanu gentamicinom. Istraživanje smo sproveli na trideset dva pacova Wistar soja koje smo podelili u četiri grupe od po 8 životinja. Kontrolna (C grupa primala je fiziološki rastvor. GT grupa je primala oralno ekstrakt zelenog čaja u dozi od 300 mg/kg. GM grupa primala je gentamicin intraperitonealno u dozi od 100 mg/kg, a GT+GM grupa primala je zajedno gentamicin i ekstrakt zelenog čaja.

  6. Changes in the treatment of Enterococcus faecalis infective endocarditis in Spain in the last 15 years: from ampicillin plus gentamicin to ampicillin plus ceftriaxone.

    Science.gov (United States)

    Pericas, J M; Cervera, C; del Rio, A; Moreno, A; Garcia de la Maria, C; Almela, M; Falces, C; Ninot, S; Castañeda, X; Armero, Y; Soy, D; Gatell, J M; Marco, F; Mestres, C A; Miro, J M

    2014-12-01

    The aim of this study was to assess changes in antibiotic resistance, epidemiology and outcome among patients with Enterococcus faecalis infective endocarditis (EFIE) and to compare the efficacy and safety of the combination of ampicillin and gentamicin (A+G) with that of ampicillin plus ceftriaxone (A+C). The study was a retrospective analysis of a prospective cohort of EFIE patients treated in our centre from 1997 to 2011. Thirty patients were initially treated with A+G (ampicillin 2 g/4 h and gentamicin 3 mg/kg/day) and 39 with A+C (ampicillin 2 g/4 h and ceftriaxone 2 g/12 h) for 4-6 weeks. Increased rates of high-level aminoglycoside resistance (HLAR; gentamicin MIC ≥512 mg/L, streptomycin MIC ≥1024 mg/L or both) were observed in recent years (24% in 1997-2006 and 49% in 2007-2011; p 0.03). The use of A+C increased over time: 1997-2001, 4/18 (22%); 2002-2006, 5/16 (31%); 2007-2011, 30/35 (86%) (p <0.001). Renal failure developed in 65% of the A+G group and in 34% of the A+C group (p 0.014). Thirteen patients (43%) in the A+G group had to discontinue treatment, whereas only one patient (3%) treated with A+C had to discontinue treatment (p <0.001). Only development of heart failure and previous chronic renal failure were independently associated with 1-year mortality, while the individual antibiotic regimen (A+C vs. A+G) did not affect outcome (OR, 0.7; 95% CI, 0.2-2.2; p 0.549). Our study shows that the prevalence of HLAR EFIE has increased significantly in recent years and that alternative treatment with A+C is safer than A+G, with similar clinical outcomes, although the sample size is too small to draw firm conclusions. Randomized controlled studies are needed to confirm these results.

  7. Activity of daptomycin or linezolid in combination with rifampin or gentamicin against biofilm-forming Enterococcus faecalis or E. faecium in an in vitro pharmacodynamic model using simulated endocardial vegetations and an in vivo survival assay using Galleria mellonella larvae.

    Science.gov (United States)

    Luther, Megan K; Arvanitis, Marios; Mylonakis, Eleftherios; LaPlante, Kerry L

    2014-08-01

    Enterococci are the third most frequent cause of infective endocarditis. A high-inoculum stationary-phase in vitro pharmacodynamic model with simulated endocardial vegetations was used to simulate the human pharmacokinetics of daptomycin at 6 or 10 mg/kg of body weight/day or linezolid at 600 mg every 12 h (q12h), alone or in combination with gentamicin at 1.3 mg/kg q12h or rifampin at 300 mg q8h or 900 mg q24h. Biofilm-forming, vancomycin-susceptible Enterococcus faecalis and vancomycin-resistant Enterococcus faecium (vancomycin-resistant enterococcus [VRE]) strains were tested. At 24, 48, and 72 h, all daptomycin-containing regimens demonstrated significantly more activity (decline in CFU/g) than any linezolid-containing regimen against biofilm-forming E. faecalis. The addition of gentamicin to daptomycin (at 6 or 10 mg/kg) in the first 24 h significantly improved bactericidal activity. In contrast, the addition of rifampin delayed the bactericidal activity of daptomycin against E. faecalis, and the addition of rifampin antagonized the activities of all regimens against VRE at 24 h. Also, against VRE, the addition of gentamicin to linezolid at 72 h improved activity and was bactericidal. Rifampin significantly antagonized the activity of linezolid against VRE at 72 h. In in vivo Galleria mellonella survival assays, linezolid and daptomycin improved survival. Daptomycin at 10 mg/kg improved survival significantly over that with linezolid against E. faecalis. The addition of gentamicin improved the efficacy of daptomycin against E. faecalis and those of linezolid and daptomycin against VRE. We conclude that in enterococcal infection models, daptomycin has more activity than linezolid alone. Against biofilm-forming E. faecalis, the addition of gentamicin in the first 24 h causes the most rapid decline in CFU/g. Of interest, the addition of rifampin decreased the activity of daptomycin against both E. faecalis and VRE.

  8. Study of aac(6'Ie-aph(2″Ia Gene in Clinical Strain of Enterococci and Identification of High-Level Gentamicin Resistante Enterococci

    Directory of Open Access Journals (Sweden)

    N. Dadfarma

    2010-10-01

    Full Text Available Introduction & Objective: Enterococci have emerged as the leading nosocomial pathogens. In addition to natural resistance to many agents, enterococci have also developed plasmid- and transposon-mediated resistance to high concentrations of aminoglycosides. High-level gentamicin resistance (HLGR of enterococci results in the failure of drug synergism with an aminoglycoside plus cell-wall-active agents. HLGR (MIC=500μg/ml strains is usually due to the presence of the aac(6'Ie-aph(2″Ia gene . Materials & Methods: In the present experimental study 142 enterococci were isolated from the patients’ species. Identification was done by using standard methods and antimicrobial susceptibility test was performed by disc diffusion technique. MIC of Gentamicin was determined by a broth micro dilution method (NCCLS. PCR was performed to detect the aac(6'Ie-aph(2″Ia gene .Presence of the gene aac(6'-Ie-aph(2″-Ia was confirmed by digest with Sca1 enzyme. A PCR product was sequenced and BLAST analyzed at the NCBI database to be confirmed. Results: 62(43.7% out of the 142 isolates, were found to exhibit HLGR phenotype. MIC ranging from 512 to >1024 μg/ml in 55 HLGR isolates. All resistant isolates except one, were found to harbor the aac(6'Ie-aph(2″Ia gene. In our strain collection, 42% of E. faecalis and 44% of E. faecium were HLGR. In the HLGR isolates the prevalence of resistance to other antibiotics and Multi Drug Resistance (MDR was higher than non–HLGR.This prevalence in E.faecium was higher than E.faecalis. The sequence was compared with a published sequence and confirmed. Conclusion: Our results indicate that high prevalence of MDR and HLGR enterococcal colonization is an important problem in our medical centers.Spread of the aac(6'-Ie-aph(2″-Ia gene was responsible for HLGR among enterococci isolated from the patients in Tehran. (Sci J Hamadan Univ Med Sci 2010;17(3:25-32

  9. PREPARATION OF MONOCLONAL ANTIBODY AND DEVELOPMENT OF AN INDIRECT COMPETITIVE ELISA METHOD FOR GENTAMICIN%庆大霉素单克隆抗体的研制及ELISA分析方法的建立

    Institute of Scientific and Technical Information of China (English)

    金仁耀; 吴建祥

    2013-01-01

    One hybridoma cell line (6H8) secreting monoclonal antibody (McAb) against gentamicin was produced by fusing mouse myeloma cells ( SP2/0) with spleen cells from BALB/C which immunized by the artificial gentamicin antigen conjugated with bovine serum albumin ( BSA). Isotype and subclass of the monoclonal antibody secreted from the hybridoma cell line (6H8) was classified as IgGl. The light chain of the McAb was identified to be Κ chain. The McAb obtained could specifically react with gentamicin and its titre of ascitic fluid detected by indirect ELISA was up to 1 × 10-7. The result of specificity analysis indicated that the McAb had no cross-reactivity with analogues of gentamicin. Based on the producted McAb, an indirect competitive ELISA was established, and its linear regression equation was y = 16. 1221n (x) -2. 0143 (R2 =0. 9934). Inhibition rate analysis showed that IC50 and IC20 values were 25. 2 μg·L-1 and 3. 9 μg·L-1 gentamicin in PBS buffer, respectively. The mean recovery of gentamicin spiked in milk was from 91% to 110%. The producted anti-gentamicin McAb and established competitive ELISA method could lay the foundation for rapid detection of gentamicin residue.%用与牛血清蛋白(BSA)交联的庆大霉素人工抗原(GM-BSA)免疫的BALB/C鼠脾细胞与SP2/0鼠骨髓瘤细胞融合,经筛选、克隆,得到1株能稳定分泌抗庆大霉素单抗的杂交瘤细胞株(6H8),经鉴定6H8的抗体类型及亚类均为IgG1,其轻链为κ链.制备单克隆抗体腹水,腹水的间接ELISA效价在1×10-7以上.该单克隆抗体与庆大霉素结构类似物均无交叉反应,具有高度特异性.以制备的单抗建立间接竞争ELISA方法,其线性回归方程为y=16.122ln(x)-2.0143(R2=0.9934),抑制中浓度IC50为25.2μg·L-1,最低检测限IC20为3.9μg·L-1.竞争ELISA方法检测鲜奶中的庆大霉素平均回收率在92%~110%之间.抗庆大霉素单抗的制备和竞争ELISA方法的建立为庆大霉素快速检测奠定了基础.

  10. Adaptation of microvolume EMIT assays for theophylline, phenobarbital, phenytoin, carbamazepine, primidone, ethosuximide, and gentamicin to a CentrifiChem chemistry analyzer.

    Science.gov (United States)

    Studts, D; Haven, G T; Kiser, E J

    1983-01-01

    We have developed microvolume EMIT procedures for theophylline, phenobarbital, phenytoin, carbamazepine, primidone, ethosuximide, and gentamicin using a centrifugal analyzer (CentrifiChem and Pipettor 1000) to reduce the manufacturer's recommended manual reagent consumption by one-sixth. In addition to developing the EMIT procedure, the performance of the analyzer and pipettor were verified. The analyzer and pipettor are capable of producing within-run precision at a 3-microliters sample volume and 210-microliters analyzer cuvette volume equal to or less than 1.5%. The performance of the EMIT procedures on the analyzer yielded spike drug recoveries of 90.8 to 106.1% for drug concentrations throughout the calibration concentration range of each assay. The percent error on standard reference material of the National Bureau of Standards ranged from a +12.0% to a -0.6% for ethosuximide, phenobarbital, phenytoin, and primidone. Patient comparison data yielded slopes from 0.930 to 1.110 for all assays. The other important feature of the adapted EMIT assay is its simplicity for use on a routine basis.

  11. Altered gene expression profile in a rat model of gentamicin-induced ototoxicity and nephrotoxicity, and the potential role of upregulated Ifi44 expression.

    Science.gov (United States)

    Hu, Jun-Gen; Fu, Yu; Xu, Jian-Ju; Ding, Xian-Ping; Xie, Hui-Qi; Li-Ling, Jesse

    2017-10-01

    As demonstrated by Alport syndrome, the co‑occurrence of auditory and urinary system malformations, and gentamicin-induced ototoxicity and nephrotoxicity, the ears and kidneys potentially share certain molecular pathways. In the present study, microarray chips were used to analyze the changes in the gene expression profile using a rat model of gentamicin‑induced ototoxicity and nephrotoxicity, using rat liver tissue as a control. A number of genes were identified to exhibit similar expression changes in the rat ears and kidney tissues, among which microtubule‑associated protein 44 (Ifi44), was selected for further analysis to validate its expression changes and confirm potential involvement in the inflammation process in the disease model. Ifi44 is a member of the type I interferon‑inducible gene family. Reverse transcription‑quantitative polymerase chain reaction, western blotting and immunohistochemistry were performed; the results demonstrated that more inflammatory cells were present in cochlear and renal parenchyma in gentamycin‑induced rats, and Ifi44 expression was increased in these two organs compared with control rats. Taken together, with its role in lupus nephritis and expression in the inner ear, the results suggested that Ifi44 is potentially involved in the inflammation associated with gentamicin‑induced ototoxicity and nephrotoxicity. The approach of the current study has also provided a strategy for delineating common pathways shared by organs involved in specific diseases.

  12. Comparative study of bacteremias caused by Enterococcus spp. with and without high-level resistance to gentamicin. The Grupo Andaluz para el estudio de las Enfermedades Infecciosas.

    Science.gov (United States)

    Caballero-Granado, F J; Cisneros, J M; Luque, R; Torres-Tortosa, M; Gamboa, F; Díez, F; Villanueva, J L; Pérez-Cano, R; Pasquau, J; Merino, D; Menchero, A; Mora, D; López-Ruz, M A; Vergara, A

    1998-02-01

    A prospective, multicenter study was carried out over a period of 10 months. All patients with clinically significant bacteremia caused by Enterococcus spp. were included. The epidemiological, microbiological, clinical, and prognostic features and the relationship of these features to the presence of high-level resistance to gentamicin (HLRG) were studied. Ninety-three patients with enterococcal bacteremia were included, and 31 of these cases were caused by HLRG (33%). The multivariate analysis selected chronic renal failure, intensive care unit stay, previous use of antimicrobial agents, and Enterococcus faecalis species as the independent risk factors that influenced the development of HLRG. The strains with HLRG showed lower levels of susceptibility to penicillin and ciprofloxacin. Clinical features (except for chronic renal failure) were similar in both groups of patients. HLRG did not influence the prognosis for patients with enterococcal bacteremia in terms of either the crude mortality rate (29% for patients with bacteremia caused by enterococci with HLRG and 28% for patients not infected with strains with HLRG) or the hospital stay after the acquisition of enterococcal bacteremia. Hemodynamic compromise, inappropriate antimicrobial therapy, and mechanical ventilation were revealed in the multivariate analysis to be the independent risk factors for mortality. Prolonged hospitalization was associated with the nosocomial acquisition of bacteremia and polymicrobial infections.

  13. Detection of kanamycin and gentamicin residues in animal-derived food using IgY antibody based ic-ELISA and FPIA.

    Science.gov (United States)

    Li, Cui; Zhang, Yaoyao; Eremin, Sergei A; Yakup, Omar; Yao, Gang; Zhang, Xiaoying

    2017-07-15

    Our aim in this study is to show that IgY antibody based immunoassays could be used to detect antibiotic residues in animal-derived food. Briefly, full antigens of gentamicin (Gent) and kanamycin (Kana) were used to immunize the laying chickens to prepare IgY antibodies. Then, these antibodies were evaluated by FPIA and ic-ELISA to detect Gent/Kana in animal-derived samples. The IC50 of FPIA and ic-ELISA based anti-Gent IgY were 7.70±0.6μg/mL and 0.32±0.06μg/mL, respectively. The IC50 of FPIA and ic-ELISA based anti-Kana IgY were 7.97±0.9μg/mL and 0.15±0.01μg/mL. The limits of detection (LOD, IC10) for FPIA based anti-Gent/Kana IgY were 0.17 and 0.007μg/mL, respectively. The LOD for ic-ELISA were both 0.001μg/mL. These results indicated that the ic-ELISA might more suitable for antibiotic residues detection than FPIA.

  14. Renoprotective effect of erdosteine in rats against gentamicin nephrotoxicity: a comparison of 99mTc-DMSA uptake with biochemical studies.

    Science.gov (United States)

    Cabuk, Mehmet; Gurel, Ahmet; Sen, Feyza; Demircan, Nejat

    2008-01-01

    Erdosteine is a mucolytic agent having antioxidant properties through its active metabolites in acute injuries induced by pharmacological drugs. This study was designed to investigate the renoprotective potential of Erdosteine against gentamicin (GM)-induced renal dysfunction by using Technetium-99 m dimercaptosuccinic acid (Tc-99 m DMSA) uptake and scintigraphy in rats. For this purpose, male Wistar rats were randomly allotted into one of the four experimental groups: Control, Erdosteine, GM, and GM + Erdosteine groups. GM and GM + Erdosteine groups received 100 mg/kg GM intramuscularly for 6 days. In addition, Erdosteine and GM + Erdosteine groups received 50 mg/kg Erdosteine orally for 6 days. Renal function tests were assessed by serum blood urea nitrogen (BUN), creatinine levels, as well as scintigraphic and tissue radioactivity measurements with Tc-99 m DMSA. Renal oxidative damage was determined by renal malondialdehyde (MDA) levels, by antioxidant enzyme activities; superoxide dismutase (SOD) and catalase (CAT) and activities of oxidant enzymes; xanthine oxidase (XO) and myeloperoxidase (MPO). GM administration resulted in marked renal lipid peroxidation, increased XO and MPO activities and decreased antioxidant enzyme activities. GM + Erdosteine group significantly had lower MDA levels, higher SOD and CAT activities and lower XO and MPO activities, when compared to GM. Also GM + Erdosteine had lower levels of serum BUN, creatinine and higher renal tissue Tc-99 m DMSA uptake and radioactivity with respect to GM. In conclusion, our results supported a protective role of Erdosteine in nephrotoxicity associated with GM treatment.

  15. Cocleotoxicidade da gentamicina por doses habituais para neonatos - estudo funcional A functional study on gentamicin-related cochleotoxicity in its conventional dose in newborns

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    Carla Luiza Baggio

    2010-02-01

    product otoacoustic emissions, before and after the use of gentamicin. RESULTS: in all the assessments, the external hair cells functional status, studied by means of the distortion product otoacoustic emissions, proved preserved. CONCLUSION: In the present study, we did not notice changes in outer hair cell function in the albino guinea pigs treated with gentamicin in the doses of 4 mg/Kg/day and 2.5 mg/Kg/day every 12 hours for 10 and 14 days.

  16. Gentamicin Blocks the ACh-Induced BK Current in Guinea Pig Type II Vestibular Hair Cells by Competing with Ca2+ at the l-Type Calcium Channel

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    Hong Yu

    2014-04-01

    Full Text Available Type II vestibular hair cells (VHCs II contain big-conductance Ca2+-dependent K+ channels (BK and L-type calcium channels. Our previous studies in guinea pig VHCs II indicated that acetylcholine (ACh evoked the BK current by triggering the influx of Ca2+ ions through l-type Ca2+ channels, which was mediated by M2 muscarinic ACh receptor (mAChRs. Aminoglycoside antibiotics, such as gentamicin (GM, are known to have vestibulotoxicity, including damaging effects on the efferent nerve endings on VHCs II. This study used the whole-cell patch clamp technique to determine whether GM affects the vestibular efferent system at postsynaptic M2-mAChRs or the membrane ion channels. We found that GM could block the ACh-induced BK current and that inhibition was reversible, voltage-independent, and dose-dependent with an IC50 value of 36.3 ± 7.8 µM. Increasing the ACh concentration had little influence on GM blocking effect, but increasing the extracellular Ca2+ concentration ([Ca2+]o could antagonize it. Moreover, 50 µM GM potently blocked Ca2+ currents activated by (--Bay-K8644, but did not block BK currents induced by NS1619. These observations indicate that GM most likely blocks the M2 mAChR-mediated response by competing with Ca2+ at the l-type calcium channel. These results provide insights into the vestibulotoxicity of aminoglycoside antibiotics on mammalian VHCs II.

  17. Nuevo esquema de tratamiento con gentamicina en niños operados A new treatment scheme for use of Gentamicin in children operated on

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    Iván Cruz-Álvarez Cantos

    2010-03-01

    Full Text Available OBJETIVO: Evaluar la efectividad de varios esquemas de tratamiento con gentamicina en pacientes pediátricos operados de apendicitis aguda. MÉTODOS: Estudio abierto, controlado y no aleatorizado; se dividió en 3 etapas en cada una de las cuales se analizaron 2 grupos de pacientes. En cada etapa se investigó la aparición de complicaciones infecciosas posquirúrgicas. Se incluyeron en el estudio niños operados de apendicitis aguda en el Hospital Pediátrico Universitario «Juan M. Márquez» desde enero de 1993 hasta diciembre del 2008 con muestras independientes en 4 grupos de 595 (G1, 522 (G2, 420 (G3 y 973 (G4 pacientes respectivamente, las cuales se parearon. RESULTADOS: La tasa de complicaciones fue de 15,1 % en G1; 13,8 % en G2; de 13,1 % en G3 y 11,6 % en G4. CONCLUSIONES: Todos los esquemas de tratamiento tuvieron similar eficacia, por lo que es válido el esquema propuesto.OBJECTIVE. To assess the effectiveness of some treatment schemes using Gentamicin in children operated on of acute apendicitis. METHODS. An open, controlled and non-random study was conducted it was divided into three stages analyzing in each two group of patients. In each stage postsurgical infectious complications were investigated. In study were included the children operated on acute appendicitis at "Juan M. Márquez" University Children Hospital from January, 1993 to December, 2008 with independent paired samples in 4 groups of patients: 595 (G1, 522 (G2, 420 (G3 AND 973 (G4, respectively. RESULTS. The complications rate was of 15.1% in G1; of 13.8 % in G2, of 13.1% in G3, and of 11.6% in G4. CONCLUSIONS. All treatment schemes had a similar efficacy validating the proposed scheme.

  18. Bone marrow-derived mesenchymal stem cells repaired but did not prevent gentamicin-induced acute kidney injury through paracrine effects in rats.

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    Luciana A Reis

    Full Text Available This study evaluated the effects of bone marrow-derived mesenchymal stem cells (BMSCs or their conditioned medium (CM on the repair and prevention of Acute Kidney Injury (AKI induced by gentamicin (G. Animals received daily injections of G up to 20 days. On the 10(th day, injections of BMSCs, CM, CM+trypsin, CM+RNase or exosome-like microvesicles extracted from the CM were administered. In the prevention groups, the animals received the BMSCs 24 h before or on the 5(th day of G treatment. Creatinine (Cr, urea (U, FENa and cytokines were quantified. The kidneys were evaluated using hematoxylin/eosin staining and immunohystochemistry. The levels of Cr, U and FENa increased during all the periods of G treatment. The BMSC transplantation, its CM or exosome injections inhibited the increase in Cr, U, FENa, necrosis, apoptosis and also increased cell proliferation. The pro-inflammatory cytokines decreased while the anti-inflammatory cytokines increased compared to G. When the CM or its exosomes were incubated with RNase (but not trypsin, these effects were blunted. The Y chromosome was not observed in the 24-h prevention group, but it persisted in the kidney for all of the periods analyzed, suggesting that the injury is necessary for the docking and maintenance of BMSCs in the kidney. In conclusion, the BMSCs and CM minimized the G-induced renal damage through paracrine effects, most likely through the RNA carried by the exosome-like microvesicles. The use of the CM from BMSCs can be a potential therapeutic tool for this type of nephrotoxicity, allowing for the avoidance of cell transplantations.

  19. Elispot assay检测牛奶中庆大霉素%Establishment of Elispot Assay for Detection of Gentamicin in Milk

    Institute of Scientific and Technical Information of China (English)

    王丹; 许杨; 何庆华; 黄志兵; 康敏

    2011-01-01

    This manuscript developt a rapid detection method Elispot assay for Gentamicin sulfate,for this, Anti-GM polyclonal antibody through GM immunogen was obtained;Establishing milk GM-Elispot assay method by spotting coating antigen on PVDF membrane, and the coating antigen and GM in samples competitive binding the site of anti-GM polyclonal, then the HRP catalyzed chromogenic substrate, according to presence or absence of color and depth for interpretation of results.Results: The detection thre-shold of this method was 10 ng/mL,detection time was within 40 minutes and it can achieve semiquantitative detection.The strip of which was stored at 4 ℃ for 90 days could be used and no cross-reaction was found with several structural analogues.The results of samples analysis obtained from the Elispot assay were in a good agreement with that of ELISA method.%为了建立快速检测牛奶中庆大霉素的Elispot assay,采用制备GM免疫抗原获得抗GM 多克隆抗体.将检测抗原点阵在PVDF膜上,通过检测抗原和样品中GM竞争结合抗GM多克隆抗体,酶标结合物催化底物显色,根据颜色的有无及深浅判读结果,从而建立了检测牛奶中GM的Elispot assay.该方法的检测阈值为10 ng/mL,检测时间为40 min,可对样品实现半定量检测.该方法制备的试纸条于4℃密封保存90 d仍可用于检测;与多种结构类似物未见交叉反应;其结果与酶联免疫方法一致.

  20. The effection of the component and the related impurities of gentamicin to the content of microbial potency%庆大霉素组分和有关物质对效价的影响

    Institute of Scientific and Technical Information of China (English)

    刘英; 王立萍

    2012-01-01

    目的 对庆大霉素组分和有关物质与效价的关系加以探讨研究,说明浊度法测定效价较管碟法测定效价的高灵敏度与高选择性,以及控制庆大霉素组分和有关物质的必要性.方法 浊度法和管碟法:中国药典2005年版二部.HPLC法:色谱柱为Venusil ASB C18(4.6mm×25cm,5μm);流动相为0.2mol/L三氟乙酸溶液-甲醇(96:4),流速为0.6mL/min,蒸发光散射检测器漂移管温度为110℃,载气(氮气)流速为2.8L/min,柱温为35℃;进样量为20μL.结果 浊度法更好地反映了庆大霉素组分和有关物质的变化;不同企业庆大霉素制剂的组分和有关物质差异较大.结论 浊度法较管碟法对组分和有关物质变化的反应灵敏度高、选择性好,更好地反应了样品的实际质量;应对庆大霉素的组分比例和有关物质严格控制,以确保药品的安全、有效.%Objective To study the effection of the component and the related impurities of gentamicin to the content of microbial potency, thus to reveal the better selection of turbidimetric assay than the cylinder-plate assay. Methods The turbidimetric assay and the cylinder-plate assay: Chinese Pharmacopeia 2005 Vol 2. HPLC method. The analytical column was Venusil ASB C18 (4.6mmx25cm, 5μm). The column temperature was 35℃. The mobilephase was consisted of the 0.2mol/L trifluoroacetic acid solution-methanol(96:4): The flow rate was 0.6mL/min, the drift tube temperature of Alltech 2000 was 110℃, the pressure of nebulizing gas was 2.8L/min, the inject volume was 20μL. Results The result of the turbidimetric assay reflect the change of the gentamicin component and the impurities bettly. Conclusion The turbidimetric assay was more specific than the cylinder -plate assay to reflect the actual change of the gentamicin component. The component and the related impurities of gentamicin should be controlled strictly to ensure the safety and the efficacy of gentamicin.

