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BMC Nephrology Dec 2014The purpose of this study was to evaluate the feasibility of utilizing an in-vitro, closed loop hemodialysis system as a method to assess drug clearance. Secondarily,...
BACKGROUND
The purpose of this study was to evaluate the feasibility of utilizing an in-vitro, closed loop hemodialysis system as a method to assess drug clearance. Secondarily, this study tested the influence of variables (blood flow rate, dialysate flow rate, and type of filter) in the hemodialysis procedure on the clearance of vancomycin and gentamicin.
METHODS
An in-vitro, closed loop hemodialysis system was constructed. The vancomycin (30 mg/L) and gentamicin (25 mg/L) were added to a simulated blood system (SBS). Four conditions (C1-C4) were tested by defining the filter (Polyflux 170H or F180) and the blood and dialysate flow rates (BFR and DFR). All hemodialysis sessions were 3 hours in length and each condition was completed in duplicate. Dialysate effluent was collected in a 50 gallon polyethylene drum. Samples were collected (in duplicate) from the SBS and the dialysate effluent at baseline and at the end of the hemodialysis session. Samples were analyzed for vancomycin and gentamicin with an ultrahigh performance liquid chromatography/tandem mass spectrometry method.
RESULTS
A total of eight 3-hour hemodialysis sessions were conducted. For all tested conditions (C1-C4), vancomycin was undetectable in the SBS at the end of dialysis. However, total vancomycin recovery in the dialysis effluent was 85±18%, suggesting that up to 15% may have adsorbed to the dialysis filter or tubing. Gentamicin clearance from SBS was >98% in all tested conditions. Average gentamicin recovery in the dialysate effluent was 99±15%.
CONCLUSION
Both vancomycin and gentamicin were readily removed by high-flux hemodialysis under all conditions studied. No significant differences in drug clearance were observed between conditions used in this in vitro study. The clinical implications of changing these hemodialysis parameters are unknown.
Topics: Dialysis Solutions; Filtration; Gentamicins; Humans; In Vitro Techniques; Metabolic Clearance Rate; Renal Dialysis; Vancomycin
PubMed: 25526750
DOI: 10.1186/1471-2369-15-204 -
Iranian Journal of Medical Sciences May 2024Antibiotic resistance is a global public health concern that has been exacerbated by the overuse and misuse of antibiotics, leading to the emergence of resistant...
BACKGROUND
Antibiotic resistance is a global public health concern that has been exacerbated by the overuse and misuse of antibiotics, leading to the emergence of resistant bacteria. The gut microbiota, often influenced by antibiotic usage, plays a crucial role in overall health. Therefore, this study aimed to investigate the prevalence of antibiotic resistant genes in the gut microbiota of Indonesian coastal and highland populations, as well as to identify vancomycin-resistant bacteria and their resistant genes.
METHODS
Stool samples were collected from 22 individuals residing in Pacet, Mojokerto, and Kenjeran, Surabaya Indonesia in 2022. The read count of antibiotic resistant genes was analyzed in the collected samples, and the bacterium concentration was counted by plating on the antibiotic-containing agar plate. Vancomycin-resistant strains were further isolated, and the presence of vancomycin-resistant genes was detected using a multiplex polymerase chain reaction (PCR).
RESULTS
The antibiotic resistant genes for tetracycline, aminoglycosides, macrolides, beta-lactams, and vancomycin were found in high frequency in all stool samples (100%) of the gut microbiota. Meanwhile, those meant for chloramphenicol and sulfonamides were found in 86% and 16% of the samples, respectively. Notably, vancomycin-resistant genes were found in 16 intrinsically resistant Gram-negative bacterial strains. Among the detected vancomycin-resistant genes, was the most prevalent (27.3%), while was the least prevalent (4.5%).
CONCLUSION
The presence of multiple vancomycin resistance genes in intrinsically resistant Gram-negative bacterial strains demonstrated the importance of the gut microbiota as a reservoir and hub for the horizontal transfer of antibiotic resistant genes.
Topics: Humans; Gastrointestinal Microbiome; Indonesia; Vancomycin Resistance; Vancomycin; Anti-Bacterial Agents; Feces; Male; Female; Bacteria; Adult; Genes, Bacterial
PubMed: 38751872
DOI: 10.30476/IJMS.2023.98767.3087 -
BioMed Research International 2018Copal® spacem is a new PMMA bone cement for fabricating spacers. This study compares elution of gentamicin, elution of vancomycin, and compressive strength of Copal®... (Comparative Study)
Comparative Study
Comparison of Elution Characteristics and Compressive Strength of Biantibiotic-Loaded PMMA Bone Cement for Spacers: Copal® Spacem with Gentamicin and Vancomycin versus Palacos® R+G with Vancomycin.
