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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 -
European Review For Medical and... Feb 2015Vancomycin (VCM) is a tricyclic glycopeptide antibiotic produced by Streptococcus orientalis. Widely used in hospitals, it is indicated to fight severe infections caused... (Review)
Review
OBJECTIVE
Vancomycin (VCM) is a tricyclic glycopeptide antibiotic produced by Streptococcus orientalis. Widely used in hospitals, it is indicated to fight severe infections caused by Gram-positive bacteria, especially with the advent of MRSA (methicillin-resistant Staphylococcus aureus), penicillin-resistant pneumococci among others. Furthermore, it is indicated for the treatment of patients allergic to penicillins and cephalosporins. Dose recommendations, dilution rates and types of infusion are controversial and also result in toxic effects. Aim of this paper was to perform a literature review showing the therapeutic and adverse effects of vancomycin.
MATERIALS AND METHODS
This is a literature review of recent articles published on MEDLINE and SciELO databases in English, Portuguese and Spanish.
RESULTS
The main adverse effects of vancomycin are: hypotension, phlebitis, nephrotoxicity, ototoxicity, hypersensitivity reactions, red man syndrome, neutropenia, chills, fever, interstitial nephritis.
CONCLUSIONS
The use of vancomycin is still very common; however, inadequate doses and prolonged therapy pose a risk of increasing minimum inhibitory concentrations (MICs), resulting in subtherapeutic levels, treatment failures and toxicity. Therefore, further studies should be conducted to optimize the administration of vancomycin, monitoring treatments from the beginning in order to ensure a safe and effective use of the drug.
Topics: Anti-Bacterial Agents; Cephalosporins; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Neutropenia; Vancomycin
PubMed: 25753888
DOI: No ID Found -
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 -
International Journal of Molecular... Feb 2022Vancomycin is the most frequently used antibiotic, accounting for up to 35% of hospitalized patients with infection, because of its optimal bactericidal effectiveness... (Review)
Review
Vancomycin is the most frequently used antibiotic, accounting for up to 35% of hospitalized patients with infection, because of its optimal bactericidal effectiveness and relatively low price. Vancomycin-associated AKI (VA-AKI) is a clinically relevant but not yet clearly understood entity in critically ill patients. The current review comprehensively summarizes the pathophysiological mechanisms of, biomarkers for, preventive strategies for, and some crucial issues with VA-AKI. The pathological manifestations of VA-AKI include acute tubular necrosis, acute tubulointerstitial nephritis (ATIN), and intratubular crystal obstruction. The proposed pathological mechanisms of VA-AKI include oxidative stress and allergic reactions induced by vancomycin and vancomycin-associated tubular casts. Concomitant administration with other nephrotoxic antibiotics, such as piperacillin-tazobactam, high vancomycin doses, and intermittent infusion strategies compared to the continuous infusion are associated with a higher risk of VA-AKI. Several biomarkers could be applied to predict and diagnose VA-AKI. To date, no promising therapy is available. Oral steroids could be considered for patients with ATIN, whereas hemodialysis might be applied to remove vancomycin from the patient. In the future, disclosing more promising biomarkers that could precisely identify populations susceptible to VA-AKI and detect VA-AKI occurrence early on, and developing pharmacological agents that could prevent or treat VA-AKI, are the keys to improve the prognoses of patients with severe infection who probably need vancomycin therapy.
Topics: Acute Kidney Injury; Animals; Anti-Bacterial Agents; Biomarkers; Humans; Vancomycin
PubMed: 35216167
DOI: 10.3390/ijms23042052 -
MSphere Jan 2021infection (CDI) is most commonly diagnosed using nucleic acid amplification tests (NAAT); the low positive predictive value of these assays results in patients... (Randomized Controlled Trial)
Randomized Controlled Trial
infection (CDI) is most commonly diagnosed using nucleic acid amplification tests (NAAT); the low positive predictive value of these assays results in patients colonized with unnecessarily receiving CDI treatment antibiotics. The risks and benefits of antibiotic treatment in individuals with such cases are unknown. Fecal samples of NAAT-positive, toxin enzyme immunoassay (EIA)-negative patients were collected before, during, and after randomization to vancomycin ( = 8) or placebo ( = 7). and antibiotic-resistant organisms (AROs) were selectively cultured from fecal and environmental samples. Shotgun metagenomics and comparative isolate genomics were used to understand the impact of oral vancomycin on the microbiome and environmental contamination. Overall, 80% of placebo patients and 71% of vancomycin patients were colonized with posttreatment. One person randomized to placebo subsequently received treatment for CDI. In the vancomycin-treated group, beta-diversity (0.0059) and macrolide-lincosamide-streptogramin (MLS) resistance genes (0.037) increased after treatment; and vancomycin-resistant enterococci (VRE) environmental contamination was found in 53% of patients and 26% of patients, respectively. We found that vancomycin alters the gut microbiota, does not permanently clear , and is associated with VRE colonization/environmental contamination. (This study has been registered at ClinicalTrials.gov under registration no. NCT03388268.) A gold standard diagnostic for infection (CDI) does not exist. An area of controversy is how to manage patients whose stool tests positive by nucleic acid amplification tests but negative by toxin enzyme immunoassay. Existing data suggest most of these patients do not have CDI, but most are treated with oral vancomycin. Potential benefits to treatment include a decreased risk for adverse outcomes if the patient does have CDI and the potential to decrease shedding/transmission. However, oral vancomycin perturbs the intestinal microbiota and promotes antibiotic-resistant organism colonization/transmission. We conducted a double-blinded randomized controlled trial to assess the risk-benefit of oral vancomycin treatment in this population. Oral vancomycin did not result in long-term clearance of , perturbed the microbiota, and was associated with colonization/shedding of vancomycin-resistant enterococci. This work underscores the need to better understand this population of patients in the context of /ARO-related outcomes and transmission.