  1. 庆大霉素中毒后豚鼠耳蜗毛细胞的再生%Regeneration of cochlear hair cells of guinea pigs following gentamicin ototoxicity

    Institute of Scientific and Technical Information of China (English)

    倪月秋; 汤浩; 崔城

    2006-01-01

    状突出物减少;停药后30 d豚鼠耳蜗第二转外毛细胞静纤毛融合、缺失、倒伏等病理改变,明显弱于庆大霉素停药1 d和3 d,同时耳蜗第三转有新生的静纤毛出现.结论:庆大霉素耳中毒后豚鼠耳蜗毛细胞损伤后存活30 d者其耳蜗毛细胞形态上有所恢复,且听性脑干反应阈值也有一定程度的恢复,说明庆大霉素耳中毒后豚鼠耳蜗毛细胞具有再生修复能力.庆大霉素损伤后的毛细胞可以再生.%BACKGROUND: Formerly, it was thought that the damaged hair cells could not have the repair ability. Recent studies demonstrate that mammal vestibule hair cells also possess certain repair ability after being destroyed.Then, whether mammalia animal cochlea hair cells possess regenerative ability after being destroyed is disputed.OBJECTIVE: To observe cochlear hair cells condition and threshold value change of auditory brainstem response (ABR) at different time following gentamicin ototoxicity by using scanning electron microscope (SEM) technique combined with ABR test, so as to investigate whether cochlear hair cells of mammals can be regenerated after being injured.DESIGN: A randomized and controlled animal experiment.SETTING: Department of Physiology, Shenyang Medical College.MATERIALS: This experiment was carried out at the Hearing Research Room of China Medical University from November 2001 to May 2002. Totally 60 healthy adult white Guinea pigs, with red eyes and sensitive auricle reflex, of clean degree, were used and randomly divided into gentamicin group and normal control group with 30 guinea pigs in each one.METHODS: 100 mg/kg gentamicin was intraperitoneally daily injected into the guinea pigs, serving as gentamicin group. Same volume of normal saline (2.5 mL/kg) was intraperitoneally daily injected into the guinea pigs,serving as normal control group. All the guinea pigs were given medication for 10 successive days. Threshold value of ABR was detected respectively pre-operatively and at the 1st, 3

  2. L-carnitine prevents gentamicin-induced impairment of hair cell in newborn guinea pigs%L-肉碱对庆大霉素致子代豚鼠毛细胞损伤干预作用

    Institute of Scientific and Technical Information of China (English)

    郝帅; 田颖; 姜菲菲; 姜学钧

    2012-01-01

    Objective To evaluate the role of L-camitine(LCAR) supplementation in hearing threshold and cochlear damage in newborn guinea pigs exposed to gentamicin in utero. Methods Pregnant albino guinea pigs were intraperitoneally injected with 100 mg/kg body weight gentamicin once a day for 7 consecutive days,or gentamicin and LCAR at gestational day 51 to 57. At postnatal day 14,the pups were examined in the distortion product otoacoustic emission( DPOAE) task. The temporal bones were immunohistochemically stained for caspase-3, using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling (TUNEL) method. Results Gentamicin used during pregnancy decreased the DPOAE threshold shifts at different frequencies of 1,2,4,5,and 8 kHz(8. 38 ±2. 28,12. 56 ±3.22,10.46 ± 1. 98,12. 22 ± 1.72,and 17.73 ±2. 16 dB,respectively). In contrast,LCAR supplementation,coincidentally with gentamicin exposure,ameliorated these changes( 14. 26 ±1.47,20. 98 ±2. 39,19. 23 ±2. 15,22.56 ± 1. 41,and 29. 13 ±3. 14 dB,respectively). In addition, gentamicin used during pregnancy increased the percentage of apoptotic cells in hair cells( 34.6% ), but LCAR supplementation decreased the percentage of apoptotic cells( 15.1% ,P <0. 05). Conclusion Our data offer a conceptual framework for designing clinical trials using a safe nutrient,LCAR,as a simple preventive strategy for gentamicin-induced ototoxicity.%目的 观察围产期L-肉碱对庆大霉素暴露致子代豚鼠听力损伤及耳蜗毛细胞凋亡的影响.方法 将18只孕中期豚鼠按体重随机分为3组,从孕51 ~57 d,对照组腹膜内注射生理盐水100 mg/kg、庆大霉素组腹膜内注射庆大霉素100 mg/kg,L-肉碱组腹膜内注射庆大霉素100 mg/kg同时以饮水方式给予L-肉碱100 mg/mL;出生后14 d,检测子代豚鼠畸变产物耳声发射(distortion product otoacoustic emission,DPOAE)改变,应用原位末端转移酶标记技术(TUNEL)染色和免疫组化检测

  3. Interferência do intervalo de administração da droga sobre a nefrotoxicidade da gentamicina em ratos Influence of the dose regimen on the gentamicin nephrotoxicity in rats

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    Verônica Cunha Rodrigues Oliveira

    2001-06-01

    Full Text Available A insuficiência renal aguda (IRA que apresenta índice de mortalidade em torno de 50%, pode ser definida como um abrupto declínio da filtração glomerular, resultante de isquemia ou toxicidade. A nefrotoxicidade por drogas é uma das etiologias mais freqüentes (27% e sugere-se que o intervalo de administração da droga pode interferir neste efeito colateral, entretanto o melhor regime de administração ainda não está bem estabelecido. Este conhecimento proporcionaria uma atuação mais direcionada de enfermagem na prevenção desta IRA hospitalar. Os resultados obtidos nesta pesquisa, indicam que a infusão única de gentamicina determina menor nefrotoxicidade, provavelmente devido à redução da sua concentração plasmática nas 24hs, diminuindo o acúmulo intracelular deste fármaco, um dos principais mecanismos celulares deste tipo de lesão. Este regime de tratamento mostra portanto vantagens quanto ao custo, efeito nefrotóxico e segurança quanto à eficácia terapêutica.The acute renal failure (ARF, that still presents a righ mortality rate (50% can be defined as an abrupt decline of the glomerular filtration, resultant of isquemic or toxicity event. The drugs nephrotoxicity is one of the most frequent cause (27% of ARF and it is suggested that the interval of administration of the drug can interfere in this side effect, however the best administration regimen is not very well established. This study evaluated the renal function of rats that received gentamicin (100mg/kg in one dose or in two doses (2x 50mg/kg,by intraperitoneal infusion. The results obtained in this research, indicated that the single infusion of gentamicin determined smaller nephrotoxicity by the reduction of serum concentration of this drug in 24 hours, decreasing the intracelular accumulation of this gentamicin, which is one of the main cellular mechanisms of this renal injury. The single dose treatment regime, otherwise, showes advantages not only related

  4. 庆大霉素-壳聚糖纳米粒治疗兔慢性骨髓炎的实验研究%Study of treatment of chronic osteomyelitis of rabbit with gentamicin loaded chitosan nanospheres

    Institute of Scientific and Technical Information of China (English)

    李亮亮; 王黎明; 金成哲; 徐燕; 唐成

    2012-01-01

    目的:探讨庆大霉素-壳聚糖纳米粒(gentamicin loaded chitosan nanospheres,GS/CS NPs)对兔慢性胫骨骨髓炎的治疗作用.方法:取48只兔制作慢性胫骨骨髓炎模型,造模3周后行大体观察及患肢X线检查.44只兔造模成功后行不同治疗,A组:未特殊治疗;B组:患肢髓腔壳聚糖纳米粒填塞;C组:患肢髓腔庆大霉素粉末填塞;D组:患肢髓腔GS/CS NPs填塞.治疗3周后行患肢X线片检查及Norden评分、髓腔大体观及髓腔内容物细菌学培养,患肢标本行组织学观察及Smeltzer病理评分.结果:治疗3周后A、B、C组均出现明显的慢性骨髓炎X线表现,髓腔脓肿形成,髓腔内容物细菌学培养阳性,组织学观察示中性粒细胞浸润、骨小梁破坏,A、B组尚可见死骨形成,D组治疗后未见明显阳性表现.Norden评分D组较A、B、C组均有统计学意义(P<0.05),Smeltzer病理评分D组较A、B、C组均有统计学意义(P<0.05).结论:庆大霉素-壳聚糖纳米粒作为局部释药系统治疗兔慢性骨髓炎具有良好的效果.%Objective; To investigate the effect of gentamicin loaded chitosan nanospheres(GS/CS NPs) on the treatment of chronic osteomyelitis of rabbit. Methods: Forty-eight rabbits were used to establish the chronic osteomyelitis model,and observation of affected limb and X-ray were done 3 weeks later. Forty-four rabbits had symptoms and signs of chronic osteomyelitis and were divided into 4 groups. Group A has no treatment,group B was treated with chitosan nanospheres,group C was treated with gentamicin sulfate, and group D was treated with GS/CS NPs. The X-Ray,observation of the bone marrow cavity,bacterial culture and the HE staining were done after 3 weeks of treatment. Results-. After 3 weeks of treatment,the X-Ray of groups A~C showed apparent signs of chronic osteomyelitis,the formation of abscess were observed in bone marrow cavity,and the cultures of the Staphylococcus aureus were positive. The HE staining of

  5. Ototoxicidade e otoproteção em orelha interna de cobaias utilizando gentamicina e amicacina: aspectos ultra-estruturais e funcionais Ototoxicity and otoprotection in the inner ear of guinea pigs using gentamicin and amikacin: ultrastructural and functional aspects

    Directory of Open Access Journals (Sweden)

    Thomaz José Marra de Aquino

    2008-12-01

    Full Text Available A ototoxicidade ainda é um desafio para medicina. A descoberta dos mecanismos endógenos autoprotetores das células ciliadas externas associados a métodos de avaliação funcional e ultra-estrutural das mesmas abriu nova perspectiva no entendimento e controle destes mecanismos. OBJETIVO: O trabalho objetivou determinar se subdoses de gentamicina protegia contra ototoxicidade da amicacina baseado nestes mecanismos e determinar se a amplitude das emissões otoacústicas teria correlação com grau de integridade das células ciliadas. MATERIAL E MÉTODO: Estudo experimental. Utilizando 31 cobaias, administrou-se soro fisiológico, gentamicina e amicacina, isoladamente e associadas, via intramuscular, por 12, 30 e 42 dias. Pesquisa de emissões otoacústicas foi realizada no início e final do experimento, comparado com estudo da integridade coclear, por microscopia eletrônica. RESULTADOS: Subdoses de gentamicina não protegeram a orelha interna contra toxicidade da amicacina; diminuições da amplitude das emissões otoacústicas apresentaram forte correlação com aumento de lesões das células ciliadas. CONCLUSÃO: Os achados contribuem para o entendimento dos mecanismos de ototoxicidade e otoproteção da orelha interna. A determinação da correlação entre amplitude de emissões e integridade celular tem grande importância no acompanhamento das lesões de células ciliadas, com possível aplicação no monitoramento de ototoxicidade por drogas em humanos.Ototoxicity is still a challenge to medicine. The discovery of self-protecting endogenous mechanisms of the outer hair cells associated with their functional and ultra-structural assessment methods has opened new horizons in the understanding and controlling of these mechanisms. AIM: this paper aimed at establishing whether or not underdoses of gentamicin could protect the inner ear against the harmful effects of amikacin, based on these protection mechanisms and determine if the

  6. A prospective, randomized, clinical study to compare the clinical safety, effectiveness, and cost of oral ofloxacin/clindamycin vs intravenous clindamycin/gentamicin for the treatment of postpartum endomyometritis.

    Science.gov (United States)

    Pietrantoni; Goss; Gall

    1998-07-01

    Objective: The primary objective of this prospective, randomized, clinical study was to compare the safety, clinical and microbiologic efficacy, and cost of oral ofloxacin in combination with clindamycin vs intravenous (IV) clindamycin/gentamicin in the early empiric treatment for hospitalized patients with mild to moderate postpartum endomyometritis. The secondary objective is to reduce total hospital and patient treatment cost. Postpartum endomyometritis is a major cause of infectious morbidity in the obstetric patient. It is the most common complication associated with cesarean delivery. Careful timing and amniotomy, limited vaginal examinations, and prophylactic antibiotics for cesarean section delivery may help to reduce the incidence and severity of endomyometritis. Endomyometritis is caused by bacteria that compose the normal cervicovaginal flora. These are anaerobic gram-positive cocci (Peptostreptococcus and Peptococcus), aerobic streptococci (Group B Streptococci and enterococci), Enterobacteriaceae, Bacteroides (B. fragilis, B. bivius, and B. disiens), and clostridium species.Ofloxacin is a synthetic broad-spectrum antibacterial agent for intravenous and oral administration. Following oral administration, the bioavailability in tablet form is 98% with maximum serum concentrations in 1 to 2 hours. Steady state concentrations are achieved after 4 doses. Ofloxacin usually is bactericidal in action. A synthetic broad-spectrum antibacterial agent for intravenous and oral administration. Ofloxacin inhibits DNA topoisomerase (ATP-hydrolyzing), commonly referred to as DNA-gyrase. DNA-gyrase causes double-stranded DNA breakage; it inhibits duplication, transcription, and repair of bacterial DNA.Methods: This is a preliminary study that has enrolled 19 evaluable patients towards the overall enrollment of 60 patients for statistical significance. Patients clinically diagnosed as having postpartum endomyometritis who meet the inclusion/exclusion criteria were

  7. Peperphentonamine hydrochloride protects against gentamicin-induced cochlea damage by lowering cochlear caspase-3 expression in guinea pigs%盐酸椒苯酮胺通过降低caspase-3表达减轻庆大霉素豚鼠耳蜗损伤

    Institute of Scientific and Technical Information of China (English)

    陈浩; 谢民强; 吴剑; 李威; 李永贺

    2014-01-01

    Objective To study the protective effect of peperphentonamine hydrochloride (PPTA) against gentamicin-induced cochlear damage and its mechanism to inhibit cell apoptosis. Methods Guinea pigs with normal hearing were randomized into control, gentamicin, and PPTA treatment groups, and the guinea pigs models of gentamicin-induced cochlear damage received intraperitoneal injection of PPTA. The changes of hearing of the guinea pigs were evaluated with auditory brainstem response (ABR) test, and the protein expression of caspase-3 in the cochlear tissue was detected using Western blotting. TUNEL staining, scanning and transmission electron microscopy were performed to observe the morphological changes of the cochlea. Results The threshold in ABR in PPTA treatment group was significantly higher than that in the control group (P<0.05) but significantly lower than that in gentamicin group. Western blotting showed a significantly increased caspase-3 expression in gentamicin group (P<0.001); caspase-3 expression in PPTA group was obviously higher than that in the control group but much lower than that in gentamicin group (P<0.001). TUNEL assay and electron microscopy revealed serious damages of the hair cells in gentamicin group with numerous apoptotic cells in the organ of Corti, stria vascularis and spiral ganglion, and such cochlear damages were obviously alleviated in PPTA group. Conclusion PPTA can protect against gentamicin-induced cochlear damage in guinea pigs by decreasing the protein expression of caspase-3 to inhibit cell apoptosis.%目的:研究盐酸椒苯酮胺(PPTA)对庆大霉素耳蜗损伤的保护作用及抗凋亡机制。方法听力正常豚鼠分3组:正常组、GM组和PPTA组。采用庆大霉素致豚鼠耳蜗损伤模型,PPTA腹腔注射,ABR分析听力变化,Western blot检测耳蜗组织中caspase-3蛋白表达,TUNEL染色、扫描电镜和透射电镜观察形态学改变。结果 ABR反应阈:GM组、PPTA组显

  8. Effects of cerebrocellular growth peptide on acid phosphatase in cochlea of gentamicin induced ototoxic guinea pigs%脑细胞生长肽对豚鼠耳蜗毛细胞内酸性磷酸酶的影响

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    康颂建; 史献君; 魏佑震; 洪岸; 李亚鲁

    2002-01-01

    目的观察脑细胞生长肽(Cerebrai cell growth peptide,CCGP)对庆大霉素(Gentamicin,GM)引起的耳中毒豚鼠耳蜗毛细胞内酸性磷酸酶(Acid phosphatase,ACP)的影响.方法分别用脑干听觉诱发电位(Brainstemauditory evoked potential,BAEP)和组织化学方法检测动物听阈的变化和耳蜗毛细胞溶酶体的变化.结果CCGP能降低GM引起的BAEP反应阈的上升幅度,能保护耳蜗毛细胞溶酶体的完整性,减轻了毛细胞的损伤.结论CCGP能降低GM的耳毒性.保护耳蜗毛细胞溶酶体的完整性,降低溶酶体水解酶逸出引起的毛细胞自溶性损伤,可能是CCGP防治GM耳毒性的机制之一.

  9. 庆大霉素中毒性耳聋豚鼠耳蜗热休克蛋白70的表达及川芎嗪的保护作用%Expression of heat shock protein 70 in cochlea of guinea pigs with gentamicin-toxic deafness and protection of ligustrazine

    Institute of Scientific and Technical Information of China (English)

    倪月秋; 汤浩; 符文双; 石丽娟

    2005-01-01

    +庆大霉素组耳蜗Corti's器、血管纹和螺旋韧带、螺旋缘、螺旋神经节4个部位细胞热休克蛋白70阳性反应产物平均灰度值明显高于庆大霉素组(92.53±2.25,88.24±4.34;125.20±1.43,121.24±0.92;98.71±0.91,96.15±1.10;118.91±0.46,117.73±1 18,t=3.925~10.415,P<0.001).③各组各部位热休克蛋白70阳性反应产物平均灰度值与听性脑干反应阈值高度相关(r=-0.8141~-0.9841,P<0.001).结论:应用川芎嗪注射液可降低听性脑干反应阈值和庆大霉素中毒耳蜗热休克蛋白70的表达,以减轻庆大霉素的耳毒性损伤,从而改善听功能.%BACKGROUND: Ligustrazine possesses the effect to reduce ototoxicity of gentamicin, whether does it antagonize the ototoxicity of gentamicin through influencing the expression of heat shock protein (HSP) 70 in cochlea of guinea pigs with gentamicin induced ototoxicity? BJECTIVE: To investigate the effect of ligustrazine on the expression of HSP70 in cochlea of guinea pigs with gentamicin induced ototoxicity through immunohistochemistry and image analysis technique in combination with the measurement of auditory brainstem response (ABR).DESIGN: A randomized controlled study, and linear correlation analysis. ETTING: Physiological Department of Shenyang Medical College and Audiological Laboratory of China Medical University.MATERIALS: Totally 40 white and red-eye healthy guinea pigs of lean grade and with keen auricle reflect, weighing 200 - 250 g, of either gender, were at random divided as gentamicin group, ligustrazine + gentamicin group, ligustrazine group, and normal control group, with 10 in each group.METHODS: Ligustrazine injection 140 mg/kg was intraperitoneally at the left side given for animals in ligustrazine + gentamicin group, and at the same time gentamicin sulfate injection 100 mg/kg was given intraperitoneally at the right side. The same dosage of gentamicin sulfate injection was intraperitoneally given for animals in gentamicin group. The same dosage of

  10. Estudo comparativo de duas técnicas farmacopéicas de avaliação da atividade antimicrobiana dos fármacos: nistatina, eritromicina, neomicina e gentamicina Comparison of two pharmacopeical thecnics to the evaluation of the antimicrobial activity of the drugs: nystatin, erythromycin, neomycin and gentamicin

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    Tatiane Margato Vital

    2004-06-01

    Full Text Available Através das técnicas de difusão em ágar com discos de papel e cilindros de aço inoxidável, analisou-se quantitativamente a atividade antimicrobiana de 123 medicamentos contendo os fármacos: nistatina (43 amostras de creme vaginal, eritromicina (14 amostras de comprimidos e 9 amostras de suspensão oral, gentamicina (33 amostras de líquido injetável e neomicina (24 amostras de creme de uso tópico, mediante as seguintes cepas de microrganismos: Saccharomyces cerevisiae ATCC 2601 para a nistatina; Staphylococcus epidermidis 12228 para a gentamicina e neomicina e Micrococcus luteus ATCC 9341 para a eritromicina. O preparo das cepas, soluções de padrão e amostra e meios de cultura nos dois métodos seguiram as recomendações da Farmacopéia Brasileira IV (1988 e Farmacopéia Americana 24 (2000. Os resultados foram analisados estatisticamente pelos testes de Fisher (p=0,05 e Student (p=0,05. Dentre as 43 amostras de nistatina creme vaginal analisadas, verificaram-se pelo teste de Student , diferenças pouco significativas (para p=0,05 de atividade antimicrobiana entre os métodos dos discos e cilindros; porém no teste de Fisher não houve diferenças. Nas amostras de eritromicina, gentamicina e neomicina não se obtiveram diferenças significativas entre os testes estatísticos de Fisher e Student. Conclui-se que, para a eritromicina, gentamicina, neomicina e nistatina, a análise de atividade antimicrobiana pela técnica dos discos de papel pode substituir a técnica dos cilindros de aço inoxidável.Through the diffusion techniques in culture media with paper disc and stainless steel cylinders the antimicrobial activity in 123 pharmaceutical preparations was evaluated: nystatin (43 samples of vaginal cream, erythromycin (14 samples of tablets and 9 of oral suspension, gentamicin (33 samples of injectable liquid and neomycin (24 samples of cream of topic use, against the microorganisms: Saccharomyces cerevisiae ATCC 2601 to nystatin

  11. Development of a Colloidal Gold Immunochromatographic Technique for Simultaneous Detection of Quinolones and Gentamicin in Milk%同时检测牛奶中喹诺酮类和庆大霉素残留的胶体金免疫层析方法研究

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    李向梅; 王战辉; 肖希龙; 王照鹏; 温凯; 吴小平; 夏曦; 武晋孝; 江海洋

    2014-01-01

    符,表明该方法准确可靠,适用于现场大批量样本的快速检测和筛选。实际操作过程中,可以采用胶体金免疫层析对样品进行现场快速初筛;筛选的疑似阳性样品,可以采用HPLC-MS/MS方法对样品中QNS和GEN的含量进一步确认。%[Objective]Quinolones and gentamicin are highly effective and broad-spectrum antibacterial drugs. They have significant antibiotic effects on gram-negative and gram-positive bacteria, and are widely used in agriculture in China. Because these two types of drug residues in foods of animal origin may cause harm to human health, therefore, in order to protect the consumers’ health, it is necessary to develop a detection method for simultaneous monitoring these two types of drugs residue level in food. A colloidal gold immunochromatographic method was developed for the simultaneous detection of 13 quinolones and gentamicin residues in milk.[Method]In this study, based on the quinolones and gentamicin monoclonal antibodies, the colloidal gold particles were prepared by sodium citrate reduction method, and mixed labeled with same ratio of these two types of monoclonal antibodies. The effect of pH and antibody amount for gold-antibody conjugation on the strip test sensitivity was investigated. Meanwhile, the coating condition of these two types of antigens was selected. A colloidal gold rapid test strip was developed to simultaneously detect 13 quinolones and gentamicin residue in milk on these bases, and the test strip using the principle of direct competition.[Result]The results showed that the method can simultaneously detect 13 quinolones and gentamicin. These 13 quinolones include enrofloxacin, ciprofloxacin, norfloxacin, flumequine, pefloxacin, ofloxacin, enoxacin, oxolinic acid, marbofloxacin, fleroxacin, orbifloxacin, danofloxacin and lomefloxacin. The test strip has no cross-reaction to other quinolones such as sarafloxacin, difloxacin, sparfloxacin and pazufloxacin, etc

  12. FDS, gentamicin, dexamethasone a- chymotrypsin treatment discharge stage of plasma cel mastitis%乳管镜下地塞米松、庆大霉素、a-糜蛋白酶治疗溢液期浆细胞性乳腺炎的疗效观察

    Institute of Scientific and Technical Information of China (English)

    张腾华

    2014-01-01

    目的:探讨乳管镜下地塞米松、庆大霉素、a-糜蛋白酶治疗溢液期浆细胞性乳腺炎的疗效。方法对我院2009年7月-2013年6月间溢液期浆细胞性乳腺炎患者29例,给予乳管镜下病变处乳管地塞米松、庆大霉素、a-糜蛋白酶混合液冲洗治疗,并进行疗效分析。结果29例患者,治疗1次治愈3例(10.3%),治疗2次治愈5例(17.2%),治疗3次以上治愈19例(65.5%),2例转行其他治疗。结论乳管镜为溢液期浆细胞性乳腺炎患者提供了一种新的、有效的治疗方法。%To explore the curative effect of FDS, gentamicin, dexamethasone a- chymotrypsin treatment discharge stage of plasma cellmastitis.Methods in our hospital from 2009 July to 2013 June 29 cases of liquid phase discharge plasma cellmastitis patients, given FDS lesions breast duct, gentamicin, dexamethasone a- chymotrypsin mixture irrigation treatment, and to analyze the effects of. Results of the 29 patients treated, 1 cured 3 cases (10.3%), 2 times of treatment 5 cases were cured (17.2%), treatment of more than 3 cured 19 cases (65.5%), 2 cases turned to other treatment. Conclusion fiberoptic ductoscopy provides a new, effective treatment for discharge period with plasma cellmastitis.

