Foster, David R; Yee, Shiyin; Bleske, Barry E; Carver, Peggy L; Shea, Michael J; Menon, Sujatha S; Ramachandran, Chandrasekharan; Welage, Lynda S; Amidon, Gordon L
Intestinal peptide transporters, including hPEPT1, facilitate the absorption of cephalosporins and angiotensin-converting enzyme inhibitors, and have been investigated as a means to improve oral drug absorption. Renal peptide transporters including hPEPT2, may also facilitate renal reabsorption of such compounds. In vitro and animal studies suggest that co-administration of peptidomimetic compounds may alter oral pharmacokinetics, although this has not been well studied in humans. The purpose of this study was to determine whether co-administration of the hPEPT substrates captopril and cephradine alters the oral pharmacokinetics of either agent. Nine healthy male volunteers received a single oral 25-mg dose of captopril, a single oral 500-mg dose of cephradine, or concurrent ingestion of captopril and cephradine in a cross-over manner. Venous blood samples were taken and captopril and cephradine pharmacokinetics were determined using noncompartmental analyses. No significant differences were observed in captopril or cephradine pharmacokinetics when administered together as compared to each agent alone (a marginal decrease in C(max) was observed for both captopril and cephradine during co-administration [5-15%]; however, differences were not statistically significant). The results of our study suggest that hPEPT1 and hPEPT2 are unlikely to contribute to clinically important drug interactions in humans.
Ustariz-Peyret, C; Coudane, J; Vert, M; Kaltsatos, V; Boisramé, B
In the field of controlled drug delivery, most of the reported work is aimed at introducing new systems, or at providing basic information on the critical parameters which affect release profiles in vitro and occasionally in vivo. The situation is totally different when one wants to fulfil the specific requirements imposed by the marketing of a sustained release device to be used in humans or in animals eaten by human beings. The control of the release characteristics is then a difficult challenge. In this work, attempts were made to combine cephradin, a hydrophilic beta-lactam antibiotic, and bioresorbable polymeric matrices of a poly(alpha-hydroxy acid) in the form of microspheres with the aim of delivering the antibiotic to cattle at a dose rate of 4-5 mg/kg/day over a 3-4 days period after i.m. injection. PLAGA aliphatic polyesters were selected because they are already FDA approved as matrices. The solvent evaporation technique using PVA as the emulsion stabilizer was selected because it is efficient and can be extended to an industrial scale. Various experimental conditions were used in order to obtain the highest encapsulation yields compatible with the desired specifications. Decreasing the volume of the aqueous phase and adding a water-miscible organic solvent/non-solvent of cephradin failed. In contrast, microspheres containing up to 30% cephradin were prepared after addition of sodium chloride to the aqueous dispersing phase. The amount of entrapped drug was raised to 40% by decreasing the temperature and the pressure. Preliminary investigations using dogs showed that 20% cephradin microspheres prepared under these conditions extended the presence of cephradin in the blood circulation up to 48 h. Increasing the load led to higher blood concentrations but shorter sustained release. The fact that the microspheres were for cattle limited the volume of the injection and thus the amount of microspheres to be administered. The other limiting factors were
Ali, A.M.M.; Ghandour, M.A.; Khodari, M.
Uranium adsorbed with cephradine is reduced on a hanging mercury drop electrode. This property was exploited in developing a highly sensitive stripping voltammetric procedure for the determination of uranium. A detection limit 2 x 10 -9 mol I -1 (0.5 μg I -1 ) of uranium ion is obtained with an 180 s accumulation time. Cyclic voltammetry was used to characterize the interfacial and redox behaviour. The effects of various parameters are discussed. Experimental conditions include the use of 5 x 10 -6 mol I -1 cephradine in 0.05 mol I -1 sodium perchlorate (pH ''approx ='' 6.5), an accumulation potential of 0.0 V versus SCE and a direct current stripping technique. The response is linear up to 5 x 10 -6 mol I -1 uranium and the relative standard deviation at 1 x 10 -7 mol I -1 ) UO 2+ is 4.4%. The effect of other metal ions was investigated. (author)
Tasić, Žaklina Z.; Petrović Mihajlović, Marija B.; Radovanović, Milan B.; Simonović, Ana T.; Antonijević, Milan M.
The effect of (6R,7R)-7-[[(2R)-2-amino-2-cyclohexa-1,4-dien-1-ylacetyl]amino]-3-methyl-8-oxo-5-thia-1-azobicyclo[4.2.0]oct-2-ene-2-carboxylic acid (cephradine) on corrosion behavior of copper in 0.9% NaCl solution was investigated. The electrochemical methods including the open circuit potential measurements, potentiodynamic polarization and electrochemical impedance spectroscopy measurements, scanning electron microscopy with energy dispersive X-ray spectroscopy and quantum chemical calculations were used for this investigation. According to the results obtained by potentiodynamic polarization, cephradine acts as mixed type inhibitor. Also, the results obtained by electrochemical impedance spectroscopy indicate that cephradine provides good copper protection in 0.9% NaCl solution. The inhibition efficiency of cephradine increases with increasing its concentration. The scanning electron microscopy with energy dispersive X-ray spectroscopy confirms that a protective layer is formed on the copper surface due to the adsorption of cephradine on the active sites on the copper surface. Adsorption of cephradine in 0.9% NaCl solution follows the Langmuir adsorption isotherm. Quantum chemical calculations are in agreement with results obtained by electrochemical measurements.
