Iterative Chemical Engineering of Vancomycin Leads to Novel Vancomycin Analogs With a High in Vitro Therapeutic Index

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Nigam M. Mishra

2018-06-01

Full Text Available Vancomycin is a glycopeptide antibiotic that inhibits transpeptidation during cell wall synthesis by binding to the D-Ala-D-Ala termini of lipid II. For long, it has been used as a last resort antibiotic. However, since the emergence of the first vancomycin-resistant enterococci in 1987, vancomycin resistance has become widespread, especially in hospitals. We have synthesized and evaluated 110 vancomycin analogs modified at the C-terminal carboxyl group of the heptapeptide moiety with R2NHR1NH2 substituents. Through iterative optimizations of the substituents, we identified vancomycin analogs that fully restore (or even exceed the original inhibitory activity against vancomycin-resistant enterococci (VRE, vancomycin-intermediate (VISA and vancomycin-resistant Staphylococcus aureus (VRSA strains. The best analogs have improved growth inhibitory activity and in vitro therapeutic indices against a broad set of VRE and methicillin-resistant S. aureus (MRSA isolates. They also exceed the activity of vancomycin against Clostridium difficile ribotypes. Vanc-39 and Vanc-42 have a low probability to provoke antibiotic resistance, and overcome different vancomycin resistance mechanisms (VanA, VanB, and VanC1.

Genomic organization of a vancomycin-resistant staphylococcus aureus

International Nuclear Information System (INIS)

Mirani, A.Z.; Jamil, N.

2013-01-01

Objective: To study the genomic organization of vancomycin resistance in a local isolate of vancomycin resistant Staphylococcus aureus (VRSA). Study Design: Experimental study. Place and Duration of Study: Department of Microbiology, University of Karachi, January 2008 through December 2010. Methodology: A vancomycin-resistant Staphylococcus aureus (VRSA-CP2) isolate (MIC 16 mu g/ml) was isolated from a local hospital of Karachi. Species identification was confirmed by Gram staining, standard biochemical tests and PCR amplification of the nuc gene. The vancomycin MIC was re-confirmed by E-test. For the genetic determination of vancomycin resistance, in-vitro amplification of vanA cassette was performed by using plasmid DNA of CP2, CP2's transformant as template on MWG Thermo-Cycler. Amplified products of vanR, vanS, vanH, vanA, vanY, orf2, orf1D, orf2E, orf-Rev and IS element genes were subjected to Sanger's electrophoresis based sequence determination using specific primers. The Basic Local Alignment Search Tool (BLAST) algorithm was used to identify sequences in GenBank with similarities to the vanA cassette genes. Results: The vancomycin-resistant isolate CP2 was found to be resistant to oxacillin, chloramphenicol, erythromycin, rifampicin, gentamicin, tetracycline and ciprofloxacin, as well. The isolate CP2 revealed four bands: one of large molecular size approx 56.4 kb and three of small size approx 6.5 kb, approx 6.1 kb and approx 1.5 kb by agarose gel electrophoresis indicating the presence of 3 plasmids. The plasmid DNA of isolate CP2 was analyzed by PCR for the presence of the van cassettes with each of the vanA , vanB and vanC specific primers. It carried vanA cassette, which comprises of vanR, vanS, vanH, vanA, vanY, and orf2. The vanA cassette of isolate CP2 also carried an insertion element (IS). However, it did not show the PCR product for orf1. Vancomycin resistance was successfully transferred from the donor CP2 to a vancomycin-sensitive recipient S

Risk of vancomycin-resistant enterococci bloodstream infection among patients colonized with vancomycin-resistant enterococci

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Ahu Kara

2015-01-01

Conclusion: In conclusion, our study found that 1.55% of vancomycin-resistant enterococci-colonized children had developed vancomycin-resistant enterococci bloodstream infection among the pediatric intensive care unit and hematology/oncology patients; according to our findings, we suggest that immunosupression is the key point for developing vancomycin-resistant enterococci bloodstream infections.

Is Vancomycine Still a Choice for Chronic Osteomyelitis Empirical Therapy in Iran?

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Izadi, Morteza; Zamani, Mohammad Mahdi; Mousavi, Seyed Ahmad; Sadat, Seyed Mir Mostafa; Siami, Zeinab; Vais Ahmadi, Noushin; Jonaidi Jafari, Nematollah; Shirvani, Shahram; Majidi Fard, Mojgan; Imani Fooladi, Abbas Ali

2012-01-01

Background Pyogenic bacteria and especially Staphylococcus aurous (S. aurous) are the most common cause of chronic osteomyelitis. Not only treatment protocol of chronic osteomyelitis occasionally is amiss but also this malady responds to treatment difficultly. Objectives This study investigates antibiotic resistance pattern of S. aurous isolated from Iranian patients who suffer from chronic osteomyelitis by two methods: disk diffusion (Kirby bauyer) and E-test (Epsilometer test) to find Vancomycin susceptibility and MIC (Minimum inhibitory concentration). Patients and Methods One hundred and thirty one patients who suffer from chronic osteomyelitis which have been referred to both governmental and private hospitals at 2010 were tried out for culturing of osteomyelitis site (sites). Antibiotic susceptibility and MIC of isolated bacteria were investigated by Kirby bauyer and E-test respectively. Results Samples were collected from bone (73.4%), surrounding tissue (14.6%) and wound discharge (12%). S. aureus was isolated from 49.6% of the samples. According to disc diffusion, methicillin resistance S. aureus (MRSA) was 75% and Vancomycin resistance S. aurous (VRSA) was 0% and based on MIC, MRSA was 68.5% and VRSA was 0%. According to MIC experiments, maximum sensitivity was against to Vancomycin (90.2%) and ciprofloxacin (54.4%) respectively but based on disc diffusion, maximum sensitivity was against to Vancomycin (97.7%) and ciprofloxacin (43.2%), respectively (P = 0.001). E-test (9.8%) in comparison with Disc diffusion (2.3%) showed higher percent of intermediate susceptibility to Vancomycin (P = 0.017). Conclusions Comparison of antibiograms and MICs showed that Kirby bauyer technique especially for detection of VISA strains is not reliable comparison with E-test. Already VRSA strains have not detected in Iranian chronic osteomyelitis, Thus Vancomycin is the first choice for chronic osteomyelitis empirical therapy in Iran yet. PMID:23483042

Evaluating guideline adherence regarding empirical vancomycin use in patients with neutropenic fever

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Daniel B. Chastain

2018-04-01

Full Text Available Objective: The purpose of this study was to evaluate the use of empirical vancomycin for patients with neutropenic fever (NF with regard to adherence to treatment guidelines. Methods: Adult patients with a diagnosis of neutropenia, who met the definition of NF as per treatment guidelines, were identified. Use of vancomycin was evaluated as part of empirical therapy and again after 72 h. Outcomes were assessed using descriptive statistics, the Chi-square or Fisher’s exact test, and univariate exact logistic regression analyses. Results: Sixty-four patients were included. Overall, inappropriate empirical vancomycin use was observed in more than 30% of patients. Of 35 patients with indications for empirical vancomycin, only 68% received it. At 72 h, appropriate vancomycin continuation, de-escalation, or discontinuation occurred in 21 of 33 patients. On univariate regression, hematological malignancy was associated with appropriate empirical vancomycin prescribing, whether initiating or withholding (odds ratio 4.0, 95% confidence interval 1.31–12.1. No variable was independently associated with inappropriate continuation at 72 h. Conclusions: There is poor guideline adherence to vancomycin prescribing as empirical therapy and at 72-h reassessment in patients with NF. Further efforts are needed to foster a more rational use of vancomycin in patients with NF. Keywords: Antibiotics, Neutropenia, Neutropenic fever, Vancomycin

Vancomycin AUC/MIC ratio and 30-day mortality in patients with Staphylococcus aureus bacteremia.

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Holmes, Natasha E; Turnidge, John D; Munckhof, Wendy J; Robinson, J Owen; Korman, Tony M; O'Sullivan, Matthew V N; Anderson, Tara L; Roberts, Sally A; Warren, Sanchia J C; Gao, Wei; Howden, Benjamin P; Johnson, Paul D R

2013-04-01

A ratio of the vancomycin area under the concentration-time curve to the MIC (AUC/MIC) of ≥ 400 has been associated with clinical success when treating Staphylococcus aureus pneumonia, and this target was recommended by recently published vancomycin therapeutic monitoring consensus guidelines for treating all serious S. aureus infections. Here, vancomycin serum trough levels and vancomycin AUC/MIC were evaluated in a "real-world" context by following a cohort of 182 patients with S. aureus bacteremia (SAB) and analyzing these parameters within the critical first 96 h of vancomycin therapy. The median vancomycin trough level at this time point was 19.5 mg/liter. There was a significant difference in vancomycin AUC/MIC when using broth microdilution (BMD) compared with Etest MIC (medians of 436.1 and 271.5, respectively; P AUC/MIC of ≥ 400 using BMD was not associated with lower 30-day all-cause or attributable mortality from SAB (P = 0.132 and P = 0.273, respectively). However, an alternative vancomycin AUC/MIC of >373, derived using classification and regression tree analysis, was associated with reduced mortality (P = 0.043) and remained significant in a multivariable model. This study demonstrated that we obtained vancomycin trough levels in the target therapeutic range early during the course of therapy and that obtaining a higher vancomycin AUC/MIC (in this case, >373) within 96 h was associated with reduced mortality. The MIC test method has a significant impact on vancomycin AUC/MIC estimation. Clinicians should be aware that the current target AUC/MIC of ≥ 400 was derived using the reference BMD method, so adjustments to this target need to be made when calculating AUC/MIC ratio using other MIC testing methods.

Evaluating guideline adherence regarding empirical vancomycin use in patients with neutropenic fever.

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Chastain, Daniel B; Wheeler, Sarah; Franco-Paredes, Carlos; Olubajo, Babatunde; Hawkins, W Anthony

2018-04-01

The purpose of this study was to evaluate the use of empirical vancomycin for patients with neutropenic fever (NF) with regard to adherence to treatment guidelines. Adult patients with a diagnosis of neutropenia, who met the definition of NF as per treatment guidelines, were identified. Use of vancomycin was evaluated as part of empirical therapy and again after 72h. Outcomes were assessed using descriptive statistics, the Chi-square or Fisher's exact test, and univariate exact logistic regression analyses. Sixty-four patients were included. Overall, inappropriate empirical vancomycin use was observed in more than 30% of patients. Of 35 patients with indications for empirical vancomycin, only 68% received it. At 72h, appropriate vancomycin continuation, de-escalation, or discontinuation occurred in 21 of 33 patients. On univariate regression, hematological malignancy was associated with appropriate empirical vancomycin prescribing, whether initiating or withholding (odds ratio 4.0, 95% confidence interval 1.31-12.1). No variable was independently associated with inappropriate continuation at 72h. There is poor guideline adherence to vancomycin prescribing as empirical therapy and at 72-h reassessment in patients with NF. Further efforts are needed to foster a more rational use of vancomycin in patients with NF. Copyright © 2018. Published by Elsevier Ltd.

Vancomycin Resistance in Staphylococcus aureus


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McGuinness, Will A.; Malachowa, Natalia; DeLeo, Frank R.

2017-01-01

The evolution of Staphylococcus aureus during the modern antibiotic era has been delineated by distinct strain emergence events, many of which include acquisition of antibiotic resistance. The relative high burden of methicillin-resistant S. aureus (MRSA) in healthcare and community settings is a major concern worldwide. Vancomycin, a glycopeptide antibiotic that inhibits cell wall biosynthesis, remains a drug of choice for treatment of severe MRSA infections. S. aureus strains exhibiting increased resistance to vancomycin, known as vancomycin intermediate-resistant S. aureus (VISA) (MIC = 4-8 µg/mL), were discovered in the 1990s. The molecular basis of resistance in VISA is polygenic and involves stepwise mutations in genes encoding molecules predominantly involved in cell envelope biosynthesis. S. aureus isolates with complete resistance to vancomycin (MIC ≥ 16 µg/mL) are termed vancomycin-resistant S. aureus (VRSA)—they were first reported in the U.S. in 2002. Resistance in VRSA is conferred by the vanA gene and operon, which is present on a plasmid. Although treatment of VRSA infections is challenging, the total number of human VRSA infections to date is limited (14 in the U.S.). By comparison, the burden of VISA is relatively high and the molecular mechanisms of resistance are less well-defined. VISA are associated with persistent infections, vancomycin treatment failure, and poor clinical outcomes. Here, we review in brief progress made toward understanding the acquisition of antibiotic resistance in S. aureus, with an emphasis on the molecular mechanisms underlying vancomycin resistance. PMID:28656013

Protective Effects of Cilastatin against Vancomycin-Induced Nephrotoxicity

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Blanca Humanes

2015-01-01

Full Text Available Vancomycin is a very effective antibiotic for treatment of severe infections. However, its use in clinical practice is limited by nephrotoxicity. Cilastatin is a dehydropeptidase I inhibitor that acts on the brush border membrane of the proximal tubule to prevent accumulation of imipenem and toxicity. The aim of this study was to investigate the potential protective effect of cilastatin on vancomycin-induced apoptosis and toxicity in cultured renal proximal tubular epithelial cells (RPTECs. Porcine RPTECs were cultured in the presence of vancomycin with and without cilastatin. Vancomycin induced dose-dependent apoptosis in cultured RPTECs, with DNA fragmentation, cell detachment, and a significant decrease in mitochondrial activity. Cilastatin prevented apoptotic events and diminished the antiproliferative effect and severe morphological changes induced by vancomycin. Cilastatin also improved the long-term recovery and survival of RPTECs exposed to vancomycin and partially attenuated vancomycin uptake by RPTECs. On the other hand, cilastatin had no effects on vancomycin-induced necrosis or the bactericidal effect of the antibiotic. This study indicates that cilastatin protects against vancomycin-induced proximal tubule apoptosis and increases cell viability, without compromising the antimicrobial effect of vancomycin. The beneficial effect could be attributed, at least in part, to decreased accumulation of vancomycin in RPTECs.

Vancomycin Molecular Interactions: Antibiotic and Enantioselective Mechanisms

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Ward, Timothy J.; Gilmore, Aprile; Ward, Karen; Vowell, Courtney

Medical studies established that vancomycin and other related macrocyclic antibiotics have an enhanced antimicrobial activity when they are associated as dimers. The carbohydrate units attached to the vancomycin basket have an essential role in the dimerization reaction. Covalently synthesized dimers were found active against vancomycin-resistant bacterial strains. A great similarity between antibiotic potential and enantioselectivity was established. A covalent vancomycin dimer was studied in capillary electrophoresis producing excellent chiral separation of dansyl amino acids. Balhimycin is a macrocyclic glycopeptide structurally similar to vancomycin. The small differences are, however, responsible for drastic differences in enantioselectivity in the same experimental conditions. Contributions from studies examining vancomycin's mechanism for antimicrobial activity have substantially aided our understanding of its mechanism in chiral recognition.

Vancomycin Utilization Evaluation: Are We Dosing Appropriately?

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Ladan Ayazkhoo

2015-10-01

Full Text Available Background: Inappropriate use of vancomycin not only increase health care costs but also contribute to the emergence of resistant organisms. Higher trough serum vancomycin concentrations (>10mg/L has been recommended for avoidance of development of resistance. We aim to compare the administered dose with recommended doses based on guideline-recommended weight-based dosing.Methods: In a cross sectional study, all patients who received vancomycin between July and October 2013, in infectious disease, internal medicine wards and emergency department of a teaching hospital in Tehran, Iran were entered to the study. Indication of vancomycin and necessary data for dose calculation including height and serum creatinine were recorded. Prescribed doses were compared with recommended doses in guidelines and calculated Glomerular filtration rate (GFR for each patient.Results: One hundred and four patients (45 females and 59 males recruited in the study. Our results indicated that, from all administered doses of vancomycin, 64.4% and 88.8% differs significantly (more than 20% based on American Pharmacist Association (AphA vancomycin monograph and guideline-recommended, weight-based vancomycin dosing (for adults, respectively.Conclusion: Underdosing of vancomycin is a major risk factor for developing resistance of gram positive organisms to this glycopeptide. Our results showed that more than half of patients receiving vancomycin are in the risk of low drug levels based on guidelines. So, having a comprehensive plan for the proper use of this drug especially designing effective internal guidelines can prevent emergence of resistance to vancomycin in future.

Frequency of Reduced Vancomycin Susceptibility among Clinical Staphylococcus aureus Isolated in Ahvaz Iran

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Mojtaba Moosavian

2015-11-01

Full Text Available Introduction:   One   of   the   most   important   agents   in   hospital-acquired   infections   is Staphylococcus aureus. Treatment of methicillin-resistant S. aureus (MRSA infections with decreased susceptibility to vancomycin has recently been more difficult. The aim of this study was to evaluate the possible presence of vancomycin intermediate S. aureus (VISA and vancomycin- resistant S. aureus (VRSA and also to determine the frequency of MRSA in clinical specimens.Methods: In this study, 195 S. aureus isolates were collected from the patients were examined. All of the isolates were identified using standard biochemical tests.  Susceptibility of S. aureus isolates against 10 antibiotics was detected by disk diffusion method and was followed by E-test and vancomycin screen agar methods. Minimum inhibitory concentration (MIC of vancomycin was determined according to the CLSI guidelines.  Also, detection of mecA gene was performed by PCR and finally, the results were compared.Results: All of the isolates were susceptible to vancomycin (i.e. MIC range of vancomycin was between 0.25-2 µg/ml. Out of 195 S. aureus isolates, 99 isolates (50.8% were resistant to methicillin, and mecA gene was detected in 96 isolates. These results also showed that the highest and lowest resistance rate of isolates was to penicillin (96.9% and chloramphenicol (0%, respectively.Conclusion: Our findings showed that vancomycin can still be used as a valuable drug for treatment of S. aureus infections in our region. However, periodic evaluation of vancomycin MIC of S. aureus isolates is critical for monitoring MRSA and preventing the spread of VISA or VRSA among patients.

Comparative Effectiveness of Vancomycin Versus Daptomycin for MRSA Bacteremia With Vancomycin MIC >1 mg/L: A Multicenter Evaluation.

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Moise, Pamela A; Culshaw, Darren L; Wong-Beringer, Annie; Bensman, Joyce; Lamp, Kenneth C; Smith, Winter J; Bauer, Karri; Goff, Debra A; Adamson, Robert; Leuthner, Kimberly; Virata, Michael D; McKinnell, James A; Chaudhry, Saira B; Eskandarian, Romic; Lodise, Thomas; Reyes, Katherine; Zervos, Marcus J

2016-01-01

Clinical studies comparing vancomycin with alternative therapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia are limited. The objective of this study was to compare outcomes of early daptomycin versus vancomycin treatment for MRSA bacteremia with high vancomycin MICs in a geographically diverse multicenter evaluation. This nationwide, retrospective, multicenter (N = 11), matched, cohort study compared outcomes of early daptomycin with vancomycin for MRSA bloodstream infection (BSI) with vancomycin MICs 1.5 to 2 µg/mL. Matching variables, based on propensity regression analysis, included age, intensive care unit (ICU), and type of BSI. Outcomes were as follows: (1) composite failure (60-day all-cause mortality, 7-day clinical or microbiologic failure, 30-day BSI relapse, or end-of-treatment failure (EOT; discontinue/change daptomycin or vancomycin because of treatment failure or adverse event]); (2) nephrotoxicity; and (2) day 4 BSI clearance. A total of 170 patients were included. The median (interquartile range) age was 60 years (50-74); the median (range) Acute Physiology and Chronic Health Evaluation II score was 15 (10-18); 31% were in an ICU; and 92% had an infectious disease consultation. BSI types included endocarditis/endovascular (39%), extravascular (55%), and central catheter (6%). The median daptomycin dose was 6 mg/kg, and the vancomycin trough level was 17 mg/L. Overall composite failure was 35% (59 of 170): 15% due to 60-day all-cause mortality, 14% for lack of clinical or microbiologic response by 7 days, and 17% due to failure at end of therapy (discontinue/change because of treatment failure or adverse event). Predictors of composite failure according to multivariate analysis were age >60 years (odds ratio, 3.7; P day 4 bacteremia clearance rates for immunocompromised patients (n = 26) (94% vs 56% for daptomycin vs vancomycin; P = 0.035). Results from this multicenter study provide, for the first time, a geographically diverse

Study on the susceptibility of Enterococcus faecalis from infectious processes to ciprofloxacin and vancomycin

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A. Genaro

2005-09-01

Full Text Available Enterococcus faecalis is considered a pathogen responsible for hospital infections and, due to its frequent multi-resistant profile, has caused preoccupations among many medical authorities. The objective of this study was to determine the antimicrobial susceptibility of 74 strains isolated from blood cultures and purulent secretions to vancomycin and ciprofloxacin through the Minimum Inhibitory Concentration (MIC and Minimum Bactericidal Concentration (MBC by using the Microdilution test. The results showed a greater efficacy of vancomycin compared to ciprofloxacin (98.6% of the strains were inhibited by vancomycin at lower concentrations: 0.06 - 1 µg/ml. However, in the MBC analysis 73% of the strains showed a MBC of vancomycin only at high concentrations (equal to or higher than 64 µg/ml. For ciprofloxacin, the strains showed a broad sensitivity with MICs and MBCs distributed along all the MIC classes. Results also revealed a probability that some strains are tolerant to vancomycin, which indicates the need of other tests to confirm this characteristic.

Relationship between Vancomycin-Resistant Staphylococcus aureus, Vancomycin-Intermediate S. aureus, High Vancomycin MIC, and Outcome in Serious S. aureus Infections

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Holmes, Natasha E.; Johnson, Paul D. R.; Howden, Benjamin P.

2012-01-01

Vancomycin has been used successfully for over 50 years for the treatment of Staphylococcus aureus infections, particularly those involving methicillin-resistant S. aureus. It has proven remarkably reliable, but its efficacy is now being questioned with the emergence of strains of S. aureus that display heteroresistance, intermediate resistance, and, occasionally, complete vancomycin resistance. More recently, an association has been established between poor outcome and infections with strain...

Synthesis and biodistribution of 99mTc-Vancomycin in a model of bacterial infection

International Nuclear Information System (INIS)

Roohi, S.; Mushtaq, A.; Malik, S.A.

2005-01-01

Vancomycin Hydrochloride is an antibiotic produced by the growth of certain strains of Streptomyces orientalis. As vancomycin hydrochloride is poorly absorbed after oral administration; it is given intravenously for therapy of systemic infections. Vancomycin was labeled with technetium-99m pertechnetate using SnCl 2 . 2H 2 O as reducing agent. The labeling efficiency depends on ligand/reductant ratio, pH, and volume of reaction mixture. Radiochemical purity and stability of 99m Tc-Vancomycin was determined by thin layer chromatography. Biodistribution studies of 99m Tc-Vancomycin were performed in a model of bacterial infection in Sprague-Dawley rats. A significantly higher accumulation of 99m Tc-Vancomycin was seen at sites of S. aureus infected animals. Whereas uptake of 99m Tc-Vancomycin in turpentine inflamed rats were quite low. (orig.)

Vancomycin

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... is in a class of medications called glycopeptide antibiotics. It works by killling bacteria in the intestines. Vancomycin will ... part of the body when taken by mouth. Antibiotics will not work for colds, flu, or other viral infections.

High Glucose Concentration Promotes Vancomycin-Enhanced Biofilm Formation of Vancomycin-Non-Susceptible Staphylococcus aureus in Diabetic Mice.

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Chi-Yu Hsu

Full Text Available We previously demonstrated that vancomycin treatment increased acquisition of eDNA and enhanced biofilm formation of drug-resistant Staphylococcus aureus through a cidA-mediated autolysis mechanism. Recently we found that such enhancement became more significant under a higher glucose concentration in vitro. We propose that besides improper antibiotic treatment, increased glucose concentration environment in diabetic animals may further enhance biofilm formation of drug-resistant S. aureus. To address this question, the diabetic mouse model infected by vancomycin-resistant S. aureus (VRSA was used under vancomycin treatment. The capacity to form biofilms was evaluated through a catheter-associated biofilm assay. A 10- and 1000-fold increase in biofilm-bound bacterial colony forming units was observed in samples from diabetic mice without and with vancomycin treatment, respectively, compared to healthy mice. By contrast, in the absence of glucose vancomycin reduced propensity to form biofilms in vitro through the increased production of proteases and DNases from VRSA. Our study highlights the potentially important role of increased glucose concentration in enhancing biofilm formation in vancomycin-treated diabetic mice infected by drug-resistant S. aureus.

Vancomycin-induced thrombocytopenia in a 60-year-old man: a case report

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Shah Ravish A

2009-06-01

reversal after his vancomycin medication was discontinued. Conclusion Thrombocytopenia is a potentially life-threatening condition. Vancomycin is often clinically overlooked as a cause of thrombocytopenia, especially in a scenario of sepsis or when there is use of heparin. Simple laboratory testing with drug-dependent antibodies can be helpful in identifying vancomycin as a cause of thrombocytopenia.

VanA and VanB Positive Vancomycin-resistant Staphylococcus aureus Among Clinical Isolates in Shiraz, South of Iran

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Sareh Saadat

2014-09-01

Full Text Available Objective: The purpose of this study was to determine the prevalence of vancomycin-resistant Staphylococcus aureus isolated from clinical samples in Shiraz hospitals. Methods: From March to December 2012, 100 S. aureus isolates (mainly from wound and blood were collected from three hospitals in Shiraz, south of Iran. After identification of Staphylococcus aureus by biochemical, microbiological and molecular methods, antibiotic susceptibility testing was performed by Kirby-Bauer disc diffusion test for 13 different antibiotics. Vancomycin-resistant Staphylococcus aureus isolates were determined by vancomycin agar screening test and PCR for vancomycin resistant genes (vanA and vanB. Results: The lowest and highest resistance was seen for quinupristin-dalfopristin (n=1 and ampicillin (n=95, respectively. Vancomycin agar screening test showed that 37 isolates can grow on these media. Further study by PCR also detected vanA and/or vanB genes in all of these strains. Also, 19 isolates showed either vanA or vanB but were susceptible according to vancomycin agar screening test. In total, vanA and vanB resistant genes were detected in 34% and 37% of clinical isolates, respectively. Conclusion: The results showed that the frequency of vancomycin resistance genes (vanA, vanB is very high in Staphylococcus aureus strains isolated from patients in south of Iran. Thus, urgent interventions are needed to keep the emergence and transmission of these isolates to a minimum.

Characterisation of the selective binding of antibiotics vancomycin and teicoplanin by the VanS receptor regulating type A vancomycin resistance in the enterococci.

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Hughes, C S; Longo, E; Phillips-Jones, M K; Hussain, R

2017-08-01

A-type resistance towards "last-line" glycopeptide antibiotic vancomycin in the leading hospital acquired infectious agent, the enterococci, is the most common in the UK. Resistance is regulated by the VanR A S A two-component system, comprising the histidine sensor kinase VanS A and the partner response regulator VanR A . The nature of the activating ligand for VanS A has not been identified, therefore this work sought to identify and characterise ligand(s) for VanS A . In vitro approaches were used to screen the structural and activity effects of a range of potential ligands with purified VanS A protein. Of the screened ligands (glycopeptide antibiotics vancomycin and teicoplanin, and peptidoglycan components N-acetylmuramic acid, D-Ala-D-Ala and Ala-D-y-Glu-Lys-D-Ala-D-Ala) only glycopeptide antibiotics vancomycin and teicoplanin were found to bind VanS A with different affinities (vancomycin 70μM; teicoplanin 30 and 170μM), and were proposed to bind via exposed aromatic residues tryptophan and tyrosine. Furthermore, binding of the antibiotics induced quicker, longer-lived phosphorylation states for VanS A , proposing them as activators of type A vancomycin resistance in the enterococci. Copyright © 2017 Diamond Light Source Ltd. Published by Elsevier B.V. All rights reserved.

Indications for vancomycin in dialysis patients.

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Golper, T A; Schulman, G; D'Agata, E M

2000-01-01

Resistance to vancomycin has emerged among Staphylococcus aureus, coagulase-negative staphylococci (CNS), and enterococci, and this emergence has particular prevalence in dialysis units. It has therefore become imperative that physicians use vancomycin judiciously. General recommendations regarding the appropriate use of vancomycin have been developed. Although in theory implementation of these guidelines should not be difficult, the medical community may be unable or unwilling to make the necessary adjustments in practice. The onslaught of cost constraints and bureaucratic encumbrance has occurred simultaneously with the increase in vancomycin resistance among pathogens commonly isolated among the dialysis population. When a patient responds to empiric antibiotic therapy and susceptibility data indicate that an antibiotic other than vancomycin would be appropriate, the clinician far too often does not make the change to this alternative. Previously there was no biological imperative to change the antibiotic. That complacency has infected an entire generation of physicians, and especially nephrologists. Furthermore, there is an active movement against change, driven by concerns such as malpractice accusations and frank errors in the interpretation of medical facts.

Derivatives of a vancomycin-resistant Staphylococcus aureus strain isolated at Hershey Medical Center.

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Bozdogan, Bülent; Ednie, Lois; Credito, Kim; Kosowska, Klaudia; Appelbaum, Peter C

2004-12-01

Antimicrobial susceptibilities and genetic relatedness of the vancomycin-resistant Staphylococcus aureus strain (VRSA) isolated at Hershey, Pa. (VRSA Hershey), and its vancomycin-susceptible and high-level-resistant derivatives were studied and compared to 32 methicillin-resistant S. aureus strains (MRSA) isolated from patients and medical staff in contact with the VRSA patient. Derivatives of VRSA were obtained by subculturing six VRSA colonies from the original culture with or without vancomycin. Ten days of drug-free subculture caused the loss of vanA in two vancomycin-susceptible derivatives for which vancomycin MICs were 1 to 4 microg/ml. Multistep selection of three VRSA clones with vancomycin for 10 days increased vancomycin MICs from 32 to 1,024 to 2,048 microg/ml. MICs of teicoplanin, dalbavancin, and oritavancin were also increased from 4, 0.5, and 0.12 to 64, 1, and 32 microg/ml, respectively. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing analysis indicated that VRSA Hershey was the vanA-acquired variety of a common MRSA clone in our hospital with sequence type 5 (ST5). Three of five vancomycin-intermediate S. aureus strains tested from geographically different areas were also ST5, and the Michigan VRSA was ST371, a one-allele variant of ST5. Derivatives of VRSA Hershey had differences in PFGE profiles and the size of SmaI fragment that carries the vanA gene cluster, indicating instability of this cluster in VRSA Hershey. However induction with vancomycin increased glycopeptide MICs and stabilized the resistance.

Vancomycin Injection

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... is in a class of medications called glycopeptide antibiotics. It works by killing bacteria that cause infections.Antibiotics such as vancomycin injection will not work for colds, flu, or other viral infections. Taking ...

Continuous infusion of vancomycin : Effective, efficient and safe

NARCIS (Netherlands)

Van Maarseveen, E.; Touw, D.; Bouma, A.; Van Zanten, A.

Aims: Vancomycin is an antibiotic which is used in (suspected or proven) bacteriaemia, peritonitis or osteomyelitis with grampositive micro-organisms. Currently in most Dutch hospitals vancomycin is administered as an intermittent infusion. As the killing of vancomycin is dependent of the AUC/MIC

Evaluation of risk factors for vancomycin-induced nephrotoxicity.

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Park, So Jin; Lim, Na Ri; Park, Hyo Jung; Yang, Jae Wook; Kim, Min-Ji; Kim, Kyunga; In, Yong Won; Lee, Young Mee

2018-05-09

Background Vancomycin is a glycopeptide antibiotic of choice for the treatment of serious infections caused by multi-resistant Gram-positive bacteria. However, vancomycin-associated nephrotoxicity (VAN) often limits its use. Previous data suggested a few risk factors of VAN, including higher mean vancomycin trough level, higher daily doses, old age, long duration of vancomycin therapy, and concomitant nephrotoxins. Objective To evaluate the incidence and risk factors of VAN and determine whether higher vancomycin trough concentrations were associated with a greater risk for VAN. Settings A retrospective, observational, single-center study at the 1960-bed university-affiliated tertiary care hospital (Samsung Medical Center), Seoul, Korea. Method A retrospective analysis of adult patients who received vancomycin parenterally in a tertiary care medical center from March 1, 2013 to June 30, 2013 was performed. We excluded patients with a baseline serum creatinine level > 2 mg/dL and those who had a history of end-stage renal disease and dialysis at baseline. The clinical characteristics were compared between patients with nephrotoxicity and those without nephrotoxicity to identify the risk factors associated with VAN. Main outcome measure Incidence of VAN and VAN-associated risk factors were analyzed. Results Of the 315 vancomycin-treated patients, nephrotoxicity occurred in 15.2% of the patients. In multivariate analysis, higher vancomycin trough concentrations of > 20 mg∕L (OR 9.57, 95% CI 2.49-36.83, p < 0.01) and intensive care unit (ICU) residence (OR 2.86, 95% CI 1.41-5.82, p < 0.01) were independently associated with VAN. Conclusion Our findings suggest that higher vancomycin trough levels and ICU residence might be associated with a greater risk for VAN. More careful monitoring of vancomycin serum trough levels and patient status might facilitate the timely prevention of VAN.

Uncommon vancomycin: induced side effects

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Rocha Jaime Luís Lopes

2002-01-01

Full Text Available Vancomycin has been used with increased frequency during the past 15 years and the most common toxicity with this drug is the "red man syndrome". Other adverse effects include neutropenia, fever, phlebitis, nephrotoxicity, ototoxicity, thrombocytopenia, interstitial nephritis, lacrimation, linear IgA bullous dermatosis, necrotizing cutaneous vasculitis and toxic epidermal necrolysis. Only two cases of vancomycin-induced Stevens-Johnson syndrome and one case of pancytopenia have been reported in the medical literature. The treatment for both situations is based on cessation of the vancomycin therapy; in cases of Stevens-Johnson syndrome, antihistamine and/or steroid agents can be used. This article reports a case of pancytopenia and a case of erythema major associated with neutropenia.

A Promising Approach to Provide Appropriate Colon Target Drug Delivery Systems of Vancomycin HCL: Pharmaceutical and Microbiological Studies

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Kadria A. Elkhodairy

2014-01-01

Full Text Available Vancomycin HCl was prepared as orally administered colon target drug delivery tablets for systemic therapy. Tablet matrices containing 10–60% of tablet weight of guar gum (F1–F6 were prepared by direct compression and subjected to in vitro release studies to explore their sustained release in the colon. Various synthetic and natural polymers were incorporated to F6 to modify the drug release rate. Different 15 matrix tablet formulations (F6–F20 were enteric coated with hydroxypropyl methyl cellulose phthalate. F6, F13 and F20 showed promising sustained release results having median dissolution time (MDT values: 8.25, 7.97, and 7.64, respectively. Microbiological assay was performed to test the efficacy of F6, F13, and F20 to inhibit clinical Staphylococcus aureus (SA isolates. Bactericidal activity of F6 was reached after 2, 4, and 24 hours of incubation against MSSA 18, MRSA 29, and MRSA 11 strains, respectively, while it was reached within 6–8 hours in case of F13, and F20 against all strains tested. F13 enhanced log microbial reduction by 1.74, 0.65 and 2.4 CFU/mL compared to F6 while it was 1, 2.57 and 1.57 compared to F20 against MSSA18, MRSA11 and MRSA29, respectively. Vancomycin HCl tablets displayed a promising sustained release in vitro and microbiological inhibitory action on all isolates tested.

A promising approach to provide appropriate colon target drug delivery systems of vancomycin HCL: pharmaceutical and microbiological studies.

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Elkhodairy, Kadria A; Afifi, Samar A; Zakaria, Azza S

2014-01-01

Vancomycin HCl was prepared as orally administered colon target drug delivery tablets for systemic therapy. Tablet matrices containing 10-60% of tablet weight of guar gum (F1-F6) were prepared by direct compression and subjected to in vitro release studies to explore their sustained release in the colon. Various synthetic and natural polymers were incorporated to F6 to modify the drug release rate. Different 15 matrix tablet formulations (F6-F20) were enteric coated with hydroxypropyl methyl cellulose phthalate. F6, F13 and F20 showed promising sustained release results having median dissolution time (MDT) values: 8.25, 7.97, and 7.64, respectively. Microbiological assay was performed to test the efficacy of F6, F13, and F20 to inhibit clinical Staphylococcus aureus (SA) isolates. Bactericidal activity of F6 was reached after 2, 4, and 24 hours of incubation against MSSA 18, MRSA 29, and MRSA 11 strains, respectively, while it was reached within 6-8 hours in case of F13, and F20 against all strains tested. F13 enhanced log microbial reduction by 1.74, 0.65 and 2.4 CFU/mL compared to F6 while it was 1, 2.57 and 1.57 compared to F20 against MSSA18, MRSA11 and MRSA29, respectively. Vancomycin HCl tablets displayed a promising sustained release in vitro and microbiological inhibitory action on all isolates tested.

Synergy of β-Lactams with Vancomycin against Methicillin-Resistant Staphylococcus aureus: Correlation of Disk Diffusion and Checkerboard Methods.

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Sy, Cheng Len; Huang, Tsi-Shu; Chen, Chii Shiang; Chen, Yao-Shen; Tsai, Hung-Chin; Wann, Shue-Renn; Wu, Kuan-Sheng; Chen, Jui-Kuang; Lee, Susan Shin-Jung; Liu, Yung-Ching

2016-03-01

Modified disk diffusion (MDD) and checkerboard tests were employed to assess the synergy of combinations of vancomycin and β-lactam antibiotics for 59 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Mu50 (ATCC 700699). Bacterial inocula equivalent to 0.5 and 2.0 McFarland standard were inoculated on agar plates containing 0, 0.5, 1, and 2 μg/ml of vancomycin. Oxacillin-, cefazolin-, and cefoxitin-impregnated disks were applied to the surface, and the zones of inhibition were measured at 24 h. The CLSI-recommended checkerboard method was used as a reference to detect synergy. The MICs for vancomycin were determined using the Etest method, broth microdilution, and the Vitek 2 automated system. Synergy was observed with the checkerboard method in 51% to 60% of the isolates when vancomycin was combined with any β-lactam. The fractional inhibitory concentration indices were significantly lower in MRSA isolates with higher vancomycin MIC combinations (P synergy in MRSA isolates with bacterial inocula equivalent to McFarland standard 0.5 were 33.0% and 62.5% for oxacillin, 45.1% and 52.4% for cefazolin, and 43.1% and 52.4% for cefoxitin when combined with 0.5 and 2 μg/ml of vancomycin, respectively. Based on our study, the simple MDD method is not recommended as a replacement for the checkerboard method to detect synergy. However, it may serve as an initial screening method for the detection of potential synergy when it is not feasible to perform other labor-intensive synergy tests. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

High-throughput determination of vancomycin in human plasma by a cost-effective system of two-dimensional liquid chromatography.

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Sheng, Yanghao; Zhou, Boting

2017-05-26

Therapeutic drug monitoring (TDM) is one of the most important services of clinical laboratories. Two main techniques are commonly used: the immunoassay and chromatography method. We have developed a cost-effective system of two-dimensional liquid chromatography with ultraviolet detection (2D-LC-UV) for high-throughput determination of vancomycin in human plasma that combines the automation and low start-up costs of the immunoassay with the high selectivity and sensitivity of the liquid chromatography coupled with mass spectrometric detection without incurring their disadvantages, achieving high cost-effectiveness. This 2D-LC system offers a large volume injection to provide sufficient sensitivity and uses simulated gradient peak compression technology to control peak broadening and to improve peak shape. A middle column was added to reduce the analysis cycle time and make it suitable for high-throughput routine clinical assays. The analysis cycle time was 4min and the peak width was 0.8min. Compared with other chromatographic methods that have been developed, the analysis cycle time and peak width for vancomycin was reduced significantly. The lower limit of quantification was 0.20μg/mL for vancomycin, which is the same as certain LC-MS/MS methods that have been recently developed and validated. The method is rapid, automated, and low-cost and has high selectivity and sensitivity for the quantification of vancomycin in human plasma, thus making it well-suited for use in hospital clinical laboratories. Copyright © 2017 Elsevier B.V. All rights reserved.

DRESS with delayed onset acute interstitial nephritis and profound refractory eosinophilia secondary to Vancomycin

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O'Meara Paloma

2011-10-01

Full Text Available Abstract Background Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS is a relatively rare clinical entity; even more so in response to vancomycin. Methods Case report. Results We present a severe case of vancomycin-induced DRESS syndrome, which on presentation included only skin, hematological and mild liver involvement. The patient further developed severe acute interstitial nephritis, eosinophilic pneumonitis, central nervous system (CNS involvement and worsening hematological abnormalities despite immediate discontinuation of vancomycin and parenteral corticosteroids. High-dose corticosteroids for a prolonged period were necessary and tapering of steroids a challenge due to rebound-eosinophilia and skin involvement. Conclusion Patients with DRESS who are relatively resistant to corticosteroids with delayed onset of certain organ involvement should be treated with a more prolonged corticosteroid tapering schedule. Vancomycin is increasingly being recognized as a culprit agent in this syndrome.

Determining vancomycin clearance in an overweight and obese population.

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Leong, Julie V B; Boro, Maureen S; Winter, Michaele

2011-04-01

Two methods of calculating vancomycin clearance were compared to determine the best body weight measure to use when dosing vancomycin for overweight and obese patients. Hospitalized veterans weighing more than 120% of their ideal body weight (IBW) with serum vancomycin concentrations (SVCs) drawn between January 1, 2003, and June 30, 2005, were eligible for study inclusion. Exclusion criteria included weight of more than 300% the IBW, unstable renal function, dialysis, uncertain vancomycin dosing or sampling times, and distribution-phase sampling. Data from January 1 through December 31, 2003 (phase 1) determined the best-fit weight for vancomycin clearance for the Leonard and Boro method. The bias and precision of the modified Leonard and Boro method using the best-fit weight for vancomycin clearance were then compared with those of the Rushing and Ambrose method for predicting SVCs from January 1, 2004, through June 30, 2005 (phase 2). Forty-eight patients were included in phase 1, with 67 SVCs for analysis. During phase 1, adjusted body weight (ABW), using the Leonard and Boro method, was superior in predicting vancomycin clearance and the resultant SVCs. A total of 96 patients were included in phase 2 of the study, with 160 SVCs for analysis. The modified Leonard and Boro method was significantly more precise than the Rushing and Ambrose method in predicting vancomycin clearance. Use of ABW proved to be superior compared with total body weight when estimating vancomycin clearance in overweight and obese patients. While there was no difference in bias between methods, the modified Leonard and Boro method was significantly more precise than the Rushing and Ambrose method in predicting SVCs when dosing vancomycin for obese patients.

Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia.

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Soriano, Alex; Marco, Francesc; Martínez, José A; Pisos, Elena; Almela, Manel; Dimova, Veselka P; Alamo, Dolores; Ortega, Mar; Lopez, Josefina; Mensa, Josep

2008-01-15

Vancomycin treatment failure in methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is not uncommon, even when MRSA is susceptible to vancomycin. The aim of our study was to evaluate whether vancomycin minimum inhibitory concentration has any influence on the mortality associated with MRSA bacteremia. A total of 414 episodes of MRSA bacteremia were prospectively followed-up from 1991 through 2005. MIC of vancomycin for the first isolate was determined by E-test. Clinical variables recorded were age, comorbidity, prior administration of vancomycin, use of corticosteroids, prognosis of underlying disease, source of bacteremia, the need for mechanical ventilation, shock, and mortality. A "treatment group" variable was created and defined as follows: (1) receipt of empirical vancomycin and an isolate with a vancomycin MIC of 1 microg/mL (38 episodes), (2) receipt of empirical vancomycin and an isolate with a vancomycin MIC of 1.5 microg/mL (90 episodes), (3) receipt of empirical vancomycin and an isolate with a vancomycin MIC of 2 microg/mL (40 episodes), and (4) receipt of inappropriate empirical therapy (246 episodes). Univariate and multivariate analyses were performed. Episodes caused by strains with a vancomycin MIC of 2 microg/mL were independently associated with a lower risk of shock (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.15-0.75). Multivariate analysis selected receipt of empirical vancomycin and an isolate with a vancomycin MIC of 2 microg/mL (OR, 6.39; 95% CI, 1.68-24.3), receipt of inappropriate empirical therapy (OR, 3.62; 95% CI, 1.20-10.9), increasing age (OR, 1.02; 95% CI, 1.00-1.04), use of corticosteroids (OR, 1.85; 95% CI, 1.04-3.29), an ultimately (OR, 10.2; 95% CI, 2.85-36.8) or rapidly (OR, 1.81; 95% CI, 1.06-3.10) fatal underlying disease, high-risk (OR, 3.60; 95% CI, 1.89-6.88) and intermediate-risk (OR, 2.18; 95% CI, 1.17-4.04) sources of bacteremia, and shock (OR, 7.38; 95% CI, 4.11-13.3) as the best predictors of

AUC-Guided Vancomycin Dosing in Adolescent Patients With Suspected Sepsis.

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Lanke, Shankar; Yu, Tian; Rower, Joseph E; Balch, Alfred H; Korgenski, E Kent; Sherwin, Catherine M

2017-01-01

Vancomycin is a first-line treatment for β-lactam-resistant Gram-positive bacterial infections. Understanding the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of vancomycin in an adolescent population is of clinical importance in this often overlooked pediatric population. This retrospective study investigated vancomycin PK-PD in an adolescent cohort (12 to 18 years of age) of 463 patients (57% male, 81% white) admitted to the Intermountain Healthcare System between January 2006 and December 2013. Population PK modeling was performed in NONMEM 7.3. Vancomycin PK was well described with a 1-compartment model that identified both body weight (WT) and creatinine clearance (CRCL) as covariates significantly impacting vancomycin disposition. The model was then utilized to determine dosing strategies that achieved the targeted area under the 24-hour time curve vs minimum inhibitory concentration (AUC 0-24 /MIC) ratio of ≥400. Additionally, these data were correlated with minimum steady-state concentrations (C ss,min ) to find an acceptable target trough concentration range in adolescents. This analysis demonstrated that C ss,min ranging from 10 to 12.5 mg/L were highly predictive of achieving an AUC 0-24 /MIC ≥400 when the MIC was ≤1 mg/L. These results suggest that the target trough concentration for adolescents may be lower than that for adults. © 2016, The American College of Clinical Pharmacology.

In vitro activity of flomoxef and cefazolin in combination with vancomycin.

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Simon, C; Simon, M

1991-01-01

207 clinical isolates from strains of patients from the University Children's Hospital of Kiel were investigated for their in vitro activity with the agar dilution method against flomoxef and cefazolin (alone and partially in combination with vancomycin). Staphylococci were also tested with other cephalosporins (cefoxitin, cefamandole, cefotaxime, cefotetan and latamoxef). Flomoxef and cefazolin always acted more vigorously on staphylococci than the other cephalosporins. Resistance of Staphylococcus aureus strains against flomoxef and cefazolin did not occur but was found in 15 and 5 of 98 Staphylococcus epidermidis strains, respectively. Enterococcus faecalis strains were always resistant against both drugs; Streptococcus faecium strains were only moderately sensitive. Combined testing of flomoxef or cefazolin with vancomycin showed synergism in almost all staphylococcal strains. Synergism was stronger when S. epidermidis strains were only weakly sensitive to or resistant against flomoxef and cefazolin in comparison to highly sensitive strains. Flomoxef (or cefazolin) acted synergistically in combination with vancomycin on E. faecalis and S. faecium with the exception of two strains of E. faecalis which showed an additive effect of both drugs.

Infection dynamics of vancomycin and inducible clindamycin resistant Enterococcus faecalis in an Indian teaching hospital

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Debasmita Dubey

2015-06-01

Full Text Available Objective: To do surveillance for vancomycin and inducible clindamycin resistance of Enterococcus faecalis (E. faecalis, a Gram-positive bacterium in a teaching hospital. Methods: E. faecalis strains isolated from clinical samples were screened for vancomycin and inducible clindamycin resistance, i.e., D-test positivity, using vancomycin screen agar and blood agar plates, respectively. For the D-test screening, erythromycin resistant (Er-r and clindamycin sensitive (Cd-s strain were used. Results: Of 265 isolated E. faecalis strains, 159 (60% were vancomycin resistant Enterococcus (VRE and 106 were vancomycin sensitive Enterococcus (VSE. Of 265 strains, 42 were constitutively resistant to clindamycin and erythromycin and of 148 Er-r and Cd-s strains, 87 (32.83% had D-test positivity, while the rest 61 strains were D-test negatives. D-test results examined with 6 hospital factors as bivalents, only 2 factors, the VSE/VRE and the presence/absence of prior antibiotic use > 90 days bivalent were statistically significant. A VRE strain with D-test positivity would be picked up 0.570 2 times more frequently than a strain with VSE and D-test positivity. Also, patients with prior antibiotic use > 90 days had 3.737 5 times more chance of picking up D-test positive strains than patients without any prior antibiotic use. Resistance pattern of E. faecalis strains to individual 14 antibiotics were recorded; the maximum values of resistance were against ampicillin 10 μg/disc and linezolid 30 μg/disc. Student’s t-test for hospital acquired and community acquired data revealed that drug resistant strains were equally prevalent in both sources. Conclusions: Prevalence of 60% VRE in both hospital and adjoining community creates consternation. In total 87 (32.83% strains had D-test positivity; patients who had used antibiotics within the last 90 days have got an ample chance of picking of D-test positive E. faecalis. D-test protocol should be followed with

Treatment of Clostridium difficile infection in mice with vancomycin alone is as effective as treatment with vancomycin and metronidazole in combination

DEFF Research Database (Denmark)

Erikstrup, Lise Tornvig; Aarup, Mie; Hagemann-Madsen, Rikke

2015-01-01

OBJECTIVE: Clostridium difficile is a major cause of nosocomial infectious diarrhoea. Treatment of C. difficile infection (CDI) depends on disease severity. A combination of vancomycin and metronidazole is often recommended in severe cases. The aim of this study was to examine, in a murine model....... difficile toxins. RESULTS: None of the mice in the vancomycin-treated group died during the treatment phase compared to a mortality of 17%, 33% and 55% in the combination, metronidazole and infected control group, respectively. Mice treated with vancomycin alone or in combination with metronidazole...... of CDI, if mice treated with a combination of vancomycin and metronidazole had a better clinical outcome than mice treated with vancomycin or metronidazole alone. DESIGN: C57BL/6J mice pretreated with an antimicrobial mixture were challenged with C. difficile VPI 10463 or phosphate-buffered saline...

Population pharmacokinetics of vancomycin in Jordanian patients

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predictors of vancomycin clearance include: weight, serum creatinine, chronic renal ... (http://www.budapestopenaccessinitiative.org/read), which permit ... reproduction in any medium, provided the original work is properly credited. ... fluid balance; and albumin levels]); (3) .... vancomycin half-life is prolonged in patients with.

Red man syndrome caused by vancomycin powder.

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Nagahama, Yasunori; VanBeek, Marta J; Greenlee, Jeremy D W

2018-04-01

Red man syndrome (RMS) is a well-known hypersensitivity reaction caused by intravenous administration of vancomycin, with symptoms ranging from flushing, erythematous rash, pruritus, mild to profound hypotension, and even cardiac arrest. RMS has not previously been described from local application of vancomycin powder in a surgical wound, a technique increasingly utilized for infection prophylaxis in many surgical disciplines including neurosurgery. We describe the first reported case of RMS as a result of local intra-wound application of vancomycin powder for infection prophylaxis. A 73-year-old male with a history of Parkinson's disease underwent 2-stage deep brain stimulation implantation surgeries. Vancomycin powder was applied locally in the surgical wounds for infection prophylaxis during both of the surgeries. The patient developed a well-demarcated, geometric erythematous pruritic rash following the second surgery that was clinically diagnosed as RMS and resolved without sequelae. Copyright © 2018 Elsevier Ltd. All rights reserved.

Biosafety of the Novel Vancomycin-loaded Bone-like Hydroxyapatite/Poly-amino Acid Bony Scaffold

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Zhi-Dong Cao

2016-01-01

Full Text Available Background: Recently, local sustained-release antibiotics systems have been developed because they can increase local foci of concentrated antibiotics without increasing the plasma concentration, and thereby effectively decrease any systemic toxicity and side effects. A vancomycin-loaded bone-like hydroxyapatite/poly-amino acid (V-BHA/PAA bony scaffold was successfully fabricated with vancomycin-loaded poly lactic-co-glycolic acid microspheres and BHA/PAA, which was demonstrated to exhibit both porosity and perfect biodegradability. The aim of this study was to systematically evaluate the biosafety of this novel scaffold by conducting toxicity tests in vitro and in vivo. Methods: According to the ISO rules for medical implant biosafety, for in vitro tests, the scaffold was incubated with L929 fibroblasts or rabbit noncoagulant blood, with simultaneous creation of positive control and negative control groups. The growth condition of L929 cells and hemolytic ratio were respectively evaluated after various incubation periods. For in vivo tests, a chronic osteomyelitis model involving the right proximal tibia of New Zealand white rabbits was established. After bacterial identification, the drug-loaded scaffold, drug-unloaded BHA/PAA, and poly (methyl methacrylate were implanted, and a blank control group was also set up. Subsequently, the in vivo blood drug concentrations were measured, and the kidney and liver functions were evaluated. Results: In the in vitro tests, the cytotoxicity grades of V-BHA/PAA and BHA/PAA-based on the relative growth rate were all below 1. The hemolysis ratios of V-BHA/PAA and BHA/PAA were 2.27% and 1.42%, respectively, both below 5%. In the in vivo tests, the blood concentration of vancomycin after implantation of V-BHA/PAA was measured at far below its toxic concentration (60 mg/L, and the function and histomorphology of the liver and kidney were all normal. Conclusion: According to ISO standards, the V-BHA/PAA scaffold

Vancomycin treatment of infective endocarditis is linked with recently acquired obesity.

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Franck Thuny

Full Text Available BACKGROUND: Gut microbiota play a major role in digestion and energy conversion of nutrients. Antibiotics, such as avoparcin (a vancomycin analogue, and probiotics, such as Lactobacillus species, have been used to increase weight in farm animals. We tested the effect of antibiotics given for infective endocarditis (IE on weight gain (WG. METHODOLOGY/PRINCIPAL FINDINGS: Forty-eight adults with a definite diagnosis of bacterial IE (antibiotic group were compared with forty-eight age-matched controls without IE. Their body mass index (BMI was collected at one month before the first symptoms and one year after hospital discharge. The BMI increased significantly and strongly in vancomycin-plus-gentamycin-treated patients (mean [+/-SE] kg/m(2, +2.3 [0.9], p = 0.03, but not in controls or in patients treated with other antibiotics. Seventeen patients had a BMI increase of >or=10%, and five of the antibiotic group developed obesity. The treatment by vancomycin-plus-gentamycin was an independent predictor of BMI increase of >or=10% (adjusted OR, 6.7; 95% CI, 1.37-33.0; p = 0.02, but not treatment with other antibiotics. Weight gain was particularly high in male patients older than 65 who did not undergo cardiac surgery. Indeed, all three vancomycin-treated patients with these characteristics developed obesity. CONCLUSIONS/SIGNIFICANCE: A major and significant weight gain can occur after a six-week intravenous treatment by vancomycin plus gentamycin for IE with a risk of obesity, especially in males older than 65 who have not undergone surgery. We speculate on the role of the gut colonization by Lactobacillus sp, a microorganism intrinsically resistant to vancomycin, used as a growth promoter in animals, and found at a high concentration in the feces of obese patients. Thus, nutritional programs and weight follow-up should be utilized in patients under such treatment.

Pediatric vancomycin use in 421 hospitals in the United States, 2008.

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Tamar Lasky

Full Text Available Recommendations to prevent the spread of vancomycin resistance have been in place since 1995 and include guidelines for inpatient pediatric use of vancomycin. The emergence of large databases allows us to describe variation in pediatric vancomycin across hospitals. We analyzed a database with hospitalizations for children under 18 at 421 hospitals in 2008.The Premier hospital 2008 database, consisting of records for 877,201 pediatric hospitalizations in 421 hospitals, was analyzed. Stratified analyses and logistic mixed effects models were used to calculate the probability of vancomycin use while considering random effects of hospital variation, hospital fixed effects and patient effects, and the hierarchical structure of the data. Most hospitals (221 had fewer than 10 hospitalizations with vancomycin use in the study period, and 47 hospitals reported no vancomycin use in 17,271 pediatric hospitalizations. At the other end of the continuum, 21 hospitals (5.6% of hospitals each had over 200 hospitalizations with vancomycin use, and together, accounted for more than 50% of the pediatric hospitalizations with vancomycin use. The mixed effects modeling showed hospital variation in the probability of vancomycin use that was statistically significant after controlling for teaching status, urban or rural location, size, region of the country, patient ethnic group, payor status, and APR-mortality and severity codes.The number and percentage of pediatric hospitalizations with vancomycin use varied greatly across hospitals and was not explained by hospital or patient characteristics in our logistic models. Public health efforts to reduce vancomycin use should be intensified at hospitals with highest use.

Occurrence of vancomycin-resistant Staphylococcus aureus in the oral cavity of patients with dental caries.

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Vellappally, Sajith; Divakar, Darshan Devang; Al Kheraif, Abdulaziz Abdullah; Ramakrishnaiah, Ravikumar; Alqahtani, Amer; Dalati, M H N; Anil, Sukumaran; Khan, Aftab Ahmed; Harikrishna Varma, P R

2017-09-01

Oral streptococci are the major group of microbes isolated from oral microflora. They represent frequent pathogens of infective endocarditis (IE), and it is assumed that in most of the cases oral streptococci are acquired via mucosa layer of oral cavity. Staphylococcus aureus is also frequently isolated from IE as it accounts for 20%-30% of all cases. Vancomycin has been the most reliable therapeutic agent against infections caused by methicillin-resistant S. aureus (MRSA). The main objective of this study was to examine the occurrence of S. aureus species in dental caries specimens. Antimicrobial susceptibility testing of S. aureus to four antibiotics namely vancomycin, linezolid, teicoplanin, and daptomycin was performed. Detection of vancomycin resistance was conducted using polymerase chain reaction. Among the tested 150 strains, 98 were MRSA and of that 54 were vancomycin sensitive and 27 were resistant. All 98 MRSA strains were positive for mecA and 36 yielded pvl, whereas 13 carried vanA and only 2 were positive for vanB. Majority of the isolates showed sensitivity toward daptomycin and linezolid. Strains of S. aureus exhibiting decreased susceptibility to different antibiotics like vancomycin, daptomycin, and linezolid severely compromise the therapeutic alternatives and require a considerable amount of time, public awareness, and integrative health-care strategies to prevent the emergence of resistance to these compounds.

Performance of the EUCAST disk diffusion method, the CLSI agar screen method, and the Vitek 2 automated antimicrobial susceptibility testing system for detection of clinical isolates of Enterococci with low- and medium-level VanB-type vancomycin resistance

DEFF Research Database (Denmark)

Hegstad, Kristin; Giske, Christian G; Haldorsen, Bjørg

2014-01-01

faecium (n=18) strains with and without nonsusceptibility to vancomycin was examined blindly in Danish (n=5), Norwegian (n=13), and Swedish (n=10) laboratories using the EUCAST disk diffusion method (n=28) and the CLSI agar screen (n=18) or the Vitek 2 system (bioMérieux) (n=5). The EUCAST disk diffusion...... method (very major error [VME] rate, 7.0%; sensitivity, 0.93; major error [ME] rate, 2.4%; specificity, 0.98) and CLSI agar screen (VME rate, 6.6%; sensitivity, 0.93; ME rate, 5.6%; specificity, 0.94) performed significantly better (P=0.02) than the Vitek 2 system (VME rate, 13%; sensitivity, 0.87; ME...... rate, 0%; specificity, 1). The performance of the EUCAST disk diffusion method was challenged by differences in vancomycin inhibition zone sizes as well as the experience of the personnel in interpreting fuzzy zone edges as an indication of vancomycin resistance. Laboratories using Oxoid agar (P

Internalization of Staphylococcus aureus in Lymphocytes Induces Oxidative Stress and DNA Fragmentation: Possible Ameliorative Role of Nanoconjugated Vancomycin

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Subhankari Prasad Chakraborty

2011-01-01

Full Text Available Staphylococcus aureus is the most frequently isolated pathogen causing bloodstream infections, skin and soft tissue infections and pneumonia. Lymphocyte is an important immune cell. The aim of the present paper was to test the ameliorative role of nanoconjugated vancomycin against Vancomycin-sensitive Staphylococcus aureus (VSSA and vancomycin-resistant Staphylococcus aureus (VRSA infection-induced oxidative stress in lymphocytes. VSSA and VRSA infections were developed in Swiss mice by intraperitoneal injection of 5×106 CFU/mL bacterial solutions. Nanoconjugated vancomycin was adminstrated to VSSA- and VRSA-infected mice at its effective dose for 10 days. Vancomycin was adminstrated to VSSA- and VRSA-infected mice at a similar dose, respectively, for 10 days. Vancomycin and nanoconjugated vancomycin were adminstrated to normal mice at their effective doses for 10 days. The result of this study reveals that in vivo VSSA and VRSA infection significantly increases the level of lipid peroxidation, protein oxidation, oxidized glutathione level, nitrite generation, nitrite release, and DNA damage and decreases the level of reduced glutathione, antioxidant enzyme status, and glutathione-dependent enzymes as compared to control group, which were increased or decreased significantly near to normal in nanoconjugated vancomycin-treated group. These findings suggest the potential use and beneficial role of nanoconjugated vancomycin against VSSA and VRSA infection-induced oxidative stress in lymphocytes.

An optimal method for generating stable vancomycin heteroresistance and intermediate susceptibility in methicillin-resistant Staphylococcus aureusblood isolates under in-vitro vancomycin pressure

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Riad Khatib

2012-12-01

Full Text Available Objectives: The relevance of vancomycin intermediately-susceptible (VISA and hetero-resistant (hVISA methicillin-resistantStaphylococcus aureus (MRSA remains uncertain because of their low frequency. In vitro attempts to generate reducedsusceptibility have been inconsistent. We describe a simple method for generating VISA/hVISA.Materials and methods: Twenty-four SCCmec type II and IV MRSA blood isolates plus USA100 and USA300 controls werecultured (107 CFU/ml in BHI broth with 0, 2 and 3 mg/L vancomycin for 10 days followed by 10 days vancomycin-freepassage.We monitored vancomycin minimum inhibitory concentration (MIC; Etest and population analysis profile-areaunder the curve (PAP-AUC ratios of tested isolate-Mu3 during and after vancomycin pressure (VP. PAP-AUC ratios 1.3 were considered consistent with susceptible, hVISA and VISA, respectively.Results: VP at 2 mg/L (VP-2 increased MIC to 3 mg/L in 20 (83.3% isolates and raised PAP-AUC ratio to hVISA (n=18; 75.0%and VISA (six; 25.0% ranges. VP-3 increased MIC to 3 and 4 mg/L in 19 (79.2% and three (12.5% isolates, respectively andraised PAP-AUC ratio to hVISA (n=3; 12.5% and VISA (n=19; 79.2% ranges. SCCmec IV isolates had lower pre-exposurePAP-AUC ratios (0.48±0.14 vs. 0.69±0.10; p<0.001 and lower MIC (1.6±0.2 vs. 1.8±0.2 mg/L; p=0.1 but MIC rise and VISA/hVISA emergence was comparable. MIC and PAP-AUC ratio rises were stable in 20/22 isolates during drug-free passages.Conclusions: VISA/hVISA readily emerges among MRSA SCCmec type II and IV isolates under VP. VP at the MIC level generateshVISA while pressure at slightly higher level results in the VISA phenotype. J Microbiol Infect Dis 2012; 2(4: 129-134Key words: Staphylococcus aureus; heteroresistance; glycopeptides; resistance; bacteremia.

Cell Wall Remodeling by a Synthetic Analog Reveals Metabolic Adaptation in Vancomycin Resistant Enterococci.

Science.gov (United States)

Pidgeon, Sean E; Pires, Marcos M

2017-07-21

Drug-resistant bacterial infections threaten to overburden our healthcare system and disrupt modern medicine. A large class of potent antibiotics, including vancomycin, operate by interfering with bacterial cell wall biosynthesis. Vancomycin-resistant enterococci (VRE) evade the blockage of cell wall biosynthesis by altering cell wall precursors, rendering them drug insensitive. Herein, we reveal the phenotypic plasticity and cell wall remodeling of VRE in response to vancomycin in live bacterial cells via a metabolic probe. A synthetic cell wall analog was designed and constructed to monitor cell wall structural alterations. Our results demonstrate that the biosynthetic pathway for vancomycin-resistant precursors can be hijacked by synthetic analogs to track the kinetics of phenotype induction. In addition, we leveraged this probe to interrogate the response of VRE cells to vancomycin analogs and a series of cell wall-targeted antibiotics. Finally, we describe a proof-of-principle strategy to visually inspect drug resistance induction. Based on our findings, we anticipate that our metabolic probe will play an important role in further elucidating the interplay among the enzymes involved in the VRE biosynthetic rewiring.

Nanoconjugated vancomycin: new opportunities for the development of anti-VRSA agents

International Nuclear Information System (INIS)

Chakraborty, Subhankari Prasad; Mahapatra, Santanu Kar; Roy, Somenath; Sahu, Sumanta Kumar; Santra, Susmita; Pramanik, Panchanan; Bal, Manjusri

2010-01-01

More than 90% of Staphylococcus strains are resistant to penicillin. In 1961 S. aureus developed resistance to methicillin (MRSA), invalidating almost all antibiotics, including the most potent β-lactams. Vancomycin, a glycopeptide antibiotic, was used for the treatment of MRSA in 1980. Vancomycin inhibits the bio-synthesis of peptidoglycan and the assembly of NAM-NAG-polypeptide into the growing peptidoglycan chain. Vancomycin resistant S. aureus (VRSA) first appeared in the USA in 2002. Folic acid tagged chitosan nanoparticles are used as Trojan horses to deliver vancomycin into bacterial cells. These nanoparticles are biocompatible and biodegradable semisynthetic polymers. These nanosized vehicles enhance the transport of vancomycin across epithelial surfaces and show its efficient drug action, which has been understood from studies of the minimum inhibitory concentration and minimum bactericidal concentration of nanoparticles of a chitosan derivative loaded with vancomycin. Tolerance values distinctly show that vancomycin loaded into nanoconjugate is very effective and has a strong bactericidal effect on VRSA.

Nanoconjugated vancomycin: new opportunities for the development of anti-VRSA agents

Energy Technology Data Exchange (ETDEWEB)

Chakraborty, Subhankari Prasad; Mahapatra, Santanu Kar; Roy, Somenath [Immunology and Microbiology Laboratory, Department of Human Physiology with Community Health, Vidyasagar University, Midnapore-721102 (India); Sahu, Sumanta Kumar; Santra, Susmita; Pramanik, Panchanan [Nanomaterials Laboratory, Department of Chemistry, Indian Institute of Technology, Kharagpur, Pin-721302 (India); Bal, Manjusri, E-mail: panchanan_123@yahoo.com [Department of Human Physiology, Calcutta University, Kolkata (India)

2010-03-12

More than 90% of Staphylococcus strains are resistant to penicillin. In 1961 S. aureus developed resistance to methicillin (MRSA), invalidating almost all antibiotics, including the most potent {beta}-lactams. Vancomycin, a glycopeptide antibiotic, was used for the treatment of MRSA in 1980. Vancomycin inhibits the bio-synthesis of peptidoglycan and the assembly of NAM-NAG-polypeptide into the growing peptidoglycan chain. Vancomycin resistant S. aureus (VRSA) first appeared in the USA in 2002. Folic acid tagged chitosan nanoparticles are used as Trojan horses to deliver vancomycin into bacterial cells. These nanoparticles are biocompatible and biodegradable semisynthetic polymers. These nanosized vehicles enhance the transport of vancomycin across epithelial surfaces and show its efficient drug action, which has been understood from studies of the minimum inhibitory concentration and minimum bactericidal concentration of nanoparticles of a chitosan derivative loaded with vancomycin. Tolerance values distinctly show that vancomycin loaded into nanoconjugate is very effective and has a strong bactericidal effect on VRSA.