  13. 阳离子脂质体介导BFGF/GFP基因对药物性耳蜗损害的防治作用%Protective and rescue effects of cationic liposome - mediated bFGF/GFP on Gentamicin - induced ototoxicity in guinea pig

    Institute of Scientific and Technical Information of China (English)

    尹金淑; 翟所强; 郭维; 胡吟燕; 时利

    2003-01-01

    目的探讨阳离子脂质体(天然碱性脂SA)携带碱性成纤维细胞生长因子/绿色荧光蛋白(bFGF/GFP)基因在豚鼠耳蜗中的表达,以及对庆大霉素所致耳蜗损害的防治作用.方法将36只豚鼠分为3组,预防组右耳园窗注入SA-bFGF/GFP复合物后次日肌肉注射庆大霉素150mg.kg-1.d-18天,治疗组先用庆大霉素8 d后次日右耳给药,对照组单用庆大霉素8 d.分别于实验前后及处死前行听觉脑干诱发电位(ABR)测试.荧光显微镜下观察耳蜗GFP的表达;用耳蜗琥珀酸脱氢酶染色铺片,扫描电镜观察毛细胞的缺失情况.结果荧光显微镜下见双侧耳蜗均有GFP表达.预防和治疗组处死前的双耳ABR阈值与对照组比较差异有显著意义(P<0.01,P<0.05),耳蜗内外毛细胞缺失数与对照组比较差异有显著意义(P<0.01,P<0.05).结论SA脂质体介导的bFGF/GFP基因单耳给药双侧耳蜗均有高效表达,并对庆大霉素所致的耳蜗损害有防治作用.%Objectiye To observe the expression of cationic liposome (Stearylamine SA) mediated bFGF/GFP gene, and evaluate the efficacy of bFGF against the damage of Gentamicin in guinea pig cochlea. Methods 36 guinea pigs were divided into 3 groups. The guinea pigs in the preventive group were inoculated SA- bFGF/GFP complexes into cochleae via round window of the right ear, and were subsequently injected with Gentamicin 150mg. Kg-1 .d-1 for 8 days. The animals in the remedial group were previously administrated Gentamicin for 8 days and then received infusion of SA- bFGF/GFP complexes from nextday. The animals in the control group were only injected with Gentamicin for 8 days. Auditory brainstem response (ABR) was measured preceding test, after test and before the animals were sacrificed, respectively. ~ expression of GFP in cochlea was observed by a fluorescent microscope. The surface preparation of cochlea was made and stained with NBT for counting the absent outer and inner hair cells

  14. Influencia de la concentración inhibitoria mínima de penicilina en la acción sinérgica de su combinación con gentamicina frente a estreptococos del grupo viridans Influence of penicillin minimal inhibitory concentration in the synergy between penicillin and gentamicin in viridans group streptococci

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    L. Vigliarolo

    2007-06-01

    isolated from significant samples in the Hospital de Pediatría "Prof. Dr. Juan P. Garrahan" was carried out. Seven mitis group isolates presenting different susceptibility patterns were selected for performing time-killing curves with penicillin, gentamicin, and penicillin plus gentamicin, using higher and lower penicillin concentrations than their minimal inhibitory concentrations. Synergy was not observed when the penicillin concentration was lower than the minimal inhibitory concentration, at least in these strains with minimal inhibitory concentrations of gentamicin ³ 16 µg/ml. When using penicillin in higher concentrations than the minimal inhibitory concentration, synergy was found in five of the seven strains. Aminoglycoside-modifying enzymes were found in the two other streptococci.

  15. 丹参注射液对庆大霉素耳中毒豚鼠耳蜗NOS活性的影响%The Effect of Salvia Miltiorrhiza on Gentamicin Ototoxicity-Induced Activity of Nitric Oxide Synthase in Cochlea of Guinea Pig

    Institute of Scientific and Technical Information of China (English)

    王爱梅; 汤浩; 沈静; 方秀斌; 王铁民

    2001-01-01

    Objective: Our purpose was to explore the protective role of Salvia Miltiorrhiza (SM) on gentamicin (GM) ototoxicity. Methods: We used NADPH-diaphorase in histochemical staining and image quantitative analysis technique, combined with auditory brainstem response (ABR) measurement to investigate the change of nitric oxide synthase (NOS) activity in cochlea of guinea pig after the injection of GM and SM. Results: Gebtamicin and SM significantly reduced NOS activity in cochlear and the threshold of ABR compared with GM alone (P<0.01); and the threshold of ABR was in high correlation with NOS activity (rGM= -0.8236 ~ -0.8662; rSM+GM= -0.8628 ~ -0.9172, P<0.01). Conclusion: Salvia Miltiorrhiza can reduce NOS activity in cochlea, alleviate GM ototoxicity, and ameliorate hearing function.%目的:探讨丹参注射液(Salvia Miltiorrhiza, SM)对庆大霉素(gentamicin, GM)耳毒性损伤的保护作用。方法:制备豚鼠药物中毒性耳聋模型,应用NADPH-黄递酶(NADPH-diaphorase, NADPH-d)组织化学染色及图像分析技术,并结合听性脑干反应(auditory brain stem response, ABR)测试,观察SM对GM耳中毒豚鼠耳蜗一氧化氮合酶(nitric oxide synthase, NOS)活性的影响及其与听阈的关系。结果:SM+GM组耳蜗NOS活性和ABR阈值均明显低于GM组(P<0.01);且ABR阈值与NOS活性变化高度相关(rGM= -0.8236 ~-0.8662; rSM+GM= -0.8628~-0.9172, P<0.01)。结论:SM可通过降低耳蜗NOS活性以减轻GM的耳毒性损伤,从而改善听功能。

  16. A study on the mechanism of neurotrophic factors for repair of nerve tissue:effects of cerebrocellular growth peptide on acid phosphatase of hair cells in cochlea of gentamicin induced ototoxic guinea pigs%神经营养因子修复神经组织机制的研究:脑细胞生长肽对豚鼠耳蜗毛细胞内酸性磷酸酶的影响

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    康颂建; 史献君; 魏佑震; 洪岸; 马天宝

    2004-01-01

    背景:脑细胞生长肽(cerebrocellular growth peptide,CCGP)对庆大霉素引起的耳蜗毛细胞内酸性磷酸酶(acid phosphatase,ACP)的变化是否有影响?对受损耳蜗组织是否有促进修复的作用?目的:观察CCGP对庆大霉素引起的耳中毒豚鼠ACP的影响.设计:随机对照研究.地点和材料:实验地点:泰山医学院听觉研究室.选用健康杂色豚鼠40只,对照组10只,肌肉注射生理盐水1 mL/(kg·d);庆大霉素组15只,肌肉注射硫酸庆大霉素80 mg/(kg·d);CCGP组15只,肌肉注射硫酸庆大霉素同庆大霉素组,并肌肉注射CCGP 1 mg/(kg·d).各组用药25d.方法:用脑干听觉诱发电位(brainstem auditory evoked potential,BAEP)和组织化学方法检测动物听阈的变化和耳蜗毛细胞ACP显色变化.主要观察指标:各组动物BAEP反应阈值和ACP显色变化.结果:用药前BAEP反应阈值[dB(peSLP)]:生理盐水组32.62±2.33,庆大霉素组31.87±2.63,CCGP组32.56±2.39.用药后BAEP反应阈值均有不同程度的升高,用药后25 d BAEP反应阈值:生理盐水组32.81±2.48,庆大霉素组56.73±17.21,CCGP组42.87±9.95,庆大霉素组、CCGP组与生理盐水组比较,差异均有显著性意义(t=3.113,4.335,P均<0.01),CCGP组与庆大霉素组比较,差异有显著性意义(t=2.700,P<0.05).ACP显色变化:生理盐水组毛细胞ACP染色呈棕褐色,毛细胞排列整齐.庆大霉素组ACP变化显著,毛细胞显色失明显;CCGP组ACP显色变化较轻,两组铺片显示有明显差别.结论:CCGP能降低庆大霉素的耳毒性,减轻由于溶酶体的破坏溢出的ACP引起的毛细胞的损伤.%BACKGROUND: Cerebrocellular growth peptides(CCGP) can affect the change of acid phosphatase(ACP) in cochlea induced by gentamicin and accelerate the repair of injured cochlear tissue is unknown. And whether inter neurotrophins have a coordinated effect is also unclear.OBJECTIVE: To investigate the effects of CCGP on ACP in cochlear hair cells of GM-induced ototoxic

  17. 纤维蛋白凝胶复合骨形态发生蛋白和庆大霉素缓释药物对感染性骨缺损的修复%Fibrin glue/bone morphogenetic protein complex plus slow-release gentamicin for repairing infected bone defects in rabbits

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    高秋明; 刘兴炎; 董晓萍; 葛宝丰; 白孟海; 陈克明

    2005-01-01

    背景:慢性骨髓炎临床处理较为棘手,手术常需分期进行,目前尚无好的方法予以一期修复.目的:探讨将纤维蛋白凝胶(FG)作为骨形态发生蛋白(BMP)及庆大霉素的共同载体,一期修复感染性骨缺损的可行性.设计:完全随机对照实验研究.单位:解放军兰州军区兰州总医院全军创伤骨科中心.材料:实验在兰州军区兰州总医院骨科研究所完成.对象为体质量1.9~2.4kg的48只成年健康青紫兰兔,雌雄不限,购自甘肃省兰州市生物制品研究所.干预:48只青紫兰兔,制作慢性骨髓炎模型,清创后造成胫骨近侧干骺端内侧1.5 cm长半环形骨缺损,采用3种方法进行处理:A组,植入FG,BMP和庆大霉素复合物;B组,植入FG/BMP复合物,C组,作为空白对照.主要观察指标:术后观察动物一般情况,做骨培养及细菌计数,X射线拍片及组织学检查.结果:A组感染控制及骨修复均良好,感染控制率、再生骨量明显优于B组.B,C两组在感染控制率上无显著差异.C组动物骨修复差.结论:FG,BMP及庆大霉素复合物具有促进成骨及抗感染的双重作用,可用于感染性骨缺损及污染严重的开放性损伤造成的骨缺损的修复.%BACKGROUND: Chronic osteomyelitis is difficult to manage clinically, and two or more operations were commonly needed. No satisfactory method for one-stage repair has been currently available.OBJECTIVE: To examine the possibility of using fibrin glue(FG) as the common carrier for both bone morphogenetic protein(BMP) and gentamicin for one-stage repair of infected bone defects.DESIGN: A completely randomized controlled experiment.SETTING: Center of Orthopaedic Surgery, Lanzhou General Hospital of Lanzhou Area Command of of Chinese PLA.MATERIALS: The experiment was conducted using 48 healthy adult Chinchilla rabbits of either sex on normal diet with body mass of 1.9 to 2.4 kg,provided by the Institute of Biological Products, Lanzhou, Gansu Province

  18. 钛表面 TiO2纳米管抗菌覆膜药物释放动力学表征及其抗菌活性体外研究%Drug-release kinetics characterization of gentamicin from TiO2 nanotubes and its antibac-terial activity in vitro

    Institute of Scientific and Technical Information of China (English)

    冯明光; 刘忠堂; 王立强; 徐丽; 杨海涛; 王健; 王海洋; 秦士新

    2015-01-01

    目的:明确钛表面TiO2纳米管抗菌覆膜药物释放动力学特征,并通过体外试验测试其抗菌活性。方法电化学氧化法在钛金属表面构建TiO2纳米管表层,利用冻干法加载庆大霉素,在磷酸盐缓冲液中进行药物释放动力学研究。选择标准表皮葡萄球菌菌株,分别在负载和未负载药物纳米管及纯钛3种钛表面进行培养,通过观察细菌粘附和活性菌落存活情况进行表面抗菌活性对比研究。结果 NTS-G庆大霉素药物释放可分为两部分:初始突发释放和后期缓慢释放,初始释放浓度为51.50μg/mL,第6 h为73.13μg/ml,大多数负载的庆大霉素大约在9 h内释放。经过一个爆发性初始释放后,庆大霉素从纳米管释放呈现一个平台期,释放量几乎保持不变,维持在89.10μg/ml水平。3种钛表面体外抗菌活性检测发现,TiO2纳米管抗菌覆膜假体表面死亡细菌菌落显著增加(P<0.05)。结论钛表面TiO2纳米管抗菌覆膜为人工关节相关感染预防提供了新途径,骨科植入材料表面纳米管抗生素覆膜具有广泛的应用潜力。%Objective To determine the release kinetics of gentamicin from the TiO2 nanotubes( TNS-G) , and to detect its an-tibacterial activity in vitro.Methods TiO2 nanotubes ( NTS) were fabricated on the titanium surface by electrochemical anodization. These nanotubes were loaded with gentamicin using a lyophilization method and vacuum drying, and its pharmacokinetics was detected in phosphate buffer.Staphylococcus aureus was used to study the antibacterial properties of the NTS-G.There were three study groups:the commercially pure titanium( Cp-Ti) group, the NTS group, and the NTS-G group.We compared the antibacterial efficacy with each other by bacterial adhesion and colony counting in bacterial culture.Results Drug release of NTS-G could be divided into two parts:initial burst release and relatively slow release

  19. Avaliação clínica da ablação uveal intravítrea com gentamicina em cães portadores de glaucoma crônico Clinical evaluation of intravitreal uveal ablation with gentamicin in chronic glaucomatous dogs

    Directory of Open Access Journals (Sweden)

    J.L.V. Chiurciu

    2007-04-01

    Full Text Available Investigou-se, clinicamente o resultado da ablação uveal intravítrea em 13 olhos cegos de cães com glaucoma crônico unilateral. Os olhos acometidos foram submetidos à ablação uveal intravítrea, por meio de injeção na câmara vítrea de 0,5ml de sulfato de gentamicina (40mg/ml associado a 0,3ml de fosfato de dexametasona (4mg/ml. As variáveis clinicas oftálmicas foram quali-quantificadas em escores, por até 48 semanas do pós-operatório; além de aspectos relacionados à dor, como variações do apetite e peso corporal. Nos sinais clínicos, de secreção ocular, blefaroespasmo, quemose, hifema e pigmentação, neovascularização, pannus e variações de apetite e peso corporal, não se notaram diferenças significativas entre os momentos. A ablação uveal intravítrea diminuiu a hiperemia conjuntival, porém acarretou aumento de opacidade corneana. A associação da ablação com antiinflamatórios tópico e sistêmico indicou não se tratar de procedimento doloroso.The purpose of the study was to investigate the clinical alterations of intravitreal uveal ablation. Thirteen irreversible blind canine eyes, presenting unilateral chronic glaucoma. All the glaucomatous eyes were submitted to intravitreal uveal ablation but the injection of 0.5ml of gentamicin sulfate solution (40mg/ml associated with 0.3ml of dexametasone phosphate (4mg/ml through the vitreous chamber. The oftalmic clinical variables were evaluated and classified in scores until 48 weeks after surgery. Clinical signs of pain, like apetite variations and body weight were also evaluated. Clinical signs of ocular discharge, blepharoespasm, quemosis, hifema and pigmentation, neovascularization, pannus and appetite variations and body weight did not show significant differences. The intravitreal uveal ablation reduced the conjunctival hyperemia, however caused increase in corneal opacity. The association of ablation with topic and sistemic antiflamatories was not a

  20. Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute

    DEFF Research Database (Denmark)

    Stravinskas, M; Horstmann, P; Ferguson, J;

    2016-01-01

    in patients treated surgically for chronic corticomedullary osteomyelitis. RESULTS: The release pattern in vitro was comparable with the obtained release in the patient studies. No recurrence was detected in the osteomyelitis group at latest follow-up (minimum 1.5 years). CONCLUSIONS: This new biphasic bone...

  1. Intravitreal vancomycin and gentamicin concentrations in patients with postoperative endophthalmitis

    NARCIS (Netherlands)

    I.M. Gan; J.T. van Dissel (Jaap); W.H. Beekhuis (Houdijn); W. Swart; J.C. van Meurs (Jan)

    2001-01-01

    textabstractBACKGROUND/AIMS: To study the intravitreal antibiotic concentrations and the efficacy of an intravitreal dosing regimen to treat patients with postoperative bacterial endophthalmitis. This regimen, based on pharmacokinetic/pharmacodynamic considerations, relies on a

  2. 21 CFR 524.1044e - Gentamicin sulfate spray.

    Science.gov (United States)

    2010-04-01

    ... chapter. (c) Conditions of use. (1) The drug is indicated for the treatment of pink eye in cattle... inches from the affected eye, with the opening directed towards the eye, and pumped once. It is advisable... eye and infectious keratoconjunctivitis caused by Moraxella bovis may produce similar signs....

  3. Effects of salvia miltiorrhiza injection on gentamicin-induced expression of nitric oxide synthase isoforms in guinea pig cochlea%丹参注射液对庆大霉素耳中毒豚鼠耳蜗NOS异构体表达的影响

    Institute of Scientific and Technical Information of China (English)

    王爱梅; 汤浩; 宝东艳; 于利

    2011-01-01

    目的:研究丹参注射液(SM)对庆大霉素(GM)耳中毒豚鼠耳蜗一氧化氮合酶(NOS)异构体表达的影响,探讨SM对GM耳毒性的防护机制.方法:40只豚鼠随机分成对照组、GM组、SM组和GM+SM组,应用SABC免疫组织化学方法及显微图像分析技术,观察NOS三型异构体在豚鼠耳蜗的表达;同时结合听脑干反应(ABR)测试,观察用药前后豚鼠听阈的变化.结果:GM+SM组豚鼠耳蜗诱导型NOS(iNOS/NOSⅡ)表达和ABR阈值均明显低于GM组(P0.7,P<0.01);而各组豚鼠耳蜗神经元型NOS(nNOS/NOS Ⅰ)和内皮型NOS(eNOS/NOS Ⅲ)表达均无显著性差异.结论:SM对GM耳中毒后豚鼠耳蜗nNOS和eNOS表达无影响,但可通过抑制GM所致iNOS高表达,以减少NO的过量生成,从而对GM的耳毒性损伤发挥防护作用.%Objective: To investigate the effects of salvia miltiorrhiza injection (SM) on gentamicin (GM)-induced expression of nitric oxide synthase(NOS) isoforms in guinea pig cochlea, and to explore the protective mechanism of SM on GM-induced ototoxicity. Methods: 40 guinea pigs were randomly assigned to 4 groups: control group, GM group, SM group and GM plus SM group. Expression of NOS isoforms in the guinea pig cochlea was detected by the SABC method of immunohistochemistry and microscope image analysis technique. Auditory threshold was tested by auditory brainstem response (ABR) measurement. Results: Inducible NOS (iNOS/NOS Ⅱ ) expression and ABR threshold in GM plus SM group were both significantly declined as compared with those in GM group (P<0.01). Moreover, change of iNOS expression was in high correlation with that of ABR threshold ( |r| > 0.7, P < 0.01 ). While expression of neuronal NOS (nNOS/NOS Ⅰ ) and endothelial NOS (eNOS / NOSⅢ ) showed no significant differences in all groups. Conclusion: SM had no effect on the expression of nNOS and eNOS, but could inhibit iNOS high-expression induced by GM to reduce excessive generation of NO, therefore SM could

  4. Effects of DAPT on Hearing and Notch2/hes1 Signaling Pathways Expression in Gentamicin-induced Hearing Injury and Repair Process in Rat%γ分泌酶抑制剂DAPT对庆大霉素致大鼠耳损伤及修复过程中听力及Notch2/hes1信号通路表达的影响

    Institute of Scientific and Technical Information of China (English)

    黄飞; 刘成福; 王小琴

    2013-01-01

    目的 观察γ分泌酶抑制剂DAPT对庆大霉素致大鼠耳损伤及修复过程中听力变化及Notch2/hes1信号通路表达的影响.方法 72只成熟大鼠随机分成三组,每组24只;对照组给予生理盐水3 ml·kg-1·d-1 腹腔注射,连继10天,庆大霉素组给予Gen 120 mg·kg-1·d-1腹腔注射,连继10天,DAPT组给予DAPT 5 mg·kg-1·d-1腹腔注射,连用5天后停用2天,再用3天,同时腹腔注射Gen 120 mg·kg-1·d-1,连继10天.各组注射前及注射后1、14、28天进行ABR检测后处死动物,应用免疫印迹蛋白、实时定量PCR观察大鼠Notch2/hes1信号通路的表达.结果 对照组注射前后ABR反应阈无明显变化,与注射前相比,DAPT组和庆大霉素组注射后1、14、28天ABR阈值均明显升高,但随时间的延长阈值有所下降(P<0.05),其中,第28天DAPT组ABR反应阈较庆大霉素组下降明显(P<0.05);与对照组相比,DAPT组和庆大霉素组Notch2/hes1的表达均明显增高(P<0.05);与庆大霉素组相比,DAPT组的Notch2/hes1表达明显降低(P<0.05).结论 在庆大霉素致耳损伤及修复过程中,DAPT可能通过抑制Notch2/hes1信号通路减轻耳蜗毛细胞损伤并促进耳蜗毛细胞修复,进而促进听功能恢复.%Objective To study the effects of DAPT on hearing and Notch2/hesl signaling pathways expres sion in gentamicin-induced hearing injury and repair process. Methods Seventy-two mature rats were randomly divided into the normal group(saline, intraperitoneal injection, 3 ml · kg-1 · d-1 ,held following the ten days) ,mod el group(Gen,120 mg · kg-1 · d-1 , intraperitoneal injection, continuous ten days) and DAPT group(Gen,120 mg · kg-1 · d-1 , intraperitoneal injection, continuous ten days;DAPT,5 mg · kg-1 · d-1 intraperitoneal injection, held following the five days, continuous three days after stop two days). Hearing changes were evaluated by auditory brainstem response (ABR) at pre-modeling and 1,14 ,28 days post-modeling. The expression of the

  5. Nephroprotective, Diuretic and Antioxidant Effects of Some Medicinal Herbs in Gentamicin-Nephrotoxic Rats

    Directory of Open Access Journals (Sweden)

    Mostafa Abbas Shalaby

    2014-02-01

    Conclusion: Aqueous extracts of Petroselinum sativum, Eruca sativa and Curcuma longa produce nephroprotective, diuretic and antioxidant effects in GM - nephrotoxic rats. These herbs may be beneficial for patients who suffer from kidney diseases and those on GM therapy. [J Intercult Ethnopharmacol 2014; 3(1.000: 1-8

  6. Sublethal Triclosan Exposure Decreases Susceptibility to Gentamicin and Other Aminoglycosides in Listeria monocytogenes

    DEFF Research Database (Denmark)

    Christensen, Ellen Gerd; Gram, Lone; Kastbjerg, Vicky Gaedt

    2011-01-01

    The human food-borne pathogen Listeria monocytogenes is capable of persisting in food processing plants despite cleaning and sanitation and is likely exposed to sublethal biocide concentrations. This could potentially affect susceptibility of the bacterium to biocides and other antimicrobial agen...... is commonly used in listeriosis treatment. The triclosan-induced resistance is, hence, of great concern. Further investigations are needed to determine the molecular mechanisms underlying the effect of triclosan....

  7. Novel Pathways for Ameliorating the Fitness Cost of Gentamicin Resistant Small Colony Variants

    DEFF Research Database (Denmark)

    Vestergaard, Martin; Paulander, Wilhelm; Leng, Bingfeng;

    2016-01-01

    Small colony variants (SCVs) of the human pathogen Staphylococcus aureus are associated with persistent infections. Phenotypically, SCVs are characterized by slow growth and they can arise upon interruption of the electron transport chain that consequently reduce membrane potential and thereby li...

  8. Efficacy of ciprofloxacin-gentamicin combination therapy in murine bubonic plague

    National Research Council Canada - National Science Library

    Lemaître, Nadine; Ricard, Isabelle; Pradel, Elizabeth; Foligné, Benoît; Courcol, René; Simonet, Michel; Sebbane, Florent

    2012-01-01

    ... (i) against Yersinia pestis in vitro and (ii) in a mouse model of bubonic plague in which animals were intravenously injected with antibiotics for five days, starting at two different times after infection (44 h and 56 h). In vitro, the CIN...

  9. The influence of cyclic loading on gentamicin release from acrylic bone cements

    NARCIS (Netherlands)

    Hendriks, JGE; Neut, D; Hazenberg, JG; Verkerke, GJ; van Horn, [No Value; van der Mei, HC; Busscher, HJ

    2005-01-01

    Antibiotic-loaded acrylic bone cement is widely used in total joint replacement to reduce infections. Walking results in cyclic loading, which has been suggested to stimulate antibiotic release. The goal of this study is to compare antibiotic release from cyclically loaded bone cement with the relea

  10. Effect of gentamicin loaded PMMA bone cement on Staphylococcus aureus biofilm formation

    NARCIS (Netherlands)

    Poelstra, KA; Busscher, HJ; Schenk, W; van Horn, [No Value; van der Mei, HC

    1999-01-01

    PMMA (poly-methyl-methacrylate) bone cement is widely used in prosthetic implant surgery and is currently prepared with vacuum-mixing for improved mechanical properties. Revision of implants due to infection occurs in about 1% of cases, mostly involving staphylococcal strains. Antibiotic loaded ceme

  11. a comparative study of the effects of colostrum and gentamicin on ...

    African Journals Online (AJOL)

    LIVINGSTON

    if colostrum (breast milk) has any effect on organisms implicated in ... collected from 100 neonates with symptoms by swabbing the lower conjunctival surfaces ... The specimens were cultured onto pre-labeled oven dried agar plates at 37 C for.

  12. Injectable hybrid delivery system composed of gellan gum, nanoparticles and gentamicin for the localized treatment of bone infections

    NARCIS (Netherlands)

    Posadowska, Urszula; Brzychczy-Włoch, Monika; Drożdż, Anna; Krok-Borkowicz, Małgorzata; Wlodarczyk-Biegun, Gosia; Dobrzyński, Piotr; Chrzanowski, Wojciech; Pamuła, Elżbieta

    2016-01-01

    Objectives: Bone infections are treated with antibiotics administered intravenously, antibiotic-releasing bone cements or collagen sponges placed directly in the infected area. These approaches render limited effectiveness due to the lack of site specificity and invasiveness of implanting cements

  13. Determination of gentamicin Sulfate by Polarimetry%旋光法测定硫酸庆大霉素含量

    Institute of Scientific and Technical Information of China (English)

    黄冬菊; 林红华; 丘建华

    2002-01-01

    本文用旋光法测定硫酸庆大霉素的含量,通过标准曲线绘制得回归方程:y=0.2223x+0.026,r=1.回收率为98.42%,相对标准偏差RSD=0.83%,本法与中国兽药典规定方法比较,更简单,易操作,适用于硫酸庆大霉素含量的快速测定.