Naz, N.; Iqbal, M.Z.
Fe(II), Co(II) and Ni(II) metal complexes of novel schiff bases derived from Cephradine and sugars (D-Glucose, L. Arabinose and D-Galactose) were synthesized and characterized by elemental analysis, magnetic susceptibility, thermal analysis, electronic absorption and FT-IR spectral studies. It has been found that schiff bases behave as bi-dentate-ligands forming complexes with 1:2 (metal:ligand) stoichiometry. the neutral nature of the complexes was confirmed by their low conductance values. The biological activities of complexes have been evaluated against two gram negative (Escherichia coli and Pseudomonas aeruginosa) and two gram positive (Bacillus subtilis and staphylococcus aureus) bacteria by Agar diffusion disc method. It has been found that the complexes have higher activity as compared to the pure Cephradine against the same bacteria. (author)
Ahmad, M.; Usman, M.; Madni, A.; Akhtar, N.; Khalid, N.; Asghar, W.
An HPLC method with high precision, accuracy and selectivity was developed and validated for the assessment of cephradine in human plasma samples. The extraction procedure was simple and accurate with single step followed by direct injection of sample into HPLC system. The extracted cephradine in spiked human plasma was separated and quantitated using reversed phase C/sub 18/ column and UV detection wavelength of 254 nm. The optimized mobile phase of new composition of 0.05 M potassium dihydrogen phosphate (pH 3.4)-acetonitrile (88: 12) was pumped at an optimum flow rate of 1 mL.min/sup 1/. The method resulted linearity in the concentration range 0.15- 20 micro g mL/sup -1/. The limit of detection (LOD) and limit of quantification (LOQ) were 0.05 and 0.150 Microg.mL/sup -1/, respectively. The accuracy of method was 98.68 %. This method can 1>e applied for bioequivalence studies and therapeutic drug monitoring as well as for the routine analysis of cephradine. (author)
Khan, A.U.; Iqbal, J.
The effect of reconstitution solvents such as water, 0.5% metronidazole solution, 0.9% sodium chloride and 5% dextrose injections, have been investigated on the kinetics of degradation of cephradine neutralised with L-arginine contained in glass, polyvinylchloride (PVC) and polyethylene pthalate (PET) containers at 5, 15 and 30 degree C. The analytical method described in USP-31 for the analysis of cephradine injection was employed in this study and validation in respect of specificity, linearity, accuracy and precision was observed. The degradation of the compound showed first-order kinetics and the degradation rate constants Kobs were found in the range of 1.84-3.07 * 10/sup -3/h (r2= 0.990-0.999) at 5 degree C, 2.3-4.2 * 10/sup -3/h (r2= 0.993-0.999) at 15 degree C and 7.18-9.97 * 10/sup -3/h (r2= 0.998-0.999) at 30 degree C, respectively. Cephradine showed maximum stability in dextrose solution followed by water, sodium chloride and metronidazole injections, however, linear effect of containers on degradation rate could not be established. The extended degradation did not change the kinetics of the reaction. The abnormal toxicity/ safety test on mice for the admixtures in different containers at various temperatures showed no abnormal toxicity. (author)
Ustariz-Peyret, C; Coudane, J; Vert, M; Kaltsatos, V; Boisramené, B
The physical entrapment of a hydrophilic drug within degradable microspheres is generally difficult because of poor entrapment yield and/or fast release, depending on the microsphere fabrication method. In order to counter the effects of drug hydrophilicity, it is proposed to covalently attach the drug to lactic acid oligomers, with the aim of achieving temporary hydrophobization and slower release controlled by the separation of the drug from the degradable link within the polymer matrix. This strategy was tested on microspheres of the antibiotic cephradin. As the prodrug form, the entrapment of the drug was almost quantitative. The prodrug did degrade in an aqueous medium, modelling body fluids, but cleavage did not occur at the drug-oligomer junction and drug molecules bearing two lactyl residual units were released. When the prodrug is entrapped within a PLAGA matrix, no release was observed within the experimental time period. However, data suggest that conjugation via a bond more sensitive to hydrolysis than the main chain PLA ester bonds should make the system work as desired.
. Italia SPA), ceftazidime, cefuroxime, cephalexin and gentamicin (Glaxo Welcome, Egypt), ceftriaxone (TA3 Pharma Group, Egypt), cefoperazone (Phizer, Egypt), nitrocefin (Glaxo,. Greenford, UK), Cephradine (Pharco, pharmaceutical, ...
Josey, W E
Therapeutic failure in vaginitis can be minimized if all cases are properly diagnosed and specific therapy is given. Use of wet mounts combined with liberal use of cultures, especially for Corynebacterium vaginale, should result in an accurate diagnosis in over 90% of cases. Treatment of choice for candidiasis is nystatin or miconazole nitrate applied topically. For trichomoniasis, metronidazole should be given orally to both sexual partners. Ampicillin, cephalexin, or cephradine are recommended for C vaginale infection.