Beta-Lactams combinations with Vancomycin provide synergy against VSSA, hVISA, and VISA.

Science.gov (United States)

Tran, Kieu-Nhi; Rybak, Michael J

2018-03-19

Background: Increasing utilization of vancomycin due to the high prevalence of methicillin-resistant S. aureus (MRSA) infections has lead to the emergence of vancomycin-intermediate S. aureus (VISA) and heterogeneous VISA (hVISA). In vitro data suggest the potential for potent synergy between several beta-lactams and vancomycin. The objective of this study is to evaluate the synergy between beta-lactams and vancomycin against MRSA that is vancomycin susceptible, vancomycin susceptible Staphylococcus aureus (VSSA), hVISA, and VISA. Methods: Fifty randomly selected clinical MRSA strains with varying susceptibility to vancomycin were evaluated for vancomycin alone and vancomycin in combination with varying concentrations of cefazolin (CFZ), cefepime (FEP), ceftaroline (CPT), and nafcillin (NAF) minimum inhibitory concentration (MIC). The potential for synergy was assessed by 24h time-kills. Results: Beta-lactams reduced vancomycin MIC values against all strains (4-16 fold reduction). In time-kill studies against MRSA, CFZ, FEP, CPT, and NAF all demonstrated a similar extent of killing at 24h, and all showed synergistic activity with vancomycin against VSSA, hVISA, and VISA. Each of these combinations was also superior to any single agent against isolates of all three phenotypes, and each was bactericidal (P synergy of vancomycin against these Staphylococcus strains. Copyright © 2018 American Society for Microbiology.

In Vitro Synergistic Effects of Double and Triple Combinations of β-Lactams, Vancomycin, and Netilmicin against Methicillin-Resistant Staphylococcus aureus Strains

Science.gov (United States)

Rochon-Edouard, Stéphanie; Pestel-Caron, Martine; Lemeland, Jean-François; Caron, François

2000-01-01

Several studies have previously reported synergistic effects between vancomycin and a given β-lactam or a given aminoglycoside against methicillin-resistant Staphylococcus aureus (MRSA) strains. The aim of our study was to exhaustively compare the effects of different combinations of a β-lactam, vancomycin, and/or an aminoglycoside against 32 clinical MRSA strains with different aminoglycoside susceptibility patterns. The effects of 26 different β-lactam–vancomycin and 8 different aminoglycoside-vancomycin combinations were first studied using a disk diffusion screening method. The best interactions with vancomycin were observed with either imipenem, cefazolin, or netilmicin. By checkerboard studies, imipenem-vancomycin and cefazolin-vancomycin each provided a synergistic bacteriostatic effect against 22 strains; the mean fractional inhibitory concentration (FIC) indexes were 0.35 and 0.46 for imipenem-vancomycin and cefazolin-vancomycin, respectively. The vancomycin-netilmicin combination provided an indifferent effect against all of the 32 strains tested; the mean of FIC index was 1.096. The mean concentrations of imipenem, cefazolin, netilmicin, and vancomycin at which FIC indexes were calculated were clinically achievable. Killing experiments were then performed using imipenem, cefazolin, netilmicin, and vancomycin at one-half of the MIC, alone and in different combinations, against 10 strains. The vancomycin-netilmicin regimen was rarely bactericidal, even against strains susceptible to netilmicin. The imipenem-vancomycin and cefazolin-vancomycin combinations were strongly bactericidal against six and five strains, respectively. The addition of netilmicin markedly enhanced the killing activity of the combination of cefazolin or imipenem plus vancomycin, but only for the MRSA strains against which the β-lactam–vancomycin combinations had no bactericidal effect. It is noteworthy that the latter strains were both susceptible to netilmicin and

Characterization of Vancomycin Reactions and Linezolid Utilization in the Pediatric Population.

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Lin, Samantha K; Mulieri, Kevin M; Ishmael, Faoud T

Red man syndrome (RMS) occurs because of non-IgE-mediated histamine release. Unlike vancomycin allergy, which necessitates the use of an alternative drug (often linezolid), RMS does not typically preclude further vancomycin use. Care should be taken to differentiate these reaction types from one another to prevent unnecessary vancomycin avoidance. To characterize vancomycin reaction types in our population, and to determine whether having a reaction consistent with RMS is associated with otherwise unexplained vancomycin avoidance and linezolid use. We retrospectively reviewed charts for children with documented vancomycin reactions. We classified the in-hospital reactions via an objective analysis and estimated the prevalence of different reaction types. We then identified children who received linezolid over 3 years, and investigated reasons for linezolid use instead of vancomycin. Of the 78 in-hospital reactions we characterized, 72 (92%) were objectively consistent with RMS, 5 we could not objectively classify (2 most likely RMS, 3 more suspicious for possible IgE-mediated allergy), and 1 was a non-RMS/non-IgE reaction. Of 60 children who received linezolid, 19 had previous reactions consistent with RMS, which should not preclude further vancomycin. Nevertheless, only 7 of 19 (37%) had a clear explanation for receiving linezolid instead of vancomycin compared with 32 of 39 (82%) children without previous vancomycin reactions (P linezolid utilization. We propose that this may be related to how reactions appear in the electronic medical record. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Methicillin-Susceptible, Vancomycin-Resistant Staphylococcus aureus, Brazil

OpenAIRE

Panesso , Diana; Planet , Paul J.; Diaz , Lorena; Hugonnet , Jean-Emannuel; Tran , Truc T.; Narechania , Apurva; Munita , José M.; Rincon , Sandra; Carvajal , Lina P.; Reyes , Jinnethe; Londono , Alejandra; Smith , Hannah; Sebra , Robert; Deikus , Gintaras; Weinstock , George M

2015-01-01

International audience; We report characterization of a methicillin-susceptible, vancomycin-resistant bloodstream isolate of Staphylococcus aureus recovered from a patient in Brazil. Emergence of vancomycin resistance in methicillin-susceptible S. aureus would indicate that this resistance trait might be poised to disseminate more rapidly among S. aureus and represents a major public health threat.

Vancomycin-Rifampin Combination Therapy Has Enhanced Efficacy against an Experimental Staphylococcus aureus Prosthetic Joint Infection

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Niska, Jared A.; Shahbazian, Jonathan H.; Ramos, Romela Irene; Francis, Kevin P.; Bernthal, Nicholas M.

2013-01-01

Treatment of prosthetic joint infections often involves a two-stage exchange, with implant removal and antibiotic spacer placement followed by systemic antibiotic therapy and delayed reimplantation. However, if antibiotic therapy can be improved, one-stage exchange or implant retention may be more feasible, thereby decreasing morbidity and preserving function. In this study, a mouse model of prosthetic joint infection was used in which Staphylococcus aureus was inoculated into a knee joint containing a surgically placed metallic implant extending from the femur. This model was used to evaluate whether combination therapy of vancomycin plus rifampin has increased efficacy compared with vancomycin alone against these infections. On postoperative day 7, vancomycin with or without rifampin was administered for 6 weeks with implant retention. In vivo bioluminescence imaging, ex vivo CFU enumeration, X-ray imaging, and histologic analysis were carried out. We found that there was a marked therapeutic benefit when vancomycin was combined with rifampin compared with vancomycin alone. Taken together, our results suggest that the mouse model used could serve as a valuable in vivo preclinical model system to evaluate and compare efficacies of antibiotics and combinatory therapy for prosthetic joint infections before more extensive studies are carried out in human subjects. PMID:23917317

Antimicrobial growth promoter ban and resistance to macrolides and vancomycin in enterococci from pigs

DEFF Research Database (Denmark)

Boerlin, P.; Wissing, A.; Aarestrup, Frank Møller

2001-01-01

Ninety-six enterococcus isolates from fecal samples of pigs receiving tylosin as an antimicrobial growth promoter and 59 isolates obtained in the same farms 5 to 6 months after the ban of antimicrobial growth promoters in Switzerland were tested for susceptibility to nine antimicrobial agents....... A clear decrease in resistance to macrolides, lincosamides, and tetracycline was visible after the ban. Vancomycin-resistant Enterococcus faecium belonged to the same clonal lineage as vancomycin-resistant isolates previously isolated from Danish pigs....

Effectiveness of local vancomycin powder to decrease surgical site infections: a meta-analysis.

Science.gov (United States)

Chiang, Hsiu-Yin; Herwaldt, Loreen A; Blevins, Amy E; Cho, Edward; Schweizer, Marin L

2014-03-01

Some surgeons use systemic vancomycin to prevent surgical site infections (SSIs), but patients who do not carry methicillin-resistant Staphylococcus aureus have an increased risk of SSIs when given vancomycin alone for intravenous prophylaxis. Applying vancomycin powder to the wound before closure could increase the local tissue vancomycin level without significant systemic levels. However, the effectiveness of local vancomycin powder application for preventing SSIs has not been established. Our objective was to systematically review and evaluate studies on the effectiveness of local vancomycin powder for decreasing SSIs. Meta-analysis. We included observational studies, quasi-experimental studies, and randomized controlled trials of patients undergoing surgical procedures that involved vancomycin powder application to surgical wounds, reported SSI rates, and had a comparison group that did not use local vancomycin powder. The primary outcome was postoperative SSIs. The secondary outcomes included deep incisional SSIs and S. aureus SSIs. We performed systematic literature searches in PubMed, the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Cochrane Central Register of Controlled Trials via Wiley, Scopus (including EMBASE abstracts), Web of Science, ClinicalTrials.gov, BMC Proceedings, ProQuest Dissertation, and Thesis in Health and Medicine, and conference abstracts from IDWeek, the Interscience Conference on Antimicrobial Agents and Chemotherapy, the Society for Healthcare Epidemiology of America, and the American Academy of Orthopedic Surgeons annual meetings, and also the Scoliosis Research Society Annual Meeting and Course. We ran the searches from inception on May 9, 2013 with no limits on date or language. After reviewing 373 titles or abstracts and 22 articles in detail, we included 10 independent studies and used a random-effects model when pooling risk estimates to assess the effectiveness of local

Optimization of a Laboratory-Developed Test Utilizing Roche Analyte-Specific Reagents for Detection of Staphylococcus aureus, Methicillin-Resistant S. aureus, and Vancomycin-Resistant Enterococcus Species▿

OpenAIRE

Mehta, Maitry S.; Paule, Suzanne M.; Hacek, Donna M.; Thomson, Richard B.; Kaul, Karen L.; Peterson, Lance R.

2008-01-01

Nasal and perianal swab specimens were tested for detection of Staphylococcus aureus and vancomycin-resistant Enterococcus species (VRE) using a laboratory-developed real-time PCR test and microbiological cultures. The real-time PCR and culture results for S. aureus were similar. PCR had adequate sensitivity, but culture was more specific for the detection of VRE.

A Rare Case of Vancomycin-Induced Linear Immunoglobulin A Bullous Dermatosis

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Pinky Jha

2017-01-01

Full Text Available Linear IgA bullous dermatosis (LABD is an autoimmune vesiculobullous disease, which is typically idiopathic but can also rarely be caused by medications or infections. Vancomycin is the most common drug associated with LABD. Lesions typically appear 24 hours to 15 days after the first dose of vancomycin. It is best characterized pathologically by subepidermal bulla (blister formation with linear IgA deposition at the dermoepidermal junction. Here we report an 86-year-old male with a history of left knee osteoarthritis who underwent a left knee arthroplasty and subsequently developed a prosthetic joint infection. This infection was treated with intravenous vancomycin as well as placement of a vancomycin impregnated joint spacer. Five days following initiation of antibiotic therapy, he presented with a vesiculobullous eruption on an erythematous base over his trunk, extremities, and oral mucosa. The eruption resolved completely when intravenous vancomycin was discontinued and colchicine treatment was begun. Curiously, complete resolution occurred despite the presence of the vancomycin containing joint spacer. The diagnosis of vancomycin-induced linear IgA bullous dermatosis was made based on characteristic clinical and histopathologic presentations.

Enantioseparation of dansyl amino acids by HPLC on a monolithic column dynamically coated with a vancomycin derivative.

Science.gov (United States)

Pittler, Elfriede; Schmid, Martin G

2010-11-01

In this work a chiral stationary phase was prepared by dynamically coating a monolithic reversed-phase HPLC column with a vancomycin-derivative as chiral selector. A hydrophobic alkyl-chain was attached to the vancomycin molecule, providing the immobilization of the chiral selector on the reversed-phase material. Dansyl amino acids were chosen as model analytes for testing the separation power of the dynamically coated phase. All investigated compounds were separated into their enantiomers. Compared with a conventionally packed vancomycin-CSP, a reversal of the enantiomer elution order was obtained. Copyright © 2010 John Wiley & Sons, Ltd.

Prevalence and distribution of VRE (vancomycin resistant enterococci and VSE (vancomycin susceptible enterococci strains in the breeding environment

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Krzysztof Skowron

2016-06-01

Full Text Available [b]Introduction.[/b] Intensive animal production causes numerous problems. Facilities connected with animal maintenance not only cause environmental pollution, but also pose a great sanitary and epidemiological threat. Long-term use of antibiotics in animal production lead animal-borne microorganisms to develop multiple resistance mechanisms, transferred to the typical environmental bacteria. [b]Objective. [/b]The aim of this study was assessment of E. faecalis, E. faecium, E. durans and E. hirae prevalence in samples gathered from swine production sectors, and determination of the contribution of VRE (vancomycin resistant enterococci strains and their resistance. The degree of relationship between isolates of each species from genus Enterococcus was also determined. [b]Materials and method.[/b] 195 isolates were obtained, from which DNA was isolated. Genus identification was conducted with the primers specific to the 16S rRNA region, and identification of the species with primers specific to sequence of gene sodA in Multiplex PCR reaction. Resistance to vancomycin (6 μg×ml -1 was tested using a screening method on Muller Hinton Agar. To assess resistance type Multiplex PCR, amplifying products corresponding to genes VanA, VanB and VanC, was conducted. Genotyping was conducted using the PCR-RAPD method. [b]Results. [/b]Among the 195 isolates, 133 (68% belonged to E. hirae. The other species contributions were respectively: E. faecalis – 21%, E. durans – 8% and E. faecium – 3%. Only 2 isolates of E. hirae, being different strains, were resistant to vancomycin. Both were representing phenotype VanC1. 60 genetically different strains were defined. The possible contamination paths involved animal feed and spreading of excrements by slaughtered individuals or on personnel’s footwear. [b]Conclusions. [/b]The obtained results indicate a very low percentage of VRE strains in the tested piggery, resulting in a low health risk to piggery

Molecular characterization of vancomycin-resistant Enterococcus faecium isolates from Bermuda.

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Patrick Eberechi Akpaka

Full Text Available Molecular characteristics of vancomycin resistant enterococci isolates from Bermuda Island is currently unknown. This study was conducted to investigate phenotypic and genotypic characteristics of VRE isolates from Bermuda Island using the chromogenic agar, E-tests, polymerase chain reaction (PCR, pulsed-field gel electrophoresis (PFGE and multilocus sequence typing (MLST. Eighteen E. faecium isolates were completely analyzed and were all resistant to vancomycin, susceptible to linezolid and quinupristin/dalfopristin, positive for vanA and esp genes. The MLST analysis confirmed most isolates were of the sequence types linked to clonal complex 17 (CC17 that is widely associated with outbreaks in hospitals. Infection control measures, antibiotic stewardship, and surveillance activities will continue to be a priority in hospital on the Island.

Phenotypic changes of methicillin-resistant Staphylococcus aureus during vancomycin therapy for persistent bacteraemia and related clinical outcome.

Science.gov (United States)

Kim, T; Kim, E S; Park, S Y; Sung, H; Kim, M-N; Kim, S-H; Lee, S-O; Choi, S-H; Jeong, J-Y; Woo, J H; Chong, Y P; Kim, Y S

2017-08-01

Persistent bacteraemia (PB) due to methicillin-resistant Staphylococcus aureus (MRSA) that fails to respond to glycopeptide therapy is a well-documented clinical problem. There are limited data on changes in agr functionality, vancomycin susceptibility and heteroresistance during MRSA PB. Thus, the frequency of these changes and their clinical significance remain unclear. Only patients with MRSA PB (≥7 days) from a prospective cohort of S. aureus bacteraemia were included. We collected isogenic paired strains and compared vancomycin MIC, vancomycin heteroresistance, and agr functionality between initial and final blood isolates. We also assessed the clinical outcome. A total of 49 patients had MRSA PB over 22 months. Bacteraemia persisted for a median of 13 days and most patients (98%) received glycopeptide as initial therapy. Among 49 isogenic pairs, only one pair showed a vancomycin MIC increase ≥2-fold by broth microdilution method, and only seven (14%) by E-test. Significant portions of initial isolates had vancomycin heteroresistance (49%) and agr dysfunction (76%). Development of vancomycin heteroresistance during PB occurred in four (16%) among 25 initial vancomycin-susceptible isolates, and acquisition of agr dysfunction occurred in two (16%) among 12 initial agr-functional isolates. Changes in the opposite direction occasionally occurred. These phenotypic changes during PB were not associated with mortality, whereas agr dysfunction of the initial isolates was significantly associated with mortality. During MRSA PB, phenotypic changes of MRSA isolates occurred occasionally under prolonged vancomycin exposure but were not significantly associated with clinical outcome. In contrast, initial agr dysfunction could be a predictor for mortality in MRSA PB.

An Approach to Optimise Therapeutic Vancomycin Dosage in a Haemodialysis Population

LENUS (Irish Health Repository)

Gunning, H

2016-10-01

Haemodialysis patients are at risk of gram-positive bacteraemia and commonly require intravenous vancomycin. Intravenously administered vancomycin is primarily excreted by the kidney and exhibits complex pharmacokinetics in haemodialysis patients; achieving therapeutic levels can be challenging. An audit in our unit showed current practises of vancomycin administration resulted in a high proportion of sub-therapeutic levels. A new protocol was developed with fixed weight-based loading and subsequent dosing guided by pre-dialysis levels, target levels were 10-20mg\\/L. Its effectiveness was prospectively evaluated between 24th September 2012, and 8th February 2013. During this period 25 patients commenced vancomycin, 15 were included. In total, 112 vancomycin levels were taken, 94 (84%) were therapeutic, this was a significant improvement compared to previous practise (odds ratio 5.4, CI 3.1-9.4, p < 0.0001). In conclusion, our study shows this protocol can consistently and reliably achieve therapeutic vancomycin levels

Trough Concentrations of Vancomycin in Patients Undergoing Extracorporeal Membrane Oxygenation.

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So Jin Park

Full Text Available To investigate the appropriateness of the current vancomycin dosing strategy in adult patients with extracorporeal membrane oxygenation (ECMO, between March 2013 and November 2013, patients who were treated with vancomycin while on ECMO were enrolled. Control group consisted of 60 patients on vancomycin without ECMO, stayed in medical intensive care unit during the same study period and with the same exclusion criteria. Early trough levels were obtained within the fourth dosing, and maintenance levels were measured at steady state. A total of 20 patients were included in the analysis in ECMO group. Sixteen patients received an initial intravenous dose of 1.0 g vancomycin followed by 1.0 g every 12 hours. The non-steady state trough level of vancomycin after starting administration was subtherapeutic in 19 patients (95.00% in ECMO group as compared with 40 patients (66.67% in the control group (p = 0.013. Vancomycin clearance was 1.27±0.51 mL/min/kg, vancomycin clearance/creatinine clearance ratio was 0.90 ± 0.37, and elimination rate constant was 0.12 ± 0.04 h-1. Vancomycin dosingfrequency and total daily dose were significantly increased after clinical pharmacokinetic services of the pharmacist based on calculated pharmacokinetic parameters (from 2.10 ± 0.72 to 2.90 ± 0.97 times/day, p = 0.002 and from 32.54 ± 8.43 to 42.24 ± 14.62mg/kg, p = 0.014 in ECMO group in contrast with those (from 2.11 ± 0.69 to 2.37 ± 0.86 times/day, p = 0.071 and from 33.91 ± 11.85 to 31.61 ± 17.50 mg/kg, p = 0.350 in the control group.Although the elimination rate for vancomycin was similar with population parameter of non ECMO patients, the current dosing strategy of our institution for vancomycinin our ICU was not sufficient to achieve the target trough in the initial period in most patients receiving ECMO.

Prevalence study of enterococus and staphylococci resistance to vancomycin isolated from urinary tract infections

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Mohammad Kazem Sharifi Yazdi

2013-07-01

Full Text Available Background: The role of gram-positive cocci especially Staphylococci species in causing urinary tract infection are well known. Among the Staphylococci species Methicillin Resistance Staphylococcus aureus (MRSA is the most important. The rate of MRSA is increasing worldwide. This is alarming because the danger of these organism in public health. Therefore the aim of this study was to determine the sensitivity of gram-positive cocci, as well as MRSA to vancomycin and other antibiotics.Methods: This was a descriptive study, and were carried out on 300 patients with urinary tract infections (UTI caused by gram-positive cocci, referred to Imam Khomeini hospital during eight months. Prior to the antibiotic sensitivity testing all the isolates were identified according to the standard conventional biochemical procedure, and then the antibiotic susceptibility test were carried out according to Bauer-Kirby method. Results: Among the gram positive cocci causing UTI, the most abundant were Staphylococcus saprophyticus (37.7%, followed by Staphylococcus epidermidis (22.3% and Staphylococcus aureus (18% respectivley. The sex distribution of patients were 163 female (54.3% and 137 male (45.7% respectively, and the prevalence rate of urinary tract infections in female was (8.6% higher than male. The rate of sensitivity of isolated Staphylococci were as followed, sensitive to vancomycine (100%, Ciprofloxacin (89.2%, rifampin (87.6%, and amikacin (71.8% respectivley, but were resistant to penicillin and amoxicillin (100%. The antibiotic sensitivity rate of isolated  Streptococci was to vancomycine (85.1%, ciprofloxacin (50.7% and penicillin (79.1% respectively.Conclusion: Vancomycin is still a suitable antibiotic for the treatment of Staphyloco-ccus infections. Although 6% rate of enterococci resistance to vancomycin is alarming, and use of this antibiotic in the treatment of other gram-positive bacteria should be done with precaution.

Comparative effectiveness of nafcillin or cefazolin versus vancomycin in methicillin-susceptible Staphylococcus aureus bacteremia

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McGregor Jessina C

2011-10-01

Full Text Available Abstract Background The high prevalence of methicillin-resistant S. aureus (MRSA has led clinicians to select antibiotics that have coverage against MRSA, usually vancomycin, for empiric therapy for suspected staphylococcal infections. Clinicians often continue vancomycin started empirically even when methicillin-susceptible S. aureus (MSSA strains are identified by culture. However, vancomycin has been associated with poor outcomes such as nephrotoxicity, persistent bacteremia and treatment failure. The objective of this study was to compare the effectiveness of vancomycin versus the beta-lactam antibiotics nafcillin and cefazolin among patients with MSSA bacteremia. The outcome of interest for this study was 30-day in-hospital mortality. Methods This retrospective cohort study included all adult in-patients admitted to a tertiary-care facility between January 1, 2003 and June 30, 2007 who had a positive blood culture for MSSA and received nafcillin, cefazolin or vancomycin. Cox proportional hazard models were used to assess independent mortality hazards comparing nafcillin or cefazolin versus vancomycin. Similar methods were used to estimate the survival benefits of switching from vancomycin to nafcillin or cefazolin versus leaving patients on vancomycin. Each model included statistical adjustment using propensity scores which contained variables associated with an increased propensity to receive vancomycin. Results 267 patients were included; 14% (38/267 received nafcillin or cefazolin, 51% (135/267 received both vancomycin and either nafcillin or cefazolin, and 35% (94/267 received vancomycin. Thirty (11% died within 30 days. Those receiving nafcillin or cefazolin had 79% lower mortality hazards compared with those who received vancomycin alone (adjusted hazard ratio (HR: 0.21; 95% confidence interval (CI: 0.09, 0.47. Among the 122 patients who initially received vancomycin empirically, those who were switched to nafcillin or cefazolin (66

Meningitis associated with Vancomycin resistant Enterococcus casseliflavus: First report

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Nilay Sefa Uçar

2011-12-01

Full Text Available Enterococci are present in the gastrointestinal system as normal floral components. In the past two decades membersof the genus Enterococcus have emerged as important nosocomial pathogens worldwide. Enterococci may cause arange of different disorders such as urinary tract, intraabdominal, and wound infections, as well as endocarditis, meningitisand bacteraemia. Nosocomial enterococcal meningitis is most commonly observed following ventriculoperitonealshunt operations. Vancomycin resistant enterococcus (VRE represents 30% of all enterococci infections.This report presents a vancomycin-resistant Enterococcus casseliflavus meningitis case in a 66-year-old patient withventriculoperitoneal shunt, which has not been reported in the literature before. Successful outcomes were obtainedwith daptomycin plus linezolid combined treatment in VRE meningitis. Treatment recommendations in VRE meningitisare also discussed in this article. J Microbiol Infect Dis 2011;1 (3:138-140

Occurrence of vancomycin-resistant and -susceptible Enterococcus spp. in reclaimed water used for spray irrigation

Energy Technology Data Exchange (ETDEWEB)

Carey, Stephanie Ann; Goldstein, Rachel E. Rosenberg [Maryland Institute for Applied Environmental Health, University of Maryland School of Public Health, College Park, MD (United States); Gibbs, Shawn G. [Department of Environmental Health, School of Public Health-Bloomington, Indiana University, Bloomington, IN (United States); Claye, Emma [Maryland Institute for Applied Environmental Health, University of Maryland School of Public Health, College Park, MD (United States); He, Xin [Department of Epidemiology and Biostatistics, University of Maryland School of Public Health, College Park, MD (United States); Sapkota, Amy R., E-mail: ars@umd.edu [Maryland Institute for Applied Environmental Health, University of Maryland School of Public Health, College Park, MD (United States)

2016-05-15

Reclaiming municipal wastewater for agricultural, environmental, and industrial purposes is increasing in the United States to combat dwindling freshwater supplies. However, there is a lack of data regarding the microbial quality of reclaimed water. In particular, no previous studies have evaluated the occurrence of vancomycin-resistant enterococci (VRE) in reclaimed water used at spray irrigation sites in the United States. To address this knowledge gap, we investigated the occurrence, concentration, and antimicrobial resistance patterns of VRE and vancomycin-susceptible enterococci at three U.S. spray irrigation sites that use reclaimed water. We collected 48 reclaimed water samples from one Mid-Atlantic and two Midwest spray irrigation sites, as well as their respective wastewater treatment plants, in 2009 and 2010. Samples were analyzed for total enterococci and VRE using standard membrane filtration. Isolates were purified and then confirmed using biochemical tests and PCR. Antimicrobial susceptibility testing was conducted using the Sensititre® microbroth dilution system. Data were analyzed by two-sample proportion tests and one-way analysis of variance. We detected total enterococci and VRE in 71% (34/48) and 4% (2/48) of reclaimed water samples, respectively. Enterococcus faecalis was the most common species identified. At the Mid-Atlantic spray irrigation site, UV radiation decreased total enterococci to undetectable levels; however, subsequent storage in an open-air pond at this site resulted in increased concentrations of enterococci. E. faecalis isolates recovered from the Mid-Atlantic spray irrigation site expressed intrinsic resistance to quinupristin/dalfopristin; however, non-E. faecalis isolates expressed resistance to quinupristin/dalfopristin (52% of isolates), vancomycin (4%), tetracycline (13%), penicillin (4%) and ciprofloxacin (17%). Our findings show that VRE are present in low numbers in reclaimed water at point-of-use at the sampled spray

Occurrence of vancomycin-resistant and -susceptible Enterococcus spp. in reclaimed water used for spray irrigation

International Nuclear Information System (INIS)

Carey, Stephanie Ann; Goldstein, Rachel E. Rosenberg; Gibbs, Shawn G.; Claye, Emma; He, Xin; Sapkota, Amy R.

2016-01-01

Reclaiming municipal wastewater for agricultural, environmental, and industrial purposes is increasing in the United States to combat dwindling freshwater supplies. However, there is a lack of data regarding the microbial quality of reclaimed water. In particular, no previous studies have evaluated the occurrence of vancomycin-resistant enterococci (VRE) in reclaimed water used at spray irrigation sites in the United States. To address this knowledge gap, we investigated the occurrence, concentration, and antimicrobial resistance patterns of VRE and vancomycin-susceptible enterococci at three U.S. spray irrigation sites that use reclaimed water. We collected 48 reclaimed water samples from one Mid-Atlantic and two Midwest spray irrigation sites, as well as their respective wastewater treatment plants, in 2009 and 2010. Samples were analyzed for total enterococci and VRE using standard membrane filtration. Isolates were purified and then confirmed using biochemical tests and PCR. Antimicrobial susceptibility testing was conducted using the Sensititre® microbroth dilution system. Data were analyzed by two-sample proportion tests and one-way analysis of variance. We detected total enterococci and VRE in 71% (34/48) and 4% (2/48) of reclaimed water samples, respectively. Enterococcus faecalis was the most common species identified. At the Mid-Atlantic spray irrigation site, UV radiation decreased total enterococci to undetectable levels; however, subsequent storage in an open-air pond at this site resulted in increased concentrations of enterococci. E. faecalis isolates recovered from the Mid-Atlantic spray irrigation site expressed intrinsic resistance to quinupristin/dalfopristin; however, non-E. faecalis isolates expressed resistance to quinupristin/dalfopristin (52% of isolates), vancomycin (4%), tetracycline (13%), penicillin (4%) and ciprofloxacin (17%). Our findings show that VRE are present in low numbers in reclaimed water at point-of-use at the sampled spray

Heterogeneous vancomycin-intermediate susceptibility in a community-associated methicillin-resistant Staphylococcus aureus epidemic clone, in a case of Infective Endocarditis in Argentina

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Vindel Ana

2011-04-01

Full Text Available Abstract Background Community-Associated Methicillin Resistant Staphylococcus aureus (CA-MRSA has traditionally been related to skin and soft tissue infections in healthy young patients. However, it has now emerged as responsible for severe infections worldwide, for which vancomycin is one of the mainstays of treatment. Infective endocarditis (IE due to CA-MRSA with heterogeneous vancomycin-intermediate susceptibility-(h-VISA has been recently reported, associated to an epidemic USA 300 CA-MRSA clone. Case Presentation We describe the occurrence of h-VISA phenotype in a case of IE caused by a strain belonging to an epidemic CA-MRSA clone, distinct from USA300, for the first time in Argentina. The isolate h-VISA (SaB2 was recovered from a patient with persistent bacteraemia after a 7-day therapy with vancomycin, which evolved to fatal case of IE complicated with brain abscesses. The initial isolate-(SaB1 was fully vancomycin susceptible (VSSA. Although MRSA SaB2 was vancomycin susceptible (≤2 μg/ml by MIC (agar and broth dilution, E-test and VITEK 2, a slight increase of MIC values between SaB1 and SaB2 isolates was detected by the four MIC methods, particularly for teicoplanin. Moreover, Sab2 was classified as h-VISA by three different screening methods [MHA5T-screening agar, Macromethod-E-test-(MET and by GRD E-test] and confirmed by population analysis profile-(PAP. In addition, a significant increase in cell-wall thickness was revealed for SaB2 by electron microscopy. Molecular typing showed that both strains, SaB1 and SaB2, belonged to ST5 lineage, carried SCCmecIV, lacked Panton-Valentine leukocidin-(PVL genes and had indistinguishable PFGE patterns (subtype I2, thereby confirming their isogenic nature. In addition, they were clonally related to the epidemic CA-MRSA clone (pulsotype I detected in our country. Conclusions This report demonstrates the ability of this epidemic CA-MRSA clone, disseminated in some regions of Argentina, to

Characterization of vancomycin-resistant and vancomycin-susceptible Enterococcus faecium isolates from humans, chickens and pigs by RiboPrinting and pulsed-field gel electrophoresis

DEFF Research Database (Denmark)

Hammerum, Anette Marie; Fussing, Vivian; Aarestrup, Frank Møller

2000-01-01

Forty-eight vancomycin-resistant and 35 vancomycin-sensitive Danish Enterococcus faecium isolates obtained from pigs, chickens and humans, as well as the human vanA reference isolate BM4147, were characterized by EcoRI RiboPrinting and Smal pulsed-field gel electrophoresis. RiboPrinting of the 84...

Vancomycin Dosing in Obese Patients: Special Considerations and Novel Dosing Strategies.

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Durand, Cheryl; Bylo, Mary; Howard, Brian; Belliveau, Paul

2018-06-01

To review the literature regarding vancomycin pharmacokinetics in obese patients and strategies used to improve dosing in this population. PubMed, EMBASE (1974 to November 2017), and Google Scholar searches were conducted using the search terms vancomycin, obese, obesity, pharmacokinetics, strategy, and dosing. Additional articles were selected from reference lists of selected studies. Included articles were those published in English with a primary focus on vancomycin pharmacokinetic parameters in obese patients and practical vancomycin dosing strategies, clinical experiences, or challenges of dosing vancomycin in this population. Volume of distribution and clearance are the pharmacokinetic parameters that most often affect vancomycin dosing in obese patients; both are increased in this population. Challenges with dosing in obese patients include inconsistent and inadequate dosing, observations that the obese population may not be homogeneous, and reports of an increased likelihood of supratherapeutic trough concentrations. Investigators have revised and developed dosing and monitoring protocols to address these challenges. These approaches improved target trough attainment to varying degrees. Some of the vancomycin dosing approaches provided promising results in obese patients, but there were notable differences in methods used to develop these approaches, and sample sizes were small. Although some approaches can be considered for validation in individual institutions, further research is warranted. This may include validating approaches in larger populations with narrower obesity severity ranges, investigating target attainment in indication-specific target ranges, and evaluating the impact of different dosing weights and methods of creatinine clearance calculation.

A specially tailored vancomycin continuous infusion regimen for renally impaired critically ill patients

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Eman Mohamed Bahgat Eldemiry

2013-10-01

Full Text Available Background: Vancomycin remains the gold standard for treatment of methicillin-resistant Staphylococcus aureus. Specially designed continuous infusion of vancomycin leads to better therapy. Methodology: A total of 40 critically ill patients who suffered from pneumonia susceptible to vancomycin, had serum creatinine >1.4 mg%, and oliguria <0.5 mL/kg/h for 6 h were included in the study with respiratory culture sensitivity to vancomycin ≤2 mg/L. Patients’ clinical, microbiological, and biological data were obtained by retrospective analysis of the corresponding medical files before and after vancomycin treatment. Patients with serum creatinine level ≥4 mg% and patients who received renal replacement therapy during the treatment period were excluded. The patients were divided into two groups—group 1 (intermittent dosing and group 2 (continuous infusion based on the following formula: rate of vancomycin continuous infusion (g/day = [0.0205 creatinine clearance (mL/min + 3.47] × [target vancomycin concentration at steady state (µg/mL] × (24/1000. Trough vancomycin serum levels were also assessed using high-performance liquid chromatographic technique. Patients’ outcomes such as clinical improvement, adverse events, and 15-day mortality were reported. Results: Group 2 showed significant reduction in blood urea nitrogen, creatinine serum levels, white blood cells, partial carbon dioxide pressure, body temperature, and Sequential Organ Failure Assessment score, while significant increase in partial oxygen pressure and saturated oxygen was also observed. A significantly shorter duration of treatment with a comparable vancomycin serum levels was also reported with group 2. Conclusion: After treatment, comparison in patients’ criteria supports the superiority of using continuous infusion of vancomycin according to this equation in renally impaired patients.

Experimental and Theoretical Studies of the Structures and Interactions of Vancomycin Antibiotics with Cell Wall Analogues

International Nuclear Information System (INIS)

Yang, Zhibo; Vorpagel, Erich R.; Laskin, Julia

2008-01-01

Surface-induced dissociation (SID) of the singly protonated complex of vancomycin antibiotic with cell wall peptide analogue (N α , N # var e psilon#-diacetyl-L-Lys-D-Ala-D-Ala) was studied using a 6 T Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FT-ICR MS) specially configured for SID experiments. The binding energy between the vancomycin and the peptide was obtained from the RRKM modeling of the time- and energy resolved fragmentation efficiency curves (TFECs) of the precursor ion and its fragments. Electronic structure calculations of the geometries, proton affinities and binding energies were performed for several model systems including vancomycin (V), vancomycin aglycon (VA), N α , N # var e psilon#-diacetyl-L-Lys-D-Ala-D-Ala, and non-covalent complexes of VA with N-acetyl-D-Ala-D-Ala and N α , N # var e psilon#-diacetyl-L-Lys-D-Ala-D-Ala at the B3LYP/6-31G(d) level of theory. Comparison between the experimental and computational results suggests that the most probable structure of the complex observed in our experiments corresponds to the neutral peptide bound to the vancomycin protonated at the secondary amino group of the N-methyl-leucine residue. The experimental binding energy of 30.9 ± 1.8 kcal/mol is in good agreement with the binding energy of 29.3 ± 2.5 kcal/mol calculated for the model system representing the preferred structure of the complex

Emergence in Asian Countries of Staphylococcus aureus with Reduced Susceptibility to Vancomycin

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Song, Jae-Hoon; Hiramatsu, Keiichi; Suh, Ji Yoeun; Ko, Kwan Soo; Ito, Teruyo; Kapi, Maria; Kiem, Sungmin; Kim, Yeon-Sook; Oh, Won Sup; Peck, Kyong Ran; Lee, Nam Yong

2004-01-01

To investigate the prevalence of Staphylococcus aureus with reduced susceptibility to vancomycin among methicillin-resistant S. aureus (MRSA) strains in Asian countries, a total of 1,357 clinical isolates of MRSA collected from 12 Asian countries were screened by using brain heart infusion agar plates containing 4 mg of vancomycin per liter. The presence of strains that were heterointermediately resistant to vancomycin (hVISA) was confirmed by population analysis. Of 347 (25.6%) MRSA isolates that grew on the screening agar plates, 58 isolates (4.3%) were hVISA. hVISA strains were found in India, South Korea, Japan, the Philippines, Singapore, Thailand, and Vietnam. However, neither vancomycin-intermediate S. aureus nor vancomycin-resistant S. aureus isolates were found among MRSA isolates from Asian countries in this survey. PMID:15561884

Vancomycin-resistant enterococcus outbreak in a pediatric intensive care unit: report of successful interventions for control and prevention

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F. Carmona

2012-02-01

Full Text Available The objective of this study is to retrospectively report the results of interventions for controlling a vancomycin-resistant enterococcus (VRE outbreak in a tertiary-care pediatric intensive care unit (PICU of a University Hospital. After identification of the outbreak, interventions were made at the following levels: patient care, microbiological surveillance, and medical and nursing staff training. Data were collected from computer-based databases and from the electronic prescription system. Vancomycin use progressively increased after March 2008, peaking in August 2009. Five cases of VRE infection were identified, with 3 deaths. After the interventions, we noted a significant reduction in vancomycin prescription and use (75% reduction, and the last case of VRE infection was identified 4 months later. The survivors remained colonized until hospital discharge. After interventions there was a transient increase in PICU length-of-stay and mortality. Since then, the use of vancomycin has remained relatively constant and strict, no other cases of VRE infection or colonization have been identified and length-of-stay and mortality returned to baseline. In conclusion, we showed that a bundle intervention aiming at a strict control of vancomycin use and full compliance with the Hospital Infection Control Practices Advisory Committee guidelines, along with contact precautions and hand-hygiene promotion, can be effective in reducing vancomycin use and the emergence and spread of vancomycin-resistant bacteria in a tertiary-care PICU.

Stoma-Closure-Induced Fulminant Pseudomembranous Colitis Recovered by Adjunctive Intracolic Vancomycin with Postural Change

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Yozo Suzuki

2010-05-01

Full Text Available A 67-year-old man with a history of low anterior resection and diverting loop transverse colostomy for rectal carcinoma developed fulminant pseudomembranous colitis after stoma closure. Oral administration of vancomycin at 0.5 g every 6 h and colonoscopy with intracolic vancomycin administration was unsuccessful, but continuation of intracolic vancomycin with postural change resulted in dramatic recovery. Postural change may extend the efficacy of intracolic vancomycin, and intracolic vancomycin should be considered as an option between conventional therapy and surgical intervention for pseudomembranous colitis.

Halloysite nanotubes as carriers of vancomycin in alginate-based wound dressing.

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Kurczewska, Joanna; Pecyna, Paulina; Ratajczak, Magdalena; Gajęcka, Marzena; Schroeder, Grzegorz

2017-09-01

The influence of an inorganic support - halloysite nanotubes - on the release rate and biological activity of the antibiotic encapsulated in alginate-based dressings was studied. The halloysite samples were loaded with approx. 10 wt.% of the antibiotic and then encapsulated in Alginate and Gelatin/Alginate gels. The material functionalized with aliphatic amine significantly extended the release of vancomycin from alginate-based gels as compared to that achieved when silica was used. After 24 h, the released amounts of the antibiotic immobilized at silica reached 70%, while for the drug immobilized at halloysite the released amount of vancomycin reached 44% for Alginate discs. The addition of gelatin resulted in even more prolonged sustained release of the drug. The antibiotic was released from the system with a double barrier with Higuchi kinetic model and Fickian diffusion mechanism. Only the immobilized drug encapsulated in Alginate gel demonstrated very good antimicrobial activity against various bacteria. The inhibition zones were greater than those of the standard discs for the staphylococci and enterococci bacteria tested. The addition of gelatin adversely affected the biological activity of the system. The inhibition zones were smaller than those of the reference samples. A reduction in the drug dose by half had no significant effect on changing the release rate and microbiological activity. The in vivo toxicity studies of the material with immobilized drug were carried out with Acutodesmus acuminatus and Daphnia magna . The material studied had no effect on the living organisms used in the bioassays. The proposed system with a double barrier demonstrated high storage stability.

Vancomycin Powder Regimen for Prevention of Surgical Site Infection in Complex Spine Surgeries.

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Van Hal, Michael; Lee, Joon; Laudermilch, Dann; Nwasike, Chinedu; Kang, James

2017-10-01

In total, 496 patients of a single surgeon cohort examining the surgical-site infection (SSI) rates with the addition of vancomycin powder in both diabetic and revision spine surgery cases. A historical control group of 652 patients were compared from the same surgeon over an earlier time period before the inception of using vancomycin powder prophylaxis. The objective of this study was to describe and compare the rates of infection in high-risk patient populations while using vancomycin powder. Vancomycin powder may not decrease an already low rate of infection. Therefore, use of vancomycin powder in high-risk patients with a higher rate of infection would potentially show benefit of vancomycin powder. In total, 496 patient charts were collected from a database of cases. Patients were included in the cohort if they had revision spinal operation or if they were diabetic. Patients in the time period July 2010 to August 2013 were included in the vancomycin protocol where 1 g of vancomycin powder was added to the wound before wound closure. Cases were considered positive if there was a positive culture or if there was sufficient clinical suspicion to treat. As a control to this cohort, 692 charts were reviewed from a earlier time period of the same surgeon and institution. In total, 28 patients of 496 (5.6%) patients in the cohort returned to the operating room for seroma, hematoma, draining wound, or infection. Sixteen of these patients (16/496, 3.2%) had a culture positive infection or were treated as an infection. This rate was significantly lower than the historical rate before the protocol. Although vancomycin does seem to be useful in decreasing SSIs, it is not a panacea. SSIs in high-risk patients were not completely eliminated by the vancomycin protocol.

Evaluation of vancomycin therapy in the adult ICUs of a teaching hospital in southern Iran

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Vazin A

2018-04-01

Full Text Available Afsaneh Vazin, Motahare Mahi Birjand, Masoud Darake Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran Background: Vancomycin resistance in intensive care units (ICUs accounts for significant morbidity and excess costs. The objective of the present study was to determine the appropriateness of vancomycin use in the various ICUs of Nemazee Hospital, Shiraz, Iran. Methods: This prospective study was performed on 95 critically ill patients (48 males and 47 females who were treated with vancomycin for at least 3 subsequent doses in 6 ICUs during 12 months. Required demographic, clinical, and paraclinical data were collected by a pharmacist. Fifteen indexes were considered for evaluation of vancomycin use. Results: Ventilator-associated hospital-acquired pneumonia (22.6%, sepsis (22.1% and CNS infection (12.6% were found to be the most important indications for vancomycin prescription. Vancomycin was prescribed empirically in 81% of patients. None of the patients received loading dose, and most of the patients received fixed dose. The rate of prolonged empiric antibiotic therapy was 68.5% in patients who received vancomycin. The mean score of vancomycin use in the ICUs of Nemazee Hospital was 7.1±0.6 out of 15, implying that the rate of vancomycin use was in accordance with the guideline proposed by the Department of Clinical Pharmacy of Nemazee Hospital based on Infectious Diseases Society of America by 47.3%. Conclusion: Based on our results, the weakness in using vancomycin was related to not administering loading dose, the practice of prescribing fixed-dose vancomycin and prolonged duration of empiric therapy. Efforts to improve the pattern of vancomycin prescription and utilization in these ICUs should be undertaken. Keywords: vancomycin, drug utilization, intensive care units

Single-Dose Bone Pharmacokinetics of Vancomycin in a Porcine Implant-Associated Osteomyelitis Model

DEFF Research Database (Denmark)

Bue, Mats; Hanberg, Pelle; Koch, Janne

2018-01-01

, vancomycin bone and soft tissue penetration during infection remains unclear. In eight pigs, implant-associated osteomyelitis was induced on day 0, using a Staphylococcus aureus strain. Following administration of 1,000 mg of vancomycin on day 5, vancomycin concentrations were obtained with microdialysis...

Enterocin A mutants identified by saturation mutagenesis enhance potency towards vancomycin-resistant Enterococci.

Science.gov (United States)

McClintock, Maria K; Kaznessis, Yiannis N; Hackel, Benjamin J

2016-02-01

Vancomycin-resistant Enterococci infections are a significant clinical problem. One proposed solution is to use probiotics, such as lactic acid bacteria, to produce antimicrobial peptides at the site of infection. Enterocin A, a class 2a bacteriocin, exhibits inhibitory activity against E. faecium and E. faecalis, which account for 86% of vancomycin-resistant Enterococci infections. In this study, we aimed to engineer enterocin A mutants with enhanced potency within a lactic acid bacterial production system. Peptide mutants resulting from saturation mutagenesis at sites A24 and T27 were efficiently screened in a 96-well plate assay for inhibition of pathogen growth. Several mutants exhibit increased potency relative to wild-type enterocin A in both liquid- and solid-medium growth assays. In particular, A24P and T27G exhibit enhanced inhibition of multiple strains of E. faecium and E. faecalis, including clinically isolated vancomycin-resistant strains. A24P and T27G enhance killing of E. faecium 8 by 13 ± 3- and 18 ± 4-fold, respectively. The engineered enterocin A/lactic acid bacteria systems offer significant potential to combat antibiotic-resistant infections. © 2015 Wiley Periodicals, Inc.

Frequency and Antibiogram of Vancomycin Resistant Enterococcus in a Tertiary Care Hospital

International Nuclear Information System (INIS)

Babar, N.; Usman, J.; Munir, T.; Gill, M. M.; Anjum, R.; Gilani, M.; Latif, M.

2014-01-01

Objective: To determine the frequency of Vancomycin Resistant Enterococcus (VRE) in a tertiary care hospital of Rawalpindi, Pakistan. Study Design: Observational, cross-sectional study. Place and Duration of Study: Department of Microbiology, Army Medical College, Rawalpindi, from May 2011 to May 2012. Methodology: Vancomycin resistant Enterococcus isolated from the clinical specimens including blood, pus, double lumen tip, ascitic fluid, tracheal aspirate, non-directed bronchial lavage (NBL), cerebrospinal fluid (CSF), high vaginal swab (HVS) and catheter tips were cultured on blood agar and MacConkey agar, while the urine samples were grown on cystine lactose electrolyte deficient agar. Later the antimicrobial susceptibility testing of the isolates was carried out using the modified Kirby-Bauer disc diffusion method on Mueller Hinton agar. Results: A total of 190 enterococci were isolated. Of these, 22 (11.57%) were found to be resistant to vancomycin. The antimicrobial sensitivity pattern revealed maximum resistance against ampicillin (86.36%) followed by erythromycin (81.81%) and gentamicin (68.18%) while all the isolates were 100% susceptible to chloramphenicol and linezolid. Conclusion: The frequency of VRE was 11.57% with the highest susceptibility to linezolid and chloramphenicol. (author)

Evaluation of body weight-based vancomycin therapy and the incidence of nephrotoxicity: a retrospective study in the northwest of China.

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Dong, Mo-Han; Wang, Jing-Wen; Wu, Yin; Chen, Bei-Yu; Yu, Min; Wen, Ai-Dong

2015-08-01

To identify specific risk factors of vancomycin-induced nephrotoxicity in China, as the relationship between vancomycin therapy (dosing and trough concentration monitoring) and nephrotoxicity has been the subject of critical debate. The cases of 90 critically ill patients who received vancomycin therapy in Xijing Hospital in the northwest of China between March 2014 and January 2015 were reviewed retrospectively. Vancomycin dosing, blood serum trough concentration, and other independent risk factors associated with nephrotoxicity were evaluated in a multivariable model. Among the 90 critically ill patients, 59 were males; mean age was 46.3 years. The indications for vancomycin use were methicillin-resistant Staphylococcus aureus-associated pneumonia, central nervous system infection, and bacteremia. Clinical pharmacists prescribed weight-based dosing, ranging from 20 to 45mg/kg/day. Fourteen (15.6%) patients developed nephrotoxicity, with serum creatinine elevated significantly from a mean (standard deviation) of 90.0 (18.8) μmol/l to 133.8 (63.2) μmol/l (p = 0.015). It was found that those with a vancomycin dosage >38mg/kg/day (50.0% vs. 11.3%, p = 0.004) and a vancomycin serum trough concentration >20mg/l (57.1% vs. 12.0%, p = 0.01) were more likely to develop nephrotoxicity. The data from this study indicate that a vancomycin dosage >38mg/kg/day and a serum trough level >20mg/l are both independent factors associated with the development of nephrotoxicity, suggesting that renal function should be monitored closely during vancomycin treatment. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

High MICs for Vancomycin and Daptomycin and Complicated Catheter-Related Bloodstream Infections with Methicillin-Sensitive Staphylococcus aureus

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Viedma, Esther; Chaves, Fernando; Lalueza, Antonio; Fortún, Jesús; Loza, Elena; Pujol, Miquel; Ardanuy, Carmen; Morales, Isabel; de Cueto, Marina; Resino-Foz, Elena; Morales-Cartagena, Alejandra; Rico, Alicia; Romero, María P.; Orellana, María Ángeles; López-Medrano, Francisco; Fernández-Ruiz, Mario; Aguado, José María

2016-01-01

We investigated the prognostic role of high MICs for antistaphylococcal agents in patients with methicillin-sensitive Staphylococcus aureus catheter-related bloodstream infection (MSSA CRBSI). We prospectively reviewed 83 episodes from 5 centers in Spain during April 2011–June 2014 that had optimized clinical management and analyzed the relationship between E-test MICs for vancomycin, daptomycin, oxacillin, and linezolid and development of complicated bacteremia by using multivariate analysis. Complicated MSSA CRBSI occurred in 26 (31.3%) patients; MICs for vancomycin and daptomycin were higher in these patients (optimal cutoff values for predictive accuracy = 1.5 μg/mL and 0.5 μg/mL). High MICs for vancomycin (hazard ratio 2.4, 95% CI 1.2–5.5) and daptomycin (hazard ratio 2.4, 95% CI 1.1–5.9) were independent risk factors for development of complicated MSSA CRBSI. Our data suggest that patients with MSSA CRBSI caused by strains that have high MICs for vancomycin or daptomycin are at increased risk for complications. PMID:27192097

Epidemiological alteration in pathogens found in ground meat in Iran: unexpected predominance of vancomycin-resistant Enterococcus faecalis

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Sadeghifard, Nourkhoda

2015-07-01

Full Text Available Colonization of the human and animal intestinal tract with potential pathogenic bacteria is correlated with the risk of contamination of food products. The current study analyzed the prevalence of and O157H7 in ground meat in Ilam, Iran. Both index organisms were identified following standard food microbiological methods. For , the susceptibility to vancomycin was tested, and PCR was used to check for the gene. was present in all 24 ground meat samples, with no O157H7 detected in samples. The analysis showed the presence of the gene in 5/24 vancomycin resistant enterococci. In conclusion, this study for the first time demonstrates the presence of vancomycin-resistant enterococci in ground meat in Iran. This observation warrants further epidemiologic investigation and should be followed up in the future.

Cost-effectiveness analysis evaluating fidaxomicin versus oral vancomycin for the treatment of Clostridium difficile infection in the United States.

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Stranges, Paul M; Hutton, David W; Collins, Curtis D

2013-01-01

Fidaxomicin is a novel treatment for Clostridium difficile infections (CDIs). This new treatment, however, is associated with a higher acquisition cost compared with alternatives. The objective of this study was to evaluate the cost-effectiveness of fidaxomicin or oral vancomycin for the treatment of CDIs. We performed a cost-utility analysis comparing fidaxomicin with oral vancomycin for the treatment of CDIs in the United States by creating a decision analytic model from the third-party payer perspective. The incremental cost-effectiveness ratio with fidaxomicin compared with oral vancomycin was $67,576/quality-adjusted life-year. A probabilistic Monte Carlo sensitivity analysis showed that fidaxomicin had an 80.2% chance of being cost-effective at a willingness-to-pay threshold of $100,000/quality-adjusted life-year. Fidaxomicin remained cost-effective under all fluctuations of both fidaxomicin and oral vancomycin costs. The decision analytic model was sensitive to variations in clinical cure and recurrence rates. Secondary analyses revealed that fidaxomicin was cost-effective in patients receiving concominant antimicrobials, in patients with mild to moderate CDIs, and when compared with oral metronidazole in patients with mild to moderate disease. Fidaxomicin was dominated by oral vancomycin if CDI was caused by the NAP1/Bl/027 Clostridium difficile strain and was dominant in institutions that did not compound oral vancomycin. Results of our model showed that fidaxomicin may be a more cost-effective option for the treatment of CDIs when compared with oral vancomycin under most scenarios tested. Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Auditory function after application of ototopical vancomycin and mupirocin solutions in a murine model.

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Rutherford, Kimberley D; Kavanagh, Katherine; Parham, Kourosh

2011-03-01

To determine whether mupirocin (440 µg/mL) and vancomycin otic drops (25 mg/mL) show evidence of ototoxicity in CBA/J mice immediately following a 7-day course of daily intratympanic (IT) injections and 1 month following treatment. Nonrandomized controlled trial. Academic hospital laboratory. Twenty CBA/J mice. Mean auditory brainstem response (ABR) thresholds increased in all drug- and saline-treated ears immediately after 7 days of IT injections but returned to baseline for most stimulus frequencies by 30 days later. This finding appeared to be correlated with the presence and subsequent resolution of tympanic membrane (TM) perforations and granulation tissue at the injection sites. Mupirocin-treated ears showed no significant difference in ABR thresholds compared to saline-treated ears. No significant differences were noted between vancomycin- and saline-treated ears, but there was a significant interaction between testing day and stimulus frequency (P injections (95% confidence interval, -13.5 to -5.5, P application of mupirocin solution (440 µg/mL) caused no significant change in the ABR thresholds in a murine model, vancomycin solution (25 mg/mL) resulted in high-frequency threshold elevations in both the ear directly injected and the contralateral ear. Mupirocin solution may be beneficial in managing otitis externa and media caused by resistant pathogens. Further studies of ototopical vancomycin are needed to define parameters governing its safe use.

Cost-effectiveness analysis of fidaxomicin versus vancomycin in Clostridium difficile infection.

Science.gov (United States)

Nathwani, Dilip; Cornely, Oliver A; Van Engen, Anke K; Odufowora-Sita, Olatunji; Retsa, Peny; Odeyemi, Isaac A O

2014-11-01

Fidaxomicin was non-inferior to vancomycin with respect to clinical cure rates in the treatment of Clostridium difficile infections (CDIs) in two Phase III trials, but was associated with significantly fewer recurrences than vancomycin. This economic analysis investigated the cost-effectiveness of fidaxomicin compared with vancomycin in patients with severe CDI and in patients with their first CDI recurrence. A 1 year time horizon Markov model with seven health states was developed from the perspective of Scottish public healthcare providers. Model inputs for effectiveness, resource use, direct costs and utilities were obtained from published sources and a Scottish expert panel. The main model outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY), for fidaxomicin versus vancomycin; ICERs were interpreted using willingness-to-pay thresholds of £20,000/QALY and £30,000/QALY. One-way and probabilistic sensitivity analyses were performed. Total costs were similar with fidaxomicin and vancomycin in patients with severe CDI (£14,515 and £14,344, respectively) and in patients with a first recurrence (£16,535 and £16,926, respectively). Improvements in clinical outcomes with fidaxomicin resulted in small QALY gains versus vancomycin (severe CDI, +0.010; patients with first recurrence, +0.019). Fidaxomicin was cost-effective in severe CDI (ICER £16,529/QALY) and dominant (i.e. more effective and less costly) in patients with a first recurrence. The probability that fidaxomicin was cost-effective at a willingness-to-pay threshold of £30,000/QALY was 60% for severe CDI and 68% in a first recurrence. Fidaxomicin is cost-effective in patients with severe CDI and in patients with a first CDI recurrence versus vancomycin. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

Leuconostoc garlicum: an unusual pathogen in the era of vancomycin therapy.

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Kumar, Anil; Augustine, Deepthi; Mehta, Asmita; Dinesh, Kavitha R; Viswam, Darsana; Philip, Rosamma

2012-01-01

Leuconostoc garlicum, belonging to the family of Leuconostocaceae, is a catalase-negative, Gram-positive ovoid cocci, intrinsically resistant to vancomycin. Clinical infection by Leuconostoc garlicum is rare. We report a case of respiratory tract infection subsequent to vancomycin therapy.

Halloysite nanotubes as carriers of vancomycin in alginate-based wound dressing

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Joanna Kurczewska

2017-09-01

Full Text Available The influence of an inorganic support – halloysite nanotubes – on the release rate and biological activity of the antibiotic encapsulated in alginate-based dressings was studied. The halloysite samples were loaded with approx. 10 wt.% of the antibiotic and then encapsulated in Alginate and Gelatin/Alginate gels. The material functionalized with aliphatic amine significantly extended the release of vancomycin from alginate-based gels as compared to that achieved when silica was used. After 24 h, the released amounts of the antibiotic immobilized at silica reached 70%, while for the drug immobilized at halloysite the released amount of vancomycin reached 44% for Alginate discs. The addition of gelatin resulted in even more prolonged sustained release of the drug. The antibiotic was released from the system with a double barrier with Higuchi kinetic model and Fickian diffusion mechanism. Only the immobilized drug encapsulated in Alginate gel demonstrated very good antimicrobial activity against various bacteria. The inhibition zones were greater than those of the standard discs for the staphylococci and enterococci bacteria tested. The addition of gelatin adversely affected the biological activity of the system. The inhibition zones were smaller than those of the reference samples. A reduction in the drug dose by half had no significant effect on changing the release rate and microbiological activity. The in vivo toxicity studies of the material with immobilized drug were carried out with Acutodesmus acuminatus and Daphnia magna. The material studied had no effect on the living organisms used in the bioassays. The proposed system with a double barrier demonstrated high storage stability.

Vancomycin resistant enterococci in farm animals – occurrence and importance

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Oskar Nilsson

2012-04-01

Full Text Available The view on enterococci has over the years shifted from harmless commensals to opportunistic but important pathogens mainly causing nosocomial infections. One important part of this development is the emergence of vancomycin resistance enterococci (VRE. The term VRE includes several combinations of bacterial species and resistance genes of which the most clinically important is Enterococcus faecium with vanA type vancomycin resistance. This variant is also the most common VRE among farm animals. The reason for VRE being present among farm animals is selection by extensive use of the vancomycin analog avoparcin for growth promotion. Once the use of avoparcin was discontinued, the prevalence of VRE among farm animals decreased. However, VRE are still present among farm animals and by spread via food products they could potentially have a negative impact on public health. This review is based on the PhD thesis Vancomycin Resistant Enterococci in Swedish Broilers – Emergence, Epidemiology and Elimination and makes a short summary of VRE in humans and food producing animals. The specific situation regarding VRE in Swedish broiler production is also mentioned.

Detection of vancomycin resistances in enterococci within 3 1/2 hours

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Schröder, U. -Ch.; Beleites, C.; Assmann, C.; Glaser, U.; Hübner, U.; Pfister, W.; Fritzsche, W.; Popp, J.; Neugebauer, U.

2015-02-01

Vancomycin resistant enterococci (VRE) constitute a challenging problem in health care institutions worldwide. Novel methods to rapidly identify resistances are highly required to ensure an early start of tailored therapy and to prevent further spread of the bacteria. Here, a spectroscopy-based rapid test is presented that reveals resistances of enterococci towards vancomycin within 3.5 hours. Without any specific knowledge on the strain, VRE can be recognized with high accuracy in two different enterococci species. By means of dielectrophoresis, bacteria are directly captured from dilute suspensions, making sample preparation very easy. Raman spectroscopic analysis of the trapped bacteria over a time span of two hours in absence and presence of antibiotics reveals characteristic differences in the molecular response of sensitive as well as resistant Enterococcus faecalis and Enterococcus faecium. Furthermore, the spectroscopic fingerprints provide an indication on the mechanisms of induced resistance in VRE.

Fidaxomicin versus Vancomycin in the Treatment of Clostridium difficile Infection: Canadian Outcomes

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Christine Lee

2016-01-01

Full Text Available Background. This analysis examined the efficacy of fidaxomicin versus vancomycin in 406 Canadian patients with Clostridium difficile infection (CDI, based on data from 2 randomized, clinical trials. Methods. Patients received fidaxomicin or vancomycin 1. Patients were assessed for clinical response recurrence of infection and sustained clinical response for 28 days after treatment completion. Patients at increased risk of recurrence were subjected to subgroup analyses. Results. Clinical response rates for fidaxomicin (90.0% were noninferior to those with vancomycin (92.2%; 95% confidence interval for difference: −7.7, 3.5. However, fidaxomicin-treated patients had lower recurrence (14.4% versus 28.0%, p=0.001 and higher sustained clinical response (77.1% versus 66.3%, p=0.016. Compared with vancomycin, fidaxomicin was associated with lower recurrence rates in all subgroups, reaching statistical significance in patients with age ≥ 65 years (16.0% versus 30.9%, p=0.026, concomitant antibiotic use (16.2% versus 38.7%, p=0.036, and non-BI strains (11.8% versus 28.3%, p=0.004. Higher sustained clinical response rates were observed for fidaxomicin compared with vancomycin in all subgroups; this was statistically significant in the non-BI subgroup (82.8% versus 69.1%, p=0.021. Conclusions. In Canadian patients, fidaxomicin was superior to vancomycin in sustaining clinical response and reducing CDI recurrence.

Vancomycin added to the wash solution of the cell-saver. Effect on bacterial contamination.

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Perez-Ferrer, A; Gredilla-Díaz, E; de Vicente-Sánchez, J; Navarro-Suay, R; Gilsanz-Rodríguez, F

2017-04-01

The aim of this study is to test whether the addition of a low-dose of antibiotic (vancomycin) to the wash solution (saline) of the cell-saver reduces the incidence of bacterial contamination of the autologous red blood cell (RBCs) concentrate recovered. Experimental, randomized, double-blind, parallel group study performed on 20 consecutive patients scheduled for posterior spinal fusion surgery. Intraoperative bleeding was processed through a cell-saver: HaemoLite ® 2+, in which the RBCs were washed according to randomization group, with saline (control group) or saline+10μg/ml -1 vancomycin (vanco group). Data regarding age, weight, processed and recovered volume, blood count, blood culture, and vancomycin concentration in RBCs concentrates obtained and incidence of fever after reinfusion were collected. Processed volume was 843±403ml and recovered volume 121±29ml, with haemoglobin concentration 10.4±5.0g/dl -1 and haematocrit 29.1±15.9% (mean±SD). Recovered RBC concentrate cultures were positive for coagulase-negative Staphylococcus in 5 cases (50%) of the control group while all cultures were negative in the vanco group (P=.016). The difference between the theoretical concentration of vancomycin administered and the concentration determined in the recovered RBC concentrate was 1.31μg/ml -1 (95% CI 1.19 to 1.43; P=.074). The addition of vancomycin at a concentration of 10ug/ml -1 to the wash solution of the cell-saver achieved similar concentrations in the autologous blood concentrate recovered allowing for bacterial removal, with negative blood cultures in all cases. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Optimization of nebulized delivery of linezolid, daptomycin, and vancomycin aerosol

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Zarogoulidis P

2014-08-01

Full Text Available Paul Zarogoulidis,1 Ioannis Kioumis,1 Sofia Lampaki,1 John Organtzis,1 Konstantinos Porpodis,1 Dionysios Spyratos,1 Georgia Pitsiou,1 Dimitris Petridis,2 Athanasia Pataka,1 Haidong Huang,3 Qiang Li,3 Lonny Yarmus,4 Wolfgang Hohenforst-Schmidt,5 Nikolaos Pezirkianidis,6 Konstantinos Zarogoulidis1 1Pulmonary Department-Oncology Unit, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Department of Food Technology, School of Food Technology and Nutrition, Alexander Technological Educational Institute, Thessaloniki, Greece; 3Department of Respiratory Diseases, Shanghai Hospital, II Military University Hospital, Shanghai, People’s Republic of China; 4Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA; 5II Medical Department, “Coburg” Regional Hospital, Coburg, Germany; 6Surgery Department, Private Cabinet, Serres, Greece Background: At this time, several antibiotics have been investigated as possibilities for aerosol administration, but local therapy has been found to be more efficient in several diseases. Materials and methods: The drugs linezolid (Zyvox, vancomycin (Voncon, and daptomycin (Cubicin were tested with three jet nebulizers with seven different residual cups and different loadings. Moreover, three ultrasound nebulizers were again tested with these drugs, with different loadings and mouthpiece attachments. Results: When drugs are combined with particular cup designs, they significantly lower the droplet size to 1.60 and 1.80 µm, which represents the best combination of Zyvox and cup G and Cubicin and cup D, respectively. Cup design D is suggested as the most effective cup for lowering the droplet size (2.30 µm when considering a higher loading level (8 mL. Conclusion: Modification of current drugs from dry powder to solution is possible, and the residual cup design plays the most important role in droplet size production when the

Antistaphylococcal Activity of DX-619 Alone and in Combination with Vancomycin, Teicoplanin, and Linezolid Assessed by Time-Kill Synergy Testing▿ †

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

2007-01-01

Time-kill synergy studies testing in vitro activity of DX-619 alone and with added vancomycin, teicoplanin, or linezolid against 101 Staphylococcus aureus strains showed synergy between DX-619 and teicoplanin at 12 to 24 h in 72 strains and between DX-619 and vancomycin in 28 strains. No synergy was found with linezolid, and no antagonism was observed with any combination. PMID:17261625

Annual Surveillance Summary: Vancomycin-Resistant Enterococci (VRE) Infections in the Military Health System (MHS), 2015

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2017-03-01

Oregon, Washington, Idaho, Montana, Wyoming, Colorado, New Mexico , Arizona, Utah, Nevada, Alaska, Hawaii. • South: Texas, Oklahoma, Arkansas, Louisiana... Diabetes and Digestive and Kidney Diseases. Washington, DC. 2007; 587–620. 27. Milburn E, Chukwuma U. Vancomycin-resistant Enterococci infections in

Recovery of vancomycin-resistant gram-positive cocci from children.