  14. Effect of commercial (vimang and hydroalcoholic extract of Mangifera indica (Mango on gentamicin-induced nephrotoxicity in rat

    Directory of Open Access Journals (Sweden)

    Abolfazl Khajavi Rad

    2011-09-01

    Conclusion: Mango products were able to improve kidney function in an established model of GM-induced nephrotoxicity in the rat. The beneficial effects of Mango on the rat kidney seem to be dose and time-dependent. However, more investigations are needed to elucidate Mango action on GM-induced renal toxicity.

  15. pRb phosphorylation regulates the proliferation of supporting cells in gentamicin-damaged neonatal avian utricle.

    Science.gov (United States)

    Wu, Jingfang; Sun, Shan; Li, Wenyan; Chen, Yan; Li, Huawei

    2014-10-01

    The ability of nonmammalian vertebrates to regenerate hair cells (HCs) after damage-induced HC loss has stimulated and inspired research in the field of HC regeneration. The protein pRb encoded by retinoblastoma gene Rb1 forces sensory progenitor cells to exit cell cycle and maintain differentiated HCs and supporting cells (SCs) in a quiescent state. pRb function is regulated by phosphorylation through the MEK/ERK or the pRb/Raf-1 signaling pathway. In our previous study, we have shown that pRb phosphorylation is crucial for progenitor cell proliferation and survival during the early embryonic stage of avian otocyst sensory epithelium development. However, in damaged avian utricle, the role of pRb in regulating the cell cycling of SCs or HCs regeneration still remains unclear. To further elucidate the function of pRb phosphorylation on SCs re-entering the cell cycle triggered by gentamycin-induced HCs damage, we isolated neonatal chicken utricles and treated them with the MEK inhibitor U0126 or the pRb/Raf-1 inhibitor RRD-251, respectively in vitro. We found that after gentamycin-induced HCs damage, pRb phosphorylation is important for the quiescent SCs re-entering the cell cycle in the neonatal chicken utricle. In addition, the proliferation of SCs decreased in a dose-dependent manner in response to both U0126 and RRD-251, which indicates that both the MEK/ERK and the pRb/Raf-1 signaling pathway play important roles in pRb phosphorylation in damaged neonatal chicken utricle. Together, these findings on the function of pRb in damaged neonatal chicken utricle improve our understanding of the regulation of the cell cycle of SCs after HCs loss and may shed light on the mammalian HC regeneration from SCs in damaged organs.

  16. Contaminated fistula following J-pouch ileoanal reservoir. Treatment with a collagen sponge containing gentamicin and metronidazole. Case report

    DEFF Research Database (Denmark)

    Nielsen, R; Bülow, Steffen; Moesgaard, F

    1991-01-01

    In a 55-year-old woman, a 1 x 5 cm fistula developed in the ileoanal anastomosis after restorative proctocolectomy with J-pouch ileoanal reservoir and temporary ileostomy for intractable ulcerative colitis. The fistula extended between the pouch and the sacral bone. Lasting closure was achieved...

  17. Comparative evaluation of topical Sodium fusidate cream in common pyodermas with topical gentamicin ointment and systemic antibiotics

    Directory of Open Access Journals (Sweden)

    Roy AK

    1996-01-01

    Full Text Available ABSTRACT: One hundred cases of common pyodermas consisting of four groups, namely impetigo, furunculosis and chronic folliculitis were taken. Each group containing twenty five cases were divided again into three subgroups. From each group, 15 were treated with 2 percent Sodium fusidate cream, 5 were with 0.1 percent Gentamycin sulphate cream and the rest 5 with systemic Erythromycin stearate. In the group of Impetigo, Bockhart′s Impetigo and Furunculosis, topical Sodium fusidate cream showed excellent result, better than Gentamycin topical and equal to that of systemic Erythromycin stearate.

  18. Magnetic targeting of surface-modified superparamagnetic iron oxide nanoparticles yields antibacterial efficacy against biofilms of gentamicin-resistant staphylococci

    NARCIS (Netherlands)

    Subbiandoss, Guruprakash; Sharifi, Shahriar; Grijpma, Dirk W.; Laurent, Sophie; van der Mei, Henny C.; Mahmoudi, Morteza; Busscher, Henk J.

    2012-01-01

    Biofilms on biomaterial implants are hard to eradicate with antibiotics due to the protection offered by the biofilm mode of growth, especially when caused by antibiotic-resistant strains. Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used in various biomedical applications, such as

  19. GENTAMICIN REDUCES BACTEREMIA AND MORTALITY-RATES ASSOCIATED WITH THE TREATMENT OF EXPERIMENTAL PERITONITIS WITH RECOMBINANT TISSUE-PLASMINOGEN ACTIVATOR

    NARCIS (Netherlands)

    van Goor, Harry; de Graaf, JS; KOOI, K; BLEICHRODT, RP

    BACKGROUND: Recombinant tissue plasminogen activator (rtPA), administered intraperitoneally, reduces intra-abdominal abscess formation in rats with fecal peritonitis at the costs of increased mortality and early Escherichia coli bacteremia. It was determined whether or not mortality and bacteremia

  20. Bone induction by composites of bioresorbable carriers and demineralized bone in rats: a comparative study of fibrin-collagen paste, fibrin sealant, and polyorthoester with gentamicin

    DEFF Research Database (Denmark)

    Pinholt, E M; Solheim, E; Bang, G

    1992-01-01

    Host tissue response and heterotopic osteoinduction by composites of demineralized bone matrix and three different substances used as bioresorbable carriers implanted in the abdominal muscles were evaluated by strontium 85 uptake and histology 4 weeks postoperatively in 60 male Wistar rats. Both...

  1. Effect of Catechins, Green tea Extract and Methylxanthines in Combination with Gentamicin Against Staphylococcus aureus and Pseudomonas aeruginosa - Combination therapy against resistant bacteria -

    OpenAIRE

    Bibi Sedigheh Fazly Bazzaz; Sahar Sarabandi; Bahman Khameneh; Hossein Hosseinzadeh

    2016-01-01

    Objectives: Bacterial resistant infections have become a global health challenge and threaten the society’s health. Thus, an urgent need exists to find ways to combat resistant pathogens. One promising approach to overcoming bacterial resistance is the use of herbal products. Green tea catechins, the major green tea polyphenols, show antimicrobial activity against resistant pathogens. The present study aimed to investigate the effect of catechins, green tea extract, and methylxanthines in com...

  2. Inhibition of gentamicin–induced renal tubular cell necrosis

    OpenAIRE

    Tavafi, Majid

    2012-01-01

    Gentamicin nephrotoxicity limit its usage against gram negative bacteria. Most researches showed that antioxidant agents improved gentamicin nephrotoxicity. According to these investigations oxidative stress play a central role in the mechanism of gentamicin induced nephrotoxicity. Recently Rafieian-Kopaei and colleagues showed that erythropoietin significantly ameliorated serum creatinine, blood urea nitrogen and tubal necrosis in gentamicin induced nephrotoxicity in rat. One of the advantag...

  3. Drug: D08013 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available e Anatomical Therapeutic Chemical (ATC) classification [BR:br08303] D DERMATOLOGIC...ALS D06 ANTIBIOTICS AND CHEMOTHERAPEUTICS FOR DERMATOLOGICAL USE D06A ANTIBIOTICS FOR TOPICAL USE D06AX Oth...r aminoglycosides J01GB03 Gentamicin D08013 Gentamicin (BAN) S SENSORY ORGANS S01 OPHTHALMOLOGICALS S01A ANT...IINFECTIVES S01AA Antibiotics S01AA11 Gentamicin D08013 Gentamicin (BAN) S02 OTOLOGICALS S02A ANTIINFECTIVES... S02AA Antiinfectives S02AA14 Gentamicin D08013 Gentamicin (BAN) S03 OPHTHALMOLOGICAL AND OTOLOGIC

  4. Curative effect of transtympanic perfusion of gentamicin on unilateral Ménière′s disease%庆大霉素鼓室注射治疗单侧梅尼埃病的疗效分析

    Institute of Scientific and Technical Information of China (English)

    聂国辉; 卢永德

    2003-01-01

    目的探讨庆大霉素破坏性治疗单侧梅尼埃病的疗效.方法选择23例年龄在24~61岁的梅尼埃病患者为治疗对象.将患耳置鼓室通气管后,每日经中耳通气管注入庆大霉素,每次12 mg,3 h 1次,每日共5次.注药前检查纯音听力及前庭功能,冰水试验反应消失或明显减弱、Frenzel眼镜下观察到破坏性眼震即可停药.23例患者平均用药216 mg,平均治疗时间3.6 d.分别随访9~11年,平均10.2年.结果 21例患者眩晕发作消失(91%),2例仍有发作;听力提高或不变17例(73%),下降6例;耳鸣减轻或消失15例(66%),不变6例,加重2例;耳闭减轻或消失21例(91%),无变化2例.患者恢复工作和生活能力21例(91%),仍轻度致残1例,重度致残1例,此例经迷路切除术眩晕消失.结论鼓室应用庆大霉素可以破坏前庭功能并消除眩晕,保存耳蜗功能.获得疗效的关键是严格选择适应证,密切监视内耳功能,掌握用药剂量与停药指征.

  5. Complete genome sequences of multidrug-resistant Campylobacter jejuni 14980A (turkey feces) and Campylobacter coli 14983A (housefly from turkey farm), harboring a novel gentamicin resistance mobile element.

    Science.gov (United States)

    Multidrug resistance (MDR) in foodborne pathogens is a major food safety and public health issue. Here we describe whole-genome sequences of two MDR strains of Campylobacter jejuni and Campylobacter coli from turkey feces and a housefly in a turkey farm. Both strains harbor a novel chromosomal genta...

  6. C-6' aminomethylation modification in gentamicin biosynthesis gene cluster%庆大霉素C-6 '位氨甲基化修饰基因的研究

    Institute of Scientific and Technical Information of China (English)

    胡育龙; 洪文荣

    2015-01-01

    探索庆大霉素C-6'位氨甲基化修饰作用的基因.首先构建用于genT基因缺失的同源重组质粒pFT104,利用接合转移导入绛红色小单孢菌G1008,筛选获得一株genT基因缺失工程菌GT106(△genT).其次构建用于GT106上genN基因缺失的重组质粒pFTN203,通过接合转移导入GT106,筛选获得一株工程菌GTN205(△genT+ genN).最后在genK基因已经明确为C-6'位甲基化酶基因的基础上,在GTN205中敲除genK基因,筛选获得到一株工程菌GTNK308(△genT+ genN+ genK).工程菌发酵产物经质谱分析结果表明,与出发菌G1008相比,GT106组分未发生变化,而GTN205不再合成庆大霉素C1,产物主要积累在庆大霉素C1a和C2,GTNK308未检测到庆大霉素C2b.结果说明,genN基因缺失阻断了庆大霉素C1与C2b的合成,表明genN基因参与修饰绛红糖胺C-6'位氨甲基化,而genT并不参与修饰绛红糖胺C-6'位氨甲基化.

  7. HPLC method using FMOC-Cl pre-column derivatization for determination of gentamicin%FMOC-Cl柱前衍生高效液相色谱法测定乳中庆大霉素

    Institute of Scientific and Technical Information of China (English)

    赵静; 钱镭; 刘鹏

    2014-01-01

    建立一种简.捷、快速的高效液相色谱法测定原料奶中庆大霉素的残留.庆大霉素经氯甲酸芴甲酯(FMOC-Cl)衍生化后用HPLC法分析.采用Diamonsil-C18(250 min×4.6 mm,5μm)色谱柱,以乙腈-水(75:25,V/V)为流动相,荧光检测器激发波长为350 nm、发射波长为450 nm.回收率在88.8%~93.2%,精密度(RSD)为1.85%~3.41%,检出限分别为1.5 μg/mL.该方法可用于原料奶中庆大霉素残留的检测.

  8. Determination of Gentamicin Residue in Bovine Muscle by High-performance Liquid Chromatography%高效液相色谱法测定牛肌肉中庆大霉素残留的研究

    Institute of Scientific and Technical Information of China (English)

    侯亚莉; 朱奎; 郭平; 李海燕; 李晓薇; 丁双阳

    2008-01-01

    本研究建立一种简捷、快速的高效液相色谱法测定牛肌肉组织中庆大霉素的残留.样品经50%三氯乙酸沉淀蛋白,上清液过MCX固相萃取小柱,洗脱液氮气吹干,经FMOC-Cl柱前衍生化,正己烷脱脂,用荧光检测器检测,激发波长260nm,发射波长315nm.该法对牛肌肉组织中庆大霉素的检测限(LOD)为25μg·g-1,定量限(LOQ)为50μg·g-1,在50、100、500μg·g-1添加水平回收率为80.4%~82.8%,批内变异系数为3.4%~6.8%.批间变异系数为5.5%~8.1%.本方法可对牛肉样品中庆大霉素残留进行分析.

  9. To tilfaelde af neonatal meningitis efter indførelse af nyt gentamicinregime

    DEFF Research Database (Denmark)

    Blaabjerg, Anne Sofie; Fenger-Grøn, Jesper; Møller, Jens Kjølseth

    2016-01-01

    Neonates with suspected or proven sepsis are treated with ampicillin and until recently with 5 mg gentamicin/kg every 24 h. New guidelines recommend the same gentamicin dose, but with longer intervals depending on gestational age. Two neonates receiving gentamicin every 48 h improved initially...

  10. Acyclovir

    Science.gov (United States)

    ... such as amikacin (Amikin), gentamicin (Garamycin), kanamycin (Kantrex), neomycin (Nes-RX, Neo-Fradin), paramomycin (Humatin), streptomycin, and tobramycin (Tobi, Nebcin); aspirin and other nonsteroidal ...

  11. Ganciclovir

    Science.gov (United States)

    ... aminoglycoside antibiotics such as amikacin (Amikin), gentamicin (Garamycin), neomycin (New-Rx, New-Fradin), netilmicin (Netromycin), streptomycin, tobramycin (Nebcin, Tobi), and others; amphotericin B (Fungizone); ...

  12. Adefovir

    Science.gov (United States)

    ... such as amikacin (Amikin), gentamicin (Garamycin), kanamycin (Kantrex), neomycin (Neo-Rx, NeoFradin), paramomycin (Humatin), streptomycin, and tobramycin (Tobi, Nebcin); amphotericin B (Fungizone); aspirin ...

  13. Colistimethate Injection

    Science.gov (United States)

    ... Abelcet, Ambisome), capreomycin (Capastat), gentamicin (Gentak, Genoptic), kanamycin, neomycin (Neo-Fradin), paromomycin, polymyxin B, sodium citrate (in Bicitra), streptomycin, tobramycin (Tobi, Tobrex), or vancomycin (Vancocin). Your doctor ...

  14. Valganciclovir

    Science.gov (United States)

    ... aminoglycoside antibiotics such as amikacin (Amikin), gentamicin (Garamycin), neomycin (Neo-Rx, Neo-Fradin), netilmycin (Netromycin), streptomycin, tobramycin (Nebcin, Tobi), and others; amphotericin B (Fungizone); ...

  15. Observation of Effect of Cold Spray with Gentamicin Solution and Chinese Medicine Mask Pack in Treatment of Facial Dermatitis%庆大霉素溶液冷喷及中药面膜联合治疗面部皮炎疗效观察

    Institute of Scientific and Technical Information of China (English)

    孙海歌

    2009-01-01

    @@ 化妆品皮炎临床很常见,影响美观,在治疗上追求快速缓解,治愈,大连市皮肤病医院美容科在2006-03/2009-03采用庆大霉素溶液冷喷及中药面膜联合治疗面部皮炎,取得了满意疗效,现报道如下.

  16. Anti-toxical effect of iminoethyl-lysine on guinea pig renal damaged by gentamicin%亚氨乙基赖氨酸对庆大霉素所致豚鼠肾脏损伤的拮抗作用

    Institute of Scientific and Technical Information of China (English)

    何青莲; 谭敏; 石灵春; 张维彬

    2002-01-01

    目的: 探讨诱生型一氧化氮合成酶抑制剂(inducible nitric oxide synthase, iNOS)亚氨乙基赖氨酸(Imi)对庆大霉素(Gen)所致豚鼠肾脏损伤的拮抗作用. 方法: 实验动物分4组:正常动物组、Gen组、Gen+Imi组和Imi组.Gen组和Gen+Imi组动物皮下均注射庆大霉素 100 mg*kg-1*d-1日,连续 10 d,同时Gen+Imi组腹腔注射Imi 10 mg*kg-1*d-1,Gen组腹腔注射等量生理盐水;正常动物组皮下与腹腔均注射等量的生理盐水.Imi组腹腔注射与Gen+Imi组等量Imi.所有动物在实验前后均行肾功能检查.所有各组肾脏均行石蜡包埋、切片、HE染色、光镜观察;同时行iNOS免疫组织化学染色. 结果: iNOS在正常动物组和Imi组肾脏呈阴性表达,在Gen+Imi组和Gen组呈阳性表达,且Gen组iNOS活性明显强于Gen+Imi组;Gen组肾脏损伤明显重于Gen+Imi组. 结论: iNOS在庆大霉素所致豚鼠肾脏损伤中呈阳性表达,Imi显著抑制iNOS活性,且对肾脏损伤有明显拮抗作用,提示一氧化氮在庆大霉素所致豚鼠肾脏损伤病理过程中起重要作用.

  17. Estudo comparativo de duas técnicas farmacopéicas de avaliação da atividade antimicrobiana dos fármacos: nistatina, eritromicina, neomicina e gentamicina Comparison of two pharmacopeical thecnics to the evaluation of the antimicrobial activity of the drugs: nystatin, erythromycin, neomycin and gentamicin

    OpenAIRE

    Tatiane Margato Vital; Cleomenes Reis; Marco Túlio Antonio García-Zapata; Luiz Carlos da Cunha

    2004-01-01

    Através das técnicas de difusão em ágar com discos de papel e cilindros de aço inoxidável, analisou-se quantitativamente a atividade antimicrobiana de 123 medicamentos contendo os fármacos: nistatina (43 amostras de creme vaginal), eritromicina (14 amostras de comprimidos e 9 amostras de suspensão oral), gentamicina (33 amostras de líquido injetável) e neomicina (24 amostras de creme de uso tópico), mediante as seguintes cepas de microrganismos: Saccharomyces cerevisiae ATCC 2601 para a nista...

  18. The protection effect of basic fibroblast factor on guinea pig toxic kidney injury induced by gentamicin%碱性成纤维生长因子对豚鼠庆大霉素肾毒性损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    魏佑震; 黄庆玉; 申姜颖; 洪岸; 康颂建

    2001-01-01

    目的研究碱性成纤维细胞生长因子(bFGF)对庆大霉素(GE)所致豚鼠肾损伤的拮抗作用.方法 20只豚鼠随机分成三组,正常对照组(N,n=6),庆大霉素对照组(G,n=7),庆大霉素bFGF组(F,n=7).G组:GE 80mg·kg-1·d-1肌肉注射,连续15d;F组:bFGF肌肉注射800U·kg-1·d-1,相隔1~2h后加GE 80mg·kg-1·d-1肌肉注射,连续15d.第16d取肾固定,石蜡包埋切片,HE染色,光镜观察肾小球、肾小管及肾间质.结果 F组与G组比较,F组肾小球毛细血管扩张、充血及内皮细胞肿胀较轻;肾小管坏死数量较少;肾小管再生、肾间质炎细胞浸润和纤维细胞增生明显.结论 bFGF对豚鼠庆大霉素肾损伤具有预防保护作用.

  19. Synergism between maggot excretions and antibiotics.

    Science.gov (United States)

    Cazander, Gwendolyn; Pawiroredjo, Janity S; Vandenbroucke-Grauls, Christina M J E; Schreurs, Marco W J; Jukema, Gerrolt N

    2010-01-01

    Maggots are successfully used to treat severe, infected wounds. This study investigated whether maggot excretions/secretions influence the antibacterial activity of different antibiotics. Minimal inhibitory concentrations and minimal bactericidal concentrations (MBC) were determined of gentamicin and flucloxacillin for Staphylococcus aureus, of penicillin for Streptococcus pyogenes, of amoxicillin and vancomycin for Enterococcus faecalis, of gentamicin for Enterobacter cloacae, and of gentamicin, tobramycin, and ciprofloxacin for Pseudomonas aeruginosa by checkerboard titration. A range of concentrations of antibiotics in combination with excretions/secretions was examined to investigate the potential of maggot excretions/secretions to affect antibacterial activity. The results showed a dose-dependent increase of the antibacterial effect of gentamicin in the presence of excretions/secretions on S. aureus. Minimal concentrations and MBC of gentamicin decreased, respectively, 64- and 32-fold. The MBC of flucloxacillin and excretions/secretions against S. aureus were also decreased. The other antibiotic and excretions/secretions combinations exerted an indifferent effect. Excretions/secretions alone did not have any antibacterial effect. The synergism between gentamicin and maggot excretions/secretions could be of direct importance in clinical practice, because it could allow the use of lower doses of gentamicin and thus minimize the risk of gentamicin-related side effects.

  20. Porous Hydroxyapatite Bioceramic Scaffolds for Drug Delivery and Bone Regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Loca, Dagnija; Locs, Janis; Salma, Kristine; Gulbis, Juris; Salma, Ilze; Berzina-Cimdina, Liga, E-mail: dagnija.loca@rtu.l [Riga Technical University, Riga Biomaterials innovation and development centre, Pulka 3/3, LV-1007, Riga (Latvia)

    2011-10-29

    The conventional methods of supplying a patient with pharmacologic active substances suffer from being very poorly selective, so that damage can occurs to the healthy tissues and organs, different from the intended target. In addition, high drug doses can be required to achieve the desired effect. An alternative approach is based on the use of implantable delivery tools, able to release the active substance in a controlled way. In the current research local drug delivery devices containing 8mg of gentamicin sulphate were prepared using custom developed vacuum impregnation technique. In vitro dissolution tests showed that gentamicin release was sustained for 12h. In order to decrease gentamicin release rate, biopolymer coatings were applied and coating structure investigated. The results showed that gentamicin release can be sustained for more than 70h for poly({epsilon}-caprolactone) coated calcium phosphate scaffolds. From poly lactic acid and polyvinyl alcohol coated scaffolds gentamicin was released within 20h and 50h, respectively.

  1. Characteristics, interactions and coating adherence of heterogeneous polymer/drug coatings for biomedical devices

    Energy Technology Data Exchange (ETDEWEB)

    McManamon, Colm [Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, Dublin 2 (Ireland); Silva, Johann P. de [Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, Dublin 2 (Ireland); School of Physics, Trinity College Dublin, Dublin 2 (Ireland); Delaney, Paul [Department of Chemistry, Supercritical Fluid Centre and Materials Section, University College Cork, Cork (Ireland); Morris, Michael A. [Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, Dublin 2 (Ireland); Department of Chemistry, Supercritical Fluid Centre and Materials Section, University College Cork, Cork (Ireland); Cross, Graham L.W., E-mail: crossg@tcd.ie [Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, Dublin 2 (Ireland); School of Physics, Trinity College Dublin, Dublin 2 (Ireland)

    2016-02-01

    With this rise in surgical procedures it is important to focus on the mobility and safety of the patient and reduce the infections that are associated with hip replacements. We examine the mechanical properties of gentamicin sulphate as a model antimicrobial layer for titanium-alloy based prosthetic hips to help prevent methicillin-resistant Staphylococcus aureus infection after surgery. A top layer of poly(lactic-co-glycolic acid) is added to maintain the properties of the gentamicin sulphate as well as providing a drug delivery system. Through the use of nanoindentation and micro-scratch techniques it is possible to determine the mechanical and adhesive properties of this system. Nanoindentation determined the modulus values for the poly(lactic-co-glycolic acid) and gentamicin sulphate materials to be 8.9 and 5.2 GPa, respectively. Micro-scratch established that the gentamicin sulphate layer is strongly adhered to the Ti alloy and forces of 30 N show no cohesive or adhesive failure. It was determined that the poly(lactic-co-glycolic acid) is ductile in nature and delaminates from the gentamicin sulphate layer of at 0.5 N. - Highlights: • Biomedical bilayer for prosthetic implant to reduce patient pain and increase patient mobility • The characterisation of the materials shows that the materials are in accordance with FDA regulations. • The mechanical properties of the gentamicin suggest that it is well adhered to the substrate. • The PLGA layer delaminates at lower forces allowing the gentamicin to fight infection.

  2. Aminoglycoside-induced hair cell death of inner ear organs causes functional deficits in adult zebrafish (Danio rerio.

    Directory of Open Access Journals (Sweden)

    Phillip M Uribe

    Full Text Available Aminoglycoside antibiotics, like gentamicin, kill inner ear sensory hair cells in a variety of species including chickens, mice, and humans. The zebrafish (Danio rerio has been used to study hair cell cytotoxicity in the lateral line organs of larval and adult animals. Little is known about whether aminoglycosides kill the hair cells within the inner ear of adult zebrafish. We report here the ototoxic effects of gentamicin on hair cells in the saccule, the putative hearing organ, and utricle of zebrafish. First, adult zebrafish received a single 30 mg/kg intraperitoneal injection of fluorescently-tagged gentamicin (GTTR to determine the distribution of gentamicin within inner ear sensory epithelia. After 4 hours, GTTR was observed in hair cells throughout the saccular and utriclar sensory epithelia. To assess the ototoxic effects of gentamicin, adult zebrafish received a single 250 mg/kg intraperitoneal injection of gentamicin and, 24 hours later, auditory evoked potential recordings (AEPs revealed significant shifts in auditory thresholds compared to untreated controls. Zebrafish were then euthanized, the inner ear fixed, and labeled for apoptotic cells (TUNEL reaction, and the stereociliary bundles of hair cells labeled with fluorescently-tagged phalloidin. Whole mounts of the saccule and utricle were imaged and cells counted. There were significantly more TUNEL-labeled cells found in both organs 4 hours after gentamicin injection compared to vehicle-injected controls. As expected, significantly fewer hair cell bundles were found along the rostral-caudal axis of the saccule and in the extrastriolar and striolar regions of the utricle in gentamicin-treated animals compared to untreated controls. Therefore, as in other species, gentamicin causes significant inner ear sensory hair cell death and auditory dysfunction in zebrafish.