PURPOSE
Copal® spacem is a new PMMA bone cement for fabricating spacers. This study compares elution of gentamicin, elution of vancomycin, and compressive strength of Copal® spacem and of Palacos® R+G at different vancomycin loadings in the powder of the cements. We hypothesized that antibiotic elution of Copal® spacem is superior at comparable compressive strength.
METHODS
Compression test specimens were fabricated using Copal® spacem manually loaded with 0.5 g gentamicin and additionally 2 g, 4 g, and 6 g of vancomycin per 40 g of cement powder (COP specimens) and using 0.5 g gentamicin premixed Palacos® R+G manually loaded with 2 g, 4 g, and 6 g of vancomycin per 40 g of cement powder (PAL specimens). These specimens were used for determination of gentamicin and vancomycin elution (in fetal calf serum, at 22°C) and for determination of compressive strength both prior and following the elution tests.
RESULTS
Cumulative gentamicin concentrations (p < 0.005) and gentamicin concentration after 28 days (p ≤ 0.043) were significantly lower for COP specimens compared to PAL specimens. Cumulative vancomycin concentrations were significantly higher (p ≤ 0.043) for COP specimens after the second day. Vancomycin concentrations after 28 days were not significantly higher for the Copal specimens loaded with 2 g and 4 g of vancomycin. Compressive strength was not significantly different between COP specimens and PAL specimens before elution tests. Compressive strength after the elution tests was significantly lower (p = 0.005) for COP specimens loaded with 2 g of vancomycin.
CONCLUSION
We could not demonstrate consistent superior antibiotic elution from Copal® spacem compared to Palacos® R+G for fabricating gentamicin and vancomycin loaded spacers. The results do not favor Copal® spacem over Palacos® R+G for the use as a gentamicin and vancomycin biantibiotic-loaded spacer.
Topics: Acrylic Resins; Bone Cements; Compressive Strength; Gentamicins; Materials Testing; Polymethyl Methacrylate; Vancomycin
PubMed: 30410931
DOI: 10.1155/2018/4323518 -
Yonsei Medical Journal Apr 2020Few studies have been investigated the in vivo efficacy of generic vancomycin products available outside of the United States. In this study, we aimed to compare the in... (Comparative Study)
Comparative Study
PURPOSE
Few studies have been investigated the in vivo efficacy of generic vancomycin products available outside of the United States. In this study, we aimed to compare the in vivo pharmacokinetics (PK) and pharmacodynamics (PD) of five generic vancomycin products available in Korea with those of the innovator.
MATERIALS AND METHODS
The in vitro vancomycin purity of each product was examined using high-pressure liquid chromatography. Single-dose PK analyses were performed using neutropenic mice. The in vivo efficacy of vancomycin products was compared with that of the innovator in dose-effect experiments (25 to 400 mg/kg per day) using a thigh-infection model with neutropenic mice.
RESULTS
Generic products had a lower proportion of vancomycin B (range: 90.3-93.8%) and a higher proportion of impurities (range: 6.2-9.7%) than the innovator (94.5% and 5.5%, respectively). In an in vivo single-dose PK study, the maximum concentration (C) values of each generic were lower than that of the innovator, and the geographic mean area under the curve ratios of four generics were significantly lower than that of the innovator (all <0.1). In the thigh-infection model, the maximum efficacies of generic products reflected in maximal effect (E) values were not significantly different from the innovator. However, the PD profile curves of some generic products differed significantly from that of the innovator in mice injected with a high level of Mu3 (all ≤0.05).
CONCLUSION
Some generic vancomycin products available in Korea showed inferior PK and PD profiles, especially in mice infected with hetero-vancomycin-resistant Staphylococcus aureus.
Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Drugs, Generic; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; Republic of Korea; Staphylococcal Infections; Staphylococcus aureus; Thigh; Treatment Failure; Vancomycin
PubMed: 32233172
DOI: 10.3349/ymj.2020.61.4.301 -
Scientific Reports Aug 2020Locally applied vancomycin is increasingly being used in primary hip and knee arthroplasty to reduce the risk of infection. Despite encouraging initial results,...