Farzana, K.; Hameed, A.
Among the samples received in pathology laboratory, Pakistan institute of Medical Science, Islamabad, 5069 samples had bacterial growth, among these 2580 (51%) samples were Gram-positive cocci and 1688 were Staphylococcus aureus during a period of two years. Out of these Gram-positive cocci 56% were resistant to penicillin group, 27% were resistant to cephalosporin group, 22% were resistant to aminoglycoside group 15% were resistant to quinolone group and 31% were resistant to other antibiotics (cotrimaxazole, erythromycin, aztreonam, vancomycin, nitrofurantion and meropenam). Antibio-grams of Gram-positive cocci were determined against various antibiotics by disc diffusion method. The rate of resistance to most of the antibiotics such as ampicillin, piperacillin, carbenicillin, penicillin, cephradine, cefotaxime, erythromycin, ceclor, ofloxacin, pefloxacin, ciprofloxacin, cotrimexazole (septran), gentamicin, meropenem, ceftazidime, erythromycin, tobramycin, enoxacin was higher when tested against the isolates collected from pus as compared to those from blood and urine. Antibiotic resistant strains were more prevalent in pus samples than other clinical isolates (blood and urine). The randomly selected 155 strains of Staphylococcus aureus when tested against five groups of antibiotics showed resistance rate against ampicillin (92%), cephradine (92%), cephradine (60%), and gentamicin (58%). However intermediate resistance was found in case of vancomicin (38%), in hospitalized and non-hospitalized patients. (author)
West, B C; Silberman, R; Otterson, W N
The first case of septicemic acute acalculous cholecystitis caused by non-O1 Vibrio cholerae is described in a healthy traveler, and biliary tract infections from V. cholerae are reviewed. Immediately after a vacation in Cancun, Mexico, a 55-year-old man developed acute cholecystitis. Blood and bile cultures grew non-O1 V. cholerae. At surgery, the gallbladder was acalculous, inflamed, distended, and nearly ruptured. Pathogenetic factors may have included diarrhea prophylaxis with bismuth subsalicylate, distension of the gallbladder from illness-induced fasting, and bacterial toxins in the gallbladder. The patient received i.v. cephapirin, followed by oral cephradine for a total of 10 days, and he made a quick and complete recovery. V. cholerae should be considered in the differential diagnosis of persons from endemic areas who present with cholecystitis or acute jaundice.
Full Text Available This study was conducted to observe the sensitivity and resistance of status of antibiotics for respiratory tract infection (RTI. Throat swab culture and sensitivity report of 383 patients revealed sensitivity profiles were observed with amoxycillin (7.9%, penicillin (33.7%, ampicillin (36.6%, co-trimoxazole (46.5%, azithromycin (53.5%, erythromycin (57.4%, cephalexin (69.3%, gentamycin (78.2%, ciprofloxacin (80.2%, cephradine (81.2%, ceftazidime (93.1%, ceftriaxone (93.1%. Sensitivity to cefuroxime was reported 93.1% cases. Resistance was found with amoxycillin (90.1%, ampicillin (64.1%, penicillin (61.4%, co-trimoxazole (43.6%, erythromycin (39.6%, and azithromycin (34.7%. Cefuroxime demonstrates high level of sensitivity than other antibiotics and supports its consideration with patients with upper RTI.
Mohamed Khaled Ibrahim
Full Text Available Antibiotic resistance in bacteria is becoming a serious problem, especially after the emergence of multidrug-resistant strains. To overcome this problem, new and effective antibacterials or resistance modulators are highly needed and plant kingdom represents a valuable source of these compounds. In this study we investigated the antibacterial and resistance modulatory activity of Aniseeds waste Residue Extract (ASWRE and Star Anise Waste Residue Extract (SAWRE (post-distillation against 100 isolates belonging to two Gram positive (Streptococcus pneumoniae and Staphylococcus aureus and four Gram negative bacteria (Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii and Pseudomonas aeruginosa. Phenolic compounds of anise wastes were determined by HPLC. The antibacterial activity of anise waste extracts assays were performed by using inhibition zone diameters, MIC and MBC. Evaluation of synergy interaction between anise waste extracts and certain known antibacterial drugs like Cephradine, Chloramphenicol, Tetracycline and Amoxicillin was carried out using disc diffusion method, MIC and the fractional inhibitory concentrations (FIC. The results showed that HPLC method has been developed for the determination of 25 phenolic compounds from waste extracts. Both ASWRE and SAWRE have significant antibacterial activity against all of the test bacteria. SAWRE was found to have higher amounts of phenolic compounds contents that might be responsible for their comparatively higher antibacteria activity than ASWRE. Irradiation at 10 and 30 kGy did not significantly affect the antibacterial activity of both ASWRE and SAWRE. The combination of anise waste extracts and the tested antibiotics mostly showed synergistic effect. Synergistic interaction was most expressed against Streptococcus pneumoniae (Sp1 and Staphylococcus aureus (Sa1 by Tetracycline and chloramphenicol; Pseudomonas aeruginosa (P2, Klebsiella pneumoniae (K3, Acinetobacter baumannii
van Esch, Sadie; Krediet, Raymond T.; Struijk, Dirk G.
