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Clinical Microbiology Reviews Jun 2023Vancomycin-resistant enterococci (VRE) are common causes of bloodstream infections (BSIs) with high morbidity and mortality rates. They are pathogens of global concern... (Review)
Review
Vancomycin-resistant enterococci (VRE) are common causes of bloodstream infections (BSIs) with high morbidity and mortality rates. They are pathogens of global concern with a limited treatment pipeline. Significant challenges exist in the management of VRE BSI, including drug dosing, the emergence of resistance, and the optimal treatment for persistent bacteremia and infective endocarditis. Therapeutic drug monitoring (TDM) for antimicrobial therapy is evolving for VRE-active agents; however, there are significant gaps in the literature for predicting antimicrobial efficacy for VRE BSIs. To date, TDM has the greatest evidence for predicting drug toxicity for the three main VRE-active antimicrobial agents daptomycin, linezolid, and teicoplanin. This article presents an overview of the treatment options for VRE BSIs, the role of antimicrobial dose optimization through TDM in supporting clinical infection management, and challenges and perspectives for the future.
Topics: Humans; Anti-Bacterial Agents; Vancomycin; Linezolid; Bacteremia; Vancomycin-Resistant Enterococci; Anti-Infective Agents; Sepsis; Gram-Positive Bacterial Infections
PubMed: 37067406
DOI: 10.1128/cmr.00059-22 -
Antimicrobial Agents and Chemotherapy May 2016The increasing number of infections produced by beta-lactam-resistant Gram-positive bacteria and the morbidity secondary to these infections make it necessary to... (Review)
Review
The increasing number of infections produced by beta-lactam-resistant Gram-positive bacteria and the morbidity secondary to these infections make it necessary to optimize the use of vancomycin. In 2009, the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Disease Pharmacists published specific guidelines about vancomycin dosage and monitoring. However, these guidelines have not been updated in the past 6 years. This review analyzes the new available information about vancomycin published in recent years regarding pharmacokinetics and pharmacodynamics, serum concentration monitoring, and optimal vancomycin dosing in special situations (obese people, burn patients, renal replacement therapy, among others). Vancomycin efficacy is linked to a correct dosage which should aim to reach an area under the curve (AUC)/MIC ratio of ≥400; serum trough levels of 15 to 20 mg/liter are considered a surrogate marker of an AUC/MIC ratio of ≥400 for a MIC of ≤1 mg/liter. For Staphylococcus aureus strains presenting with a MIC >1 mg/liter, an alternative agent should be considered. Vancomycin doses must be adjusted according to body weight and the plasma trough levels of the drug. Nephrotoxicity has been associated with target vancomycin trough levels above 15 mg/liter. Continuous infusion is an option, especially for patients at high risk of renal impairment or unstable vancomycin clearance. In such cases, vancomycin plasma steady-state level and creatinine monitoring are strongly indicated.
Topics: Anti-Bacterial Agents; Drug Administration Schedule; Humans; Microbial Sensitivity Tests; Staphylococcus aureus; Vancomycin
PubMed: 26856841
DOI: 10.1128/AAC.03147-14 -
Canadian Journal of Microbiology Jan 2020The emergence of multidrug-resistant bacteria demands innovations in the development of new antibiotics. For decades, the glycopeptide antibiotic vancomycin has been... (Review)
Review
The emergence of multidrug-resistant bacteria demands innovations in the development of new antibiotics. For decades, the glycopeptide antibiotic vancomycin has been considered as the "last resort" treatment of severe infections caused by Gram-positive bacteria. Since the discovery of the first vancomycin-resistant enterococci strains in the late 1980s, the number of resistances has been steadily rising, with often life-threatening consequences. As an alternative to the generation of completely new substances, novel approaches focus on structural modifications of established antibiotics such as vancomycin to overcome these resistances. Here, we provide an overview of several promising modifications of vancomycin to restore its efficacy against vancomycin-resistant enterococci.
Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Structure-Activity Relationship; Vancomycin; Vancomycin Resistance
PubMed: 31545906
DOI: 10.1139/cjm-2019-0309 -
Pharmacotherapy Apr 2020Recent vancomycin PK/PD and toxicodynamic studies enable a reassessment of the current dosing and monitoring guideline in an attempt to further optimize the efficacy and...