  3. Synthesis of Bioactive Gelatin-siloxane Hybrids for Bone Tissue Engineering and Evaluation of Its Drug Release Behaviors in vitro

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Porous and bioactive gentamicin sulfate-loaded gelatin-siloxane hybrids were successfully synthesized by using a combined sol-gel processing, post-gelation soaking, and freeze-drying process. A bone-like apatite layer was able to form in the Ca2 + -containing porous gentamicin-loaded hybrids upon soaking in a simulated body fluid (SBF) up to 1 day. The drug release of gentamicin sulfate was with a burst, followed by an almost constant release up to 7 days. And the rate of release in acidic medium was lower than that in the neutral and basic media.

  4. Prevalence and antibiogram of bacterial isolates from urinary tract infections at Dessie Health Research Laboratory, Ethiopia

    Directory of Open Access Journals (Sweden)

    Mulugeta Kibret

    2014-02-01

    Conclusions: In the study area resistance rates to erythromycin, amoxycillin and tetracycline were high. Since most isolates were sensitive to nitrofurantoin and gentamicin, they are considered as appropriate antimicrobials for empirical treatment urinary tract infections.

  5. Characterisation of recently emerged multiple antibiotic-resistant Salmonella enterica serovar typhimurium DT104 and other multiresistant phage types from Danish pig herds

    DEFF Research Database (Denmark)

    Baggesen, Dorte Lau; Aarestrup, Frank Møller

    1998-01-01

    A total of 670 isolates of Salmonella enterica were isolated from Danish pig herds, phage typed and tested for susceptibility to amoxycillin + clavulanate, ampicillin, colistin, enrofloxacin, gentamicin, neomycin, spectinomycin, streptomycin, tetracyclines, and trimethoprim + sulphadiazine. S ent...

  6. Streptomycin interference in Jaffe reaction - Possible false positive creatinine estimation in excessive dose exposure

    DEFF Research Database (Denmark)

    Syal, Kirtimaan; Srinivasan, Anand; Banerjee, Dibyajyoti

    2013-01-01

    Objectives: To study the potential of commonly used aminoglycoside antibiotics to form non-creatinine chromogen with alkaline picrate reagent. Design and methods: We studied the non-creatinine chromogen formation of various concentrations of streptomycin, amikacin, kanamycin, netilmicin, gentamicin...

  7. Antibiotics and renal branching morphogenesis: comparison of toxicities

    NARCIS (Netherlands)

    Bueters, R.R.G.; Kusters, L.J.; Klaasen, A.; Heuvel, L.P.W.J. van den; Schreuder, M.F.

    2014-01-01

    BACKGROUND: Many premature born neonates receive antibiotic drugs to treat infections, which are applied during active nephrogenesis. We studied the impact of clinical concentrations of gentamicin and alternatives, ceftazidime and meropenem, on ureteric branching. METHODS: Mice metanephroi were diss

  8. Innovations in Wound Infection Prevention and Management and Antimicrobial Countermeasures

    Science.gov (United States)

    2011-01-24

    therapies to treat wound infections – Acinetobacter baumannii , Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, extended...conventional antibiotics – converted Acinetobacter baumannii once resistant to kanamycin & gentamicin to susceptibility – Compound in Phase I clinical testing

  9. Laser based enhancement of susceptibility of bacteria to antibiotic

    Science.gov (United States)

    Reznick, Yana; Banin, Ehud; Lipovsky, Anat; Lubart, Rachel; Zalevsky, Zeev

    2012-03-01

    Our objective is to test the effect of pulsed (Q-switched) and continuous wave (CW) laser light at wavelength of 532nm on the viability of free-living stationary phase bacteria with and without gentamicin (an antibiotic) treatment. Free living stationary phase gram negative bacteria (Pseudomonas aeruginosa strain PAO1) was immersed in Luria Broth (LB) solution and exposed to Q-switched and CW lasers with and without the addition of the antibiotic gentamicin. Cell viability was determined at different time points. Laser treatment alone did not reduce cell viability compared to untreated control and the gentamicin treatment alone only resulted in a 0.5 log reduction in the viable count for P. aeruginosa. The combined laser and gentamicin treatment, however, resulted in a synergistic effect and viability was reduced by 8 log's for P. aeruginosa PAO1.

  10. Antimicrobial resistance pattern of Escherichia coli isolated from patients with urinary tract infection (UTI in Yasuj city during 1391-1392.

    Directory of Open Access Journals (Sweden)

    A Sharifi

    2014-07-01

    Conclusion: It is recommended to treat urinary tract infections by using fewer antibiotics such as Amoxicillin / Clavulanic acid and co-trimoxazole, and administration of ciprofloxacin and gentamicin should be used with caution.

  11. Inhibition effects of antibiotics ampicillin and gentamycin on the methanogenic activity of anaerobic biomass

    Directory of Open Access Journals (Sweden)

    Mahnaz Heidari

    2012-01-01

    Conclusion: At the same concentrations, ampicillin showed more inhibitory effect than gentamicin on anaerobic decomposition of biomass. Within the used VFAs, the inhibitory effects of propionic acid was greater than acetic acid and butyric acid.

  12. a profile of wound infections in national hospital abuja

    African Journals Online (AJOL)

    boaz

    Iregbu KC1, Uwaezuoke NS, Nwajiobi-Princewill IP, Eze SO, Medugu N , Shettima S, Modibbo Z. .... particularly to the third generation cephalosporins and gentamicin. This level ... Wonud infections in two health institutionsin Ile Ife, Nigeria:A.

  13. JMBR VOLUME 14 Number 2.cdr

    African Journals Online (AJOL)

    FINEPRINT

    agents namely, Gentamicin, Cefuroxime, Ceftriaxone and Norfloxacin singly and also in combination with ..... ciprofloxacin, minocycline, cloxacillin, and vancomycin) ... removal or deletion of the resistance factor which may have been an ...

  14. Antibiogram profile of pathogens isolated from processed cow meat ...

    African Journals Online (AJOL)

    2016-06-30

    Jun 30, 2016 ... ... of meat is carcass which represents the ideal meat after removal of head, hide, .... 72.7% respectively, while Ciprofloxacin, Peflacine and Gentamycin had ... to Rifampicin, Norfloxacin, Gentamicin, Levofloxacin, ciprofloxacin,.

  15. Drug: D10302 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ES IN COMBINATION S01CA Corticosteroids and antiinfectives in combination S01CA02 Prednisolone and antiinfectives D10302 Prednisolone acetate - gentamicin mixt PubChem: 163312333 ...

  16. Preliminary In Vitro Evaluation of an Adjunctive Therapy for Extremity Wound Infection Reduction: Rapidly Resorbing Local Antibiotic Delivery

    Science.gov (United States)

    2009-07-01

    grade calcium sulfate dihydrate powder (Terra Alba; US Gypsum, Chicago, IL) with 0.40 g sodium carboxymethylcellulose (CMC; Hercules, Wilmington, DE...A solution was prepared by mixing an antibiotic [0.42 g amikacin (amikacin sulfate; Bedford Labs., Bedford, OH), gentamicin (gentamicin sulfate; MP...and S. aureus were grown overnight at 378C in trypticase soy broth (TSB). Conical tubes were prepared with 1.75 ml of TSB and 200 ml of antibiotic

  17. Carissa carandas Linn. fruit extract ameliorates gentamicin–induced nephrotoxicity in rats via attenuation of oxidative stress

    OpenAIRE

    Jayesh B. Dhodi; Deepavali R. Thanekar; Snehal N. Mestry; Archana R Juvekar

    2015-01-01

    Objective: To elucidate the mechanism of action of methanolic extract of Carissa carandas fruits (MCCF) in attenuation of diabetic nephropathy using gentamicin induced nephrotoxicity model. Methods: Extract was daily administered to Sprague Dawley rats at doses of 100, 200 and 400 mg/kg for 8 days along with intramuscular injection of gentamicin (80 mg/kg). After completion of the study, serum was analyzed for blood urea nitrogen, albumin and creatinine; urine (24 h) was analyzed for album...

  18. Voltammetric estimation of the content of antibiotics in veterinary preparations

    OpenAIRE

    2016-01-01

    The voltammetric method for determination of tylosin tartrate, gentamicin sulfate, and cefalexin in veterinary preparations was for the first time developed. Electrochemical behavior of these antibiotics on the mercury film electrode was studied, and the working conditions (background electrolyte, deposition potential) were defined for getting analytical signals using the voltammetry. The methods of real objects preparation for determination of tylosin tartrate, gentamicin sulfate, and cefale...

  19. Comparison of the efficacy of diclofenac and betamethasone following strabismus surgery

    OpenAIRE

    Wright, M.; Butt, Z; McIlwaine, G; Fleck, B.

    1997-01-01

    AIMS—To compare the relative anti-inflammatory potency and safety of topical diclofenac-gentamicin with beta methasone-neomycin following strabismus surgery.
METHODS—A single centre, single observer, prospective, randomised, and double masked clinical trial of 25 children undergoing bilateral symmetrical horizontal strabismus surgery was carried out. One eye received diclofenac-gentamicin and the contralateral eye received betamethasone-neomycin; both treatments were instilled four times a da...

  20. Analytical accuracy of determinations of aminoglycoside concentrations by enzyme multiplied immunoassay, fluorescence polarization immunoassay, and radioimmunoassay in the presence of heparin.

    OpenAIRE

    O?Connell, M. E.; Heim, K L; Halstenson, C E; Matzke, G R

    1984-01-01

    The accuracy of gentamicin, netilmicin, and tobramycin concentration determinations by enzyme multiplied immunoassay technique (EMIT; Syva Corp., Palo Alto, Calif.), fluorescence polarization immunoassay (TDx; Abbott Diagnostics, Irving, Tex.), and radioimmunoassay were compared in the presence of 0 to 3,000 USP units of porcine heparin per ml. Gentamicin, netilmicin, and tobramycin concentrations determined by EMIT decreased by 10 and 50% in the presence of 75 and 1,000 USP units/ml, 2 and 5...

  1. A Case Report of Rash at Peritoneal Dialysis Exit Site

    Directory of Open Access Journals (Sweden)

    Elvira O. Gosmanova MD, FASN

    2015-11-01

    Full Text Available The International Society for Peritoneal Dialysis recommends the regular application of topical antibiotic-containing preparations in addition to a routine exit site care to reduce the risk of exit site infection (ESI. Among these prophylactic antimicrobial preparations, topical gentamicin is one of the widely used and effective antibiotics for prevention of ESI and peritonitis in peritoneal dialysis (PD patients. Overall, topical gentamicin is well tolerated; however, its use can be associated with the development of allergic contact dermatitis (ACD. We describe a first reported case of PD catheter exit site contact ACD due to topical gentamicin mimicking ESI. The patient in this report developed worsening violaceous in color and pruritic rash surrounding the PD catheter exit site that appeared 3 weeks after the initiation of gentamicin cream. The association between development of rash and initiation of topical gentamicin led to a suspicion of local reaction to gentamicin rather than ESI. Skin biopsy confirmed ACD. Discontinuation of the provoking agent and subsequent treatment with topical hydrocortisone application led to a resolution of the exit site rash. Any rash at a PD catheter exit site should be considered infectious until proven otherwise. However, it is important to be aware of noninfectious etiologies of exit site rashes as the treatment of these 2 conditions differs.

  2. Drug delivery using novel nanoplexes against a Salmonella mouse infection model

    Science.gov (United States)

    Ranjan, A.; Pothayee, N.; Seleem, M.; Jain, N.; Sriranganathan, N.; Riffle, J. S.; Kasimanickam, R.

    2010-03-01

    A novel methodology for incorporating gentamicin into macromolecular complexes with anionic homo- and block copolymers via cooperative electrostatic interactions is described. Block copolymers of poly(ethylene oxide- b-sodium acrylate) (PEO- b-PAA- +Na) or poly(ethylene oxide- b-sodium methacrylate) (PEO- b-PMA- +Na) were blended with PAA- Na+ and complexed with the polycationic antibiotic gentamicin. Gentamicin nanoplexes made with PEO- b-PMA- +Na/PAA- +Na (PMPG) and analogous nanoplexes with PEO- b-PAA- +Na/PAA- +Na (PAPG) had mean intensity average diameters of 120 and 90 nm, zeta potentials of -17 and -11 mv, and incorporated 26% and 23% by weight of gentamicin, respectively. Gentamicin release rates at physiological pH from nanoplexes were relatively slow. PAPG and PMPG as drug delivery systems for treating murine salmonellosis at doses similar to the free gentamicin experiments resulted in reduced numbers of viable bacteria in the liver and spleen. Polymeric nanoplexes developed by this methodology can potentially improve targeting of intracellular pathogens.

  3. Drug delivery using novel nanoplexes against a Salmonella mouse infection model

    Energy Technology Data Exchange (ETDEWEB)

    Ranjan, A. [Virginia Polytechnic Institute and State University, Department of Large Animal Clinical Sciences (United States); Pothayee, N. [Virginia Polytechnic Institute and State University, Macromolecules and Interfaces Institute (United States); Seleem, M. [Virginia Polytechnic Institute and State University, Institute for Critical Technology and Applied Science (United States); Jain, N.; Sriranganathan, N., E-mail: nathans@vt.ed [Virginia Polytechnic Institute and State University, Department of Biomedical Sciences and Pathobiology (United States); Riffle, J. S. [Virginia Polytechnic Institute and State University, Macromolecules and Interfaces Institute (United States); Kasimanickam, R. [Virginia Polytechnic Institute and State University, Department of Large Animal Clinical Sciences (United States)

    2010-03-15

    A novel methodology for incorporating gentamicin into macromolecular complexes with anionic homo- and block copolymers via cooperative electrostatic interactions is described. Block copolymers of poly(ethylene oxide-b-sodium acrylate) (PEO-b-PAA{sup -+}Na) or poly(ethylene oxide-b-sodium methacrylate) (PEO-b-PMA{sup -+}Na) were blended with PAA{sup -} Na{sup +} and complexed with the polycationic antibiotic gentamicin. Gentamicin nanoplexes made with PEO-b-PMA{sup -+}Na/PAA{sup -+}Na (PMPG) and analogous nanoplexes with PEO-b-PAA{sup -+}Na/PAA{sup -+}Na (PAPG) had mean intensity average diameters of 120 and 90 nm, zeta potentials of -17 and -11 mv, and incorporated 26% and 23% by weight of gentamicin, respectively. Gentamicin release rates at physiological pH from nanoplexes were relatively slow. PAPG and PMPG as drug delivery systems for treating murine salmonellosis at doses similar to the free gentamicin experiments resulted in reduced numbers of viable bacteria in the liver and spleen. Polymeric nanoplexes developed by this methodology can potentially improve targeting of intracellular pathogens.

  4. Cymbopogon citratus protects against the renal injury induced by toxic doses of aminoglycosides in rabbits

    Directory of Open Access Journals (Sweden)

    N Ullah

    2013-01-01

    Full Text Available Renal injury is the most common side-effect of aminoglycosides. These antimicrobial drugs are particularly effective against Gram-negative microorganisms. The present study was conducted to investigate the renal protective activity of Cymbopogon citratus in gentamicin-induced nephrotoxicity. Male rabbits were divided into four groups (n=6 including group 1 (0.9% saline treated, group 2 (80 mg/kg/day gentamicin-treated, group 3 (200 mg/kg/day Cymbopogon citratus treated and group 4 (80 mg/kg/day gentamicin and 200 mg/kg/day Cymbopogon citratus treated. Biochemical kidney functioning parameters, urinary enzymes and histopathological examination were performed. The results of the present study showed that simultaneous administration of Cymbopogon citrates and gentamicin significantly protected alteration in body weight, blood urea nitrogen, serum creatinine, creatinine clearance, serum uric acid, serum electrolytes, urinary volume, urinary protein, urinary lactate dehydrogenase and urinary alkaline phosphatase induced by gentamicin. Histological examination of the kidney also suggested the same. It is concluded from the current study that co-administration of Cymbopogon citratus with gentamicin for 3 weeks successfully prevented renal damage associated with aminoglycosides.

  5. Antibiotic combinatorial approach utilized against extended spectrum beta-lactamase (ESBL bacteria isolates from Enugu, South Eastern Nigeria

    Directory of Open Access Journals (Sweden)

    Ruth A. Afunwa

    2014-04-01

    Full Text Available Introduction: Antibiotic options in the treatment of extended spectrum beta-lactamase (ESBL producing bacteria are very limited. The purpose of this study was to analyze several commonly applied antibiotics in quite various novel combinations for use against ESBL-producing bacteria isolates.Methods: Total of 460 samples of urine, throat and anal swab were collected from volunteers and patients from nursery, primary and secondary schools and from other individuals in the community. Hospital and community isolates comprised of 65% and 35% respectively. The identification and characterization of the isolates were done by standard culturing and in vitro antibiotic sensitivity procedures.Results: The antibiotic combination studies showed that the combination of gentamicin with the other antibiotics had predominantly synergistic effects. The percentage synergistic effect for the combinations of gentamicin/pefloxacin was 69%, gentamicin/[Amoxicillin and clavulanic acid] 72%, gentamicin/ceftriaxone 68%, gentamicin/cefuroxime 81.9%, and gentamicin/ciprofloxacin 80.6%, against the community and hospital derived ESBL producing organisms of both Enterobacteriaceae and Pseudomonas species.Conclusion: Good antimicrobial monitoring exercise and corresponding antimicrobial screening activities should work towards a dynamic approach to generate effective treatment options using combination therapy.

  6. Antibiotics and iron-limiting conditions and their effect on the production and composition of outer membrane vesicles secreted from clinical isolates of extraintestinal pathogenic E. coli.

    Science.gov (United States)

    Chan, Kin W; Shone, Clifford; Hesp, J Richard

    2017-01-01

    The focus of this study was to characterize the effect of clinically relevant stress-inducing conditions on the production and composition of proinflammatory outer membrane vesicles (OMVs) produced from ST131 extraintestinal pathogenic Escherichia coli (ExPEC) clinical isolates. A label-free method (relative normalized spectral index quantification, SINQ) was used to identify changes in the respective OMV proteomes following exposure of the ExPEC strains to antibiotics and low iron. Nanoparticle tracking analysis was used to quantify changes in abundance and size of OMVs produced by the gentamicin-resistant (GenR) and gentamicin-sensitive (GenS) ExPEC strains. Up to a 13.1-fold increase in abundance of particles were detected when the gentamicin-sensitive strain was exposed to a range of gentamicin concentrations. In contrast, no increase was observed for the gentamicin-resistant strain. Iron-limiting conditions had minimal effect on OMV production for either strain. Marked changes in the OMV proteome were observed for both strains including increases in Hsp100/Clp proteins, ATP-dependent ClpP protease, and regulatory proteins. These data provide information on changes in the composition of OMV particles derived from ExPEC strains generated in response to clinically relevant conditions. We show that the levels of the proinflammatory OMVs increase for gentamicin-sensitive ExPEC exposed to the antibiotic. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Hydrogel Antimicrobial Capture Coatings for Endotracheal Tubes: A Pharmaceutical Strategy Designed to Prevent Ventilator-Associated Pneumonia.

    Science.gov (United States)

    Jones, David S; McCoy, Colin P; Andrews, Gavin P; McCrory, Roisin M; Gorman, Sean P

    2015-08-01

    This paper presents a novel strategy for the prevention of ventilator-associated pneumonia that involves coating poly(vinyl chloride, PVC) endotracheal tubes (ET) with hydrogels that may be subsequently used to entrap nebulized antimicrobial solutions. Candidate hydrogels were prepared containing a range of ratios of hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAA) from 100:0 to 70:30 using free radical polymerization and, when required, simultaneous attachment to PVC was performed. The mechanical properties, glass transition temperatures, swelling kinetics, uptake of gentamicin from an aqueous medium, and gentamicin release were characterized. Increasing the MAA content of the hydrogels significantly decreased the ultimate tensile strength, % elongation at break, Young's modulus, and increased the glass transition temperature, the swelling ratio, and gentamicin uptake. Microbial (Staphylococcus aureus and Pseudomonas aeruginosa) adherence to control (drug-free) hydrogels was observed; however, while adherence to gentamicin-containing p(HEMA) occurred, no adherence occurred to gentamicin-containing HEMA:MAA copolymers. Antimicrobial persistence of gentamicin-containing hydrogels was examined by determining the zone of inhibition against each microorganism on successive days. Hydrogel composition affected the observed antimicrobial persistence, with the hydrogel composed of 70:30 HEMA:MAA exhibiting >20 days persistence against S. aureus and P. aeruginosa, respectively. To simulate clinical use, the hydrogels (coated onto PVC) were first exposed to a nebulized solution of gentamicin (4 mL, 80 mg for 20 min), and then to nebulized bacteria (4 mL ca. 1×10(9) colony forming units mL(-1), 30 min). Viable bacteria were not observed on the gentamicin-treated p(HEMA: MAA) copolymers, whereas growth was observed on gentamicin-treated p(HEMA). In light of the excellent antimicrobial activity and physicochemical properties, p(HEMA: MAA) copolymers composed of

  8. Genetic basis of persister tolerance to aminoglycosides in Escherichia coli.

    Science.gov (United States)

    Shan, Yue; Lazinski, David; Rowe, Sarah; Camilli, Andrew; Lewis, Kim

    2015-04-07

    Persisters are dormant variants that form a subpopulation of drug-tolerant cells largely responsible for the recalcitrance of chronic infections. However, our understanding of the genetic basis of antibiotic tolerance remains incomplete. In this study, we applied transposon sequencing (Tn-Seq) to systematically investigate the mechanism of aminoglycoside tolerance in Escherichia coli. We constructed a highly saturated transposon library that covered the majority of E. coli genes and promoter regions and exposed a stationary-phase culture to a lethal dose of gentamicin. Tn-Seq was performed to evaluate the survival of each mutant to gentamicin exposure. We found that the disruption of several distinct pathways affected gentamicin tolerance. We identified 105 disrupted gene/promoter regions with a more than 5-fold reduction in gentamicin tolerance and 37 genes with a more than 5-fold increased tolerance. Functional cluster analysis suggests that deficiency in motility and amino acid synthesis significantly diminished persisters tolerant to gentamicin, without changing the MIC. Amino acid auxotrophs, including serine, threonine, glutamine, and tryptophan auxotrophs, exhibit strongly decreased tolerance to gentamicin, which cannot be restored by supplying the corresponding amino acids to the culture. Interestingly, supplying these amino acids to wild-type E. coli sensitizes stationary-phase cells to gentamicin, possibly through the inhibition of amino acid synthesis. In addition, we found that the deletion of amino acid synthesis genes significantly increases gentamicin uptake in stationary phase, while the deletion of flagellar genes does not affect gentamicin uptake. We conclude that activation of motility and amino acid biosynthesis contributes to the formation of persisters tolerant to gentamicin. Persisters are responsible for the recalcitrance of chronic infections to antibiotics. The pathways of persister formation in E. coli are redundant, and our understanding

  9. Regional limb perfusion for antibiotic treatment of experimentally induced septic arthritis.

    Science.gov (United States)

    Whithair, K J; Bowersock, T L; Blevins, W E; Fessler, J F; White, M R; Van Sickle, D C

    1992-01-01

    Septic arthritis was induced in one antebrachiocarpal joint of seven horses by the intra-articular injection of 1 mL Staphylococcus aureus suspension containing a mean of 10(5) colony-forming units. Twenty-four hours after inoculation, four horses were treated by regional perfusion with 1 g of gentamicin sulfate, and three horses received 2.2 mg/kg gentamicin sulfate intravenously (IV) every 6 hours. Synovial fluid was collected for culture and cytology at regular intervals, and the synovial membranes were collected for culture and histologic examination at euthanasia 24 hours after the first treatment. Gentamicin concentration in the septic synovial fluid after three successful perfusions was 221.2 +/- 71.4 (SD) micrograms/mL; after gentamicin IV, it was 7.6 +/- 1.6 (SD) micrograms/mL. The mean leukocyte count in the inoculated joints decreased significantly by hour 24 in the successfully perfused joints. Terminal bacterial cultures of synovial fluid and synovial membranes were negative in two horses with successfully perfused joints. S. aureus was isolated from the infected joints in all three horses treated with gentamicin IV.

  10. Characteristics, interactions and coating adherence of heterogeneous polymer/drug coatings for biomedical devices.

    Science.gov (United States)

    McManamon, Colm; de Silva, Johann P; Delaney, Paul; Morris, Michael A; Cross, Graham L W

    2016-02-01

    With this rise in surgical procedures it is important to focus on the mobility and safety of the patient and reduce the infections that are associated with hip replacements. We examine the mechanical properties of gentamicin sulphate as a model antimicrobial layer for titanium-alloy based prosthetic hips to help prevent methicillin-resistant Staphylococcus aureus infection after surgery. A top layer of poly(lactic-co-glycolic acid) is added to maintain the properties of the gentamicin sulphate as well as providing a drug delivery system. Through the use of nanoindentation and micro-scratch techniques it is possible to determine the mechanical and adhesive properties of this system. Nanoindentation determined the modulus values for the poly(lactic-co-glycolic acid) and gentamicin sulphate materials to be 8.9 and 5.2GPa, respectively. Micro-scratch established that the gentamicin sulphate layer is strongly adhered to the Ti alloy and forces of 30N show no cohesive or adhesive failure. It was determined that the poly(lactic-co-glycolic acid) is ductile in nature and delaminates from the gentamicin sulphate layer of at 0.5N.