♦ Background: Peritonitis in peritoneal dialysis (PD) patients can lead to technique failure and contributes to infection-related mortality. Peritonitis prevention and optimization of treatment are therefore important in the care for PD patients. In the present study, we analyzed the incidence of peritonitis, causative pathogens, clinical outcomes, and trends in relation to three major treatment changes that occurred from 1979 onward: use of a disconnect system since 1988, daily mupirocin at the exit-site since 2001, and exclusive use of biocompatible dialysis solutions since 2004. ♦ Methods: In this analysis of prospectively collected data, we included peritonitis episodes from the start of PD at our center in August 1979 to July 2010. Incident PD patients were allocated to one of four groups: Group 1 - 182 patients experiencing 148 first peritonitis episodes between 1979 and 1987, before the introduction of the disconnect system; Group 2 - 352 patients experiencing 239 first episodes of peritonitis between 1988 and 2000, before implementation of daily mupirocin application at the catheter exit-site; Group 3 - 79 patients experiencing 50 first peritonitis episodes between 2001 and 2003, before the switch to biocompatible solutions; and Group 4-118 patients experiencing 91 first peritonitis episodes after 2004. Cephradine was used as initial antibiotic treatment. ♦ Results: In 32 years, 731 adult patients started PD, and 2234 episodes of peritonitis in total were diagnosed and treated. Of those episodes, 88% were cured with medical treatment only, and 10% resulted in catheter removal. In 3% of the episodes, the patient died during peritonitis. Median time to a first peritonitis episode increased from 40 days for group 1 to 150 for group 2, 269 for group 3, and 274 for group 4. The overall peritonitis rate and the gram-positive and gram-negative peritonitis rates showed a time-trend of decline. However, the duration of antibiotic treatment increased over time
M. IQBAL, I. A. SHAH, A. ALI, M. A. KHAN AND S. JAN
Full Text Available The present study was conducted for the isolation of bacterial agents and in vitro antibiogram of the isolates from the yolk and visceral organs of up to one week old broiler and layer chicks suffering from omphalitis. Samples from the yolk and visceral organs were aseptically collected and cultured on various selective and differential media. The isolated organisms were identified and subjected to commonly used antibiotics for determination of antibiogram. During the period of 39 months (May, 2002 to August, 2005, 330 samples from yolk and visceral organs were taken from those chicks which were not medicated with antibiotics, as per history provided by the poultry farmers. Among these, 223(68% showed bacterial growth. Various bacteria isolated were Escherichia coli (47.93%, proteus (5.87%, mixed infection (3.59%, streptococci (2.89%, klebsiella (1.79%, salmonella (0.5%, staphylococci (0.5%, pseudomonas (0.5%, pasteurella (0.5% and yarseinia (0.5%. The antibiotics found most effective were Norfloxacin (45.3%, Enrofloxacin (36.81%, Gentamicin (33.21%, Chloramphenicol (33.21%, Cephradin (25.1%, Augmentine (24.7%, Kanammycin (17.5% and Ampicillin (12.1%.
Mahmoud A. Omar
Full Text Available A simple, reliable, and sensitive kinetic spectrophotometric method was developed for determination of eight cephalosporin antibiotics, namely, Cefotaxime sodium, Cephapirin sodium, Cephradine dihydrate, Cephalexin monohydrate, Ceftazidime pentahydrate, Cefazoline sodium, Ceftriaxone sodium, and Cefuroxime sodium. The method depends on oxidation of each of studied drugs with alkaline potassium permanganate. The reaction is followed spectrophotometrically by measuring the rate of change of absorbance at 610 nm. The initial rate and fixed time (at 3 minutes methods are utilized for construction of calibration graphs to determine the concentration of the studied drugs. The calibration graphs are linear in the concentration ranges 5–15 g mL−1 and 5–25 g mL−1 using the initial rate and fixed time methods, respectively. The results are validated statistically and checked through recovery studies. The method has been successfully applied for the determination of the studied cephalosporins in commercial dosage forms. Statistical comparisons of the results with the reference methods show the excellent agreement and indicate no significant difference in accuracy and precision.
Osman, K M; Elhariri, M
The use of antibiotic feed additives in broiler chickens results in a high prevalence of resistance among their enteric bacteria, with a consequent emergence of antibiotic resistance in zoonotic enteropathogens. Despite growing concerns about the emergence of antibiotic-resistant strains, which show varying prevalences in different geographic regions, little work has been done to investigate this issue in the Middle East. This study provides insight into one of the world's most common and financially crippling poultry diseases, necrotic enteritis caused by Clostridium perfringens. The study was designed to determine the prevalence of antibiotic resistance in C. perfringens isolates from clinical cases of necrotic enteritis in broiler chickens in Egypt. A total of 125 isolates were obtained from broiler flocks in 35 chicken coops on 17 farms and were tested using the disc diffusion method. All 125 isolates were resistant to gentamicin, streptomycin, oxolinic acid, lincomycin, erythromycin and spiramycin. The prevalence of resistance to other antibiotics was also high: rifampicin (34%), chloramphenicol (46%), spectinomycin (50%), tylosin-fosfomycin (52%), ciprofloxacin (58%), norfloxacin (67%), oxytetracycline (71%), flumequine (78%), enrofloxacin (82%), neomycin (93%), colistin (94%), pefloxacin (94%), doxycycline (98%) and trimethoprim-sulfamethoxazole (98%). It is recommended that C. perfringens infections in Egypt should be treated with antibiotics for which resistant isolates are rare at present; namely, amoxicillin, ampicillin, cephradine, fosfomycin and florfenicol.