Executive Summary: Therapeutic Monitoring of Vancomycin for Serious Methicillin-Resistant Staphylococcus aureus Infections: A Revised Consensus Guideline and Review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases...
BACKGROUND
Recent vancomycin PK/PD and toxicodynamic studies enable a reassessment of the current dosing and monitoring guideline in an attempt to further optimize the efficacy and safety of vancomycin therapy. The area-under-the-curve to minimum inhibitory concentration (AUC/MIC) has been identified as the most appropriate pharmacokinetic/pharmacodynamic (PK/PD) target for vancomycin. The 2009 vancomycin consenus guidelines recommended specific trough concentrations as a surrogate marker for AUC/MIC. However, more recent toxicodynamic studies have reported an increase in nephrotoxicity associated with trough monitoring.
METHODS AND RESULTS
This is the executive summary of the new vancomycin consensus guidelines for dosing and monitoring vancomycin therapy and was developed by the American Society of Health-Systems Pharmacists, Infectious Diseases Society of America, Pediatric Infectious Diseases Society and the Society of Infectious Diseases Pharmacists vancomycin consensus guidelines committee.
CONCLUSIONS
The recommendations provided in this document are intended to assist the clinician in optimizing vancomycin for the treatment of invasive MRSA infections in adult and pediatric patients. An AUC/MIC by broth microdilution (BMD) ratio of 400 to 600 (assuming MICBMD of 1 mg/L) should be advocated as the target to achieve clinical efficacy while improving patient safety for patients with serious MRSA infections. In such cases, AUC-guided dosing and monitoring is the most accurate and optimal way to manage vancomycin therapy.
Topics: Anti-Bacterial Agents; Drug Monitoring; Humans; Methicillin-Resistant Staphylococcus aureus; Practice Guidelines as Topic; Societies, Medical; Societies, Pharmaceutical; Staphylococcal Infections; United States; Vancomycin
PubMed: 32227354
DOI: 10.1002/phar.2376 -
Science Translational Medicine May 2023Bacterial bloodstream infections (BSIs) resulting in late-onset sepsis affect up to half of extremely preterm infants and have substantial morbidity and mortality....
Bacterial bloodstream infections (BSIs) resulting in late-onset sepsis affect up to half of extremely preterm infants and have substantial morbidity and mortality. Bacterial species associated with BSIs in neonatal intensive care units (NICUs) commonly colonize the preterm infant gut microbiome. Accordingly, we hypothesized that the gut microbiome is a reservoir of BSI-causing pathogenic strains that increase in abundance before BSI onset. We analyzed 550 previously published fecal metagenomes from 115 hospitalized neonates and found that recent ampicillin, gentamicin, or vancomycin exposure was associated with increased abundance of Enterobacteriaceae and Enterococcaceae in infant guts. We then performed shotgun metagenomic sequencing on 462 longitudinal fecal samples from 19 preterm infants (cases) with BSI and 37 non-BSI controls, along with whole-genome sequencing of the BSI isolates. Infants with BSI caused by Enterobacteriaceae were more likely than infants with BSI caused by other organisms to have had ampicillin, gentamicin, or vancomycin exposure in the 10 days before BSI. Relative to controls, gut microbiomes of cases had increased relative abundance of the BSI-causing species and clustered by Bray-Curtis dissimilarity according to BSI pathogen. We demonstrated that 11 of 19 (58%) of gut microbiomes before BSI, and 15 of 19 (79%) of gut microbiomes at any time, harbored the BSI isolate with fewer than 20 genomic substitutions. Last, BSI strains from the Enterobacteriaceae and Enterococcaceae families were detected in multiple infants, indicating BSI-strain transmission. Our findings support future studies to evaluate BSI risk prediction strategies based on gut microbiome abundance in hospitalized preterm infants.