  11. Penetapan kadar gentamisin dalam sediaan krim dengan kromatografi lapis tipis - densitometri

    Directory of Open Access Journals (Sweden)

    Isnaeni Yudi Haryanto

    2016-11-01

    Full Text Available The used of Gentamicin is still regarded for overcoming infectious diseases. Several preparations of the gentamicin are available in the market as injection, eye or ear drops, and topical dosage forms. Based on the standard method, determination of the gentamicin is carried out by microbiological assay. Several instrumental method have been reported. In this research, Thin Layer Chromatography-Densitometry (TLC-Densitometry has been validated and used for determining gentamicin in cream dosage form. The TLC was carried out on a Silica gel GF254 using KH2PO4 20% and ninhidrin 2% solution (in ethanol 96% as eluent and spots visualization respectively. Three spots appeared on the chromatogram having Rf value 0.51, 0.47, and 0.36. All the spots gave maximum absorption at 400 nm. The spot with Rf value of 0.51 was the highest intensity. Limit of Detection (LoD and Limit of quantitation (LoQ of the major component was 0.019 and 0.064 respectively. The other validation characteristics met the requirement for determination of gentamicin in the cream dosage form.

  12. Acute diplopia posterior to chemical laberinthectomy

    Directory of Open Access Journals (Sweden)

    Santos-Gorjón P

    2012-04-01

    Full Text Available SummaryIntroduction: Chemical laberinthectomy with gentamicin is an ambulatory procedure with a low rate of iatrogenical effects. We present a case with a rare complication and review the especifical literature. Clinical repport: We present a women with a left Meniere´s syndrome. A corticoid intratimpanic threathment was done and we don’t get control of symptoms. A gentamicin laberinthectomy was done, and an accute diplopia with no other clinical manifestations appears. Discussion: 95% of Ménière´s symptoms gets control with medical theathments. Security of gentamicin is accepted since 80`s decade. Susceptibility of action in inner ear is variable. We have to use minimal dosis of gentamicin to have control of the disease. Monitoring with VHIT is a new diagnosys arm to avoid complications. No references of diplopia postlaberintectomy was collected on medical literature. It´s very important control ocular movements by a recording metod or Frenzel glasses. Conclussion: Intratimpanic therapy is a secure metod. A diplopia postlaberinthectomy is undiagnosed. Usually no speciffic treathment is required. We have to use all recurses to detect a earl abolition of vestible and use minimal dose of gentamicin as possible.

  13. Phospholipon 90H (P90H)-based PEGylated microscopic lipospheres delivery system for gentamicin:an antibiotic evaluation

    Institute of Scientific and Technical Information of China (English)

    Mumuni Audu Momoh; Charles Okechukwu Esimone

    2012-01-01

    Objective: To formulate gentamicin liposphere by solvent-melting method using lipids and polyethylene glycol 4 000 (PEG-4 000) for oral administration. Methods: Gentamicin lipospheres were prepared by melt-emulsification using 30% w/w Phospholipon® 90H in Beeswax as the lipid matrix containing PEG-4 000. These lipospheres were characterized by evaluating on encapsulation efficiency, loading capacity, change in pH and the release profile. Antimicrobial activities were evaluated against Escherichia coli, Pseudomonas aeruginosa, Salmonella paratyphii and Staphylococcus aureus using the agar diffusion method. Results:Photomicrographs revealed spherical particles within a micrometer range with minimal growth after 1 month. The release of gentamicin in vitro varied widely with the PEG-4 000 contents. Moreover, significant (P>0.05) amount of gentamicin was released in vivo from the formulation. The encapsulation and loading capacity were all high, indicating the ability of the lipids to take up the drug. The antimicrobial activities were very high especially against Pseudomonas compare to other test organisms. This strongly suggested that the formulation retain its bioactive characteristics. Conclusions: This study strongly suggest that the issue of gentamicin stability and poor absorption in oral formulation could be adequately addressed by tactical engineering of lipid drug delivery systems such as lipospheres.

  14. On the Enhanced Antibacterial Activity of Antibiotics Mixed with Gold Nanoparticles

    Directory of Open Access Journals (Sweden)

    Shantrokha AN

    2009-01-01

    Full Text Available Abstract The bacterial action of gentamicin and that of a mixture of gentamicin and 15-nm colloidal-gold particles onEscherichia coliK12 was examined by the agar-well-diffusion method, enumeration of colony-forming units, and turbidimetry. Addition of gentamicin to colloidal gold changed the gold color and extinction spectrum. Within the experimental errors, there were no significant differences in antibacterial activity between pure gentamicin and its mixture with gold nanoparticles (NPs. Atomic absorption spectroscopy showed that upon application of the gentamicin-particle mixture, there were no gold NPs in the zone of bacterial-growth suppression in agar. Yet, free NPs diffused into the agar. These facts are in conflict with the earlier findings indicating an enhancement of the bacterial activity of similar gentamicin–gold nanoparticle mixtures. The possible causes for these discrepancies are discussed, and the suggestion is made that a necessary condition for enhancement of antibacterial activity is the preparation of stable conjugates of NPs coated with the antibiotic molecules.

  15. Intratympanic therapy in Meniere's syndrome or disease: up to date evidence for clinical practice.

    Science.gov (United States)

    Syed, M I; Ilan, O; Nassar, J; Rutka, J A

    2015-12-01

    Meniere's syndrome or disease (MS/D) is typically characterised by episodic vertigo, aural fullness, tinnitus and fluctuating hearing loss. There are multiple options available for treatment with variation in consensus on the best intervention. To evaluate the evidence on the efficacy of intratympanic therapies [steroids, gentamicin, antivirals and other therapies] on the frequency and severity of vertigo and other symptoms of MS/D. A literature search was performed on AMED, EMBASE, HMIC, MEDLINE, PsycINFO, BNI, CINAHL, HEALTH BUSINESS ELITE, CENTRAL and Cochrane Ear, Nose and Throat disorders group trials register using various MeSH. The search was restricted to English and human subjects, and the last date of search was December 2014. Randomised controlled trials of intratympanic therapies [steroids, gentamicin antivirals and latanoprost] versus a placebo or another treatment. We analysed 8 RCT's comparing intratympanic steroids, gentamicin, ganciclovir (antiviral) and latanoprost versus another form of intratympanic treatment or placebo. On the basis of 6 RCT's (n = 242), there is evidence to support the effectiveness of intratympanic steroids and gentamicin to control symptoms of vertigo in MS/D albeit with a risk of hearing loss with gentamicin. However, there was no consensus found on doses or treatment protocols. There was no evidence to support the use of other forms of intratympanic therapy (antivirals and latanoprost) in MS/D. © 2015 John Wiley & Sons Ltd.

  16. Antimicrobial susceptibility testing of Haemophilus parainfluenzae by a kinetic killing-curve method.

    Science.gov (United States)

    Jemsek, J G; Martin, R R; Greenberg, S B; Gentry, L O

    1980-03-01

    A kinetic killing-curve method, designed to mimic several aspects of clinical therapy in endocarditis, was used to test 10 strains of Haemophilus parainfluenzae against 28 antibiotic regimens. In an effort to simulate changing in vivo levels of antibiotic in serum, concentrations of three penicillins, three cephalosporins, gentamicin, and chloramphenicol were sequentially adjusted over a 12-hr period. Against six beta-lactamase-negative strains, gentamicin in combination with penicillin or cephalosporin invariably resulted in an additive or synergistic effect. Chloramphenicol and a penicillin or cephalosporin usually displayed an indifferent effect, but chloramphenicol was often antagonistic when combined with gentamicin. With four beta-lactamase-positive strains, variable responses were noted to penicillin-aminoglycoside combinations; cephalosporin-aminoglycoside combinations were usually synergistic. This dynamic approach to killing-curve studies may be more appropriate than a static system for in vitro examination of the effect of antimicrobial combinations against selected organisms.

  17. Synergistic activity of coriander oil and conventional antibiotics against Acinetobacter baumannii.

    Science.gov (United States)

    Duarte, A; Ferreira, S; Silva, F; Domingues, F C

    2012-02-15

    In this study we investigated the existence of synergistic antibacterial effect between coriander (Coriandrum sativum L.) essential oil and six different antibacterial drugs (cefoperazone, chloramphenicol, ciprofloxacin, gentamicin, tetracycline and piperacillin). The antibacterial activity of coriander oil was assessed using microdilution susceptibility testing and synergistic interaction by checkerboard assays. The association of coriander essential oil with chloramphenicol, ciprofloxacin, gentamicin and tetracycline against Acinetobacter baumannii showed in vitro effectiveness, which is an indicator of a possible synergistic interaction against two reference strains of A. baumannii (LMG 1025 and LMG 1041) (FIC index from 0.047 to 0.375). However, when tested the involvement between coriander essential oil and piperacillin or cefoperazone, the isobolograms and FIC index showed an additive interaction. The in vitro interaction could improve the antimicrobial effectiveness of ciprofloxacin, gentamicin and tetracycline and may contribute to resensitize A. baumannii to the action of chloramphenicol.

  18. Voltammetric estimation of the content of antibiotics in veterinary preparations

    Directory of Open Access Journals (Sweden)

    Slepchenko Galina

    2016-01-01

    Full Text Available The voltammetric method for determination of tylosin tartrate, gentamicin sulfate, and cefalexin in veterinary preparations was for the first time developed. Electrochemical behavior of these antibiotics on the mercury film electrode was studied, and the working conditions (background electrolyte, deposition potential were defined for getting analytical signals using the voltammetry. The methods of real objects preparation for determination of tylosin tartrate, gentamicin sulfate, and cefalexin were offered. The techniques for the voltammetric determination of antibiotics in the veterinary preparations may be used in cefalexin ranging from 0.1 to 2.0 g/dm3, tylosin tartrate in the range from 0.1 to 1.7 g/dm3, and gentamicin sulfate from 0.1 to 1.5 g/dm3 (Sr is not more than 25 %

  19. Effects of antibiotics on the contractility and Ca2+ transients of rat cardiac myocytes.

    Science.gov (United States)

    Belus, A; White, E

    2001-01-26

    We have compared the effects of streptomycin sulphate, gentamicin sulphate and neomycin sulphate on cell shortening (our index of contractility) and intracellular Ca2+ ([Ca2+](i)) transients of rat ventricular myocytes. All three agents abolished shortening and [Ca2+](i), transients but streptomycin was significantly less potent than the other agents. The IC(50) of streptomycin was 0.37 mM for shortening and 0.78 mM for [Ca2+](i), approximately an order of magnitude greater than equivalent values for gentamicin and neomycin. Gentamicin and streptomycin shortened the action potential duration of most cells but prolonged the action potential duration of others. We therefore conclude that multiple ionic mechanisms affecting action potential duration are modulated by these antibiotics. Our observations are consistent with the negative inotropic effect of antibiotics being caused by a decrease in Ca2+ influx causing a reduction in the [Ca2+](i) transient.

  20. Simultaneous detection of both nitric oxide and reactive oxygen species in guinea pig vestibular sensory cells.

    Science.gov (United States)

    Takumida, Masaya; Anniko, Matti

    2002-01-01

    Gentamicin-induced production of reactive oxygen species (ROS) and of nitric oxide (NO) in the vestibular end organs of the guinea pig was investigated by applying two new fluorescence indicators, 4,5-diaminofluorescein diacetate for direct detection of NO and dihydrotetramethylrosamine for ROS. The vestibular sensory cells produced both NO and ROS after exposure to gentamicin. A nonspecific inhibitor of NO synthase, L-NAME, inhibited the production of NO but did not appear to affect the production of ROS following exposure to gentamicin. In contrast, a radical scavenger, D-methionine, or the neurotrophin BDNF suppressed the production of ROS, in turn stimulating NO production. These findings could indicate that both NO and ROS play an important role in aminoglycoside ototoxicity. Copyright 2002 S. Karger AG, Basel

  1. A biodegradable thermoset polymer made by esterification of citric acid and glycerol.

    Science.gov (United States)

    Halpern, Jeffrey M; Urbanski, Richard; Weinstock, Allison K; Iwig, David F; Mathers, Robert T; von Recum, Horst A

    2014-05-01

    A new biomaterial, a degradable thermoset polymer, was made from simple, economical, biocompatable monomers without the need for a catalyst. Glycerol and citric acid, nontoxic and renewable reagents, were crosslinked by a melt polymerization reaction at temperatures from 90 to 150°C. Consistent with a condensation reaction, water was determined to be the primary byproduct. The amount of crosslinking was controlled by the reaction conditions, including temperature, reaction time, and ratio between glycerol and citric acid. Also, the amount of crosslinking was inversely proportional to the rate of degradation. As a proof-of-principle for drug delivery applications, gentamicin, an antibiotic, was incorporated into the polymer with preliminary evaluations of antimicrobial activity. The polymers incorporating gentamicin had significantly better bacteria clearing of Staphylococcus aureus compared to non-gentamicin gels for up to 9 days.

  2. [Safety evaluation of micronomicin VIII. Teratogenicity studies in rabbits after intravenous injection].

    Science.gov (United States)

    Hara, T; Fujita, T; Takahashi, H; Deguchi, T

    1983-11-01

    Micronomicin (MCR) is a new aminoglycoside antibiotic produced by Micromonospora sagamiensis var. nonreducans which was isolated from soil collected at Sagamihara City by Nara et al. This antibiotic shows a close similarity to gentamicin C components in physical and chemical properties. The antibacterial activity of MCR is broad-spectrum and almost equal to that of gentamicin C complex. MCR exhibits particularly high activity against Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc. as well as against some Pseudomonas aeruginosa strains resistant to gentamicin C1a. Teratogenicity studies of MCR in rabbits were carried out by intravenous injection for safety evaluation (Dose; 25, 50 mg/kg and 70 mg/kg). The results of studies are as follows. Fetal malformation attributable to MCR was not observed at any dose. There was no adverse effect on new borns at any dose.

  3. [Safety evaluation of micronomicin. III. Teratogenicity studies in rats].

    Science.gov (United States)

    Hara, T; Nishikawa, S; Miyazaki, H; Ohguro, Y

    1983-01-01

    Micronomicin (MCR) is a new aminoglycoside antibiotic produced by Micromonospora sagamiensis var. nonreducans which was isolated from soil collected at Sagamihara by Nara et al. The purified antibiotic showed a close similarity to gentamicin C complex in physical and chemical properties. The antibacterial activity of MCR is broad-spectrum and almost equal to that of gentamicin C complex. MCR exhibits particularly high activity against Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc. and high activity against some Pseudomonas aeruginosa strains resistant to gentamicin C1a. Teratogenicity studies of MCR in rats were carried out by intravenous injection for safety evaluation (Dose; 25, 50 mg/kg and 75 mg/kg). The results of studies are as follows. 1. Fetal malformation attributable to MCR was not observed at any dose. 2. Suppression of maternal weight gain was observed at the dose levels of 50 mg/kg and over. 3. There was no adverse effect on new borns at any dose.

  4. Early transcriptional response to aminoglycoside antibiotic suggests alternate pathways leading to apoptosis of sensory hair cells in the mouse inner ear

    Directory of Open Access Journals (Sweden)

    Neil eSegil

    2015-05-01

    Full Text Available Aminoglycoside antibiotics are the drug of choice for treating many bacterial infections, but their administration results in hearing loss in nearly one fourth of the patients who receive them. Several biochemical pathways have been implicated in aminoglycoside antibiotic ototoxicity; however, little is known about how hair cells respond to aminoglycoside antibiotics at the transcriptome level. Here we have investigated the genome-wide response to the aminoglycoside antibiotic gentamicin. Using organotypic cultures of the perinatal organ of Corti, we performed RNA sequencing using cDNA libraries obtained from FACS-purified hair cells. Within 3 hours of gentamicin treatment, the messenger RNA level of more than three thousand genes in hair cells changed significantly. Bioinformatic analysis of these changes highlighted several known signal transduction pathways, including the JNK pathway and the NF-κB pathway, in addition to genes involved in the stress response, apoptosis, cell cycle control, and DNA damage repair. In contrast, only 698 genes, mainly involved in cell cycle and metabolite biosynthetic processes, were significantly affected in the non-hair cell population. The gene expression profiles of hair cells in response to gentamicin share a considerable similarity with those previously observed in gentamicin-induced nephrotoxicity. Our findings suggest that previously observed early responses to gentamicin in hair cells in specific signaling pathways are reflected in changes in gene expression. Additionally, the observed changes in gene expression of cell cycle regulatory genes indicate a disruption of the postmitotic state, which may suggest an alternative pathway regulating gentamicin-induced hair cell death. This work provides a more comprehensive view of aminoglycoside antibiotic ototoxicity, and thus contribute to identifying potential pathways or therapeutic targets to alleviate this important side effect of aminoglycoside

  5. Long-term leptin treatment exerts a pro-apoptotic effect on renal tubular cells via prostaglandin E2 augmentation.

    Science.gov (United States)

    Hsu, Yung-Ho; Cheng, Chung-Yi; Chen, Yen-Cheng; Chen, Tso-Hsiao; Sue, Yuh-Mou; Tsai, Wei-Lun; Chen, Cheng-Hsien

    2012-08-15

    Adipokine leptin reportedly acts on the kidney in pathophysiological states. However, the influence of leptin on renal tubular epithelial cells is still unclear. Gentamicin, a widely used antibiotic for the treatment of bacterial infection, can cause nephrotoxicity. This study aims to investigate the influence of long-term leptin treatment on gentamicin-induced apoptosis in rat renal tubular cells (NRK-52E) and mice. We monitored apoptosis and molecular mechanisms using annexin V/ propidium iodide staining and small interfering RNA transfection. In NRK-52E cells, leptin reduced gentamicin-induced apoptosis at 24h, but significantly increased apoptosis at 48 h. Long-term treatment of leptin decreased Bcl-x(L) expression and increased caspase activity in gentamicin-treated NRK-52E cells. Leptin also increased the expression of cyclooxygenase-2 (COX-2) and its product, prostaglandin E(2) (PGE(2)), in a dose-dependent manner. The COX-2 inhibitor, NS398 (N-[2-(Cyclohexyloxy)-4- nitrophenyl]methanesulfonamide), blocked PGE(2) augmentation and the pro-apoptotic effects of leptin. The addition of PGE(2) recovered the pro-apoptotic effect of leptin in NS398-treated NRK-52E cells. In a mouse animal model, a 10 day leptin treatment significantly increased gentamicin-induced apoptotic cells in proximal tubules. NS398 treatment inhibited this in vivo pro-apoptotic effect of leptin. Results reveal that long-term elevation of leptin induces COX-2-mediated PGE(2) augmentation in renal tubular cells, and then increases these cells' susceptibility to gentamicin-induced apoptosis.

  6. Early In Vitro and In Vivo Development of High-Level Daptomycin Resistance Is Common in Mitis Group Streptococci after Exposure to Daptomycin

    Science.gov (United States)

    García-de-la-Mària, Cristina; Pericas, Juan M.; del Río, Ana; Castañeda, Ximena; Vila-Farrés, Xavier; Armero, Yolanda; Espinal, Paula A.; Cervera, Carlos; Soy, Dolors; Falces, Carlos; Ninot, Salvador; Almela, Manel; Mestres, Carlos A.; Gatell, Jose M.; Vila, Jordi; Moreno, Asuncion; Marco, Francesc

    2013-01-01

    The development of high-level daptomycin resistance (HLDR; MIC of ≥256 mg/liter) after exposure to daptomycin has recently been reported in viridans group streptococcus (VGS) isolates. Our study objectives were as follows: to know whether in vitro development of HLDR after exposure to daptomycin was common among clinical isolates of VGS and Streptococcus bovis; to determine whether HLDR also developed during the administration of daptomycin to treat experimental endocarditis caused by the daptomycin-susceptible, penicillin-resistant Streptococcus mitis strain S. mitis 351; and to establish whether combination with gentamicin prevented the development of HLDR in vitro and in vivo. In vitro studies were performed with 114 VGS strains (mitis group, 92; anginosus group, 10; mutans group, 8; and salivarius group, 4) and 54 Streptococcus bovis strains isolated from 168 consecutive patients with infective endocarditis diagnosed between 1995 and 2010. HLDR was only observed after 24 h of exposure to daptomycin in 27% of the mitis group, including 27% of S. mitis isolates, 47% of S. oralis isolates, and 13% of S. sanguis isolates. In our experimental model, HLDR was detected in 7/11 (63%) and 8/12 (67%) isolates recovered from vegetations after 48 h of daptomycin administered at 6 mg/kg of body weight/24 h and 10 mg/kg/24 h, respectively. In vitro, time-kill experiments showed that daptomycin plus gentamicin was bactericidal against S. mitis 351 at tested concentrations of 0.5 and 1 times the MIC and prevented the development of HLDR. In vivo, the addition of gentamicin at 1 mg/kg/8 h to both daptomycin arms prevented HLDR in 21 out of 23 (91%) rabbits. Daptomycin plus gentamicin was at least as effective as vancomycin plus gentamicin. In conclusion, HLDR develops rapidly and frequently in vitro and in vivo among mitis group streptococci. Combining daptomycin with gentamicin enhanced its activity and prevented the development of HLDR in most cases. PMID:23478959

  7. Hair cell regeneration or the expression of related factors that regulate the fate specification of supporting cells in the cochlear ducts of embryonic and posthatch chickens.

    Science.gov (United States)

    Jiang, Lingling; Jin, Ran; Xu, Jincao; Ji, Yubin; Zhang, Meiguang; Zhang, Xuebo; Zhang, Xinwen; Han, Zhongming; Zeng, Shaoju

    2016-02-01

    Hair cells in posthatch chickens regenerate spontaneously through mitosis or the transdifferentiation of supporting cells in response to antibiotic injury. However, how embryonic chicken cochleae respond to antibiotic treatment remains unknown. This study is the first to indicate that unlike hair cells in posthatch chickens, the auditory epithelium was free from antibiotic injury (25-250 mg gentamicin/kg) in embryonic chickens, although FITC-conjugated gentamicin actually reached embryonic hair cells. Next, we examined and counted the cells and performed labeling for BrdU, Sox2, Atoh1/Math1, PV or p27(kip1) (triple or double labeling) in the injured cochlea ducts after gentamicin treatment at 2 h (h), 15 h, 24 h, 2 days (d), 3 d and 7 d after BrdU treatment in posthatch chickens. Our results indicated that following gentamicin administration, proliferating cells (BrdU+) were labeled for Atoh1/Math1 in the damaged areas 3d after gentamicin administration, whereas hair cells (PV+) renewed through mitosis (BrdU+) or direct transdifferentiation (BrdU-) were evident only after 5 d of gentamicin administration. In addition, Sox2 expression was up-regulated in triggered supporting cells at an early stage of regeneration, but stopped at the advent of mature hair cells. Our study also indicated that p27(kip1) was expressed in both hair cells and supporting cells but was down-regulated in a subgroup of the supporting cells that gave rise to hair cells. These data and the obtained dynamic changes of the cells labeled for BrdU, Sox2, Atoh1/Math1, PV or p27(kip1) are useful for understanding supporting cell behaviors and their fate specification during hair cell regeneration.

  8. Mammalin cochlear supporting cells transdifferentiation into outer hair cells

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective To study the recovery of the outer hair cells in the bat cochlea after gentamicin exposure. Methods Bats were injected with a daily dose of gentamicin for 15 consecutive days and bromodeoxyuridine (BrdU) was given from day 16 to day 40 of this recovery phase. Hearing was assessed by overt acoustic behavior and auditory brainstem responses analysis, which was performed one day prior to the first injection and a day after the last injection (day 16). On day 40 animals were sacrificed for detection o...

  9. N-Acetylcysteine in the prevention of ototoxicity

    DEFF Research Database (Denmark)

    Tepel, Martin

    2007-01-01

    Prevention of ototoxicity after the administration of aminoglycoside antibiotics has been notably difficult, in particular in patients with chronic kidney disease. Feldman et al. report that oral administration of 600 mg N-acetylcysteine twice daily significantly ameliorates gentamicin-induced ot......Prevention of ototoxicity after the administration of aminoglycoside antibiotics has been notably difficult, in particular in patients with chronic kidney disease. Feldman et al. report that oral administration of 600 mg N-acetylcysteine twice daily significantly ameliorates gentamicin......-induced ototoxicity in hemodialysis patients. That approach may help to prevent aminoglycoside-induced hearing loss in these high-risk patients in daily practice....

  10. Acanthamoeba castellanii an environmental host for Shigella dysenteriae and Shigella sonnei.

    Science.gov (United States)

    Saeed, Amir; Abd, Hadi; Edvinsson, Benjamin; Sandström, Gunnar

    2009-01-01

    The interaction between Shigella dysenteriae or Shigella sonnei and Acanthamoeba castellanii was studied by viable counts, gentamicin assay and electron microscopy. The result showed that Shigella dysenteriae or Shigella sonnei grew and survived in the presence of amoebae for more than 3 weeks. Gentamicin assay showed that the Shigella were viable inside the Acanthamoeba castellanii which was confirmed by electron microscopy that showed the Shigella localized in the cytoplasm of the Acanthamoeba castellanii. In conclusion, the relationship between Shigella dysenteriae and Shigella sonnei with Acanthamoeba castellanii is symbiotic, and accordingly free-living amoebae may serve as a transmission reservoir for Shigella in water.

  11. Activation of the SOS response increases the frequency of small colony variants

    DEFF Research Database (Denmark)

    Vestergaard, Martin; Paulander, Wilhelm Erik Axel; Ingmer, Hanne

    2015-01-01

    with different mechanism of action influence the formation of SCVs that are resistant to otherwise lethal concentrations of the aminoglycoside, gentamicin. We found that exposure of S. aureus to fluoroquinolones and mitomycin C increased the frequency of gentamicin resistant SCVs, while other antibiotic classes...... failed to do so. The higher proportion of SCVs in cultures exposed to fluoroquinolones and mitomycin C compared to un-exposed cultures correlate with an increased mutation rate monitored by rifampicin resistance and followed induction of the SOS DNA damage response. CONCLUSION: Our observations suggest...