Yu Seungho; Lee Myunjoo; Lee Byungjin
Reports in the literature show that pharmaceuticals used in human and animal husbandry are present in soil, sediment, surface water, and groundwater. Cephalosporin belongs to a group of β-lactam antibiotics active against bacteria by interfering with the ability of bacteria to form cell walls, and is one of the widely used antibiotics in today's human medicine practice. For the study of cephalosporin oxidation by radiation, irradiations were performed with a 60 Co source available at Korea Atomic Energy Research Institute in Korea. 30 mg/L and 50 mg/L of Cefaclor and Cephradine in solution, respectively, were irradiated at 0-100 kGy. Both antibiotics were completely transformed into the byproducts at 600 Gy. No differences in results were found after purging with N 2 and O 2 gases, respectively. However, maximum 20% of COD and TOC were removed with N 2 purged, while more than 60% with O 2 purged at lower than 10 kGy. Almost 100% removal efficiency was obtained with O 2 purged at 100 kGy. In order to investigate the effect of various radicals produced, methanol and thiourea were used as radical scavengers. The experimental results showed that ·OH radical was mainly responsible for the oxidation of Cephaolosporins. (authors)
Shin, Ji Hye; Nam, Ji Hyun; Lee, Dong Hun; Yu, Seung Ho; Lee, Myun Joo
The pollution of antibiotics is a major cause of spreading antibiotics resistant bacteria in the environment. Applications of ozonation, UV, and γ-ray irradiations have been introduced to remove antibiotics in the effluents from wastewater treatment system. In this study, we compared the chemical (HPLC) and biological (antimicrobial susceptibility test, AMS) assays in measuring of the concentrations of residual antibiotics after γ-ray and UV irradiation. Most samples were degraded by γ-ray irradiation (1 ∼ 2 kGy). However, lincomycin and tetracycline were not degraded by UV irradiation. The concentration of residual antibiotics, that was treated with γ-ray and UV irradiation, measuring by bioassay was similar to HPLC. The concentrations of γ-ray irradiated cephradine measured by AMS test were 2 times higher than of HPLC assay, indicating AMS test is more sensitive than HPLC assay. These results indicate that γ-ray irradiation technique is more useful than UV irradiation, and biological assay is more useful to detect the antibiotics and toxic intermediates in antibiotics degradation
Full Text Available The objective of this work was the phylogenetic characterization of local clinical isolates of uropathogenic E. coli with respect to drug resistance. A total of 59 uropathogenic E. coli responsible for community acquired urinary tract infections were included in this study. A triplex PCR was employed to segregate each isolate into four different phylogenetic groups (A, B1, B2 and D. Drug resistance was evaluated by disc diffusion method. The drugs used were ampicillin, aztreonam, cefixime, cefoperazone, ceftriaxone, cephradine among β-lactam group; amikacin, gentamicin, and streptomycin among aminoglycosides; nalidixic acid and ciprofloxacin from quinolones; trimethoprim-sulfomethoxazole, and tetracycline. Among 59 uropathogenic E. coli isolates majority belonged to phylogenetic group B2 (50% where as 19% each belonged to groups A and B1, and 12% to group D. All the isolates were multiple drug resistant (MDR. Most effective drugs against Group A, B1, and B2 were gentamicin, amikacin and cefixime; ceftriaxone and quinolones; and ceftriaxone and amikacin, respectively. Group D isolates were found to be highly resistant to all drugs. Our results have shown emergence of MDR isolates among uropathogenic E. coli with dominance of phylogenetic group B2. However, it was found that group D isolates were though less frequent, more drug resistant as compared with group B2. Groups A and B1 were relatively uncommon. Amikacin, ceftriaxone and gentamicin were the most effective drugs in general.
Nies, Anne T; Damme, Katja; Schaeffeler, Elke; Schwab, Matthias
Antimicrobial drugs are essential in the treatment of infectious diseases. A better understanding of transport processes involved in drug disposition will improve the predictability of drug-drug interactions with consequences for drug response. Multidrug And Toxin Extrusion (MATE; SLC47A) proteins are efflux transporters mediating the excretion of several antimicrobial drugs as well as other organic compounds into bile and urine, thereby contributing to drug disposition. This review summarizes current knowledge of the structural and molecular features of human MATE transporters including their functional role in drug transport with a specific focus on antimicrobial drugs. The PubMed database was searched using the terms "MATE1," "MATE-2K," "MATE2," "SLC47A1," "SLC47A2," and "toxin extrusion protein" (up to June 2012). MATE proteins have been recognized as important transporters mediating the final excretion step of cationic drugs into bile and urine. These include the antiviral drugs acyclovir, amprenavir, and ganciclovir, the antibiotics cephalexin, cephradine and levofloxacin, as well as the antimalarial agents chloroquine and quinine. It is therefore important to enhance our understanding of the role of MATEs in drug extrusion with particular emphasis on the functional consequences of genetic variants on disposition of these antimicrobial drugs.