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Green, M; Wadowsky, R M; Barbadora, K

1990-01-01

A cross-sectional survey of vancomycin-resistant gram-positive cocci (VRGPC) in the feces of children was initiated after several bacteremic infections with these organisms occurred at our hospital. A selective medium consisting of colistin-nalidixic acid agar, 5% sheep blood, vancomycin (5 mg/liter), and amphotericin B (8 mg/liter) was developed to isolate VRGPC. A single stool specimen submitted to the clinical microbiology laboratory from each of 48 patients was inoculated onto the medium....

Prophylactic intracameral vancomycin: efficacy in preventing endophthalmitis after cataract surgery

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Manash Kumar Goswami

2016-01-01

Full Text Available Background and objective: Post Operative endophthalmitis is rare but devastating complication in ocular surgery. The present study determined the efficacy of intracameral vancomycin after phaco-emusification cataract surgery to prevent endophthalmitis. Method: A total of 768 cases who had undergone phaco-emusification cataract surgery were included in the study. Every alternate patient received 0.5 ml injection of vancomycin (1mg in 0.1 ml in the anterior chamber after completion of phaco-emulcification and formation of anterior chamber. All the patients were examined for symptoms and signs of bacterial endophthalmitis at 24 hrs, 7 days, 15 days and subsequently at 1, 3 and 6 months following surgery. Results: No endophthalmitis case was recorded at any time period during 6 month follow up in either group. However, significantly higher number of cases in vancomycin group had cells in anterior chamber and disturbances in visual acuity at day 15 following surgery. Conclusion: Vancomycin did not have any prophylactic role in preventing endophthalmitis. Proper aseptic measures are important to prevent any infection in ocular surgery. IMC J Med Sci 2016; 10(1: 24-28

The cost effectiveness of vancomycin for preventing infections after shoulder arthroplasty: a break-even analysis.

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Hatch, M Daniel; Daniels, Stephen D; Glerum, Kimberly M; Higgins, Laurence D

2017-03-01

Increasing methicillin resistance and recognition of Propionibacterium acnes as a cause of infection in shoulder arthroplasty has led to the adoption of local vancomycin powder application as a more effective method to prevent expensive periprosthetic infections. However, no study has analyzed the cost effectiveness of vancomycin powder for preventing infection after shoulder replacement. Cost data for infection-related care of 16 patients treated for deep periprosthetic shoulder infection was collected from our institution for the break-even analysis. An equation was developed and applied to the data to determine how effective vancomycin powder would need to be at reducing a baseline infection rate to make prophylactic use cost effective. The efficacy of vancomycin (absolute risk reduction [ARR]) was evaluated at different unit costs, baseline infection rates, and average costs of treating infection. We determined vancomycin to be cost effective if the initial infection rate decreased by 0.04% (ARR). Using the current costs of vancomycin reported in the literature (range: $2.50/1000 mg to $44/1000 mg), we determined vancomycin to be cost effective with an ARR range of 0.01% at a cost of $2.50/1000 mg to 0.19% at $44/1000 mg. Baseline infection rate does not influence the ARR obtained at any specific cost of vancomycin or the cost of treating infection. We have derived and used a break-even equation to assess efficacy of prophylactic antibiotics during shoulder surgery. We further demonstrated the prophylactic administration of local vancomycin powder during shoulder arthroplasty to be a highly cost-effective practice. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Balancing vancomycin efficacy and nephrotoxicity: should we be aiming for trough or AUC/MIC?

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Patel, Karisma; Crumby, Ashley S; Maples, Holly D

2015-04-01

Sixty years later, the question that still remains is how to appropriately utilize vancomycin in the pediatric population. The Infectious Diseases Society of America published guidelines in 2011 that provide guidance for dosing and monitoring of vancomycin in adults and pediatrics. However, goal vancomycin trough concentrations of 15-20 μg/mL for invasive infections caused by methicillin-resistant Staphylococcus aureus were based primarily on adult pharmacokinetic and pharmacodynamic data that achieved an area under the curve to minimum inhibitory concentration ratio (AUC/MIC) of ≥400. Recent pediatric literature shows that vancomycin trough concentrations needed to achieve the target AUC/MIC are different than the adult goal troughs cited in the guidelines. This paper addresses several thoughts, including the role of vancomycin AUC/MIC in dosing strategies and safety monitoring, consistency in laboratory reporting, and future directions for calculating AUC/MIC in pediatrics.

AUC versus peak-trough dosing of vancomycin: applying new pharmacokinetic paradigms to an old drug.

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Brown, Daniel L; Lalla, Christina D; Masselink, Andrew J

2013-08-01

To compare and contrast the pharmacokinetic/pharmacodynamic foundations of traditional "peak-trough" vancomycin dosing methods versus newer "area under the curve" (AUC) strategies. To propose a new AUC-based dosing chart for empirically determining an initial vancomycin dosing regimen designed to achieve a desired AUC24 using the minimum inhibitory concentration (MIC), creatinine clearance (CrCl), and vancomycin clearance (ClVanco). Peak-trough vancomycin dosing is designed to achieve a Cpeak of 20-40 mg/L and a Ctrough of 10-15 or 15-20 mg/L, depending on the severity of the infection and the nature of the pathogen. New treatment guidelines for vancomycin suggest that therapy should achieve an AUC24/MIC of ≥400. AUC-based vancomycin dosing derives the daily dose from ClVanco, MIC, and the desired AUC24/MIC, without consideration of the patient's weight. A vancomycin dosing chart is proposed that estimates ClVanco using the following formula developed by Matzke et al: ClVanco in L/h = [(CrClmL/min × 0.689) + 3.66] × 0.06, which simplifies to (CrClmL/min × 0.41) + 0.22. Two levels of dosing are included-high dose (Ctrough: 15-20 mg/L) and moderate dose (Ctrough: 10-15 mg/L). Although the chart has not been validated clinically, it represents the product of standard dosing equations that are used to determine a starting dosing regimen based on well-established vancomycin pharmacokinetic parameters. An understanding of pharmacokinetic and pharmacodynamic principles, including the relevance of AUC in relation to MIC, enables clinicians to make the best use of vancomycin dosing options. The proposed dosing chart is pharmacokinetically valid but has yet to be applied clinically. It provides a foundation for further study of how clinicians can determine an optimal AUC-based starting vancomycin dosing regimen without having to derive ClVanco or AUC24.

Randomized prospective study comparing vancomycin with teicoplanin in the treatment of infections associated with Hickman catheters.

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Smith, S R; Cheesbrough, J; Spearing, R; Davies, J M

1989-08-01

In 72 episodes of suspected or proven Hickman-catheter-associated infection occurring in 59 patients with various hematological disorders, patients were assigned to treatment with either vancomycin or teicoplanin in a randomized nonblinded prospective study. Of 60 episodes evaluable for response, 28 were treated with vancomycin and 32 were treated with teicoplanin. Sixteen infective episodes were microbiologically documented in the vancomycin group, and twenty-one were microbiologically documented in the teicoplanin group. Microbiologically and clinically documented infections treated with vancomycin had an 80% response rate, compared with a 69% response rate for those treated with teicoplanin (P = 0.316). Adverse events occurred in nine (25%) of the episodes in the vancomycin group, compared with three (8%) in the teicoplanin group (P = 0.044). Teicoplanin may provide an effective alternative to vancomycin in the treatment of Hickman-catheter-associated infection in patients with hematological malignancies.

Comparing the ocular surface effects of topical vancomycin and linezolid for treating bacterial keratitis.

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Akova Budak, Berna; Baykara, Mehmet; Kıvanç, Sertaç Argun; Yilmaz, Hakan; Cicek, Serhat

2016-01-01

Vancomycin is the gold standard in combination therapy for severe and resistant gram-positive keratitis and in particular for Methicillin-resistant Staphylococcus aureus (MRSA) infections. The aim of this study was to report the ocular surface toxicity and scoring in patients whose treatment shifted to topical linezolid/ceftazidime from topical vancomycin/ceftazidime due to their vancomycin intolerance. A retrospective, interventional case series of bacterial keratitis was treated with topical linezolid (one drop of 0.2% solution per eye), administered hourly until epithelization and then gradually decreased. The number and extent of punctate epithelial erosions were noted across the entire surface of the cornea. Ocular discomfort was assessed by means of (a) patient-reported pain upon instillation of the medication (vancomycin/linezolid), (b) reported burning sensation between doses and (c) reported foreign-body sensation. No ocular surface toxicity related to linezolid use was noted. Patients were followed for at least 2 months after treatment between April and December 2013. Of the seven patients included in the study (age range: 2-88 years; five females, two males), complete epithelization and resolution was achieved in five patients. One patient was treated with linezolid after penetrating keratoplasty. The second culture of another patient with impending perforation despite linezolid/ceftazidime therapy yielded Fusarium spp., so he underwent tectonic keratoplasty. The mean ocular surface score was 9.4 ± 1.6 during vancomycin treatment and 5.9 ± 1.3 during linezolid treatment after discontinuation of vancomycin. The topical linezolid score was significantly lower (p = 0.027). Topical linezolid may be better tolerated, according to the mean ocular surface score, than topical vancomycin by some patients and can be considered an alternative for patients who do not well tolerate vancomycin.

Currently used dosage regimens of vancomycin fail to achieve therapeutic levels in approximately 40% of intensive care unit patients.

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Obara, Vitor Yuzo; Zacas, Carolina Petrus; Carrilho, Claudia Maria Dantas de Maio; Delfino, Vinicius Daher Alvares

2016-01-01

This study aimed to assess whether currently used dosages of vancomycin for treatment of serious gram-positive bacterial infections in intensive care unit patients provided initial therapeutic vancomycin trough levels and to examine possible factors associated with the presence of adequate initial vancomycin trough levels in these patients. A prospective descriptive study with convenience sampling was performed. Nursing note and medical record data were collected from September 2013 to July 2014 for patients who met inclusion criteria. Eighty-three patients were included. Initial vancomycin trough levels were obtained immediately before vancomycin fourth dose. Acute kidney injury was defined as an increase of at least 0.3mg/dL in serum creatinine within 48 hours. Considering vancomycin trough levels recommended for serious gram-positive infection treatment (15 - 20µg/mL), patients were categorized as presenting with low, adequate, and high vancomycin trough levels (35 [42.2%], 18 [21.7%], and 30 [36.1%] patients, respectively). Acute kidney injury patients had significantly greater vancomycin trough levels (p = 0.0055, with significance for a trend, p = 0.0023). Surprisingly, more than 40% of the patients did not reach an effective initial vancomycin trough level. Studies on pharmacokinetic and dosage regimens of vancomycin in intensive care unit patients are necessary to circumvent this high proportion of failures to obtain adequate initial vancomycin trough levels. Vancomycin use without trough serum level monitoring in critically ill patients should be discouraged.

Recovery of vancomycin-resistant gram-positive cocci from children.

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Green, M; Wadowsky, R M; Barbadora, K

1990-03-01

A cross-sectional survey of vancomycin-resistant gram-positive cocci (VRGPC) in the feces of children was initiated after several bacteremic infections with these organisms occurred at our hospital. A selective medium consisting of colistin-nalidixic acid agar, 5% sheep blood, vancomycin (5 mg/liter), and amphotericin B (8 mg/liter) was developed to isolate VRGPC. A single stool specimen submitted to the clinical microbiology laboratory from each of 48 patients was inoculated onto the medium. Plates were incubated at 35 degrees C with 5% carbon dioxide and examined at 24, 48, and 72 h. Susceptibilities were determined by broth microdilution. A total of 14 isolates from 11 of 48 (22%) children were recovered. The density of growth ranged from a single colony to 2+. The VRGPC were identified as Leuconostoc lactis (n = 2), Lactobacillus confusus (n = 4), Enterococcus species (n = 5), and Lactococcus lactis (n = 3). One strain of Lactobacillus confusus was recovered from both the stool and the blood of one of these patients. The MICs of vancomycin were 4 micrograms/ml for one of the isolates, 8 micrograms/ml for four of the isolates, and more than 16 micrograms/ml for the remaining eight isolates. All isolates were susceptible to both penicillin and ampicillin. Only 1 of the 11 children had received prior treatment with vancomycin. We conclude that low concentrations of VRGPC may be common in the gastrointestinal tracts of children.

Comparative effectiveness of linezolid versus vancomycin as definitive antibiotic therapy for heterogeneously resistant vancomycin-intermediate coagulase-negative staphylococcal central-line-associated bloodstream infections in a neonatal intensive care unit.

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Blanchard, A C; Fortin, E; Laferrière, C; Goyer, I; Moussa, A; Autmizguine, J; Quach, C

2017-06-01

Heterogeneously resistant vancomycin-intermediate coagulase-negative staphylococci (hVICoNS) are emerging pathogens causing central-line-associated bloodstream infections (CLABSIs) in neonatal intensive care unit (NICU) patients. Given the burden of disease associated with CLABSI and the current lack of therapeutic guidelines, we aimed to compare the effectiveness of linezolid versus vancomycin used as the definitive antibiotic therapy for hVICoNS CLABSI. We performed a retrospective cohort study of infants with hVICoNS CLABSI from a single NICU between 2009 and 2014, treated with either linezolid or vancomycin as definitive antibiotic therapy. CLABSI duration, early and late recurrence and in-hospital mortality were compared using propensity score-adjusted proportional hazards and logistic regression models. Of 89 infants with hVICoNS CLABSI, 33 (37.1%) treated with linezolid were compared with 56 (62.9%) treated with vancomycin. The median duration of CLABSI was 5 (range 1-12) versus 4 days (range 0-14) ( P  =   0.11), early recurrences were 3.0% versus 7.1% ( P  =   0.42), late recurrences 0% versus 14.3% ( P  =   0.02) and mortality 27.3% versus 28.6% ( P  =   0.90), when treated with linezolid versus vancomycin, respectively. When adjusting using a continuous propensity score, linezolid had an HR of 0.78 (95% CI 0.48-1.27) for CLABSI duration, an OR of 0.23 (95% CI 0.02-2.56) for early recurrence and an OR of 0.9 (95% CI 0.3-2.67) for mortality, relative to vancomycin. There was no statistically significant difference between linezolid and vancomycin when used as definitive treatment for hVICoNS CLABSI in NICU patients, in terms of CLABSI duration, recurrence or all-cause mortality. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Clinical and economic benefits of fidaxomicin compared to vancomycin for Clostridium difficile infection.

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Gallagher, Jason C; Reilly, Joseph P; Navalkele, Bhagyashri; Downham, Gemma; Haynes, Kevin; Trivedi, Manish

2015-11-01

We studied the clinical and economic impact of a protocol encouraging the use of fidaxomicin as a first-line drug for treatment of Clostridium difficile infection (CDI) in patients hospitalized during a 2-year period. This study evaluated patients who received oral vancomycin or fidaxomicin for the treatment of CDI during a 2-year period. All included patients were eligible for administration of fidaxomicin via a protocol that encouraged its use for selected patients. The primary clinical endpoint was 90-day readmission with a diagnosis of CDI. Hospital charges and insurance reimbursements for readmissions were calculated along with the cost of CDI therapy to estimate the financial impact of the choice of therapy. Recurrences were seen in 10/49 (20.4%) fidaxomicin patients and 19/46 (41.3%) vancomycin patients (P = 0.027). In a multivariate analysis that included determinations of severity of CDI, serum creatinine increases, and concomitant antibiotic use, only fidaxomicin was significantly associated with decreased recurrence (adjusted odds ratio [aOR], 0.33; 95% confidence interval [CI], 0.12 to 0.93). The total lengths of stay of readmitted patients were 183 days for vancomycin and 87 days for fidaxomicin, with costs of $454,800 and $196,200, respectively. Readmissions for CDI were reimbursed on the basis of the severity of CDI, totaling $151,136 for vancomycin and $107,176 for fidaxomicin. Fidaxomicin drug costs totaled $62,112, and vancomycin drug costs were $6,646. We calculated that the hospital lost an average of $3,286 per fidaxomicin-treated patient and $6,333 per vancomycin-treated patient, thus saving $3,047 per patient with fidaxomicin. Fidaxomicin use for CDI treatment prevented readmission and decreased hospital costs compared to use of oral vancomycin. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Suppression by Saccharomyces boulardii of toxigenic Clostridium difficile overgrowth after vancomycin treatment in hamsters.

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Elmer, G W; McFarland, L V

1987-01-01

Saccharomyces boulardii prevented the development of high counts of Clostridium difficile, high titers of toxin B, and positive latex agglutination tests after cessation of vancomycin treatment for hamsters. The protocol used was designed to stimulate relapse of human C. difficile-associated colitis. S. boulardii was protective in this model. PMID:3566236

Antibiotic Resistance Patterns of Enterococci and Occurrence of Vancomycin-Resistant Enterococci in Raw Minced Beef and Pork in Germany

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Klein, Günter; Pack, Alexander; Reuter, Gerhard

1998-01-01

The food chain, especially raw minced meat, is thought to be responsible for an increase in the incidence of vancomycin-resistant enterococci (VRE) in human nosocomial infections. Therefore, 555 samples from 115 batches of minced beef and pork from a European Union-licensed meat-processing plant were screened for the occurrence of VRE. The processed meat came from 45 different slaughterhouses in Germany. Enterococci were isolated directly from Enterococcosel selective agar plates and also from Enterococcosel selective agar plates supplemented with 32 mg of vancomycin per liter. In addition, peptone broth was used in a preenrichment procedure, and samples were subsequently plated onto Enterococcosel agar containing vancomycin. To determine resistance, 209 isolates from 275 samples were tested with the glycopeptides vancomycin, teicoplanin, and avoparcin and 19 other antimicrobial substances by using a broth microdilution test. When the direct method was used, VRE were found in 3 of 555 samples (0.5%) at a concentration of 1.0 log CFU/g of minced meat. When the preenrichment procedure was used, 8% of the samples were VRE positive. Our findings indicate that there is a low incidence of VRE in minced meat in Germany. In addition, the resistance patterns of the VRE isolates obtained were different from the resistance patterns of clinical isolates. A connection between the occurrence of VRE in minced meat and nosocomial infections could not be demonstrated on the basis of our findings. PMID:9572958

Clinical Utility and Safety of a Model-Based Patient-Tailored Dose of Vancomycin in Neonates.

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Leroux, Stéphanie; Jacqz-Aigrain, Evelyne; Biran, Valérie; Lopez, Emmanuel; Madeleneau, Doriane; Wallon, Camille; Zana-Taïeb, Elodie; Virlouvet, Anne-Laure; Rioualen, Stéphane; Zhao, Wei

2016-04-01

Pharmacokinetic modeling has often been applied to evaluate vancomycin pharmacokinetics in neonates. However, clinical application of the model-based personalized vancomycin therapy is still limited. The objective of the present study was to evaluate the clinical utility and safety of a model-based patient-tailored dose of vancomycin in neonates. A model-based vancomycin dosing calculator, developed from a population pharmacokinetic study, has been integrated into the routine clinical care in 3 neonatal intensive care units (Robert Debré, Cochin Port Royal, and Clocheville hospitals) between 2012 and 2014. The target attainment rate, defined as the percentage of patients with a first therapeutic drug monitoring serum vancomycin concentration achieving the target window of 15 to 25 mg/liter, was selected as an endpoint for evaluating the clinical utility. The safety evaluation was focused on nephrotoxicity. The clinical application of the model-based patient-tailored dose of vancomycin has been demonstrated in 190 neonates. The mean (standard deviation) gestational and postnatal ages of the study population were 31.1 (4.9) weeks and 16.7 (21.7) days, respectively. The target attainment rate increased from 41% to 72% without any case of vancomycin-related nephrotoxicity. This proof-of-concept study provides evidence for integrating model-based antimicrobial therapy in neonatal routine care. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Ultra high performance liquid chromatography-tandem mass spectrometry vs. commercial immunoassay for determination of vancomycin plasma concentration in children. Possible implications for everyday clinical practice.

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Barco, Sebastiano; Castagnola, Elio; Gennai, Iulian; Barbagallo, Laura; Loy, Anna; Tripodi, Gino; Cangemi, Giuliana

2016-10-01

Vancomycin therapeutic drug monitoring (TDM) is necessary for effective and safetherapy. The aim of the this paper was to develop a specific and robust ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for vancomycin quantification starting from low plasma volumes to be applied for the routine TDM in children. Samples from children receiving intravenous vancomycin were analysed using a TSQ Quantum Access MAX Triple Quadrupole system coupled with an Accela 1250 UHPLC system after a rapid protein precipitation. Gradient separation chromatography was carried out using a Hypersil GOLD aQ C18 column (50 × 2.1 mm, particle size 1.9 μm). Method performance was validated following international guidelines. UHPLC-MS/MS allowed a rapid and specific quantification of vancomycin over the range 0.1-128 μg/mL from 50 μL of plasma with high reproducibility and accuracy in the absence of matrix effect. The comparison with the commercial immunoassay performed on 138 samples demonstrated the presence of a proportional bias. The concentrations of vancomycin measured with immunoassay were found to be 4.5% (95% CI: 1.3-7.7) higher than those determined with UHPLC-MS/MS. Importantly, a clinical discordance was found in about 10% of samples analysed. This new UHPLC-MS/MS method is accurate and specific for the measurement of vancomycin starting from small (50 μL) plasma volumes. The use of UHPLC-MS/MS is recommended to prevent a misclassification of therapeutic or toxic vancomycin levels in paediatrics.

Delayed-Onset Post-Keratoplasty Endophthalmitis Caused by Vancomycin-Resistant Enterococcus faecium

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Julio C. Hernandez-Camarena

2012-10-01

Full Text Available Background: Vancomycin-resistant Enterococcus (VRE endophthalmitis after penetrating keratoplasty (PKP is very rare, the management is a challenge due to both the pattern of antibiotic resistance and the aggressive nature of the infectious process. We report the first delayed-onset case of VRE endophthalmitis after PKP. Materials and Methods: Case report of a 51-year-old female with a 7-week history of PKP who arrived at the emergency room with signs and symptoms of endophthalmitis. Initial visual acuity was light perception, and a posterior pole exam was not possible due to the intense vitreous reaction. Mode B ultrasound was used to assess the posterior pole. The patient underwent pars plana vitrectomy and received intravitreous antibiotics. Results: Vitreous stains and cultures were positive for Enterococcus faecium resistant to vancomycin. Donor rim cultures and viral PCR were negative. Treatment was carried out by repeated intravitreal antibiotics and systemic linezolid. Clinical improvement was seen after the second dose of intravitreous antibiotics and systemic linezolid, but visual acuity remained at light perception consistent with the ischemic changes observed in the posterior pole. Conclusion: VRE endophthalmitis might be associated with positive donor rim cultures. Prompt use of systemic linezolid in addition to intravitreous antibiotics is recommendable, but even with prompt treatment, visual prognosis is guarded.

Surveillance and endemic vancomycin-resistant enterococci: some success in control is possible.

LENUS (Irish Health Repository)

Morris-Downes, M

2010-07-01

Vancomycin-resistant enterococci (VRE) are prevalent in many Irish hospitals. We analysed surveillance data from 2001 to 2008 in a centre where VRE is endemic. All clinically significant enterococci were tested for susceptibility to vancomycin. All intensive care unit admissions were screened on admission and weekly thereafter. Interventions included isolating\\/cohorting VRE patients, monthly prevalence surveys of VRE patients, the introduction of an electronic alert system, programmes to improve hand and environmental hygiene, and the appointment of an antibiotic pharmacist. There was a significant increase in the number of positive VRE screening samples from 2001 (1.96 patients with positive VRE screens per 10 000 bed-days) to 2006 (4.98 per 10 000 bed-days) (P < or = 0.001) with a decrease in 2007 (3.18 per 10 000 bed-days) (P < or = 0.01). The number of VRE bloodstream infections (BSI) increased from 0.09 BSI per 10 000 bed-days in 2001 to 0.78 per 10 000 bed-days in 2005 (P < or = 0.001) but decreased subsequently. Linear regression analysis indicated a significant association between new cases of VRE and non-isolated VRE patients, especially between May 2005 and December 2006 [P=0.009; 95% confidence interval (CI): 0.08-0.46] and between May 2005 and December 2008 (P = 0.008; 95% CI: 0.06-0.46). Routine surveillance for VRE together with other measures can control VRE BSI and colonisation, even where VRE is endemic, and where facilities are constrained.

Titanium-tethered vancomycin prevents resistance to rifampicin in Staphylococcus aureus in vitro.

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Martin Rottman

Full Text Available Rifampicin is currently recognized as the most potent drug against Gram positive implant related infections. The use of rifampicin is limited by the emergence of bacterial resistance, which is often managed by coadministration of a second antibiotic. The purpose of this study was to determine the effectiveness of soluble rifampicin in combination with vancomycin tethered to titanium metal as a means to control bacterial growth and resistance in vitro. Bacterial growth was inhibited when the vancomycin-tethered titanium discs were treated with Staphylococcus aureus inocula of ≤2×10⁶ CFU, however inocula greater than 2×10⁶ CFU/disc adhered and survived. The combination of surface-tethered vancomycin with soluble rifampicin enhanced the inhibitory effect of rifampicin for an inoculum of 10⁶ CFU/cm² by one dilution (combination MIC of 0.008 mg/L versus 0.015 mg/L for rifampicin alone. Moreover, surface tethered vancomycin prevented the emergence of a rifampicin resistant population in an inoculum of 2×10⁸ CFU.

Controlled release of vancomycin from thin sol-gel films on implant surfaces successfully controls osteomyelitis.

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Adams, Christopher S; Antoci, Valentin; Harrison, Gerald; Patal, Payal; Freeman, Terry A; Shapiro, Irving M; Parvizi, Javad; Hickok, Noreen J; Radin, Shula; Ducheyne, Paul

2009-06-01

Peri-prosthetic infection remains a serious complication of joint replacement surgery. Herein, we demonstrate that a vancomycin-containing sol-gel film on Ti alloy rods can successfully treat bacterial infections in an animal model. The vancomycin-containing sol-gel films exhibited predictable release kinetics, while significantly inhibiting S. aureus adhesion. When evaluated in a rat osteomyelitis model, microbiological analysis indicated that the vancomycin-containing sol-gel film caused a profound decrease in S. aureus number. Radiologically, while the control side showed extensive bone degradation, including abscesses and an extensive periosteal reaction, rods coated with the vancomycin-containing sol-gel film resulted in minimal signs of infection. MicroCT analysis confirmed the radiological results, while demonstrating that the vancomycin-containing sol-gel film significantly protected dense bone from resorption and minimized remodeling. These results clearly demonstrate that this novel thin sol-gel technology can be used for the targeted delivery of antibiotics for the treatment of periprosthetic as well as other bone infections. Copyright 2008 Orthopaedic Research Society

Prophylactic Vancomycin Drops Reduce the Severity of Early Bacterial Keratitis in Keratoprosthesis

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Konstantopoulos, Aris; Tan, Xiao Wei; Goh, Gwendoline Tze Wei; Saraswathi, Padmanabhan; Chen, Liyan; Nyein, Chan Lwin; Zhou, Lei; Beuerman, Roger; Tan, Donald Tiang Hwee; Mehta, Jod

2015-01-01

Background Artificial cornea transplantation, keratoprosthesis, improves vision for patients at high risk of failure with human cadaveric cornea. However, post-operative infection can cause visual loss and implant extrusion in 3.2–17% of eyes. Long-term vancomycin drops are recommended following keratoprosthesis to prevent bacterial keratitis. Evidence, though, in support of this practice is poor. We investigated whether prophylactic vancomycin drops prevented bacterial keratitis in an animal keratoprosthesis model. Methodology Twenty-three rabbits were assigned either to a prophylactic group (n = 13) that received vancomycin 1.4% drops 5 times/day from keratoprosthesis implantation to sacrifice, or a non-prophylactic group (n = 10) that received no drops. All rabbits had Staphylococcus aureus inoculation into the cornea at 7–12 days post-implantation and were sacrificed at predetermined time-points. Prophylactic and non-prophylactic groups were compared with slit-lamp photography (SLP), anterior segment optical coherence tomography (AS-OCT), and histology, immunohistochemistry and bacterial quantification of excised corneas. Corneal vancomycin pharmacokinetics were studied in 8 additional rabbits. Results On day 1 post-inoculation, the median SLP score and mean±SEM AS-OCT corneal thickness (CT) were greater in the non-prophylactic than the prophylactic group (11 vs. 1, p = 0.049 and 486.9±61.2 vs. 327.4±37.1 μm, p = 0.029 respectively). On days 2 and 4, SLP scores and CT were not significantly different. Immunohistochemistry showed a greater CD11b+ve/non-CD11b+ve cell ratio in the non-prophylactic group (1.45 vs. 0.71) on day 2. Bacterial counts were not significantly different between the two groups. Corneal vancomycin concentration (2.835±0.383 μg/ml) exceeded minimum inhibitory concentration (MIC) for Staphylococcus aureus only after 16 days of vancomycin drops. Two of 3 rabbits still developed infection despite bacterial inoculation after 16 days of

Prophylactic Vancomycin Drops Reduce the Severity of Early Bacterial Keratitis in Keratoprosthesis.

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Aris Konstantopoulos

Full Text Available Artificial cornea transplantation, keratoprosthesis, improves vision for patients at high risk of failure with human cadaveric cornea. However, post-operative infection can cause visual loss and implant extrusion in 3.2-17% of eyes. Long-term vancomycin drops are recommended following keratoprosthesis to prevent bacterial keratitis. Evidence, though, in support of this practice is poor. We investigated whether prophylactic vancomycin drops prevented bacterial keratitis in an animal keratoprosthesis model.Twenty-three rabbits were assigned either to a prophylactic group (n = 13 that received vancomycin 1.4% drops 5 times/day from keratoprosthesis implantation to sacrifice, or a non-prophylactic group (n = 10 that received no drops. All rabbits had Staphylococcus aureus inoculation into the cornea at 7-12 days post-implantation and were sacrificed at predetermined time-points. Prophylactic and non-prophylactic groups were compared with slit-lamp photography (SLP, anterior segment optical coherence tomography (AS-OCT, and histology, immunohistochemistry and bacterial quantification of excised corneas. Corneal vancomycin pharmacokinetics were studied in 8 additional rabbits.On day 1 post-inoculation, the median SLP score and mean±SEM AS-OCT corneal thickness (CT were greater in the non-prophylactic than the prophylactic group (11 vs. 1, p = 0.049 and 486.9±61.2 vs. 327.4±37.1 μm, p = 0.029 respectively. On days 2 and 4, SLP scores and CT were not significantly different. Immunohistochemistry showed a greater CD11b+ve/non-CD11b+ve cell ratio in the non-prophylactic group (1.45 vs. 0.71 on day 2. Bacterial counts were not significantly different between the two groups. Corneal vancomycin concentration (2.835±0.383 μg/ml exceeded minimum inhibitory concentration (MIC for Staphylococcus aureus only after 16 days of vancomycin drops. Two of 3 rabbits still developed infection despite bacterial inoculation after 16 days of prophylactic drops

Pseudomonas aeruginosa Alters Staphylococcus aureus Sensitivity to Vancomycin in a Biofilm Model of Cystic Fibrosis Infection

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Giulia Orazi

2017-07-01

Full Text Available The airways of cystic fibrosis (CF patients have thick mucus, which fosters chronic, polymicrobial infections. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most prevalent respiratory pathogens in CF patients. In this study, we tested whether P. aeruginosa influences the susceptibility of S. aureus to frontline antibiotics used to treat CF lung infections. Using our in vitro coculture model, we observed that addition of P. aeruginosa supernatants to S. aureus biofilms grown either on epithelial cells or on plastic significantly decreased the susceptibility of S. aureus to vancomycin. Mutant analyses showed that 2-n-heptyl-4-hydroxyquinoline N-oxide (HQNO, a component of the P. aeruginosa Pseudomonas quinolone signal (PQS system, protects S. aureus from the antimicrobial activity of vancomycin. Similarly, the siderophores pyoverdine and pyochelin also contribute to the ability of P. aeruginosa to protect S. aureus from vancomycin, as did growth under anoxia. Under our experimental conditions, HQNO, P. aeruginosa supernatant, and growth under anoxia decreased S. aureus growth, likely explaining why this cell wall-targeting antibiotic is less effective. P. aeruginosa supernatant did not confer additional protection to slow-growing S. aureus small colony variants. Importantly, P. aeruginosa supernatant protects S. aureus from other inhibitors of cell wall synthesis as well as protein synthesis-targeting antibiotics in an HQNO- and siderophore-dependent manner. We propose a model whereby P. aeruginosa causes S. aureus to shift to fermentative growth when these organisms are grown in coculture, leading to reduction in S. aureus growth and decreased susceptibility to antibiotics targeting cell wall and protein synthesis.

Treatment of osteomyelitis defects by a vancomycin-loaded gelatin/β-tricalcium phosphate composite scaffold

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Zhou, J.; Zhou, X. G.; Wang, J. W.; Zhou, H.; Dong, J.

2018-01-01

Objective In the present study, we aimed to assess whether gelatin/β-tricalcium phosphate (β-TCP) composite porous scaffolds could be used as a local controlled release system for vancomycin. We also investigated the efficiency of the scaffolds in eliminating infections and repairing osteomyelitis defects in rabbits. Methods The gelatin scaffolds containing differing amounts of of β-TCP (0%, 10%, 30% and 50%) were prepared for controlled release of vancomycin and were labelled G-TCP0, G-TCP1, G-TCP3 and G-TCP5, respectively. The Kirby-Bauer method was used to examine the release profile. Chronic osteomyelitis models of rabbits were established. After thorough debridement, the osteomyelitis defects were implanted with the scaffolds. Radiographs and histological examinations were carried out to investigate the efficiency of eliminating infections and repairing bone defects. Results The prepared gelatin/β-TCP scaffolds exhibited a homogeneously interconnected 3D porous structure. The G-TCP0 scaffold exhibited the longest duration of vancomycin release with a release duration of eight weeks. With the increase of β-TCP contents, the release duration of the β-TCP-containing composite scaffolds was decreased. The complete release of vancomycin from the G-TCP5 scaffold was achieved within three weeks. In the treatment of osteomyelitis defects in rabbits, the G-TCP3 scaffold showed the most efficacious performance in eliminating infections and repairing bone defects. Conclusions The composite scaffolds could achieve local therapeutic drug levels over an extended duration. The G-TCP3 scaffold possessed the optimal porosity, interconnection and controlled release performance. Therefore, this scaffold could potentially be used in the treatment of chronic osteomyelitis defects. Cite this article: J. Zhou, X. G. Zhou, J. W. Wang, H. Zhou, J. Dong. Treatment of osteomyelitis defects by a vancomycin-loaded gelatin/β-tricalcium phosphate composite scaffold. Bone Joint Res

Effect of nosocomial vancomycin-resistant enterococcal bacteremia on mortality, length of stay, and costs.

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Song, Xiaoyan; Srinivasan, Arjun; Plaut, David; Perl, Trish M

2003-04-01

To determine the impact of vancomycin-resistant enterococcal bacteremia on patient outcomes and costs by assessing mortality, excess length of stay, and charges attributable to it. A population-based, matched, historical cohort study. A 1,025-bed, university-based teaching facility and referral hospital. Two hundred seventy-seven vancomycin-resistant enterococcal bacteremia case-patients and 277 matched control-patients identified between 1993 and 2000. The crude mortality rate was 50.2% and 19.9% for case-patients and control-patients, respectively, yielding a mortality rate of 30.3% attributable to vancomycin-resistant enterococcal bacteremia. The excess length of hospital stay attributable to vancomycin-resistant enterococcal bacteremia was 17 days, of which 12 days were spent in intensive care units. On average, dollars 77,558 in extra charges was attributable to each vancomycin-resistant enterococcal bacteremia. To adjust for severity of illness, 159 pairs of case-patients and control-patients, who had the same severity of illness (All Patient Refined-Diagnosis Related Group complexity level), were further analyzed. When patients were stratified by severity of illness, the crude mortality rate was 50.3% among case-patients compared with 27.7% among control-patients, accounting for an attributable mortality rate of 22.6%. Attributable excess length of stay and charges were 17 days and dollars 81,208, respectively. Vancomycin-resistant enterococcal bacteremia contributes significantly to excess mortality and economic loss, once severity of illness is considered. Efforts to prevent these infections will likely be cost-effective.

Intravenous Vancomycin Associated With the Development of Nephrotoxicity in Patients With Class III Obesity.

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Choi, Yookyung Christy; Saw, Stephen; Soliman, Daniel; Bingham, Angela L; Pontiggia, Laura; Hunter, Krystal; Chuang, Linda; Siemianowski, Laura A; Ereshefsky, Benjamin; Hollands, James M

2017-11-01

A consensus statement recommends initial intravenous (IV) vancomycin dosing of 15-20 mg/kg every 8- 24 hours, with an optional 25- to 30-mg/kg loading dose. Although some studies have shown an association between weight and the development of vancomycin-associated nephrotoxicity, results have been inconsistent. To evaluate the correlation between incidence of nephrotoxicity associated with weight-based IV vancomycin dosing strategies in nonobese and obese patients. This retrospective cohort study evaluated hospitalized adult patients admitted who received IV vancomycin. Patients were stratified into nonobese (body mass index [BMI] obesity class I and II (BMI 30-39.9kg/m 2 ), and obesity class III (BMI≥40 kg/m 2 ) groups; patients who were overweight but not obese were excluded. Incidence of nephrotoxicity and serum vancomycin trough concentrations were evaluated. Of a total of 62 documented cases of nephrotoxicity (15.1%), 13 (8.7%), 23 (14.3%), and 26 (26.3%) cases were observed in nonobese, obesity class I and II, and obesity class III groups, respectively ( P=0.002). Longer durations of therapy ( P20 mg/L ( Pobesity were 3-times as likely to develop nephrotoxicity when compared with nonobese patients (odds ratio [OR]=2.99; CI=1.12-7.94) and obesity class I and II patients (OR=3.14; CI=1.27-7.75). Obesity and other factors are associated with a higher risk of vancomycin-associated nephrotoxicity.

Vancomycin-resistant Staphylococcus aureus (VRSA) in hepatic cirrhosis patient: a case report

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Ramazoni, M.; Siregar, M. L.; Jamil, K. F.

2018-03-01

The irrational use of vancomycin in methicillin-resistant Staphylococcus aureus (MRSA) infections result in the emergence of vancomycin-resistant Staphylococcus aureus (VRSA) pathogen, which can pose a threat to the world healthcare. A 32-year-old male with hepatic cirrhosis patient admitted with recurrent gastrointestinal bleeding with a wound in his left leg since 6 months ago; the result microbiological culture showed a VRSA with minimum inhibitory concentration (MIC) vancomycin ≥32μg/mL The patient was treated with trimethoprim/sulfamethoxazole combination according to cultural sensitivity. The second microbiological culture showed thesame result. VRSA is a rare and difficult condition to handle. The success of therapy for this VRSA case warn us how important to cut the S. aureus distribution chain with a high level of resistance.

Vancomycin intoxication in a patient with inappropriate antidiuretic hormone syndrome and diarrhea

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Patricia Hidalgo-Collazos

2015-07-01

Full Text Available Vancomycin is an antibiotic used for infections by gram-positive bacteria with a two-compartment pharmacokinetic model. Its monitoring has an established therapeutic range (10-20 mg/L to prevent nephrotoxicity and ototoxicity due to supratherapeutic levels, and inefficiency and development of resistance by subtherapeutic levels. Nephrotoxicity for vancomycin monotherapy at standard doses according to pathogen and typical regimens (usual dose: 15-20 mg/kg/12 h is rare and usually reversible. Moreover, monitoring plasma concentrations allows to achieve concentrations within therapeutic range to allow safe and effective drug use. The renal hypoperfusion can cause pre-renal damage, resulting in elevated levels of serum creatinine, resulting in decreased antibiotic elimination and nephrotoxicity. We report a case of unexpected vancomycin nephrotoxicity in a patient with syndrome Inappropriate antidiuretic hormone secretion associated paraneoplastic

Gene Expression Analysis Reveals New Possible Mechanisms of Vancomycin-Induced Nephrotoxicity and Identifies Gene Markers Candidates

OpenAIRE

Dieterich, Christine; Puey, Angela; Lyn, Sylvia; Swezey, Robert; Furimsky, Anna; Fairchild, David; Mirsalis, Jon C.; Ng, Hanna H.

2008-01-01

Vancomycin, one of few effective treatments against methicillin-resistant Staphylococcus aureus, is nephrotoxic. The goals of this study were to (1) gain insights into molecular mechanisms of nephrotoxicity at the genomic level, (2) evaluate gene markers of vancomycin-induced kidney injury, and (3) compare gene expression responses after iv and ip administration. Groups of six female BALB/c mice were treated with seven daily iv or ip doses of vancomycin (50, 200, and 400 mg/kg) or saline, and...

Peak Measurement for Vancomycin AUC Estimation in Obese Adults Improves Precision and Lowers Bias.

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Pai, Manjunath P; Hong, Joseph; Krop, Lynne

2017-04-01

Vancomycin area under the curve (AUC) estimates may be skewed in obese adults due to weight-dependent pharmacokinetic parameters. We demonstrate that peak and trough measurements reduce bias and improve the precision of vancomycin AUC estimates in obese adults ( n = 75) and validate this in an independent cohort ( n = 31). The precision and mean percent bias of Bayesian vancomycin AUC estimates are comparable between covariate-dependent ( R 2 = 0.774, 3.55%) and covariate-independent ( R 2 = 0.804, 3.28%) models when peaks and troughs are measured but not when measurements are restricted to troughs only ( R 2 = 0.557, 15.5%). Copyright © 2017 American Society for Microbiology.

Our experiences with vancomycin-resistant enterococci in Jesenice General hospital

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Helena Ribič

2007-11-01

Full Text Available Background: Vancomycin-resistant enterococci (VRE present a great problem in health care, especially because of their resistance to many groups of antibiotics and because of the way of their spreading in health care and long-term care institutions. Genes responsible for resistance to vancomycin can be transmitted to other species of enterococci and also to other grampositive cocci, for example Staphylococcus aureus. Experts anticipate that failure to control methicilin-resistant S. aureus and VRE may make control of vancomycin-resistant S. aureus impossible.Methods: In the medical microbiology laboratory of Institute Public Health Kranj we perform microbiology diagnosis for Jesenice General Hospital, where surveillance culturing for VRE started in May 2007. Until 15th June, 364 surveillance samples for VRE were taken from 92 patients. We also analysed the results of enterococci that were isolated in our laboratory during routine work in the period from 2004 to 2006.Results: In the three-year period we isolated 1593 strains of enterococci and among them 7 strains were VRE. In the Jesenice General Hospital, the first strain of vancomycin-resistant Enterococcus faecium was isolated in May 2007 in a patient, treated in internal intensive care unit. Nine strains of VRE with the same resistance type in nine patients followed the first case. The first four patients with VRE were moved from the same hospital. Among next six patients the common risk factor was contact with VRE positive patient.Conclusions: Control of VRE strains claims for intensive action. Active surveillance of colonised and infected patients, contact precautions with barrier isolation, intensive hand hygiene measures, aggressive environmental decontamination and prudent use of antimicrobials are needed.

In Vitro Assessment of Electric Currents Increasing the Effectiveness of Vancomycin Against Staphylococcus epidermidis Biofilms.

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Haddad, Peter A; Mah, Thien-Fah; Mussivand, Tofy

2016-08-01

Biofilms are communities of bacteria that can cause infections which are resistant to the immune system and antimicrobial treatments, posing a significant threat for patients with implantable and indwelling medical devices. The purpose of our research was to determine if utilizing specific parameters for electric currents in conjunction with antibiotics could effectively treat a highly resistant biofilm. Our study evaluated the impact of 16 μg/mL of vancomycin with or without 22 or 333 μA of direct electric current (DC) generated by stainless steel electrodes against 24-, 48-, and 72-h-old Staphylococcus epidermidis biofilms formed on titanium coupons. An increase in effectiveness of vancomycin was observed with the combination of 333 μA of electric current against 48-h-old biofilms (P value = 0.01) as well as in combination with 22 μA of electric current against 72-h-old biofilms (P value = 0.04); 333 μA of electric current showed the most significant impact on the effectiveness of vancomycin against S. epidermidis biofilms demonstrating a bioelectric effect previously not observed against this strain of bacteria. © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

The Role of Vancomycin on Meningitis

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Ahmed I. Shatat and P.I.C.U team

2014-06-01

Conclusion: After the previous discussion of the results obtained from this study, the researchers concluded that most of the cases diagnosed meningitis was aseptic and there was no need for antibiotics. Also in those who diagnosed as bacterial vancomycin was not essential in all cases, this confirmed by the absence of any differences in the outcome. [Cukurova Med J 2014; 39(3.000: 501-511

Cross-transmission of vancomycin-resistant Enterococcus in patients undergoing dialysis and kidney transplant

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D. Fram

2010-01-01

Full Text Available The objective of this study was to investigate the occurrence of vancomycin-resistant Enterococcus (VRE cross-transmission between two patient groups (long-term dialysis and kidney transplant patients. Molecular typing, by automated ribotyping with the RiboPrinter Microbial Characterization System (Qualicon, USA, was used to analyze VRE isolates from 31 fecal samples of 320 dialysis patients and 38 fecal samples of 280 kidney transplant patients. Clonal spread of E. faecalis and E. casseliflavus was observed intragroup, but not between the two groups of patients. In turn, transmission of E. gallinarum and E. faecium between the groups was suggested by the finding of vancomycin-resistant isolates belonging to the same ribogroup in both dialysis and transplant patients. The fact that these patients were colonized by VRE from the same ribogroup in the same health care facility provides evidence for cross-transmission and supports the adoption of stringent infection control measures to prevent dissemination of these bacteria.

Vancomycin gene selection in the microbiome of urban Rattus norvegicus from hospital environment

DEFF Research Database (Denmark)

Arn Hansen, Thomas; Joshi, Tejal; Larsen, Anders Rhod

2016-01-01

for the presence of antibiotic resistance genes. We show that despite the shared resistome within samples from the same geographic locations, samples from hospital area carry significantly abundant vancomycin resistance genes. The observed pattern is consistent with a selection for vancomycin genes in the R...

Dissemination of antibiotic resistance in methicillin-resistant Staphylococcus aureus and vancomycin-resistant S aureus strains isolated from hospital effluents.

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Mandal, Santi M; Ghosh, Ananta K; Pati, Bikas R

2015-12-01

Vancomycin-resistant Staphylococcus aureus (VRSA) and methicillin-resistant S aureus (MRSA) strains were examined in hospital effluents. Most S aureus strains are resistant to methicillin (MRSA), followed by tetracycline. Approximately 15% of MRSA strains are also resistant to vancomycin (VRSA). All VRSA strains developed a VanR/VanS-regulated 2-component system of VanA-type resistance in their genome. Results indicate that there is a possibility of developing resistance to aminoglycosides by VRSA strains in the near future. Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Utilization Pattern of Vancomycin in a University Teaching Hospital ...

African Journals Online (AJOL)

HP

vis a vis to the Hospital Infection Control Practices Advisory Committee (HICPAC) guidelines and the ... effective against most Gram-positive bacteria ... Proper use of TDM procedures along ..... between antecedent vancomycin treatment and.

Population Pharmacokinetic Model for Vancomycin Used in Open Heart Surgery: Model-Based Evaluation of Standard Dosing Regimens.

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Alqahtani, Saeed A; Alsultan, Abdullah S; Alqattan, Hussain M; Eldemerdash, Ahmed; Albacker, Turki B

2018-04-23

The purpose of this study was to investigate the population pharmacokinetics of vancomycin in patients undergoing open heart surgery. In this observational pharmacokinetic study, multiple blood samples were drawn over a 48-h period of intravenous vancomycin in patients who were undergoing open heart surgery. Blood samples were analysed using the Architect i4000SR Immunoassay Analyzer. Population pharmacokinetic models were developed using Monolix 4.4 software. Pharmacokinetic-pharmacodynamic (PK-PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. One-hundred and sixty-eight blood samples were analysed from 28 patients. The pharmacokinetics of vancomycin was best described by a two-compartment model with between-subject variability in CL, V of the central compartment, and V of the peripheral compartment. CL and central compartment V of vancomycin were related to CL CR , body weight, and albumin concentration. Dosing simulations showed that standard dosing regimens of 1 and 1.5 g failed to achieve the PK-PD target of AUC 0--24 /MIC > 400 for an MIC of 1 mg/L, while high weight-based dosing regimens were able to achieve the PK-PD target. In summary, administration of standard doses of 1 and 1.5 g of vancomycin two times daily provided inadequate antibiotic prophylaxis in patients undergoing open heart surgery. The same findings were obtained when 15 mg/kg and 20 mg/kg doses of vancomycin were administered. Achieving the PK-PD target required higher doses (25 mg/kg and 30 mg/kg) of vancomycin. Copyright © 2018 American Society for Microbiology.

Synchrotron radiation infrared microspectroscopy to assess the activity of vancomycin against endocarditis vegetation bacteria.

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Batard, Eric; Jamme, Frédéric; Montassier, Emmanuel; Bertrand, Dominique; Caillon, Jocelyne; Potel, Gilles; Dumas, Paul

2011-06-01

Infrared microspectroscopy was used to show that vancomycin alters infrared spectra of endocarditis vegetation bacteria, and that vancomycin effects on bacterial biochemical contents are unevenly distributed between peripheral and central areas of bacterial masses. Infrared microspectroscopy is useful to study the activity of antibacterial agents against bacteria in tissues. Copyright © 2011 Elsevier B.V. All rights reserved.

The need to assay the real MIC when making the decision to eradicate Staphylococcus aureus with vancomycin

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Hanna Tomczak

2013-09-01

Full Text Available Purpose: The aim of the study was a comparison of the MIC (minimal inhibitory concentration evaluated in the automatic system Vitek 2 and the real MIC of vancomycin by the Etest method for S. aureus strains isolated from clinical materials.Material and Methods: Over a twelve-month study period we compared the results obtained with two commercial methods – the automatic system VITEK 2 and the real MIC by Etest – for 359 strains of S. aureus isolated from clinical materials.Results: Most of the strains of S. aureus were cultured from wounds (84, the ear (60 and nose (42. MSSA (methicillin-sensitive Staphylococcus aureus was isolated in 342 cases and MRSA (methicillin-resistant Staphylococcus aureus in 17 cases. The test with the Vitek automatic method showed that vancomycin had MIC values of ≤1.0 μg/ml in more than 96�0and 2.0 μg/ml in over 3�0of cases. Using the Etest technique MIC ≤ 1.0 μg/ml was obtained in only 16.4�0of cases and values of >1.0 μg/ml in 83.6�0of cases.Discussion: In view of such big differences between the MIC values obtained with the two methods the authors suggest that the Etest method of assaying the real MIC is more useful than the automatic method.

Annual Surveillance Summary: Vancomycin-Resistant Enterococci (VRE) Infections in the Military Health System (MHS), 2016

Science.gov (United States)

2017-06-01

policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government . i i VRE in the MHS: Annual Summary 2016 Prepared...continually increased from 1.16 infections per 100,000 persons in 2013 to 1.60 infections per 100,000 persons in 2015. A recent meta -analysis of VRE...associated with infections caused by vancomycin-resistant enterococci in the United States: systematic literature review and meta -analysis. Infect

Preparation and biodistribution of [201Tl](III)vancomycin complex in normal rats

International Nuclear Information System (INIS)

Jalilian, A.R.; Hosseini, M.A.; Karimian, A.; Saddadi, F.; Sadeghi, M.

2006-01-01

Thallium-201 (T 1/2 = 3.04 days) in Tl + form was converted to Tl 3+ cation in presence of O 3 in 6 M HCl controlled by RTLC/gel electrophoresis methods. The final evaporated activity was reacted with vancomycin (VAN) in water to yield [ 201 Tl](III)VAN. The best results were obtained at room temperature in water after 30 min with a radiochemical yield >99%, after mixing the reactants followed by SPE purification using Si Sep-Pak. The studies showed that thallic ion is mostly incorporated into vancomycin with a radiochemical purity of more than 98 ± 1% by RTLC. A specific activity of about 4.14·10 10 Bq/mmol was obtained. Radiochemical purity and stability of 201 Tl-VAN in the preparation and in presence of human serum was determined up to 5.5 days. Biodistribution study of 201 Tl(III)-vancomycin in normal rats was performed up to 52 h. (authors)

Review on Usage of Vancomycin in Livestock and Humans: Maintaining Its Efficacy, Prevention of Resistance and Alternative Therapy

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Panditharathnalage Nishantha Kumara Wijesekara

2017-01-01

Full Text Available Vancomycin is one of the “last-line” classes of antibiotics used in the treatment of life-threatening infections caused by Gram-positive bacteria. Even though vancomycin was discovered in the 1950s, it was widely used after the 1980s for the treatment of infections caused by methicillin-resistant Staphylococci, as the prevalence of these strains were increased. However, it is currently evident that vancomycin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci have developed for various reasons, including the use of avaparcin—an analog of vancomycin—as a feed additive in livestock. Therefore, prophylactic and empiric use of antibiotics and their analogues need to be minimized. Herein we discuss the rational use of vancomycin in treating humans, horses, farm animals, and pet animals such as dogs, cats, and rabbits. In present day context, more attention should be paid to the prevention of the emergence of resistance to antibiotics in order to maintain their efficacy. In order to prevent emergence of resistance, proper guidance for the responsible use of antimicrobials is indispensable. Therefore, almost all stakeholders who use antibiotics should have an in-depth understanding of the antibiotic that they use. As such, it is imperative to be aware of the important aspects of vancomycin. In the present review, efforts have been made to discuss the pharmacokinetics and pharmacodynamics, indications, emergence of resistance, control of resistance, adverse effects, and alternative therapy for vancomycin.

From penicillin-streptomycin to amikacin-vancomycin: antibiotic decontamination of cardiovascular homografts in Singapore.

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Wee Ling Heng

Full Text Available BACKGROUND: In February 2012, the National Cardiovascular Homograft Bank (NCHB became the first tissue bank outside of North America to receive accreditation from the American Association of Tissue Banks. From 2008 to 2009, NCHB had been decontaminating its cardiovascular homografts with penicillin and streptomycin. The antibiotic decontamination protocol was changed in January 2010 as amikacin and vancomycin were recommended, in order to cover bacteria isolated from post-recovery and post- antibiotic incubation tissue cultures. AIM: The objective of this study is to determine the optimal incubation conditions for decontamination of homografts by evaluating the potencies of amikacin and vancomycin in different incubation conditions. Retrospective reviews of microbiological results were also performed for homografts recovered from 2008 to 2012, to compare the effectiveness of penicillin-streptomycin versus the amikacin-vancomycin regimens. METHODS: Based on microbiological assays stated in United States Pharmacopeia 31, potency of amikacin was evaluated by turbidimetric assay using Staphylococcus aureus, while vancomycin was by diffusion assay using Bacillus subtilis sporulate. Experiments were performed to investigate the potencies of individual antibiotic 6-hours post incubation at 4°C and 37°C and 4°C for 24 hours, after the results suggested that amikacin was more potent at lower temperature. FINDINGS: Tissue incubation at 4°C for 24 hours is optimal for both antibiotics, especially for amikacin, as its potency falls drastically at 37°C. CONCLUSION: The decontamination regimen of amikacin-vancomycin at 4°C for 24 hours is effective. Nevertheless, it is imperative to monitor microbiological trends closely and evaluate the efficacy of current antibiotics regimen against emerging strains of micro-organisms.

Clinical Outcome with Oral Linezolid and Rifampin Following Recurrent Methicillin-Resistant Staphylococcus aureus Bacteremia Despite Prolonged Vancomycin Treatment

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Jon-David Schwalm

2004-01-01

Full Text Available Drug-resistant Gram-positive bacteria, especially Staphylococcus aureus, are emerging as the predominant organisms involved in both nosocomial and community-acquired infections. Since the 1980s, vancomycin has been the first-line antibiotic used to treat methicillin-resistant S aureus. However, allergy and intolerance to vancomycin, the increasing number of vancomycin clinical failures and the existence of vancomycin intermediate-susceptible isolates of S aureus suggest that new antibiotics are needed. This paper reports the only known case of a successful clinical outcome with long term oral linezolid and rifampin therapy in the management of recurrent and persistent methicillin-resistant S aureus bacteremia with metastatic infections despite prolonged vancomycin use. More than two years since the initiation of linezolid and rifampin, the study patient has been clinically well with no evidence of adverse drug reactions including cytopenia and hepatic toxicities. Physicians must be aware of the novel developments in antibiotic therapy to treat drug-resistant bacterial infections.

vanI: a novel d-Ala-d-Lac vancomycin resistance gene cluster found in Desulfitobacterium hafniense

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Kruse, T.; Levisson, M.; Vos, de W.M.; Smidt, H.

2014-01-01

The glycopeptide vancomycin was until recently considered a drug of last resort against Gram-positive bacteria. Increasing numbers of bacteria, however, are found to carry genes that confer resistance to this antibiotic. So far, 10 different vancomycin resistance clusters have been described. A

Vancomycin resistant enterococci in urine cultures: Antibiotic susceptibility trends over a decade at a tertiary hospital in the United Kingdom.

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Toner, Liam; Papa, Nathan; Aliyu, Sani H; Dev, Harveer; Lawrentschuk, Nathan; Al-Hayek, Samih

2016-03-01

Enterococci are a common cause of urinary tract infection and vancomycin-resistant strains are more difficult to treat. The purpose of this surveillance program was to assess the prevalence of and determine the risk factors for vancomycin resistance in adults among urinary isolates of Enterococcus sp. and to detail the antibiotic susceptibility profile, which can be used to guide empirical treatment. From 2005 to 2014 we retrospectively reviewed 5,528 positive Enterococcus sp. urine cultures recorded in a computerized laboratory results database at a tertiary teaching hospital in Cambridge, United Kingdom. Of these cultures, 542 (9.8%) were vancomycin resistant. No longitudinal trend was observed in the proportion of vancomycin-resistant strains over the course of the study. We observed emerging resistance to nitrofurantoin with rates climbing from near zero to 40%. Ampicillin resistance fluctuated between 50% and 90%. Low resistance was observed for linezolid and quinupristin/dalfopristin. Female sex and inpatient status were identified as risk factors for vancomycin resistance. The incidence of vancomycin resistance among urinary isolates was stable over the last decade. Although resistance to nitrofurantoin has increased, it still serves as an appropriate first choice in uncomplicated urinary tract infection caused by vancomycin-resistant Enterococcus sp.

Vancomycin resistant enterococci in urine cultures: Antibiotic susceptibility trends over a decade at a tertiary hospital in the United Kingdom

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Liam Toner

2016-03-01

Full Text Available Purpose: Enterococci are a common cause of urinary tract infection and vancomycin-resistant strains are more difficult to treat. The purpose of this surveillance program was to assess the prevalence of and determine the risk factors for vancomycin resistance in adults among urinary isolates of Enterococcus sp. and to detail the antibiotic susceptibility profile, which can be used to guide empirical treatment. Materials and Methods: From 2005 to 2014 we retrospectively reviewed 5,528 positive Enterococcus sp. urine cultures recorded in a computerized laboratory results database at a tertiary teaching hospital in Cambridge, United Kingdom. Results: Of these cultures, 542 (9.8% were vancomycin resistant. No longitudinal trend was observed in the proportion of vancomycin- resistant strains over the course of the study. We observed emerging resistance to nitrofurantoin with rates climbing from near zero to 40%. Ampicillin resistance fluctuated between 50% and 90%. Low resistance was observed for linezolid and quinupristin/ dalfopristin. Female sex and inpatient status were identified as risk factors for vancomycin resistance. Conclusions: The incidence of vancomycin resistance among urinary isolates was stable over the last decade. Although resistance to nitrofurantoin has increased, it still serves as an appropriate first choice in uncomplicated urinary tract infection caused by vancomycin- resistant Enterococcus sp.

Postcataract endophthalmitis prophylaxis using irrigation, incision hydration, and eye pressurization with vancomycin

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Schelonka LP

2015-07-01

Full Text Available Lee P Schelonka,1 Margaret A SaBell2 1Department of Opthalmology, Kaiser Permanente Lone Tree Medical Offices, Lone Tree, 2Department of Infection Control, Kaiser Permanente Lone Tree Medical Offices, Lone Tree, Denver, CO, USA Purpose: This study aimed to determine whether switching from balanced salt solution (BSS to vancomycin 20 g/mL BSS for incision hydration and eye pressurization reduces the rate of postcataract endophthalmitis.Methods: This was a patient safety/quality improvement project, including all patients undergoing cataract surgery at the Kaiser Permanente Colorado Ophthalmology Department from January 2002 to December 2014. Throughout the study, patients received vancomycin 20 µg/mL in the irrigating solution. During the baseline period from 2002 to 2005, surgeons pressurized eyes and hydrated incisions with plain BSS. During the intervention period from 2006 through 2014, surgeons switched from BSS to the vancomycin/BSS irrigating solution for eye pressurization and incision hydration.Results: A total of 57,263 cataract operations were performed by 24 surgeons at seven surgical centers: 12,400 in the baseline period and 44,863 in the intervention period. The rate of postcataract endophthalmitis declined significantly from 5/12,400 (rate: 0.4/1,000 in the baseline period to 1/44,863 (rate: 0.022/1,000 during the intervention period (odds ratio [OR]: 18.1, 95% confidence interval [CI]: 2.11–154.9; χ2=13.5, P=0.00024. Accounting for an estimated 2.05-fold risk reduction due to confounding variables, the risk reduction attributed to the intervention remained significant: (adjusted OR: 8.78, 95% CI: 1.73–44.5; χ2=10.06, P=0.0015. Since 2009, we have not experienced any cases of postcataract endophthalmitis after 32,753 operations.Conclusion: We experienced a significant reduction in postcataract endophthalmitis when we switched from BSS to the vancomycin/BSS irrigating solution for incision hydration and eye pressurization

Evaluation of vancomycin MIC creep in methicillin-resistant Staphylococcus aureus infections-a systematic review and meta-analysis.

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Diaz, R; Afreixo, V; Ramalheira, E; Rodrigues, C; Gago, B

2018-02-01

Vancomycin is currently the primary option treatment for methicillin-resistant Staphylococcus aureus (MRSA). However, an increasing number of MRSA isolates with high MICs, within the susceptible range (vancomycin MIC creep), are being reported worldwide. Resorting to a meta-analysis approach, this study aims to assess the evidence of vancomycin MIC creep. We searched for studies in the PubMed database. The inclusion criteria for study eligibility included the possibility of retrieving the reported data values of vancomycin MIC and information concerning the applied MIC methodology. The mean values of vancomycin MICs, of all 29 234 S. aureus isolates reported in the 55 studies included in the meta-analysis, were 1.23 mg/L (95% CI 1.13-1.33) and 1.20 mg/L (95% CI 1.13-1.28) determined by Etest and broth microdilution method, respectively. No significant differences were observed between these two methodologies. We found negative correlation between pooled mean/pooled proportion and time strata. We have found no evidence of the MIC creep phenomenon. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Identification of VanN-type vancomycin resistance in an Enterococcus faecium isolate from chicken meat in Japan.

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Nomura, Takahiro; Tanimoto, Koichi; Shibayama, Keigo; Arakawa, Yoshichika; Fujimoto, Shuhei; Ike, Yasuyoshi; Tomita, Haruyoshi

2012-12-01

Five VanN-type vancomycin-resistant Enterococcus faecium strains were isolated from a sample of domestic chicken meat in Japan. All isolates showed low-level resistance to vancomycin (MIC, 12 mg/liter) and had the same pulsed-field gel electrophoresis profile. The vancomycin resistance was encoded on a large plasmid (160 kbp) and was expressed constitutively. The VanN-type resistance operon was identical to the first resistance operon to be reported, with the exception of a 1-bp deletion in vanT(N) and a 1-bp substitution in vanS(N).

Superior sensitivity and decreased time to detection with the Bactec Peds Plus/F system compared to the BacT/Alert Pediatric FAN blood culture system.

Science.gov (United States)

Sullivan, K V; Turner, N N; Lancaster, D P; Shah, A R; Chandler, L J; Friedman, D F; Blecker-Shelly, D L

2013-12-01

Here, we compare the sensitivities and times to detection (TTD) of BacT/Alert Pediatric FAN (PF) and Bactec Peds Plus blood culture bottles. Test bottles were inoculated with 2 ml of banked whole blood, 1-ml aliquots of antibiotic suspension, and organisms diluted to simulate a bacteremia level of 10 to 100 CFU/ml. The control bottles were inoculated with 3 ml of banked blood and organism suspensions only. The organism-drug combinations were Staphylococcus epidermidis and vancomycin, methicillin-resistant Staphylococcus aureus and vancomycin, Streptococcus pneumoniae, vancomycin, and ceftriaxone, Streptococcus agalactiae, ampicillin, and cefotaxime, Escherichia coli, cefotaxime, and cefepime, Pseudomonas aeruginosa, piperacillin-tazobactam, cefepime, and gentamicin, Neisseria meningitidis and ceftriaxone, and Haemophilus influenzae and ceftriaxone. The control and test bottle combinations were tested in duplicate. The bottles were incubated for 5 days; 32 control and 104 test bottles were incubated. Overall, the bacterial recovery rates for the PF and Peds Plus bottles were 37% and 62%, 94% and 100% in the controls, 19% and 50% in the test bottles, and 33% and 92% in the bottles with vancomycin, respectively. No bacteria were recovered from the bottles with S. pneumoniae, S. agalactiae, E. coli, N. meningitidis, or H. influenzae in combination with cefotaxime or ceftriaxone. The Peds Plus system detected P. aeruginosa in bottles with cefepime and piperacillin-tazobactam, but the PF system recovered bacteria only in bottles with trough levels of piperacillin-tazobactam. The mean TTD were shorter in the Peds Plus system controls (14.2 versus 18.0 h; P = 0.001) and the test bottles (14.3 versus 17.8 h; P = 0.008) than in the PF bottles. Overall, we demonstrated superior sensitivity, TTD, and antibiotic neutralization in the Bactec Peds Plus system compared to those in the Pediatric FAN system.

Identifying the Interaction of Vancomycin With Novel pH-Responsive Lipids as Antibacterial Biomaterials Via Accelerated Molecular Dynamics and Binding Free Energy Calculations.

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Ahmed, Shaimaa; Vepuri, Suresh B; Jadhav, Mahantesh; Kalhapure, Rahul S; Govender, Thirumala

2018-06-01

Nano-drug delivery systems have proven to be an efficient formulation tool to overcome the challenges with current antibiotics therapy and resistance. A series of pH-responsive lipid molecules were designed and synthesized for future liposomal formulation as a nano-drug delivery system for vancomycin at the infection site. The structures of these lipids differ from each other in respect of hydrocarbon tails: Lipid1, 2, 3 and 4 have stearic, oleic, linoleic, and linolenic acid hydrocarbon chains, respectively. The impact of variation in the hydrocarbon chain in the lipid structure on drug encapsulation and release profile, as well as mode of drug interaction, was investigated using molecular modeling analyses. A wide range of computational tools, including accelerated molecular dynamics, normal molecular dynamics, binding free energy calculations and principle component analysis, were applied to provide comprehensive insight into the interaction landscape between vancomycin and the designed lipid molecules. Interestingly, both MM-GBSA and MM-PBSA binding affinity calculations using normal molecular dynamics and accelerated molecular dynamics trajectories showed a very consistent trend, where the order of binding affinity towards vancomycin was lipid4 > lipid1 > lipid2 > lipid3. From both normal molecular dynamics and accelerated molecular dynamics, the interaction of lipid3 with vancomycin is demonstrated to be the weakest (∆G binding  = -2.17 and -11.57, for normal molecular dynamics and accelerated molecular dynamics, respectively) when compared to other complexes. We believe that the degree of unsaturation of the hydrocarbon chain in the lipid molecules may impact on the overall conformational behavior, interaction mode and encapsulation (wrapping) of the lipid molecules around the vancomycin molecule. This thorough computational analysis prior to the experimental investigation is a valuable approach to guide for predicting the encapsulation

Structural and Functional Adaptation of Vancomycin Resistance VanT Serine Racemases.