Locally applied vancomycin is increasingly being used in primary hip and knee arthroplasty to reduce the risk of infection. Despite encouraging initial results, considerable debate remains on the basis of the data currently available. In particular, it has been unclear up to now whether local vancomycin is suitable to further reduce the risk of infection even if the rate of infection is already low (< 1%). In this monocentric retrospective cohort study, all primary total hip and knee arthroplasties performed between 2013 and 2018 were included. After a change in procedure at the hospital, 1 g vancomycin powder was applied intraarticularly before wound closure. The remaining perioperative procedure was constant over the investigation period. The follow-up was one year. The presence of an infection according to the currently valid MSIS criteria was defined as the endpoint. In patients with TKA two infections (0.3%) were observed under vancomycin prophylaxis in contrast to 44 infections (1.3%) in the control group (p = 0.033). In patients with THA two infections (0.5%) were observed under vancomycin prophylaxis and 48 infections (1.1%) in the control group without local vancomycin but this difference was statistically not significant. No wound complications requiring revision were observed as a result of the vancomycin. On the basis of the results of this study, intraarticular application of vancomycin powder in total hip and knee arthroplasty may be considered. Prospective randomized studies have to confirm this promising results prior a common recommendation.Level of Evidence III Retrospective cohort study.
Topics: Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Bacteria; Body Mass Index; Case-Control Studies; Humans; Injections, Intra-Articular; Powders; Prosthesis-Related Infections; Vancomycin
PubMed: 32747743
DOI: 10.1038/s41598-020-69958-0 -
Cleveland Clinic Journal of Medicine Jul 2011Because a significant proportion of Staphylococcus aureus strains as well as most coagulase-negative staphylococci are resistant to penicillin and semisynthetic... (Review)
Review
Because a significant proportion of Staphylococcus aureus strains as well as most coagulase-negative staphylococci are resistant to penicillin and semisynthetic beta-lactam drugs, the need for vancomycin and related antibiotics has never been greater. Effective use of vancomycin requires knowledge of dosing parameters and selection of target trough levels appropriate to the specific infection and to the pathogen being treated. For clinicians, it is vital to remain up-to-date with evolving definitions for vancomycin susceptibility, with new interpretations of efficacy, and with information on toxicity.
Topics: Anti-Bacterial Agents; Area Under Curve; Drug Therapy, Combination; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcal Infections; Vancomycin
PubMed: 21724929
DOI: 10.3949/ccjm.78a.10168 -
Revista Da Sociedade Brasileira de... Apr 2016Vancomycin is the first-line agent for the treatment of bacteremia, endocarditis, pneumonia, cellulitis, and osteomyelitis. Pancytopenia is an uncommon adverse effect of...
Vancomycin is the first-line agent for the treatment of bacteremia, endocarditis, pneumonia, cellulitis, and osteomyelitis. Pancytopenia is an uncommon adverse effect of vancomycin therapy, with only a few cases of vancomycin-related neutropenia and pancytopenia described in the literature. We describe a case of a 56-year-old man who was diagnosed with chronic paraspinal abscess and started on intravenous vancomycin. He was re-admitted two weeks later with new-onset pancytopenia. Discontinuation of vancomycin resulted in improved cell counts. Physicians should monitor cell counts in patients who are on long-term intravenous vancomycin.
Topics: Abscess; Anti-Bacterial Agents; Humans; Male; Middle Aged; Pancytopenia; Spinal Diseases; Vancomycin
PubMed: 27192600
DOI: 10.1590/0037-8682-0263-2015 -
Antimicrobial Agents and Chemotherapy Oct 2011For enterococcal implant-associated infections, the optimal treatment regimen has not been defined. We investigated the activity of daptomycin, vancomycin, and...
For enterococcal implant-associated infections, the optimal treatment regimen has not been defined. We investigated the activity of daptomycin, vancomycin, and gentamicin (and their combinations) against Enterococcus faecalis in vitro and in a foreign-body infection model. Antimicrobial activity was investigated by time-kill and growth-related heat production studies (microcalorimetry) as well as with a guinea pig model using subcutaneously implanted cages. Infection was established by percutaneous injection of E. faecalis in the cage. Antibiotic treatment for 4 days was started 3 h after infection. Cages were removed 5 days after end of treatment to determine the cure rate. The MIC, the minimal bactericidal concentration (MBC) in the logarithmic phase, and the MBC in the stationary phase were 1.25, 5, and >20 μg/ml for daptomycin, 1, >64, and >64 μg/ml for vancomycin, and 16, 32, and 4 μg/ml for gentamicin, respectively. In vitro, gentamicin at subinhibitory concentrations improved the activity against E. faecalis when combined with daptomycin or vancomycin in the logarithmic and stationary phases. In the animal model, daptomycin cured 25%, vancomycin 17%, and gentamicin 50% of infected cages. In combination with gentamicin, the cure rate for daptomycin increased to 55% and that of vancomycin increased to 33%. In conclusion, daptomycin was more active than vancomycin against adherent E. faecalis, and its activity was further improved by the addition of gentamicin. Despite a short duration of infection (3 h), the cure rates did not exceed 55%, highlighting the difficulty of eradicating E. faecalis from implants already in the early stage of implant-associated infection.