Full Text Available ABSTRACT: BACKGROUND: Mastitis can be caused by ineffective positioning of the baby at the breast or restricted feeding. Infective mastitis is commonly caused by Staphylococcus aureus . The prevalence of mastitis in breastfeeding women may reach 33%. Effective milk removal, pain medication and antibiotic therapy have been the mainstays of treatment. OBJECTIVES: This review aims to examine the effectiveness of antibiotic therapies in relieving symptoms for breastfeeding women with mastitis with or without laboratory investigation. METHODS: Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2012, contacted investigators and other content experts known to us for unpublished trials and scanned the reference lists of retrieved articles. Selection criteria: We selected randomised controlled trials (RCTs and quasi-RCTs comparing the effectiveness of various types of antibiotic therapies or antibiotic therapy versus alternative therapies for the treatment of mastitis. Data collection and analysis: Two review authors independently assessed trial quality and extracted data. When in dispute, we consulted a third author. MAIN RESULTS: Two trials met the inclusion criteria. One small trial (n = 25 compared amoxicillin with cephradine and found no significant difference between the two antibiotics in terms of symptom relief and abscess formation. Another, older study compared breast emptying alone as 'supportive therapy' versus antibiotic therapy plus supportive therapy, and no therapy. The findings of the latter study suggested faster clearance of symptoms for women using antibiotics, although the study design was problematic. AUTHORS CONCLUSIONS: There is insufficient evidence to confirm or refute the effectiveness of antibiotic therapy for the treatment of lactational mastitis. There is an urgent need to conduct high-quality, double-blinded RCTs to determine whether antibiotics should be used in this
Tamijevendane, S; Saravanane, R; Rajesh, R; Sivacoumar, R
The formulation and implementation of regulatory standards for the ultimate disposal and reuse of transformed products of antibiotic drugs and solvents have been a pending issue in the waste management of pharmaceutical industries especially in the developing countries like India. A case study has been identified and the current issues in one of the major pharmaceutical industry (manufacturing cephalosporin drugs) located in Chennai, India, has been discussed for the possible implementation of anaerobically transformed intermediates of antibiotic pharmaceutical waste sludge. The objective of the study was to determine the effect of bioaugmentation on the convertibility of anaerobically transformed intermediates of antibiotic pharmaceutical waste sludge into residuals and biocompost. Cephalosporin is a common name refers to cephradine (C16H19N3O4S) and cephalexin (C16H17N3O4S.H2O). Based on the critical examination of results, the industry is looking for the alternatives of either direct disposal of 7-amino-3-deacetoxycephalosporanic acid (7-ADCA) and phenyl acetic acid or for further degradation and disposal, which will essentially require additional cost and maintenance. The present regulatory standard implemented in India does not envisage such disposal alternatives and hence this would invite suggestions and recommendations of the expertise for the possible implementation on the pending issue in the antibiotic based pharmaceutical industries. The presence of cephalosporin increases total strength (Chemical Oxygen Demand) of the effluent and indirectly increases the cost of the treatment. Hence the biotransformation of cephalosporin either alone or in combination with other energetic compounds, offers the potential for an economical and environment friendly disposal alternative for the anaerobically transformed intermediates of antibiotic pharmaceutical waste sludge.