Topics: Infant; Infant, Newborn; Humans; Infant, Premature; Gastrointestinal Microbiome; Intensive Care Units, Neonatal; Vancomycin; Sepsis; Bacterial Infections; Bacteria; Gentamicins; Ampicillin
PubMed: 37134153
DOI: 10.1126/scitranslmed.adg5562 -
Antimicrobial Agents and Chemotherapy Feb 2018We hypothesized that dosing vancomycin to achieve trough concentrations of >15 mg/liter overdoses many adults compared to area under the concentration-time curve... (Clinical Trial)
Clinical Trial
We hypothesized that dosing vancomycin to achieve trough concentrations of >15 mg/liter overdoses many adults compared to area under the concentration-time curve (AUC)-guided dosing. We conducted a 3-year, prospective study of vancomycin dosing, plasma concentrations, and outcomes. In year 1, nonstudy clinicians targeted trough concentrations of 10 to 20 mg/liter (infection dependent) and controlled dosing. In years 2 and 3, the study team controlled vancomycin dosing with BestDose Bayesian software to achieve a daily, steady-state AUC/MIC ratio of ≥400, with a maximum AUC value of 800 mg · h/liter, regardless of trough concentration. For Bayesian estimation of AUCs, we used trough samples in years 1 and 2 and optimally timed samples in year 3. We enrolled 252 adults who were ≥18 years old with ≥1 available vancomycin concentration. Only 19% of all trough concentrations were therapeutic versus 70% of AUCs ( < 0.0001). After enrollment, median trough concentrations by year were 14.4, 9.7, and 10.9 mg/liter ( = 0.005), with 36%, 7%, and 6% over 15 mg/liter ( < 0.0001). Bayesian AUC-guided dosing in years 2 and 3 was associated with fewer additional blood samples per subject (3.6, 2.0, and 2.4; = 0.003), shorter therapy durations (8.2, 5.4, and 4.7 days; = 0.03), and reduced nephrotoxicity (8%, 0%, and 2%; = 0.01). The median inpatient stay was 20 days among nephrotoxic patients versus 6 days ( = 0.002). There was no difference in efficacy by year, with 42% of patients having microbiologically proven infections. Compared to trough concentration targets, AUC-guided, Bayesian estimation-assisted vancomycin dosing was associated with decreased nephrotoxicity, reduced per-patient blood sampling, and shorter length of therapy, without compromising efficacy. These benefits have the potential for substantial cost savings. (This study has been registered at ClinicalTrials.gov under registration no. NCT01932034.).
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Area Under Curve; Bacteria; Bayes Theorem; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Vancomycin; Young Adult
PubMed: 29203493
DOI: 10.1128/AAC.02042-17 -
The Medical Clinics of North America Jul 1995Vancomycin is a nontoxic glycopeptide antibiotic most often used to treat serious gram-positive infections, C. difficile diarrhea/colitis, and endocarditis and... (Review)
Review
Vancomycin is a nontoxic glycopeptide antibiotic most often used to treat serious gram-positive infections, C. difficile diarrhea/colitis, and endocarditis and hemodialysis shunt prophylaxis. Vancomycin should not be added to drug regimens for gram-positive coverage, and the empiric use of vancomycin should be discouraged to avoid the emergence of VRE. Vancomycin serum levels are no longer necessary or cost effective in most patients because vancomycin is not nephrotoxic.
Topics: Bacterial Infections; Drug Interactions; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Vancomycin
PubMed: 7791425
DOI: 10.1016/s0025-7125(16)30041-4 -
PloS One 2021To compare between current evidence of novel glycopeptides against vancomycin for the treatment of gram-positive bacterial infections. (Meta-Analysis)
Meta-Analysis
Efficacy and safety of novel glycopeptides versus vancomycin for the treatment of gram-positive bacterial infections including methicillin resistant Staphylococcus aureus: A systematic review and meta-analysis.
OBJECTIVE
To compare between current evidence of novel glycopeptides against vancomycin for the treatment of gram-positive bacterial infections.
METHODOLOGY
A systematic review and meta-analysis was done. Major databases were searched for eligible randomized control trials that assessed clinical success, microbiological success and safety profile of novel glycopeptides versus vancomycin for infections caused by gram-positive bacteria.