Topics: Administration, Oral; Adult; Aged; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Feces; Female; Gastrointestinal Microbiome; Humans; Male; Metagenomics; Middle Aged; Vancomycin; Vancomycin-Resistant Enterococci
PubMed: 33441409
DOI: 10.1128/mSphere.00936-20 -
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 -
Advanced Drug Delivery Reviews Nov 2014The delivery of personalized antimicrobial therapy is a critical component in the treatment of patients with invasive infections. Vancomycin, the drug of choice for... (Review)
Review
The delivery of personalized antimicrobial therapy is a critical component in the treatment of patients with invasive infections. Vancomycin, the drug of choice for infections due to methicillin-resistant Staphylococcus aureus, requires the use of therapeutic drug monitoring (TDM) for delivery of optimal therapy. Current guidance on vancomycin TDM includes the measurement of a trough concentration as a surrogate for achieving an AUC to minimum inhibitory concentration (MIC) by broth microdilution (AUC/MICBMD) ratio≥400. Although trough-only monitoring has been widely integrated into clinical practice, there is a high degree of inter-individual variability between a measured trough concentration and the actual AUC value. The therapeutic discordance between AUC and trough may lead to suboptimal outcomes among patients with infections due to less susceptible pathogens or unnecessarily increase the probability of acute kidney injury (AKI) in others. Given the potentially narrow vancomycin AUC range for optimal effect and minimal AKI, clinicians need a "real-time" system to predict accurately the AUC with limited pharmacokinetic (PK) sampling. This article reviews two innovative approaches for calculating the vancomycin AUC in clinical practice based on one or two drug concentrations. One such approach involves the use of Bayesian computer software programs to estimate the "true" vancomycin AUC value with minimal PK sampling and provide AUC-guided dosing recommendations at the bedside. An alternative involves use of two concentrations (peak and trough) and simple analytic equations to estimate AUC values. Both approaches provide considerable improvements over the current trough-only concentration monitoring method.
Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Drug Delivery Systems; Drug Monitoring; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcal Infections; Vancomycin
PubMed: 24910345
DOI: 10.1016/j.addr.2014.05.016 -
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 -
Pediatrics Apr 2022Inappropriate vancomycin use is common in children's hospitals. We report a quality improvement (QI) intervention to reduce vancomycin use in our tertiary care PICU.
BACKGROUND AND OBJECTIVES
Inappropriate vancomycin use is common in children's hospitals. We report a quality improvement (QI) intervention to reduce vancomycin use in our tertiary care PICU.
METHODS
We retrospectively quantified the prevalence of infections caused by organisms requiring vancomycin therapy, including methicillin-resistant Staphylococcus aureus (MRSA), among patients with suspected bacterial infections. Guided by these data, we performed 3 QI interventions over a 3-year period, including (1) stakeholder education, (2) generation of a consensus-based guideline for empiric vancomycin use, and (3) implementation of this guideline through clinical decision support. Vancomycin use in days of therapy (DOT) per 1000 patient days was measured by using statistical process control charts. Balancing measures included frequency of bacteremia due to an organism requiring vancomycin not covered with empiric therapy, 30-day mortality, and cardiovascular, respiratory, and renal organ dysfunction.
RESULTS
Among 1276 episodes of suspected bacterial infection, a total of 19 cases of bacteremia (1.5%) due to organisms requiring vancomycin therapy were identified, including 6 MRSA bacteremias (0.5%). During the 3-year QI project, overall vancomycin DOT per 1000 patient days in the PICU decreased from a baseline mean of 182 DOT per 1000 patient days to 109 DOT per 1000 patient days (a 40% reduction). All balancing measures were unchanged, and all cases of MRSA bacteremia were treated empirically with vancomycin.
CONCLUSION
Our interventions reduced overall vancomycin use in the PICU without evidence of harm. Provider education and consensus building surrounding indications for empiric vancomycin use were key strategies.
Topics: Anti-Bacterial Agents; Child; Critical Illness; Humans; Methicillin-Resistant Staphylococcus aureus; Retrospective Studies; Staphylococcal Infections; Vancomycin
PubMed: 35362066
DOI: 10.1542/peds.2021-052165