Hoque, Md. Anamul; Hossain, Mohammed Delwar; Khan, Mohammed Abdullah
Highlights: • We carry out the interaction of cephalosporin drugs with DTAB conductometrically. • We examine the effect of drugs on the critical micelle concentration of DTAB. • Three critical micelle concentrations are obtained for drug- DTAB system. • Electrostatic and hydrophobic interactions between drugs and DTAB are proposed. • Drug supported micelle formation of DTAB is much favoured in aq. solution of K 2 SO 4 . -- Abstract: The interaction of three cephalosporin drugs namely cefadroxyl monohydrate (CFM), cephalexin monohydrate (CLM) and cephradine monohydrate (CDM) with dodecyltrimethylammonium Bromide (DTAB) has been carried out by conductance measurements in aqueous medium and in aqueous solution of K 2 SO 4 salt over temperature range of (303.15 to 318.15) K. For pure DTAB and drug-DTAB systems, three critical micelle concentrations were obtained. The third critical micelle concentration (c ∗ 3 ) indicates that the spherical micelle turns into rod shape that is sphere to rod transition. The c ∗ values of DTAB are changed due to the addition of cephalosporin drugs. In addition, the change of the values of c ∗ 1 , c ∗ 2 and c ∗ 3 with increase of the concentration of drugs indicate the presence of interaction between drug and DTAB. The c ∗ values indicate that micellization for the cephalosporins-surfactant systems in water follow the order: CFM-surfactant ∗ values for the cephalosporins - DTAB systems in aqueous K 2 SO 4 are lower in magnitude than those in pure water and the values decrease with increase of the concentrations of K 2 SO 4 at a particular temperature. A significant decrease of c ∗ values in the presence of K 2 SO 4 for cephalosporins-DTAB systems indicates that drug supported ionic micelle formation is much favoured in aqueous K 2 SO 4 solution compared to that in pure water. For cephalosporin-DTAB systems, ΔG 0 m values are negative which indicate that the drugs mediated ionic micelle formation processes are
Vazquez, Juan C; Abalos, Edgardo
Urinary tract infections, including pyelonephritis, are serious complications that may lead to significant maternal and neonatal morbidity and mortality. There is a large number of drugs, and combination of them, available to treat urinary tract infections, most of them tested in non-pregnant women. Attempts to define the optimal antibiotic regimen for pregnancy have, therefore, been problematic. The objective of this review was to determine, from the best available evidence from randomised controlled trials, which agent is the most effective for the treatment of symptomatic urinary tract infections during pregnancy in terms of cure rates, recurrent infection, incidence of preterm delivery and premature rupture of membranes, admission to neonatal intensive care unit, need for change of antibiotic, and incidence of prolonged pyrexia. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (November 2009) and reference lists of articles. We considered all trials where the intention was to allocate participants randomly to one of at least two alternative treatments for any symptomatic urinary tract infection. Both review authors assessed trial quality and extracted data. We included 10 studies, recruiting a total of 1125 pregnant women. In most of the comparisons there were no significant differences between the treatments under study with regard to cure rates, recurrent infection, incidence of preterm delivery, admission to neonatal intensive care unit, need for change of antibiotic and incidence of prolonged pyrexia. When cefuroxime and cephradine were compared, there were better cure rates (29/49 versus 41/52) and fewer recurrences (20/49 versus 11/52) in the cefuroxime group. There was only one other statistically significant difference when comparing outpatient versus inpatient treatment. Gestational age at birth was greater in women from the outpatient group (38.86 versus 37.21), while birthweight was on average greater in the inpatient group
Leroy, P; Decolin, D; Nicolas, S; Archimbault, P; Nicolas, A
Residues of two antibacterial agents, cephalexin and colistin, co-administered by intramuscular injection to calves, were quantified in four different tissues (muscle, fat, liver and kidney) by column switching HPLC and by a microbiological method. For cephalexin assay, tissue samples with cephradin as internal standard were homogenized in a 5% trichloroacetic acid solution and filtrates were injected onto a concentration precolumn filled with LiChroprep RP-18 (25-40 microns). A clean-up step was incorporated by flowing a mobile phase (methanol-0.01 M phosphate buffer (pH 3.0); 15:85, v/v) through the enrichment column before elution on a LiChrospher RP-18e (5 microns) column with a methanol-phosphate buffer (30:70, v/v) at a flow rate of 1 ml min-1. Spectrometric detection was at 260 nm. An additional "off-line" washing step of extracts with methylene chloride was operated to achieve higher selectivity in the case of liver and kidney samples. The limit for quantitative assay was 0.045 micrograms g-1 with relative standard deviations in the range 5-8% and recoveries within 70%. For microbiological assay of colistin, samples were homogenized in 0.1 M hydrochloric acid-acetonitrile mixtures (3:1, v/v, for kidney and liver; 3:2, v/v, for fat and muscle). The supernatants were assayed by the cylinder plate method after evaporation to dryness under vacuum. Bordetella bronchiseptica ATCC 4617 was chosen as test organism. After a 3-h diffusion step at room temperature, the medium was incubated at 37 degrees C for 18 h and then the diameter of the growth inhibition zones was measured. Sensitivity reached 0.10-0.15 micrograms g-1. Results from the analysed samples over a 7-28 day period after drug administration show that no cephalexin was found at concentrations higher than the quantitation limit in the four test tissues and that colistin was found in muscle (injection site only) for 15 days and in kidney for 21 days.