Science.gov (United States)

Meziane-Cherif, Djalal; Stogios, Peter J; Evdokimova, Elena; Egorova, Olga; Savchenko, Alexei; Courvalin, Patrice

2015-08-11

Vancomycin resistance in Gram-positive bacteria results from the replacement of the D-alanyl-D-alanine target of peptidoglycan precursors with D-alanyl-D-lactate or D-alanyl-D-serine (D-Ala-D-Ser), to which vancomycin has low binding affinity. VanT is one of the proteins required for the production of D-Ala-D-Ser-terminating precursors by converting L-Ser to D-Ser. VanT is composed of two domains, an N-terminal membrane-bound domain, likely involved in L-Ser uptake, and a C-terminal cytoplasmic catalytic domain which is related to bacterial alanine racemases. To gain insight into the molecular function of VanT, the crystal structure of the catalytic domain of VanTG from VanG-type resistant Enterococcus faecalis BM4518 was determined. The structure showed significant similarity to type III pyridoxal 5'-phosphate (PLP)-dependent alanine racemases, which are essential for peptidoglycan synthesis. Comparative structural analysis between VanTG and alanine racemases as well as site-directed mutagenesis identified three specific active site positions centered around Asn696 which are responsible for the L-amino acid specificity. This analysis also suggested that VanT racemases evolved from regular alanine racemases by acquiring additional selectivity toward serine while preserving that for alanine. The 4-fold-lower relative catalytic efficiency of VanTG against L-Ser versus L-Ala implied that this enzyme relies on its membrane-bound domain for L-Ser transport to increase the overall rate of d-Ser production. These findings illustrate how vancomycin pressure selected for molecular adaptation of a housekeeping enzyme to a bifunctional enzyme to allow for peptidoglycan remodeling, a strategy increasingly observed in antibiotic-resistant bacteria. Vancomycin is one of the drugs of last resort against Gram-positive antibiotic-resistant pathogens. However, bacteria have evolved a sophisticated mechanism which remodels the drug target, the D-alanine ending precursors in cell wall

Success of linezolid therapy for postneurosurgical ventriculitis due to vancomycin-resistant Enterococcus faecium: case report and literature review

Institute of Scientific and Technical Information of China (English)

JiaJi Qiu; Jie Tang; DeLing Li

2016-01-01

Background:Vancomycin-resistant Enterococcus faecium ventriculitis is one of the most severe events in postneurosurgical intracranial infections.There are no guidelines recommending an appropriate treatment before.Case presentation:This case presents a successful linezolid treatment for post-neurosurgical vancomycin-resistant Enterococcus faecium ventriculitis of a 24-year-old man in the department of neurosurgery,Beijing Tiantan Hospital.Conclusions:Linezolid should be considered as one of the important methods for the treatment of postneurosurgical intracranial infections caused by vancomycin-resistant Enterococcus.

The Relationship Between Vancomycin Trough Concentrations and AUC/MIC Ratios in Pediatric Patients: A Qualitative Systematic Review.

Science.gov (United States)

Tkachuk, Stacey; Collins, Kyle; Ensom, Mary H H

2018-04-01

In adults, the area under the concentration-time curve (AUC) divided by the minimum inhibitory concentration (MIC) is associated with better clinical and bacteriological response to vancomycin in patients with methicillin-resistant Staphylococcus aureus who achieve target AUC/MIC ≥ 400. This target is often extrapolated to pediatric patients despite the lack of similar evidence. The impracticalities of calculating the AUC in practice means vancomycin trough concentrations are used to predict the AUC/MIC. This review aimed to determine the relationship between vancomycin trough concentrations and AUC/MIC in pediatric patients. We searched the MEDLINE and Embase databases, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials using the medical subject heading (MeSH) terms vancomycin and AUC and pediatric* or paediatric*. Articles were included if they were published in English and reported a relationship between vancomycin trough concentrations and AUC/MIC. Of 122 articles retrieved, 11 met the inclusion criteria. One trial reported a relationship between vancomycin trough concentrations, AUC/MIC, and clinical outcomes but was likely underpowered. Five studies found troughs 6-10 mg/l were sufficient to attain an AUC/MIC > 400 in most general hospitalized pediatric patients. One study in patients undergoing cardiothoracic surgery found a trough of 18.4 mg/l achieved an AUC/MIC > 400. Two oncology studies reported troughs ≥ 15 mg/l likely attained an AUC/MIC ≥ 400. In critical care patients: one study found a trough of 9 mg/l did not attain the AUC/MIC target; another found 7 mg/l corresponded to an AUC/MIC of 400. Potential vancomycin targets varied based on the population studied but, for general hospitalized pediatric patients, troughs of 6-10 mg/l are likely sufficient to achieve AUC/MIC ≥ 400. For MIC ≥ 2 mg/l, higher troughs are likely necessary to achieve an AUC/MIC ≥ 400. More

Fidaxomicin versus vancomycin for Clostridium difficile infection: meta-analysis of pivotal randomized controlled trials.

Science.gov (United States)

Crook, Derrick W; Walker, A Sarah; Kean, Yin; Weiss, Karl; Cornely, Oliver A; Miller, Mark A; Esposito, Roberto; Louie, Thomas J; Stoesser, Nicole E; Young, Bernadette C; Angus, Brian J; Gorbach, Sherwood L; Peto, Timothy E A

2012-08-01

Two recently completed phase 3 trials (003 and 004) showed fidaxomicin to be noninferior to vancomycin for curing Clostridium difficile infection (CDI) and superior for reducing CDI recurrences. In both studies, adults with active CDI were randomized to receive blinded fidaxomicin 200 mg twice daily or vancomycin 125 mg 4 times a day for 10 days. Post hoc exploratory intent-to-treat (ITT) time-to-event analyses were undertaken on the combined study 003 and 004 data, using fixed-effects meta-analysis and Cox regression models. ITT analysis of the combined 003/004 data for 1164 patients showed that fidaxomicin reduced persistent diarrhea, recurrence, or death by 40% (95% confidence interval [CI], 26%-51%; P < .0001) compared with vancomycin through day 40. A 37% (95% CI, 2%-60%; P = .037) reduction in persistent diarrhea or death was evident through day 12 (heterogeneity P = .50 vs 13-40 days), driven by 7 (1.2%) fidaxomicin versus 17 (2.9%) vancomycin deaths at <12 days. Low albumin level, low eosinophil count, and CDI treatment preenrollment were risk factors for persistent diarrhea or death at 12 days, and CDI in the previous 3 months was a risk factor for recurrence (all P < .01). Fidaxomicin has the potential to substantially improve outcomes from CDI.

Evaluating the Effect of a Web-Based E-Learning Tool for Health Professional Education on Clinical Vancomycin Use: Comparative Study.

Science.gov (United States)

Bond, Stuart Evan; Crowther, Shelley P; Adhikari, Suman; Chubaty, Adriana J; Yu, Ping; Borchard, Jay P; Boutlis, Craig Steven; Yeo, Wilfred Winston; Miyakis, Spiros

2018-02-26

Internet-based learning for health professional education is increasing. It offers advantages over traditional learning approaches, as it enables learning to be completed at a time convenient to the user and improves access where facilities are geographically disparate. We developed and implemented the Vancomycin Interactive (VI) e-learning tool to improve knowledge on the clinical use of the antibiotic vancomycin, which is commonly used for treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA). The aims of this study were to evaluate the effect of the VI e-learning tool on (1) survey knowledge scores and (2) clinical use of vancomycin among health professionals. We conducted a comparative pre-post intervention study across the 14 hospitals of two health districts in New South Wales, Australia. A knowledge survey was completed by nurses, doctors, and pharmacists before and after release of a Web-based e-learning tool. Survey scores were compared with those obtained following traditional education in the form of an email intervention. Survey questions related to dosing, administration, and monitoring of vancomycin. Outcome measures were survey knowledge scores among the three health professional groups, vancomycin plasma trough levels, and vancomycin approvals recorded on a computerized clinical decision support system. Survey response rates were low at 26.87% (577/2147) preintervention and 8.24% (177/2147) postintervention. The VI was associated with an increase in knowledge scores (maximum score=5) among nurses (median 2, IQR 1-2 to median 2, IQR 1-3; Pe-learning tool achieved higher overall scores than those who did not (Pe-learning tool was not shown to be significantly more effective than the comparator email in the clinical use of vancomycin, as measured by plasma levels within the therapeutic range. The e-learning tool was associated with improved knowledge scores among nurses, whereas the comparator email was associated with

Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity

DEFF Research Database (Denmark)

Vrieze, Anne; Out, Carolien; Fuentes, Susana

2014-01-01

.i.d. At baseline and after 1 week of therapy, fecal microbiota composition (Human Intestinal Tract Chip phylogenetic microarray), fecal and plasma bile acid concentrations as well as insulin sensitivity (hyperinsulinemic euglycemic clamp using [6,6-(2)H2]-glucose tracer) were measured. RESULTS: Vancomycin reduced...... (pinsulin sensitivity (p... of vancomycin significantly impacts host physiology by decreasing intestinal microbiota diversity, bile acid dehydroxylation and peripheral insulin sensitivity in subjects with metabolic syndrome. These data show that intestinal microbiota, particularly of the Firmicutes phylum contributes to bile acid...

Influence of Rifampin Therapy on Serum Bactericidal Activity in the Presence of Cloxacillin and Vancomycin

Directory of Open Access Journals (Sweden)

Andrew MR Mackenzie

1990-01-01

Full Text Available In this study the effect of rifampin on serum inhibitory and serum bactericidal titres was examined. Sera were prepared from pooled human serum to contain vancomycin (10 mg/L, cloxacillin (5 mg/L or rifampin (1 mg/L, and the combinations cloxacillin/rifampin and vancomycin/rifampin. These five sera were tested by a microtitre method for serum inhibitory power and serum bactericidal titre against 11 strains of Staphylococcus aureus. A 48 h incubation period was required to detect full colony growth for subculture plates. It was found with all strains that the effect of the addition of rifampin to the other two antibiotics was to increase the serum inhibitory power, lower the serum bactericidal titre, increase the inhibitory/cidal ratio, and slow colony growth on subculture. In the clinical part of the study it was shown that only three of 38 sera (8% from patients receiving betalactam or vanomycin but not rifampin gave an inhibitory/cidal ratio greater than 8, but that nine of 10 sera (90% from patients receiving rifampin in addition to betalactam or vancomycin gave a ratio greater than 8 (P<0.001. The study verified that the effect of rifampin in serum was to increase inhibitory power and decrease bactericidal titre. The clinical significance of these results is not known and it is suggested that a high ratio of inhibitory to bactericidal titre in the presence of rifampin is to be expected, and that a low bactericidal titre under these circumstances is not necessarily an indication to modify therapy.

Comparison of in vitro efficacy of linezolid and vancomycin by determining their minimum inhibitory concentrations against methicillin resistant Staphylococcus aureus (MRSA)

International Nuclear Information System (INIS)

Kaleem, F.; Usman, J.; Hassan, A.

2011-01-01

Objectives: To compare the in vitro activities of vancomycin and linezolid against methicillin resistant Staphyloccus aureus in our set up to help in formulating a better empirical treatment and reduce the emergence of vancomycin resistant Staphylococcus aureus. Methods: The study was conducted over a period of 6 months(July 1, 2009 - Dec 1, 2009). Fifty Methicillin resistant Staphylococcus aureus isolated from the clinical isolates of Military Hospital Rawalpindi were subjected to the determination of Minimum inhibitory concentrations of linezolid and vancomycin using E-strips. Results: All the isolated organisms were uniformly susceptible to both the antibiotics. Vancomycin showed higher minimum inhibitory concentrations (MICs) as compared to linezolid MICs. Conclusion: This study suggests that linezolid and vancomycin have similar in vitro efficacy for methicillin resistant Staphyloccus aureus infections. (author)

Evaluation of Ceftobiprole in a Rabbit Model of Aortic Valve Endocarditis Due to Methicillin-Resistant and Vancomycin-Intermediate Staphylococcus aureus

OpenAIRE

Chambers, Henry F.

2005-01-01

Ceftobiprole is a novel broad-spectrum cephalosporin that binds with high affinity to PBP 2a, the methicillin-resistance determinant of staphylococci, and is active against methicillin- and vancomycin-resistant Staphylococcus aureus. Ceftobiprole was compared to vancomycin in a rabbit model of methicillin-resistant S. aureus aortic valve endocarditis. Ceftobiprole and vancomycin were equally effective against endocarditis caused by methicillin-resistant S. aureus strain 76, whereas ceftobipro...

Avaliação da sensibilidade a antimicrobianos de 87 amostras clínicas de enterococos resistentes à vancomicina Antimicrobial susceptibility testing of 87 clinical isolates of vancomycin-resistant enterococci

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I.H. Saraiva

1997-09-01

tratamento de infecções causadas por enterococos multirresistentes ainda é um desafio, e vários esquemas já vêm sendo propostos na literatura. São necessários, no entanto, mais trabalhos analisando a efetividade clínica dessas combinações de antibióticos antes que recomendações definitivas possam ser feitas.OBJECTIVES. 1 To evaluate the antimicrobial susceptibility pattern of vancomycin-resistant enterococci to the antimicrobial agents that are commonly used to treat enterococci infections and to some alternative drugs. 2 To evaluate the accuracy of E test for susceptibility testing enterococci. MATERIAL AND METHOD. We evaluated 87 clinical VRE isolates that were selected from a previous study which analyzed 1936 clinical isolates collected and processed in 97 US medical centers in the last quarter of 1992. The isolates were identified to the species level by using the API 20S System, the Vitek gram-positive identification cards and a modified version of the conventional method proposed by Facklam and Collins. The in vitro susceptibility testing was performed by broth microdilution, E test and disk diffusion methods, following the criteria described by the National Committee for Clinical Laboratory Standards (NCCLS. The VRE isolates were tested against antimicrobial agents commonly used to treat enterococci infections (vancomycin, teicoplanin, ampicillin, penicillin, gentamicin and streptomycin and against ten potential alternative drugs (chloramphenicol, doxycycline, sparfloxacin, ciprofloxacin, clinafloxacin, erythromycin, spectinomycin, trospectomycin, trimetoprim-sulfametoxazol and novobiocin. RESULTS. Our results showed a high rate of resistance to ampicillin and penicillin (86%. High level resistance to gentamicin and streptomycin was demonstrated by 82% and 85% respectively. Although teicoplanin and vancomycin belong to the same antibiotic group (glycopeptide, 29% of VRE were susceptible to teicoplanin. Among the alternative drugs, trospectomycin

Replacement of Antibodies in Pseudo-ELISAs: Molecularly Imprinted Nanoparticles for Vancomycin Detection.

Science.gov (United States)

Canfarotta, Francesco; Smolinska-Kempisty, Katarzyna; Piletsky, Sergey

2017-01-01

The enzyme-linked immunosorbent assay (ELISA) is a widely employed analytical test used to quantify a given molecule. It relies on the use of specific antibodies, linked to an enzyme, to target the desired molecule. The reaction between the enzyme and its substrate gives rise to the analytical signal that can be quantified. Thanks to their robustness and low cost, molecularly imprinted polymer nanoparticles (nanoMIPs) are a viable alternative to antibodies. Herein, we describe the synthesis of nanoMIPs imprinted for vancomycin and their subsequent application in an ELISA-like format for direct replacement of antibodies.

Effect of dual delivery of antibiotics (vancomycin and cefazolin) and BMP-7 from chitosan microparticles on Staphylococcus epidermidis and pre-osteoblasts in vitro

Energy Technology Data Exchange (ETDEWEB)

Mantripragada, Venkata P. [Biomedical Engineering Program, The University of Toledo, Toledo, OH 43614-5807 (United States); Jayasuriya, Ambalangodage C., E-mail: a.jayasuriya@utoledo.edu [Biomedical Engineering Program, The University of Toledo, Toledo, OH 43614-5807 (United States); Department of Orthopaedic Surgery, The University of Toledo, Toledo, OH 43614-5807 (United States)

2016-10-01

The main aims of this manuscript are to: i) determine the effect of commonly used antibiotics to treat osteoarticular infections on osteoblast viability, ii) study the dual release of the growth factor (BMP-7) and antibiotics (vancomycin and cefazolin) from chitosan microparticles iii) demonstrate the bioactivity of the antibiotics released in vitro on Staphylococcus epidermidis. The novelty of this work is dual delivery of growth factor and antibiotic from the chitosan microparticles in a controlled manner without affecting their bioactivity. Cefazolin and vancomycin have different therapeutic concentrations for their action in vivo and therefore, two different concentrations of the drugs were used. Osteoblast cytotoxicity test concluded that cefazolin concentrations of 50 and 100 μg/ml were found to have positive influence on osteoblast proliferation. A significant increase in osteoblast proliferation was observed in the presence of cefazolin and BMP-7 in comparison with BMP-7 alone group; indicating cefazolin might play a role in osteoblast proliferation. On the other hand, vancomycin concentration of 1000 μg/ml was found to significantly reduce (p < 0.01) osteoblast proliferation in comparison with controls. The microbial study indicated that cefazolin at a minimum concentration of 21.5 μg/ml could inhibit ~ 85% growth of S. epidermidis, whereas vancomycin at a concentration of 30 μg/ml was found to inhibit ~ 80% bacterial growth. - Highlights: • Bacterial infections involve the inflammatory destruction of joint and bone. • Vancomycin and cefazolin half-life is limited to a few hours. • Dual delivery of growth factor and antibiotic from the chitosan microparticles. • Bioactivity of antibiotics released by the microparticles was protected.

Effect of dual delivery of antibiotics (vancomycin and cefazolin) and BMP-7 from chitosan microparticles on Staphylococcus epidermidis and pre-osteoblasts in vitro

International Nuclear Information System (INIS)

Mantripragada, Venkata P.; Jayasuriya, Ambalangodage C.

2016-01-01

The main aims of this manuscript are to: i) determine the effect of commonly used antibiotics to treat osteoarticular infections on osteoblast viability, ii) study the dual release of the growth factor (BMP-7) and antibiotics (vancomycin and cefazolin) from chitosan microparticles iii) demonstrate the bioactivity of the antibiotics released in vitro on Staphylococcus epidermidis. The novelty of this work is dual delivery of growth factor and antibiotic from the chitosan microparticles in a controlled manner without affecting their bioactivity. Cefazolin and vancomycin have different therapeutic concentrations for their action in vivo and therefore, two different concentrations of the drugs were used. Osteoblast cytotoxicity test concluded that cefazolin concentrations of 50 and 100 μg/ml were found to have positive influence on osteoblast proliferation. A significant increase in osteoblast proliferation was observed in the presence of cefazolin and BMP-7 in comparison with BMP-7 alone group; indicating cefazolin might play a role in osteoblast proliferation. On the other hand, vancomycin concentration of 1000 μg/ml was found to significantly reduce (p < 0.01) osteoblast proliferation in comparison with controls. The microbial study indicated that cefazolin at a minimum concentration of 21.5 μg/ml could inhibit ~ 85% growth of S. epidermidis, whereas vancomycin at a concentration of 30 μg/ml was found to inhibit ~ 80% bacterial growth. - Highlights: • Bacterial infections involve the inflammatory destruction of joint and bone. • Vancomycin and cefazolin half-life is limited to a few hours. • Dual delivery of growth factor and antibiotic from the chitosan microparticles. • Bioactivity of antibiotics released by the microparticles was protected.

Repeated batch production of vancomycin using synthetic cotton fibers

African Journals Online (AJOL)

Administrator

2011-09-28

Sep 28, 2011 ... The production of vancomycin by free and immobilized cells of Amycolatopsis orientalis was .... ceutical Industries Company (EIPICO)] and the inhibition zone ... production medium showed a marked loss in the first ... secondary metabolic enzymes of immobilized cells, as ... of cells in an economic way.

Clinical and economic consequences of vancomycin and fidaxomicin for the treatment of Clostridium difficile infection in Canada.

Science.gov (United States)

Wagner, Monika; Lavoie, Louis; Goetghebeur, Mireille

2014-03-01

Clostridium difficile infection (CDI) represents a public health problem with increasing incidence and severity. To evaluate the clinical and economic consequences of vancomycin compared with fidaxomicin in the treatment of CDI from the Canadian health care system perspective. A decision-tree model was developed to compare vancomycin and fidaxomicin for the treatment of severe CDI. The model assumed identical initial cure rates and included first recurrent episodes of CDI (base case). Treatment of patients presenting with recurrent CDI was examined as an alternative analysis. Costs included were for study medication, physician services and hospitalization. Cost effectiveness was measured as incremental cost per recurrence avoided. Sensitivity analyses of key input parameters were performed. In a cohort of 1000 patients with an initial episode of severe CDI, treatment with fidaxomicin led to 137 fewer recurrences at an incremental cost of $1.81 million, resulting in an incremental cost of $13,202 per recurrence avoided. Among 1000 patients with recurrent CDI, 113 second recurrences were avoided at an incremental cost of $18,190 per second recurrence avoided. Incremental costs per recurrence avoided increased with increasing proportion of cases caused by the NAP1/B1/027 strain. Results were sensitive to variations in recurrence rates and treatment duration but were robust to variations in other parameters. The use of fidaxomicin is associated with a cost increase for the Canadian health care system. Clinical benefits of fidaxomicin compared with vancomycin depend on the proportion of cases caused by the NAP1/B1/027 strain in patients with severe CDI.

Gene expression analysis reveals new possible mechanisms of vancomycin-induced nephrotoxicity and identifies gene markers candidates.

Science.gov (United States)

Dieterich, Christine; Puey, Angela; Lin, Sylvia; Lyn, Sylvia; Swezey, Robert; Furimsky, Anna; Fairchild, David; Mirsalis, Jon C; Ng, Hanna H

2009-01-01

Vancomycin, one of few effective treatments against methicillin-resistant Staphylococcus aureus, is nephrotoxic. The goals of this study were to (1) gain insights into molecular mechanisms of nephrotoxicity at the genomic level, (2) evaluate gene markers of vancomycin-induced kidney injury, and (3) compare gene expression responses after iv and ip administration. Groups of six female BALB/c mice were treated with seven daily iv or ip doses of vancomycin (50, 200, and 400 mg/kg) or saline, and sacrificed on day 8. Clinical chemistry and histopathology demonstrated kidney injury at 400 mg/kg only. Hierarchical clustering analysis revealed that kidney gene expression profiles of all mice treated at 400 mg/kg clustered with those of mice administered 200 mg/kg iv. Transcriptional profiling might thus be more sensitive than current clinical markers for detecting kidney damage, though the profiles can differ with the route of administration. Analysis of transcripts whose expression was changed by at least twofold compared with vehicle saline after high iv and ip doses of vancomycin suggested the possibility of oxidative stress and mitochondrial damage in vancomycin-induced toxicity. In addition, our data showed changes in expression of several transcripts from the complement and inflammatory pathways. Such expression changes were confirmed by relative real-time reverse transcription-polymerase chain reaction. Finally, our results further substantiate the use of gene markers of kidney toxicity such as KIM-1/Havcr1, as indicators of renal injury.

Reduced susceptibility to vancomycin and biofilm formation in methicillin-resistant Staphylococcus epidermidis isolated from blood cultures

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Luiza Pinheiro

2014-11-01

Full Text Available This study aimed to correlate the presence of ica genes, biofilm formation and antimicrobial resistance in 107 strains of Staphylococcus epidermidis isolated from blood cultures. The isolates were analysed to determine their methicillin resistance, staphylococcal cassette chromosome mec (SCCmec type, ica genes and biofilm formation and the vancomycin minimum inhibitory concentration (MIC was measured for isolates and subpopulations growing on vancomycin screen agar. The mecA gene was detected in 81.3% of the S. epidermidis isolated and 48.2% carried SCCmec type III. The complete icaADBC operon was observed in 38.3% of the isolates; of these, 58.5% produced a biofilm. Furthermore, 47.7% of the isolates grew on vancomycin screen agar, with an increase in the MIC in 75.9% of the isolates. Determination of the MIC of subpopulations revealed that 64.7% had an MIC ≥ 4 μg mL-1, including 15.7% with an MIC of 8 μg mL-1 and 2% with an MIC of 16 μg mL-1. The presence of the icaADBC operon, biofilm production and reduced susceptibility to vancomycin were associated with methicillin resistance. This study reveals a high level of methicillin resistance, biofilm formation and reduced susceptibility to vancomycin in subpopulations of S. epidermidis. These findings may explain the selection of multidrug-resistant isolates in hospital settings and the consequent failure of antimicrobial treatment.

A meta-analysis of metronidazole and vancomycin for the treatment of Clostridium difficile infection, stratified by disease severity.

Science.gov (United States)

Di, Xiuzhen; Bai, Nan; Zhang, Xin; Liu, Bin; Ni, Wentao; Wang, Jin; Wang, Kai; Liang, Beibei; Liu, Youning; Wang, Rui

2015-01-01

The aim of this meta-analysis was to compare the efficacy of metronidazole and vancomycin for the treatment of Clostridium difficile infection, especially to investigate which agent was superior for treating either mild or severe C. difficile infection. A meta-analysis of randomized controlled trials and cohort studies identified in Pubmed, Embase, and the Cochrane Library was conducted. Four randomized controlled trials and two cohort studies involving 1218 patients were included in this meta-analysis. Metronidazole was inferior to vancomycin for treating C. difficile infection in terms of both initial clinical cure rates (risk ratio, RR=0.91, 95% confidence interval, CI=0.84-0.98, p=0.02) and sustained cure rates (RR=0.88, 95% CI=0.82-0.96, p=0.003). For mild C. difficile infection, the efficacy of metronidazole and vancomycin resulted in similar clinical cure rates (RR=0.94, 95% CI=0.84-1.04, p=0.21) and sustained cure rates (RR=0.93, 95% CI=0.83-1.05, p=0.26). For severe C. difficile infection the efficacy of vancomycin was superior to metronidazole in terms of clinical cure rates (RR=0.81, 95% CI=0.69-0.95, p=0.009), whereas sustained cure rates were similar (RR=0.86, 95% CI=0.72-1.02, p=0.08). Regarding microbiological cure metronidazole therapy was as effective as vancomycin therapy (RR=0.88, 95% CI=0.64-1.21, p=0.43). Recurrence rates with metronidazole and vancomycin for both mild C. difficile infection (RR=0.95, 95% CI=0.56-1.60, p=0.85) and severe C. difficile infection (RR=1.27, 95% CI=0.85-1.91, p=0.25) were not different. Likewise, no difference in all-cause mortality was found as well (RR=0.87, 95% CI=0.56-1.35, p=0.53). In conclusion, vancomycin provides improved initial clinical and sustained cure rates in patients with C. difficile infection compared with metronidazole, especially in patients with severe C. difficile infection. In view of these data, vancomycin may be considered first line therapy for severe C. difficile infection. Copyright �

Vancomycin-Resistant Enterococci and Bacterial Community Structure following a Sewage Spill into an Aquatic Environment

Science.gov (United States)

Young, Suzanne; Nayak, Bina; Sun, Shan; Badgley, Brian D.; Rohr, Jason R.

2016-01-01

ABSTRACT Sewage spills can release antibiotic-resistant bacteria into surface waters, contributing to environmental reservoirs and potentially impacting human health. Vancomycin-resistant enterococci (VRE) are nosocomial pathogens that have been detected in environmental habitats, including soil, water, and beach sands, as well as wildlife feces. However, VRE harboring vanA genes that confer high-level resistance have infrequently been found outside clinical settings in the United States. This study found culturable Enterococcus faecium harboring the vanA gene in water and sediment for up to 3 days after a sewage spill, and the quantitative PCR (qPCR) signal for vanA persisted for an additional week. Culturable levels of enterococci in water exceeded recreational water guidelines for 2 weeks following the spill, declining about five orders of magnitude in sediments and two orders of magnitude in the water column over 6 weeks. Analysis of bacterial taxa via 16S rRNA gene sequencing showed changes in community structure through time following the sewage spill in sediment and water. The spread of opportunistic pathogens harboring high-level vancomycin resistance genes beyond hospitals and into the broader community and associated habitats is a potential threat to public health, requiring further studies that examine the persistence, occurrence, and survival of VRE in different environmental matrices. IMPORTANCE Vancomycin-resistant enterococci (VRE) are harmful bacteria that are resistant to the powerful antibiotic vancomycin, which is used as a last resort against many infections. This study followed the release of VRE in a major sewage spill and their persistence over time. Such events can act as a means of spreading vancomycin-resistant bacteria in the environment, which can eventually impact human health. PMID:27422829

Vancomycin gene selection in the microbiome of urban Rattus norvegicus from hospital environment

DEFF Research Database (Denmark)

Arn Hansen, Thomas; Joshi, Tejal; Larsen, Anders Rhod

2016-01-01

Widespread use of antibiotics has resulted in selection pressure on genes that make bacteria non-responsive to antibiotics. These antibiotic-resistant bacteria are currently a major threat to global health. There are various possibilities for the transfer of antibiotic resistance genes. It has be....... norvegicus microbiome, potentially driven by the outflow of antibiotics and antibiotic-resistant bacteria into the wastewater systems. Carriage of vancomycin resistance may suggest that R. norvegicus is acting as a reservoir for possible transmission to the human population....

Genetic pathway in acquisition and loss of vancomycin resistance in a methicillin resistant Staphylococcus aureus (MRSA strain of clonal type USA300.

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Susana Gardete

2012-02-01

Full Text Available An isolate of the methicillin-resistant Staphylococcus aureus (MRSA clone USA300 with reduced susceptibility to vancomycin (SG-R (i.e, vancomycin-intermediate S. aureus, VISA and its susceptible "parental" strain (SG-S were recovered from a patient at the end and at the beginning of an unsuccessful vancomycin therapy. The VISA phenotype was unstable in vitro generating a susceptible revertant strain (SG-rev. The availability of these 3 isogenic strains allowed us to explore genetic correlates of antibiotic resistance as it emerged in vivo. Compared to the susceptible isolate, both the VISA and revertant strains carried the same point mutations in yycH, vraG, yvqF and lspA genes and a substantial deletion within an intergenic region. The revertant strain carried a single additional frameshift mutation in vraS which is part of two component regulatory system VraSR. VISA isolate SG-R showed complex alterations in phenotype: decreased susceptibility to other antibiotics, slow autolysis, abnormal cell division and increased thickness of cell wall. There was also altered expression of 239 genes including down-regulation of major virulence determinants. All phenotypic properties and gene expression profile returned to parental levels in the revertant strain. Introduction of wild type yvqF on a multicopy plasmid into the VISA strain caused loss of resistance along with loss of all the associated phenotypic changes. Introduction of the wild type vraSR into the revertant strain caused recovery of VISA type resistance. The yvqF/vraSR operon seems to function as an on/off switch: mutation in yvqF in strain SG-R turns on the vraSR system, which leads to increase in vancomycin resistance and down-regulation of virulence determinants. Mutation in vraS in the revertant strain turns off this regulatory system accompanied by loss of resistance and normal expression of virulence genes. Down-regulation of virulence genes may provide VISA strains with a "stealth

Modulating activity of vancomycin and daptomycin on the expression of autolysis cell-wall turnover and membrane charge genes in hVISA and VISA strains.

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Viviana Cafiso

Full Text Available Glycopeptides are still the gold standard to treat MRSA (Methicillin Resistant Staphylococcus aureus infections, but their widespread use has led to vancomycin-reduced susceptibility [heterogeneous Vancomycin-Intermediate-Staphylococcus aureus (hVISA and Vancomycin-Intermediate-Staphylococcus aureus (VISA], in which different genetic loci (regulatory, autolytic, cell-wall turnover and cell-envelope positive charge genes are involved. In addition, reduced susceptibility to vancomycin can influence the development of resistance to daptomycin. Although the phenotypic and molecular changes of hVISA/VISA have been the focus of different papers, the molecular mechanisms responsible for these different phenotypes and for the vancomycin and daptomycin cross-resistance are not clearly understood. The aim of our study was to investigate, by real time RT-PCR, the relative quantitative expression of genes involved in autolysis (atl-lytM, cell-wall turnover (sceD, membrane charges (mprF-dltA and regulatory mechanisms (agr-locus-graRS-walKR, in hVISA and VISA cultured with or without vancomycin and daptomycin, in order to better understand the molecular basis of vancomycin-reduced susceptibility and the modulating activity of vancomycin and daptomycin on the expression of genes implicated in their reduced susceptibility mechanisms. Our results show that hVISA and VISA present common features that distinguish them from Vancomycin-Susceptible Staphylococcus aureus (VSSA, responsible for the intermediate glycopeptide resistance i.e. an increased cell-wall turnover, an increased positive cell-wall charge responsible for a repulsion mechanism towards vancomycin and daptomycin, and reduced agr-functionality. Indeed, VISA emerges from hVISA when VISA acquires a reduced autolysis caused by a down-regulation of autolysin genes, atl/lytM, and a reduction of the net negative cell-envelope charge via dltA over-expression. Vancomycin and daptomycin, acting in a similar

Rapid and easy detection of low-level resistance to vancomycin in methicillin-resistant Staphylococcus aureus by matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

Science.gov (United States)

Asakura, Kota; Azechi, Takuya; Sasano, Hiroshi; Matsui, Hidehito; Hanaki, Hideaki; Miyazaki, Motoyasu; Takata, Tohru; Sekine, Miwa; Takaku, Tomoiku; Ochiai, Tomonori; Komatsu, Norio; Shibayama, Keigo; Katayama, Yuki; Yahara, Koji

2018-01-01

Vancomycin-intermediately resistant Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) are associated with treatment failure. hVISA contains only a subpopulation of cells with increased minimal inhibitory concentrations, and its detection is problematic because it is classified as vancomycin-susceptible by standard susceptibility testing and the gold-standard method for its detection is impractical in clinical microbiology laboratories. Recently, a research group developed a machine-learning classifier to distinguish VISA and hVISA from vancomycin-susceptible S. aureus (VSSA) according to matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) data. Nonetheless, the sensitivity of hVISA classification was found to be 76%, and the program was not completely automated with a graphical user interface. Here, we developed a more accurate machine-learning classifier for discrimination of hVISA from VSSA and VISA among MRSA isolates in Japanese hospitals by means of MALDI-TOF MS data. The classifier showed 99% sensitivity of hVISA classification. Furthermore, we clarified the procedures for preparing samples and obtaining MALDI-TOF MS data and developed all-in-one software, hVISA Classifier, with a graphical user interface that automates the classification and is easy for medical workers to use; it is publicly available at https://github.com/bioprojects/hVISAclassifier. This system is useful and practical for screening MRSA isolates for the hVISA phenotype in clinical microbiology laboratories and thus should improve treatment of MRSA infections.

Assessing outcomes of adult oncology patients treated with linezolid versus daptomycin for bacteremia due to vancomycin-resistant Enterococcus.

Science.gov (United States)

Patel, Khilna; Kabir, Rubiya; Ahmad, Samrah; Allen, Steven L

2016-04-01

The incidence and severity of vancomycin-resistant Enterococcus blood stream infections continue to rise and is a significant burden in the healthcare setting. Literature thus far is minimal regarding treatment outcomes in patients with malignancy and vancomycin-resistant Enterococcus bacteremia. Appropriate antibiotic selection is vital to treatment success due to high rates of resistance, limited antimicrobials and mortality in this patient population. We conducted this study to determine whether treatment outcomes differed between cancer patients treated with linezolid and those treated with daptomycin for vancomycin-resistant Enterococcus bacteremia. This single-center, retrospective study included adult patients hospitalized on the oncology service with documented vancomycin-resistant Enterococcus faecium or Enterococcus faecalis bacteremia who received at least 48 h of either linezolid or daptomycin as primary treatment. A total of 65 patients were included in the analysis. Thirty-two patients received daptomycin as primary treatment, and 33 patients received linezolid as primary treatment. Twenty-six (76.5%) patients in the linezolid cohort versus 22 (71%) patients in the daptomycin cohort achieved microbiological cure (p = 0.6141). Median length of stay in days (30 vs. 42, p = 0.0714) and mortality (7/32 (20.6%) vs. 8/33 (25.8%), p = 0.6180) were also similar between the linezolid and daptomycin treated patients, respectively. No differences in microbiological cure, length of stay or mortality were identified between the groups. This study suggests that linezolid and daptomycin are each reasonable options for treating vancomycin-resistant Enterococcus bacteremia in oncology patients. Further prospective, randomized controlled trials are needed to assess the optimal treatment for vancomycin-resistant Enterococcus bacteremia in this patient population. © The Author(s) 2014.

High-Level Vancomycin-Resistant Staphylococcus aureus (VRSA in Iran: A Systematic Review

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Emran Askari

2015-10-01

Full Text Available Background: Staphylococcus aureus is a major human pathogen world- wide. Vancomycin has been used for decades to treat multidrug resistant S. aureus. Ten years has passed since the first report of vancomycin re- sistant S. aureus (VRSA. The objective of this systematic review was to determine  the total number of VRSA isolates that have been reported from Iran.Methods:  Search terms reflected “Iran”, “vancomycin” and “S. aureus” were  searched  in the ISI web  of knowledge,  PubMed,  SciVerse,  and Google scholar. Also two Persian scientific databases and 13 recent na- tional congresses  were investigated.  Articles / abstracts working on S. aureus in Iran, evaluating vancomycin MIC and / or PCR of vanA/B were included in this systematic review.Results: Out of the 3484 records found in mentioned resources, 13 re-lated studies were included in the final analysis. The result showed that at least 24 VRSA isolates which have been reported from Iran up to Sep- tember 2012.Conclusion: It seems that many Iranian researchers did not follow a spe- cific guideline for reporting and confirming VRSA. Establishing an Ira- nian reference center where studies on VRSA can be registered, evaluat- ed and confirmed is strongly recommended.

Novel Inhibitors of Staphyloxanthin Virulence Factor in Comparison with Linezolid and Vancomycin versus Methicillin-Resistant, Linezolid-Resistant, and Vancomycin-Intermediate Staphylococcus aureus Infections in Vivo.

Science.gov (United States)

Ni, Shuaishuai; Wei, Hanwen; Li, Baoli; Chen, Feifei; Liu, Yifu; Chen, Wenhua; Xu, Yixiang; Qiu, Xiaoxia; Li, Xiaokang; Lu, Yanli; Liu, Wenwen; Hu, Linhao; Lin, Dazheng; Wang, Manjiong; Zheng, Xinyu; Mao, Fei; Zhu, Jin; Lan, Lefu; Li, Jian

2017-10-12

Our previous work ( Wang et al. J. Med. Chem. 2016 , 59 , 4831 - 4848 ) revealed that effective benzocycloalkane-derived staphyloxanthin inhibitors against methicillin-resistant Staphylococcus aureus (S. aureus) infections were accompanied by poor water solubility and high hERG inhibition and dosages (preadministration). In this study, 92 chroman and coumaran derivatives as novel inhibitors have been addressed for overcoming deficiencies above. Derivatives 69 and 105 displayed excellent pigment inhibitory activities and low hERG inhibition, along with improvement of solubility by salt type selection. The broad and significantly potent antibacterial spectra of 69 and 105 were displayed first with normal administration in the livers and hearts in mice against pigmented S. aureus Newman, Mu50 (vancomycin-intermediate S. aureus), and NRS271 (linezolid-resistant S. aureus), compared with linezolid and vancomycin. In summary, both 69 and 105 have the potential to be developed as good antibacterial candidates targeting virulence factors.

Persistence of Vancomycin Resistance in Multiple Clones of Enterococcus faecium Isolated from Danish Broilers 15 Years after the Ban of Avoparcin

DEFF Research Database (Denmark)

Bortolaia, Valeria; Mander, Manuela; Jensen, Lars Bogø

2015-01-01

associated with a transferable nontypeable plasmid lineage occurring in multiple E. faecium clones. Coselection of sequence type 842 by tetracycline use only partly explained the persistence of vancomycin resistance in the absence of detectable plasmid coresistance and toxin-antitoxin systems....

Comparative Evaluation of Serotonin Toxicity among Veterans Affairs Patients Receiving Linezolid and Vancomycin

Science.gov (United States)

Patel, N.; Rivera, A.; Tristani, L.; Lazariu, V.; Vandewall, H.; McNutt, L. A.

2013-01-01

Despite the theoretical risk of serotonin toxicity (ST) with linezolid, “real-world” clinical evaluations of the risk of ST in patients receiving linezolid have been limited to case reports and noncomparator studies. An observational, matched-cohort study was conducted to evaluate the risk of ST among hospitalized patients who received linezolid or vancomycin at the Upstate New York Veterans Affairs Healthcare Network (Veterans Integrated Service Network 2 [VISN-2]). Matching criteria included VISN-2 hospital, hospital ward, prior hospital length of stay, age, and baseline platelet counts. The patients' electronic medical records were evaluated for symptoms consistent with ST and the Hunter serotonin toxicity criteria (HSTC) using an intensive, natural word search algorithm. The study included 251 matched pairs. Demographics and comorbidities were similar between groups. Over half of the study population received at least one concurrent medication with serotonergic activity. Receipt of agents with serotonergic activity was more pronounced in the vancomycin group, and the higher frequency was due to concomitant antihistamine and antiemetic use. Antidepressant use, including selective serotonin reuptake inhibitors (SSRIs), was similar between groups. No patients in either group were found to meet the criteria using the word search algorithm for ST. Fewer linezolid patients than vancomycin patients met the HSTC overall (3.2% versus 8.8%) and when stratified by receipt of a concurrent serotonergic agent (4.3% versus 12.4%). Of the patients meeting the HSTC, most had past or present comorbidities that may have contributed to or overlapped the HSTC. This study of hospitalized patients revealed comparably low frequencies of adverse events potentially related to ST among patients who received linezolid or vancomycin. PMID:24041888

Presence of virulence factors in Enterococcus faecalis and Enterococcus faecium susceptible and resistant to vancomycin

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Carolina Baldisserotto Comerlato

2013-08-01

Full Text Available Despite the increasing importance of Enterococcus as opportunistic pathogens, their virulence factors are still poorly understood. This study determines the frequency of virulence factors in clinical and commensal Enterococcus isolates from inpatients in Porto Alegre, Brazil. Fifty Enterococcus isolates were analysed and the presence of the gelE, asa1 and esp genes was determined. Gelatinase activity and biofilm formation were also tested. The clonal relationships among the isolates were evaluated using pulsed-field gel electrophoresis. The asa1, gelE and esp genes were identified in 38%, 60% and 76% of all isolates, respectively. The first two genes were more prevalent in Enterococcus faecalis than in Enterococcus faecium, as was biofilm formation, which was associated with gelE and asa1 genes, but not with the esp gene. The presence of gelE and the activity of gelatinase were not fully concordant. No relationship was observed among any virulence factors and specific subclones of E. faecalis or E. faecium resistant to vancomycin. In conclusion, E. faecalis and E. faecium isolates showed significantly different patterns of virulence determinants. Neither the source of isolation nor the clonal relationship or vancomycin resistance influenced their distribution.

A dirty cause of vancomycin-mediated Henoch-Schonlein purpura: oxygen tubing is not a foley.

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Shah, Nikhil H; Kline, Kristopher P; Shukla, Manas K

2017-06-20

A 59-year-old male presented with methicillin-resistant Staphylococcus aureus bacteraemia from a prostatic abscess and was treated with vancomycin. Two weeks into his treatment course, he developed severe joint pains, abdominal pain with bloody, mucinous stools and a diffuse palpable purpuric rash on his extremities. Biopsy of the rash showed IgA immune-complex deposition consistent with Henoch-Schönlein purpura. After treatment with glucocorticoids, his symptoms resolved completely. Vancomycin is an extremely commonly used antibiotic with certain well-known adverse effects. Henoch-Schönlein purpura, a vasculitis involving abdominal pain, arthralgias and palpable purpura, is a much less common side effect, as seen in this patient. Given that vancomycin is widely used internationally, clinicians should be aware of the risks entailed by its use. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Isolation of vancomycin resistant Enterococcus faecium from food

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Wegener, Henrik Caspar; Madsen, Mogens; Nielsen, Niels

1997-01-01

was not detected in 124 samples of pork and 128 samples of beef from retail outlets by the direct plating method. An additional enrichment step in nutrient broth supplemented with vancomycin enhanced the detection rate of VREF by approximately three times compared to the direct plating method when investigating...... the same 160 samples of broilers by the two methods. The implications and public health aspects of VREF in food is discussed....

Minimum inhibitory concentration of vancomycin to methicillin resistant Staphylococcus aureus isolated from different clinical samples at a tertiary care hospital in Nepal

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Arjun Ojha Kshetry

2016-07-01

Full Text Available Abstract Background Methicillin resistant Staphylococcus aureus (MRSA has evolved as a serious threat to public health. It has capability to cause infections not only in health care settings but also in community. Due to the multidrug resistance shown by MRSA, there are limited treatment options for the infections caused by this superbug. Vancomycin is used as the drug of choice for the treatment of infections caused by MRSA. Different studies from all around the world have documented the emergence of strains of S. aureus those are intermediate sensitive or resistant to vancomycin. And recently, there have been reports of reduced susceptibility of MRSA to vancomycin, from Nepal also. So the main purpose of this study was to determine the minimum inhibitory concentration (MIC of vancomycin to methicillin resistant S. aureus isolated from different clinical specimens. Methods Total 125 strains of S. aureus isolated from different clinical samples at KIST Medical College and Teaching Hospital, Lalitpur, Nepal from Nov 2012 to June 2013, were subjected to MRSA detection by cefoxitin disc diffusion method. The minimum inhibitory concentrations of vancomycin to confirmed MRSA strains were determined by agar dilution method. Yellow colored colonies in mannitol salt agar, which were gram positive cocci, catalase positive and coagulase positive were confirmed to be S. aureus. Results Among, total 125 S. aureus strains isolated; 47(37.6% were MRSA. Minimum inhibitory concentrations of vancomycin to the strains of MRSA ranged from 0.125 μg/ml to 1 μg/ml. Conclusion From our findings we concluded that the rate of isolation of MRSA among all the strains of S. aureus isolated from clinical samples was very high. However, none of the MRSA strains were found to be vancomycin intermediate-sensitive or vancomycin-resistant.

Evaluating the Relationship between Vancomycin Trough Concentration and 24-Hour Area under the Concentration-Time Curve in Neonates.

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Tseng, Sheng-Hsuan; Lim, Chuan Poh; Chen, Qi; Tang, Cheng Cai; Kong, Sing Teang; Ho, Paul Chi-Lui

2018-04-01

Bacterial sepsis is a major cause of morbidity and mortality in neonates, especially those involving methicillin-resistant Staphylococcus aureus (MRSA). Guidelines by the Infectious Diseases Society of America recommend the vancomycin 24-h area under the concentration-time curve to MIC ratio (AUC 24 /MIC) of >400 as the best predictor of successful treatment against MRSA infections when the MIC is ≤1 mg/liter. The relationship between steady-state vancomycin trough concentrations and AUC 24 values (mg·h/liter) has not been studied in an Asian neonatal population. We conducted a retrospective chart review in Singapore hospitals and collected patient characteristics and therapeutic drug monitoring data from neonates on vancomycin therapy over a 5-year period. A one-compartment population pharmacokinetic model was built from the collected data, internally validated, and then used to assess the relationship between steady-state trough concentrations and AUC 24 A Monte Carlo simulation sensitivity analysis was also conducted. A total of 76 neonates with 429 vancomycin concentrations were included for analysis. Median (interquartile range) was 30 weeks (28 to 36 weeks) for postmenstrual age (PMA) and 1,043 g (811 to 1,919 g) for weight at the initiation of treatment. Vancomycin clearance was predicted by weight, PMA, and serum creatinine. For MRSA isolates with a vancomycin MIC of ≤1, our major finding was that the minimum steady-state trough concentration range predictive of achieving an AUC 24 /MIC of >400 was 8 to 8.9 mg/liter. Steady-state troughs within 15 to 20 mg/liter are unlikely to be necessary to achieve an AUC 24 /MIC of >400, whereas troughs within 10 to 14.9 mg/liter may be more appropriate. Copyright © 2018 American Society for Microbiology.

Berberine blocks the relapse of Clostridium difficile infection in C57BL/6 mice after standard vancomycin treatment.

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Lv, Zhi; Peng, Guoli; Liu, Weihua; Xu, Hufeng; Su, JianRong

2015-07-01

Vancomycin is a preferred antibiotic for treating Clostridium difficile infection (CDI) and has been associated with a rate of recurrence of CDI of as high as 20% in treated patients. Recent studies have suggested that berberine, an alternative medical therapy for gastroenteritis and diarrhea, exhibits several beneficial effects, including induction of anti-inflammatory responses and restoration of the intestinal barrier function. This study investigated the therapeutic effects of berberine on preventing CDI relapse and restoring the gut microbiota in a mouse model. Berberine was administered through gavage to C57BL/6 mice with established CDI-induced intestinal injury and colitis. The disease activity index (DAI), mean relative weight, histopathology scores, and levels of toxins A and B in fecal samples were measured. An Illumina sequencing-based analysis of 16S rRNA genes was used to determine the overall structural change in the microbiota in the mouse ileocecum. Berberine administration significantly promoted the restoration of the intestinal microbiota by inhibiting the expansion of members of the family Enterobacteriaceae and counteracting the side effects of vancomycin treatment. Therapy consisting of vancomycin and berberine combined prevented weight loss, improved the DAI and the histopathology scores, and effectively decreased the mortality rate. Berberine prevented CDIs from relapsing and significantly improved survival in the mouse model of CDI. Our data indicate that a combination of berberine and vancomycin is more effective than vancomycin alone for treating CDI. One of the possible mechanisms by which berberine prevents a CDI relapse is through modulation of the gut microbiota. Although this conclusion was generated in the case of the mouse model, use of the combination of vancomycin and berberine and represent a novel therapeutic approach targeting CDI. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Endophthalmitis caused by gram-positive bacteria resistant to vancomycin: Clinical settings, causative organisms, antimicrobial susceptibilities, and treatment outcomes

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Hegde Sharat Shivaramaiah

2018-06-01

Full Text Available Purpose: To report the clinical settings, causative organisms, antimicrobial susceptibilities, and treatment outcomes of patients with endophthalmitis caused by gram-positive bacteria resistant to vancomycin. Methods: Retrospective case series of all patients with culture-proven endophthalmitis caused by gram-positive bacteria resistant to vancomycin between January 2010 and December 2016 in LV Prasad Eye Institute, Visakhapatnam, India. Results: The current study included 14 patients. The clinical settings were post-cataract surgery in 8/14 (57.1% and open globe injury in 6/14 (42.8%. Primary intervention for all patients included tap and intravitreal antibiotic injection. During subsequent follow-up, pars plana vitrectomy was performed in 6 patients and one patient underwent penetrating keratoplasty. Mean number of intravitreal antibiotic injections performed were 3.4 per patient. The most common organisms isolated were coagulase-negative Staphylococci in 6/14 (42.8%, Staphylococcus aureus in 5/14 (35.7%, Streptococcus sp in 2/14 (14.2% and Bacillus sp in 1/14 (7.14%. In addition to vancomycin, resistance to multiple drugs (three or more groups of antibiotics was found in all 14 cases. Antimicrobial susceptibility results showed susceptibility to amikacin in 7/14 (50.0%, gatifloxacin in 6/14 (42.8%, moxifloxacin in 3/13 (23.0%, cefazoline in 5/14 (35.7%, cefuroxime in 3/14 (21.4%, ciprofloxacin in 2/14 (14.2% and linezolid in 5/5 (100%. The mean duration of follow-up was 30.7 weeks (6 weeks–90 weeks. At last follow-up, visual acuity (VA of 20/200 or better was recorded in 7/14 (50% and VA < 5/200 occurred in 7/14 (50%. Conclusion and importance: Antimicrobial susceptibility testing may help in selection of suitable antimicrobial agents for repeat intravitreal injection. Inspite of retreatment with intravitreal antibiotics, these patients generally had poor VA outcomes. Keywords: Coagulase-negative Staphylococci, Endophthalmitis

Vancomycin AUC/MIC and Corresponding Troughs in a Pediatric Population.

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Kishk, Omayma A; Lardieri, Allison B; Heil, Emily L; Morgan, Jill A

2017-01-01

Adult guidelines suggest an area under the curve/minimum inhibitory concentration (AUC/MIC) > 400 corresponds to a vancomycin trough serum concentration of 15 to 20 mg/L for methicillin-resistant Staphylococcus aureus infections, but obtaining these troughs in children are difficult. The primary objective of this study was to assess the likelihood that 15 mg/kg of vancomycin every 6 hours in a child achieves an AUC/MIC > 400. This retrospective chart review included pediatric patients >2 months to AUCs were calculated four times using three pharmacokinetic methods. A total of 36 patients with 99 vancomycin trough serum concentrations were assessed. Baseline characteristics were similar between groups. For troughs in group 1 (n = 55), the probability of achieving an AUC/MIC > 400 ranged from 16.4% to 90.9% with a median trough concentration of 11.4 mg/L, while in group 2 (n = 44) the probability of achieving AUC/MIC > 400 ranged from 15.9% to 54.5% with mean trough concentration of 9.2 mg/L. The AUC/MICs were not similar between the different pharmacokinetic methods used; however, a trapezoidal equation (Method A) yielded the highest correlation coefficient (r 2 = 0.59). When dosing every 6 hours, an AUC/MIC of 400 correlated to a trough serum concentration of 11 mg/L. The probability of achieving an AUC/MIC > 400 using only a trough serum concentration and an MIC with patients receiving 15 mg/kg every 6 hours is variable based on the method used to calculate the AUC. An AUC/MIC of 400 in children correlated to a trough concentration of 11 mg/L using a trapezoidal Method to calculate AUC.

An investigation of vancomycin minimum inhibitory concentration creep among methicillin-resistant Staphylococcus aureus strains isolated from pediatric patients and healthy children in Northern Taiwan.

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Chang, Chia-Ning; Lo, Wen-Tsung; Chan, Ming-Chin; Yu, Ching-Mei; Wang, Chih-Chien

2017-06-01

The phenomenon of vancomycin minimum inhibitory concentration (MIC) creep is an increasingly serious problem in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. In this study, we investigated the vancomycin and daptomycin MIC values of MRSA strains isolated from pediatric patients and MRSA colonized healthy children. Then, we assessed whether there was evidence of clonal dissemination for strains with an MIC to vancomycin of ≥ 1.5 μg/mL. We collected clinical MRSA isolates from pediatric patients and from healthy children colonized with MRSA during 2008-2012 at a tertiary medical center in northern Taiwan and obtained vancomycin and daptomycin MIC values using the Etest method. Pulse-field gel electrophoresis (PFGE) and staphylococcal cassette chromosome (SCCmec) typing were used to assess clonal dissemination for strains with an MIC to vancomycin of ≥ 1.5 μg/mL. A total 195 MRSA strains were included in this study; 87 were isolated patients with a clinical MRSA infection, and the other 108 strains from nasally colonized healthy children. Vancomycin MIC≥1.5 μg/mL was seen in more clinical isolates (60/87, 69%) than colonized isolates (32/108, 29.6%), p < 0.001. The PFGE typing of both strains revealed multiple pulsotypes. Vancomycin MIC creeps existed in both clinical MRSA isolates and colonized MRSA strains. Great diversity of PFGE typing was in both strains collected. There was no association between the clinical and colonized MRSA isolates with vancomycin MIC creep. Copyright © 2016. Published by Elsevier B.V.

Prevalence and Removal Efficiency of Enterococcal Species and Vancomycin-resistant Enterococci of a Hospital Wastewater Treatment Plant

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Fatemeh Karimi

2016-12-01

Full Text Available Simultaneous presence of various antibiotics and bacteria in hospital wastewaters creates a suitable environment, in which the bacteria, such as ‎enterococci become resistant to the antibiotics. The aim of this study was to evaluate the performance of different units of the hospital wastewater treatment plant (HWTP to remove Enterococcus spp and Vancomycin-resistant Enterococcus (VRE. The study was performed on the 27 samples collected from HWTP in Hamedan, Iran during December 2014 to August 2015. Enterococcus spp and VRE were identified by biochemical tests and then the isolates were confirmed by PCR. Finally, the antibiotic susceptibility test was performed using disk diffusion methods. Of the 27 samples examined, 315 a total of enterococcal isolates were obtained. Of the 315 isolates of enterococci investigated, 162 (51.42% were identified as E. faecium, 87 (27.61% as E. hirae, 35 (11.11% as E. faecalis, 11 (3.5% as E. gallinarum, 7 (2.22% as E. casseliflavus, 4 (1.26% E. avium, and 9 (2.85% isolates VR E. faecium.The results of antibiotic susceptibility testing showed that of the total 315 isolates, 146 (46.34% were resistance to tetracycline, 9 (2.85% were resistance to vancomycin and Teicoplanin. Lower antibiotic resistance was seen with Nitrofurantoin 2 (1.26%. This study indicates a high prevalence of multidrug resistance among E. faecium isolated from HWTP, thus, it could be considered as a threat to the health and safety of ‎wastewater workers and even public health.

Efficacy of a synthetic antimicrobial peptidomimetic versus vancomycin in a Staphylococcus epidermidis device-related murine peritonitis model

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Cavanagh, Jorunn Pauline; Granslo, Hildegunn Norbakken; Fredheim, Elizabeth Aarag

2013-01-01

Objectives Biofilm-forming Staphylococcus epidermidis is a prevalent cause of peritonitis during peritoneal dialysis. We compared the efficacy of a synthetic antimicrobial peptidomimetic (Ltx21) versus vancomycin in a murine model mimicking a device-related peritonitis. Methods Silicone implants......, pre-colonized with an S. epidermidis biofilm, were inserted into the peritoneal cavity of BALB/c mice. Three groups (36 mice in each) with pre-colonized implants received intraperitoneal treatment with Ltx21, vancomycin or placebo. Mice were euthanized on day 3 (n = 12), day 6 (n = 12) or day 8 (n...... = 12) post-implantation. Controls were mice with sterile implants (n = 18) and mice without surgery (n = 6). Bacterial reductions in cfu were analysed from implants and peritoneal fluid (PF). Inflammatory responses in serum and PF were measured. Results Vancomycin resulted in a stronger reduction...

[Vancomycin-resistant enterococci - the nature of resistance and risk of transmission from animals to humans].

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Hermanovská, Lýdia; Bardoň, Jan; Čermák, Pavel

2016-06-01

Enterococci are part of the normal intestinal flora of humans and animals. Under certain circumstances, they are capable of extraintestinal conversion to opportunistic pathogens. They cause endogenous as well as exogenous community and nosocomial infections. The gastrointestinal tract of mammals provides them with favorable conditions for acquisition and spread of resistance genes, for example to vancomycin (van), from other symbiotic bacteria. Thus, vancomycin-resistant enterococci (VRE) become potential reservoirs and vectors of the van genes. Their occurrence in the population of the Czech Republic was first reported by Kolář et al. in 1997. Some variants of the vanA gene cluster carried on Tn1546 which encode resistance to vancomycin are identical in humans and in animals. It means that animals, especially cattle, poultry and pigs, could be an important reservoir of VRE for humans. Kolář and Bardoň detected VRE in animals in the Czech Republic for the first time in 2000. In Europe, the glycopeptide antibiotic avoparcin, used as a growth stimulator, is responsible for selection of VRE strains in animals. Strains of Enterococcus faecium from animals may offer genes of antimicrobial resistance to other enterococci or they can be directly dangerous to human. This is demonstrated by finding isolates of E. faecalis from human patients and from pigs having very similar profiles of resistance and virulence genes. The goal of the paper was to point out the similarity between isolates of human and animal strains of enterococci resistant to vancomycin, and the possibility of their bilateral transfer between humans and animals.

Evaluation of the automated system Vitek2 for identification and antimicrobial susceptibility testing of Brazilian Gram-positive cocci strains

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Pedro Alves d'Azevedo

Full Text Available Automated instruments offer many advantages for clinical laboratories. Nevertheless, they can have problems identifying and determining susceptibilities of some pathogens. Vitek® 2 (bioMérieux is an automated system that was recently introduced to Brazil. We evaluated the performance of this equipment for Brazilian isolates that had been characterized using reference identification and antimicrobial susceptibility testing methods. Ninety-nine strains of Gram-positive cocci from a local reference center collection were analyzed, consisting of 50 coagulasenegative Staphylococcus (CoNS and 49 Enterococcus and related species. Vitek® 2 correctly identified 79.8% (79/99 of the isolates. Oxacillin resistance was detected in 76% (19/25 of resistant S. epidermidis strains and in 88% (22/25 of other resistant CoNS species strains. Vancomycin resistance was detected in 100% (20/20 of resistant Enterococcus and related species strains. Vitek® 2 performed very well for the identification of S. epidermidis and non-epidermidis staphylococci, and for the detection of vancomycin resistance in Enterococcus and related species. However, the system needs improvement in order to provide reliable results for the characterization of some CoNS species, identification of Enterococcus and related species and for detecting oxacillin resistance in CoNS.

Linezolid Versus Vancomycin in the Empiric Treatment of Nosocomial Pneumonia: A Cost-Utility Analysis Incorporating Results from the ZEPHyR Trial.

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Collins, Curtis D; Schwemm, Ann K

2015-07-01

To examine the cost-effectiveness of vancomycin versus linezolid in the empiric treatment of nosocomial pneumonias incorporating results from a recent prospective, double-blind, multicenter, controlled trial in adults with suspected methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. A decision-analytic model examining the cost-effectiveness of linezolid versus vancomycin for the empiric treatment of nosocomial pneumonia was created. Publicly available cost, efficacy, and utility data populated relevant model variables. A probabilistic sensitivity analysis varied parameters in 10,000 Monte-Carlo simulations, and univariate sensitivity analyses assessed the impact of model uncertainties and the robustness of our conclusions. Results indicated that the cost per quality-adjusted life-year (QALY) increased 6% ($22,594 vs. $23,860) by using linezolid versus vancomycin for nosocomial pneumonia. The incremental cost per QALY gained by using linezolid over vancomycin was $6,089, and the incremental cost per life saved was $68,615 with the use of linezolid. Vancomycin dominated linezolid in the subset of patients with documented MRSA. The incremental cost per QALY gained using linezolid if no mortality benefit exists between agents or a 60-day time horizon was analyzed was $19,608,688 and $443,662, respectively. Linezolid may be a cost-effective alternative to vancomycin in the empiric treatment of patients with suspected MRSA nosocomial pneumonia; however, results of our model were highly variable on a number of important variables and assumptions including mortality differences and time frame analyzed. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

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

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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

Use of 8.4% Sodium Bicarbonate in Buffering Commonly Administered Vancomycin Hydrochloride Solutions for Use with Midline or Peripheral Line Catheters.

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Puertos, Enrique; Spencer, Melissa

2015-01-01

The primary objective of this study was to evaluate the use of 8.4% sodium bicarbonate in the buffering of commonly administered vancomycin hydrochloride solutions for use with midline or peripheral line catheters. Nine admixtures of vancomycin hydrochloride were aseptically prepared for this study. Vancomycin hydrochloride solutions were prepared in triplicates in the following strengths, 1 gram, 2 grams, and 3 grams, which were added to 250-mL bags of sodium chloride 0.9% injection (with overfill). To each prepared solution of vancomycin hydrochloride, 0.5 mL of 8.4% sodium bicarbonate was added. The pH was measured to obtain a baseline level. At day 9, the pH of each sample was measured and compared to those at baseline. The osmolality of each sample was also measured. There was no statistical difference in the pH at baseline and at day 9 (α = 0.05, P = 0.347). A solution of vancomycin hydrochloride that is compounded in 250 mL of sodium chloride 0.9% injection (including overfill) and buffered with 0.5 mL of 8.4% sodium bicarbonate maintained a pH in the range of 5 to 9 and an osmolality in the range of 150 mOsm/kg to 500 mOsm/kg.

Lavage with allicin in combination with vancomycin inhibits biofilm formation by Staphylococcus epidermidis in a rabbit model of prosthetic joint infection.

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Haohan Zhai

Full Text Available BACKGROUND AND AIM: The present anti-infection strategy for prosthetic joint infections (PJI includes the use of antibiotics and surgical treatments, but the bacterial eradication rates are still low. One of the major challenges is the formation of biofilm causing poor bacterial eradication. Recently it has been reported that allicin (diallyl thiosulphinate, an antibacterial principle of garlic, can inhibit bacteria adherence and prevent biofilm formation in vitro. However, whether allicin could inhibit biofilm formation in vivo is unknown. The aim of this study was to investigate the effects of allicin on biofilm formation, and whether allicin could potentiate the bactericidal effect of vancomycin in a rabbit PJI model. METHODS: A sterile stainless-steel screw with a sterile ultra-high molecular weight polyethylene washer was inserted into the lateral femoral condyle of the right hind knee joint of rabbit, and 1 mL inoculum containing 104 colony-forming units of Staphylococcus epidermidis was inoculated into the knee joint (n = 32. Fourteen days later, rabbits randomly received one of the following 4 treatments using continuous lavages: normal saline, vancomycin (20 mcg/mL, allicin (4 mg/L, or allicin (4 mg/L plus vancomycin (20 mcg/mL. Three days later, the washer surface biofilm formation was examined by scanning electron microscopy (SEM. The bacterial counts within the biofilm of implanted screws were determined by bacterial culture. RESULTS: The lowest number of viable bacterial counts of Staphylococcus epidermidis recovered from the biofilm was in the rabbits treated with allicin plus vancomycin (P<0.01 vs. all other groups. The biofilm formation was significantly reduced or undetectable by SEM in rabbits receiving allicin or allicin plus vancomycin. CONCLUSION: Intra-articular allicincan inhibit biofilm formation and enhance the bactericidal effect of vancomycin on implant surface in vivo. Allicin in combination with vancomycin may be

Direct replacement of antibodies with molecularly imprinted polymer nanoparticles in ELISA--development of a novel assay for vancomycin.

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Chianella, Iva; Guerreiro, Antonio; Moczko, Ewa; Caygill, J Sarah; Piletska, Elena V; De Vargas Sansalvador, Isabel M Perez; Whitcombe, Michael J; Piletsky, Sergey A

2013-09-03

A simple and straightforward technique for coating microplate wells with molecularly imprinted polymer nanoparticles (nanoMIPs) to develop assays similar to the enzyme-linked immunosorbent assay (ELISA) is presented here for the first time. NanoMIPs were synthesized by a solid-phase approach with an immobilized vancomycin (template) and characterized using Biacore 3000, dynamic light scattering, and electron microscopy. Immobilization, blocking, and washing conditions were optimized in microplate format. The detection of vancomycin was achieved in competitive binding experiments with a horseradish peroxidase-vancomycin conjugate. The assay was capable of measuring vancomycin in buffer and in blood plasma within the range of 0.001-70 nM with a detection limit of 0.0025 nM (2.5 pM). The sensitivity of the assay was 3 orders of magnitude better than a previously described ELISA based on antibodies. In these experiments, nanoMIPs have shown high affinity and minimal interference from blood plasma components. Immobilized nanoMIPs were stored for 1 month at room temperature without any detrimental effects to their binding properties. The high affinity of nanoMIPs and the lack of a requirement for cold chain logistics make them an attractive alternative to traditional antibodies used in ELISA.

Antimicrobial susceptibility against penicillin, ampicillin and vancomycin of viridans group Streptococcus in oral microbiota of patients at risk of infective endocarditis.