RESULTS
This meta-analysis included eleven trials (7289 participants) comparing telavancin, dalbavancin and oritavancin with vancomycin. No differences were detected between novel glycopeptides and vancomycin for the treatment of skin and soft tissue infections (SSTIs) among modified intent-to-treat patients (OR: 1.04, CI: 0.92-1.17) as well as within the clinically evaluable patients (OR: 1.09, CI: 0.91-1.30). Data analysed from SSTIs, HAP and bacteremia studies on telavancin showed insignificant high clinical response in microbiologically evaluable patients infected with methicillin resistant Staphylococcus aureus (MRSA) (OR: 1.57, CI: 0.94-2.62, p: 0.08) and in the eradication of MRSA (OR: 1.39, CI: 0.99-1.96, P:0.06). Dalbavancin was non-inferior to vancomycin for the treatment of osteomyelitis in a phase II trial, while it was superior to vancomycin for the treatment of bacteremia in a phase II trial. Data analysed from all trials showed similar rates of all-cause mortality between compared antibiotics groups (OR: 0.67, CI: 0.11-4.03). Telavancin was significantly related with higher adverse events (OR: 1.24, CI: 1.07-1.44, P: <0.01) while dalbavancin and oritavancin were associated with significant fewer adverse events (OR: 0.73, CI: 0.57-0.94, p: 0.01; OR: 0.72, CI: 0.59-0.89, p: <0.01 respectively).
CONCLUSION
Efficacy and safety profiles of both dalbavancin and oritavancin were the same as vancomycin in the treatment of gram-positive bacterial infections in different clinical settings, while telavancin might be an effective alternative to vancomycin in MRSA infections, but caution is required during its clinical use due to the high risk of adverse events, especially nephrotoxicity.
Topics: Anti-Bacterial Agents; Glycopeptides; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Methicillin-Resistant Staphylococcus aureus; Treatment Outcome; Vancomycin
PubMed: 34843561
DOI: 10.1371/journal.pone.0260539 -
Drugs Jul 2017Vancomycin is a glycopeptide antibiotic that is active against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Nephrotoxicity, which is... (Review)
Review
Vancomycin is a glycopeptide antibiotic that is active against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Nephrotoxicity, which is usually reversible, is the most serious common adverse effect of vancomycin. Vancomycin-associated nephrotoxicity prolongs hospital stays, imposes a need for additional antibiotics and, in rare circumstances, dialysis treatment, and increases medical costs and mortality. Risk factors for nephrotoxicity include the dose and duration of vancomycin treatment, serum trough concentration, patient characteristics, and concomitant receipt of nephrotoxins. Contemporary guidelines recommend targeting vancomycin trough concentrations of ≥10 mg/L to prevent resistance and trough concentrations of 15-20 mg/L to optimize outcomes. There is significant correlation between vancomycin trough serum concentrations and the incidence of vancomycin-associated nephrotoxicity; however, evidence of an association between trough concentrations and efficacy is less convincing. Routine monitoring of serum vancomycin concentrations consumes time and limited healthcare resources and may not be cost effective. The use of alternative antibacterial agents that do not require monitoring would free up pharmacy resources. This time could then be devoted to initiatives such as pharmacist-led antibiotic stewardship programs that are known to reduce antibiotic use and promote improved patient outcomes.
Topics: Anti-Bacterial Agents; Health Care Costs; Humans; Incidence; Kidney Diseases; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Retrospective Studies; Risk Factors; Staphylococcal Infections; Vancomycin
PubMed: 28573434
DOI: 10.1007/s40265-017-0764-7 -
Chemical Reviews Sep 2017A review of efforts that have provided total syntheses of vancomycin and related glycopeptide antibiotics, their agylcons, and key analogues is provided. It is a tribute... (Review)
Review
A review of efforts that have provided total syntheses of vancomycin and related glycopeptide antibiotics, their agylcons, and key analogues is provided. It is a tribute to developments in organic chemistry and the field of organic synthesis that not only can molecules of this complexity be prepared today by total synthesis but such efforts can be extended to the preparation of previously inaccessible key analogues that contain deep-seated structural changes. With the increasing prevalence of acquired bacterial resistance to existing classes of antibiotics and with the emergence of vancomycin-resistant pathogens (VRSA and VRE), the studies pave the way for the examination of synthetic analogues rationally designed to not only overcome vancomycin resistance but provide the foundation for the development of even more powerful and durable antibiotics.
Topics: Anti-Bacterial Agents; Glycopeptides; Humans; Molecular Conformation; Vancomycin; Vancomycin Resistance
PubMed: 28437097
DOI: 10.1021/acs.chemrev.6b00820