Rafiq, Muhammad Salman; Rafiq, Muhammad Imran; Khan, Taimur; Rafiq, Maria; Khan, Mah Muneer
To determine the effectiveness of simple control measures on the infection status and characteristics of methicillin-resistant Staphylococcus aureus including susceptibility patterns among health professionals and patients in a teaching hospital. The cross-sectional study was conducted from September 2013 to January 2014, and comprised samples collected from healthcare personnel and patients in the various units of Khyber Teaching Hospital, Peshawar. The specimens were collected before and one month after the implementation of simple control measures for outbreak prevention of methicillin-resistant Staphylococcus aureus. These were tested for culture and antimicrobial susceptibility. Data about methicillin-sensitive and methicillin-resistant Staphylococcus aureus infection, wound characteristics and susceptibility patterns was collected and effectiveness of simple control measures was determined. SPSS 20 was used for statistical analysis. Of the total 390 isolates, 180(46.2%) were Staphylococcus aureus; 77(19.7%) from healthcare personnel and 103(26.4%) from patients. Of these, 164(42.1%) were methicillin-sensitive and 16(4.1%) were methicillin-resistant. Among the patients, 38(15.1%) methicillin-sensitive and 8(3.2%) methicillin-resistant isolates were recovered from wounds or skin and soft tissues. Pus with 33(13.1%) and 4(1.6%) cases respectively was the second most common source. Among methicillin-resistant isolates, resistance to Linezolid was 0%, all were resistant to Oxacillin, Cefoxitin, Amoxicillin, Cefotaxime and Cephradine, and resistance to both Co-Amoxiclav and Ciprofloxacin was 87.5%. After one month of implementation of simple control measures, the number of methicillin-resistant cases among healthcare professionals and patients dropped from 4(2.9%) and 7(10.8%) to 1(0.7%) and 5(2.7%), respectively. Methicillin-resistant and methicillin-sensitive Staphylococcus aureus differed in their anti-microbial susceptibility profiles. Selection of antibiotics
Wang, Chun-Li; Fan, Yang-Bin; Lu, Hsiao-Hwa; Tsai, Tung-Hu; Tsai, Ming-Cheng; Wang, Hui-Po
L-dopa has been used for Parkinson's disease management for a long time. However, its wide variety in the rate and the extent of absorption remained challenge in designing suitable therapeutic regime. We report here a design of using D-phenylglycine to guard L-dopa for better absorption in the intestine via intestinal peptide transporter I (PepT1). D-phenylglycine was chemically attached on L-dopa to form D-phenylglycine-L-dopa as a dipeptide prodrug of L-dopa. The cross-membrane transport of this dipeptide and L-dopa via PepT1 was compared in brush-boarder membrane vesicle (BBMV) prepared from rat intestine. The intestinal absorption was compared by in situ jejunal perfusion in rats. The pharmacokinetics after i.v. and p.o. administration of both compounds were also compared in Wistar rats. The striatal dopamine released after i.v. administration of D-phenylglycine-L-dopa was collected by brain microdialysis and monitored by HPLC. Anti-Parkinsonism effect was determined by counting the rotation of 6-OHDA-treated unilateral striatal lesioned rats elicited rotation with (+)-methamphetamine (MA). The BBMV uptake of D-phenylglycine-L-dopa was inhibited by Gly-Pro, Gly-Phe and cephradine, the typical PepT1 substrates, but not by amino acids Phe or L-dopa. The cross-membrane permeability (Pm*) determined in rat jejunal perfusion of D-phenylglycine-L-dopa was higher than that of L-dopa (2.58 ± 0.14 vs. 0.94 ± 0.10). The oral bioavailability of D-phenylglycine-L-dopa was 31.7 times higher than that of L-dopa in rats. A sustained releasing profile of striatal dopamine was demonstrated after i. v. injection of D-phenylglycine-L-dopa (50 mg/kg), indicated that D-phenylglycine-L-dopa might be a prodrug of dopamine. D-phenylglycine-L-dopa was more efficient than L-dopa in lowering the rotation of unilateral striatal lesioned rats (19.1 ± 1.7% vs. 9.9 ± 1.4%). The BBMV uptake studies indicated that D-phenylglycine facilitated the transport of L-dopa through the intestinal
Full Text Available Abstract Background l-Dopa has been used for Parkinson's disease management for a long time. However, its wide variety in the rate and the extent of absorption remained challenge in designing suitable therapeutic regime. We report here a design of using d-phenylglycine to guard l-dopa for better absorption in the intestine via intestinal peptide transporter I (PepT1. Methods d-Phenylglycine was chemically attached on l-dopa to form d-phenylglycine-l-dopa as a dipeptide prodrug of l-dopa. The cross-membrane transport of this dipeptide and l-dopa via PepT1 was compared in brush-boarder membrane vesicle (BBMV prepared from rat intestine. The intestinal absorption was compared by in situ jejunal perfusion in rats. The pharmacokinetics after i.v. and p.o. administration of both compounds were also compared in Wistar rats. The striatal dopamine released after i.v. administration of d-phenylglycine-l-dopa was collected by brain microdialysis and monitored by HPLC. Anti-Parkinsonism effect was determined by counting the rotation of 6-OHDA-treated unilateral striatal lesioned rats elicited rotation with (+-methamphetamine (MA. Results The BBMV uptake of d-phenylglycine-l-dopa was inhibited by Gly-Pro, Gly-Phe and cephradine, the typical PepT1 substrates, but not by amino acids Phe or l-dopa. The cross-membrane permeability (Pm* determined in rat jejunal perfusion of d-phenylglycine-l-dopa was higher than that of l-dopa (2.58 ± 0.14 vs. 0.94 ± 0.10. The oral bioavailability of d-phenylglycine-l-dopa was 31.7 times higher than that of l-dopa in rats. A sustained releasing profile of striatal dopamine was demonstrated after i. v. injection of d-phenylglycine-l-dopa (50 mg/kg, indicated that d-phenylglycine-l-dopa might be a prodrug of dopamine. d-Phenylglycine-l-dopa was more efficient than l-dopa in lowering the rotation of unilateral striatal lesioned rats (19.1 ± 1.7% vs. 9.9 ± 1.4%. Conclusion The BBMV uptake studies indicated that d