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Süzük, Serap; Kaşkatepe, Banu; Çetin, Mustafa

2016-09-01

The viridans group Streptococci (VGS) are most abundant in the mouth; in some instances they might emerge as pathogens particularly in infective endocarditis (IE). In this study, we aimed to define and determine the susceptibility against antibiotics of VGS that are members of the oral microbiota of patients exhibiting a risk of developing IE. Forty-nine patients at risk of infective endocarditis were included in the study. Identification of the bacteria was performed using API STREP (bioMérieux, France). Gradient test strips (E-Test, France) were used to determine MIC of the bacteria against penicillin, ampicillin, and vancomycin. The distribution of the isolated VGS groups was determined as follows: Streptococcus mitis 32.6% and anginosus group - 32.6%, S. sanguinis group - 16.3%, S. mutans group - 12.2%, and S. salivarius group - 6.1%. The rates of resistance and reduced sensitivity of the isolates for penicillin and ampicillin were determined at 61.2% and 55.1%, respectively. However, all isolates were found to be susceptible to vancomycin. We conclude that the antimicrobial resistance of VGS should be determined on a regular basis locally, and decisions on therapeutic and prophylactic interventions should be given taking this resistance into consideration.

Vancomycin analogues containing monosaccharides exhibit improved antibiotic activity: a combined one-pot enzymatic glycosylation and chemical diversification strategy.

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Thayer, Desiree A; Wong, Chi-Huey

2006-09-18

Many natural products contain carbohydrate moieties that contribute to their biological activity. Manipulation of the carbohydrate domain of natural products through multiple glycosylations to identify new derivatives with novel biological activities has been a difficult and impractical process. We report a practical one-pot enzymatic approach with regeneration of cosubstrates to synthesize analogues of vancomycin that contain an N-alkyl glucosamine, which exhibited marked improvement in antibiotic activity against a vancomycin-resistant strain of Enterococcus.

An economic model to compare linezolid and vancomycin for the treatment of confirmed methicillin-resistant Staphylococcus aureus nosocomial pneumonia in Germany

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Patel DA

2014-10-01

Full Text Available Dipen A Patel,1 Andre Michel,2 Jennifer Stephens,1 Bertram Weber,3 Christian Petrik,4 Claudie Charbonneau5 1Health Economic and Outcomes Research, Pharmerit International, Bethesda, MD, USA; 2Klinikum Hanau GmbH, Hanau, Germany; 3Health Technology Assessment and Outcomes Research, 4Anti-infectives, Pfizer, Berlin, Germany; 5Pfizer International Operations, Pfizer France, Paris, France Background: Across Europe, methicillin-resistant Staphylococcus aureus (MRSA is considered to be the primary cause of nosocomial pneumonia (NP. In Germany alone, approximately 14,000 cases of MRSA-associated NP occur annually, which may have a significant impact on health care resource use and associated economic costs. The objective of this study was to investigate the economic impact of linezolid compared with that of vancomycin in the treatment of hospitalized patients with MRSA-confirmed NP in the German health care system. Methods: A 4-week decision tree model incorporated published data and expert opinion on clinical parameters, resource use, and costs (2012 euros was constructed. The base case first-line treatment duration for patients with MRSA-confirmed NP was 10 days. Treatment success (survival, failure due to lack of efficacy, serious adverse events, and mortality were possible outcomes that could impact costs. Alternate scenarios were analyzed, such as varying treatment duration (7 or 14 days or treatment switch due to a serious adverse event/treatment failure (at day 5 or 10. Results: The model calculated total base case inpatient costs of €15,116 for linezolid and €15,239 for vancomycin. The incremental cost-effectiveness ratio favored linezolid (versus vancomycin, with marginally lower costs (by €123 and greater efficacy (+2.7% absolute difference in the proportion of patients successfully treated for MRSA NP. Approximately 85%–87% of the total treatment costs were attributed to hospital stay (primarily in the intensive care unit

Efficacy and Safety of Metronidazole Monotherapy versus Vancomycin Monotherapy or Combination Therapy in Patients with Clostridium difficile Infection: A Systematic Review and Meta-Analysis.

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Rui Li

Full Text Available Clostridium difficile infection (CDI has become a global epidemiological problem for both hospitalized patients and outpatients. The most commonly used drugs to treat CDI are metronidazole and vancomycin. The aim of this study was to compare the efficacy and safety of metronidazole monotherapy with vancomycin monotherapy and combination therapy in CDI patients.A comprehensive search without publication status or other restrictions was conducted. Studies comparing metronidazole monotherapy with vancomycin monotherapy or combination therapy in patients with CDI were considered eligible. Meta-analysis was performed using the Mantel-Haenszel fixed-effects model, and odds ratios (ORs with 95% confidence intervals (95% CIs were calculated and reported.Of the 1910 records identified, seventeen studies from thirteen articles (n = 2501 patients were included. No statistically significant difference in the rate of clinical cure was found between metronidazole and vancomycin for mild CDI (OR = 0.67, 95% CI (0.45, 1.00, p = 0.05 or between either monotherapy and combination therapy for CDI (OR = 1.07, 95% CI (0.58, 1.96, p = 0.83; however, the rate of clinical cure was lower for metronidazole than for vancomycin for severe CDI (OR = 0.46, 95% CI (0.26, 0.80, p = 0.006. No statistically significant difference in the rate of CDI recurrence was found between metronidazole and vancomycin for mild CDI (OR = 0.99, 95% CI (0.40, 2.45, p = 0.98 or severe CDI (OR = 0.98, 95% CI (0.63, 1.53, p = 0.94 or between either monotherapy and combination therapy for CDI (OR = 0.91, 95% CI (0.66, 1.26, p = 0.56. In addition, there was no significant difference in the rate of adverse events (AEs between metronidazole and vancomycin (OR = 1.18, 95% CI (0.80, 1.74, p = 0.41. In contrast, the rate of AEs was significantly lower for either monotherapy than for combination therapy (OR = 0.30, 95% CI (0.17, 0.51, p < 0.0001.Metronidazole and vancomycin are equally effective for the

Observed Antagonistic Effect of Linezolid on Daptomycin or Vancomycin Activity against Biofilm-Forming Methicillin-Resistant Staphylococcus aureus in an In Vitro Pharmacodynamic Model

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Luther, Megan K.

2015-01-01

Pharmacodynamic activity in antibiotic combinations of daptomycin, vancomycin, and linezolid was investigated in a 48-h in vitro pharmacodynamic model. Using human-simulated free drug concentrations, activity against clinical biofilm-forming methicillin-resistant Staphylococcus aureus isolates was evaluated. Linezolid antagonized vancomycin activity at 24 and 48 h. Linezolid antagonized daptomycin at 24 and 48 h depending on dose and strain. Adding daptomycin increased vancomycin activity at 48 h (P < 0.03). These results may be strain dependent and require further clinical investigation. PMID:26369963

Effect of amikacin, cephalothin, clindamycin and vancomycin on in vitro fibroblast growth

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Fernanda Timm Seabra Souza

2004-01-01

Full Text Available The effect of four antibiotics (amikacin, clindamycin, cephalothin and vancomycin was investigated considering that bacterial infection in fibroblasts cultures is a very frequent event. The investigation included the effect of the antibiotics on fibroblast growth and on the activity of the enzyme glucocerebrosidase. The antibiotics were added to the fibroblast cultures and cell growth was evaluated by counting the number of cells and their viability. After cell harvesting, the enzyme activity and content of protein were measured. The results allowed us to conclude that none of the antibiotics affected the cellular number nor the cellular viability. The content of protein decreased when cephalothin and clindamycin were added to the cultures, and glucocerebrosidase was affected in the presence of amikacin. Vancomycin did not interfere with any of the parameters analyzed, so it was chosen to be used in cell cultures to prevent the contamination by gram positive bacteria.

AUC/MIC Pharmacodynamic Target Is Not a Good Predictor of Vancomycin Efficacy in Methicillin-Resistant Staphylococcus aureus Experimental Endocarditis.

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Castañeda, Ximena; García-de-la-Mària, Cristina; Gasch, Oriol; Pericas, Juan M; Armero, Yolanda; Soy, Dolors; García-González, Javier; Falces, Carlos; Ninot, Salvador; Almela, Manel; Ambrosioni, Juan; Quintana, Eduardo; Vidal, Barbara; Fuster, David; Llopis, Jaume; Soto, Sara; Moreno, Asuncion; Marco, Francesc; Miró, Jose M

2017-06-01

The aim of this in vivo study was to compare the efficacy of vancomycin at standard doses (VAN-SD) to that of VAN at adjusted doses (VAN-AD) in achieving a VAN area under the curve/MIC ratio (AUC/MIC) of ≥400 against three methicillin-resistant Staphylococcus aureus (MRSA) strains with different microdilution VAN MICs in an experimental endocarditis model. The valve vegetation bacterial counts after 48 h of VAN therapy were compared, and no differences were observed between the two treatment groups for any of the three strains tested. Overall, for VAN-SD and VAN-AD, the rates of sterile vegetations were 15/45 (33.3%) and 21/49 (42.8%) ( P = 0.343), while the medians (interquartile ranges [IQRs]) for log 10 CFU/g of vegetation were 2 (0 to 6.9) and 2 (0 to 4.5) ( P = 0.384), respectively. In conclusion, this VAN AUC/MIC pharmacodynamic target was not a good predictor of vancomycin efficacy in MRSA experimental endocarditis. Copyright © 2017 American Society for Microbiology.

Healthcare-associated vancomycin resistant Enterococcus faecium infections in the Mansoura University Hospitals intensive care units, Egypt

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Dalia Moemen

2015-09-01

Full Text Available Vancomycin resistant Enterococcus faecium (VREF ia an emerging and challenging nosocomial pathogen. This study aimed to determine the prevalence, risk factors and clonal relationships between different VREF isolates in the intensive care units (ICUs of the university hospitals in our geographic location. This prospective study was conducted from July, 2012 until September, 2013 on 781 patients who were admitted to the ICUs of the Mansoura University Hospitals (MUHs, and fulfilled the healthcare-associated infection (HAI criteria. Susceptibility testing was determined using the disk diffusion method. The clonal relationships were evaluated with pulsed field gel electrophoresis (PFGE. Out of 52 E. faecium isolates, 12 (23.1% were vancomycin resistant. The significant risk factors for the VREF infections were: transfer to the ICU from a ward, renal failure, an extended ICU stay and use of third-generation cephalosporins, gentamicin, or ciprofloxacin. PFGE with the 12 isolates showed 9 different patterns; 3 belonged to the same pulsotype and another 2 carried a second pulsotypes. The similar pulsotypes isolates were isolated from ICUs of one hospital (EICUs; however, all of the isolates from the other ICUs had different patterns. Infection control policy, in conjunction with antibiotic stewardship, is important to combat VREF transmission in these high-risk patients.

Bacillus coagulans GBI-30, 6086 limits the recurrence of Clostridium difficile-Induced colitis following vancomycin withdrawal in mice

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2012-01-01

Background Recently, we found that the probiotic strain Bacillus coagulans GBI-30, 6086 (GanedenBC30) improved indices of Clostridium difficile (C. difficile)-induced colitis in mice (Fitzpatrick et al., Gut Pathogens, 2011). Our goal was to determine if BC30 could also prevent the recurrence of C. difficile-induced colitis in mice, following initial treatment with vancomycin. During study days 0 through 5, mice were treated with antibiotics. On day 6, the C. difficile strain VPI 10463 was given by oro-gastric gavage at ≈ 5x104 CFU to induce colitis. Mice were treated on study days 6 to 10 with vancomycin (50 mg/kg) (vanco) or vehicle (saline) by gavage. On days 10 to16, mice were dosed by gavage with saline vehicle or BC30 (2 x 109 CFU per day). Mice were monitored for mortality, weight loss and diarrhea. On study days 14, 16 and 17, stools and colons were collected for analyzing other parameters of colitis. Results The mean stool consistency score in Vehicle/C.difficile/Vanco mice increased from 0.4 (day 10) to a range of 1.1 to 1.4 (days 14 to 17), indicating the recurrence of colitis. On days 13 through 17, the stool consistency scores for the vancomycin/BC30 mice were significantly lower (p< 0.05) than for the vancomycin/vehicle cohort of animals. On day 17, 88.9% of mice treated with BC30 had normal stools, while this value was 0% with vehicle treatment (p value = 0.0004). Colonic myeloperoxidase (Units/2 cm colon) was significantly (p < 0.05) reduced from 4.3 ± 0.7 (Vehicle/C.difficile/Vanco) to 2.6 ± 0.2 (BC30/C. Difficle/Vanco). The colonic histology score and Keratinocyte derived-chemokine level in the colon were also lower in BC30 treated mice. Summary In BC30-treated mice, there was evidence of better stool consistency, as well as improved biochemical and histological indices of colitis, following initial treatment of animals with vancomycin. Conclusion BC30 limited the recurrence of CD-induced colitis following vancomycin withdrawal in mice. PMID

Bacillus coagulans GBI-30, 6086 limits the recurrence of Clostridium difficile-Induced colitis following vancomycin withdrawal in mice.

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Fitzpatrick, Leo R; Small, Jeffrey S; Greene, Wallace H; Karpa, Kelly D; Farmer, Sean; Keller, David

2012-10-22

Recently, we found that the probiotic strain Bacillus coagulans GBI-30, 6086 (GanedenBC30) improved indices of Clostridium difficile (C. difficile)-induced colitis in mice (Fitzpatrick et al., Gut Pathogens, 2011). Our goal was to determine if BC30 could also prevent the recurrence of C. difficile-induced colitis in mice, following initial treatment with vancomycin. During study days 0 through 5, mice were treated with antibiotics. On day 6, the C. difficile strain VPI 10463 was given by oro-gastric gavage at ≈ 5x104 CFU to induce colitis. Mice were treated on study days 6 to 10 with vancomycin (50 mg/kg) (vanco) or vehicle (saline) by gavage. On days 10 to16, mice were dosed by gavage with saline vehicle or BC30 (2 x 109 CFU per day). Mice were monitored for mortality, weight loss and diarrhea. On study days 14, 16 and 17, stools and colons were collected for analyzing other parameters of colitis. The mean stool consistency score in Vehicle/C.difficile/Vanco mice increased from 0.4 (day 10) to a range of 1.1 to 1.4 (days 14 to 17), indicating the recurrence of colitis. On days 13 through 17, the stool consistency scores for the vancomycin/BC30 mice were significantly lower (p< 0.05) than for the vancomycin/vehicle cohort of animals. On day 17, 88.9% of mice treated with BC30 had normal stools, while this value was 0% with vehicle treatment (p value = 0.0004). Colonic myeloperoxidase (Units/2 cm colon) was significantly (p < 0.05) reduced from 4.3 ± 0.7 (Vehicle/C.difficile/Vanco) to 2.6 ± 0.2 (BC30/C. Difficle/Vanco). The colonic histology score and Keratinocyte derived-chemokine level in the colon were also lower in BC30 treated mice. In BC30-treated mice, there was evidence of better stool consistency, as well as improved biochemical and histological indices of colitis, following initial treatment of animals with vancomycin. BC30 limited the recurrence of CD-induced colitis following vancomycin withdrawal in mice.

Modeling the economic impact of linezolid versus vancomycin in confirmed nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus.

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Patel, Dipen A; Shorr, Andrew F; Chastre, Jean; Niederman, Michael; Simor, Andrew; Stephens, Jennifer M; Charbonneau, Claudie; Gao, Xin; Nathwani, Dilip

2014-07-22

We compared the economic impacts of linezolid and vancomycin for the treatment of hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA)-confirmed nosocomial pneumonia. We used a 4-week decision tree model incorporating published data and expert opinion on clinical parameters, resource use and costs (in 2012 US dollars), such as efficacy, mortality, serious adverse events, treatment duration and length of hospital stay. The results presented are from a US payer perspective. The base case first-line treatment duration for patients with MRSA-confirmed nosocomial pneumonia was 10 days. Clinical treatment success (used for the cost-effectiveness ratio) and failure due to lack of efficacy, serious adverse events or mortality were possible clinical outcomes that could impact costs. Cost of treatment and incremental cost-effectiveness per successfully treated patient were calculated for linezolid versus vancomycin. Univariate (one-way) and probabilistic sensitivity analyses were conducted. The model allowed us to calculate the total base case inpatient costs as $46,168 (linezolid) and $46,992 (vancomycin). The incremental cost-effectiveness ratio favored linezolid (versus vancomycin), with lower costs ($824 less) and greater efficacy (+2.7% absolute difference in the proportion of patients successfully treated for MRSA nosocomial pneumonia). Approximately 80% of the total treatment costs were attributed to hospital stay (primarily in the intensive care unit). The results of our probabilistic sensitivity analysis indicated that linezolid is the cost-effective alternative under varying willingness to pay thresholds. These model results show that linezolid has a favorable incremental cost-effectiveness ratio compared to vancomycin for MRSA-confirmed nosocomial pneumonia, largely attributable to the higher clinical trial response rate of patients treated with linezolid. The higher drug acquisition cost of linezolid was offset by lower treatment failure

Persistence of vancomycin-resistant enterococci (VRE) in broiler houses after the avoparcin ban

DEFF Research Database (Denmark)

Heuer, Ole Eske; Pedersen, Karl; Jensen, Lars Bogø

2002-01-01

The glycopeptide growth promoter avoparcin was banned from animal production in the EU in 1997 due to concern for the spread of vancomycin-resistant enterococci (VRE) from food animals to humans. In recent Norwegian and Danish studies, extensive occurrence of VRE on broiler farms and in broiler......, and disinfection of the houses between rotations, and two consecutive broiler flocks from each house were sampled by taking cloacal swabs from the broilers at the time of slaughter. A total of 69 vancomycin-resistant Enterococcus faecium isolates obtained from broiler flocks and broiler houses were subjected......-isolates from different broiler houses and from flocks reared in different houses appeared to be genetically unrelated. These findings indicated that VRE was transmitted between consecutive broiler flocks by clones of resistant. bacteria surviving in the broiler houses despite cleaning and disinfection between...

In vitro activities of ramoplanin, teicoplanin, vancomycin, linezolid, bacitracin, and four other antimicrobials against intestinal anaerobic bacteria.

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Citron, D M; Merriam, C V; Tyrrell, K L; Warren, Y A; Fernandez, H; Goldstein, E J C

2003-07-01

By using an agar dilution method, the in vitro activities of ramoplanin, teicoplanin, vancomycin, linezolid, and five other agents were determined against 300 gram-positive and 54 gram-negative strains of intestinal anaerobes. Ramoplanin was active at Eubacterium, Actinomyces, Propionibacterium, and Peptostreptococcus spp. were inhibited by spp. were >or=256 microg/ml. Ramoplanin displays excellent activity against C. difficile and other gram-positive enteric anaerobes, including vancomycin-resistant strains; however, it has poor activity against most gram-negative anaerobes and thus potentially has a lesser effect on the ecological balance of normal fecal flora.

Wounds, Functional Disability, and Indwelling Devices Are Associated With Cocolonization by Methicillin-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococci in Southeast Michigan

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Flannery, Erika L.; Wang, Linda; Zöllner, Sebastian; Foxman, Betsy; Mobley, Harry L. T.; Mody, Lona

2011-01-01

Cocolonization with methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) is a precursor to vancomycin-resistant S. aureus emergence. MRSA/VRE cocolonization incidence is higher among skilled nursing facility residents with functional disability and indwelling devices and occurs more frequently in wounds than other anatomical sites.

Direct replacement of antibodies with molecularly imprinted polymer (MIP) nanoparticles in ELISA – development of a novel assay for vancomycin

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Chianella, Iva; Guerreiro, Antonio; Moczko, Ewa; Caygill, J. Sarah; Piletska, Elena V.; Perez De Vargas Sansalvador, Isabel M.; Whitcombe, Michael J.; Piletsky, Sergey A.

2016-01-01

A simple and straightforward technique for coating microplate wells with molecularly imprinted polymer nanoparticles (nanoMIPs) to develop ELISA type assays is presented here for the first time. NanoMIPs were synthesized by a solid phase approach with immobilized vancomycin (template) and characterized using Biacore 3000, dynamic light scattering and electron microscopy. Immobilization, blocking and washing conditions were optimized in microplate format. The detection of vancomycin was achieved in competitive binding experiments with a HRP-vancomycin conjugate. The assay was capable of measuring vancomycin in buffer and in blood plasma within the range 0.001-70 nM with a detection limit of 0.0025 nM (2.5 pM). The sensitivity of the assay was three orders of magnitude better than a previously described ELISA based on antibodies. In these experiments nanoMIPs have shown high affinity and minimal interference from blood plasma components. Immobilized nanoMIPs were stored for 1 month at room temperature without any detrimental effects to their binding properties. The high affinity of nanoMIPs and the lack of a requirement for cold chain logistics make them an attractive alternative to traditional antibodies used in ELISA. PMID:23947402

Dispersion of the vancomycin resistance genes vanA and vanC of Enterococcus isolated from Nile tilapia on retail sale: A public health hazard

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Kamelia Mahmoud Osman

2016-08-01

Full Text Available Although normally regarded harmless commensals, enterococci may cause a range of different infections in humans, including urinary tract infections, sepsis, and endocarditis. The acquisition of vancomycin resistance by enterococci (VRE has seriously affected the treatment and infection control of these organisms. VRE are frequently resistant to all antibiotics that are effective treatment for vancomycin-susceptible enterococci, which leaves clinicians treating VRE infections with limited therapeutic options. With VRE emerging as a global threat to public health, we aimed to isolate, identify enterococci species from tilapia and their resistance to van-mediated glycopeptide (vanA and vanC as well as the presence of enterococcal surface protein (esp using conventional and molecular methods. The cultural, biochemical (Vitek 2 system and PCR results revealed eight Enterococcus isolates from the 80 fish samples (10% to be further identified as E. faecalis (6/8, 75% and E gallinarum (2/8, 25%. Intraperitoneal injection of healthy Nile tilapia with the eight Enterococcus isolates caused significant morbidity (70% within 3 days and 100% mortality at 6 days post injection with general signs of septicemia. All of the eight Enterococcus isolates were found to be resistant to tetracycline. The 6/6 E. faecalis isolates were susceptible for penicillin, nitrofurantoin, gentamicin, and streptomycin. On the other hand 5/6 were susceptible for ampicillin, vancomycin, chloramphenicol and ciprofloxacin. The two isolates of E. gallinarum were sensitive to rifampicin and ciprofloxacin and resistant to vancomycin, chloramphenicol and erythromycin. Molecular characterization proved that they all presented the prototypic vanC element. On the whole, one of the two vancomycin resistance gene was present in 3/8 of the enterococci isolates, while the esp virulence gene was present in 1/8 of the enterococci isolates. The results in this study emphasise the potential role

Pharmacist-led implementation of a vancomycin guideline across medical and surgical units: impact on clinical behavior and therapeutic drug monitoring outcomes

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Phillips CJ

2015-10-01

Full Text Available Cameron J Phillips,1–3 David L Gordon3,4 1Division of Pharmacy, SA Pharmacy, Flinders Medical Centre, Bedford Park, 2School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, 3Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University, Adelaide, 4Department of Microbiology and Infectious Diseases, SA Pathology, Flinders Medical Centre, Bedford Park, SA, Australia Background: Vancomycin is the antibiotic of choice for the treatment of serious infections such as methicillin-resistant Staphylococcus aureus (MRSA. Inappropriate prescribing of vancomycin can lead to therapeutic failure, antibiotic resistance, and drug toxicity. Objective: To examine the effectiveness of pharmacist-led implementation of a clinical practice guideline for vancomycin dosing and monitoring in a teaching hospital. Methods: An observational pre–post study design was undertaken to evaluate the implementation of the vancomycin guideline. The implementation strategy principally involved education, clinical vignettes, and provision of pocket guidelines to accompany release of the guideline to the hospital Intranet. The target cohort for clinical behavioral change was junior medical officers, as they perform the majority of prescribing and monitoring of vancomycin in hospitals. Assessment measures were recorded for vancomycin prescribing, therapeutic drug monitoring, and patient outcomes. Results: Ninety-nine patients, 53 pre- and 46 post-implementation, were included in the study. Prescribing of a loading dose increased from 9% to 28% (P=0.02, and guideline adherence to starting maintenance dosing increased from 53% to 63% (P=0.32. Dose adjustment by doctors when blood concentrations were outside target increased from 53% to 71% (P=0.12, and correct timing of initial concentration measurement increased from 43% to 57% (P=0.23. Appropriately timed trough concentrations improved from 73% to 81% (P=0.08. Pre-dose (trough

Weissella confusa: a rare cause of vancomycin-resistant Gram-positive bacteraemia.

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Kumar, Anil; Augustine, Deepthi; Sudhindran, S; Kurian, Anu M; Dinesh, Kavitha R; Karim, Shamsul; Philip, Rosamma

2011-10-01

We describe a case of bacteraemia caused by Weissella confusa in a 48-year-old male who was operated on for adenocarcinoma of the gastro-oesophageal junction and maintained on total parenteral nutrition. Blood cultures were positive for a vancomycin-resistant streptococcus-like organism which was identified as W. confusa by 16S rRNA gene sequencing.

Fidaxomicin versus Vancomycin as a First-Line Treatment for Clostridium difficile-Associated Diarrhea in Specific Patient Populations: A Pharmacoeconomic Evaluation.

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Reveles, Kelly R; Backo, Jennifer L; Corvino, Frank A; Zivkovic, Marko; Broderick, Kelly C

2017-12-01

The reduction in recurrent Clostridium difficile-associated diarrhea (CDAD) with fidaxomicin therapy may reduce hospital readmissions and lead to lower overall CDAD costs. However, studies assessing the cost-effectiveness of fidaxomicin as first-line therapy from the U.S. hospital perspective are lacking. This study evaluated the costs associated with utilizing fidaxomicin or vancomycin as a first-line therapy for CDAD in specific patient populations from a U.S. hospital perspective. A decision-analytic model was developed to estimate total costs (hospitalization and drug costs) associated with using fidaxomicin or vancomycin as first-line therapy for a first episode and up to two recurrences of CDAD in five patient populations: general population, elderly, patients receiving concomitant antibiotics, and patients with renal impairment or cancer. The total cost of CDAD treatment using fidaxomicin first line in the general population was $14,442 per patient versus $14,179 per patient with vancomycin first line. In subgroup analyses, fidaxomicin use resulted in total hospital cost savings of $616 per patient in patients with cancer and $312 in patients with concomitant antibiotic use; vancomycin use was associated with total hospital cost savings of $243 per patient in the elderly and $371 in patients with renal impairment. Fidaxomicin as first-line CDAD therapy is associated with similar total costs as compounded vancomycin oral solution in the general population. In elderly and renally impaired patients, slight increases in hospital cost were observed with fidaxomicin therapy, and in patients with cancer or concomitant antibiotic use, hospital cost savings were observed. © 2017 Pharmacotherapy Publications, Inc.

Release of Gentamicin and Vancomycin from Preformed Spacers in Infected Total Hip Arthroplasties: Measurement of Concentrations and Inhibitory Activity in Patients’ Drainage Fluids and Serum

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Dario Regis

2013-01-01

Full Text Available Gentamicin (G and vancomycin (V concentrations in drainage fluids obtained from patients during the first 24 hours after implantation of antibiotic-loaded polymethylmethacrylate (PMMA spacers in two-stage revision of infected total hip arthroplasty were studied. The inhibitory activity of drainage fluids against different multiresistant clinical isolates was investigated as well. Seven hips were treated by implantation of industrial G-loaded spacers. Vancomycin was added by manually mixing with PMMA bone cement. Serum and drainage fluid samples were collected 1, 4, and 24 hours after spacer implantation. Antibiotics concentrations and drains bactericidal titer of combination were determined against multiresistant staphylococcal strains. The release of G and V from PMMA cement at the site of infection was prompt and effective. Serum levels were below the limit of detection. The local release kinetics of G and V from PMMA cement was similar, exerting a pronounced, combined inhibitory effect in the implant site. The inhibitory activity of drainage fluids showed substantial intersubject variability related to antibiotic concentrations and differed according to the pathogens tested. Gentamicin and vancomycin were released from temporary hip spacers at bactericidal concentrations, and their use in combination exerted strong inhibition against methicillin-resistant S. aureus and Coagulase Negative Staphylococci strains.

The potential of vancomycin-resistant enterococci to persist in fermented and pasteurised meat products.

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Houben, J H

2003-11-15

Experiments with 148 isolates of vancomycin-resistant enterococci (VRE) were performed to assess their potential to persist and grow in fermented sausages and pasteurised meat products. All strains were meat isolates and Van-type A, except a single VanC1 strain. In total, 143 strains of Enterococcus faecium were involved. Eight selected strains were examined for their potential to grow at high salt and nitrite levels and at reduced pH. The same isolates were used in experiments with fermented sausages. All available strains were subjected to heating tests in meat suspensions with added curing ingredients. All but one of the eight tested isolates grew at pH 4.0 in tryptone soya broth (TSB). With the combination of 8% w/w NaCl, 400 ppm NaNO2 and 0.5% w/w glucose in the meat suspension, all isolates grew at 37 degrees C, whereas none grew at 7 degrees C even after 56 days. With the addition of 10% w/w NaCl, 200 ppm NaNO2 and 0.5% w/w glucose, still one E. faecium isolate grew at 37 degrees C, although very slowly. Overall, the strains tolerated high salt and nitrite concentrations and reduced pH very well, even beyond levels applied in the regular production of fermented and/or pasteurised meat products. The tested strains could be isolated after the fermentation and further ripening of "boerenmetworst" and "snijworst". Overall, their colony counts decreased on average about 1 log-unit over a period of 60 days after batter manufacture. All 148 isolates demonstrated a relatively weak thermal resistance compared to results for selected vancomycin-sensitive enterococci strains reported in the literature and to results collected under identical experimental conditions in this laboratory. None of the strains (log inoculation level about 5-6 ml(-1) for each isolate) could be cultured after heating at 70 degrees C for 10 min.

An investigation of vancomycin minimum inhibitory concentration creep among methicillin-resistant Staphylococcus aureus strains isolated from pediatric patients and healthy children in Northern Taiwan

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Chia-Ning Chang

2017-06-01

Conclusion: Vancomycin MIC creeps existed in both clinical MRSA isolates and colonized MRSA strains. Great diversity of PFGE typing was in both strains collected. There was no association between the clinical and colonized MRSA isolates with vancomycin MIC creep.

Long-term Conventionally Dosed Vancomycin Therapy In Patients With Orthopaedic Implant-related Infections Seems As Effective And Safe As Long-term Penicillin Or Clindamycin Therapy. A Retrospective Cohort Study Of 103 Patients.

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Aleman, Jacomien; Moojen, Dirk Jan F; van Ogtrop, Marc L; Poolman, Rudolf W; Franssen, Eric J F

2018-01-01

Objectives : Antimicrobial therapy is one of the cornerstones of orthopaedic implant-related infections (OIRI) treatment. Infections with Gram-positive bacteria are often treated with vancomycin, penicillin or clindamycin. A recent IDSA guideline suggests increasing the dose of vancomycin to increase the trough vancomycin target serum concentrations. This is deemed necessary because of an observed decrease in vancomycin susceptibility among Gram-positive bacteria. However, elevated vancomycin concentrations are correlated with the risk of nephrotoxicity, especially with prolonged therapy. Compared to most countries, rates of resistance against antibiotics among bacteria in the Netherlands are lower for currently available antibiotics, therefore lower target concentrations of vancomycin are probably efficacious for the treatment of infections. In this study we evaluated the efficacy and safety of long-term conventionally dosed vancomycin therapy, as an initial therapy for OIRI, and compared this with long-term penicillin and clindamycin therapy, as initial therapy, in patients with Gram-positive orthopaedic implant-related infections. Methods : A retrospective, observational study was conducted in 103 adult patients treated for OIRI, with vancomycin, penicillin or clindamycin for at least 10 days. The target trough serum concentration of vancomycin was 10-15 mg/l. Results : 74% of our patients were treated successfully with vancomycin, as initial therapy, (no reinfection within 1 year) versus 55% of our patients treated with either an antibiotic of the penicillin class (mostly flucloxacillin) or clindamycin (p=0.08), as initial therapy. For patients treated with vancomycin we observed a serum creatinine increase of 6 μmol/l, for patients treated with either an antibiotic of the penicillin class or clindamycin the serum creatinine increase was 4 μmol/l (p=0.395). Conclusions : In our population of patients with OIRI long-term treatment with conventionally dosed

Cost-effectiveness analysis on the use of fidaxomicin and vancomycin to treat Clostridium difficile infection in France.

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Watt, Maureen; Dinh, Aurélien; Le Monnier, Alban; Tilleul, Patrick

2017-07-01

Fidaxomicin is a macrocyclic antibiotic with proven efficacy against Clostridium difficile infection (CDI) in adults. It was licensed in France in 2012, but, due to higher acquisition costs compared with existing treatments, healthcare providers require information on its cost/benefit profile. To compare healthcare costs and health outcomes of fidaxomicin and vancomycin, as reference treatment for CDI. A Markov model was used to simulate the treatment pathway, over 1 year, of adult patients with CDI receiving fidaxomicin or vancomycin. Several patient sub-groups (severe CDI; recurrent CDI; concomitant antibiotics; cancer; renal failure; elderly) were evaluated. Cost-effectiveness was analyzed based on cure and recurrence rates derived from published randomized clinical trials comparing fidaxomicin and vancomycin, and costs calculated from the payer perspective using French hospitalization data and drug cost databases. Model outputs included costs in euros (reference year 2014) and health outcomes (recurrence; sustained cure rates). Alternative scenario and sensitivity analyses were performed using data from other clinical trials in CDI, including one conducted in real-life clinical practice in France. Drug acquisition costs were €1,692 higher in fidaxomicin-treated patients, but this was offset by the lower hospitalization costs with fidaxomicin, which were reduced by €1,722. The reduction in the cost of hospitalization was driven by the significantly lower number of recurrences in fidaxomicin-treated patients, offsetting the acquisition cost of fidaxomicin in all sub-groups except recurrent CDI and concomitant antibiotics. This study demonstrated that, despite higher acquisition costs, the lower recurrence rate with fidaxomicin resulted in cost savings or low incremental costs compared with vancomycin.

Treatment of MRSA pneumonia: Clinical and economic comparison of linezolid vs. vancomycin – a retrospective analysis of medical charts and re-imbursement data of real-life patient populations

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Wilke, Michael H.

2017-01-01

Full Text Available Objectives: To supplement the data collected in randomized clinical trials, the present study in patients with methicillin resistant (MRSA pneumonia was conducted to explore the clinical effectiveness of linezolid and vancomycin in a routine clinical setting. Further, the overall costs of the patients' stay in the intensive care unit (ICU were compared.Methods: This was a retrospective analysis of medical and reimbursement data of adult patients who were treated for MRSA pneumonia with linezolid or vancomycin. Since the subjects were not randomly assigned to treatments, propensity score adjustment was applied to reduce a potential selection bias.Results: In total, 226 patients were included; 95 received linezolid and 131 received vancomycin as initial therapy for MRSA pneumonia. Switches to another antibiotic were observed in 4 patients (4.2% receiving linezolid and in 23 patients (17.6% receiving vancomycin (logistic regression analysis; odds ratio linezolid/vancomycin: 0.183; 95% confidence interval [CI]: 0.052–0.647; p<0.01. All-cause in-hospital mortality was also lower in patients receiving linezolid (22 patients [23.2%] vs. 54 patients [41.2%] (logistic regression analysis; odds ratio linezolid/vancomycin: 0.351; 95% CI: 0.184–0.671; p<0.01. The analysis of the total costs of stay in ICU did not reveal any major differences between the two treatment groups (cost ratio linezolid/vancomycin: 1.29; 95% CI: 0.84–1.98; p=0.24.Conclusions: These findings confirm in a routine clinical setting that linezolid is a valuable therapeutic alternative to vancomycin for the treatment of MRSA pneumonia. However, prospective studies in real-life patient populations are warranted.

ISOLATION AND PURIFICATION OF STREPTOMYCES SPP. PRODUCING VANCOMYCIN

International Nuclear Information System (INIS)

EL-KABBANY, H.M.I.

2008-01-01

Soil samples obtained from different governments in Egypt were analyzed to determine the presence of types of antibiotic producing actinomycetes using starch-nitrite agar, starch-casein nitrate agar and Czapek's Dox agar as culture media. Different Streptomyces spp. were isolated. The Streptomyces (S.) isolates encountered were S. violochromogens, S. violaceus-nigar and S. orientalis and known as standard Vancomycin producers. The optimum conditions of S. orientalis; incubation period, initial pH and incubation temperature, were determined. In addition, physical properties; appearance, melting point, solubility, mass spectrophotometer of ultra violet (UV) and the effect of gamma rays, were also determined

Empiric guideline-recommended weight-based vancomycin dosing and mortality in methicillin-resistant Staphylococcus aureus bacteremia: a retrospective cohort study

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Hall Ronald G

2012-04-01

Full Text Available Abstract Background No studies have evaluated the effect of guideline-recommended weight-based dosing on in-hospital mortality of patients with methicillin-resistant Staphylococcus aureus bacteremia. Methods This was a multicenter, retrospective, cohort study of patients with methicillin-resistant Staphylococcus aureus bacteremia receiving at least 48 hours of empiric vancomycin therapy between 01/07/2002 and 30/06/2008. We compared in-hospital mortality for patients treated empirically with weight-based, guideline-recommended vancomycin doses (at least 15 mg/kg/dose to those treated with less than 15 mg/kg/dose. We used a general linear mixed multivariable model analysis with variables identified a priori through a conceptual framework based on the literature. Results A total of 337 patients who were admitted to the three hospitals were included in the cohort. One-third of patients received vancomycin empirically at the guideline-recommended dose. Guideline-recommended dosing was not associated with in-hospital mortality in the univariable (16% vs. 13%, OR 1.26 [95%CI 0.67-2.39] or multivariable (OR 0.71, 95%CI 0.33-1.55 analysis. Independent predictors of in-hospital mortality were ICU admission, Pitt bacteremia score of 4 or greater, age 53 years or greater, and nephrotoxicity. Conclusions Empiric use of weight-based, guideline-recommended empiric vancomycin dosing was not associated with reduced mortality in this multicenter study.

Vancomycin-resistant enterococci (VRE) in broiler flocks 5 years after the avoparcin ban

DEFF Research Database (Denmark)

Heuer, Ole Eske; Pedersen, Karl; Andersen, J.S.

2002-01-01

The glycopeptide growth promoter avoparcin was banned from animal production in Denmark in 1995. In this study, we investigated the occurrence of vancomycin-resistant enterococci (VRE) in broiler flocks in the absence of the selective pressure exerted by the use of avoparcin. One hundred sixty...

Association between Vancomycin Day 1 Exposure Profile and Outcomes among Patients with Methicillin-Resistant Staphylococcus aureus Infective Endocarditis

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Casapao, Anthony M.; Lodise, Thomas P.; Davis, Susan L.; Claeys, Kimberly C.; Kullar, Ravina; Levine, Donald P.

2015-01-01

Given the critical importance of early appropriate therapy, a retrospective cohort (2002 to 2013) was performed at the Detroit Medical Center to evaluate the association between the day 1 vancomycin exposure profile and outcomes among patients with MRSA infective endocarditis (IE). The day 1 vancomycin area under the concentration-time curve (AUC0–24) and the minimum concentration at 24 h (Cmin 24) was estimated for each patient using the Bayesian procedure in ADAPT 5, an approach shown to accurately predict the vancomycin exposure with low bias and high precision with limited pharmacokinetic sampling. Initial MRSA isolates were collected and vancomycin MIC was determined by broth microdilution (BMD) and Etest. The primary outcome was failure, defined as persistent bacteremia (≥7 days) or 30-day attributable mortality. Classification and regression tree analysis (CART) was used to determine the vancomycin exposure variables associated with an increased probability of failure. In total, 139 patients met study criteria; 76.3% had right-sided IE, 16.5% had left-sided IE, and 7.2% had both left and right-sided IE. A total of 89/139 (64%) experienced failure by composite definition. In the CART analysis, failure was more pronounced in patients with an AUC0–24/MIC as determined by BMD of ≤600 relative to those with AUC0–24/MIC as determined by BMD of >600 (69.8% versus 54.7%, respectively, P = 0.073). In the logistic regression analysis, an AUC/MIC as determined by BMD of ≤600 (adjusted odds ratio, 2.3; 95% confidence interval, 1.01 to 5.37; P = 0.047) was independently associated with failure. Given the retrospective nature of the present study, further prospective studies are required but these data suggest that patients with an AUC0–24/MIC as determined by BMD of ≤600 present an increased risk of failure. PMID:25753631

Clinical study on the incidence of vancomycin intraocular injection in treatment with suppurative endophthalmitis

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Yi-Qin Duan

2015-05-01

Full Text Available AIM:To estimate the clinical significance of the microculture of humor and vitreous and vancomycin intraocular injection in treatment of suppurative endophthalmitis associated with intraocular foreign bodies.METHODS: Totally 65 patients with penetrating eye trauma and retained intraocular foreign bodies in emergency operation and intraocular injection from January 2012 to September 2014 were regarded as the study group, another 62 patients with penetrating eye trauma and retained intraocular foreign bodies in emergency operation without intraocular injection before August 2011 were regarded as the control group. Aqueous humor and vitreous humor were taken from each patient of the study group and the control group for bacteria and fungus cultivation. The study group was treated with 1mg vancomycin intraocular injection after operation, while the control group was not. RESULTS: The incidence of endophthalmitis in the control group was 16%(10 cases, while in the study group was 3%(2 cases, with significant difference between two groups(x2=6.32, PP>0.05. The positive rate of vitreous humor germiculture in study group was 14%(9 cases, and the incidence of endophthalmitis was 3%. The positive rate of vitreous humor germiculture in control group was 11%(7 casesand the incidence of endophthalmitis was 16%, with significant differences between two groups(PCONCLUSION: Intraocular foreign bodies treated with emergency operation and vancomycin intraocular injections can decrease the incidence of suppurative endophthalmitis and have a good vision prognosis for the second stage of operation.

Impact of Serum Vancomycin Trough Levels in the Treatment of Central Nervous System Shunt Infections Caused by Coagulase-Negative Staphylococci.

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Gibson, Ashley; Kaplan, Sheldon L; Vallejo, Jesus G

2018-04-26

Coagulase-negative staphylococci (CoNS) are a common cause of pediatric ventricular shunt infections. The Infectious Diseases Society of America recommends vancomycin serum troughs of 15-20 µg/mL when treating CoNS shunt infections in adult patients. We report a series of pediatric cases of CoNS shunt infections in which clinical cure was obtained with troughs < 15 µg/mL. These findings question the relevance of this recommendation in pediatric patients. © 2018 S. Karger AG, Basel.

Therapeutic Success of Rifaximin for Clostridium difficile Infection Refractory to Metronidazole and Vancomycin

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George Tannous

2010-09-01

Full Text Available We report the case of a 46-year-old white male with confirmed Clostridium difficile infection for >4 weeks after fluoroquinolone therapy. The patient received two courses of metronidazole 500 mg three times daily (t.i.d. during which time diarrhea resolved; however, symptoms recurred 14–15 days after treatment termination. He received a 2-week course of vancomycin 125 mg four times daily, with symptoms recurring 10 days after treatment conclusion. The patient then received a pulsed tapering schedule of vancomycin with adjunctive Saccharomyces boulardii. Diarrhea recurred 12 days after treatment completion. He received rifaximin 400 mg t.i.d. while hospitalized for diarrhea-associated complications. Symptoms resolved within 24 h. The patient received a 4-week regimen of rifaximin 400 mg orally t.i.d. after discharge. No further episodes of diarrhea were reported within 6 months after treatment termination. The present case supports the potential benefit of rifaximin for the treatment of recurrent Clostridium difficile infection.

Activity of vancomycin, linezolid, and daptomycin against staphylococci and enterococci isolated in 5 Greek hospitals during a 5-year period (2008-2012).

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Papadimitriou-Olivgeris, Matthaios; Kolonitsiou, Fevronia; Zerva, Loukia; Lebessi, Evangelia; Koutsia, Chryssa; Drougka, Eleanna; Sarrou, Styliani; Giormezis, Nikolaos; Vourli, Sofia; Doudoulakakis, Anastassios; Konsolakis, Christos; Marangos, Markos; Anastassiou, Evangelos D; Petinaki, Efthimia; Spiliopoulou, Iris

2015-12-01

The tendency of vancomycin, linezolid, and daptomycin MICs was investigated among 6920 staphylococci and enterococci during a 5-year period. Antimicrobial consumption was determined. Decrease of vancomycin MIC was detected associated with reduction in consumption. Linezolid and daptomycin remained active. An upward trend of linezolid MIC for methicillin-resistant staphylococci was observed. Copyright © 2015 Elsevier Inc. All rights reserved.

The Impact of AUC-Based Monitoring on Pharmacist-Directed Vancomycin Dose Adjustments in Complicated Methicillin-Resistant Staphylococcus aureus Infection.

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Stoessel, Andrew M; Hale, Cory M; Seabury, Robert W; Miller, Christopher D; Steele, Jeffrey M

2018-01-01

This study aimed to assess the impact of area under the curve (AUC)-based vancomycin monitoring on pharmacist-initiated dose adjustments after transitioning from a trough-only to an AUC-based monitoring method at our institution. A retrospective cohort study of patients treated with vancomycin for complicated methicillin-resistant Staphylococcus aureus (MRSA) infection between November 2013 and December 2016 was conducted. The frequency of pharmacist-initiated dose adjustments was assessed for patients monitored via trough-only and AUC-based approaches for trough ranges: 10 to 14.9 mg/L and 15 to 20 mg/L. Fifty patients were included: 36 in the trough-based monitoring and 14 in the AUC-based-monitoring group. The vancomycin dose was increased in 71.4% of patients when troughs were 10 to 14.9 mg/L when a trough-only approach was used and in only 25% of patients when using AUC estimation ( P = .048). In the AUC group, the dose was increased only when AUC/minimum inhibitory concentration (MIC) AUC/MIC ≥400. The AUC-based monitoring did not significantly increase the frequency of dose reductions when trough concentrations were 15 to 20 mg/L (AUC: 33.3% vs trough: 4.6%; P = .107). The AUC-based monitoring resulted in fewer patients with dose adjustments when trough levels were 10 to 14.9 mg/L. The AUC-based monitoring has the potential to reduce unnecessary vancomycin exposure and warrants further investigation.

Stimulated phase-shift acoustic nanodroplets enhance vancomycin efficacy against methicillin-resistant Staphylococcus aureus biofilms

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Guo H

2017-06-01

Full Text Available Hao Guo,1 Ziming Wang,1 Quanyin Du,1 Pan Li,2 Zhigang Wang,2 Aimin Wang1 1Department of Orthopedics, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China; 2Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China Purpose: Bacterial biofilms on the surface of prostheses are becoming a rising concern in managing prosthetic joint infections. The inherent resistant features of biofilms render traditional antimicrobial therapy unproductive and revision surgery outcomes uncertain. This situation has prompted the exploration of novel antimicrobial strategies. The synergy of ultrasound microbubbles and vancomycin has been proposed as an efficient alternative for biofilm eradication. The purpose of this study was to evaluate the anti-biofilm effect of stimulated phase-shift acoustic nanodroplets (NDs combined with vancomycin.Materials and methods: We fabricated lipid phase-shift NDs with a core of liquid perfluoropentane. A new phase change mode for NDs incorporating an initial unfocused low-intensity pulsed ultrasound for 5 minutes and a subsequent incubation at 37°C into a 24-hour duration was developed. Methicillin-resistant Staphylococcus aureus (MRSA biofilms were incubated with vancomycin and NDs under the hybrid stimulation. Biofilm morphology following treatment was determined using confocal laser scanning microscopy and scanning electron microscopy. Resazurin assay was used to quantify bactericidal efficacy against MRSA biofilm bacteria.Results: NDs treated sequentially with ultrasound and heating at 37°C achieved gradual and substantial ND vaporization and cavitation in a successive process. NDs after stimulation were capable of generating stronger destruction on biofilm structure which was best characterized by residual circular arc margins and more dead bacteria. Furthermore, NDs

Efficacy of Vancomycin-based Continuous Triple Antibiotic Irrigation in Immediate, Implant-based Breast Reconstruction

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Lisa M. Hunsicker, MD, FACS

2017-12-01

Conclusions:. Continuous breast irrigation with a vancomycin-based triple antibiotic solution is a safe and effective accompaniment for immediate implant reconstruction. Use of intramuscular anesthetic injection for postoperative pain control allows the elastomeric infusion pump to be available for local tissue antibiotic irrigation.

Typing of vancomycin-resistant enterococci from Danish hospitals

DEFF Research Database (Denmark)

Lester, C H; Olsen, S S; Schønheyder, Henrik Carl

2009-01-01

locus sequence typing (MLST) was performed on the vancomycin-resistant E. faecium isolates. Results: The collection consisted of 45 E. faecium and 16 E. faecalis isolates which originated from 12 different hospitals. Thirty three of 45 E. faecium isolates were vanA positive and the remaining 12 isolates...... were vanB positive. All but one of the E. faecalis isolates contained the vanB gene (n = 15) and the remaining isolate contained the vanA gene. MLST of the 45 E. faecium isolates revealed 10 different sequence types (ST). The STs were ST18 (n = 21), ST203 (n = 8), ST78 (n = 3), ST192 (n = 3), ST412 (n...

Identification and molecular characterization of Van A-type vancomycin-resistant Enterococcus faecalis in Northeast of Brazil

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Marinalda Anselmo Vilela

2006-11-01

Full Text Available The isolation of vancomycin resistant enterococci (VRE in Brazil has rapidly increased, following the world wide tendency. We report in the present study the first isolation of vancomycin resistant Enterococcus faecalis (VRE in the Northeast of Brazil. The four VRE isolates were characterized for antimicrobial susceptibility, genotypic typing by macro restriction of chromosomal DNA followed by pulsed-field gel electrophoresis and for characterization of the Tn1546-like element and plasmid contents. The isolates showed resistance to multiple antibiotics and a single genotype profile, suggesting the dissemination of a single clone among the patients. Tn1546 associated to genetic elements as plasmids shows the importance of infection control measures to avoid the spreading of glycopetide resistance by conjugative transfer of VanA elements.

Crystallization and preliminary X-ray analysis of a d-Ala:d-Ser ligase associated with VanG-type vancomycin resistance

International Nuclear Information System (INIS)

Weber, Patrick; Meziane-Cherif, Djalal; Haouz, Ahmed; Saul, Frederick A.; Courvalin, Patrice

2009-01-01

The VanG d-alanine:d-serine ligase was crystallized in complex with ADP and diffraction data were collected at 2.35 Å resolution. Acquired VanG-type resistance to vancomycin in Enterococcus faecalis BM4518 arises from inducible synthesis of peptidoglycan precursors ending in d-alanyl-d-serine, to which vancomycin exhibits low binding affinity. VanG, a d-alanine:d-serine ligase, catalyzes the ATP-dependent synthesis of the d-Ala-d-Ser dipeptide, which is incorporated into the peptidoglycan synthesis of VanG-type vancomycin-resistant strains. Here, the purification, crystallization and preliminary crystallographic analysis of VanG in complex with ADP are reported. The crystal belonged to space group P3 1 21, with unit-cell parameters a = b = 116.1, c = 177.2 Å, and contained two molecules in the asymmetric unit. A complete data set has been collected to 2.35 Å resolution from a single crystal under cryogenic conditions using synchrotron radiation

Design and Implementation of a Novel Web-Based E-Learning Tool for Education of Health Professionals on the Antibiotic Vancomycin.

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Bond, Stuart Evan; Crowther, Shelley P; Adhikari, Suman; Chubaty, Adriana J; Yu, Ping; Borchard, Jay P; Boutlis, Craig Steven; Yeo, Wilfred Winston; Miyakis, Spiros

2017-03-30

Traditional approaches to health professional education are being challenged by increased clinical demands and decreased available time. Web-based e-learning tools offer a convenient and effective method of delivering education, particularly across multiple health care facilities. The effectiveness of this model for health professional education needs to be explored in context. The study aimed to (1) determine health professionals' experience and knowledge of clinical use of vancomycin, an antibiotic used for treatment of serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and (2) describe the design and implementation of a Web-based e-learning tool created to improve knowledge in this area. We conducted a study on the design and implementation of a video-enhanced, Web-based e-learning tool between April 2014 and January 2016. A Web-based survey was developed to determine prior experience and knowledge of vancomycin use among nurses, doctors, and pharmacists. The Vancomycin Interactive (VI) involved a series of video clips interspersed with question and answer scenarios, where a correct response allowed for progression. Dramatic tension and humor were used as tools to engage users. Health professionals' knowledge of clinical vancomycin use was obtained from website data; qualitative participant feedback was also collected. From the 577 knowledge survey responses, pharmacists (n=70) answered the greatest number of questions correctly (median score 4/5), followed by doctors (n=271; 3/5) and nurses (n=236; 2/5; Puser feedback from 51 participants following completion of the VI. Feedback was predominantly positive with themes of "entertaining," "engaging," and "fun" identified; however, there were some technical issues identified relating to accessibility from different operating systems and browsers. A novel Web-based e-learning tool was successfully developed combining game design principles and humor to improve user engagement. Knowledge

Combined use of vancomycin-modified Ag-coated magnetic nanoparticles and secondary enhanced nanoparticles for rapid surface-enhanced Raman scattering detection of bacteria.

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Wang, Chongwen; Gu, Bing; Liu, Qiqi; Pang, Yuanfeng; Xiao, Rui; Wang, Shengqi

2018-01-01

Pathogenic bacteria have always been a significant threat to human health. The detection of pathogens needs to be rapid, accurate, and convenient. We present a sensitive surface-enhanced Raman scattering (SERS) biosensor based on the combination of vancomycin-modified Ag-coated magnetic nanoparticles (Fe 3 O 4 @Ag-Van MNPs) and Au@Ag nanoparticles (NPs) that can effectively capture and discriminate bacterial pathogens from solution. The high-performance Fe 3 O 4 @Ag MNPs were modified with vancomycin and used as bacteria capturer for magnetic separation and enrichment. The modified MNPS were found to exhibit strong affinity with a broad range of Gram-positive and Gram-negative bacteria. After separating and rinsing bacteria, Fe 3 O 4 @Ag-Van MNPs and Au@Ag NPs were synergistically used to construct a very large number of hot spots on bacteria cells, leading to ultrasensitive SERS detection. The dominant merits of our dual enhanced strategy included high bacterial-capture efficiency (>65%) within a wide pH range (pH 3.0-11.0), a short assay time (<30 min), and a low detection limit (5×10 2 cells/mL). Moreover, the spiked tests show that this method is still valid in milk and blood samples. Owing to these capabilities, the combined system enabled the sensitive and specific discrimination of different pathogens in complex solution, as verified by its detection of Gram-positive bacterium Escherichia coli , Gram-positive bacterium Staphylococcus aureus , and methicillin-resistant S. aureus . This method has great potential for field applications in food safety, environmental monitoring, and infectious disease diagnosis.

Polyelectrolyte complex of vancomycin as a nanoantibiotic: Preparation, in vitro and in silico studies

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Sikwal, Dhiraj R.; Kalhapure, Rahul S.; Rambharose, Sanjeev; Vepuri, Suresh; Soliman, Mahmoud; Mocktar, Chunderika; Govender, Thirumala, E-mail: govenderth@ukzn.ac.za

2016-06-01

Delivery of antibiotics by various nanosized carriers is proving to be a promising strategy to combat limitations associated with conventional dosage forms and the ever-increasing drug resistance problem. This method entails improving the pharmacokinetic parameters for accumulation at the target infection site and reducing their adverse effects. It has been proposed that antibiotic nanoparticles themselves are more effective delivery system than encapsulating the antibiotic in a nanosystem. In this study, we report on nanoparticles of vancomycin (VCM) by self-assembled amphiphilic–polyelectrolyte complexation between VCM hydrochloride and polyacrylic acid sodium (PAA). The size, polydispersity index and zeta potential of the developed nanoplexes were 229.7 ± 47.76 nm, 0.442 ± 0.075, − 30.4 ± 5.3 mV respectively, whereas complexation efficiency, drug loading and percentage yield were 75.22 ± 1.02%, 58.40 ± 1.03% and 60.60 ± 2.62% respectively. An in vitro cytotoxicity study on three mammalian cell lines using MTT assays confirmed the biosafety of the newly formulated nanoplexes. Morphological investigations using scanning electron microscope showed cube shaped hexagonal-like particles. In vitro drug release studies revealed that the drug was completely released from the nanoplexes within 12 h. In silico studies revealed that the nano-aggregation was facilitated by means of self-association of VCM in the presence of the polymer. The supramolecular pattern of the drug self-association was found to be similar to that of the VCM dimer observed in the crystal structure of the VCM available in Protein Data Bank. In vitro antibacterial activity against susceptible and resistant Staphylococcus aureus proved that the potency of VCM was retained after being formulated as the nanoplex. In conclusion, VCM nanoplexes could be a promising nanodrug delivery system to treat infections of S. aureus origin. - Highlights: • Self-assembly of vancomycin to form cube

Polyelectrolyte complex of vancomycin as a nanoantibiotic: Preparation, in vitro and in silico studies

International Nuclear Information System (INIS)

Sikwal, Dhiraj R.; Kalhapure, Rahul S.; Rambharose, Sanjeev; Vepuri, Suresh; Soliman, Mahmoud; Mocktar, Chunderika; Govender, Thirumala

2016-01-01

Delivery of antibiotics by various nanosized carriers is proving to be a promising strategy to combat limitations associated with conventional dosage forms and the ever-increasing drug resistance problem. This method entails improving the pharmacokinetic parameters for accumulation at the target infection site and reducing their adverse effects. It has been proposed that antibiotic nanoparticles themselves are more effective delivery system than encapsulating the antibiotic in a nanosystem. In this study, we report on nanoparticles of vancomycin (VCM) by self-assembled amphiphilic–polyelectrolyte complexation between VCM hydrochloride and polyacrylic acid sodium (PAA). The size, polydispersity index and zeta potential of the developed nanoplexes were 229.7 ± 47.76 nm, 0.442 ± 0.075, − 30.4 ± 5.3 mV respectively, whereas complexation efficiency, drug loading and percentage yield were 75.22 ± 1.02%, 58.40 ± 1.03% and 60.60 ± 2.62% respectively. An in vitro cytotoxicity study on three mammalian cell lines using MTT assays confirmed the biosafety of the newly formulated nanoplexes. Morphological investigations using scanning electron microscope showed cube shaped hexagonal-like particles. In vitro drug release studies revealed that the drug was completely released from the nanoplexes within 12 h. In silico studies revealed that the nano-aggregation was facilitated by means of self-association of VCM in the presence of the polymer. The supramolecular pattern of the drug self-association was found to be similar to that of the VCM dimer observed in the crystal structure of the VCM available in Protein Data Bank. In vitro antibacterial activity against susceptible and resistant Staphylococcus aureus proved that the potency of VCM was retained after being formulated as the nanoplex. In conclusion, VCM nanoplexes could be a promising nanodrug delivery system to treat infections of S. aureus origin. - Highlights: • Self-assembly of vancomycin to form cube

Association between Accessory Gene Regulator Polymorphism and Mortality among Critically Ill Patients Receiving Vancomycin for Nosocomial MRSA Bacteremia: A Cohort Study

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Angélica Cechinel

2016-01-01

Full Text Available Background. Polymorphism of the accessory gene regulator group II (agr in methicillin-resistant Staphylococcus aureus (MRSA is predictive of vancomycin failure therapy. Nevertheless, the impact of group II agr expression on mortality of patients with severe MRSA infections is not well established. Objective. The goal of our study was to evaluate the association between agr polymorphism and all-cause in-hospital mortality among critically ill patients receiving vancomycin for nosocomial MRSA bacteremia. Methods. All patients with documented bacteremia by MRSA requiring treatment in the ICU between May 2009 and November 2011 were included in the study. Cox proportional hazards regression was performed to evaluate whether agr polymorphism was associated with all-cause in-hospital mortality. Covariates included age, APACHE II score, initial C-reactive protein plasma levels, initial serum creatinine levels, vancomycin minimum inhibitory concentration, vancomycin serum levels, and time to effective antibiotic administration. Results. The prevalence of group I and group II agr expression was 52.4% and 47.6%, respectively. Bacteremia by MRSA group III or group IV agr was not documented in our patients. The mean APACHE II of the study population was 24.3 (standard deviation 8.5. The overall cohort mortality was 66.6% (14 patients. After multivariate analysis, initial plasma C-reactive protein levels (P=0.01, initial serum creatinine levels (P=0.008, and expression of group II agr (P=0.006 were positively associated with all-cause in-hospital mortality. Patients with bacteremia by MRSA with group II agr expression had their risk of death increased by 12.6 times when compared with those with bacteremia by MRSA with group I agr expression. Conclusion. Group II agr polymorphism is associated with an increase in mortality in critically ill patients with bacteremia by MRSA treated with vancomycin.

Short communication: β-Lactam resistance and vancomycin heteroresistance in Staphylococcus spp. isolated from bovine subclinical mastitis.

Science.gov (United States)

Mello, Priscila Luiza; Pinheiro, Luiza; Martins, Lisiane de Almeida; Brito, Maria Aparecida Vasconcelos Paiva; Ribeiro de Souza da Cunha, Maria de Lourdes

2017-08-01

The use of antimicrobial agents has led to the emergence of resistant bacterial strains over a relatively short period. Furthermore, Staphylococcus spp. can produce β-lactamase, which explains the survival of these strains in a focus of infection despite the use of a β-lactam antibiotic. The aim of this study was to evaluate the resistance of Staphylococcus spp. isolated from bovine subclinical mastitis to oxacillin and vancomycin (by minimum inhibitory concentration) and to detect vancomycin heteroresistance by a screening method. We also evaluated β-lactamase production and resistance due to hyperproduction of this enzyme and investigated the mecA and mecC genes and performed staphylococcal cassette chromosome mec typing. For this purpose, 181 Staphylococcus spp. isolated from mastitis subclinical bovine were analyzed. Using the phenotypic method, 33 (18.2%) of Staphylococcus spp. were resistant to oxacillin. In contrast, all isolates were susceptible to vancomycin, and heteroresistance was detected by the screening method in 13 isolates. Production of β-lactamase was observed in 174 (96%) of the Staphylococcus spp. isolates. The mecA gene was detected in 8 isolates, all of them belonging to the species Staphylococcus epidermidis, and staphylococcal cassette chromosome mec typing revealed the presence of type I and type IV isolates. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The Murine Lung Microbiome Changes During Lung Inflammation and Intranasal Vancomycin Treatment

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Barfod, Kenneth Klingenberg; Vrankx, Katleen; Mirsepasi-Lauridsen, Hengameh Chloé; Hansen, Jitka Stilund; Hougaard, Karin Sørig; Larsen, Søren Thor; Ouwenhand, Arthur C.; Krogfelt, Karen Angeliki

2015-01-01

Most microbiome research related to airway diseases has focused on the gut microbiome. This is despite advances in culture independent microbial identification techniques revealing that even healthy lungs possess a unique dynamic microbiome. This conceptual change raises the question; if lung diseases could be causally linked to local dysbiosis of the local lung microbiota. Here, we manipulate the murine lung and gut microbiome, in order to show that the lung microbiota can be changed experimentally. We have used four different approaches: lung inflammation by exposure to carbon nano-tube particles, oral probiotics and oral or intranasal exposure to the antibiotic vancomycin. Bacterial DNA was extracted from broncho-alveolar and nasal lavage fluids, caecum samples and compared by DGGE. Our results show that: the lung microbiota is sex dependent and not just a reflection of the gut microbiota, and that induced inflammation can change lung microbiota. This change is not transferred to offspring. Oral probiotics in adult mice do not change lung microbiome detectible by DGGE. Nasal vancomycin can change the lung microbiome preferentially, while oral exposure does not. These observations should be considered in future studies of the causal relationship between lung microbiota and lung diseases. PMID:26668669

Comparison of Linezolid and Vancomycin for Methicillin-Resistant Staphylococcus aureus Pneumonia: Institutional Implications.

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Tong, ManShan C; Wisniewski, Christopher S; Wolf, Bethany; Bosso, John A

2016-07-01

Recent studies suggesting clinical superiority of linezolid over vancomycin in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia led to a change in our institution's clinical pathway/order form for hospital-acquired pneumonia, positioning linezolid as the preferred agent. Our objective was to assess the impact of this change within our institution. Retrospective electronic medical records review. The analysis for this observational study included eligible patients admitted to our medical center between May 1, 2011, and August 31, 2014, with ICD-9 codes for MRSA and pneumonia. Included patients were at least 18 years of age and had vancomycin or linezolid initiated at least 2 days after admission and continued for at least 2 consecutive days. The primary end points were extent of antibiotic use before and after order form change and length of stay (LOS) and hospital charges in the two treatment groups. A secondary aim was to detect any gross discrepancies in patient outcomes such as treatment duration, mechanical ventilation duration, all-cause mortality rate, nephrotoxicity, and 30-day readmission between the two treatment groups. Outcomes in 227 patients were assessed. Linezolid use increased 16.2% subsequent to the change in the order form. Although not statistically significant, the median hospital admission charge was $6200 lower in patients treated with linezolid compared with those treated with vancomycin ($25,900 vs $32,100). Hospital LOS was significantly associated with Charlson Comorbidity Index score (plinezolid treatment, and these patients were more likely to be discharged (shorter LOS). Although linezolid use increased markedly with this pathway/order form change, no negative institutional consequences or unfavorable patient outcomes were detected, justifying the change in policy from these perspectives. © 2016 Pharmacotherapy Publications, Inc.

Efficacy of linezolid compared to vancomycin in an experimental model of pneumonia induced by methicillin-resistant Staphylococcus aureus in ventilated pigs.

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Martinez-Olondris, Pilar; Rigol, Montserrat; Soy, Dolors; Guerrero, Laura; Agusti, Carlos; Quera, Maria Angels; Li Bassi, Gianluigi; Esperatti, Mariano; Luque, Nestor; Liapikou, Manto; Filella, Xavier; Marco, Francesc; de la Bellacasa, Jordi Puig; Torres, Antoni

2012-01-01

To assess the efficacy of linezolid compared with vancomycin in an experimental model of pneumonia induced by methicillin-resistant Staphylococcus aureus (MRSA) in ventilated pigs. Forty pigs (30 kg) were intubated and challenged via bronchoscopy with a suspension of 106 colony forming units of MRSA into every lobe. Afterwards, pigs were ventilated up to 96 hours. Twelve hours after bacterial inoculation, the animals were randomized into 4 groups of treatment: group 1, control; group 2, vancomycin twice daily; group 3, continuous infusion of vancomycin; and group 4, linezolid. Clinical and laboratory parameters were monitored throughout the study. Bacterial cultures of bronchoalveolar lavage fluid and lung tissue samples were performed at the end of the study. Measurements of histopathology derangements of lung samples and studies of intrapulmonary drug penetration were performed. A total of 34 animals completed the study. No differences in clinical and laboratory parameters were observed. The percentage of bronchoalveolar lavage fluid and lung tissue samples with positive cultures for MRSA in controls and groups 2, 3, and 4 was respectively 75%, 11%, 11%, and 0% (p pneumonia in 95%, 69%, 58%, and 57% and signs of severe pneumonia in 48%, 29%, 22%, and 0% of controls and groups 2, 3, and 4, respectively (p treatments. In this animal model of MRSA pneumonia, linezolid showed a better efficacy than vancomycin showed because of a better pharmacokinetics/pharmacodynamics index.

Typing of vancomycin-resistant enterococci with MALDI-TOF mass spectrometry in a nosocomial outbreak setting

DEFF Research Database (Denmark)

Holzknecht, B J; Dargis, R; Pedersen, M

2018-01-01

OBJECTIVES: To investigate the usefulness of matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) typing as a first-line epidemiological tool in a nosocomial outbreak of vancomycin-resistant Enterococcus faecium (VREfm). METHODS: Fifty-five VREfm isolates...

Clostridium difficile Infection and Patient-Specific Antimicrobial Resistance Testing Reveals a High Metronidazole Resistance Rate.