Topics: Animals; Anti-Bacterial Agents; Daptomycin; Drug Therapy, Combination; Enterococcus faecalis; Gentamicins; Gram-Positive Bacterial Infections; Guinea Pigs; Male; Microbial Sensitivity Tests; Prosthesis-Related Infections; Vancomycin
PubMed: 21807979
DOI: 10.1128/AAC.00141-11 -
Antimicrobial Agents and Chemotherapy Aug 1973The in vitro activity of vancomycin and combinations of vancomycin-gentamicin and vancomycin-streptomycin against enterococci was investigated. The minimal inhibitory...
The in vitro activity of vancomycin and combinations of vancomycin-gentamicin and vancomycin-streptomycin against enterococci was investigated. The minimal inhibitory concentration of vancomycin for 99 of 100 enterococcal strains isolated clinically was 3.12 mug or less/ml. When cultures of eight strains were incubated with vancomycin, regardless of the inoculum size (10(6), 10(5), or 10(4)) and concentration of vancomycin (10 or 20 mug/ml), there was no significant reduction in the number of viable enterococci at 6, 24, and 48 h. Gentamicin and streptomycin in concentrations attainable clinically were not effective against enterococci. Vancomycin combined with gentamicin or streptomycin was tested against 41 enterococcal strains. With the combination of vancomycin at 10 mug/ml and gentamicin at 4 mug/ml or vancomycin at 5 mug/ml and gentamicin at 4 mug/ml, synergism was demonstrated against all 41 strains at 6 h. The combination of vancomycin at 10 mug/ml and streptomycin at 10 mug/ml was only synergistic against 25 of 41 strains at 6 h, and only 22 of 41 strains were affected synergistically at 6 h by vancomycin at 5 mug/ml with streptomycin at 10 mug/ml. With few exceptions, the enhanced killing was more pronounced at 24 and 48 h. The combination of vancomycin and gentamicin or vancomycin and streptomycin (where in vitro studies demonstrate synergism) may be a useful alternate therapy in enterococcal endocarditis.
Topics: Bacteria; Drug Synergism; Enterobacteriaceae; Gentamicins; Microbial Sensitivity Tests; Streptomycin; Vancomycin
PubMed: 4790933
DOI: 10.1128/AAC.4.2.120 -
Antimicrobial Agents and Chemotherapy 2014The current vancomycin therapeutic guidelines recommend the use of only trough concentrations to manage the dosing of adults with Staphylococcus aureus infections. Both...
The current vancomycin therapeutic guidelines recommend the use of only trough concentrations to manage the dosing of adults with Staphylococcus aureus infections. Both vancomycin efficacy and toxicity are likely to be related to the area under the plasma concentration-time curve (AUC). We assembled richly sampled vancomycin pharmacokinetic data from three studies comprising 47 adults with various levels of renal function. With Pmetrics, the nonparametric population modeling package for R, we compared AUCs estimated from models derived from trough-only and peak-trough depleted versions of the full data set and characterized the relationship between the vancomycin trough concentration and AUC. The trough-only and peak-trough depleted data sets underestimated the true AUCs compared to the full model by a mean (95% confidence interval) of 23% (11 to 33%; P = 0.0001) and 14% (7 to 19%; P < 0.0001), respectively. In contrast, using the full model as a Bayesian prior with trough-only data allowed 97% (93 to 102%; P = 0.23) accurate AUC estimation. On the basis of 5,000 profiles simulated from the full model, among adults with normal renal function and a therapeutic AUC of ≥400 mg · h/liter for an organism for which the vancomycin MIC is 1 mg/liter, approximately 60% are expected to have a trough concentration below the suggested minimum target of 15 mg/liter for serious infections, which could result in needlessly increased doses and a risk of toxicity. Our data indicate that adjustment of vancomycin doses on the basis of trough concentrations without a Bayesian tool results in poor achievement of maximally safe and effective drug exposures in plasma and that many adults can have an adequate vancomycin AUC with a trough concentration of <15 mg/liter.
Topics: Adult; Anti-Bacterial Agents; Area Under Curve; Humans; Microbial Sensitivity Tests; Vancomycin
PubMed: 24165176
DOI: 10.1128/AAC.01653-13