  12. Genome-Wide Identification of Antimicrobial Intrinsic Resistance Determinants in Staphylococcus aureus

    DEFF Research Database (Denmark)

    Vestergaard, Martin; Leng, Bingfeng; Haaber, Jakob

    2016-01-01

    The emergence of antimicrobial resistance severely threatens our ability to treat bacterial infections. While acquired resistance has received considerable attention, relatively little is known of intrinsic resistance that allows bacteria to naturally withstand antimicrobials. Gene products......, atpA, atpB, atpG and atpH, reduced the minimum inhibitory concentration (MIC) of gentamicin 16-fold. To elucidate the potential of the screen, we examined treatment efficacy in the Galleria mellonella infection model. Gentamicin efficacy was significantly improved, when treating larvae infected...

  13. Effect of vaginal douching and different semen extenders on bacterial load and fertility in turkeys.

    Science.gov (United States)

    Omprakash, A V; Venkatesh, G

    2006-08-01

    1. A study on artificial insemination of Beltsville Small White turkeys investigated the effect on bacterial load and fertility of vaginal douching with diluents containing Gentamicin 400 microg/ml and different semen extenders. 2. Irrespective of the extenders used, vaginal douching with Gentamicin reduced the microbial load of the vagina with resultant improvement in fertility and hatchability and corresponding reduction in embryonic mortality. 3. Eggs from hens inseminated with semen extended with Beltsville Poultry Semen Extender (BPSE) diluent along with vaginal douching showed a trend towards higher per cent fertility and per cent hatchability of total and fertile eggs set compared to other extenders, though this was non-significant.

  14. Tris-EDTA no teste de sensibilidade antimicrobiana in vitro em amostras de Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Tanaka E.M.

    2002-01-01

    Full Text Available In vitro antimicrobial susceptibility of strains of Pseudomonas aeruginosa by standard diffusion disk test and a modified method, by the addition Tris-EDTA, was evaluated. Increase in sensitivity of agent using modified method was observed mainly in aminoglycosides (amikacin, gentamicin, tobramycin, quinolones (ofloxacin and norfloxacin and cephalosporins (cefoperazone and ceftazidime groups. by standard diffusion disk test and a modified method, by the addition Tris-EDTA, was evaluated. Increase in sensitivity of agent using modified method was observed mainly in aminoglycosides (amikacin, gentamicin, tobramycin, quinolones (ofloxacin and norfloxacin and cephalosporins (cefoperazone and ceftazidime groups.

  15. Mitochondrial 12S Ribosomal RNA A1555G Mutation Associated with Cardiomyopathy and Hearing Loss following High-Dose Chemotherapy and Repeated Aminoglycoside Exposure

    DEFF Research Database (Denmark)

    Skou, Anne-Sofie; Tranebjærg, Lisbeth; Jensen, Tim

    2014-01-01

    A 19-month-old girl with the A1555G mitochondrial mutation in the 12S ribosomal RNA gene and acute myelogenous leukemia developed dilated cardiomyopathy and bilateral sensorineural hearing loss before undergoing allogeneic stem cell transplantation. She had received gentamicin during episodes...

  16. Prosthetic valve endocarditis caused by Acinetobacter calcoaceticus subsp. lwoffi.

    OpenAIRE

    Weinberger, I. (Ingeburg); Davidson, E.; Rotenberg, Z; Fuchs, J; Agmon, J

    1987-01-01

    Acinetobacter spp. are uncommon etiologic agents of prosthetic valve endocarditis. Two patients with Acinetobacter calcoaceticus subsp. lwoffi prosthetic valve endocarditis are described. The patients were successfully treated with antibiotics (cefotaxime sodium and gentamicin sulfate); thus, we suggest medical treatment rather than early valve replacement in this particular type of infection.

  17. Aminoglycoside Resistance and Susceptibility Testing Errors in Acinetobacter baumannii-calcoaceticus Complex

    Science.gov (United States)

    2010-04-01

    evaluated AMEs detected by a combination of phenotypic inference and DNA hybridization in 1,189 Acineto- bacter sp. isolates from South Africa, Europe...resistance is prevalent, amikacin was used in greater quantities than gentamicin and tobramycin. While high rates of amikacin resistance in Acineto- bacter

  18. Vertigo Perception and Quality of Life in Patients after Surgical Treatment of Vestibular Schwannoma with Pretreatment Prehabituation by Chemical Vestibular Ablation.

    Science.gov (United States)

    Čada, Zdeněk; Balatková, Zuzana; Chovanec, Martin; Čakrt, Ondřej; Hrubá, Silvie; Jeřábek, Jaroslav; Zvěřina, Eduard; Profant, Oliver; Fík, Zdeněk; Komarc, Martin; Betka, Jan; Kluh, Jan; Černý, Rudolf

    2016-01-01

    Surgical removal of vestibular schwannoma causes acute vestibular symptoms, including postoperative vertigo and oscillopsia due to nystagmus. In general, the dominant symptom postoperatively is vertigo. Preoperative chemical vestibular ablation can reduce vestibular symptoms postoperatively. We used 1.0 mL of 40 mg/mL nonbuffered gentamicin in three intratympanic installations over 2 days, 2 months preoperatively in 10 patients. Reduction of vestibular function was measured by the head impulse test and the caloric test. Reduction of vestibular function was found in all gentamicin patient groups. After gentamicin vestibular ablation, patients underwent home vestibular exercising for two months. The control group consisted of 10 patients who underwent only home vestibular training two months preoperatively. Postoperative rates of recovery and vertigo in both groups were evaluated with the Glasgow Benefit Inventory (GBI), the Glasgow Health Status Inventory (GHSI), and the Dizziness Handicap Inventory questionnaires, as well as survey of visual symptoms by specific questionnaire developed by us. There were no statistically significant differences between both groups with regard to the results of questionnaires. Patients who received preoperative gentamicin were more resilient to optokinetic and optic flow stimulation (p < 0.05). This trial is registered with clinical study registration number NCT02963896.

  19. Characteristics of Tularemia in Kosovo 2010

    Directory of Open Access Journals (Sweden)

    Mr.Sc. Izet Sadiku

    2011-12-01

    Conclusions: In this late decade in our country, tularemia continues to be a disease that represents a healthcare problem. Glandular forms of tularemia dominate in Kosovo. Treatment with gentamicin has had good effects. Incision and drainage of the inflamed glands has shown to be a good method in accelerating the recovery of patient. Prophylaxis has to be applied for prevention of the disease.

  20. A teratological study of aminoglycoside antibiotic treatment during pregnancy.

    Science.gov (United States)

    Czeizel, A E; Rockenbauer, M; Olsen, J; Sørensen, H T

    2000-01-01

    The aim of this study was to investigate the teratogenicity of aminoglycoside antibiotics, such as parenteral gentamicin, streptomycin, tobramycin and oral neomycin, during pregnancy. Pair analysis of cases with congenital abnormalities and matched healthy controls was carried out. The setting was the population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-96. In total, 38,151 pregnant women who had newborn infants without any defects (control group) and 22,865 pregnant women who had foetuses or newborns with congenital abnormalities were included in the study. 38 (0.16%) and 42 (0.11%) pregnant women in the case and control groups, respectively, were treated with the aminoglycosides studied. A teratogenic potential of gentamicin and neomycin was not indicated by a comparison of the occurrence of aminoglycoside antibiotic treatments in the total control group as referent with the figures of different congenital abnormality groups. In addition, the case-control pair analysis during the second-third months of pregnancy did not show a teratogenic risk of gentamicin and neomycin. The conclusion of this study is that treatment with parenteral gentamicin and oral neomycin during pregnancy presents no detectable teratogenic risk to the foetus, when restricted to structural developmental disturbances.

  1. Collagen/chitosan based two-compartment and bi-functional dermal scaffolds for skin regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Feng [Department of Plastic Surgery and Burns, Shenzhen Second People' s Hospital, Shenzhen 518035 (China); Wang, Mingbo [Key Laboratory of Biomedical Materials and Implants, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057 (China); She, Zhending [Key Laboratory of Biomedical Materials and Implants, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057 (China); Shenzhen Lando Biomaterials Co., Ltd., Shenzhen 518057 (China); Fan, Kunwu; Xu, Cheng [Department of Plastic Surgery and Burns, Shenzhen Second People' s Hospital, Shenzhen 518035 (China); Chu, Bin; Chen, Changsheng [Key Laboratory of Biomedical Materials and Implants, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057 (China); Shi, Shengjun, E-mail: shengjunshi@yahoo.com [The Burns Department of Zhujiang Hospital, Southern Medical University, Guangzhou 510280 (China); Tan, Rongwei, E-mail: tanrw@landobiom.com [Key Laboratory of Biomedical Materials and Implants, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057 (China); Shenzhen Lando Biomaterials Co., Ltd., Shenzhen 518057 (China)

    2015-07-01

    Inspired from the sophisticated bilayer structures of natural dermis, here, we reported collagen/chitosan based two-compartment and bi-functional dermal scaffolds. Two functions refer to mediating rapid angiogenesis based on recombinant human vascular endothelial growth factor (rhVEGF) and antibacterial from gentamicin, which were encapsulated in PLGA microspheres. The gentamicin and rhVEGF encapsulated PLGA microspheres were further combined with collagen/chitosan mixtures in low (lower layer) and high (upper layer) concentrations, and molded to generate the two-compartment and bi-functional scaffolds. Based on morphology and pore structure analyses, it was found that the scaffold has a distinct double layered porous and connective structure with PLGA microspheres encapsulated. Statistical analysis indicated that the pores in the upper layer and in the lower layer have great variations in diameter, indicative of a two-compartment structure. The release profiles of gentamicin and rhVEGF exceeded 28 and 49 days, respectively. In vitro culture of mouse fibroblasts showed that the scaffold can facilitate cell adhesion and proliferation. Moreover, the scaffold can obviously inhibit proliferation of Staphylococcus aureus and Serratia marcescens, exhibiting its unique antibacterial effect. The two-compartment and bi-functional dermal scaffolds can be a promising candidate for skin regeneration. - Highlights: • The dermal scaffold is inspired from the bilayer structures of natural dermis. • The dermal scaffold has two-compartment structures. • The dermal scaffold containing VEGF and gentamicin encapsulated PLGA microspheres • The dermal scaffold can facilitate cell adhesion and proliferation.

  2. Late-Onset Enterobacter cloacae Sepsis in Very-Low-Birth-Weight Neonates: Experience in a Medical Center

    Directory of Open Access Journals (Sweden)

    Hsiao-Neng Chen

    2009-02-01

    Conclusion: E. cloacae infection in VLBW neonates usually presents with non-specific symptoms and signs. Early recognition of sepsis and empirical combination of piperacillin (or piperacillin and tazobactam and gentamicin (or amikacin may be useful for treatment of sepsis caused by this highly virulent pathogen.

  3. Enterococcus faecalis infective endocarditis

    DEFF Research Database (Denmark)

    Dahl, Anders; Rasmussen, Rasmus V; Bundgaard, Henning;

    2013-01-01

    Because of the nephrotoxic effects of aminoglycosides, the Danish guidelines on infective endocarditis were changed in January 2007, reducing gentamicin treatment in enterococcal infective endocarditis from 4 to 6 weeks to only 2 weeks. In this pilot study, we compare outcomes in patients with En...... with Enterococcus faecalis infective endocarditis treated in the years before and after endorsement of these new recommendations....

  4. Performance evaluation of nanoclay enriched anti-microbial hydrogels for biomedical applications

    Directory of Open Access Journals (Sweden)

    Sonali Karnik

    2016-02-01

    Full Text Available A major factor contributing to the failure of orthopedic and orthodontic implants is post-surgical infection. Coating metallic implant surfaces with anti-microbial agents has shown promise but does not always prevent the formation of bacterial biofilms. Furthermore, breakdown of these coatings within the human body can cause release of the anti-microbial drugs in an uncontrolled or unpredictable fashion. In this study, we used a calcium alginate and calcium phosphate cement (CPC hydrogel composite as the base material and enriched these hydrogels with the anti-microbial drug, gentamicin sulfate, loaded within a halloysite nanotubes (HNTs. Our results demonstrate a sustained and extended release of gentamicin from hydrogels enriched with the gentamicin-loaded HNTs. When tested against the gram-negative bacteria, the hydrogel/nanoclay composites showed a pronounced zone of inhibition suggesting that anti-microbial doped nanoclay enriched hydrogels can prevent the growth of bacteria. The release of gentamicin sulfate for a period of five days from the nanoclay-enriched hydrogels would supply anti-microbial agents in a sustained and controlled manner and assist in preventing microbial growth and biofilm formation on the titanium implant surface. A pilot study, using mouse osteoblasts, confirmed that the nanoclay enriched surfaces are also cell supportive as osteoblasts readily, proliferated and produced a type I collagen and proteoglycan matrix.

  5. Structure and function of the human megalin receptor

    DEFF Research Database (Denmark)

    Dagil, Robert

    of aminoglycosides during antibacterial treatment, which can lead to nephro- and ototoxic side-effects. This thesis presents new insights into the structure-function relation of the megalin receptor. The interaction between megalin and several natural protein ligands as well as the aminoglycoside gentamicin...

  6. Infectious Complications of Open Type III Tibial Fractures among Combat Casualties

    Science.gov (United States)

    2007-08-15

    13) 10 20 (M, IIIb) ESBL Klebsiella pneumoniae (3) Ampicillin, gentamicin, imipenem-cilastatin (2)d MSSA (16) Union (25) 11 27 (M, IIIb) Acb (15...CoNS, coagulase-negative staphylococci; ESBL , extended-spectrum b-lactamase–producing; M, male; MRSA, methicillin resistant Staph- ylococcus aureus

  7. Stability of antibiotics and amino acids in two synthetic L-amino acid solutions commonly used for total parenteral nutrition in children

    DEFF Research Database (Denmark)

    Colding, H; Andersen, G E

    1978-01-01

    The stability and interaction at 29 degrees C of ampicillin, carbenicillin, gentamicin, and polymyxin B were examined in a common electrolyte solution, invertose darrow, and in two synthetic l-amino acid solutions, one commercial (vamin with fructose; Vitrum) and the other a neonatal preparation ...

  8. Ciprofloxacin treatment of bacterial peritonitis associated with chronic ambulatory peritoneal dialysis caused by Neisseria cinerea.

    Science.gov (United States)

    Taegtmeyer, M; Saxena, R; Corkill, J E; Anijeet, H; Parry, C M

    2006-08-01

    Bacterial peritonitis is a well-recognized complication of chronic ambulatory peritoneal dialysis (CAPD) in patients with end-stage renal failure. We present a case of peritonitis due to an unusual pathogen, Neisseria cinerea, unresponsive to the standard intraperitoneal (i.p.) vancomycin and gentamicin, which responded rapidly to oral ciprofloxacin.

  9. In vitro susceptibility of Citrobacter species to various antimicrobial agents.

    OpenAIRE

    Samonis, G.; Ho, D H; Gooch, G F; Rolston, K V; Bodey, G P

    1987-01-01

    The in vitro activities of 16 antimicrobial agents against 14 clinical isolates of Citrobacter diversus and 27 isolates of Citrobacter freundii were studied. C. freundii isolates were more resistant, being susceptible only to amikacin, netilmicin, gentamicin, imipenem, ciprofloxacin, and enoxacin. C. diversus isolates were susceptible to many more of the agents tested.

  10. The Phage Lysin PlySs2 Decolonizes Streptococcus suis from Murine Intranasal Mucosa

    Science.gov (United States)

    Gilmer, Daniel B.; Schmitz, Jonathan E.; Thandar, Mya; Euler, Chad W.; Fischetti, Vincent A.

    2017-01-01

    Streptococcus suis infects pigs worldwide and may be zoonotically transmitted to humans with a mortality rate of up to 20%. S. suis has been shown to develop in vitro resistance to the two leading drugs of choice, penicillin and gentamicin. Because of this, we have pursued an alternative therapy to treat these pathogens using bacteriophage lysins. The bacteriophage lysin PlySs2 is derived from an S. suis phage and displays potent lytic activity against most strains of that species including serotypes 2 and 9. At 64 μg/ml, PlySs2 reduced multiple serotypes of S. suis by 5 to 6-logs within 1 hour in vitro and exhibited a minimum inhibitory concentration (MIC) of 32 μg/ml for a S. suis serotype 2 strain and 64 μg/ml for a serotype 9 strain. Using a single 0.1-mg dose, the colonizing S. suis serotype 9 strain was reduced from the murine intranasal mucosa by >4 logs; a 0.1-mg dose of gentamicin reduced S. suis by 5-logs. While resistance to gentamicin was induced after systematically increasing levels of gentamicin in an S. suis culture, the same protocol resulted in no observable resistance to PlySs2. Thus, PlySs2 has both broad and high killing activity against multiple serotypes and strains of S. suis, making it a possible tool in the control and prevention of S. suis infections in pigs and humans. PMID:28046082

  11. Antimicrobial resistance and in vitro biofilm-forming ability of enterococci from intensive and extensive farming broilers.

    Science.gov (United States)

    Oliveira, M; Santos, V; Fernandes, A; Bernardo, F; Vilela, C L

    2010-05-01

    Enterococci, major broiler intestinal colonizers, play a recognized role in antimicrobial resistance transmission. Several virulence mechanisms, such as biofilm expression, have been identified. Minimum inhibitory concentrations of vancomycin, enrofloxacin, oxytetracycline, streptomycin, and gentamicin and biofilm production of 34 isolates from intensive and extensive farming system broilers were evaluated. All isolates were susceptible to vancomycin. In extensive-reared broilers (n = 18), resistance to enrofloxacin, oxytetracycline, streptomycin, and gentamicin was high (83.33, 55.56, 100, and 83.33%, respectively). Intensive farming broilers (n = 16) showed a lower resistance level for enrofloxacin and streptomycin and a higher resistance level for oxytetracycline and gentamicin. The relation between antimicrobial susceptibility and farming system was not significant for all drugs tested (P > or = 0.05). Enterococci produced biofilm at 24 h (47.0%), 48 h (55.9%), and 72 h (58.8%). Resistance to gentamicin and streptomycin was related to biofilm production at all time points (P or = 0.05). Poultry are colonized by biofilm-producing and antimicrobial-resistant enterococci, independently of the farming system. Results show a relation between resistance to the majority of the drugs tested and biofilm production, which reenforces the importance of these virulence factors in animal and public health.

  12. Enzymatic method for inactivation of aminoglycosides during measurement of postantibiotic effect

    NARCIS (Netherlands)

    J.G. den Hollander (Jan); J.W. Mouton (Johan); I.A.J.M. Bakker-Woudenberg (Irma); F.P. Vleggaar (Frank); M.P.J. van Goor (Marie-Louise); H.A. Verbrugh (Henri)

    1996-01-01

    textabstractTo determine the postantibiotic effect of aminoglycosides, two methods are currently being used to remove the test drug: repeated washing and dilution. An enzymatic inactivation method of removing gentamicin and tobramycin was developed and compared with the dilution me

  13. Serogroups and antimicrobial susceptibility among Escherichia coli isolated from farmed mink (Mustela vison Schreiber) in Denmark

    DEFF Research Database (Denmark)

    Vulfson, L.; Pedersen, Karl; Chriel, M.;

    2001-01-01

    , the most frequent being O2 (11.0%). O78 (11.0%), O153 (7.1%). O25 (5.7%). O6 (4.8%). and O15 (4.8%). but diarrhoea was not associated with specific serogroups. All isolates were sensitive to enrofloxacin, neomycin, gentamicin and colistin. In contrast, considerable variations in susceptibility were found...

  14. Serogroups and antimicrobiological susceptability among Escherichia coli isolated from farmed mink (Mustela vison Schreiber) in Denmark

    DEFF Research Database (Denmark)

    Vulfson, L.; Pedersen, K.; Chriél, Mariann;

    2001-01-01

    , the most frequent being O2 (11.0%), O78 (11.0%), O153 (7.1%), O25 (5.7%), O6 (4.8%), and O15 (4.8%), but diarrhoea was not associated with specific serogroups. All isolates were sensitive to enrofloxacin, neomycin, gentamicin and colistin. In contrast, considerable variations in susceptibility were found...

  15. Serogroups and antimicrobial susceptibility among Escherichia coli isolated from farmed mink (Mustela vison Schreiber) in Denmark

    DEFF Research Database (Denmark)

    Vulfson, L.; Pedersen, Karl; Chriel, M.

    2001-01-01

    , the most frequent being O2 (11.0%). O78 (11.0%), O153 (7.1%). O25 (5.7%). O6 (4.8%). and O15 (4.8%). but diarrhoea was not associated with specific serogroups. All isolates were sensitive to enrofloxacin, neomycin, gentamicin and colistin. In contrast, considerable variations in susceptibility were found...

  16. DETERMINATION OF AMINOGLYCOSIDES IN FOOD BY FLUORESCENCE POLARIZATION IMMUNOASSAY

    OpenAIRE

    FARAFONOVA O.V.; Eremin, S. A.; ERMOLAEVA T.N.; VASILIEV S.V.

    2015-01-01

    The methodic for quantitative determination of aminoglycoside antibiotics (gentamicin, kanamycin, streptomycin, amikacin, neomycin) in food by polarization fluorescent immunoassay (FPIA) is developed. The size and structure influence of a fluorescent molecule on a fluorescence polarization degree is analyzed. Affinity constants of antibodies to compounds and tracers were estimated, optimized working concentration of tracers and antibodies that provide the maximum value of analytical signal. M...

  17. The Evolving Field of Biodefence: Therapeutic Developments and Diagnostics

    Science.gov (United States)

    2005-04-01

    atic antiviral drug cidofovir seems to be effective against many orthopoxviruses, and is potentially useful for the treatment of smallpox and...Protocol 24–48 h Vaccinia vaccine, cidofovir Tularaemia A 1–21 days >2 weeks Level A Protocol 3 days Streptomycin, gentamicin Ebola A 4–21 days 7

  18. Effect of Readthrough Treatment in Fibroblasts of Patients Affected by Lysosomal Diseases Caused by Premature Termination Codons.

    Science.gov (United States)

    Matalonga, Leslie; Arias, Ángela; Tort, Frederic; Ferrer-Cortés, Xènia; Garcia-Villoria, Judit; Coll, Maria Josep; Gort, Laura; Ribes, Antonia

    2015-10-01

    Aminoglycoside antibiotics, such as gentamicin, may induce premature termination codon (PTC) readthrough and elude the nonsense-mediated mRNA decay mechanism. Because PTCs are frequently involved in lysosomal diseases, readthrough compounds may be useful as potential therapeutic agents. The aim of our study was to identify patients responsive to gentamicin treatment in order to be used as positive controls to further screen for other PTC readthrough compounds. With this aim, fibroblasts from 11 patients affected by 6 different lysosomal diseases carrying PTCs were treated with gentamicin. Treatment response was evaluated by measuring enzymatic activity, abnormal metabolite accumulation, mRNA expression, protein localization, and cell viability. The potential effect of readthrough was also analyzed by in silico predictions. Results showed that fibroblasts from 5/11 patients exhibited an up to 3-fold increase of enzymatic activity after gentamicin treatment. Accordingly, cell lines tested showed enhanced well-localized protein and/or increased mRNA expression levels and/or reduced metabolite accumulation. Interestingly, these cell lines also showed increased enzymatic activity after PTC124 treatment, which is a PTC readthrough-promoting compound. In conclusion, our results provide a proof-of-concept that PTCs can be effectively suppressed by readthrough drugs, with different efficiencies depending on the genetic context. The screening of new compounds with readthrough activity is a strategy that can be used to develop efficient therapies for diseases caused by PTC mutations.

  19. Deciphering the resistome of the widespread P. aeruginosa ST175 international high-risk clone through whole genome sequencing

    DEFF Research Database (Denmark)

    Cabot, Gabriel; López-Causapé, Carla; Ocampo-Sosa, Alain A.

    2016-01-01

    specific ampR mutations leading to ampC overexpression, specific mutations in oprD conferring carbapenem resistance or a mexZ mutation leading to MexXY overexpression. All isolates additionally harbored an aadB gene conferring gentamicin and tobramycin resistance. Several other resistance traits were...

  20. Risk factors for extended-spectrum beta-lactamase-producing Serratia marcescens and Klebsiella pneumoniae acquisition in a neonatal intensive care unit.

    Science.gov (United States)

    Crivaro, V; Bagattini, M; Salza, M F; Raimondi, F; Rossano, F; Triassi, M; Zarrilli, R

    2007-10-01

    We investigated the molecular epidemiology of gentamicin-resistant, extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae and Serratia marcescens, and risk factors associated with their acquisition in a neonatal intensive care unit (NICU) of a university hospital in Italy. During the study period (April-November 2004), S. marcescens was responsible for six infections and 31 colonisations, while K. pneumoniae was responsible for six infections and 103 colonisations. Concurrent isolation of both organisms occurred in 24 neonates. Molecular typing identified one major pulsed-field gel electrophoresis pattern each for S. marcescens and K. pneumoniae strains isolated during the study period. An 80 kb plasmid containing bla(SHV-12), bla(TEM-1) and aac(6')-Ib genes, isolated from both S. marcescens and K. pneumoniae strains, and showing identical restriction profiles, transferred resistance to third-generation cephalosporins to a previously susceptible Escherichia coli host. Birthweight, gestational age and use of invasive devices were significantly associated with S. marcescens and K. pneumoniae acquisition on univariate analysis, while empiric antimicrobial treatment with ampicillin and gentamicin, and duration of hospital stay, proved to be the only independent risk factors. In conclusion, conjugal plasmid transfer and empiric antimicrobial therapy with ampicillin and gentamicin might have contributed to the selection and spread of gentamicin-resistant ESBL-producing Enterobacteriaceae in the NICU.