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Barkin, Jodie A; Sussman, Daniel A; Fifadara, Nimita; Barkin, Jamie S

2017-04-01

Clostridium difficile (CD) infection (CDI) causes marked morbidity and mortality, accounting for large healthcare expenditures annually. Current CDI treatment guidelines focus on clinical markers of patient severity to determine the preferred antibiotic regimen of metronidazole versus vancomycin. The antimicrobial resistance patterns for patients with CD are currently unknown. The aim of this study was to define the antimicrobial resistance patterns for CD. This study included all patients with stools sent for CD testing to a private laboratory (DRG Laboratory, Alpharetta, Georgia) in a 6-month period from across the USA. Patient data was de-identified, with only age, gender, and zip-code available per laboratory protocol. All samples underwent PCR testing followed by hybridization for CD toxin regions A and B. Only patients with CD-positive PCR were analyzed. Antimicrobial resistance testing using stool genomic DNA evaluated presence of imidazole- and vancomycin-resistant genes using multiplex PCR gene detection. Of 2743, 288 (10.5%) stool samples were positive for CD. Six were excluded per protocol. Of 282, 193 (69.4%) were women, and average age was 49.4 ± 18.7 years. Of 282, 62 were PCR positive for toxins A and B, 160 for toxin A positive alone, and 60 for toxin B positive alone. Antimicrobial resistance testing revealed 134/282 (47.5%) patients resistant to imidazole, 17 (6.1%) resistant to vancomycin, and 9 (3.2%) resistant to imidazole and vancomycin. CD-positive patients with presence of imidazole-resistant genes from stool DNA extract was a common phenomenon, while vancomycin resistance was uncommon. Similar to treatment of other infections, antimicrobial resistance testing should play a role in CDI clinical decision-making algorithms to enable more expedited and cost-effective delivery of patient care.

Contamination of the Clinical Microbiology Laboratory with Vancomycin-Resistant Enterococci and Multidrug- Resistant Enterobacteriaceae: Implications for Hospital and Laboratory Workers

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Collins, Susan M.; Hacek, Donna M.; Degen, Lisa A.; Wright, Marc O.; Noskin, Gary A.; Peterson, Lance R.

2001-01-01

We surveyed environmental surfaces in our clinical microbiology laboratory to determine the prevalence of vancomycin-resistant enterococci (VRE) and multidrug-resistant Enterobacteriaceae (MDRE) during a routine working day. From a total of 193 surfaces, VRE were present on 20 (10%) and MDRE were present on 4 (2%) of the surfaces tested. In a subsequent survey after routine cleaning, all of the 24 prior positive surfaces were found to be negative. Thus, those in the laboratory should recognize that many surfaces may be contaminated by resistant organisms during routine processing of patient specimens. PMID:11574615

Polymyxin-B and vancomycin-associated acute kidney injury in critically ill patients.

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Soares, Douglas de Sousa; Reis, André da Fonte; Silva Junior, Geraldo Bezerra da; Leite, Tacyano Tavares; Parente Filho, Sérgio Luiz Arruda; Rocha, Carina Vieira de Oliveira; Daher, Elizabeth De Francesco

2017-05-01

This study aims to investigate renal toxicities of Polymyxin B and Vancomycin among critically ill patients and risk factors for acute kidney injury (AKI). This is a cross-sectional study conducted with patients admitted to an intensive care unit (ICU) of a tertiary hospital in Brazil. Patients were divided into two groups: those who used association of Polymyxin B + Vancomycin (Group I) and those who used only Polymyxin B (Group II). Risk factors for AKI were also analyzed. A total of 115 patients were included. Mean age was 59.2 ± 16.1 years, and 52.2% were males. Group I presented higher GFR (117.1 ± 70.5 vs. 91.5 ± 50 ml/min/1.73 m², p = 0.02) as well as lower creatinine (0.9 ± 0.82 vs. 1.0 ± 0.59 mg/dL, p = 0.014) and urea (51.8 ± 23.7 vs. 94.5 ± 4.9 mg/dL, p = 0.006) than group II on admission. Group I also manifested significantly higher incidence of AKI than group II (62.7% vs. 28.5%, p = 0.005), even when stratified according to RIFLE criteria ('Risk' 33.9% vs. 10.7%; 'Injury' 10.2% vs. 8.9%; 'Failure' 18.6% vs. 8.9%; p = 0.03). Accumulated Polymyxin B dose > 10 million IU was an independent predictor for AKI (OR = 2.72, 95% CI = 1.13-6.51, p = 0.024). Although patients who received Polymyxin B plus vancomycin had more favorable clinical profile and higher previous GFR, they presented a higher AKI incidence than those patients who received Polymyxin B alone. Cumulative Polymyxin B dose > 10 million IU was independently associated to AKI.

Therapeutic drug monitoring by radioimmunoassay: Determination of aminoglycoside antibiotics and vancomycin in plasma

International Nuclear Information System (INIS)

Glaubitt, D.; Drechsler, H.J.; Knoch, K.; Siafarikas, K.

1984-01-01

Radioimmunoassay of aminoglycoside antibiotics (gentamicin, tobramycin, netilmicin) or vancomycin in plasma may considerably aid to assess their appropriate dosage and, if necessary, to rapidly adjust it to the assumed requirement. Thus the dosage of the antibiotic is kept large enough as to lead to the desired therapeutic result but not as high as to cause side effects. (orig.)

Vancomycin pre-treatment impairs tissue healing in experimental colitis: Importance of innate lymphoid cells.

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Zhao, Di; Cai, Chenwen; Zheng, Qing; Jin, Shuang; Song, Dongjuan; Shen, Jun; Ran, Zhihua

2017-01-29

The interplay between luminal microbes and innate immunity during colonic epithelial repair has been well noted. At the same time, antibiotic has widely been used during flare-ups of ulcerative colitis. The possible effects of luminal microbiota disruption caused by antibiotics usage on epithelial repairing have been scarcely discussed. Innate lymphoid cells (ILCs) embedded in the lamina propria can be modulated by gut microbes, resulting in altered colonic IL-22/pSTAT3 levels, which is considered a prominent molecular axis in tissue repairing after epithelium damage. This study aimed to investigate whether antibiotics could interfere with ILCs-dependent tissue repair. Dextran sodium sulfate (DSS)-induced colitis was established in mice pre-treated with reagent of different antibiotic spectrum. Both morphological and molecular markers of tissue repair after DSS cessation were detected. ILCs population and function status were also recorded. Further attention was paid to the response of dendritic cells after antibiotics treatment, which were claimed to regulate colonic ILC3s in an IL-23 dependent way. Using of vancomycin resulted in delayed tissue repairing after experimental colitis. Both colonic IL-22/pSTAT3 axis and ILC3 population were found decreased in this situation. Vancomycin treatment diminished the upstream IL-23 and producer dendritic cell population. The reduced dendritic cell number may due to inadequate chemokines and colony-stimulating factors supply. Presence of vancomycin-sensitive microbiota is required for the maturation of ILC3-activating dendritic cells hence maintain the sufficient IL-22/pSTAT3 level in the colon during tissue healing. Manipulation of colonic microbiota may help achieve colonic mucosal healing post inflammation and injury. Copyright © 2016. Published by Elsevier Inc.

Comparison of Rates of Nephrotoxicity Associated with Vancomycin in Combination with Piperacillin-Tazobactam Administered as an Extended versus Standard Infusion.

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Mousavi, Mariam; Zapolskaya, Tanya; Scipione, Marco R; Louie, Eddie; Papadopoulos, John; Dubrovskaya, Yanina

2017-03-01

Despite recent reports of relatively high rates (16-37%) of acute kidney injury (AKI) in patients receiving the combination of intravenous piperacillin-tazobactam (PTZ) and vancomycin, data are limited evaluating the impact of PTZ infusion strategy on the occurrence of nephrotoxicity. The objective of this study was to compare the rates of nephrotoxicity in patients receiving vancomycin in combination with PTZ administered as an extended infusion (EI) versus a standard infusion (SI). Single-center, retrospective, matched-cohort study. Large academic tertiary care hospital. Two hundred eighty adults with a creatinine clearance (CrCl) of 40 ml/minute or higher who received at least 96 hours of vancomycin plus PTZ EI (140 patients) or vancomycin plus PTZ SI (140 patients) between January 1, 2009, and December 31, 2011, and between January 1, 2013, and December 31, 2014 (year 2012 was skipped due the closure of inpatient units following Superstorm Sandy); 48 patients in each group were admitted to the intensive care unit. The median age of all patients was 67 (interquartile range [IQR] 54-77) years, and CrCl was 75 (IQR 55-107) ml/minute. Nephrotoxicity was assessed by the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) and Acute Kidney Injury Network (AKIN) criteria. Rates of AKI, according to these criteria, were similar between groups: 17.9% versus 17.1% (p=1) and 32.9% versus 29.3% (p=0.596) for the PTZ EI and PTZ SI groups, respectively. When controlling for residual differences between groups in a conditional logistic regression analysis, no association was observed between receipt of PTZ EI and RIFLE-defined AKI (odds ratio 0.522, 95% confidence interval 0.043-6.295, p=0.609). Time to onset of nephrotoxicity was 4 (IQR 3-6) days, with no significant difference noted between groups (p=0.887). Our findings suggest a similar rate of nephrotoxicity between patients who received vancomycin in combination with PTZ EI versus PTZ SI. These results need

Sustained release vancomycin-coated titanium alloy using a novel electrostatic dry powder coating technique may be a potential strategy to reduce implant-related infection.

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Han, Jing; Yang, Yi; Lu, Junren; Wang, Chenzhong; Xie, Youtao; Zheng, Xuebin; Yao, Zhenjun; Zhang, Chi

2017-07-24

In order to tackle the implant-related infection, a novel way was developed in this study to coat vancomycin particles mixed with controlled release coating materials onto the surface of titanium alloy by using an electrostatic dry powder coating technique. To characterize this sustained release antibacterial coating, surface morphology, in vitro and in vivo drug release were sequentially evaluated. In vitro cytotoxicity was tested by Cell Counting Kit-8 (CCK-8) assay and cytological changes were observed by inverted microscope. The antibacterial properties against MRSA, including a bacterial growth inhibition assay and a colony-counting test by spread plate method were performed. Results indicated that the vancomycin-coated sample was biocompatible for Human osteoblast cell line MG-63 and displayed effective antibacterial ability against MRSA. The coating film was revealed uniform by scanning electron microscopy. Both the in vitro and in vivo drug release kinetics showed an initially high release rate, followed by an extended period of sustained drug release over 7 days. These results suggest that with good biocompatibility and antibacterial ability, the sustained release antibacterial coating of titanium alloy using our novel electrostatic dry powder coating process may provide a promising candidate for the treatment of orthopedic implant-related infection.

Selective vancomycin detection using optical fibre long period gratings functionalised with molecularly imprinted polymer nanoparticles.

Science.gov (United States)

Korposh, Sergiy; Chianella, Iva; Guerreiro, Antonio; Caygill, Sarah; Piletsky, Sergey; James, Stephen W; Tatam, Ralph P

2014-05-07

An optical fibre long period grating (LPG) sensor modified with molecularly imprinted polymer nanoparticles (nanoMIPs) for the specific detection of antibiotics is presented. The operation of the sensor is based on the measurement of changes in refractive index induced by the interaction of nanoMIPs deposited onto the cladding of the LPG with free vancomycin (VA). The binding of nanoMIPs to vancomycin was characterised by a binding constant of 4.3 ± 0.1 × 10(-8) M. The lowest concentration of analyte measured by the fibre sensor was 10 nM. In addition, the sensor exhibited selectivity, as much smaller responses were obtained for high concentrations (∼700 μM) of other commonly prescribed antibiotics such as amoxicillin, bleomycin and gentamicin. In addition, the response of the sensor was characterised in a complex matrix, porcine plasma, spiked with 10 μM of VA.

Are Vancomycin Trough Concentrations of 15 to 20 mg/L Associated With Increased Attainment of an AUC/MIC ≥ 400 in Patients With Presumed MRSA Infection?

Science.gov (United States)

Hale, Cory M; Seabury, Robert W; Steele, Jeffrey M; Darko, William; Miller, Christopher D

2017-06-01

To determine whether there is an association between higher vancomycin trough concentrations and attainment of a calculated area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) ≥400. A retrospective analysis was conducted among vancomycin-treated adult patients with a positive methicillin-resistant Staphylococcus aureus (MRSA) culture. Attainment of a calculated AUC/MIC ≥400 was compared between patients with troughs in the reference range of 15 to 20 mg/L and those with troughs in the following ranges: 20 mg/L. Nephrotoxicity was assessed as a secondary outcome based on corrected average vancomycin troughs over 10 days of treatment. Overall, 226 patients were reviewed and 100 included. Relative to troughs ≥10, patients with vancomycin troughs AUC/MIC ≥400 (odds ratio [OR] 0.27, 95% confidence interval [CI]: 0.01-0.75). No difference was found in the attainment of an AUC/MIC ≥400 in patients with troughs of 10 to 14.9 mg/L and >20 mg/L when compared to patients with troughs of 15 to 20 mg/L. The mean corrected average vancomycin trough was higher in patients developing nephrotoxicity compared to those who did not (19.5 vs 14.5 mg/L, P AUC/MIC target relative to troughs of 10 to 14.9 mg/L but may increase nephrotoxicity risk.

Simple and rapid quantification of vancomycin in serum, urine and peritoneal/pleural effusion via UHPLC-MS/MS applicable to personalized antibiotic dosing research.

Science.gov (United States)

Javorska, Lenka; Krcmova, Lenka Kujovska; Solich, Petr; Kaska, Milan

2017-08-05

Management of the therapy of life-threatening bacterial infection is extremely based on an optimal antibiotic treatment. Achieving the correct vancomycin dosage in blood and target tissues can be complicated in special situations, e.g., where large fluid sequestration and/or acute renal failure occur. A UHPLC-MS/MS method operating in electrospray (ESI) positive ion mode was applied for the determination of vancomycin in serum, urine and peritoneal/pleural effusion. Sample pretreatment was composed of dilution and simple protein precipitation where only a small volume (50μL) of serum, urine or peritoneal/pleural effusion was required. The separation of vancomycin was performed on a Meteoric Core C18 BIO column (100×4.6mm, 2.7μm) by gradient elution with 0.1% formic acid in water and acetonitrile. The total time of analysis was 4.5min. The method was found to be linear in the range of 2-60μM (or 0.5-10μM) for serum, 0.27-10μM (or 2-60μM) for peritoneal/pleural effusion and 25-300μM for urine, which was adequate for the determination of vancomycin in patient samples. The intra- and inter-day precision was below 8% RSD, and accuracy was from 89 to 104%. The UHPLC/MS-MS method offers a fast and reliable approach to determine vancomycin concentrations in three different human body fluid samples (serum, urine and peritoneal/pleural effusion) with a simple sample pretreatment that was the same for all selected specimens. This method should be applicable to large sample series in clinical (pharmacokinetic/pharmacodynamic) studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical outcomes of linezolid and vancomycin in patients with nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus stratified by baseline renal function: a retrospective, cohort analysis.

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Liu, Ping; Capitano, Blair; Stein, Amy; El-Solh, Ali A

2017-05-22

The primary objective of this study is to assess whether baseline renal function impacts treatment outcomes of linezolid and vancomycin (with a dose-optimized regimen) for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. We conducted a retrospective cohort analysis of data generated from a prospective, randomized, controlled clinical trial (NCT 00084266). The analysis included 405 patients with culture-proven MRSA pneumonia. Baseline renal function was stratified based on creatinine clearance. Clinical and microbiological success rates and presence of nephrotoxicity were assessed at the end of treatment (EOT) and end of study (EOS). Multivariate logistic regression analyses of baseline patient characteristics, including treatment, were performed to identify independent predictors of efficacy. Vancomycin concentrations were analyzed using a nonlinear mixed-effects modeling approach. The relationships between vancomycin exposures, pharmacokinetic-pharmacodynamic index (trough concentration, area under the curve over a 24-h interval [AUC 0-24 ], and AUC 0-24 /MIC) and efficacy/nephrotoxicity were assessed in MRSA pneumonia patients using univariate logistic regression or Cox proportional hazards regression analysis approach. After controlling for use of vasoactive agents, choice of antibiotic therapy and bacteremia, baseline renal function was not correlated with clinical and microbiological successes in MRSA pneumonia at either end of treatment or at end of study for both treatment groups. No positive association was identified between vancomycin exposures and efficacy in these patients. Higher vancomycin exposures were correlated with an increased risk of nephrotoxicity (e.g., hazards ratio [95% confidence interval] for a 5 μg/ml increase in trough concentration: 1.42 [1.10, 1.82]). In non-dialysis patients, baseline renal function did not impact the differences in efficacy or nephrotoxicity with treatment of linezolid versus vancomycin in MRSA

Prevalence and determinants of fecal colonization with vancomycin-resistant Enterococcus in hospitalized patients in The Netherlands

NARCIS (Netherlands)

van den Braak, N.; Ott, A.; van Belkum, A.; Kluytmans, J. A.; Koeleman, J. G.; Spanjaard, L.; Voss, A.; Weersink, A. J.; Vandenbroucke-Grauls, C. M.; Buiting, A. G.; Verbrugh, H. A.; Endtz, H. P.

2000-01-01

To determine the prevalence and determinants of fecal carriage of vancomycin-resistant enterococci (VRE) in intensive care unit (ICU), hematology-oncology, and hemodialysis patients in The Netherlands. Descriptive, multicenter study, with yearly 1-week point-prevalence assessments between 1995 and

[Study of marine actinomycetes isolated from the central coast of Peru and their antibacterial activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis].

Science.gov (United States)

León, Jorge; Aponte, Juan José; Rojas, Rosario; Cuadra, D'Lourdes; Ayala, Nathaly; Tomás, Gloria; Guerrero, Marco

2011-06-01

To determine the antimicrobial potential of marine actinomycetes against drug-resistant pathogens represented by strains of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE). Strains of actinomycetes (29) isolated from marine sediment were evaluated by their characteristics in two culture media and by testing their inhibitory capacity by in vitro antagonism against multi-drug resistant (MDR) pathogenic bacteria for MRSA and VRE. Organic extracts of 3 selected actinomicetes were processed to determine the minimum inhibitory concentration (MIC) of the active compound. Most isolated actinomycetes belong to a homogeneous group of write-gray actinomycetes with a good growth in Marine Agar. The inhibitory rates of the isolates were above 85% for both pathogens with inhibition zones greater than 69 and 78 mm in diameter for MRSA and VRE respectively. Dichloromethane extracts of 3 isolates (I-400A, B1-T61, M10-77) showed strong inhibitory activity of both pathogens, M10-77 being the highest actinomycete strain with antibiotic activity against methicillin-resistant S. aureus ATCC 43300 and vancomycin-resistant E. faecalis ATCC 51299 with a minimum inhibitory concentrations (MIC) of 7.9 and 31.7 μg/ml respectively. Phylogenetic analysis of M10-77 strain showed 99% similarity with the marine species Streptomyces erythrogriseus. Marine sediments of the central coast of Peru, are a source of actinomycetes strains showing high capacity to produce bioactive compounds able to inhibit pathogens classified as multi-drug-resistant such as methicillin-resistant S. aureus and vancomycin-resistant E. faecalis.

CORRELATION BETWEEN HYDROPHOBICITY AND RESISTANCE TO NONOXYNOL-9 AND VANCOMYCIN FOR UROGENITAL ISOLATES OF LACTOBACILLI

NARCIS (Netherlands)

TOMECZEK, L; REID, G; CUPERUS, PL; MCGROARTY, JA; VANDERMEI, HC; BRUCE, AW; KHOURY, AE; BUSSCHER, HJ

1992-01-01

Seven clinical isolates of lactobacilli were found to be relatively hydrophobic with a mean water-contact angle of 66 +/- 15 degrees, and to be susceptible to 1% nonoxynol-9 and vancomycin. However, seven other strains were relatively hydrophilic with a mean water-contact angle of 32 +/- 13 degrees,

Vancomycin-Resistance Enterococci Infections in the Department of the Defense: Annual Report 2013

Science.gov (United States)

2014-08-01

str.r.:lioos, S€’ £l "r:’hi fl!’:: lil<i~lin ,:l ddc ~o.r-c.;s, !]:l:ho:>r rr:, aY. nflinttlirir~ :he !::f;, ·nod c ol ’ HO: Io ~:·rnhlir’U ;;· ;d ro...16. Morris JG, et al. Enterococci resistant to multiple antimicrobial agents, including vancomycin: establishment of endemicity in a university

Successful prevention of the transmission of vancomycin-resistant enterococci in a Brazilian public teaching hospital

Directory of Open Access Journals (Sweden)

Flávia Alves Ferreira Rossini

2012-04-01

Full Text Available INTRODUCTION: Vancomycin-resistant enterococci (VRE can colonize or cause infections in high-risk patients and contaminate the environment. Our objective was to describe theepidemiological investigation of an outbreak of VRE, the interventions made, and their impact on its control. METHODS: We conducted a retrospective, descriptive, non-comparative study by reviewing the charts of patients with a VRE-positive culture in the University Hospital of Campinas State University, comprising 380 beds, 40 of which were in intensive care units (ICUs, who were admitted from February 2008-January 2009. Interventions were divided into educational activity, reviewing the workflow processes, engineering measures, and administrative procedures. RESULTS: There were 150 patients, 139 (92.7% colonized and 11 (7.3% infected. Seventy-three percent were cared for in non-ICUs (p = 0.028. Infection was more frequent in patients with a central-line (p = 0.043, mechanical ventilation (p = 0.013, urinary catheter (p = 0.049, or surgical drain (p = 0.049. Vancomycin, metronidazole, ciprofloxacin, and third-generation cephalosporin were previously used by 47 (31.3%, 31 (20.7%, 24 (16%, and 24 (16% patients, respectively. Death was more frequent in infected (73% than in colonized (17% patients (p < 0.001. After the interventions, the attack rate fell from 1.49 to 0.33 (p < 0.001. CONCLUSIONS: Classical risk factors for VRE colonization or infection, e.g., being cared for in an ICU and previous use of vancomycin, were not found in this study. The conjunction of an educational program, strict adhesion to contact precautions, and reinforcement of environmental cleaning were able to prevent the dissemination of VRE.

Presence of the resistance genes vanC1 and pbp5 in phenotypically vancomycin and ampicillin susceptible Enterococcus faecalis.

Science.gov (United States)

Schwaiger, Karin; Bauer, Johann; Hörmansdorfer, Stefan; Mölle, Gabriele; Preikschat, Petra; Kämpf, Peter; Bauer-Unkauf, Ilse; Bischoff, Meike; Hölzel, Christina

2012-08-01

Ampicillin and vancomycin are important antibiotics for the therapy of Enterococcus faecalis infections. The ampicillin resistance gene pbp5 is intrinsic in Enterococcus faecium. The vanC1 gene confers resistance to vancomycin and serves as a species marker for Enterococcus gallinarum. Both genes are chromosomally located. Resistance to ampicillin and vancomycin was determined in 484 E. faecalis of human and porcine origin by microdilution. Since E. faecalis are highly skilled to acquire resistance genes, all strains were investigated for the presence of pbp5 (and, in positive strains, for the penicillin-binding protein synthesis repressor gene psr) and vanC1 (and, in positive strains, for vanXYc and vanT) by using polymerase chain reaction (PCR). One porcine and one human isolate were phenotypically resistant to ampicillin; no strain was vancomycin resistant. Four E. faecalis (3/1 of porcine/human origin) carried pbp5 (MIC=1 mg/L), and four porcine strains were vanC1 positive (minimum inhibitory concentration [MIC]=1 mg/L). Real-time reverse transcriptase (RT)-PCR revealed that the genes were not expressed. The psr gene was absent in the four pbp5-positive strains; the vanXYc gene was absent in the four vanC1-positive strains. However, vanT of the vanC gene cluster was detected in two vanC1-positive strains. To our knowledge, this is the first report on the presence of pbp5, identical with the "E. faecium pbp5 gene," and of vanC1/vanT in E. faecalis. Even if resistance is not expressed in these strains, this study shows that E. faecalis have a strong ability to acquire resistance genes-and potentially to spread them to other bacteria. Therefore, close monitoring of this species should be continued.

Simultaneous determination of vancomycin and ceftazidime in cerebrospinal fluid in craniotomy patients by high-performance liquid chromatography.

Science.gov (United States)

Ye, Guangming; Cai, Xuejian; Wang, Biao; Zhou, Zhongxian; Yu, Xiaohua; Wang, Weibin; Zhang, Jiandong; Wang, Yuhai; Dong, Jierong; Jiang, Yunyun

2008-11-04

A simple, accurate and rapid method for simultaneous analysis of vancomycin and ceftazidime in cerebrospinal fluid (CSF), utilizing high-performance liquid chromatography (HPLC), has been developed and thoroughly validated to satisfy strict FDA guidelines for bioanalytical methods. Protein precipitation was used as the sample pretreatment method. In order to increase the accuracy, tinidazole was chosen as the internal standard. Separation was achieved on a Diamonsil C18 column (200 mm x 4.6mm I.D., 5 microm) using a mobile phase composed of acetonitrile and acetate buffer (pH 3.5) (8:92, v/v) at room temperature (25 degrees C), and the detection wavelength was 240 nm. All the validation data, such as accuracy, precision, and inter-day repeatability, were within the required limits. The method was applied to determine vancomycin and ceftazidime concentrations in CSF in five craniotomy patients.

A Pooled Analysis of the Phase 3 REVIVE Trials: Randomized, Double-blind Studies to EValuate the Safety and Efficacy of Iclaprim Versus Vancomycin for trEatment of Acute Bacterial Skin and Skin Structure Infections.

Science.gov (United States)

Huang, David B; Corey, G Ralph; Holland, Thomas L; Lodise, Thomas; O'Riordan, William; Wilcox, Mark H; File, Thomas M; Dryden, Matthew; Balser, Barbara; Desplats, Eve; Torres, Antoni

2018-05-18

Iclaprim, a diaminopyrimidine antibiotic, was compared with vancomycin for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSIs) in two studies (REVIVE-1 and REVIVE-2). We explored the efficacy and tolerability of iclaprim in a pooled analysis of results from both studies. REVIVE-1 and REVIVE-2 were Phase 3, double-blind, randomized (1:1), multicenter, active-controlled, non-inferiority (margin of 10%) trials, each designed to enroll 600 patients a piece with ABSSSI. The studies used identical study protocols. Iclaprim 80 mg and vancomycin 15 mg/kg were administered IV every 12 hours for 5-14 days. The primary endpoint was a ≥20% reduction from baseline in lesion size (early clinical response [ECR]) at the early time point (48 to 72 hours after the start of study drug) in the intent-to-treat population. In REVIVE-1, ECR at the early time point was 80.9% with iclaprim vs. 81.0% with vancomycin (treatment difference, -0.13%; 95% confidence interval, -6.42% to 6.17%). In REVIVE-2, ECR was 78.3% with iclaprim vs. 76.7% with vancomycin (treatment difference: 1.58%, 95% CI: -5.10% to 8.26%). The pooled ECR was 79.6% with iclaprim vs. 78.8% with vancomycin (treatment difference: 0.75%, 95% CI: -3.84 to 5.35%). Iclaprim and vancomycin were comparable for the incidence of mostly mild adverse events, except for a higher incidence of elevated serum creatinine with vancomycin (n=7) compared with iclaprim (n=0). Iclaprim achieved noninferiority compared with vancomycin for early clinical response at the early time point and secondary endpoints with a similar safety profile in two Phase 3 studies for the treatment of ABSSSI suspected or confirmed to be caused by Gram-positive pathogens. NCT02600611 and NCT02607618. Copyright © 2018. Published by Elsevier B.V.

Nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus treated with linezolid or vancomycin: A secondary economic analysis of resource use from a Spanish perspective.

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Rello, J; Nieto, M; Solé-Violán, J; Wan, Y; Gao, X; Solem, C T; De Salas-Cansado, M; Mesa, F; Charbonneau, C; Chastre, J

2016-11-01

Adopting a unique Spanish perspective, this study aims to assess healthcare resource utilization (HCRU) and the costs of treating nosocomial pneumonia (NP) produced by methicillin-resistant Staphylococcus aureus (MRSA) in hospitalized adults using linezolid or vancomycin. An evaluation is also made of the renal failure rate and related economic outcomes between study groups. An economic post hoc evaluation of a randomized, double-blind, multicenter phase 4 study was carried out. Nosocomial pneumonia due to MRSA in hospitalized adults. The modified intent to treat (mITT) population comprised 224 linezolid- and 224 vancomycin-treated patients. Costs and HCRU were evaluated between patients administered either linezolid or vancomycin, and between patients who developed renal failure and those who did not. Analysis of HCRU outcomes and costs. Total costs were similar between the linezolid- (€17,782±€9,615) and vancomycin-treated patients (€17,423±€9,460) (P=.69). The renal failure rate was significantly lower in the linezolid-treated patients (4% vs. 15%; Prenal failure (€19,626±€10,840 vs. €17,388±€9,369; P=.14). Among the patients who developed renal failure, HCRU (days on mechanical ventilation: 13.2±10.7 vs. 7.6±3.6 days; P=.21; ICU stay: 14.4±10.5 vs. 9.9±6.6 days; P=.30; hospital stay: 19.5±9.5 vs. 16.1±11.0 days; P=.26) and cost (€17,219±€8,792 vs. €20,263±€11,350; P=.51) tended to be lower in the linezolid- vs. vancomycin-treated patients. There were no statistically significant differences in costs per patient-day between cohorts after correcting for mortality (€1000 vs. €1,010; P=.98). From a Spanish perspective, there were no statistically significant differences in total costs between the linezolid and vancomycin pneumonia cohorts. The drug cost corresponding to linezolid was partially offset by fewer renal failure adverse events. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Biodegradable drug-eluting nanofiber-enveloped implants for sustained release of high bactericidal concentrations of vancomycin and ceftazidime: in vitro and in vivo studies

Directory of Open Access Journals (Sweden)

Hsu YH

2014-09-01

Full Text Available Yung-Heng Hsu,1,2 Dave Wei-Chih Chen,1 Chun-Der Tai,3 Ying-Chao Chou,1,2 Shih-Jung Liu,2 Steve Wen-Neng Ueng,1 Err-Cheng Chan4 1Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Guishan Township, 2Department of Mechanical Engineering, Chang Gung University, Guishan Township, 3Graduate Institute of Medical Mechatronics, Chang Gung University, Guishan Township, 4School of Medical Technology, Chang Gung University, Guishan Township, Taiwan Abstract: We developed biodegradable drug-eluting nanofiber-enveloped implants that provided sustained release of vancomycin and ceftazidime. To prepare the biodegradable nanofibrous membranes, poly(D,L-lactide-co-glycolide and the antibiotics were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into biodegradable drug-eluting membranes, which were then enveloped on the surface of stainless plates. An elution method and a high-performance liquid chromatography assay were employed to characterize the in vivo and in vitro release rates of the antibiotics from the nanofiber-enveloped plates. The results showed that the biodegradable nanofiber-enveloped plates released high concentrations of vancomycin and ceftazidime (well above the minimum inhibitory concentration for more than 3 and 8 weeks in vitro and in vivo, respectively. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity ranged from 25% to 100%. In addition, the serum creatinine level remained within the normal range, suggesting that the high vancomycin concentration did not affect renal function. By adopting the electrospinning technique, we will be able to manufacture biodegradable drug-eluting implants for the long-term drug delivery of different antibiotics. Keywords: biodegradable nanofiber-enveloped plates, electrospinning, antibiotics, release characteristics

The adsorption of tetracycline and vancomycin onto nanodiamond with controlled release.

Science.gov (United States)

Giammarco, James; Mochalin, Vadym N; Haeckel, James; Gogotsi, Yury

2016-04-15

The unique properties and tailorable surface of detonation nanodiamonds have given rise to an abundance of potential biomedical applications. Very little is known about the details of adsorption/desorption equilibria of drugs on/from nanodiamonds with different purity, surface chemistry, and agglomeration state. The studies presented here delve into the details of adsorption and desorption of tetracycline (TET) and vancomycin (VAN) on nanodiamond, which are critically important for the rational design of the nanodiamond drug delivery systems. The nanodiamonds studied in these experiments were as-received (ND), purified and carboxyl terminated (ND-COOH), and aminated (ND-NH2). The monolayer capacities of the drugs loaded onto the nanodiamonds are reported herein using Langmuir and Freundlich isotherm models. The results from the desorption studies demonstrate that, by changing the pH environment of drug loaded nanodiamond using buffers of pH 4.09, 7.45, 8.02, and a phosphate buffered saline (PBS) solution, the drug release can effectively be triggered. Copyright © 2016 Elsevier Inc. All rights reserved.

Efficacy and Safety of Oritavancin Relative to Vancomycin for Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in the Outpatient Setting: Results From the SOLO Clinical Trials.

Science.gov (United States)

Lodise, Thomas P; Redell, Mark; Armstrong, Shannon O; Sulham, Katherine A; Corey, G Ralph

2017-01-01

The objective of this analysis was to evaluate the efficacy and safety of oritavancin compared with vancomycin for patients with acute bacterial skin and skin structure infections (ABSSSIs) who received treatment in the outpatient setting in the Phase 3 SOLO clinical trials. SOLO I and SOLO II were 2 identically designed comparative, multicenter, double-blind, randomized studies to evaluate the efficacy and safety of a single 1200-mg dose of intravenous (IV) oritavancin versus 7-10 days of twice-daily IV vancomycin for the treatment of ABSSSI. Protocols were amended to allow enrolled patients to complete their entire course of antimicrobial therapy in an outpatient setting. The primary efficacy outcome was a composite endpoint (cessation of spread or reduction in size of the baseline lesion, absence of fever, and no rescue antibiotic at early clinical evaluation [ECE]) (48 to 72 hours). Key secondary endpoints included investigator-assessed clinical cure 7 to 14 days after end of treatment (posttherapy evaluation [PTE]) and 20% or greater reduction in lesion area at ECE. Safety was assessed until day 60. Seven hundred ninety-two patients (oritavancin, 392; vancomycin, 400) received entire course of treatment in the outpatient setting. Efficacy response rates at ECE and PTE were similar (primary composite endpoint at ECE: 80.4% vs 77.5% for oritavancin and vancomycin, respectively) as was incidence of adverse events. Five patients (1.3%) who received oritavancin and 9 (2.3%) vancomycin patients were subsequently admitted to a hospital. Oritavancin provides a single-dose alternative to multidose vancomycin for treatment of ABSSSI in the outpatient setting. © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Nurses' experience with vancomycin-resistant enterococci (VRE).

Science.gov (United States)

Mitchell, Ann; Cummins, Teresa; Spearing, Natalie; Adams, June; Gilroy, Lisa

2002-01-01

The emergence and spread of resistant organisms, in particular vancomycin-resistant enterococci (VRE), is an issue facing all staff in acute hospitals. This study explored how nurses coped with the responsibility of halting further spread of this organism during an outbreak. VRE-positive patients were cohorted with nurses who cared for them in an endeavour to contain the spread of VRE. The majority of nurses found the situation extremely stressful because of the need to act as 'gatekeepers' responsible for educating and monitoring the practices of staff and visitors. The nurses reported that they felt they were inadequately supported, were blamed for the outbreak, and that they had an increased workload as they took on duties of other staff. The results reinforce the need for a multidisciplinary team approach to education and control of VRE, more support for nursing staff cohorted with VRE-positive patients, and stringent adherence to infection control measures by all hospital staff.

Clinical response and hospital costs associated with the empirical use of vancomycin and linezolid for hospital-acquired pneumonia in a Chinese tertiary care hospital: a retrospective cohort study

Directory of Open Access Journals (Sweden)

Song Y

2014-10-01

Full Text Available Yuanlin Song,1,* Yicheng Yang,2,* Wendong Chen,3,4 Wei Liu,2 Kai Wang,2 Xuehai Li,5 Ke Wang,2 Manny Papadimitropoulos,3,6 William Montgomery7 1Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 2Lilly Suzhou Pharmaceutical Co, Ltd, Shanghai Branch, Shanghai, People's Republic of China; 3Division of Social and Administrative Pharmacy, Leslie Dan Faculty of Pharmacy, University of Toronto, 4Normin Health, Toronto, ON, Canada; 5VitalStrategic Research Institute, Shanghai, People's Republic of China; 6Global Health Outcomes Research, Eli Lilly, Indianapolis, IN, USA; 7Eli Lilly Australia Pty Ltd, West Ryde, NSW, Australia *These authors contributed equally to this work Aims: To evaluate clinical outcomes and allocation of hospital costs associated with empirical use of vancomycin or linezolid for hospital-acquired pneumonia (HAP in the People's Republic of China. Methods: Hospital episodes including HAP treated by vancomycin or linezolid between 2008 and 2012 in a Chinese tertiary care hospital were retrospectively identified from hospital administrative databases. Propensity score methods created best-matched pairs for the antibiotics. The matched pairs were used for adjusted comparisons on clinical response and allocation of hospital costs. Multiple regression analyses adjusting residual imbalance after matching were performed to confirm adjusted comparisons. Results: Sixty matched pairs were created. Adjusted comparisons between vancomycin and linezolid showed similar clinical response rates (clinical cure: 30.0% versus 31.7%, respectively; P=0.847; treatment failure: 55.0% versus 45.0%, respectively; P=0.289 but a significantly lower in-hospital mortality rate for vancomycin (3.3% versus 18.3%, respectively; P=0.013. After further adjusting for the imbalanced variables between matched treatment groups, the risks of treatment failure associated with the two antibiotics were comparable (odds ratio: 1.139; P=0.308 and there was

The effects of amoxicillin and vancomycin on parameters reflecting cholesterol metabolism.

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Baumgartner, S; Reijnders, D; Konings, M C J M; Groen, A K; Lütjohann, D; Goossens, G H; Blaak, E E; Plat, J

2017-10-01

Changes in the microbiota composition have been implicated in the development of obesity and type 2 diabetes. However, not much is known on the involvement of gut microbiota in lipid and cholesterol metabolism. In addition, the gut microbiota might also be a potential source of plasma oxyphytosterol and oxycholesterol concentrations (oxidation products of plant sterols and cholesterol). Therefore, the aim of this study was to modulate the gut microbiota by antibiotic therapy to investigate effects on parameters reflecting cholesterol metabolism and oxyphytosterol concentrations. A randomized, double blind, placebo-controlled trial was performed in which 55 obese, pre-diabetic men received oral amoxicillin (broad-spectrum antibiotic), vancomycin (antibiotic directed against Gram-positive bacteria) or placebo (microcrystalline cellulose) capsules for 7days (1500mg/day). Plasma lipid and lipoprotein, non-cholesterol sterol, bile acid and oxy(phyto)sterol concentrations were determined at baseline and after 1-week intervention. Plasma secondary bile acids correlated negatively with cholestanol (marker for cholesterol absorption, r=-0.367; Pcholesterol synthesis, r=0.430; Pcholesterol metabolism, plasma TAG, total cholesterol, LDL-C or HDL-C concentrations as compared to placebo. In addition, both antibiotic treatments did not affect individual isoforms or total plasma oxyphytosterol or oxycholesterol concentrations. Despite strong correlations between plasma bile acid concentrations and cholesterol metabolism (synthesis and absorption), amoxicillin and vancomycin treatment for 7days did not affect plasma lipid and lipoprotein, plasma non-cholesterol sterol and oxy(phyto)sterol concentrations in obese, pre-diabetic men. Copyright © 2017 Elsevier B.V. All rights reserved.

Vancomycin resistant Enterococcus spp. from crows and their environment in metropolitan Washington State, USA: Is there a correlation between VRE positive crows and the environment?

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Roberts, Marilyn C; No, David B; Marzluff, John M; Delap, Jack H; Turner, Robert

2016-10-15

Vancomycin-resistant enterococci [VRE] have been isolated from municipal, hospital and agricultural wastewater, recreational beaches, wild animals, birds and food animals around the world. In this study, American crows (Corvus brachyrhynchos) from sewage treatment plants (WWTP), dairy farms, and a large roost in a restored wetland with corresponding environmental samples were cultured for VRE. A total of 245 samples [156 crows, 89 environmental] were collected and screened for acquired vanA, vanB and/or intrinsic vanC1 genes. Samples were enriched overnight in BHI supplemented with 20μg/mL aztreonam, 4μg/mL vancomycin and plated on m-Enterococcus agar media supplemented with 6μg/mL vancomycin. Selected colonies were grown on BHI media supplemented with 18μg/mL vancomycin. Of these, 24.5% of the crow and 55% the environmental/cow samples were VRE positive as defined by Enterococcus spp. able to grow on media supplemented with 18μg/mL vancomycin. A total of 122 VRE isolates, 43 crow and 79 environmental isolates were screened, identified to species level using 16S sequencing and further characterized. Four vanA E. faecium and multiple vanC1 E. gallinarum were identified from crows isolated from three sites. E. faecium vanA and E. gallinarum vanC1 along with other Enterococcus spp. carrying vanA, vanB, vanC1 were isolated from three environments. All enterococci were multidrug resistant. Crows were more likely to carry vanA E. faecium than either the cow feces or wetland waters/soils. Comparing E. gallinarum vanC1 from crows and their environment would be useful in determining whether crows share VRE strains with their environment. Copyright © 2016 Elsevier B.V. All rights reserved.

Analysis of the world epidemiological situation among vancomycin-resistant Enterococcus faecium infections and the current situation in Poland

Science.gov (United States)

Talaga-Ćwiertnia, Katarzyna; Bulanda, Małgorzata

2018-01-01

Vancomycin-resistant Enterococcus faecium (VREfm) strains have become an important hospital pathogen due to their rapid spread, high mortality rate associated with infections and limited therapeutic options. Vancomycin resistance is predominantly mediated by VanA or VanB phenotypes, which differ as regards maintaining sensitivity to teicoplanin in the VanB phenotype. The majority of VREfm cases in the United States, Europe, Korea, South America and Africa are currently caused by the VanA phenotype. However, the epidemics in Australia and Singapore are chiefly brought about by the VanB phenotype. The rate of VREfm isolate spread varies greatly. The greatest percentage of VREfm is now recorded in the USA, Ireland and Australia. Supervision of VRE is implemented to varying degrees. Therefore, the epidemiological situation in some countries is difficult to assess due to limited data or lack thereof.

Cierny-Mader Type III chronic osteomyelitis: the results of patients treated with debridement, irrigation, vancomycin beads and systemic antibiotics

Science.gov (United States)

Karaduman, Mert

2007-01-01

Cierny-Mader (C-M) Type III osteomyelitis is defined as a localised lesion with both medullary and cortical involvement that is stable mechanically after debridement. The treatment of C-M Type III osteomyelitisis is difficult and requires a precise protocol to achieve a disease-free long-term follow-up. We report here the results of our study on 26 patients (19 men and 7 women; average age: 34.7 years) with C-M Type III osteomylelitis who were treated with radical debridement, irrigation, vancomycin-impregnated custom-made beads and culture-specific systemic antibiotics. Those patients with metaphyseal involvement were treated with deroofing of the cortex and debridement by means of a “trough” (16 patients); those with diaphyseal involvement were treated with both intramedullary reaming and debridement from a trough (ten patients). Antibiotic cement rods were used as an additional therapy in five patients with diaphyseal involvement. Recurrence developed in three patients and was attributed to inadequate debridement; all three patients were treated again in the same manner with success. The mean follow-up is currently 3.6 years (range: 2–6 years). All of the patients have normal clinical, radiographic and laboratory parameters, and all are ambulatory and have returned to their pretreatment level of activity or better. We conclude that C-M Type III chronic osteomyelitis can be safely treated with this protocol. PMID:17375299

Enviromnental contamination during a vancomycin-resistant Enterococci outbreak at a hospital in Argentina

OpenAIRE

Zarate, Mariela Soledad; Gales, Ana [UNIFESP; Jordd-Vargas, L'fiana; Yahni, Diego; RelloSo, Silvia; Bonvehi, Pablo; Monteiro, Jussimara [UNIFESP; Campos-Pignatari, Antonio [UNIFESP; Smayevsky, Jorgelina [UNIFESP

2007-01-01

INTRODUCTION. Vancomycin-resistant enterococci isolates (VRE) have caused numerous outbreaks in intensive care units (ICUs). A contaminated hospital environment, the hands of health care workers (HCW), and carrier patients may play important roles in perpetuating the chain of transmission in these outbreaks. the aims of this study were to report the first VRE outbreak in our center and assess the role of environmental contamination and HCW hands in the spread of new cases of enterococcal infe...

Optimisation of the synthesis of vancomycin-selective molecularly imprinted polymer nanoparticles using automatic photoreactor

OpenAIRE

Muzyka, Kateryna; Karim, Khalku; Guerreiro, Antonio; Poma, Alessandro; Piletsky, Sergey

2014-01-01

A novel optimized protocol for solid-state synthesis of molecularly imprinted polymer nanoparticles (nanoMIPs) with specificity for antibiotic vancomycin is described. The experimental objective was optimization of the synthesis parameters (factors) affecting the yield of obtained nanoparticles which have been synthesized using the first prototype of an automated solid-phase synthesizer. Applications of experimental design (or design of experiments) in optimization of nanoMIP yield were carri...

Role of the transmembrane domain of the VanT serine racemase in resistance to vancomycin in Enterococcus gallinarum BM4174.

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Arias, C A; Peña, J; Panesso, D; Reynolds, P

2003-03-01

Enterococcus gallinarum BM4175 (a vancomycin-susceptible derivative of BM4174 obtained by insertional inactivation of vanC-1) was transformed with plasmid constructs pCA10 (containing the genes necessary for resistance, vanC-1-XYc-T), pJP1 (with a fragment lacking the DNA encoding the transmembrane region of VanT, -vanC-1-XYc-T((Delta))(2-322)-) and with plasmids containing fragments encoding either the transmembrane (mvanT(1-322)) or racemase (svanT(323-698)) domains of VanT under the control of a constitutive promoter. Accumulated peptidoglycan precursors were measured in all strains in the presence of L-Ser, D-Ser (50 mM) or in the absence of any growth supplement. Uptake of 0.1 mM L-[(14)C]serine was also determined in BM4174, BM4175 and BM4175/pCA10. Vancomycin resistance was restored in BM4175 transformed with pCA10(C-1-XYc-T), and the profile of peptidoglycan precursors was similar to wild-type E. gallinarum BM4174. Transformation of E. gallinarum BM4175 with plasmid pJP1(vanC-1-XYc-T((Delta))(2-322)) resulted in: (i) vancomycin MICs remaining within susceptible levels (VanT is likely to be involved in the transport of L-Ser, and that in its absence the resistance phenotype is compromised.

Increasing Incidence of Linezolid-Intermediate or -Resistant, Vancomycin-Resistant Enterococcus faecium Strains Parallels Increasing Linezolid Consumption▿

OpenAIRE

Scheetz, Marc H.; Knechtel, Stephanie A.; Malczynski, Michael; Postelnick, Michael J.; Qi, Chao

2008-01-01

Clinical enterococcal resistance to linezolid is defined by the presence of the G2576T mutation. We evaluated the incidence of genetically proven linezolid resistance among vancomycin-resistant Enterococcus faecium strains and linezolid consumption for a possible association. A relationship was found (r2 = 0.73, P = 0.03) and predicts increasing resistance with current trends of linezolid use.

Routine disc diffusion antimicrobial susceptibility testing of Clostridium difficile and association with PCR ribotype 027

DEFF Research Database (Denmark)

Holt, H M; Danielsen, T K; Justesen, U S

2015-01-01

Reduced susceptibility to metronidazole and vancomycin in Clostridium difficile has been reported, which emphasises the need for simple antimicrobial susceptibility testing methods. The aim of this study was to apply a published disc diffusion method and zone diameter breakpoint correlates...... the published breakpoint (difficile PCR ribotype 027 isolates had smaller zone...... diameters than non-027 isolates. The disc diffusion method is very simple and inexpensive, and the published zone diameter breakpoints will detect C. difficile isolates with reduced susceptibility to metronidazole and vancomycin....

Comparison of vancomycin and linezolid in patients with peripheral vascular disease and/or diabetes in an observational European study of complicated skin and soft-tissue infections due to methicillin-resistant Staphylococcus aureus.

Science.gov (United States)

Eckmann, C; Nathwani, D; Lawson, W; Corman, S; Solem, C; Stephens, J; Macahilig, C; Li, J; Charbonneau, C; Baillon-Plot, N; Haider, S

2015-09-01

Suboptimal antibiotic penetration into soft tissues can occur in patients with poor circulation due to peripheral vascular disease (PVD) or diabetes. We conducted a real-world analysis of antibiotic treatment, hospital resource use and clinical outcomes in patients with PVD and/or diabetes receiving linezolid or vancomycin for the treatment of methicillin-resistant Staphylococcus aureus complicated skin and soft-tissue infections (MRSA cSSTIs) across Europe. This subgroup analysis evaluated data obtained from a retrospective, observational medical chart review study that captured patient data from 12 European countries. Data were obtained from the medical records of patients ≥ 18 years of age, hospitalized with an MRSA cSSTI between 1 July 2010 and 30 June 2011 and discharged alive by 31 July 2011. Hospital length of stay and length of treatment were compared between the treatment groups using inverse probability of treatment weights to adjust for clinical and demographic differences. A total of 485 patients had PVD or diabetes and received treatment with either vancomycin (n = 258) or linezolid (n = 227). After adjustment, patients treated with linezolid compared with vancomycin respectively had significantly shorter hospital stays (17.9 ± 13.6 vs. 22.6 ± 13.6 days; p linezolid and vancomycin groups, respectively (p linezolid compared with vancomycin. Copyright © 2015. Published by Elsevier Ltd.

Outbreak of vancomycin-resistant Enterococcus faecium in a haematology unit: risk factor assessment and successful control of the epidemic

NARCIS (Netherlands)

Timmers, Gert Jan; van der Zwet, Wil C.; Simoons-Smit, Ina M.; Savelkoul, Paul H. M.; Meester, Helena H. M.; Vandenbroucke-Grauls, Christina M. J. E.; Huijgens, Peter C.

2002-01-01

We describe an outbreak of vancomycin-resistant Enterococcus faecium (VRE) on the haematology ward of a Dutch university hospital. After the occurrence of three consecutive cases of bacteraemia with VRE, strains were genotyped and found to be identical. During the next 4 months an intensive

The effect of diabetes mellitus on outcomes of patients with nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus: data from a prospective double-blind clinical trial comparing treatment with linezolid versus vancomycin.

Science.gov (United States)

Equils, Ozlem; da Costa, Christopher; Wible, Michele; Lipsky, Benjamin A

2016-09-06

The presence of diabetes mellitus increases the risk of several severe infections, but data on its effect on treatment outcomes in patients with nosocomial pneumonia (NP) caused by methicillin-resistant Staphylococcus aureus (MRSA) are limited. We retrospectively analyzed data from a double-blind, randomized, multi-center, international clinical trial of culture-confirmed MRSA NP that compared treatment with linezolid to vancomycin. Specifically, we evaluated the clinical and microbiologic outcomes of patients with and without diabetes in the modified intent to treat population at end-of-treatment (EOT) and end-of-study (EOS, 7-30 days post-EOT). Among 448 enrolled patients 183 (40.8 %) had diabetes mellitus, 87 (47.5 %) of whom received linezolid and 96 (52.5 %) vancomycin. Baseline demographic and clinical characteristics were similar for the two treatment groups. Clinical success rates at EOS were 57.6 % with linezolid and 39.3 % with vancomycin, while microbiological success rates were 58.9 % with linezolid and 41.1 % with vancomycin. Among diabetic patients, rates of mortality and study drug-related adverse effects were similar between the treatment groups. Overall day 28 mortality rates were higher among diabetic patients compared to non-diabetic patients (23.5 vs 14.7 %, respectively: RD = 8.8 %, 95 % CI [1.4, 16.3]). Among diabetic patients with MRSA NP, treatment with linezolid, compared to vancomycin, was associated with higher clinical and microbiologic success rates, and comparable adverse event rates. NCT00084266 .

Tedizolid susceptibility in linezolid- and vancomycin-resistant Enterococcus faecium isolates.

Science.gov (United States)

Klupp, E-M; Both, A; Belmar Campos, C; Büttner, H; König, C; Christopeit, M; Christner, M; Aepfelbacher, M; Rohde, H

2016-12-01

Vancomycin-resistant enterococci (VRE) are of ever-increasing importance, most notably in high-risk patient populations. Therapy options are often limited for these isolates, and apart from tigecycline and daptomycin, oxazolidinone linezolid is frequently administered. The broad usage of linezolid, however, has driven the emergence of linezolid-resistant VRE strains (LR-VRE), further shortening therapeutic options. Second-generation oxazolidinone tedizolid has the advantage of being active against a specific subset of LR-VRE, i.e. isolates expressing the plasmid-encoded chloramphenicol-florfenicol resistance (cfr) gene. Here we tested tedizolid activity in a collection of 30 LR Enterococcus faecium VRE (MIC range 32-256 mg/l) isolated between 2012 and 2015 from clinical and screening specimens. By pulsed field gel electrophoresis (PFGE) isolates were assigned to 16 clonal lineages. In three cases, linezolid-susceptible progenitor isolates of LR-VRE were isolated, thus demonstrating the de-novo emergence of the linezolid-resistant phenotype. PCR did not detect cfr, cfr(B) or novel oxazolidinone resistance gene optrA in LR-VRE. All isolates, however, carried mutations within the 23S rDNA. Compared to linezolid, tedizolid MICs were lower in all isolates (MIC range 2-32 mg/l), but remained above the FDA tedizolid breakpoint for E. faecalis at 0.5 mg/l. Thus, related to the predominant resistance mechanism, tedizolid is of limited value for treatment of most LR-VRE and represents a therapeutic option only for a limited subset of isolates.

An Outbreak of Vancomycin-Resistant Enterococcus faecium in an Acute Care Pediatric Hospital: Lessons from Environmental Screening and a Case-Control Study

Directory of Open Access Journals (Sweden)

Steven J Drews

2008-01-01

Full Text Available BACKGROUND: The present study describes a vancomycin-resistant enterococci (VRE outbreak investigation and a case-control study to identify risk factors for VRE acquisition in a tertiary care pediatric hospital.

Activity of daptomycin- and vancomycin-loaded poly-epsilon-caprolactone microparticles against mature staphylococcal biofilms

Directory of Open Access Journals (Sweden)

Santos Ferreira I

2015-07-01

Full Text Available Inês Santos Ferreira,1 Ana F Bettencourt,1 Lídia MD Gonçalves,1 Stefanie Kasper,2 Bertrand Bétrisey,3 Judith Kikhney,2 Annette Moter,2 Andrej Trampuz,4 António J Almeida1 1Research Institute for Medicines (iMed.ULisboa, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal; 2Biofilmcenter, German Heart Institute Berlin, Berlin, Germany; 3Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; 4Center for Musculoskeletal Surgery, Charité – University Medicine Berlin, Berlin, Germany Abstract: The aim of the present study was to develop novel daptomycin-loaded poly-epsilon-caprolactone (PCL microparticles with enhanced antibiofilm activity against mature biofilms of clinically relevant bacteria, methicillin-resistant Staphylococcus aureus (MRSA and polysaccharide intercellular adhesin-positive Staphylococcus epidermidis. Daptomycin was encapsulated into PCL microparticles by a double emulsion-solvent evaporation method. For comparison purposes, formulations containing vancomycin were also prepared. Particle morphology, size distribution, encapsulation efficiency, surface charge, thermal behavior, and in vitro release were assessed. All formulations exhibited a spherical morphology, micro­meter size, and negative surface charge. From a very early time stage, the released concentrations of daptomycin and vancomycin were higher than the minimal inhibitory concentration and continued so up to 72 hours. Daptomycin presented a sustained release profile with increasing concentrations of the drug being released up to 72 hours, whereas the release of vancomycin stabilized at 24 hours. The antibacterial activity of the microparticles was assessed by isothermal microcalorimetry against planktonic and sessile MRSA and S. epidermidis. Regarding planktonic bacteria, daptomycin-loaded PCL microparticles presented the highest antibacterial activity against both strains. Isothermal

Transposon characterization of vancomycin-resistant Enterococcus faecium (VREF) and dissemination of resistance associated with transferable plasmids

DEFF Research Database (Denmark)

Migura, Lourdes Garcia; Liebana, Ernesto; Jensen, Lars Bogø

2007-01-01

Objectives: VanA glycopeptide resistance has persisted on broiler farms in the UK despite the absence of the antimicrobial selective pressure, avoparcin. This study aimed to investigate the contribution of horizontal gene transfer of Tn 1546 versus clonal spread in the dissemination of the resist......Objectives: VanA glycopeptide resistance has persisted on broiler farms in the UK despite the absence of the antimicrobial selective pressure, avoparcin. This study aimed to investigate the contribution of horizontal gene transfer of Tn 1546 versus clonal spread in the dissemination...... plasmid replicons, associated with antimicrobial resistance on several unrelated farms. Conclusions: Horizontal transfer of vancomycin resistance may play a more important role in the persistence of antimicrobial resistance than clonal spread. The presence of different plasmid replicons, associated...... with antimicrobial resistance on several unrelated farms, illustrates the ability of these enterococci to acquire and disseminate mobile genetic elements within integrated livestock systems....

Biochemical characterization of systemic bacteria in bananas, sensitivity to antibiotics and plant phytotoxicity during shoot proliferation

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Janiffe Peres de Oliveira

2016-04-01

Full Text Available The objective of this work was to characterize the biochemically systemic bacterial isolated from banana plants, to evaluate the bacterial sensitivity to antibiotics, and to determine the phytotoxicity of banana shoots during in vitro proliferation. Systemic bacteria belonging to the Klebsiella and Aeromonas genera were isolated from the “Maravilha” (FHIA 01 AAAB, “Preciosa” (PV 4285 AAAB and “Thap Maeo” (AAB varieties and were then characterized. Tests of shoot sensitivity to antibiotics were performed, and the minimum inhibitory concentration (MIC and phytotoxic effects of selected antibiotics to plants were determined. Among the 20 antibiotics evaluated, the strains showed sensitivity to cefaclor, cefalexin, cefalotin, nalidixic acid, chloramphenicol, and vancomycin. However, during MIC determination, the best results were obtained with cefaclor, vancomycin or nalidixic acid alone in concentrations ranging from 512 to 1,024 mg L-1. In culture medium, cefaclor at 1,024 mg L-1 was the only antibiotic to affect the multiplication and the shoot survival in culture.

An open-label, pragmatic, randomized controlled clinical trial to evaluate the comparative effectiveness of daptomycin versus vancomycin for the treatment of complicated skin and skin structure infection.

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Kauf, Teresa L; McKinnon, Peggy; Corey, G Ralph; Bedolla, John; Riska, Paul F; Sims, Matthew; Jauregui-Peredo, Luis; Friedman, Bruce; Hoehns, James D; Mercier, Renée-Claude; Garcia-Diaz, Julia; Brenneman, Susan K; Ng, David; Lodise, Thomas

2015-11-07

Treatment of complicated skin and skin structure infection (cSSSI) places a tremendous burden on the health care system. Understanding relative resource utilization associated with different antimicrobials is important for decision making by patients, health care providers, and payers. The authors conducted an open-label, pragmatic, randomized (1:1) clinical study (N = 250) to compare the effectiveness of daptomycin with that of vancomycin for treatment of patients hospitalized with cSSSI caused by suspected or documented methicillin-resistant Staphylococcus aureus infection. The primary study end point was infection-related length of stay (IRLOS). Secondary end points included health care resource utilization, cost, clinical response, and patient-reported outcomes. Patient assessments were performed daily until the end of antibiotic therapy or until hospital discharge, and at 14 days and 30 days after discharge. No difference was found for IRLOS, total LOS, and total inpatient cost between cohorts. Hospital LOS contributed 85.9% to the total hospitalization cost, compared with 6.4% for drug costs. Daptomycin showed a nonsignificant trend toward a higher clinical success rate, compared with vancomycin, at treatment days 2 and 3. In the multivariate analyses, vancomycin was associated with a lower likelihood of day 2 clinical success (odds ratio [OR] = 0.498, 95% confidence interval [CI], 0.249-0.997; P < 0.05). This study did not provide conclusive evidence of the superiority of one treatment over the other in terms of clinical, economic, or patient outcomes. The data suggest that physician and patient preference, rather than drug acquisition cost, should be the primary driver of initial antibiotic selection for hospitalized patients with cSSSI. ClinicalTrials.gov: NCT01419184 (Date: August 16, 2011).

Identification of putative drug targets in Vancomycin-resistant Staphylococcus aureus (VRSA) using computer aided protein data analysis.

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Hasan, Md Anayet; Khan, Md Arif; Sharmin, Tahmina; Hasan Mazumder, Md Habibul; Chowdhury, Afrin Sultana

2016-01-01

Vancomycin-resistant Staphylococcus aureus (VRSA) is a Gram-positive, facultative aerobic bacterium which is evolved from the extensive exposure of Vancomycin to Methicillin resistant S. aureus (MRSA) that had become the most common cause of hospital and community-acquired infections. Due to the emergence of different antibiotic resistance strains, there is an exigency to develop novel drug targets to address the provocation of multidrug-resistant bacteria. In this study, in-silico genome subtraction methodology was used to design potential and pathogen specific drug targets against VRSA. Our study divulged 1987 proteins from the proteome of 34,549 proteins, which have no homologues in human genome after sequential analysis through CD-HIT and BLASTp. The high stringency analysis of the remaining proteins against database of essential genes (DEG) resulted in 169 proteins which are essential for S. aureus. Metabolic pathway analysis of human host and pathogen by KAAS at the KEGG server sorted out 19 proteins involved in unique metabolic pathways. 26 human non-homologous membrane-bound essential proteins including 4 which were also involved in unique metabolic pathway were deduced through PSORTb, CELLO v.2.5, ngLOC. Functional classification of uncharacterized proteins through SVMprot derived 7 human non-homologous membrane-bound hypothetical essential proteins. Study of potential drug target against Drug Bank revealed pbpA-penicillin-binding protein 1 and hypothetical protein MQW_01796 as the best drug target candidate. 2D structure was predicted by PRED-TMBB, 3D structure and functional analysis was also performed. Protein-protein interaction network of potential drug target proteins was analyzed by using STRING. The identified drug targets are expected to have great potential for designing novel drugs against VRSA infections and further screening of the compounds against these new targets may result in the discovery of novel therapeutic compounds that can be

Cost-Effectiveness Comparison of Fidaxomicin and Vancomycin for Treatment of Clostridium difficile Infection: A Markov Model Based on Data from a South West Balkan Country in Socioeconomic Transition.

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Marković, Veroljub; Kostić, Marina; Iličković, Ivana; Janković, Slobodan M

2014-09-01

Recent studies have shown that fidaxomicin, a novel antibiotic, can reduce the rate of complications and mortality in patients with colitis induced by Clostridium difficile. Introduction of fidaxomicin in clinical practice is limited by its high costs. The purpose of this study was to estimate the cost effectiveness of using fidaxomicin versus vancomycin in patients with colitis induced by C. difficile who did not respond to oral metronidazole. We constructed a Markov model that was than simulated by Monte-Carlo simulation using 1000 virtual patients with colitis induced by C. difficile. The perspective in our model was institutional. The time horizon was 3 months. Values of transition probabilities and therapy outcomes were estimated from the available literature, the prices of health services were obtained from the Republic Institute for Health Insurance Tariff Book, and the price of fidaxomicin was derived from data gained from the drug manufacturer. The total costs of treating one statistical patient for 3 months with fidaxomicin were higher (48,106.19 ± 118.07 Republic of Serbia dinars [RSD]; 95% confidence interval 47,988.12-48,224.27) than the total costs of treating with vancomycin (25,872.85 ± 41.44 RSD; 95% confidence interval 25,831.41-25,914.29). Our results showed that the treatment of infections induced by C. difficile with fidaxomicin correlated with a lower rate of mortality and with a smaller number of colectomies. The incremental cost-effectiveness ratio of fidaxomicin versus vancomycin for colitis induced by C. difficile per saved life was estimated at 2.97 million RSD and for one avoided colectomy at 10.07 million RSD. Results of our model indicate that fidaxomicin is a cost-effective therapy compared with vancomycin in patients with colitis induced by C. difficile if the outcome is life-year saved. However, if the outcome is the number of avoided colectomies, then fidaxomycin is not a cost-effective option compared with vancomycin. Copyright

Epidemiology of Extended-Spectrum beta-Lactamase-Producing E-coli and Vancomycin-Resistant Enterococci in the Northern Dutch-German Cross-Border Region

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Zhou, Xuewei; Garcia-Cobos, Silvia; Ruijs, Gijs J. H. M.; Kampinga, Greetje A.; Arends, Jan P.; Borst, Dirk M.; Moller, Lieke V.; Holman, Nicole D.; Schuurs, Theo A.; van Coppenraet, Lesla E. Bruijnesteijn; Weel, Jan F.; van Zeijl, Jan H.; Koeck, Robin; Rossen, John W. A.; Friedrich, Alexander W.

2017-01-01

Objectives: To reveal the prevalence and epidemiology of extended-spectrum β-lactamase (ESBL)- and/or plasmid AmpC (pAmpC)- and carbapenemase (CP) producing Enterobacteriaceae and vancomycin-resistant enterococci (VRE) across the Northern Dutch-German border region. Methods: A point-prevalence study

Synergistic effect of Carum copticum and Mentha piperita essential oils with ciprofloxacin, vancomycin, and gentamicin on Gram-negative and Gram-positive bacteria

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Talei, Gholam-Reza; Mohammadi, Mohsen; Bahmani, Mahmoud; Kopaei, Mahmoud Rafieian

2017-01-01

Background: Infectious diseases have always been an important health issue in human communities. In the recent years, much research has been conducted on antimicrobial effects of nature-based compounds because of increased prevalence of antibiotic resistance. The present study was conducted to investigate synergistic effect of Carum copticum and Mentha piperita essential oils with ciprofloxacin, vancomycin, and gentamicin on Gram-negative and Gram-positive bacteria. Materials and Methods: In this experimental study, the synergistic effects of C. copticum and M. piperita essential oils with antibiotics on Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC 29212), Escherichia coli (ATCC 8739), Pseudomonas aeruginosa (ATCC 9027), Staphylococcus epidermidis (ATCC 14990), and Listeria monocytogenes (ATCC 7644) were studied according to broth microdilution and the MIC and fractional inhibitory concentration (FIC) of these two essential oils determined. Results: C. copticum essential oil at 30 μg/ml could inhibit S. aureus, and in combination with vancomycin, decreased MIC from 0.5 to 0.12 μg/ml. Moreover, the FIC was derived 0.24 μg/ml which represents a potent synergistic effect with vancomycin against S. aureus growth. C. copticum essential oil alone or combined with other antibiotics is effective in treating bacterial infections. Conclusions: In addition, C. copticum essential oil can strengthen the activities of certain antibiotics, which makes it possible to use this essential oil, especially in drug resistance or to lower dosage or toxicity of the drugs. PMID:28929050

Energy Systems Test Area (ESTA). Power Systems Test Facilities

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Situ, Cindy H.

2010-01-01

This viewgraph presentation provides a detailed description of the Johnson Space Center's Power Systems Facility located in the Energy Systems Test Area (ESTA). Facilities and the resources used to support power and battery systems testing are also shown. The contents include: 1) Power Testing; 2) Power Test Equipment Capabilities Summary; 3) Source/Load; 4) Battery Facilities; 5) Battery Test Equipment Capabilities Summary; 6) Battery Testing; 7) Performance Test Equipment; 8) Battery Test Environments; 9) Battery Abuse Chambers; 10) Battery Abuse Capabilities; and 11) Battery Test Area Resources.

Screening municipal wastewater effluent and surface water used for drinking water production for the presence of ampicillin and vancomycin resistant enterococci

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Taucer-Kapteijn, M.; Hoogenboezem, Wim; Heiliegers, Laura; de Bolster, Danny; Medema, G.

2016-01-01

The emergence of clinical enterococcal isolates that are resistant to both ampicillin and vancomycin is a cause of great concern, as therapeutic alternatives for the treatment of infections caused by such organisms are becoming limited. Aquatic environments could play a role in the dissemination

Detection of Fusobacterium nucleatum in two cases of empyema and lung abscess using paromomycin-vancomycin supplemented Brucella HK agar.

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Nagaoka, Kentaro; Yanagihara, Katsunori; Morinaga, Yoshitomo; Kohno, Shigeru

2017-02-01

Fusobacterium nucleatum was found in patients with empyema or pulmonary abscess, using paromomycin-vancomycin Brucella HK agar. In vitro examination revealed that growth of the strains differed significantly in different media. Clinicians should be aware that suboptimal F. nucleatum cultivation methods may result in an underestimation of its frequency. Copyright © 2016 Elsevier Ltd. All rights reserved.

Vancomycin-modified Fe3O4@SiO2@Ag microflowers as effective antimicrobial agents

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Wang C

2017-04-01

Full Text Available Chongwen Wang,1,2,* Kehan Zhang,2,* Zhe Zhou,2,* Qingjun Li,2 Liting Shao,2 Rong Zhang Hao,3 Rui Xiao,2 Shengqi Wang1,2 1College of Life Sciences & Bio-Engineering, Beijing University of Technology, 2Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing Institute of Radiation Medicine, Beijing, 3Institute for Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Nanomaterials combined with antibiotics exhibit synergistic effects and have gained increasing interest as promising antimicrobial agents. In this study, vancomycin-modified magnetic-based silver microflowers (Van/Fe3O4@SiO2@Ag microflowers were rationally designed and prepared to achieve strong bactericidal ability, a wide antimicrobial spectrum, and good recyclability. High-performance Fe3O4@SiO2@Ag microflowers served as a multifunction-supporting matrix and exhibited sufficient magnetic response property due to their 200 nm Fe3O4 core. The microflowers also possessed a highly branched flower-like Ag shell that provided a large surface area for effective Ag ion release and bacterial contact. The modified-vancomycin layer was effectively bound to the cell wall of bacteria to increase the permeability of the cell membrane and facilitate the entry of the Ag ions into the bacterium, resulting in cell death. As such, the fabricated Van/Fe3O4@SiO2@Ag microflowers were predicted to be an effective and environment-friendly antibacterial agent. This hypothesis was verified through sterilization of Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus, with minimum inhibitory concentrations of 10 and 20 µg mL-1, respectively. The microflowers also showed enhanced effect compared with bare Fe3O4@SiO2@Ag microflowers and free-form vancomycin, confirming the synergistic effects of the combination of the

A Phase 3, Randomized, Double-Blind, Multicenter Study to Evaluate the Safety and Efficacy of Intravenous Iclaprim Vs Vancomycin for the Treatment of Acute Bacterial Skin and Skin Structure Infections Suspected or Confirmed to be Due to Gram-Positive Pathogens: REVIVE-1.

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Huang, David B; O'Riordan, William; Overcash, J Scott; Heller, Barry; Amin, Faisal; File, Thomas M; Wilcox, Mark H; Torres, Antoni; Dryden, Matthew; Holland, Thomas L; McLeroth, Patrick; Shukla, Rajesh; Corey, G Ralph

2018-04-03

Our objective in this study was to demonstrate the safety and efficacy of iclaprim compared with vancomycin for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSIs). REVIVE-1 was a phase 3, 600-patient, double-blinded, randomized (1:1), active-controlled trial among patients with ABSSSI that compared the safety and efficacy of iclaprim 80 mg fixed dose with vancomycin 15 mg/kg, both administered intravenously every 12 hours for 5-14 days. The primary endpoint of this study was a ≥20% reduction in lesion size (early clinical response [ECR]) compared with baseline among patients randomized to iclaprim or vancomycin at the early time point (ETP), 48 to 72 hours after the start of administration of study drug in the intent-to-treat population. ECR among patients who received iclaprim and vancomycin at the ETP was 80.9% (241 of 298) of patients receiving iclaprim compared with 81.0% (243 of 300) of those receiving vancomycin (treatment difference, -0.13%; 95% confidence interval, -6.42%-6.17%). Iclaprim was well tolerated in the study, with most adverse events categorized as mild. Iclaprim achieved noninferiority (10% margin) at ETP compared with vancomycin and was well tolerated in this phase 3 clinical trial for the treatment of ABSSSI. Based on these results, iclaprim appears to be an efficacious and safe treatment for ABSSSI suspected or confirmed to be due to gram-positive pathogens. NCT02600611.

Simultaneous and Direct Determination of Vancomycin and Cephalexin in Human Plasma by Using HPLC-DAD Coupled with Second-Order Calibration Algorithms

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Le-Qian Hu

2012-01-01

Full Text Available A simple, rapid, and sensitive method for the simultaneous determination of vancomycin and cephalexin in human plasma was developed by using HPLC-DAD with second-order calibration algorithms. Instead of a completely chromatographic separation, mathematical separation was performed by using two trilinear decomposition algorithms, that is, PARAFAC-alternative least squares (PARAFAC-ALSs and self-weight-alternative-trilinear-decomposition- (SWATLD- coupled high-performance liquid chromatography with DAD detection. The average recoveries attained from PARAFAC-ALS and SWATLD with the factor number of 4 (N=4 were 101±5% and 102±4% for vancomycin, and 96±3% and 97±3% for cephalexininde in real human samples, respectively. The statistical comparison between PARAFAC-ALS and SWATLD is demonstrated to be similar. The results indicated that the combination of HPLC-DAD detection with second-order calibration algorithms is a powerful tool to quantify the analytes of interest from overlapped chromatographic profiles for complex analysis of drugs in plasma.

Ceftaroline-Resistant, Daptomycin-Tolerant, and Heterogeneous Vancomycin-Intermediate Methicillin-Resistant Staphylococcus aureus Causing Infective Endocarditis.

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Nigo, Masayuki; Diaz, Lorena; Carvajal, Lina P; Tran, Truc T; Rios, Rafael; Panesso, Diana; Garavito, Juan D; Miller, William R; Wanger, Audrey; Weinstock, George; Munita, Jose M; Arias, Cesar A; Chambers, Henry F

2017-03-01

We report a case of infective endocarditis (IE) caused by ceftaroline-resistant, daptomycin-tolerant, and heterogeneous vancomycin-intermediate methicillin-resistant S. aureus (MRSA). Resistance to ceftaroline emerged in the absence of drug exposure, and the E447K substitution in the active site of PBP2a previously associated with ceftaroline resistance was identified. Additionally, we present evidence of patient-to-patient transmission of the strain within the same unit. This case illustrates the difficulties in treating MRSA IE in the setting of a multidrug-resistant phenotype. Copyright © 2017 American Society for Microbiology.

Comparison of M.I.C.E. and Etest with CLSI agar dilution for antimicrobial susceptibility testing against oxacillin-resistant Staphylococcus spp.

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Eloiza H Campana

Full Text Available OBJECTIVE: The main objective of this study was to comparatively evaluate the performance of M.I.C.E. and Etest methodologies to that of agar dilution for determining the antimicrobial susceptibility profile of oxacillin-resistant Staphylococcus spp. METHODS: A total of 100 oxacillin-resistant Staphylococcus spp. isolates were collected from hospitalized patients at a teaching hospital. Antimicrobial susceptibility testing for vancomycin, teicoplanin and linezolid was performed using the reference CLSI agar dilution method (2009, Etest and M.I.C.E. methodologies. The MIC values were interpreted according to CLSI susceptibility breakpoints and compared by regression analysis. RESULTS: In general, the essential agreement (±1-log2 between M.I.C.E. and CLSI agar dilution was 93.0%, 84.0% and 77.0% for linezolid, teicoplanin and vancomycin, respectively. Essential agreement rates between M.I.C.E. and Etest were excellent (>90.0% for all antibiotics tested. Both strips (M.I.C.E. and Etest yielded two very major errors for linezolid. Unacceptable minor rates were observed for teicoplanin against CoNS and for vancomycin against S. aureus. CONCLUSIONS: According to our results, linezolid and teicoplanin MICs against all staphylococci and S. aureus, respectively, were more accurately predicted by M.I.C.E. strips. However, the Etest showed better performance than M.I.C.E. for predicting vancomycin MICs against all staphylococci. Thus, microbiologists must be aware of the different performance of commercially available gradient strips against staphylococci.

The relationship between the use of flucloxacillin, vancomycin, aminoglycosides and ciprofloxacin and the susceptibility patterns of coagulase-negative staphylococci recovered from blood cultures.

NARCIS (Netherlands)

Mulder, JG; Kosterink, JGW; Degener, JE

1997-01-01

Antibiotic use is a cause of selection of multiresistant bacterial strains. Over three years (1990-1992) we studied the relation between the use of flucloxacillin, vancomycin, aminoglycosides and ciprofloxacin and the susceptibility of coagulase-negative staphylococci (CNS) recovered from blood

A polycarboxylic/amino functionalized hyaluronic acid derivative for the production of pH sensible hydrogels in the prevention of bacterial adhesion on biomedical surfaces.

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Palumbo, Fabio Salvatore; Bavuso Volpe, Antonella; Cusimano, Maria Grazia; Pitarresi, Giovanna; Giammona, Gaetano; Schillaci, Domenico

2015-01-15

A graft copolymer derivative of hyaluronic acid bearing pendant amino and short polymethacrylate portions (HA-EDA-BMP-MANa) has been employed for the production of a pH sensible vancomycin releasing hydrogel and studied in vitro to test its potential anti adhesive property against Staphylococcus aureus colonization. The copolymer obtained through atom transfer radical polymerization bears chargeable (carboxyl and amino groups) portions and it could be formulated as a hydrogel at a concentration of 10%w/v. The HA-EDA-BMP-MANa hydrogels, produced at three different pH values (5, 6 and 7, respectively), were formulated with or without the addition of vancomycin (2%w/v). The vancomycin release profiles were detected and related to the starting hydrogel pH values, demonstrating that the systems were able to sustain the release of drug for more than 48 h. S. aureus adhesion tests were performed on glass culture plates and hydroxyapatite doped titanium surfaces, comparing the performances of HA-EDA-BMP-MANa hydrogel formulations (obtained with and without vancomycin) with similar formulations obtained using unmodified hyaluronic acid. The non fouling property of a selected HA-EDA-BMP-MANa hydrogel (without vancomycin) was also assayed with a BSA adsorption test. We found that the HA-EDA-BMP-MANa hydrogel even without vancomycin prevented bacterial adhesion on investigated surfaces. Copyright © 2014. Published by Elsevier B.V.

Genomic, Transcriptomic and Metabolomic Studies of Two Well-Characterized, Laboratory-Derived Vancomycin-Intermediate Staphylococcus aureus Strains Derived from the Same Parent Strain

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Dipti S. Hattangady

2015-02-01

Full Text Available Complete genome comparisons, transcriptomic and metabolomic studies were performed on two laboratory-selected, well-characterized vancomycin-intermediate Staphylococcus aureus (VISA derived from the same parent MRSA that have changes in cell wall composition and decreased autolysis. A variety of mutations were found in the VISA, with more in strain 13136p−m+V20 (vancomycin MIC = 16 µg/mL than strain 13136p−m+V5 (MIC = 8 µg/mL. Most of the mutations have not previously been associated with the VISA phenotype; some were associated with cell wall metabolism and many with stress responses, notably relating to DNA damage. The genomes and transcriptomes of the two VISA support the importance of gene expression regulation to the VISA phenotype. Similarities in overall transcriptomic and metabolomic data indicated that the VISA physiologic state includes elements of the stringent response, such as downregulation of protein and nucleotide synthesis, the pentose phosphate pathway and nutrient transport systems. Gene expression for secreted virulence determinants was generally downregulated, but was more variable for surface-associated virulence determinants, although capsule formation was clearly inhibited. The importance of activated stress response elements could be seen across all three analyses, as in the accumulation of osmoprotectant metabolites such as proline and glutamate. Concentrations of potential cell wall precursor amino acids and glucosamine were increased in the VISA strains. Polyamines were decreased in the VISA, which may facilitate the accrual of mutations. Overall, the studies confirm the wide variability in mutations and gene expression patterns that can lead to the VISA phenotype.

Avaliação da tolerância à vancomicina em 395 cepas hospitalares de Staphylococcus aureus resistentes à oxacilina Evaluation of the tolerance to vancomycin in 395 oxacillin-resistant Staphylococcus aureus strains isolated from Brazilian hospitals

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Geraldo A. Oliveira

2001-01-01

Full Text Available O objetivo deste estudo foi avaliar a presença de tolerância à vancomicina em cepas de Staphylococcus aureus resistentes à oxacilina (Orsa isoladas de quatro hospitais da cidade de São Paulo. Foram estudadas 395 cepas Orsa isoladas de pacientes hospitalizados entre outubro de 1998 e maio de 2000. A determinação da concentração inibitória mínima (CIM e da concentração bactericida mínima (CBM para vancomicina foi realizada conforme padronizado pelo National Committee for Clinical Laboratory Standards (NCCLS. A tolerância à vancomicina foi definida como a razão CBM/CIM > ou = 32. Do total de cepas estudadas, 10,4% apresentaram CIM de 0,5µg/ml para vancomicina; 41,3%, CIM de 1µg/ml; 42,2%, CIM de 2µg/ml; e 6,1%, CIM de 4µg/ml. Em média, 49,1% dos Orsa apresentaram tolerância à vancomicina. Em conclusão, a tolerância à vancomicina entre as cepas Orsa foi considerada elevada. Conseqüentemente, aumentam as chances de falhas no tratamento com vancomicina, além de aumentar o risco da emergência de Staphylococcus aureus vancomicina-intermediário.The objective of this study was to evaluate the presence of tolerance to vancomycin in oxacillin-resistant Staphylococcus aureus (Orsa strains isolated from four hospitals in the city of São Paulo. From October/1998 to May/2000 we analysed 395 Orsa strains isolated from hospitalized patients. MIC and MBC to vancomycin were determined as standardised by National Committee for Clinical Laboratory Standards (NCCLS. Tolerance was defined as the ratio MBC/MIC > or = 32. The results showed that 10.4% of the Orsa strains presented a MIC of 0.5µg/mL for vancomycin, 41.3% presented a MIC of 1µg/mL, 42.2% a MIC of 2µg/mL and 6.1% a MIC of 4µg/mL. On average, 49,1% of the Orsa presented tolerance to vancomycin. We conclude that the tolerance to vancomycin amongst the Orsa strains was considered high. These high levels of tolerance augment the chances of failure in the treatment with

Efficacy of linezolid, teicoplanin, and vancomycin in prevention of an experimental polytetrafluoroethylene graft infection model caused by methicillin-resistant Staphylococcus aureus.

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Mese, Bulent; Bozoglan, Orhan; Elveren, Serdal; Eroglu, Erdinc; Gul, Mustafa; Celik, Ahmet; Ciralik, Harun; Yildirimdemir, Halil Ibrahim; Yasim, Alptekin

2015-03-27

The aim of this study was to evaluate the effectiveness of linezolid, teicoplanin, and vancomycin in prevention of prosthetic vascular graft infections in a vascular graft infection model. Fifty rats were divided into 5 groups. A polytetrafluoroethylene graft was implanted on the back of each rat. Methicillin-resistant Staphylococcus aureus (MRSA) strain was inoculated into all rats except Group 1. Group 2 was not given any treatment, Group 3 received linezolid, Group 4 received vancomycin, and Group 5 received teicoplanin. The grafts were removed for microbiological and histological examinations on the 7th day. In addition, C-reactive protein and prealbumin levels and leukocyte counts in obtained blood specimens were determined. Group 1 did not have infection. Group 2 had bacteria 5.7 × 10(4) CFU/cm(2). Group 3 and Group 4 had less bacterial growth. Group 5 had no bacterial growth. The number of bacteria was significantly higher in Group 2 than in the other experimental groups and the control group (pprevention of prosthetic vascular graft infections.

Bacillus coagulans GBI-30, 6086 limits the recurrence of Clostridium difficile-Induced colitis following vancomycin withdrawal in mice

OpenAIRE

Fitzpatrick, Leo R; Small, Jeffrey S; Greene, Wallace H; Karpa, Kelly D; Farmer, Sean; Keller, David

2012-01-01

Abstract Background Recently, we found that the probiotic strain Bacillus coagulans GBI-30, 6086 (GanedenBC30) improved indices of Clostridium difficile (C. difficile)-induced colitis in mice (Fitzpatrick et al., Gut Pathogens, 2011). Our goal was to determine if BC30 could also prevent the recurrence of C. difficile-induced colitis in mice, following initial treatment with vancomycin. During study days 0 through 5, mice were treated with antibiotics. On day 6, the C. difficile strain VPI 104...

Prevalence of Methicillin and Vancomycin resistant Staphylococcus aureus colonization in nasopharynx; Amir-Alam hospital, 2005

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Hasibi M

2007-07-01

Full Text Available Background: Staphylococcus aureus is one of the most common causes of nosocomial infections with high morbidity and mortality rate. Traditionally, methicillin resistant staphylococcus aureus has been considered a major nosocomial pathogen in healthcare facilities, but in the past decade, it has been observed emerging in the community as well. Informations regarding hospital microbial colonization could be an important step for prevention of nosocomial infections. Our objective was clarifying the prevalence of methicillin resistant and vancomycin resistant staphylococcus aureus colonization in nasopharynx. Methods: A descriptive cross sectional study was carried on 106 patients and nursing staff of surgery and hemodialysis wards in Amir-Alam hospital from April 2005 to July 2005. The samples were collected from nasal region of cases using cotton swab by two experienced technician and were sent to laboratory for culture and antibiogram. Results: Twenty six (29.5% out of 106 cases were nasopharyngeal carriers of staphylococcus aureus. Eight cases (7.5% had methicillin resistant staphylococcus aureus. The most frequent colonization rate was seen in hemodialysis nursing staff and in all of them methicillin resistant staphylococcus aureus was reported. Carrier rates in hemodialysis patients were twice compared to surgery ward patients. The interesting point was that no sample of vancomycin resistant staphylococcus aureus was isolated. Conclusion: Prevalence of methicillin resistant staphylococcus aureus colonization seems to be increased; therefore proper management for controlling this problem is mandatory. The results of the present study suggest that the prevalence of methicillin resistant staphylococcus aureus infections is higher than was expected in Iran and vigorous preventive strategies should therefore be taken to stop the growth of this major health problem.

Presence of the vancomycin resistance gene cluster vanC1, vanXYc, and vanT in Enterococcus casseliflavus.

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Hölzel, Christina; Bauer, Johann; Stegherr, Eva-Maria; Schwaiger, Karin

2014-04-01

The three chromosomally located clustered genes vanC1, vanXYc, and vanT confer intrinsic resistance to vancomycin and are used for species identification of Enterococcus gallinarum. In this study, 28 strains belonging to the E. gallinarum/casseliflavus group isolated from cloacal swabs from laying hens were screened for the presence of vanC1. As confirmed by species-specific multiplex PCR, 11 vanC1-positive strains were identified as E. gallinarum. Surprisingly, one yellow pigmented strain, verified as E. casseliflavus by species-specific multiplex PCR, was also vanC1 positive; vanXYc and vanT were additionally detectable in this strain. To our knowledge, this is the first report of vanC1, vanXYc, and vanT in E. casseliflavus. The minimum inhibitory concentration of vancomycin was 4 mg/L. Real-time reverse transcription-PCR revealed that none of the clustered genes was expressed in this strain. Even if the genes seem not to be active, there is a certain risk that they will be transferred to other bacteria where they might be functionally expressed. Therefore, it may be advisable to expand the search for vanC1, vanXYc, and vanT from E. gallinarum to other (enterococcal) species. This study confirms that enterococci live up to their name as being reservoir bacteria and should therefore always be closely monitored.

Role of MbtH-like Proteins in the Adenylation of Tyrosine during Aminocoumarin and Vancomycin Biosynthesis*

Science.gov (United States)

Boll, Björn; Taubitz, Tatjana; Heide, Lutz

2011-01-01

MbtH-like proteins consist of ∼70 amino acids and are encoded in the biosynthetic gene clusters of non-ribosomally formed peptides and other secondary metabolites derived from amino acids. Recently, several MbtH-like proteins have been shown to be required for the adenylation of amino acid in non-ribosomal peptide synthesis. We now investigated the role of MbtH-like proteins in the biosynthesis of the aminocoumarin antibiotics novobiocin, clorobiocin, and simocyclinone D8 and of the glycopeptide antibiotic vancomycin. The tyrosine-adenylating enzymes CloH, SimH, and Pcza361.18, involved in the biosynthesis of clorobiocin, simocyclinone D8, and vancomycin, respectively, required the presence of MbtH-like proteins in a 1:1 molar ratio, forming heterotetrameric complexes. In contrast, NovH, involved in novobiocin biosynthesis, showed activity in the absence of MbtH-like proteins. Comparison of the active centers of CloH and NovH showed only one amino acid to be different, i.e. Leu-383 versus Met-383. Mutation of this amino acid in CloH (L383M) indeed led to MbtH-independent adenylating activity. All investigated tyrosine-adenylating enzymes exhibited remarkable promiscuity for MbtH-like proteins from different pathways and organisms. YbdZ, the MbtH-like protein from the expression host Escherichia coli, was found to bind to adenylating enzymes during expression and to influence their biochemical properties markedly. Therefore, the use of ybdZ-deficient expression hosts is important in biochemical studies of adenylating enzymes. PMID:21890635

Small test SDHW systems

DEFF Research Database (Denmark)

Vejen, Niels Kristian

1999-01-01

Three small test SDHW systems was tested in a laboratory test facility.The three SDHW systems where all based on the low flow principe and a mantle tank but the design of the systems where different.......Three small test SDHW systems was tested in a laboratory test facility.The three SDHW systems where all based on the low flow principe and a mantle tank but the design of the systems where different....

Vancomycin resistant enterococci (VRE in Swedish sewage sludge

Directory of Open Access Journals (Sweden)

Aspan Anna

2009-05-01

Full Text Available Abstract Background Antimicrobial resistance is a serious threat in veterinary medicine and human healthcare. Resistance genes can spread from animals, through the food-chain, and back to humans. Sewage sludge may act as the link back from humans to animals. The main aims of this study were to investigate the occurrence of vancomycin resistant enterococci (VRE in treated sewage sludge, in a Swedish waste water treatment plant (WWTP, and to compare VRE isolates from sewage sludge with isolates from humans and chickens. Methods During a four month long study, sewage sludge was collected weekly and cultured for VRE. The VRE isolates from sewage sludge were analysed and compared to each other and to human and chicken VRE isolates by biochemical typing (PhenePlate, PFGE and antibiograms. Results Biochemical typing (PhenePlate-FS and pulsed field gel electrophoresis (PFGE revealed prevalence of specific VRE strains in sewage sludge for up to 16 weeks. No connection was found between the VRE strains isolated from sludge, chickens and humans, indicating that human VRE did not originate from Swedish chicken. Conclusion This study demonstrated widespread occurrence of VRE in sewage sludge in the studied WWTP. This implies a risk of antimicrobial resistance being spread to new farms and to the society via the environment if the sewage sludge is used on arable land.

Investigation of the potential for mutational resistance to XF-73, retapamulin, mupirocin, fusidic acid, daptomycin, and vancomycin in methicillin-resistant Staphylococcus aureus isolates during a 55-passage study.

Science.gov (United States)

Farrell, David J; Robbins, Marion; Rhys-Williams, William; Love, William G

2011-03-01

XF-73 is a dicationic porphyrin drug with rapid Gram-positive antibacterial activity currently undergoing clinical trials for the nasal decolonization of Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA). In multistep (55-passage) resistance selection studies in the presence of subinhibitory concentrations of XF-73, retapamulin, mupirocin, fusidic acid, and vancomycin against four Network on Antimicrobial Resistance in Staphylococcus aureus MRSA strains, there was no >4-fold increase in the MIC for XF-73 after 55 passages. In contrast, there was an increase in the MICs for retapamulin (from 0.25 μg/ml to 4 to 8 μg/ml), for mupirocin (from 0.12 μg/ml to 16 to 512 μg/ml), for fusidic acid (from 0.12 μg/ml to 256 μg/ml), and for vancomycin (from 1 μg/ml to 8 μg/ml in two of the four strains tested). Further investigations using S. aureus NRS384 (USA300) and daptomycin demonstrated a 64-fold increase in the MIC after 55 passages (from 0.5 μg/ml to 32 μg/ml) with a >4-fold increase in the MIC obtained after only five passages. Sequencing analysis of selected isolates confirmed previously reported point mutations associated with daptomycin resistance. No cross-resistance to XF-73 was observed with the daptomycin-resistant strains, suggesting that whereas the two drugs act on the bacterial cell membrane, their specific site of action differs. XF-73 thus represents the first in a new class of antibacterial drugs, which (unlike the comparator antibiotics) after 55 passages exhibited a ≤4-fold increase in MIC against the strains tested. Antibacterial drugs with a low propensity for inducing bacterial resistance are much needed for the prevention and treatment of multidrug-resistant bacteria both within and outside the hospital setting.

Vancomycin, linezolid and daptomycin susceptibility pattern among clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA from Sub- Himalyan Center

Directory of Open Access Journals (Sweden)

Afzal Husain

2018-01-01

CONCLUSION: MIC creep was observed with vancomycin. Although linezolid MIC was within the susceptible zone, more than 40% strains showing MIC 3 μg/ml may herald the future development of either resistant or heteroresistant. Daptomycin showed good sensitivity against MRSA isolates. Therefore, it could be considered as an alternative agent for the treatment of infections caused by MRSA. However, it should be reserved where this class has a clear therapeutic advantage over other anti-MRSA drugs.

Test System Impact on System Availability

DEFF Research Database (Denmark)

Pau, L. F.

1987-01-01

The specifications are presented for an imperfect automatic test system (ATS) (test frequency distribution, reliability, false alarm rate, nondetection rate) in order to account for the availability, readiness, mean time between unscheduled repairs (MTBUR), reliability, and maintenance of the sys......The specifications are presented for an imperfect automatic test system (ATS) (test frequency distribution, reliability, false alarm rate, nondetection rate) in order to account for the availability, readiness, mean time between unscheduled repairs (MTBUR), reliability, and maintenance...... of the system subject to monitoring and test. A time-dependent Markov model is presented, and applied in three cases, with examples of numerical results provided for preventive maintenance decisions, design of an automatic test system, buffer testing in computers, and data communications....

New liquid chromatography-tandem mass spectrometry method for routine TDM of vancomycin in patients with both normal and impaired renal functions and comparison with results of polarization fluoroimmunoassay in light of varying creatinine concentrations.

Science.gov (United States)

Brozmanová, Hana; Kacířová, Ivana; Uřinovská, Romana; Šištík, Pavel; Grundmann, Milan

2017-06-01

A new LC-MS/MS method with simple sample extraction and a relatively short period of vancomycin analysis for routine therapeutic drug monitoring was developed and validated. 50μL serum was precipitated using 20μL 33% trichloroacetic acid and 0.5mol/L NH 4 OH was added to increase pH before analysis. A RP BEH C18, 1.7μm, 2.1×50mm column maintained at 30°C and tobramycin as internal standard were used. Mass detection was performed in positive electrospray mode. The results obtained with LC-MS/MS method were correlated with an FPIA assay (Abbott AxSYM) using mouse monoclonal antibody. Subjects were divided into three groups according to creatinine levels (53.5±19.1, 150.2±48.4, 471.7±124.7μmol/L) and Passing-Bablok regression analysis and Bland-Altman analysis were used to compare vancomycin concentrations. The results of subjects with both normal and higher creatinine levels correlated very well and the linear regression model equations were near ideal (LC-MS VAN =0.947×Abbott VAN +0.192 and LC-MS VAN =0.973×Abbott VAN -0.411 respectively). Dialyzed patients with the highest creatinine levels showed about 14% greater vancomycin concentration with the FPIA assay (LC-MS VAN =0.866×Abbott VAN +2.127). This overestimation probably due to the presence of the metabolite CDP ought not to be of clinical relevance owing to the wide range of recommended vancomycin concentration. Copyright © 2017 Elsevier B.V. All rights reserved.

Cost Comparison of Linezolid Versus Vancomycin for Treatment of Complicated Skin and Skin-Structure Infection Caused by Methicillin-Resistant Staphylococcus aureus in Quebec

Directory of Open Access Journals (Sweden)

Martine Pettigrew

2012-01-01

Full Text Available BACKGROUND: In Canada, complicated skin and skin-structure infection (cSSSI caused by methicillin-resistant Staphylococcus aureus (MRSA is usually treated with antibiotics in hospital, with a follow-up course at home for stable patients. The cost implications of using intravenous and oral linezolid instead of intravenous vancomycin in Canadian clinical practice have not been examined.

Staphylococcus aureus: methicillin-susceptible S. aureus to methicillin-resistant S. aureus and vancomycin-resistant S. aureus.

Science.gov (United States)

Rehm, Susan J; Tice, Alan

2010-09-15

The evolution of methicillin-resistant and vancomycin-resistant Staphylococcus aureus has demanded serious review of antimicrobial use and development of new agents and revised approaches to prevent and overcome drug resistance. Depending on local conditions and patient risk factors, empirical therapy of suspected S. aureus infection may require coverage of drug-resistant organisms with newer agents and novel antibiotic combinations. The question of treatment with inappropriate antibiotics raises grave concerns with regard to methicillin-resistant S. aureus selection, overgrowth, and increased virulence. Several strategies to reduce the nosocomial burden of resistance are suggested, including shortened hospital stays and outpatient parenteral antimicrobial therapy of the most serious infections.

Test report - caustic addition system operability test procedure

International Nuclear Information System (INIS)

Parazin, R.E.

1995-01-01

This Operability Test Report documents the test results of test procedure WHC-SD-WM-OTP-167 ''Caustic Addition System Operability Test Procedure''. The Objective of the test was to verify the operability of the 241-AN-107 Caustic Addition System. The objective of the test was met

SPECTR System Operational Test Report

International Nuclear Information System (INIS)

Landman, W.H. Jr.

2011-01-01

This report overviews installation of the Small Pressure Cycling Test Rig (SPECTR) and documents the system operational testing performed to demonstrate that it meets the requirements for operations. The system operational testing involved operation of the furnace system to the design conditions and demonstration of the test article gas supply system using a simulated test article. The furnace and test article systems were demonstrated to meet the design requirements for the Next Generation Nuclear Plant. Therefore, the system is deemed acceptable and is ready for actual test article testing.

Misidentification of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals in Tripoli, Libya

Science.gov (United States)

Ahmed, Mohamed O.; Abuzweda, Abdulbaset R.; Alghazali, Mohamed H.; Elramalli, Asma K.; Amri, Samira G.; Aghila, Ezzeddin Sh.; Abouzeed, Yousef M.

2010-01-01

Background Methicillin-resistant Staphylococcus aureus (MRSA) is a nosocomial (hospital-acquired) pathogen of exceptional concern. It is responsible for life-threatening infections in both the hospital and the community. Aims To determine the frequency of MRSA misidentification in hospitals in Tripoli, Libya using current testing methods. Methods One hundred and seventy S. aureus isolates previously identified as MRSA were obtained from three hospitals in Tripoli. All isolates were reidentified by culturing on mannitol salt agar, API 20 Staph System and retested for resistance to methicillin using the cefoxitin disk diffusion susceptibility test and PBP2a. D-tests and vancomycin E-tests (Van-E-tests) were also performed for vancomycin-resistant isolates. Results Of the 170 isolates examined, 86 (51%) were confirmed as MRSA (i.e. 49% were misidentified as MRSA). Fifteen (17%) of the confirmed MRSA strains exhibited inducible clindamycin resistance. Of the 86 confirmed MRSA isolates, 13 (15%) were resistant to mupirocin, 53 (62%) were resistant to ciprofloxacin, 41 (48%) were resistant to trimethoprim-sulfamethoxazole, and none were resistant to linezolid. Although disc-diffusion testing indicated that 23 (27%) of the isolates were resistant to vancomycin, none of the isolates were vancomycin-resistant by Van-E-test. Conclusions Misidentification of nosocomial S. aureus as MRSA is a serious problem in Libyan hospitals. There is an urgent need for the proper training of microbiology laboratory technicians in standard antimicrobial susceptibility procedures and the implementation of quality control programs in microbiology laboratories of Libyan hospitals. PMID:21483574

Phenotypic and genotypic characterization of vancomycin-resistant Enterococcus faecium clinical isolates from two hospitals in Mexico: First detection of VanB phenotype-vanA genotype.

Science.gov (United States)

Bocanegra-Ibarias, Paola; Flores-Treviño, Samantha; Camacho-Ortiz, Adrián; Morfin-Otero, Rayo; Villarreal-Treviño, Licet; Llaca-Díaz, Jorge; Martínez-Landeros, Erik Alan; Rodríguez-Noriega, Eduardo; Calzada-Güereca, Andrés; Maldonado-Garza, Héctor Jesús; Garza-González, Elvira

2016-01-01

Enterococcus faecium has emerged as a multidrug-resistant nosocomial pathogen involved in outbreaks worldwide. Our aim was to determine the antimicrobial susceptibility, biofilm production, and clonal relatedness of vancomycin-resistant E. faecium (VREF) clinical isolates from two hospitals in Mexico. Consecutive clinical isolates (n=56) were collected in two tertiary care hospitals in Mexico from 2011 to 2014. VREF isolates were characterized by phenotypic and molecular methods including pulsed-field gel electrophoresis (PFGE). VREF isolates were highly resistant to vancomycin, erythromycin, norfloxacin, high-level streptomycin, and teicoplanin, and showed lower resistance to tetracycline, nitrofurantoin and quinupristin-dalfopristin. None of the isolates were resistant to linezolid. The vanA gene was detected in all isolates. Two VanB phenotype-vanA genotype isolates, highly resistant to vancomycin and susceptible to teicoplanin, were detected. Furthermore, 17.9% of the isolates were classified as biofilm producers, and the espfm gene was found in 98.2% of the isolates. A total of 37 distinct PFGE patterns and 6 clones (25% of the isolates as clone A, 5.4% as clone B, and 3.6% each as clone C, D, E, and F) were detected. Clone A was detected in 5 different wards of the same hospital during 14 months of surveillance. The high resistance to most antimicrobial agents and the moderate cross-transmission of VREF detected accentuates the need for continuous surveillance of E. faecium in the hospital setting. This is also the first reported incidence of the E. faecium VanB phenotype-vanA genotype in the Americas. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Vancomycin resistance in Enterococcus faecium isolated from Danish chicken meat is located on a pVEF4-like plasmid persisting in poultry for 18 years

DEFF Research Database (Denmark)

Leinweber, Helena Augusta Katharina; Alotaibi, Sulaiman Mohammed I; Overballe-Petersen, Søren

2018-01-01

traits of VREfm in Danish retail chicken meat. Three out of 40 samples (7.5%) from two slaughterhouses yielded VREfm (vancomycin MIC > 32mg/L). This is the first report of VREfm in Danish retail poultry meat since 2010 (DANMAP). All three VREfm belonged to the sequence type ST32, cluster type CT1068...

Evaluation of the in vitro ocular toxicity of the fortified antibiotic eye drops prepared at the Hospital Pharmacy Departments

Directory of Open Access Journals (Sweden)

Anxo Fernández-Ferreiro

2016-12-01

Full Text Available The use of parenteral antibiotic eye drop formulations with non-marketed compositions or concentrations, commonly called fortified antibiotic eye drops, is a common practice in Ophthalmology in the hospital setting. The aim of this study was to evaluate the in vitro ocular toxicity of the main fortified antibiotic eye drops prepared in the Hospital Pharmacy Departments. We have conducted an in vitro experimental study in order to test the toxicity of gentamicin, amikacin, cefazolin, ceftazidime, vancomycin, colistimethate sodium and imipenem-cilastatin eye drops; their cytotoxicity and acute tissue irritation have been evaluated. Cell-based assays were performed on human stromal keratocytes, using a cell-based impedance biosensor system [xCELLigence Real-Time System Cell Analyzer (RTCA], and the Hen’s Egg Test for the ocular irritation tests. All the eye drops, except for vancomycin and imipenem, have shown a cytotoxic effect dependent on concentration and time; higher concentrations and longer exposure times will cause a steeper decline in the population of stromal keratocytes. Vancomycin showed a major initial cytotoxic effect, which was reverted over time; and imipenem appeared as a non-toxic compound for stromal cells. The eye drops with the highest irritating effect on the ocular surface were gentamicin and vancomycin. Those antibiotic eye drops prepared at the Hospital Pharmacy Departments included in this study were considered as compounds potentially cytotoxic for the ocular surface; this toxicity was dependent on the concentration used

Human and Swine Hosts Share Vancomycin-Resistant Enterococcus faecium CC17 and CC5 and Enterococcus faecalis CC2 Clonal Clusters Harboring Tn1546 on Indistinguishable Plasmids

DEFF Research Database (Denmark)

Freitas, Ana R.; Coque, Teresa M.; Novais, Carla

2011-01-01

clonally related Enterococcus faecium clonal complex 5 (CC5) isolates (17 sequence type 6 [ST6], 6 ST5, 5 ST185, 1 ST147, and 1 ST493) were obtained from feces of swine and healthy humans. This collection included isolates widespread among pigs of European Union (EU) countries since the mid-1990s. Each ST...... comprised isolates showing similar pulsed-field gel electrophoresis (PFGE) patterns (≤6 bands difference; >82% similarity). Some CC5 PFGE subtype strains from swine were indistinguishable from hospital vancomycin-resistant enterococci (VRE) causing infections. A truncated variant of Tn1546 (encoding...... resistance to vancomycin) and tcrB (coding for resistance to copper) were consistently located on 150- to 190-kb plasmids (rep(pLG1)). E. faecium CC17 (ST132) isolates from pig manure and two clinical samples showed identical PFGE profiles and contained a 60-kb mosaic plasmid (rep(Inc18) plus rep...

Intraperitoneal Vancomycin Plus Either Oral Moxifloxacin or Intraperitoneal Ceftazidime for the Treatment of Peritoneal Dialysis-Related Peritonitis: A Randomized Controlled Pilot Study.

Science.gov (United States)

Xu, Rong; Yang, Zhikai; Qu, Zhen; Wang, Huan; Tian, Xue; Johnson, David W; Dong, Jie

2017-07-01

Intraperitoneal administration of antibiotics is recommended as a first treatment for managing peritoneal dialysis (PD)-related peritonitis. However, the efficacy of oral administration of quinolones has not been well studied. Randomized controlled pilot study. 80 eligible patients with PD-related peritonitis from Peking University First Hospital (40 in each arm). Intraperitoneal vancomycin, 1g, every 5 days plus oral moxifloxacin, 400mg, every day (treatment group) versus intraperitoneal vancomycin, 1g, every 5 days plus intraperitoneal ceftazidime, 1g, every day (control group). The primary end point was complete resolution of peritonitis, and secondary end points were primary or secondary treatment failure. PD effluent white blood cell count. Baseline demographic and clinical characteristics of the 2 groups were comparable. There were 24 and 22 Gram-positive organisms, 6 and 7 Gram-negative organisms, 9 and 10 culture-negative samples, and 1 and 1 fungal sample in the treatment and control groups, respectively. Complete resolution of peritonitis was achieved in 78% and 80% of cases in the treatment and control groups, respectively (OR, 0.86; 95% CI, 0.30-2.52; P=0.8). There were 3 and 1 cases of relapse in the treatment and control groups, respectively. Primary and secondary treatment failure rates were not significantly different (33% vs 20% and 10% vs 13%, respectively). In each group, there was 1 peritonitis-related death and 6 transfers to hemodialysis therapy. During the 3-month follow-up period, 7 and 3 successive episodes of peritonitis occurred in the treatment and control groups, respectively. Only 2 adverse drug reactions (mild nausea and mild rash, respectively) were observed in the 2 groups. Sample size was relatively small and the eligibility ratio was low. Also, the number of peritonitis episodes was low, limiting the power to detect a difference between groups. This pilot study suggests that intraperitoneal vancomycin with oral moxifloxacin is a

A novel mode of regulation of the Staphylococcus aureus Vancomycin-resistance-associated response regulator VraR mediated by Stk1 protein phosphorylation.

Science.gov (United States)

Canova, Marc J; Baronian, Grégory; Brelle, Solène; Cohen-Gonsaud, Martin; Bischoff, Markus; Molle, Virginie

2014-04-25

The Staphylococcus aureus Vancomycin-resistance-associated response regulator VraR is known as an important response regulator, member of the VraTSR three-component signal transduction system that modulates the expression of the cell wall stress stimulon in response to a number of different cell wall active antibiotics. Given its crucial role in regulating gene expression in response to antibiotic challenges, VraR must be tightly regulated. We report here for the first time in S. aureus convergence of two major signal transduction systems, serine/threonine protein kinase and two (three)-component systems. We demonstrate that VraR can be phosphorylated by the staphylococcal Ser/Thr protein kinase Stk1 and that phosphorylation negatively affects its DNA-binding properties. Mass spectrometric analyses and site-directed mutagenesis identified Thr106, Thr119, Thr175 and Thr178 as phosphoacceptors. A S. aureus ΔvraR mutant expressing a VraR derivative that mimics constitutive phosphorylation, VraR_Asp, still exhibited markedly decreased antibiotic resistance against different cell wall active antibiotics, when compared to the wild-type, suggesting that VraR phosphorylation may represent a novel and presumably more general mechanism of regulation of the two (three)-component systems in staphylococci. Copyright © 2014 Elsevier Inc. All rights reserved.

Determination of antimicrobial resistance to extended-spectrum cephalosporin, quinolones, and vancomycin in selected human enteric pathogens from Prince Edward Island, Canada.

Science.gov (United States)

Awosile, Babafela; German, Gregory; Rodriguez-Lecompte, Juan Carlos; Saab, Matthew E; Heider, Luke C; McClure, J Trenton

2018-04-05

The aim of this study was to determine the frequency of fecal carriage of vancomycin-resistant Enterococcus spp. and Escherichia coli with reduced susceptibilities to extended-spectrum cephalosporins (ESCs) and quinolones in humans on Prince Edward Island, Canada. Convenience fecal samples from individuals on Prince Edward Island were screened phenotypically using selective culture and genotypically using multiplex polymerase chain reactions to detect E. coli and Enterococcus spp. resistant to critically important antimicrobials. Twenty-six (5.3%) of 489 individuals had E. coli with reduced susceptibility to ESCs. Twenty-five (96.2%) of the 26 isolates harbored bla TEM , 18 (69.2%) harbored bla CMY-2 , 16 (61.5%) harbored bla CTX-M groups, 2 (7.7%) harbored bla SHV genes. None of the ESC-resistant E. coli was positive for carbapenem resistance. Twenty-one (8.3%) of 253 individuals had E. coli isolates with reduced quinolone susceptibility. All 21 isolates were positive for at least 1 qnr gene, with 3 (14.3%) isolates positive for qnrB, 5 (23.8%) positive for qnrS, and 13 (61.9%) positive for both qnrB and qnrS genes. All the enterococci isolates were vancomycin-susceptible. Higher susceptibility to the critically important antimicrobials was found in this study. This study can serve as a baseline for future antimicrobial resistance surveillance within this region.

Efficacy and safety of fidaxomicin compared with oral vancomycin for the treatment of adults with Clostridium difficile-associated diarrhea: data from the OPT-80-003 and OPT-80-004 studies.

Science.gov (United States)

Chen, Luke F; Anderson, Deverick J

2012-06-01

Clostridium difficile is emerging as one of the most important and devastating pathogens affecting hospitalized populations around the world. The incidence of C. difficile infection is increasing and disease severity is worsening. Thus, an effective alternative to metronidazole and oral vancomycin is urgently needed. Two Phase III trials, OPT-80-003 and OPT-80-004, showed that oral fidaxomicin for 10 days was noninferior compared with treatment with oral vancomycin among adult patients with toxin-positive C. difficile-associated diarrhea (CDAD). Furthermore, fidaxomicin was associated with a lower rate of recurrence of CDAD within 4 weeks of completion of therapy. The safety and tolerability of fidaxomicin was consistent with earlier studies and established that fidaxomicin is an efficacious and well-tolerated treatment option for CDAD. Despite these potential advantages, the cost-effectiveness of this expensive agent remains poorly understood.

Error response test system and method using test mask variable

Science.gov (United States)

Gender, Thomas K. (Inventor)

2006-01-01

An error response test system and method with increased functionality and improved performance is provided. The error response test system provides the ability to inject errors into the application under test to test the error response of the application under test in an automated and efficient manner. The error response system injects errors into the application through a test mask variable. The test mask variable is added to the application under test. During normal operation, the test mask variable is set to allow the application under test to operate normally. During testing, the error response test system can change the test mask variable to introduce an error into the application under test. The error response system can then monitor the application under test to determine whether the application has the correct response to the error.

Effect of Coadministration of Vancomycin and BMP-2 on Cocultured Staphylococcus aureus and W-20-17 Mouse Bone Marrow Stromal Cells in Vitro

Science.gov (United States)

2012-07-01

and maintained in Dulbecco’s modified Eagle’s medium (DMEM) with 10% fetal bovine serum (FBS), a 1% antibiotic/antimycotic mixture, 5 ml of L...osteoblastic differen- tiation when cells are challenged with the parasitic S. aureus bac- teria in coculture. ALP-specific activities in the...release of vancomycin and tobramycin from impregnated human and bovine bone grafts. J. Antimicrob. Chemother. 46:423– 428. 48. Younger EM, Chapman MW

Optimisation of the synthesis of vancomycin-selective molecularly imprinted polymer nanoparticles using automatic photoreactor

Science.gov (United States)

Muzyka, Kateryna; Karim, Khalku; Guerreiro, Antonio; Poma, Alessandro; Piletsky, Sergey

2014-03-01

A novel optimized protocol for solid-state synthesis of molecularly imprinted polymer nanoparticles (nanoMIPs) with specificity for antibiotic vancomycin is described. The experimental objective was optimization of the synthesis parameters (factors) affecting the yield of obtained nanoparticles which have been synthesized using the first prototype of an automated solid-phase synthesizer. Applications of experimental design (or design of experiments) in optimization of nanoMIP yield were carried out using MODDE 9.0 software. The factors chosen in the model were the amount of functional monomers in the polymerization mixture, irradiation time, temperature during polymerization, and elution temperature. In general, it could be concluded that the irradiation time is the most important and the temperature was the least important factor which influences the yield of nanoparticles. Overall, the response surface methodology proved to be an effective tool in reducing time required for optimization of complex experimental conditions.

Data Link Test and Analysis System/ATCRBS Transponder Test System Technical Reference

Science.gov (United States)

1990-05-01

This document references material for personnel using or making software changes : to the Data Link Test and Analysis System (DATAS) for Air Traffic Control Radar : Beacon System (ATCRBS) transponder testing and data collection. This is one of : a se...

Inspection system performance test procedure

International Nuclear Information System (INIS)

Jensen, C.E.

1995-01-01

This procedure establishes requirements to administer a performance demonstration test. The test is to demonstrate that the double-shell tank inspection system (DSTIS) supplied by the contractor performs in accordance with the WHC-S-4108, Double-Shell Tank Ultrasonic Inspection Performance Specification, Rev. 2-A, January, 1995. The inspection system is intended to provide ultrasonic (UT) and visual data to determine integrity of the Westinghouse Hanford Company (WHC) site underground waste tanks. The robotic inspection system consists of the following major sub-systems (modules) and components: Mobile control center; Deployment module; Cable management assembly; Robot mechanism; Ultrasonic testing system; Visual testing system; Pneumatic system; Electrical system; and Control system

Portable Health Algorithms Test System

Science.gov (United States)

Melcher, Kevin J.; Wong, Edmond; Fulton, Christopher E.; Sowers, Thomas S.; Maul, William A.

2010-01-01

A document discusses the Portable Health Algorithms Test (PHALT) System, which has been designed as a means for evolving the maturity and credibility of algorithms developed to assess the health of aerospace systems. Comprising an integrated hardware-software environment, the PHALT system allows systems health management algorithms to be developed in a graphical programming environment, to be tested and refined using system simulation or test data playback, and to be evaluated in a real-time hardware-in-the-loop mode with a live test article. The integrated hardware and software development environment provides a seamless transition from algorithm development to real-time implementation. The portability of the hardware makes it quick and easy to transport between test facilities. This hard ware/software architecture is flexible enough to support a variety of diagnostic applications and test hardware, and the GUI-based rapid prototyping capability is sufficient to support development execution, and testing of custom diagnostic algorithms. The PHALT operating system supports execution of diagnostic algorithms under real-time constraints. PHALT can perform real-time capture and playback of test rig data with the ability to augment/ modify the data stream (e.g. inject simulated faults). It performs algorithm testing using a variety of data input sources, including real-time data acquisition, test data playback, and system simulations, and also provides system feedback to evaluate closed-loop diagnostic response and mitigation control.

In vitro activities of the new semisynthetic glycopeptide telavancin (TD-6424), vancomycin, daptomycin, linezolid, and four comparator agents against anaerobic gram-positive species and Corynebacterium spp.

Science.gov (United States)

Goldstein, Ellie J C; Citron, Diane M; Merriam, C Vreni; Warren, Yumi A; Tyrrell, Kerin L; Fernandez, Helen T

2004-06-01

Telavancin is a new semisynthetic glycopeptide anti-infective with multiple mechanisms of action, including inhibition of bacterial membrane phospholipid synthesis and inhibition of bacterial cell wall synthesis. We determined the in vitro activities of telavancin, vancomycin, daptomycin, linezolid, quinupristin-dalfopristin, imipenem, piperacillin-tazobactam, and ampicillin against 268 clinical isolates of anaerobic gram-positive organisms and 31 Corynebacterium strains using agar dilution methods according to National Committee for Clinical Laboratory Standards procedures. Plates with daptomycin were supplemented with Ca(2+) to 50 mg/liter. The MICs at which 90% of isolates tested were inhibited (MIC(90)s) for telavancin and vancomycin were as follows: Actinomyces spp. (n = 45), 0.25 and 1 microg/ml, respectively; Clostridium difficile (n = 14), 0.25 and 1 microg/ml, respectively; Clostridium ramosum (n = 16), 1 and 4 microg/ml, respectively; Clostridium innocuum (n = 15), 4 and 16 microg/ml, respectively; Clostridium clostridioforme (n = 15), 8 and 1 microg/ml, respectively; Eubacterium group (n = 33), 0.25 and 2 microg/ml, respectively; Lactobacillus spp. (n = 26), 0.5 and 4 microg/ml, respectively; Propionibacterium spp. (n = 34), 0.125 and 0.5 microg/ml, respectively; Peptostreptococcus spp. (n = 52), 0.125 and 0.5 microg/ml, respectively; and Corynebacterium spp. (n = 31), 0.03 and 0.5 microg/ml, respectively. The activity of TD-6424 was similar to that of quinupristin-dalfopristin for most strains except C. clostridioforme and Lactobacillus casei, where quinupristin-dalfopristin was three- to fivefold more active. Daptomycin had decreased activity (MIC > 4 microg/ml) against 14 strains of Actinomyces spp. and all C. ramosum, Eubacterium lentum, and Lactobacillus plantarum strains. Linezolid showed decreased activity (MIC > 4 microg/ml) against C. ramosum, two strains of C. difficile, and 15 strains of Lactobacillus spp. Imipenem and piperacillin

Collecting Samples for Testing

Science.gov (United States)

... Creatinine Ratio Valproic Acid Vancomycin Vanillylmandelic Acid (VMA) VAP Vitamin A Vitamin B12 and Folate Vitamin D ... that used for CSF in that they require aspiration of a sample of the fluid through a ...

Vancomycin-functionalised Ag-TiO{sub 2} phototoxicity for bacteria

Energy Technology Data Exchange (ETDEWEB)

Wan Yi [Chinese Academy of Sciences, Key Lab of Corrosion Science, Shandong Province, Institute of Oceanology, 7 Nanhai Road, Qingdao 266071 (China); Zhang Dun, E-mail: zhangdun@ms.qdio.ac.cn [Chinese Academy of Sciences, Key Lab of Corrosion Science, Shandong Province, Institute of Oceanology, 7 Nanhai Road, Qingdao 266071 (China); Wang Yi; Qi Peng; Wu Jiajia; Hou Baorong [Chinese Academy of Sciences, Key Lab of Corrosion Science, Shandong Province, Institute of Oceanology, 7 Nanhai Road, Qingdao 266071 (China)

2011-02-15

Research highlights: {yields} A multivalent interaction between Van-Ag-TiO{sub 2} and SRB. {yields} Van-Ag-TiO{sub 2} allow for selective photokilling of pathogen. {yields} Van-Ag-TiO{sub 2} show certain bactericidal property in dark. - Abstract: This study reports on the synthesis of vancomycin (Van)-functionalised Ag-TiO{sub 2} nanoparticles and their enhanced bactericidal activities. Van-Ag-TiO{sub 2} nanoparticles were prepared by nanoparticle deposition and chemical cross-linking reactions. The catalysts showed high efficiency for the degradation of methylene blue under ultraviolet (UV) illumination. The photocatalytic inactivation of the sulphate-reducing bacteria, Desulfotomaculum, was also studied under UV light irradiation and in the dark using aqueous mixtures of Ag, Ag-SiO{sub 2}, Ag-TiO{sub 2}, and Van-Ag-TiO{sub 2}. The Van-Ag-TiO{sub 2} nanoparticles showed a capacity to target Van-sensitive bacteria. They also effectively prevented bacterial cell growth through the functionalised nanoparticles under UV irradiation for 1 h. To investigate the specificity of the catalyst phototoxicity, a Van-resistant bacteria, Vibrio anguillarum, was used as the negative control. The results indicated that Van-Ag-TiO{sub 2} nanoparticles had a higher selective phototoxicity for Van-sensitive bacteria. Therefore, the antibiotic molecule-functionalised core-shell nanoparticles allow for selective photokilling of pathogenic bacteria.

Silver(I)-promoted conversion of thioamides to amidines: divergent synthesis of a key series of vancomycin aglycon residue 4 amidines that clarify binding behavior to model ligands.

Science.gov (United States)

Okano, Akinori; James, Robert C; Pierce, Joshua G; Xie, Jian; Boger, Dale L

2012-05-30

Development of a general Ag(I)-promoted reaction for the conversion of thioamides to amidines is disclosed. This reaction was employed to prepare a key series of vancomycin aglycon residue 4 substituted amidines that were used to clarify their interaction with model ligands of peptidoglycan precursors and explore their resulting impact on antimicrobial properties.

Staphylococcus aureus Central Nervous System Infections in Children.

Science.gov (United States)

Vallejo, Jesus G; Cain, Alexandra N; Mason, Edward O; Kaplan, Sheldon L; Hultén, Kristina G

2017-10-01

Central nervous system (CNS) infections caused by Staphylococcus aureus are uncommon in pediatric patients. We review the epidemiology, clinical features and treatment in 68 patients with a S. aureus CNS infection evaluated at Texas Children's Hospital. Cases of CNS infection in children with positive cerebrospinal fluid cultures or spinal epidural abscess (SEA) for S. aureus at Texas Children's Hospital from 2001 to 2013 were reviewed. Seventy cases of S. aureus CNS infection occurred in 68 patients. Forty-nine cases (70%) were secondary to a CNS device, 5 (7.1%) were postoperative meningitis, 9 (12.8%) were hematogenous meningitis and 7 (10%) were SEAs. Forty-seven (67.2%) were caused by methicillin-sensitive S. aureus (MSSA) and 23 (32.8%) by methicillin-resistant S. aureus (MRSA). Community-acquired infections were more often caused by MRSA that was clone USA300/pvl. Most patients were treated with nafcillin (MSSA) or vancomycin (MRSA) with or without rifampin. Among patients with MRSA infection, 50% had a serum vancomycin trough obtained with the median level being 10.6 μg/mL (range: 5.4-15.7 μg/mL). Only 1 death was associated with S. aureus infection. The epidemiology of invasive of S. aureus infections continues to evolve with MSSA accounting for most of the infections in this series. The majority of cases were associated with neurosurgical procedures; however, hematogenous S. aureus meningitis and SEA occurred as community-acquired infections in patients without predisposing factors. Patients with MRSA CNS infections had a favorable response to vancomycin, but the beneficial effect of combination therapy or targeting vancomycin trough concentrations of 15-20 μg/mL remains unclear.

Detection of Methicillin Resistant Staphylococcus aureus and Determination of Minimum Inhibitory Concentration of Vancomycin for Staphylococcus aureus Isolated from Pus/Wound Swab Samples of the Patients Attending a Tertiary Care Hospital in Kathmandu, Nepal

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Raghabendra Adhikari

2017-01-01

Full Text Available The present study was conducted to evaluate the performance of cefoxitin disc diffusion method and oxacillin broth microdilution method for detection of methicillin resistant S. aureus (MRSA, taking presence of mecA gene as reference. In addition, inducible clindamycin resistance and beta-lactamase production were studied and minimum inhibitory concentration (MIC of vancomycin for S. aureus isolates was determined. A total of 711 nonrepeated pus/wound swab samples from different anatomic locations were included in the study. The Staphylococcus aureus was identified on the basis of colony morphology, Gram’s stain, and biochemical tests. A total of 110 (15.47% S. aureus isolates were recovered, of which 39 (35.50% isolates were identified as MRSA by cefoxitin disc diffusion method. By oxacillin broth microdilution method, 31.82% of the Staphylococcus aureus isolates were found to be MRSA. However, mecA gene was present in only 29.1% of the isolates. Further, beta-lactamase production was observed in 71.82% of the isolates, while inducible clindamycin resistance was found in 10% of S. aureus isolates. The MIC value of vancomycin for S. aureus ranged from 0.016 μg/mL to 1 μg/mL. On the basis of the absolute sensitivity (100%, both phenotypic methods could be employed for routine diagnosis of MRSA in clinical microbiology laboratory; however cefoxitin disc diffusion could be preferred over MIC method considering time and labour factor.

A novel dressing for the combined delivery of platelet lysate and vancomycin hydrochloride to chronic skin ulcers: Hyaluronic acid particles in alginate matrices.

Science.gov (United States)

Rossi, S; Mori, M; Vigani, B; Bonferoni, M C; Sandri, G; Riva, F; Caramella, C; Ferrari, F

2018-06-15

The aim of the present work was to develop a medication allowing for the combined delivery of platelet lysate (PL) and an anti-infective model drug, vancomycin hydrochloride (VCM), to chronic skin ulcers. A simple method was set up for the preparation of hyaluronic acid (HA) core-shell particles, loaded with PL and coated with calcium alginate, embedded in a VCM containing alginate matrix. Two different CaCl 2 concentrations were investigated to allow for HA/PL core-shell particle formation. The resulting dressings were characterized for mechanical and hydration properties and tested in vitro (on fibroblasts) and ex-vivo (on skin biopsies) for biological activity. They were found of sufficient mechanical strength to withstand packaging and handling stress and able to absorb a high amount of wound exudate and to form a protective gel on the lesion area. The CaCl 2 concentration used for shell formation did not affect VCM release from the alginate matrix, but strongly modified the release of PGFAB (chosen as representative of growth factors present in PL) from HA particles. In vitro and ex vivo tests provided sufficient proof of concept of the ability of dressings to improve skin ulcers healing. Copyright © 2018 Elsevier B.V. All rights reserved.

In vitro study of vancomycin release and osteoblast-like cell growth on structured calcium phosphate-collagen

International Nuclear Information System (INIS)

Pon-On, Weeraphat; Charoenphandhu, Narattaphol; Teerapornpuntakit, Jarinthorn; Thongbunchoo, Jirawan; Krishnamra, Nateetip; Tang, I-Ming

2013-01-01

A drug delivery vehicle consisting of spherical calcium phosphate-collagen particles covered by flower-like (SFCaPCol) blossoms composed of nanorod building blocks and their cellular response is studied. The spherical structure was achieved by a combination of sonication and freeze-drying. The SFCaPCol blossoms have a high surface area of approximately 280 m 2 g −1 . The blossom-like formation having a high surface area allows a drug loading efficiency of 77.82%. The release profile for one drug, vancomycin (VCM), shows long term sustained release in simulated body fluid (SBF), in a phosphate buffer saline (PBS, pH 7.4) solution and in culture media over 2 weeks with a cumulative release ∼ 53%, 75% and 50%, respectively, over the first 7 days. The biocompatibility of the VCM-loaded SFCaPCol scaffold was determined by in vitro cell adhesion and proliferation tests of rat osteoblast-like UMR-106 cells. MTT tests indicated that UMR-106 cells were viable after exposure to the VCM loaded SFCaPCol, meaning that the scaffold (the flower-like blossoms) did not impair the cell's viability. The density of cells on the substrate was seen to increase with increasing cultured time. - Graphical abstract: A spherical calcium phosphate-collagen with flower-like blossoms consisting of nanorod building blocks (SFCaPCol) particles was achieved by a combination of sonication and freeze-drying. In vitro drug release profile and the biocompatibility of the VCM-loaded SFCaPCol composite cell adhesion and proliferation in rat osteoblast-like UMR-106 cells were determined for biomaterial applications. Highlights: ► SFCaPCol and VCM-loaded SFCaPCol composite were synthesized by a combination of ultra sonication and freeze-drying. ► VCM drug-loaded SFCaPCol composite was used as substrate for the growth of rat osteoblast-like UMR-106 cells. ► Controlled release of VCM from the composite is critically medium dependent. ► The VCM-loaded SFCaPCol composite is also bioactive by in

In Vitro Synergy of Telavancin and Rifampin Against Enterococcus faecium Resistant to Both Linezolid and Vancomycin.

Science.gov (United States)

Pankey, George A; Ashcraft, Deborah S

2013-01-01

An emerging pathogen is Enterococcus faecium resistant to both linezolid and vancomycin (LRVRE). Antimicrobial combinations may be required for therapy and need to be evaluated. The combination of daptomycin and rifampin has demonstrated good in vitro activity against gram-positive bacteria, including E faecium. Telavancin, a newer lipoglycopeptide, has shown in vitro activity against E faecium. We evaluated the combination of telavancin and rifampin and compared the results to the combination of daptomycin and rifampin used previously on the same isolates. Twenty-four genetically unique (by pulsed-field gel electrophoresis), clinical LRVRE isolates were collected in the United States from 2001-2004. Etest minimal inhibitory concentrations (MICs) (μg/mL) were 0.064-8 for telavancin, 1-4 for daptomycin, and 0.012 to >32 for rifampin. In vitro synergy testing was performed in triplicate by an Etest MIC:MIC ratio method, and summation fractional inhibitory concentration (ΣFIC) was calculated: synergy ≤0.5; indifference >0.5-4; and antagonism >4. The Etest method showed synergy (ΣFICs of 0.1-0.5) with telavancin + rifampin in 20/24 (83%) isolates and indifference (ΣFICs of 0.6-0.8) in 4/24 (17%) isolates. Similarly, the daptomycin + rifampin combination showed synergy (ΣFICs of 0.1-0.5) in 21/24 (88%) isolates and indifference (ΣFICs of 0.6-1.0) in 3/24 (12%) isolates by the Etest method. No antagonism was found. In vitro synergy with both combinations (rifampin + telavancin or daptomycin) was 83% and 88%, respectively, by Etest against these LRVRE isolates. Although both daptomycin and telavancin in combination with rifampin showed a high incidence of synergistic activity, further in vitro synergy testing with this combination should be performed against additional E faecium isolates. In vitro synergy may or may not translate into in vivo effectiveness.

CLINICAL ISOLATES OF MECA, METHICILLIN, VANCOMYCIN RESISTANCE S. AUREUS; ESBLs PRODUCING K.PNEUMONIA, E.COLI, P. AUREGENOSA FROM VARIOUS CLINICAL SOURCE AND ITS ANTIMICROBIAL RESISTANCE PATTERNS

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Ismail Mahmud Ali, Amirthalingam R

2015-01-01

Full Text Available Background and Objective: Antimicrobial resistance has turned into a key medical and public health crisis globally since the injudicious use of magic bullets (drugs. Aim of this study is focused on the clinical isolate and their percentages of resistant to antibiotics in gram positive bacteria such as MRSA, VRSA, and MSSA are common causes of nosocomical, skin structure infections, bacteremia and infection of other systems; ESBLs producing Enterobacteriaceae (E. coli, Klebsiella spp. is common agent of urinary tract, bloodstream, pulmonary and intra-abdominal infections and carbapenem resistant P. aeruginosa with its complete antimicrobial patterns which are currently practiced in this population. Methods: There are one hundred and fourteen (114 various clinical isolates, isolated from various clinical samples like throat swab, urine, pus, sputum, and blood culture, identified as specific isolate with resistance patterns were analyzed by BD phoenix-100 the auto analyzer. Results: Off 114 clinical isolate, 6 mecA-mediated resistance (cefoxitin>8mgc/ml, 11 methicillin resistance, 18 β lactam/βlactamase inhibitor, 12 methicillin sensitive and 3 vancomycin (>16µg/ml resistance S. aureus have been isolated from overall 50 isolate of S.aureus. In addition, there are 27 P.aeruginosa, 15 ESBLs from overall of 25 K. pneumoniae and 7 ESBLs out of 12 Escherichia coli species have been isolated. The resistance and susceptibility pattern percentages have been graphically represented for each isolates. Conclusion: Current study revealed that the drug classes of β lactam/βlactamase inhibitor having high resistance rate with S.aureus, P.aureginosa, K. pneumoniae and E. coli isolate. Also, some of other drug classes such as cepham and tetracycline having higher resistance rate with P.aureginosa and K.pneumoniae. In addition, the vancomycin resistances S. aureus have been isolated and reported as first time in this population.

Energy Systems Test Area (ESTA) Electrical Power Systems Test Operations: User Test Planning Guide

Science.gov (United States)

Salinas, Michael J.

2012-01-01

Test process, milestones and inputs are unknowns to first-time users of the ESTA Electrical Power Systems Test Laboratory. The User Test Planning Guide aids in establishing expectations for both NASA and non-NASA facility customers. The potential audience for this guide includes both internal and commercial spaceflight hardware/software developers. It is intended to assist their test engineering personnel in test planning and execution. Material covered includes a roadmap of the test process, roles and responsibilities of facility and user, major milestones, facility capabilities, and inputs required by the facility. Samples of deliverables, test article interfaces, and inputs necessary to define test scope, cost, and schedule are included as an appendix to the guide.

Collision-induced dissociation of noncovalent complexes between vancomycin antibiotics and peptide ligand stereoisomers: evidence for molecular recognition in the gas phase

DEFF Research Database (Denmark)

Jørgensen, Thomas J. D.; Delforge, D; Remacle, J

1999-01-01

In solution, the antibiotics of the vancomycin group bind stereospecifically to peptides with the C-terminal sequence: -L-Lys-D-Ala-D-Ala, Substitution by a L-Ala at either of the two C-terminal residues causes a dramatic decrease in the binding affinity to the antibiotics. This solution behavior...... is clearly reflected in electrospray ionization (ESI) mass spectra obtained from equimolar mixtures of an antibiotic, an isotopically labelled peptide ligand and an unlabelled peptide stereoisomer. Using collision-induced dissociation (CID) we have probed the gas phase stability of isomeric (1:1) noncovalent...

TOC-39, a novel parenteral broad-spectrum cephalosporin with excellent activity against methicillin-resistant Staphylococcus aureus.