  1. BACTERIAL SPECTRUM AND PATTERN OF ANTIMICROBIAL SENSITIVITY AMONG OUTPATIENTS WITH PNEUMONIA IN A TERTIARY CARE HOSPITAL

    Directory of Open Access Journals (Sweden)

    Sushma

    2015-04-01

    Full Text Available OBJECTIVES: To outline the spectrum of bacteria causing pneumonia and the pattern of antimicrobial sensitivity in outpatients with pneumonia in a tertiary care hospital in Himachal Pradesh. METHODS: Sputum of 108 immuno competent pneumonia patients attending outpatient departments of Medicine and Pulmonary medicine of Dr. R. P. Government Medical College , Kangra at Tanda was sent for Gram staining and culture and sensitivity testing. RESULTS: Commensals were detected in most of the cases (32 , 29.6% followed by Staphylococcus aureus in 17(15.7% and Streptococcus pneumoniae in 16(14.8%. This was followed by three Gram negative organisms namely E Coli (11 , 10.2% , Pseudomonas (10 , 9.2% and Klebsiella (8 , 7.2%. No growth was obtained in 7(6.5% and other organisms were isolated in 7(6.5% specimens. Staphylococcus aureus was sensitive to vancomycin , clindamycin , cefoxitin , azithromycin and cotrimoxazole. Streptococcus pneumoniae was found to be sensitive to vancomycin , clindamycin , gentamicin , azithromycin , penicillin , cotrimoxazole , amoxicillin +clavulanic acid. Klebsiella was found to be sensitive to imipenem , azithromycin , ciprofloxacin , gentamicin and amoxicillin +clavulanic acid. E coli was sensitive to imipenem , gentamicin and amoxicillin +clavulanic acid. Pseudomonas aeruginosa was found to be sensitive to gentamicin , cefta zidime , imipenem , ticarcillin and piperacillin. CONCLUSION: Staphylococcus aureus and Streptococcus pneumoniae are the commonest organism causing pneumonia. Streptococcus pneumoniae is resistant to many antibiotics. Azithromycin can be the first line therapy for pneumonia.

  2. tuberculosis in Malawi

    African Journals Online (AJOL)

    96 per 100,000 in Ntcheu and 103 per 100,000 inI\\/Iangochi (source: National TB Control ... DRUG TREATMENTS FOR HIV-RELATED DISEASES. AND STIs. ... women: high risk (GUS~HR). Gentamicin .... thereafter every month - a private room was used for .... time, they received education and retraining in the diagnosis.

  3. Conditional probability analysis of multidrug resistance in Gram-negative bacilli isolated from tertiary medical institutions in South Korea during 1999-2009.

    Science.gov (United States)

    Kim, Yong-Hak

    2016-01-01

    Multidrug resistance of Gram-negative bacilli is a major problem globally. However, little is known about the combined probability of resistance to various antibiotics. In this study, minimum inhibitory concentrations of widely used antibiotics were determined using clinical isolates of Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii, randomly chosen from strain collections created during 1999-2009 in tertiary medical institutions in Seoul, South Korea. To analyze combined efficacy of antibiotics against a subgroup of isolates, conditional probabilities were determined based on arbitrary, non-independent patterns of antimicrobial susceptibility and resistance. Multidrug resistance, defined as resistance to three or more classes of antibiotics, was observed in the following order: A. baumannii (96%), P. aeruginosa (65%), E. coli (52%), and K. pneumoniae (7%). A. baumannii strains resistant to gentamicin were found to be resistant to a number of antibiotics, except for colistin and polymyxin B. Resistance to gentamicin following exposure to this antibiotic was highly likely to lead to multidrug resistance in all four microbes. This study shows a causal relationship between gentamicin resistance and the prevalence of multidrug resistance in clinical isolates of Gramnegative bacilli in South Korea during 1999-2009 and suggests the importance of prudent use of gentamicin in hospitals.

  4. Development of biofilm-targeted antimicrobial wound dressing for the treatment of chronic wound infections.

    Science.gov (United States)

    Ng, Shiow-Fern; Leow, Hon-Lunn

    2015-01-01

    It has been established that microbial biofilms are largely responsible for the recalcitrance of many wound infections to conventional antibiotics. It was proposed that the efficacy of antibiotics could be optimized via the inhibition of bacterial biofilm growth in wounds. The combination of antibiofilm agent and antibiotics into a wound dressing may be a plausible strategy in wound infection management. Xylitol is an antibiofilm agent that has been shown to inhibit the biofilm formation. The purpose of this study was to develop an alginate film containing xylitol and gentamicin for the treatment of wound infection. Three films, i.e. blank alginate film (SA), alginate film with xylitol (F5) and alginate film with xylitol and gentamicin (AG), were prepared. The films were studied for their physical properties, swelling ratio, moisture absorption, moisture vapor transmission rate (MVTR), mechanical and rheology properties, drug content uniformity as well as in vitro drug release properties. Antimicrobial and antibiofilm in vitro studies on Staphylococcus aureus and Pseudomonas aeruginosa were also performed. The results showed that AG demonstrates superior mechanical properties, rheological properties and a higher MVTR compared with SA and F5. The drug flux of AG was higher than that of commercial gentamicin cream. Furthermore, antimicrobial studies showed that AG is effective against both S. aureus and P. aeruginosa, and the antibiofilm assays demonstrated that the combination was effective against biofilm bacteria. In summary, alginate films containing xylitol and gentamicin may potentially be used as new dressings for the treatment of wound infection.

  5. Polyprenols of Ginkgo biloba Enhance Antibacterial Activity of Five Classes of Antibiotics

    Directory of Open Access Journals (Sweden)

    Ran Tao

    2016-01-01

    Full Text Available Polyprenol (GBP from Ginkgo biloba Leaves (GBL is an important lipid with many bioactive effects. The effect of GBP on antibacterial properties of five antibiotics belonging to different classes was through analysis of inhibition halos, MIC, and FIC index. And we studied the time-killing curves and Ca2+ mobilization assay in Staphylococcus aureus cells treated with GBP microemulsion and gentamicin sulfate under MIC/2 conditions. These results showed that the GBP microemulsion (average diameter 90.2 nm combining with gentamicin sulfate had the highest enhancing antibacterial effect against Staphylococcus aureus, and the MIC value was 33.0 μg/mL. The increase of the antibacterial effect of tested antibiotics was positively correlated with the decrease of the average diameter of GBP microemulsion. Moreover, GBP microemulsion enhanced antibacterial effect and prolonged antibacterial time of GBP combining with gentamicin sulfate against Staphylococcus aureus. GBP microemulsion could enhance the ability of gentamicin inducing an increase in intracellular calcium concentrations to Staphylococcus aureus. GBP microemulsion could help some classes of antibiotics to inhibit or kill bacteria. This study supports the fact that GBP microemulsion obviously can not only reduce the dosage of some classes of antibiotics, but also reduce the frequency of the antibiotic use in vitro.

  6. Polyprenols of Ginkgo biloba Enhance Antibacterial Activity of Five Classes of Antibiotics

    Science.gov (United States)

    Ye, Jianzhong; Zhou, Hao; Chen, Hongxia

    2016-01-01

    Polyprenol (GBP) from Ginkgo biloba Leaves (GBL) is an important lipid with many bioactive effects. The effect of GBP on antibacterial properties of five antibiotics belonging to different classes was through analysis of inhibition halos, MIC, and FIC index. And we studied the time-killing curves and Ca2+ mobilization assay in Staphylococcus aureus cells treated with GBP microemulsion and gentamicin sulfate under MIC/2 conditions. These results showed that the GBP microemulsion (average diameter 90.2 nm) combining with gentamicin sulfate had the highest enhancing antibacterial effect against Staphylococcus aureus, and the MIC value was 33.0 μg/mL. The increase of the antibacterial effect of tested antibiotics was positively correlated with the decrease of the average diameter of GBP microemulsion. Moreover, GBP microemulsion enhanced antibacterial effect and prolonged antibacterial time of GBP combining with gentamicin sulfate against Staphylococcus aureus. GBP microemulsion could enhance the ability of gentamicin inducing an increase in intracellular calcium concentrations to Staphylococcus aureus. GBP microemulsion could help some classes of antibiotics to inhibit or kill bacteria. This study supports the fact that GBP microemulsion obviously can not only reduce the dosage of some classes of antibiotics, but also reduce the frequency of the antibiotic use in vitro. PMID:27642597

  7. Association of the novel aminoglycoside resistance determinant RmtF with NDM carbapenemase in Enterobacteriaceae isolated in India and the UK

    DEFF Research Database (Denmark)

    Hidalgo, Laura; Hopkins, Katie L; Gutierrez, Belen;

    2013-01-01

    16S rRNA methyltransferases are an emerging mechanism conferring high-level resistance to clinically relevant aminoglycosides and have been associated with important mechanisms such as NDM-1. We sought genes encoding these enzymes in isolates highly resistant (MIC >200 mg/L) to gentamicin and ami...

  8. Development of an in vivo model for study of intestinal invasion by Salmonella enterica in chickens

    DEFF Research Database (Denmark)

    Aabo, Søren; Christensen, J.P.; Chadfield, M.S.

    2000-01-01

    , followed by a 1-h incubation with gentamicin in order to kill noninvading bacteria. After euthanasia, Salmonella invasiveness was measured as tissue-associated counts relative to a reference strain. The ability of Salmonella invasion was 1 log(10) CFU higher per 42-mm(2) mucosal tissue in the anterior than...

  9. Recurrent peritoneal dialysis-related peritonitis caused by Microbacterium resistens.

    Science.gov (United States)

    Gallois, Emmanuelle; Lamy, Thomas; Fines-Guyon, Marguerite; Lobbedez, Thierry; Cattoir, Vincent

    2014-05-01

    We report a case of a recurrent peritonitis due to Microbacterium resistens in a 71-year-old male patient undergoing peritoneal dialysis (PD). Importantly, this Gram-positive rod was intrinsically resistant to cephalosporins and vancomycin, classically used in PD-related peritonitis treatment. His infection resolved after several weeks of appropriate therapy (amoxicillin plus gentamicin) and PD catheter removal.

  10. Characterization of Escherichia coli Phylogenetic Groups ...

    African Journals Online (AJOL)

    high surface hydrophobicity, toxin (hemolysin and CNF) ... Triplex polymerase chain reaction was used to classify the phylogenetic groups; hemolysin ... was detected by combination disk method; AmpC was detected by AmpC disk test, ... Quick Response Code: ... norfloxacin (10 μg), amikacin (30 μg), gentamicin (10 μg),.

  11. Vertigo Perception and Quality of Life in Patients after Surgical Treatment of Vestibular Schwannoma with Pretreatment Prehabituation by Chemical Vestibular Ablation

    Directory of Open Access Journals (Sweden)

    Zdeněk Čada

    2016-01-01

    Full Text Available Surgical removal of vestibular schwannoma causes acute vestibular symptoms, including postoperative vertigo and oscillopsia due to nystagmus. In general, the dominant symptom postoperatively is vertigo. Preoperative chemical vestibular ablation can reduce vestibular symptoms postoperatively. We used 1.0 mL of 40 mg/mL nonbuffered gentamicin in three intratympanic installations over 2 days, 2 months preoperatively in 10 patients. Reduction of vestibular function was measured by the head impulse test and the caloric test. Reduction of vestibular function was found in all gentamicin patient groups. After gentamicin vestibular ablation, patients underwent home vestibular exercising for two months. The control group consisted of 10 patients who underwent only home vestibular training two months preoperatively. Postoperative rates of recovery and vertigo in both groups were evaluated with the Glasgow Benefit Inventory (GBI, the Glasgow Health Status Inventory (GHSI, and the Dizziness Handicap Inventory questionnaires, as well as survey of visual symptoms by specific questionnaire developed by us. There were no statistically significant differences between both groups with regard to the results of questionnaires. Patients who received preoperative gentamicin were more resilient to optokinetic and optic flow stimulation (p<0.05. This trial is registered with clinical study registration number NCT02963896.

  12. Immunochemical detection of aminoglycosides in milk and kidney

    NARCIS (Netherlands)

    Haasnoot, W.; Stouten, P.; Cazemier, G.; Lommen, A.; Nouws, J.F.M.; Keukens, H.J.

    1999-01-01

    In 1996, the European Union established provisional maximum residue limits (MRL) for gentamicin, neomycin, streptomycin and dihydrostreptomycin in milli and tissue (0.1-5 mg kg-1). For the detection of these four aminoglycosides, three enzyme linked immunosorbent assays (ELISA) for applications in m

  13. Characterization of Antimicrobial Resistance of Listeria monocytogenes Strains Isolated from a Pork Processing Plant and Its Respective Meat Markets in Southern China

    DEFF Research Database (Denmark)

    Li, Lili; Olsen, Rikke Heidemann; Ye, Lei;

    2016-01-01

    ) being predominant (42.3%, 33/78). Antimicrobial resistance was most frequently observed for tetracycline (20.5%, 16/78), streptomycin (9.0%, 7/78), cefotaxime (7.7%, 6/78), and gentamicin (6.4%, 5/78). Multiple resistances occurred among 10.2% (8/78) isolates. All strains were sensitive to ampicillin...

  14. Neonatal bloodstream infections in a Ghanaian Tertiary Hospital: Are the current antibiotic recommendations adequate?

    Science.gov (United States)

    Labi, Appiah-Korang; Obeng-Nkrumah, Noah; Bjerrum, Stephanie; Enweronu-Laryea, Christabel; Newman, Mercy Jemima

    2016-10-24

    Diagnosis of bloodstream infections (BSI) in neonates is usually difficult due to minimal symptoms at presentation; thus early empirical therapy guided by local antibiotic susceptibility profile is necessary to improve therapeutic outcomes. A review of neonatal blood cultures submitted to the microbiology department of the Korle-Bu Teaching Hospital was conducted from January 2010 through December 2013. We assessed the prevalence of bacteria and fungi involved in BSI and the susceptibility coverage of recommended empiric antibiotics by Ghana Standard Treatment guidelines and the WHO recommendations for managing neonatal sepsis. The national and WHO treatment guidelines recommend either ampicillin plus gentamicin or ampicillin plus cefotaxime for empiric treatment of neonatal BSI. The WHO recommendations also include cloxacillin plus gentamicin. We described the resistance profile over a 28-day neonatal period using multivariable logistic regression analysis with linear or restricted cubic splines. A total of 8,025 neonatal blood culture reports were reviewed over the four-year period. Total blood culture positivity was 21.9 %. Gram positive organisms accounted for most positive cultures, with coagulase negative staphylococci (CoNS) being the most frequently isolated pathogen in early onset infections (EOS) (59.1 %) and late onset infections (LOS) (52.8 %). Susceptibility coverage of early onset bacterial isolates were 20.7 % to ampicillin plus cefotaxime, 32.2 % to the combination of ampicillin and gentamicin, and 71.7 % to cloxacillin plus gentamicin. For LOS, coverage was 24.6 % to ampicillin plus cefotaxime, 36.2 % to the combination ampicillin and gentamicin and 63.6 % to cloxacillin plus gentamicin. Cloxacillin plus gentamicin remained the most active regimen for EOS and LOS after exclusion of BSI caused by CoNS. For this regimen, the adjusted odds of resistance decreased between 12-34 % per day from birth to day 3 followed by the slowest rate of

  15. Aminoglycoside inhibition of Staphylococcus aureus biofilm formation is nutrient dependent.

    Science.gov (United States)

    Henry-Stanley, Michelle J; Hess, Donavon J; Wells, Carol L

    2014-06-01

    Biofilms represent microbial communities, encased in a self-produced matrix or extracellular polymeric substance. Microbial biofilms are likely responsible for a large proportion of clinically significant infections and the multicellular nature of biofilm existence has been repeatedly associated with antibiotic resistance. Classical in vitro antibiotic-susceptibility testing utilizes artificial growth media and planktonic microbes, but this method may not account for the variability inherent in environments subject to biofilm growth in vivo. Experiments were designed to test the hypothesis that nutrient concentration can modulate the antibiotic susceptibility of Staphylococcus aureus biofilms. Developing S. aureus biofilms initiated on surgical sutures, and in selected experiments planktonic cultures, were incubated for 16 h in 66 % tryptic soy broth, 0.2 % glucose (1× TSBg), supplemented with bactericidal concentrations of gentamicin, streptomycin, ampicillin or vancomycin. In parallel experiments, antibiotics were added to growth medium diluted one-third (1/3× TSBg) or concentrated threefold (3× TSBg). Following incubation, viable bacteria were enumerated from planktonic cultures or suture sonicates, and biofilm biomass was assayed using spectrophotometry. Interestingly, bactericidal concentrations of gentamicin (5 µg gentamicin ml(-1)) and streptomycin (32 µg streptomycin ml(-1)) inhibited biofilm formation in samples incubated in 1/3× or 1× TSBg, but not in samples incubated in 3× TSBg. The nutrient dependence of aminoglycoside susceptibility is not only associated with biofilm formation, as planktonic cultures incubated in 3× TSBg in the presence of gentamicin also showed antibiotic resistance. These findings appeared specific for aminoglycosides because biofilm formation was inhibited in all three growth media supplemented with bactericidal concentrations of the cell wall-active antibiotics, ampicillin and vancomycin. Additional experiments

  16. Hybrid wound dressings with controlled release of antibiotics: Structure-release profile effects and in vivo study in a guinea pig burn model.

    Science.gov (United States)

    Zilberman, Meital; Egozi, Dana; Shemesh, Maoz; Keren, Aviad; Mazor, Eytan; Baranes-Zeevi, Maya; Goldstein, Nyra; Berdicevsky, Israela; Gilhar, Amos; Ullmann, Yehuda

    2015-08-01

    Over the last decades, wound dressings have evolved from a crude traditional gauze dressing to tissue-engineered scaffolds. Many types of wound dressing formats are commercially available or have been investigated. We developed and studied hybrid bilayer wound dressings which combine a drug-loaded porous poly(dl-lactic-co-glycolic acid) top layer with a spongy collagen sublayer. Such a structure is very promising because it combines the advantageous properties of both layers. The antibiotic drug gentamicin was incorporated into the top layer for preventing and/or defeating infections. In this study, we examined the effect of the top layer's structure on the gentamicin release profile and on the resulting in vivo wound healing. The latter was tested on a guinea pig burn model, compared to the neutral non-adherent dressing material Melolin® (Smith & Nephew) and Aquacel® Ag (ConvaTec). The release kinetics of gentamicin from the various studied formulations exhibited burst release values between 8% and 38%, followed by a drug elution rate that decreased with time and lasted for at least 7 weeks. The hybrid dressing, with relatively slow gentamicin release, enabled the highest degree of wound healing (28%), which is at least double that obtained by the other dressing formats (8-12%). It resulted in the lowest degree of wound contraction and a relatively low amount of inflammatory cells compared to the controls. This dressing was found to be superior to hybrid wound dressings with fast gentamicin release and to the neat hybrid dressing without drug release. Since this dressing exhibited promising results and does not require frequent bandage changes, it offers a potentially valuable concept for treating large infected burns.

  17. In vitro synergy, pharmacodynamics, and postantibiotic effect of 11 antimicrobial agents against Rhodococcus equi.

    Science.gov (United States)

    Giguère, Steeve; Lee, Elise A; Guldbech, Kristen M; Berghaus, Londa J

    2012-11-09

    There are no studies investigating interactions between clarithromycin or azithromycin and rifampin or other commonly used antimicrobial agents against virulent isolates of Rhodococcus equi. In addition, there is no published data on the postantibiotic effects (PAEs) and pharmacodynamics properties of antimicrobial agents against R. equi. The objectives were to assess in vitro interactions, pharmacodynamics, and PAEs of 11 antimicrobial agents belonging to various antimicrobial classes against R. equi. Antimicrobial agents investigated (erythromycin, clarithromycin, azithromycin, rifampin, amikacin, gentamicin, enrofloxacin, vancomycin, imipenem, ceftiofur, and doxycycline) were selected based on in vitro activity against large numbers of isolates of R. equi and frequency of use in foals or humans infected with R. equi. Three virulent strains of R. equi were evaluated by time-kill curves and checkerboard assays, and the postantibiotic effect was measured at 5×MIC. Only amikacin, gentamicin, enrofloxacin, and vancomycin were bactericidal against R. equi. Combinations including a macrolide (erythromycin, clarithromycin, azithromycin) and either rifampin or doxycycline, and the combination doxycycline-rifampin were synergistic. Combinations containing amikacin and erythromycin, clarithromycin, azithromycin, or rifampin and the combination gentamicin-rifampin were antagonistic. The PAEs of rifampin, erythromycin, clarithromycin, vancomycin, and doxycycline were relatively long with median values ranging between 4.5 and 6.5h. Azithromycin, gentamicin, and imipenem had intermediate PAEs ranging between 3.3 and 3.5h. Amikacin, enrofloxacin, and ceftiofur had shorter PAEs ranging between 1.3 and 2.1h. Gentamicin, amikacin, enrofloxacin, and doxycycline exhibited concentration-dependent activity whereas erythromycin, clarithromycin, azithromycin, rifampin, ceftiofur, imipenem, and vancomycin exhibited time-dependent activity against R. equi. Copyright © 2012 Elsevier B

  18. Comparative efficacies of antibiotics in a rat model of meningoencephalitis due to Listeria monocytogenes.

    Science.gov (United States)

    Michelet, C; Leib, S L; Bentue-Ferrer, D; Täuber, M G

    1999-07-01

    The antibacterial activities of amoxicillin-gentamicin, trovafloxacin, trimethoprim-sulfamethoxazole (TMP-SMX) and the combination of trovafloxacin with TMP-SMX were compared in a model of meningoencephalitis due to Listeria monocytogenes in infant rats. At 22 h after intracisternal infection, the cerebrospinal fluid was cultured to document meningitis, and the treatment was started. Treatment was instituted for 48 h, and efficacy was evaluated 24 h after administration of the last dose. All tested treatment regimens exhibited significant activities in brain, liver, and blood compared to infected rats receiving saline (P amoxicillin plus gentamicin was more active than all of the other regimens, and trovafloxacin was more active than TMP-SMX (bacterial titers of 4.1 +/- 0.5 log10 CFU/ml for amoxicillin-gentamicin, 5.0 +/- 0.4 log10 CFU/ml for trovafloxacin, and 5.8 +/- 0.5 log10 CFU/ml for TMP-SMX; P < 0.05). In liver, amoxicillin-gentamicin and trovafloxacin were similarly active (2.8 +/- 0.8 and 2.7 +/- 0.8 log10 CFU/ml, respectively) but more active than TMP-SMX (4.4 +/- 0. 6 log10 CFU/ml; P < 0.05). The combination of trovafloxacin with TMP-SMX did not alter the antibacterial effect in the brain, but it did reduce the effect of trovafloxacin in the liver. Amoxicillin-gentamicin was the most active therapy in this study, but the activity of trovafloxacin suggests that further studies with this drug for the treatment of Listeria infections may be warranted.

  19. Simplified antibiotic regimens for treatment of clinical severe infection in the outpatient setting when referral is not possible for young infants in Pakistan (Simplified Antibiotic Therapy Trial [SATT]): a randomised, open-label, equivalence trial.

    Science.gov (United States)

    Mir, Fatima; Nisar, Imran; Tikmani, Shiyam S; Baloch, Benazir; Shakoor, Sadia; Jehan, Fyezah; Ahmed, Imran; Cousens, Simon; Zaidi, Anita K M

    2017-02-01

    Parenteral antibiotic therapy for young infants (aged 0-59 days) with suspected sepsis is sometimes not available or feasible in countries with high neonatal mortality. Outpatient treatment could save lives in such settings. We aimed to assess the equivalence of two simplified antibiotic regimens, comprising fewer injections and oral rather than parenteral administration, compared with a reference treatment for young infants with clinical severe infection. We undertook the Simplified Antibiotic Therapy Trial (SATT), a three-arm, randomised, open-label, equivalence trial in five communities in Karachi, Pakistan. We enrolled young infants (aged 0-59 days) who either presented at a primary health-care clinic or were identified by a community health worker with signs of clinical severe infection. We included infants who were not critically ill and whose family refused admission. We randomly assigned infants to either intramuscular procaine benzylpenicillin and gentamicin once a day for 7 days (reference); oral amoxicillin twice daily and intramuscular gentamicin once a day for 7 days; or intramuscular procaine benzylpenicillin and gentamicin once a day for 2 days followed by oral amoxicillin twice daily for 5 days. The primary outcome was treatment failure within 7 days of enrolment and the primary analysis was per protocol. We judged experimental treatments as efficacious as the reference if the upper bound of the 95% CI for the difference in treatment failure was less than 5·0. This trial is registered at ClinicalTrials.gov, number NCT01027429. Between Jan 1, 2010, and Dec 26, 2013, 2780 infants were deemed eligible for the trial, of whom 2453 (88%) were enrolled. Because of inadequate clinical follow-up or treatment adherence, 2251 infants were included in the per-protocol analysis. 820 infants (747 per protocol) were assigned the reference treatment of procaine benzylpenicillin and gentamicin, 816 (751 per protocol) were allocated amoxicillin and gentamicin, and

  20. The potential of methylethylpiridinol in treatment of bacterial infections caused by Klebsiella pneumoniae (experimental study

    Directory of Open Access Journals (Sweden)

    V. M. Brykhanov

    2016-01-01

    Full Text Available Aim. Investigated the activity of methylethylpiridinol (6-methyl-2-ethyl-pyridin-3-ol hydrochloride in the comprehensive treatment of the experimental bacterial infection caused by Klebsiella pneumoniae.Materials and methods. The study was conducted on clinical isolates of Klebsiella pneumoniae. At the first stage of the study (in vitro studied the effect of methylethylpiridinol in concentrations 0,25–4 mM on the growth of the strain and the activity of the sublethal concentrations of antibiotics – gentamicin, ciprofloxacin, tetracycline, ceftazidime. In the second stage of the study (in vivo in rats Wistar simulated bacterial peritonitis by intraperitoneal injection of a suspension of Klebsiella pneumoniae and investigated the effect of methylethylpiridinol (80 mg/kg on the effectiveness of antibiotic therapy with gentamicin (30 mg/kg, ciprofloxacin (50 mg/kg, ceftazidime (120 mg/kg or tetracycline (80 mg/kg. The animal blood plasma was determined ceruloplasmin concentration (marker of the intensity of infectious-inflammatory process and thiobarbiturate-jet products, erythrocytes – the concentration of reduced glutathione, catalase and glutathione peroxidase.Results. It is found that a methylethylpiridinol inhibits the development of periodic bacterial cultures, but exhibits a pronounced antagonism with respect to gentamicin. Antioxidant slightly increases the activity of ciprofloxac