Science.gov (United States)

Hanaki, H; Akagi, H; Masaru, Y; Otani, T; Hyodo, A; Hiramatsu, K

1995-01-01

TOC-39, a new parenteral cephalosporin, is a hydroxyimino-type cephem antibiotic with vinylthio-pyridyl moiety at the 3 position. TOC-39 was evaluated for antibacterial activity against various clinically isolated strains. TOC-39 had excellent activity, stronger than that of methicillin, oxacillin, the cephalosporins tested, imipenem, gentamicin, minocycline, tobramycin, ofloxacin, and ciprofloxacin against methicillin-resistant Staphylococcus aureus (MRSA) and had an MIC comparable to that of vancomycin (the MICs of TOC-39 and vancomycin for 90% of the strains tested were 3.13 and 1.56 micrograms/ml, respectively). Against Enterococcus faecalis strains, which are resistant to cephalosporins, TOC-39 was twice as active as ampicillin. Against methicillin-susceptible S. aureus, coagulase-negative Staphylococcus spp., and Streptococcus pneumoniae, TOC-39 was twice as active as or more active than cefotiam, ceftazidime, flomoxef, and cefpirome. Against Streptococcus pyogenes, TOC-39 was superior to cefotiam, ceftazidime, and flomoxef and was similar to cefpirome. In addition, the activity of TOC-39 was equal to or greater than that of cefotiam, ceftazidime, flomoxef, and cefpirome against Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Morganella morganii. In terms of bactericidal effect against MRSA, TOC-39 was superior to vancomycin. No mutant resistant to TOC-39 or vancomycin was obtained from susceptible MRSA strains. In murine systemic infection models, TOC-39 showed potent activity against S. aureus and E. coli. Against highly MRSA, the activity of TOC-39 was comparable to that of vancomycin. PMID:7625799

Energy Systems High-Pressure Test Laboratory | Energy Systems Integration

Science.gov (United States)

Facility | NREL Energy Systems High-Pressure Test Laboratory Energy Systems High-Pressure Test Laboratory In the Energy Systems Integration Facility's High-Pressure Test Laboratory, researchers can safely test high-pressure hydrogen components. Photo of researchers running an experiment with a hydrogen fuel

Evolution of a test article handling system for the SP-100 ground engineering system test

International Nuclear Information System (INIS)

Shen, E.J.; Schweiger, L.J.; Miller, W.C.; Gluck, R.; Devies, S.M.

1987-04-01

A simulated space environment test of a flight prototypic SP-100 reactor, control system, and flight shield will be conducted at the Hanford Engineering Development Laboratory (HEDL). The flight prototypic components and the supporting primary heat removal system are collectively known as the Nuclear Assembly Test Article (TA). The unique configuration and materials of fabrication for the Test Article require a specialized handling facility to support installation, maintenance, and final disposal operations. Westinghouse Hanford Company, the Test Site Operator, working in conjunction with General Electric Company, the Test Article supplier, developed and evaluated several handling concepts resulting in the selection of a reference Test Article Handling System. The development of the reference concept for the handling system is presented

A Modified Shunt System for the Management of Pyogenic Hydrocephalus

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Abdul Naveed Khan

2017-01-01

Full Text Available BACKGROUND: To describe the structure and efficacy of a modified cerebrospinal fluid (CSF shunt system with Bhatti CSF access chamber and ventriculoperitoneal shunt, for the management of hydrocephalus associated with pyogenic ventriculitis. METHODS: This was an observational study performed at the National Medical Center and Ziauddin Medical University, Karachi, Pakistan. Chemically bonded Bhatti CSF access chamber and ventriculoperitoneal shunt was inserted into 443 patients with hydrocephalus and pyogenic ventriculitis to allow injection of antibiotics into the lateral ventricles. RESULTS: In all patients, symptoms and signs of hydrocephalus were relieved immediately after shunt insertion and infection brought under control within two weeks of intraventricular injection of antibiotics (vancomycin or linezolid, via the CSF access chamber. In two patients peritoneal catheter was blocked by a precipitate of vancomycin. Reduction in the dose of intraventricular vancomycin from 50mg to 20mg and increased dilution (additional 2ml of 0.9% N/S solution prevented recurrence of this complication. All patients recovered from ventriculitis within two weeks of initiating this treatment. Follow-up was from 3 months to 2 years to monitor continued relief of hydrocephalus and absence of recurrence of ventriculitis. CONCLUSION: Bhatti CSF access chamber and the ventriculoperitoneal shunt is the only system available at present that fulfills the management of hydrocephalus associated with pyogenic ventriculitis. It provides continuous internal drainage of CSF combined with access to the ventricles for injection of antibiotics.

Space Fission System Test Effectiveness

International Nuclear Information System (INIS)

Houts, Mike; Schmidt, Glen L.; Van Dyke, Melissa; Godfroy, Tom; Martin, James; Bragg-Sitton, Shannon; Dickens, Ricky; Salvail, Pat; Harper, Roger

2004-01-01

Space fission technology has the potential to enable rapid access to any point in the solar system. If fission propulsion systems are to be developed to their full potential, however, near-term customers need to be identified and initial fission systems successfully developed, launched, and utilized. One key to successful utilization is to develop reactor designs that are highly testable. Testable reactor designs have a much higher probability of being successfully converted from paper concepts to working space hardware than do designs which are difficult or impossible to realistically test. ''Test Effectiveness'' is one measure of the ability to realistically test a space reactor system. The objective of this paper is to discuss test effectiveness as applied to the design, development, flight qualification, and acceptance testing of space fission systems. The ability to perform highly effective testing would be particularly important to the success of any near-term mission, such as NASA's Jupiter Icy Moons Orbiter, the first mission under study within NASA's Project Prometheus, the Nuclear Systems Program

Test results of HTTR control system

International Nuclear Information System (INIS)

Motegi, Toshihiro; Iigaki, Kazuhiko; Saito, Kenji; Sawahata, Hiroaki; Hirato, Yoji; Kondo, Makoto; Shibutani, Hideki; Ogawa, Satoru; Shinozaki, Masayuki; Mizushima, Toshihiko; Kawasaki, Kozo

2006-06-01

The plant control performance of the IHX helium flow rate control system, the PPWC helium flow rate control system, the secondary helium flow rate control system, the inlet temperature control system, the reactor power control system and the outlet temperature control system of the HTTR are obtained through function tests and power-up tests. As the test results, the control systems show stable control response under transient condition. Both of inlet temperature control system and reactor power control system shows stable operation from 30% to 100%, respectively. This report describes the outline of control systems and test results. (author)

Testing lifting systems in nuclear facilities

International Nuclear Information System (INIS)

Kling, H.; Laug, R.

1984-01-01

Lifting systems in nuclear facilities must be inspected at regular intervals after having undergone their first acceptance test. These inspections are frequently carried out by service firms which not only employ the skilled personnel required for such jobs but also make available the necessary test equipment. The inspections in particular include a number of sophisticated load tests for which test load systems have been developed to allow lifting systems to be tested so that reactor specific boundary conditions are taken into account. In view of the large number of facilities to be inspected, the test load system is a modular system. (orig.) [de

Comparison of topical fixed-combination fortified vancomycin-amikacin (VA solution) to conventional separate therapy in the treatment of bacterial corneal ulcer.

Science.gov (United States)

Chiang, C-C; Lin, J-M; Chen, W-L; Chiu, Y-T; Tsai, Y-Y

2009-02-01

In an in vitro study, fixed-combination fortified vancomycin and amikacin ophthalmic solutions (VA solution) had the same potency and stable physical properties as the separate components. In this retrospective clinical study, we evaluated the efficacy of the topical VA solution in the treatment of bacterial corneal ulcer and comparison with separate topical fortified vancomycin and amikacin. Separate topical fortified eye drops was used prior to January 2004 and switched to the VA solution afterwards in the treatment of bacterial corneal ulcer. The medical records of 223 patients diagnosed with bacterial corneal ulcers between January 2002 and December 2005 were reviewed retrospectively. There were 122 patients in the VA group and 101 in the separate group. Cure was defined as complete healing of the ulcer accompanied by a nonprogressive stromal infiltrate on two consecutive visits. No significant difference was found between the VA and separate therapy group. The mean treatment duration was 15.4 days in the VA group and 16.1 days in the separate therapy group. The average hospital stay was 5.4 days (VA) and 7.2 days (separate antibiotics). Stromal infiltration regressed significantly without further expansion in both groups. All corneal ulcers completely re-epithelialized without complications related to drugs. VA solution provided similar efficacy to the conventional separate therapy in the treatment of bacterial corneal ulcers; however, it is more convenient and tolerable, promotes patient's compliance, avoids the washout effect, and reduces nurse utilization. Hence, VA solution is a good alternative to separate therapy.

Characterization and modelling of VanT: a novel, membrane-bound, serine racemase from vancomycin-resistant Enterococcus gallinarum BM4174.

Science.gov (United States)

Arias, C A; Martín-Martinez, M; Blundell, T L; Arthur, M; Courvalin, P; Reynolds, P E

1999-03-01

Sequence determination of a region downstream from the vanXYc gene in Enterococcus gallinarum BM4174 revealed an open reading frame, designated vanT, that encodes a 698-amino-acid polypeptide with an amino-terminal domain containing 10 predicted transmembrane segments. The protein contained a highly conserved pyridoxal phosphate attachment site in the C-terminal domain, typical of alanine racemases. The protein was overexpressed in Escherichia coli, and serine racemase activity was detected in the membrane but not in the cytoplasmic fraction after centrifugation of sonicated cells, whereas alanine racemase activity was located almost exclusively in the cytoplasm. When the protein was overexpressed as a polypeptide lacking the predicted transmembrane domain, serine racemase activity was detected in the cytoplasm. The serine racemase activity was partially (64%) inhibited by D-cycloserine, whereas host alanine racemase activity was almost totally inhibited (97%). Serine racemase activity was also detected in membrane preparations of constitutively vancomycin-resistant E. gallinarum BM4174 but not in BM4175, in which insertional inactivation of the vanC-1 D-Ala:D-Ser ligase gene probably had a polar effect on expression of the vanXYc and vanT genes. Comparative modelling of the deduced C-terminal domain was based on the alignment of VanT with the Air alanine racemase from Bacillus stearothermophilus. The model revealed that almost all critical amino acids in the active site of Air were conserved in VanT, indicating that the C-terminal domain of VanT is likely to adopt a three-dimensional structure similar to that of Air and that the protein could exist as a dimer. These results indicate that the source of D-serine for peptidoglycan synthesis in vancomycin-resistant enterococci expressing the VanC phenotype involves racemization of L- to D-serine by a membrane-bound serine racemase.

Intestinal Microbiota Containing Barnesiella Species Cures Vancomycin-Resistant Enterococcus faecium Colonization

Science.gov (United States)

Bucci, Vanni; Caballero, Silvia; Djukovic, Ana; Toussaint, Nora C.; Equinda, Michele; Lipuma, Lauren; Ling, Lilan; Gobourne, Asia; No, Daniel; Taur, Ying; Jenq, Robert R.; van den Brink, Marcel R. M.; Xavier, Joao B.

2013-01-01

Bacteria causing infections in hospitalized patients are increasingly antibiotic resistant. Classical infection control practices are only partially effective at preventing spread of antibiotic-resistant bacteria within hospitals. Because the density of intestinal colonization by the highly antibiotic-resistant bacterium vancomycin-resistant Enterococcus (VRE) can exceed 109 organisms per gram of feces, even optimally implemented hygiene protocols often fail. Decreasing the density of intestinal colonization, therefore, represents an important approach to limit VRE transmission. We demonstrate that reintroduction of a diverse intestinal microbiota to densely VRE-colonized mice eliminates VRE from the intestinal tract. While oxygen-tolerant members of the microbiota are ineffective at eliminating VRE, administration of obligate anaerobic commensal bacteria to mice results in a billionfold reduction in the density of intestinal VRE colonization. 16S rRNA gene sequence analysis of intestinal bacterial populations isolated from mice that cleared VRE following microbiota reconstitution revealed that recolonization with a microbiota that contains Barnesiella correlates with VRE elimination. Characterization of the fecal microbiota of patients undergoing allogeneic hematopoietic stem cell transplantation demonstrated that intestinal colonization with Barnesiella confers resistance to intestinal domination and bloodstream infection with VRE. Our studies indicate that obligate anaerobic bacteria belonging to the Barnesiella genus enable clearance of intestinal VRE colonization and may provide novel approaches to prevent the spread of highly antibiotic-resistant bacteria. PMID:23319552

Prevalence of methicillin-resistant staphylococci isolated from different biological samples at Policlinico Umberto I of Rome: correlation with vancomycin susceptibility

Directory of Open Access Journals (Sweden)

Maria Teresa Mascellino

2011-03-01

Full Text Available The methicillin-resistance is increasing all over the world in the last decade. It is more frequent among coagulase-negative staphylococci (MRCoNS; infact the 52% of S. epidermidis strains results to be resistant to methicillin.The methicillin-resistant strains also show a reduced sensitivity towards the first-line agents such as glycopeptides and other antibiotics commonly used in therapy such as trimethoprim-sulphamethoxazole, imipenem, gentamycin, fosfomycin and chlarytromicin. Unlike MRSA (Methicillin-resistant S. aureus, MRCoNS resistance to glycopeptides generally concerns teicoplanin. Although vancomycin resistance is rare in Staphylococcus isolates, the detected shift towards higher values of MICs might affect patient’s clinical outcome.

Minicomputer controlled test system for process control and monitoring systems

International Nuclear Information System (INIS)

Worster, L.D.

A minicomputer controlled test system for testing process control and monitoring systems is described. This system, in service for over one year, has demonstrated that computerized control of such testing has a real potential for expanding the scope of the testing, improving accuracy of testing, and significantly reducing the time required to do the testing. The test system is built around a 16-bit minicomputer with 12K of memory. The system programming language is BASIC with the addition of assembly level routines for communication with the peripheral devices. The peripheral devices include a 100 channel scanner, analog-to-digital converter, visual display, and strip printer. (auth)

Proactive infection control measures to prevent nosocomial transmission of vancomycin-resistant enterococci in Hong Kong.

Science.gov (United States)

Cheng, Vincent Chi-Chung; Tai, Josepha Wai-Ming; Chen, Jonathan Hon-Kwan; So, Simon Yung-Chun; Ng, Wing-Chun; Hung, Ivan Fan-Ngan; Leung, Sally Sau-Man; Wong, Sally Cheuk-Ying; Chan, Tuen-Ching; Chan, Felix Hon-Wai; Ho, Pak-Leung; Yuen, Kwok-Yung

2014-10-01

The study describes a proactive infection control approach to prevent nosocomial transmission of vancomycin-resistant enterococci (VRE) and tests if this approach is effective for controlling multiple-drug resistant organisms in a nonendemic setting. In response to the increasing prevalence of VRE in Hong Kong since 2011, we adopted a multifaceted assertive approach in our health care network. This included active surveillance culture, extensive contact tracing, directly observed hand hygiene in conscious patients before they received meals and medications, stringent hand hygiene and environmental cleanliness, and an immediate feedback antimicrobial stewardship program. We report the occurrence of VRE outbreaks in our hospital after institution of these measures and compared with the concurrent occurrence in other public hospitals in Hong Kong. Between July 1, 2011 and November 13, 2013, VRE was identified in 0.32% (50/15,851) of admission episodes by active surveillance culture. The risk of VRE carriage was three times higher in patients with a history of hospitalization outside our hospital networks in the past 3 months (0.56% vs. 0.17%; p = 0.001) compared with those who were not. Extensive contact tracing involving 3277 patient episodes was performed in the investigation for the 25 VRE index patients upon whom implementation of contact precautions was delayed (more than 48 hours of hospitalization). One episode of VRE outbreak was identified in our hospital network, compared with the 77 VRE outbreaks reported in the other hospital networks (controls) without these proactive infection control measures. Our multifaceted assertive proactive infection control approach can minimize the nosocomial transmission and outbreak of VRE in a nonendemic area. Copyright © 2014. Published by Elsevier B.V.

Fatigue tests of dowel-socket systems

International Nuclear Information System (INIS)

Chiang, D.D.

1976-01-01

A test program was conducted to determine the fatigue behavior of LHTGR fuel element dowel/socket systems. Two dowel/socket systems, namely, a four-dowel system and a five-dowel system, were tested to failure under shear loads applied through a fatigue test apparatus to simulate repetitive loading during a seismic event

System Performance and Testing

NARCIS (Netherlands)

Frei, U.; Oversloot, H.

2004-01-01

This chapter compares and contrasts the system performance of two widely used solar thermal systems using testing and simulation programs. Solar thermal systems are used in many countries for heating domestically used water. In addition to the simple thermosiphon systems, better designed pumped

Early life treatment with vancomycin propagates Akkermansia muciniphila and reduces diabetes incidence in the NOD mouse

DEFF Research Database (Denmark)

Hansen, Camilla Hartmann Friis; Krych, Lukasz; Nielsen, Dennis Sandris

2012-01-01

, a glycopeptide antibiotic specifically directed against Gram-positive bacteria, could influence immune homeostasis and the development of diabetic symptoms in the NOD mouse model for diabetes. Methods: Accordingly, one group of mice received vancomycin from birth until weaning (day 28), while another group...... lower for the neonatally treated group compared with the untreated group, whereas the insulitis score and blood glucose levels were significantly lower for the mice treated as adults compared with the other groups. Mucosal inflammation was investigated by intracellular cytokine staining of the small...... genera of Gram-positive and Gram-negative microbes while, interestingly, one single species, Akkermansia muciniphila, became dominant. Conclusions/interpretation: The early postnatal period is a critical time for microbial protection from type 1 diabetes and it is suggested that the mucolytic bacterium A...

Aerococcus urinae and Aerococcus sanguinicola

DEFF Research Database (Denmark)

Carkaci, Derya; Nielsen, Xiaohui C.; Fuursted, Kurt

2017-01-01

, cefotaxime, meropenem, vancomycin, linezolid, and rifampicin. Methods: Three susceptibility testing methods were used; disk diffusion according to The European Committee on Antimicrobial Susceptibility Testing (EUCAST) standardized disk diffusion methodology and MIC determination with Etest and broth...... were found susceptible to all six antimicrobial agents: penicillin, cefotaxime, meropenem, vancomycin, linezolid, and rifampicin....

Characterization of a vancomycin-resistant Enterococcus faecalis (VREF) isolate from a dog with mastitis: further evidence of a clonal lineage of VREF in New Zealand.

Science.gov (United States)

Manson, Janet M; Keis, Stefanie; Smith, John M B; Cook, Gregory M

2003-07-01

We report here on the characterization of a vancomycin-resistant Enterococcus faecalis (VREF) isolated from a dog with mastitis. The isolate was positive for the vanA, ermB, and tet(M) genes, with vanA and ermB carried on the same transferable plasmid. Comparison of this isolate with VREF from poultry and human sources in New Zealand demonstrated identical SmaI macrorestriction patterns and Tn1546-like elements. This is further evidence of a clonal lineage of VREF in New Zealand.

Harmonization of antimicrobial susceptibility testing among veterinary diagnostic laboratories in the five Nordic countries

DEFF Research Database (Denmark)

Petersen, A.; Aarestrup, Frank Møller; Hofshagen, Merete

2003-01-01

A total of 100 bacterial strains (25 Escherichia coli, 25 Salmonella enterica, 25 Staphylococcus aureus, and 25 Enterococcus strains) and four reference strains were tested for susceptibility toward 8-12 antimicrobial agents in 12 veterinary diagnostic laboratories in the five Nordic countries...... reported as vancomycin resistant. Ten laboratories identified the Enterococcus spp. to species level. All five Enterococcus faecium and 10 Enterococcus faecalis selected from the strain collection at the Danish Veterinary Institute were correctly identified by all laboratories, whereas some problems were...

Light Duty Utility Arm system pre-operational (cold test) test plan

International Nuclear Information System (INIS)

Bennett, K.L.

1995-01-01

The Light Duty Utility (LDUA) Cold Test Facility, located in the Hanford 400 Area, will be used to support cold testing (pre- operational tests) of LDUA subsystems. Pre-operational testing is composed of subsystem development testing and rework activities, and integrated system qualification testing. Qualification testing will be conducted once development work is complete and documentation is under configuration control. Operational (hot) testing of the LDUA system will follow the testing covered in this plan and will be covered in a separate test plan

Testing on air cleaning systems: Testing of the components in-place tests

International Nuclear Information System (INIS)

Billard, F.; Brion, J.

1967-01-01

The reliability of air cleaning systems is dependent on testing they are submitted to. Although in-place tests are the most important as they act as final tests upon achieved plants, component tests are necessary too. They allow detection of defective units before they are installed, partition of unit defects from mounting defects and they are more sensitive. For similar reasons, material teats are most useful. The various tests are described, about aerosol filters for one part, iodine trap for the other. The checked features are: materials nature, units sizes, efficiency, air resistance, flammability, humidity resistance, temperature resistance, adsorbent friability, etc... On iodine trapping systems, small check traps, working by-pass with the main trap are periodically subjected to efficiency test. This control allow to cut down the in-place tests frequency, particularly when poisoning from organic vapours is to be feared. (authors) [fr

Safety testing for LHC access system

CERN Document Server

Valentini, F; Ninin, P; Scibile, S

2008-01-01

In the domain of Safety Real-Time Systems the problem of testing represents always a big effort in terms of time, costs and efficiency to guarantee an adequate coverage degree. Exhaustive tests may, in fact, not be practicable for large and distributed systems. This paper describes the testing process followed during the validation of the CERN's LHC Access System [1], responsible for monitoring and preventing physical risks for the personnel accessing the underground areas. In the paper we also present a novel strategy for the testing problem, intended to drastically reduce the time for the test patterns generation and execution. In particular, we propose a methodology for blackbox testing that relies on the application of Model Checking techniques. Model Checking is a formal method from computer science, commonly adopted to prove correctness of system’s models through an automatic system’s state space exploration against some property formulas.

SP-100 nuclear assembly test: Test assembly functional requirements and system arrangement

International Nuclear Information System (INIS)

Fallas, T.T.; Gluck, R.; Motwani, K.; Clay, H.; O'Neill, G.

1991-01-01

This paper describes the functional requirements and the system that will be tested to validate the reactor, flight shield, and flight controller of the SP-100 Generic Flight System (GFS). The Nuclear Assembly Test (NAT) consists of the test article (SP-100 reactor with control devices and the flight shield) and its supporting systems. The NAT test assembly is being designed by GE. Westinghouse Hanford Company (WHC) is designing the test cell and vacuum vessel system that will contain the NAT test assembly (Renkey et al. 1989). Preliminary design reviews have been completed and the final design is under way

CMIF ECLS system test findings

Science.gov (United States)

Schunk, Richard G.; Carrasquillo, Robyn L.; Ogle, Kathyrn Y.; Wieland, Paul O.; Bagdigian, Robert M.

1989-01-01

During 1987 three Space Station integrated Environmental Control and Life Support System (ECLSS) tests were conducted at the Marshall Space Flight Center (MSFC) Core Module Integration Facility (CMIF) as part of the MSFC ECLSS Phase II test program. The three tests ranged in duration from 50 to 150 hours and were conducted inside of the CMIF module simulator. The Phase II partial integrated system test configuration consisted of four regenerative air revitalization subsystems and one regenerative water reclamation subsystem. This paper contains a discussion of results and lessons learned from the Phase II test program. The design of the Phase II test configuration and improvements made throughout the program are detailed. Future plans for the MSFC CMIF test program are provided, including an overview of planned improvements for the Phase III program.

High Power Alternator Test Unit (ATU) Electrical System Test

Science.gov (United States)

Birchenough, Arthur; Hervol, David

2007-01-01

The Alternator Test Unit (ATU) in the Lunar Power System Facility (LPSF) located at the NASA Glenn Research Center (GRC) in Cleveland, OH was used to simulate the operating conditions and evaluate the performance of the ATU and it s interaction with various LPSF components in accordance with the JIMO AC Power System Requirements. The testing was carried out at the breadboard development level. Results of these tests will be used for the development and validation of analytical models for performance and lifetime prediction.

Risk of surgical site infection, acute kidney injury, and Clostridium difficile infection following antibiotic prophylaxis with vancomycin plus a beta-lactam versus either drug alone: A national propensity-score-adjusted retrospective cohort study.

Science.gov (United States)

Branch-Elliman, Westyn; Ripollone, John E; O'Brien, William J; Itani, Kamal M F; Schweizer, Marin L; Perencevich, Eli; Strymish, Judith; Gupta, Kalpana

2017-07-01

The optimal regimen for perioperative antimicrobial prophylaxis is controversial. Use of combination prophylaxis with a beta-lactam plus vancomycin is increasing; however, the relative risks and benefits associated with this strategy are unknown. Thus, we sought to compare postoperative outcomes following administration of 2 antimicrobials versus a single agent for the prevention of surgical site infections (SSIs). Potential harms associated with combination regimens, including acute kidney injury (AKI) and Clostridium difficile infection (CDI), were also considered. Using a multicenter, national Veterans Affairs (VA) cohort, all patients who underwent cardiac, orthopedic joint replacement, vascular, colorectal, and hysterectomy procedures during the period from 1 October 2008 to 30 September 2013 and who received planned manual review of perioperative antimicrobial prophylaxis regimen and manual review for the 30-day incidence of SSI were included. Using a propensity-adjusted log-binomial regression model stratified by type of surgical procedure, the association between receipt of 2 antimicrobials (vancomycin plus a beta-lactam) versus either single agent alone (vancomycin or a beta-lactam) and SSI was evaluated. Measures of association were adjusted for age, diabetes, smoking, American Society of Anesthesiologists score, preoperative methicillin-resistant Staphylococcus aureus (MRSA) status, and receipt of mupirocin. The 7-day incidence of postoperative AKI and 90-day incidence of CDI were also measured. In all, 70,101 procedures (52,504 beta-lactam only, 5,089 vancomycin only, and 12,508 combination) with 2,466 (3.5%) SSIs from 109 medical centers were included. Among cardiac surgery patients, combination prophylaxis was associated with a lower incidence of SSI (66/6,953, 0.95%) than single-agent prophylaxis (190/12,834, 1.48%; crude risk ratio [RR] 0.64, 95% CI 0.49, 0.85; adjusted RR 0.61, 95% CI 0.46, 0.83). After adjusting for SSI risk, no association

Risk of surgical site infection, acute kidney injury, and Clostridium difficile infection following antibiotic prophylaxis with vancomycin plus a beta-lactam versus either drug alone: A national propensity-score-adjusted retrospective cohort study.

Directory of Open Access Journals (Sweden)

Westyn Branch-Elliman

2017-07-01

Full Text Available The optimal regimen for perioperative antimicrobial prophylaxis is controversial. Use of combination prophylaxis with a beta-lactam plus vancomycin is increasing; however, the relative risks and benefits associated with this strategy are unknown. Thus, we sought to compare postoperative outcomes following administration of 2 antimicrobials versus a single agent for the prevention of surgical site infections (SSIs. Potential harms associated with combination regimens, including acute kidney injury (AKI and Clostridium difficile infection (CDI, were also considered.Using a multicenter, national Veterans Affairs (VA cohort, all patients who underwent cardiac, orthopedic joint replacement, vascular, colorectal, and hysterectomy procedures during the period from 1 October 2008 to 30 September 2013 and who received planned manual review of perioperative antimicrobial prophylaxis regimen and manual review for the 30-day incidence of SSI were included. Using a propensity-adjusted log-binomial regression model stratified by type of surgical procedure, the association between receipt of 2 antimicrobials (vancomycin plus a beta-lactam versus either single agent alone (vancomycin or a beta-lactam and SSI was evaluated. Measures of association were adjusted for age, diabetes, smoking, American Society of Anesthesiologists score, preoperative methicillin-resistant Staphylococcus aureus (MRSA status, and receipt of mupirocin. The 7-day incidence of postoperative AKI and 90-day incidence of CDI were also measured. In all, 70,101 procedures (52,504 beta-lactam only, 5,089 vancomycin only, and 12,508 combination with 2,466 (3.5% SSIs from 109 medical centers were included. Among cardiac surgery patients, combination prophylaxis was associated with a lower incidence of SSI (66/6,953, 0.95% than single-agent prophylaxis (190/12,834, 1.48%; crude risk ratio [RR] 0.64, 95% CI 0.49, 0.85; adjusted RR 0.61, 95% CI 0.46, 0.83. After adjusting for SSI risk, no

Test Telemetry And Command System (TTACS)

Science.gov (United States)

Fogel, Alvin J.

1994-01-01

The Jet Propulsion Laboratory has developed a multimission Test Telemetry and Command System (TTACS) which provides a multimission telemetry and command data system in a spacecraft test environment. TTACS reuses, in the spacecraft test environment, components of the same data system used for flight operations; no new software is developed for the spacecraft test environment. Additionally, the TTACS is transportable to any spacecraft test site, including the launch site. The TTACS is currently operational in the Galileo spacecraft testbed; it is also being provided to support the Cassini and Mars Surveyor Program projects. Minimal personnel data system training is required in the transition from pre-launch spacecraft test to post-launch flight operations since test personnel are already familiar with the data system's operation. Additionally, data system components, e.g. data display, can be reused to support spacecraft software development; and the same data system components will again be reused during the spacecraft integration and system test phases. TTACS usage also results in early availability of spacecraft data to data system development and, as a result, early data system development feedback to spacecraft system developers. The TTACS consists of a multimission spacecraft support equipment interface and components of the multimission telemetry and command software adapted for a specific project. The TTACS interfaces to the spacecraft, e.g., Command Data System (CDS), support equipment. The TTACS telemetry interface to the CDS support equipment performs serial (RS-422)-to-ethernet conversion at rates between 1 bps and 1 mbps, telemetry data blocking and header generation, guaranteed data transmission to the telemetry data system, and graphical downlink routing summary and control. The TTACS command interface to the CDS support equipment is nominally a command file transferred in non-real-time via ethernet. The CDS support equipment is responsible for

Vitrification Facility integrated system performance testing report

International Nuclear Information System (INIS)

Elliott, D.

1997-01-01

This report provides a summary of component and system performance testing associated with the Vitrification Facility (VF) following construction turnover. The VF at the West Valley Demonstration Project (WVDP) was designed to convert stored radioactive waste into a stable glass form for eventual disposal in a federal repository. Following an initial Functional and Checkout Testing of Systems (FACTS) Program and subsequent conversion of test stand equipment into the final VF, a testing program was executed to demonstrate successful performance of the components, subsystems, and systems that make up the vitrification process. Systems were started up and brought on line as construction was completed, until integrated system operation could be demonstrated to produce borosilicate glass using nonradioactive waste simulant. Integrated system testing and operation culminated with a successful Operational Readiness Review (ORR) and Department of Energy (DOE) approval to initiate vitrification of high-level waste (HLW) on June 19, 1996. Performance and integrated operational test runs conducted during the test program provided a means for critical examination, observation, and evaluation of the vitrification system. Test data taken for each Test Instruction Procedure (TIP) was used to evaluate component performance against system design and acceptance criteria, while test observations were used to correct, modify, or improve system operation. This process was critical in establishing operating conditions for the entire vitrification process

Detection Antibiotic Resistance of Enviromental Bacterial Strains

Directory of Open Access Journals (Sweden)

Huda Zuheir Majeed

2018-05-01

Full Text Available      Antibiotics are randomly prescribed  for veterinary and human medication. Antibiotics by little number are used by human , animals are digested uncompletely  in their digestive system and ended up in communal sewage and hospitals, eventually discharge in environmental water sources directly with no processing.     Water itself consider as major factor of dispersal of bacteria between different environmental components. Besides, bacteria had  transferable genetic mobile elements to different sites of soil, water and humans.       Environmental swabs were collected locally including 50 swabs of hospital environment , 15 samples of poultry feces and chicken guts , 20 sample of heavy water and 15 sample of fish tank to identify16 isolate of Staphylococcus (4 isolate of Staphylococus aureus and 12 isolate of coagulase –ve Staphylococcus , 19 isolate of Enterococcus spp. , 7 isolates of Pseudomonas and 5 environment isolates for each Shigella spp.  and Salmonella spp. .           Teicoplanin and Vancomycin sensitivity test of isolates was done , showing that 2out of 16 isolates of Staphylococcus (12.5% were Vancomycin-resistant , and 3out of 19 isolates of Enterococcus (15.7 % were Vancomycin-resistant, while the rest of isolates were Vancomycin- sensitive. From other side , all isolates was Teicoplanin- sensitive except only 1 Enterococcus spp. Isolate which was intermediate . The range of the Vancomycin MIC were (6-64 µg/ml . Vancomycin resistant isolates , showed that some isolates have one plasmid band after Extraction of their DNA.

Test plan: Brayton Isotope Power System Ground Demonstration System (BIPS-GDS)

International Nuclear Information System (INIS)

1976-01-01

The purpose of this test plan is to provide an overall outline of all testing to be accomplished on the GDS. Included in this test plan are administrative requirements, instrumentation accuracies, instrumentation, equipment definitions, system test setup, and facility installation. The test program will enable collection of sufficient data to establish material, component, and system design integrity. The data will also be used to establish and evaluate component and system performance and reliability characteristics, verification of proper system component integration prior to initiation of Phase II, and flight system (FS) development

Continuous Improvement in Battery Testing at the NASA/JSC Energy System Test Area

Science.gov (United States)

Boyd, William; Cook, Joseph

2003-01-01

The Energy Systems Test Area (ESTA) at the Lyndon B. Johnson Space Center in Houston, Texas conducts development and qualification tests to fulfill Energy System Division responsibilities relevant to ASA programs and projects. EST A has historically called upon a variety of fluid, mechanical, electrical, environmental, and data system capabilities spread amongst five full-service facilities to test human and human supported spacecraft in the areas of propulsion systems, fluid systems, pyrotechnics, power generation, and power distribution and control systems. Improvements at ESTA are being made in full earnest of offering NASA project offices an option to choose a thorough test regime that is balanced with cost and schedule constraints. In order to continue testing of enabling power-related technologies utilized by the Energy System Division, an especially proactive effort has been made to increase the cost effectiveness and schedule responsiveness for battery testing. This paper describes the continuous improvement in battery testing at the Energy Systems Test Area being made through consolidation, streamlining, and standardization.

The role of side stream dark field microvasculature imaging in a rare case of vancomycin-resistant enterococcal endocarditis complicated by heparin-induced thrombocytopenia

Directory of Open Access Journals (Sweden)

Janak Bechar

2016-01-01

Full Text Available Sidestream dark field (SDF imaging allows direct visualization of microvascular architecture and function. We examine the role of an SDF imaging device in visualizing the sub-lingual microvasculature as a surrogate for splanchnic microperfusion. We demonstrate good correlation between current monitoring techniques and the SDF imaging device in a rare case of vancomycin-resistant enterococcal (VRE sepsis along with heparin-induced thrombocytopenia (HIT. To the best of our knowledge, VRE endocarditis with concurrent HIT has not been described in literature. The role of SDF imaging may predict the earlier need for escalation of care, improving morbidity and mortality.

Testing Infrastructure for Operating System Kernel Development

DEFF Research Database (Denmark)

Walter, Maxwell; Karlsson, Sven

2014-01-01

Testing is an important part of system development, and to test effectively we require knowledge of the internal state of the system under test. Testing an operating system kernel is a challenge as it is the operating system that typically provides access to this internal state information. Multi......-core kernels pose an even greater challenge due to concurrency and their shared kernel state. In this paper, we present a testing framework that addresses these challenges by running the operating system in a virtual machine, and using virtual machine introspection to both communicate with the kernel...... and obtain information about the system. We have also developed an in-kernel testing API that we can use to develop a suite of unit tests in the kernel. We are using our framework for for the development of our own multi-core research kernel....

Development of Final Running Test System for Digital Systems

Energy Technology Data Exchange (ETDEWEB)

Lee, Kwang-Dae; Lee, Eui-Jong; Lim, Hee-Taek; Kim, Min-Seok [KHNP Central Research Institute, Daejeon (Korea, Republic of)

2016-10-15

In nuclear industry, the newly designed systems to upgrade are qualified to meet IEEE standards and the regulatory guidelines for their functions, performance and reliability requirements. Failure Mode and Effect Analysis, Fault Tree Analysis, and Hazard Analysis have been used to improve the reliability of the control system. To ensure the completeness of the software, the verification and validation processes are carried out during the development process. In spite of the many efforts depending on the analysis and procedures, there are limitations to improve the reliability. The lessons learned from the currently installed system failures show the incompleteness of the final integration test. The current point-to-point and logic-to-logic separate test procedures manually performed by the engineers can cause some procedures missed and have effects on the critical functions. The design processes of the digital systems are met in accordance with the international standards and regulatory guidelines. The lessons learned from the failures of the running digital systems showed the limitations of the current verification and validation efforts. The various improvements and attempts have been considered including the expert review processes and the completeness of the test. In this paper, the Final Running Test Method evaluating the completeness of the digital system using the control patterns and the Test System Architecture are proposed.

Development of Final Running Test System for Digital Systems

International Nuclear Information System (INIS)

Lee, Kwang-Dae; Lee, Eui-Jong; Lim, Hee-Taek; Kim, Min-Seok

2016-01-01

In nuclear industry, the newly designed systems to upgrade are qualified to meet IEEE standards and the regulatory guidelines for their functions, performance and reliability requirements. Failure Mode and Effect Analysis, Fault Tree Analysis, and Hazard Analysis have been used to improve the reliability of the control system. To ensure the completeness of the software, the verification and validation processes are carried out during the development process. In spite of the many efforts depending on the analysis and procedures, there are limitations to improve the reliability. The lessons learned from the currently installed system failures show the incompleteness of the final integration test. The current point-to-point and logic-to-logic separate test procedures manually performed by the engineers can cause some procedures missed and have effects on the critical functions. The design processes of the digital systems are met in accordance with the international standards and regulatory guidelines. The lessons learned from the failures of the running digital systems showed the limitations of the current verification and validation efforts. The various improvements and attempts have been considered including the expert review processes and the completeness of the test. In this paper, the Final Running Test Method evaluating the completeness of the digital system using the control patterns and the Test System Architecture are proposed

A/T test system for production line; Seisan line yo A/T test system

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-03-10

This paper introduces an A/T test system for production line made by Meidensha, Inc. Rates and technology of mounting auto-transmissions (A/T) in recent automobiles are improving year after year. A/T production line testers were fabricated and supplied, including those for European countries. This system has the following features: the system employs low inertia AC motor, and is capable of performing tests in close conditions to actual cars; an insulated gate bipolar transistor (IGBT) inverter was employed to achieve control accuracy improvement and noise reduction; high-velocity transient measurement is possible by using a computer system based on the WindowsNT; a solenoid current slant control was employed to respond to electronically controlled A/T; and noise and vibration shift feeling instrumentation can also be used on option. Number of supply is four sets of front engine/front wheel drive (FF) car A/T testers for overseas countries, and two sets of FF A/T tests for use in Japan. (NEDO)

21 CFR 862.3610 - Methamphetamine test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Methamphetamine test system. 862.3610 Section 862....3610 Methamphetamine test system. (a) Identification. A methamphetamine test system is a device intended to measure methamphetamine, a central nervous system stimulating drug, in serum, plasma, and urine...

Launch Control System Software Development System Automation Testing

Science.gov (United States)

Hwang, Andrew

2017-01-01

The Spaceport Command and Control System (SCCS) is the National Aeronautics and Space Administration's (NASA) launch control system for the Orion capsule and Space Launch System, the next generation manned rocket currently in development. This system requires high quality testing that will measure and test the capabilities of the system. For the past two years, the Exploration and Operations Division at Kennedy Space Center (KSC) has assigned a group including interns and full-time engineers to develop automated tests to save the project time and money. The team worked on automating the testing process for the SCCS GUI that would use streamed simulated data from the testing servers to produce data, plots, statuses, etc. to the GUI. The software used to develop automated tests included an automated testing framework and an automation library. The automated testing framework has a tabular-style syntax, which means the functionality of a line of code must have the appropriate number of tabs for the line to function as intended. The header section contains either paths to custom resources or the names of libraries being used. The automation library contains functionality to automate anything that appears on a desired screen with the use of image recognition software to detect and control GUI components. The data section contains any data values strictly created for the current testing file. The body section holds the tests that are being run. The function section can include any number of functions that may be used by the current testing file or any other file that resources it. The resources and body section are required for all test files; the data and function sections can be left empty if the data values and functions being used are from a resourced library or another file. To help equip the automation team with better tools, the Project Lead of the Automated Testing Team, Jason Kapusta, assigned the task to install and train an optical character recognition (OCR

Experimental fast reactor JOYO MK-III functional test. Primary auxiliary cooling system test

International Nuclear Information System (INIS)

Karube, Koji; Akagi, Shinji; Terano, Toshihiro; Onuki, Osamu; Ito, Hideaki; Aoki, Hiroshi; Odo, Toshihiro

2004-03-01

This paper describes the results of primary auxiliary cooling system, which were done as a part of JOYO MK-III function test. The aim of the tests was to confirm the operational performance of primary auxiliary EMP and the protection system including siphon breaker of primary auxiliary cooling system. The items of the tests were: (Test No.): (Test item). 1) SKS-117: EMP start up test. 2) SKS-118-1: EMP start up test when pony motor running. 3) SKS-121: Function test of siphon breaker. The results of the tests satisfied the required performance, and demonstrated successful operation of primary auxiliary cooling system. (author)

LuxS/AI-2 system is involved in antibiotic susceptibility and autolysis in Staphylococcus aureus NCTC 8325.

Science.gov (United States)

Xue, Ting; Zhao, Liping; Sun, Baolin

2013-01-01

Current treatment for Staphylococcus aureus infections relies heavily upon the cell wall synthesis inhibitor antibiotics such as penicillin, oxacillin, vancomycin and teicoplanin. Increasing antibiotic resistance requires the development of new approaches to combating infection. Autoinducer-2 (AI-2) exists widely both in Gram-negative and Gram-positive pathogens and is suggested as a universal language for intraspecies and interspecies communication. This study demonstrates the association between AI-2 signalling and cell wall synthesis inhibitor antibiotic susceptibility in S. aureus. In addition, a luxS mutant exhibited decreased autolysis and upregulated vancomycin resistance-associated VraRS two-component regulatory system. This finding may provide novel clues for antimicrobial therapy in S. aureus infection. Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

BMFT-UPTF densitometer system test report

International Nuclear Information System (INIS)

Menkhaus, D.E.

1985-11-01

This report documents acceptance test results performed on the five Upper Plenum Test Facility (UPTF) three-beam densitometer systems and spare parts. The five densitometer systems are used on the UPTF four hot legs and broken cold leg to measure average chordal-beam densities. The primary objectives of the tests performed were: to verify all assemblies fit as designed (mechanical fitup); to ensure radiation levels met the criteria (<2.5 mR/h); to verify that design accuracy requirements were met (performance tests); and to verify proper operation of the densitometer systems (functional checks). 15 figs., 11 tabs

System Testing of Desktop and Web Applications

Science.gov (United States)

Slack, James M.

2011-01-01

We want our students to experience system testing of both desktop and web applications, but the cost of professional system-testing tools is far too high. We evaluate several free tools and find that AutoIt makes an ideal educational system-testing tool. We show several examples of desktop and web testing with AutoIt, starting with simple…

Test software for BESIII MDC electronics system

International Nuclear Information System (INIS)

Zhang Hongyu; Sheng Huayi; Zhu Haitao; Ji Xiaolu; Zhao Dongxu

2006-01-01

This paper presents the design of Test System Software for BESIII MDC Electronics. Two kinds of test systems, SBS VP7 based and PowerPC based systems, and their corresponding test software are introduced. The software is developed in LabVIEW 7.1 and Microsoft Visual C++ 6.0, some test functions of the software, as well as their user interfaces, are described in detail. The software has been applied in hardware debugging, performance test and long term stability test. (authors)

Preoperational test report, primary ventilation system

Energy Technology Data Exchange (ETDEWEB)

Clifton, F.T.

1997-11-04

This represents a preoperational test report for Primary Ventilation Systems, Project W-030. Project W-030 provides a ventilation upgrade for the four Aging Waste Facility tanks. The system provides vapor space filtered venting of tanks AY101, AY102, AZ101, AZ102. The tests verify correct system operation and correct indications displayed by the central Monitor and Control System.

Preoperational test report, primary ventilation system

International Nuclear Information System (INIS)

Clifton, F.T.

1997-01-01

This represents a preoperational test report for Primary Ventilation Systems, Project W-030. Project W-030 provides a ventilation upgrade for the four Aging Waste Facility tanks. The system provides vapor space filtered venting of tanks AY101, AY102, AZ101, AZ102. The tests verify correct system operation and correct indications displayed by the central Monitor and Control System

Operational test report, integrated system test (ventilation upgrade)

International Nuclear Information System (INIS)

HARTY, W.M.

1999-01-01

Operational Final Test Report for Integrated Systems, Project W-030 (Phase 2 test, RECIRC and HIGH-HEAT Modes). Project W-030 provides a ventilation upgrade for the four Aging Waste Facility tanks, including upgraded vapor space cooling and filtered venting of tanks AY101, AY102, AZ101, AZ102

Operational test report integrated system test (ventilation upgrade)

Energy Technology Data Exchange (ETDEWEB)

HARTY, W.M.

1999-10-05

Operational Final Test Report for Integrated Systems, Project W-030 (Phase 2 test, RECIRC and HIGH-HEAT Modes). Project W-030 provides a ventilation upgrade for the four Aging Waste Facility tanks, including upgraded vapor space cooling and filtered venting of tanks AY101, Ay102, AZ101, AZ102.

Ship Systems Survivability Test Site

Data.gov (United States)

Federal Laboratory Consortium — Area for testing survivability of shipboard systems to include electrical, communications, and fire suppression. Multipurpose test range for supporting gun firing,...

Internal testing of pipe systems with IRIS inspection system

International Nuclear Information System (INIS)

1986-01-01

The internal piping inspection system IRIS allows inside testing of pipes with an internal diameter of NW 70 as a minimum, and of any horizontal or vertical layout of the piping system. Visual testing is done by means of an integrated CCD video system with high resolution power. Technical data are given and examples of applications, in the German and English language. (DG) [de

Test results of six-month test of two water electrolysis systems

Science.gov (United States)

Mills, E. S.; Wells, G. W.

1972-01-01

The two water electrolysis systems used in the NASA space station simulation 90-day manned test of a regenerative life support system were refurbished as required and subjected to 26-weeks of testing. The two electrolysis units are both promising systems for oxygen and hydrogen generation and both needed extensive long-term testing to evaluate the performance of the respective cell design and provide guidance for further development. Testing was conducted to evaluate performance in terms of current, pressure, variable oxygen demands, and orbital simulation. An automatic monitoring system was used to record, monitor and printout performance data at one minute, ten minute or one-hour intervals. Performance data is presented for each day of system operation for each module used during the day. Failures are analyzed, remedial action taken to eliminate problems is discussed and recommendations for redesign for future space applications are stated.

System design description for the whole element furnace testing system

International Nuclear Information System (INIS)

Ritter, G.A.; Marschman, S.C.; MacFarlan, P.J.; King, D.A.

1998-05-01

This document provides a detailed description of the Hanford Spent Nuclear Fuel (SNF) Whole Element Furnace Testing System located in the Postirradiation Testing Laboratory G-Cell (327 Building). Equipment specifications, system schematics, general operating modes, maintenance and calibration requirements, and other supporting information are provided in this document. This system was developed for performing cold vacuum drying and hot vacuum drying testing of whole N-Reactor fuel elements, which were sampled from the 105-K East and K West Basins. The proposed drying processes are intended to allow dry storage of the SNF for long periods of time. The furnace testing system is used to evaluate these processes by simulating drying sequences with a single fuel element and measuring key system parameters such as internal pressures, temperatures, moisture levels, and off-gas composition

Excitation system testing in HPP 'Uvac'

Directory of Open Access Journals (Sweden)

Milojčić Nemanja

2011-01-01

Full Text Available The excitation system of hydro unit in HPP 'Uvac' and results of testings of excitation system performed for achieving of unit's mathematical model are presented in this paper. Description of excitation system equipment, parameters of regulators and results obtained after testings are presented. The presented results showed that the regulators are properly adjusted and that the excitation system is completely functional and reliable.

The Systems Test Architect: Enabling The Leap From Testable To Tested

Science.gov (United States)

2016-09-01

is and it would require some “fine-tuning.” [w] Mr. Peart finally has a physical architecture, and feels confident that it will meet the desired ...test and evaluation in systems engineering, this thesis examines the concept that test and evaluation, based on its desired early involvement in the...the documented roles of test and evaluation in systems engineering, this thesis examines the concept that test and evaluation, based on its desired

21 CFR 862.3660 - Phenobarbital test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Phenobarbital test system. 862.3660 Section 862....3660 Phenobarbital test system. (a) Identification. A phenobarbitol test system is a device intended to measure phenobarbital, an antiepileptic and sedative-hypnotic drug, in human specimens. Measurements...

Evaluation of the synergistic potential of vancomycin combined with other antimicrobial agents against methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus spp strains

Directory of Open Access Journals (Sweden)

Lívia Viganor da Silva

2011-02-01

Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA and coagulase-negative Staphylococcus spp (CNS are the most common pathogens that cause serious long term infections in patients. Despite the existence of new antimicrobial agents, such as linezolid, vancomycin (VAN remains the standard therapy for the treatment of infections caused by these multidrug-resistant strains. However, the use of VAN has been associated with a high frequency of therapeutic failures in some clinical scenarios, mainly with decreasing concentration of VAN. This work aims to evaluate the synergic potential of VAN plus sulfamethoxazole/trimethoprim (SXT, VAN plus rifampin (RIF and VAN plus imipenem (IPM in sub-minimum inhibitory concentrations against 22 clinical strains of MRSA and CNS. The checkerboard method showed synergism of VAN/RIF and VAN/SXT against two and three of the 22 strains, respectively. The combination of VAN with IPM showed synergistic effects against 21 out of 22 strains by the E-test method. Four strains were analyzed by the time-kill curve method and synergistic activity was observed with VAN/SXT, VAN/RIF and especially VAN/IPM in sub-inhibitory concentrations. It would be interesting to determine if synergy occurs in vivo. Evidence of in vivo synergy could lead to a reduction of the standard VAN dosage or treatment time.

Acceptance test procedure, 241-SY-101 Flexible Receiver System, Phase III testing

International Nuclear Information System (INIS)

Ritter, G.A.

1994-01-01

This Acceptance Test Procedure is for the 241-SY-101 Flexible Receiver System, Phase III Testing. This procedure will test the sealing integrity of the Flexible Receiver System to ensure that release of waste and aerosols will be minimized during the removal of the test mixer pump from tank SY-101

Programmable, automated transistor test system

Science.gov (United States)

Truong, L. V.; Sundburg, G. R.

1986-01-01

A programmable, automated transistor test system was built to supply experimental data on new and advanced power semiconductors. The data will be used for analytical models and by engineers in designing space and aircraft electric power systems. A pulsed power technique was used at low duty cycles in a nondestructive test to examine the dynamic switching characteristic curves of power transistors in the 500 to 1000 V, 10 to 100 A range. Data collection, manipulation, storage, and output are operator interactive but are guided and controlled by the system software.

Influence of an independent quarterly audit on publicly reported vancomycin-resistant enterocococi bacteremia data in Ontario, Canada.

Science.gov (United States)

Prematunge, Chatura; Policarpio, Michelle E; Johnstone, Jennie; Adomako, Kwaku; Nadolny, Emily; Lam, Freda; Li, Ye; Brown, Kevin A; Garber, Gary

2018-04-13

All Ontario hospitals are mandated to self-report vancomycin-resistant enterocococi (VRE) bacteremias to Ontario's Ministry of Health and Long-term Care for public reporting purposes. Independent quarterly audits of publicly reported VRE bacteremias between September 2013 and June 2015 were carried out by Public Health Ontario. VRE bacteremia case-reporting errors between January 2009 and August 2013 were identified by a single retrospective audit. Employing a quasiexperimental pre-post study design, the relative risk of VRE bacteremia reporting errors before and after quarterly audits were modeled using Poisson regression adjusting for hospital type, case counts reported to the Ministry of Health and Long-term Care, and autocorrelation via generalized estimating equation. Overall, 24.5% (126 out of 514) of VRE bacteremias were reported in error; 114 out of 367 (31%) VRE bacteremias reported before quarterly audits and 12 out of 147 (8.1%) reported after audits were found to be incorrect. In adjusted analysis, quarterly audits of VRE bacteremias were associated with significant reductions in reporting errors when compared with before quarterly auditing (relative risk, 0.17; 95% confidence interval, 0.05-0.63). Risk of reporting errors among community hospitals were greater than acute teaching hospitals of the region (relative risk, 4.39; 95% CI, 3.07-5.70). This study found independent quarterly audits of publicly reported VRE bacteremias to be associated with significant reductions in reporting errors. Public reporting systems should consider adopting routine data audits and hospital-targeted training to improve data accuracy. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Test-driven modeling of embedded systems

DEFF Research Database (Denmark)

Munck, Allan; Madsen, Jan

2015-01-01

To benefit maximally from model-based systems engineering (MBSE) trustworthy high quality models are required. From the software disciplines it is known that test-driven development (TDD) can significantly increase the quality of the products. Using a test-driven approach with MBSE may have...... a similar positive effect on the quality of the system models and the resulting products and may therefore be desirable. To define a test-driven model-based systems engineering (TD-MBSE) approach, we must define this approach for numerous sub disciplines such as modeling of requirements, use cases...... suggest that our method provides a sound foundation for rapid development of high quality system models....

Programmable automated transistor test system

International Nuclear Information System (INIS)

Truong, L.V.; Sundberg, G.R.

1986-01-01

The paper describes a programmable automated transistor test system (PATTS) and its utilization to evaluate bipolar transistors and Darlingtons, and such MOSFET and special types as can be accommodated with the PATTS base-drive. An application of a pulsed power technique at low duty cycles in a non-destructive test is used to examine the dynamic switching characteristic curves of power transistors. Data collection, manipulation, storage, and output are operator interactive but are guided and controlled by the system software. In addition a library of test data is established on disks, tapes, and hard copies for future reference

Availability of periodically tested systems

International Nuclear Information System (INIS)

Signoret, J.P.

1979-01-01

There is at the present time a need in accurate models to asess the availability of periodically tested stand-by systems. This paper shows how to improve the well known 'saw-tooth curve' model in order to take into account various reliability parameters. A model is developed to assess the pointwise and the mean availabilities of periodically tested stand-by systems. Exact and approxination formulae are given. In addition, the model developed herein leads to optimize the test interval in order to minimize the mean unavailability. A safety diesel in a nuclear power plant is given as an example

21 CFR 862.1225 - Creatinine test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Creatinine test system. 862.1225 Section 862.1225....1225 Creatinine test system. (a) Identification. A creatinine test system is a device intended to measure creatinine levels in plasma and urine. Creatinine measurements are used in the diagnosis and...

21 CFR 862.3040 - Alcohol test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alcohol test system. 862.3040 Section 862.3040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED....3040 Alcohol test system. (a) Identification. An alcohol test system is a device intented to measure...

21 CFR 862.1035 - Albumin test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Albumin test system. 862.1035 Section 862.1035....1035 Albumin test system. (a) Identification. An albumin test system is a device intended to measure the albumin concentration in serum and plasma. Albumin measurements are used in the diagnosis and...

Open Architecture Data System for NASA Langley Combined Loads Test System

Science.gov (United States)

Lightfoot, Michael C.; Ambur, Damodar R.

1998-01-01

The Combined Loads Test System (COLTS) is a new structures test complex that is being developed at NASA Langley Research Center (LaRC) to test large curved panels and cylindrical shell structures. These structural components are representative of aircraft fuselage sections of subsonic and supersonic transport aircraft and cryogenic tank structures of reusable launch vehicles. Test structures are subjected to combined loading conditions that simulate realistic flight load conditions. The facility consists of two pressure-box test machines and one combined loads test machine. Each test machine possesses a unique set of requirements or research data acquisition and real-time data display. Given the complex nature of the mechanical and thermal loads to be applied to the various research test articles, each data system has been designed with connectivity attributes that support both data acquisition and data management functions. This paper addresses the research driven data acquisition requirements for each test machine and demonstrates how an open architecture data system design not only meets those needs but provides robust data sharing between data systems including the various control systems which apply spectra of mechanical and thermal loading profiles.

21 CFR 862.1210 - Creatine test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Creatine test system. 862.1210 Section 862.1210....1210 Creatine test system. (a) Identification. A creatine test system is a device intended to measure creatine (a substance synthesized in the liver and pancreas and found in biological fluids) in plasma...

21 CFR 862.1065 - Ammonia test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ammonia test system. 862.1065 Section 862.1065....1065 Ammonia test system. (a) Identification. An ammonia test system is a device intended to measure ammonia levels in blood, serum, and plasma, Ammonia measurements are used in the diagnosis and treatment...

21 CFR 862.3600 - Mercury test system.

Science.gov (United States)

2010-04-01

....3600 Mercury test system. (a) Identification. A mercury test system is a device intended to measure mercury, a heavy metal, in human specimens. Measurements obtained by this device are used in the diagnosis... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Mercury test system. 862.3600 Section 862.3600...

Space Launch System Scale Model Acoustic Test Ignition Overpressure Testing

Science.gov (United States)

Nance, Donald; Liever, Peter; Nielsen, Tanner

2015-01-01

The overpressure phenomenon is a transient fluid dynamic event occurring during rocket propulsion system ignition. This phenomenon results from fluid compression of the accelerating plume gas, subsequent rarefaction, and subsequent propagation from the exhaust trench and duct holes. The high-amplitude unsteady fluid-dynamic perturbations can adversely affect the vehicle and surrounding structure. Commonly known as ignition overpressure (IOP), this is an important design-to environment for the Space Launch System (SLS) that NASA is currently developing. Subscale testing is useful in validating and verifying the IOP environment. This was one of the objectives of the Scale Model Acoustic Test, conducted at Marshall Space Flight Center. The test data quantifies the effectiveness of the SLS IOP suppression system and improves the analytical models used to predict the SLS IOP environments. The reduction and analysis of the data gathered during the SMAT IOP test series requires identification and characterization of multiple dynamic events and scaling of the event waveforms to provide the most accurate comparisons to determine the effectiveness of the IOP suppression systems. The identification and characterization of the overpressure events, the waveform scaling, the computation of the IOP suppression system knockdown factors, and preliminary comparisons to the analytical models are discussed.

Space Launch System Scale Model Acoustic Test Ignition Overpressure Testing

Science.gov (United States)

Nance, Donald K.; Liever, Peter A.

2015-01-01

The overpressure phenomenon is a transient fluid dynamic event occurring during rocket propulsion system ignition. This phenomenon results from fluid compression of the accelerating plume gas, subsequent rarefaction, and subsequent propagation from the exhaust trench and duct holes. The high-amplitude unsteady fluid-dynamic perturbations can adversely affect the vehicle and surrounding structure. Commonly known as ignition overpressure (IOP), this is an important design-to environment for the Space Launch System (SLS) that NASA is currently developing. Subscale testing is useful in validating and verifying the IOP environment. This was one of the objectives of the Scale Model Acoustic Test (SMAT), conducted at Marshall Space Flight Center (MSFC). The test data quantifies the effectiveness of the SLS IOP suppression system and improves the analytical models used to predict the SLS IOP environments. The reduction and analysis of the data gathered during the SMAT IOP test series requires identification and characterization of multiple dynamic events and scaling of the event waveforms to provide the most accurate comparisons to determine the effectiveness of the IOP suppression systems. The identification and characterization of the overpressure events, the waveform scaling, the computation of the IOP suppression system knockdown factors, and preliminary comparisons to the analytical models are discussed.

21 CFR 866.5040 - Albumin immunological test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Albumin immunological test system. 866.5040... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5040 Albumin immunological test system. (a) Identification. An albumin immunological test system is a device that consists of...

Frequency modulation system test procedure shuttle task 501 approach and landing test configuration

Science.gov (United States)

Doland, G. D.

1976-01-01

Shuttle Task 501 is an in-line task to test the performance and compatibility of radiofrequency links between the SSO and ground, and relay via a satellite. Under Shuttle Task 501 approach and landing test (ALT) phase only a limited portion of the communication and tracking (C&T) equipment is to be tested. The principal item to be tested is a frequency modulated (FM) data link. To test this RF link, an ALT FM System was designed, constructed, and the console wiring verified. A step-by-step procedure to be used to perform the ALT FM system is presented. The ALT FM system test is to be performed prior to delivery of the equipment to the Electronic Systems Test Laboratory (ESTL).

21 CFR 862.3110 - Antimony test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antimony test system. 862.3110 Section 862.3110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3110 Antimony test system. (a) Identification. A...

A Physical Protection Systems Test Bed for International Counter-Trafficking System Development

International Nuclear Information System (INIS)

Stinson, Brad J.; Kuhn, Michael J.; Donaldson, Terrence L.; Richardson, Dave; Rowe, Nathan C.; Younkin, James R.; Pickett, Chris A.

2011-01-01

Physical protection systems have a widespread impact on the nuclear industry in areas such as nuclear safeguards, arms control, and trafficking of illicit goods (e.g., nuclear materials) across international borders around the world. Many challenges must be overcome in design and deployment of foreign border security systems such as lack of infrastructure, extreme environmental conditions, limited knowledge of terrain, insider threats, and occasional cultural resistance. Successful security systems, whether it be a system designed to secure a single facility or a whole border security system, rely on the entire integrated system composed of multiple subsystems. This test bed is composed of many unique sensors and subsystems, including wireless unattended ground sensors, a buried fiber-optic acoustic sensor, a lossy coaxial distributed sensor, wireless links, pan-tilt-zoom cameras, mobile power generation systems, unmanned aerial vehicles, and fiber-optic-fence intrusion detection systems. A Common Operating Picture software architecture is utilized to integrate a number of these subsystems. We are currently performance testing each system for border security and perimeter security applications by examining metrics such as probability of sense and a qualitative understanding of the sensors vulnerability of defeat. The testing process includes different soil conditions for buried sensors (e.g., dry, wet, and frozen) and an array of different tests including walking, running, stealth detection, and vehicle detection. Also, long term sustainability of systems is tested including performance differences due to seasonal variations (e.g. summer versus winter, while raining, in foggy conditions). The capabilities of the test bed are discussed. Performance testing results, both at the individual component level and integrated into a larger system for a specific deployment (in situ), help illustrate the usefulness and need for integrated testing facilities to carry out this

Cascade Distiller System Performance Testing Interim Results

Science.gov (United States)

Callahan, Michael R.; Pensinger, Stuart; Sargusingh, Miriam J.

2014-01-01

The Cascade Distillation System (CDS) is a rotary distillation system with potential for greater reliability and lower energy costs than existing distillation systems. Based upon the results of the 2009 distillation comparison test (DCT) and recommendations of the expert panel, the Advanced Exploration Systems (AES) Water Recovery Project (WRP) project advanced the technology by increasing reliability of the system through redesign of bearing assemblies and improved rotor dynamics. In addition, the project improved the CDS power efficiency by optimizing the thermoelectric heat pump (TeHP) and heat exchanger design. Testing at the NASA-JSC Advanced Exploration System Water Laboratory (AES Water Lab) using a prototype Cascade Distillation Subsystem (CDS) wastewater processor (Honeywell d International, Torrance, Calif.) with test support equipment and control system developed by Johnson Space Center was performed to evaluate performance of the system with the upgrades as compared to previous system performance. The system was challenged with Solution 1 from the NASA Exploration Life Support (ELS) distillation comparison testing performed in 2009. Solution 1 consisted of a mixed stream containing human-generated urine and humidity condensate. A secondary objective of this testing is to evaluate the performance of the CDS as compared to the state of the art Distillation Assembly (DA) used in the ISS Urine Processor Assembly (UPA). This was done by challenging the system with ISS analog waste streams. This paper details the results of the AES WRP CDS performance testing.

Unit Testing for Command and Control Systems

Science.gov (United States)

Alexander, Joshua

2018-01-01

Unit tests were created to evaluate the functionality of a Data Generation and Publication tool for a command and control system. These unit tests are developed to constantly evaluate the tool and ensure it functions properly as the command and control system grows in size and scope. Unit tests are a crucial part of testing any software project and are especially instrumental in the development of a command and control system. They save resources, time and costs associated with testing, and catch issues before they become increasingly difficult and costly. The unit tests produced for the Data Generation and Publication tool to be used in a command and control system assure the users and stakeholders of its functionality and offer assurances which are vital in the launching of spacecraft safely.

Controlling for endogeneity in attributable costs of vancomycin-resistant enterococci from a Canadian hospital.

Science.gov (United States)

Lloyd-Smith, Patrick

2017-12-01

Decisions regarding the optimal provision of infection prevention and control resources depend on accurate estimates of the attributable costs of health care-associated infections. This is challenging given the skewed nature of health care cost data and the endogeneity of health care-associated infections. The objective of this study is to determine the hospital costs attributable to vancomycin-resistant enterococci (VRE) while accounting for endogeneity. This study builds on an attributable cost model conducted by a retrospective cohort study including 1,292 patients admitted to an urban hospital in Vancouver, Canada. Attributable hospital costs were estimated with multivariate generalized linear models (GLMs). To account for endogeneity, a control function approach was used. The analysis sample included 217 patients with health care-associated VRE. In the standard GLM, the costs attributable to VRE are $17,949 (SEM, $2,993). However, accounting for endogeneity, the attributable costs were estimated to range from $14,706 (SEM, $7,612) to $42,101 (SEM, $15,533). Across all model specifications, attributable costs are 76% higher on average when controlling for endogeneity. VRE was independently associated with increased hospital costs, and controlling for endogeneity lead to higher attributable cost estimates. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Molecular Analysis of Vancomycin-Resistant Enterococci Isolated from Regional Hospitals in Trinidad and Tobago

Directory of Open Access Journals (Sweden)

Patrick E. Akpaka

2016-01-01

Full Text Available Geographic spread of vancomycin-resistant enterococci (VRE clones in cities, countries, or even continents has been identified by molecular techniques. This study aimed at characterizing virulent genes and determining genetic relatedness of 45 VRE isolates from Trinidad and Tobago using molecular tools, including polymerase chain reaction, pulsed-field gel electrophoresis (PFGE, and Random Amplification Polymorphic DNA (RAPD. The majority (84% of the isolates were Enterococcus faecium possessing vanA gene while the rest (16% were Enterococcus faecalis possessing vanB. The esp gene was found in all 45 VRE isolates while hyl genes were found only in E. faecium species. The E. faecium species expressed five distinct PFGE patterns. The predominant clones with similar or common patterns belonged to clones one and three, and each had 11 (29% of the VRE isolates. Plasmid content was identified in representative isolates from each clonal group. By contrast, the E. faecalis species had one PFGE pattern suggesting the presence of an occult and limited clonal spread. The emergence of VRE in the country seems to be related to intra/interhospital dissemination of an epidemic clone carrying the vanA element. Therefore, infection control measures will be warranted to prevent any potential outbreak and spread of VRE in the country.

Waste retrieval sluicing system data acquisition system acceptance test report

International Nuclear Information System (INIS)

Bevins, R.R.

1998-01-01

This document describes the test procedure for the Project W-320 Tank C-106 Sluicing Data Acquisition System (W-320 DAS). The Software Test portion will test items identified in the WRSS DAS System Description (SD), HNF-2115. Traceability to HNF-2115 will be via a reference that follows in parenthesis, after the test section title. The Field Test portion will test sensor operability, analog to digital conversion, and alarm setpoints for field instrumentation. The W-320 DAS supplies data to assist thermal modeling of tanks 241-C-106 and 241-AY-102. It is designed to be a central repository for information from sources that would otherwise have to be read, recorded, and integrated manually. Thus, completion of the DAS requires communication with several different data collection devices and output to a usable PC data formats. This test procedure will demonstrate that the DAS functions as required by the project requirements stated in Section 3 of the W-320 DAS System Description, HNF-2115

Evolution of a test article handling system for the SP-100 GES test

International Nuclear Information System (INIS)

Shen, E.J.; Schweiger, L.J.; Miller, W.C.; Gluck, R.; Davies, S.M.

1987-01-01

A simulated space environment test of a flight prototypic SP-100 reactor, control system, and flight shield will be conducted at the Hanford Engineering Development Laboratory (HEDL). The flight prototypic components and the supporting primary heat removal system are collectively known as the nuclear assembly test article (TA). The unique configuration and materials of fabrication for the Test Article require a specialized handling facility to support installation, maintenance, and final disposal operation. The test site operator, working in conjunction with the test article supplier, developed and evaluated several handling concepts resulting in the selection of a reference test article handling system. The development of the reference concept for the handling system is presented