Dataset Information

Relationship between vancomycin exposure and outcomes among patients with MRSA bloodstream infections with vancomycin Etest® MIC values of 1.5mg/L: A pilot study.

ABSTRACT: Data suggest that vancomycin is less effective for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) with vancomycin Etest® MIC (MICEtest) ?1.5 mg/L. No published studies have evaluated the relationship between vancomycin exposure and outcomes among patients with MRSA BSIs vancomycin MICEtest ?1.5 mg/L. This study was a retrospective cohort of 71 hospitalized, adult, non-dialysis patients with MRSA BSIs treated with vancomycin. All but three patients had a vancomycin MICEtest of 1.5 mg/L. Achievement of CART-derived AUC24-48h of at least 550 mg*h/L (AUC24-48h/MIC of 366 mg*h/L) was associated with a lower incidence of treatment failure. In multivariate analyses, the risk ratio was 0.45 for the CART-derived AUC24-48h threshold, indicating that achievement of the CART-derived AUC24-48h threshold of 550 was associated with a 2-fold decrease in treatment failure. These findings suggest a potential association between vancomycin exposure and outcomes in patients with MRSA BSIs with MICEtest ?1.5 mg/L. As this study was retrospective, these findings provide the basis for a future large-scale, multi-center prospective study.

SUBMITTER: Martirosov DM

PROVIDER: S-EPMC5512425 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Relationship between vancomycin exposure and outcomes among patients with MRSA bloodstream infections with vancomycin Etest® MIC values of 1.5mg/L: A pilot study.

Martirosov D M DM Bidell M R MR Pai M P MP Scheetz M H MH Rosenkranz S L SL Lodise T P TP

Diagnostic microbiology and infectious disease 20170402 3

Data suggest that vancomycin is less effective for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) with vancomycin Etest® MIC (MIC<sub>Etest</sub>) ≥1.5 mg/L. No published studies have evaluated the relationship between vancomycin exposure and outcomes among patients with MRSA BSIs vancomycin MIC<sub>Etest</sub> ≥1.5 mg/L. This study was a retrospective cohort of 71 hospitalized, adult, non-dialysis patients with MRSA BSIs treated with vancomycin. All but three pat ...[more]

PMID: 28449844

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Project description:Vancomycin remains the mainstay treatment for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) despite increased treatment failures. Daptomycin has been shown to improve clinical outcomes in patients with BSIs caused by MRSA isolates with vancomycin MICs of >1 mg/liter, but these studies relied on automated testing systems. We evaluated the outcomes of BSIs caused by MRSA isolates for which vancomycin MICs were determined by standard broth microdilution (BMD). A retrospective, matched cohort of patients with MRSA BSIs treated with vancomycin or daptomycin from January 2010 to March 2015 was completed. Patients were matched using propensity-adjusted logistic regression, which included age, Pitt bacteremia score, primary BSI source, and hospital of care. The primary endpoint was clinical failure, which was a composite endpoint of the following metrics: 30-day mortality, bacteremia with a duration of ?7 days, or a change in anti-MRSA therapy due to persistent or worsening signs or symptoms. Secondary endpoints included MRSA-attributable mortality and the number of days of MRSA bacteremia. Independent predictors of failure were determined through conditional backwards-stepwise logistic regression with vancomycin BMD MIC forced into the model. A total of 262 patients were matched. Clinical failure was significantly higher in the vancomycin cohort than in the daptomycin cohort (45.0% versus 29.0%; P = 0.007). All-cause 30-day mortality was significantly higher in the vancomycin cohort (15.3% versus 6.1%; P = 0.024). These outcomes remained significant when stratified by vancomycin BMD MIC. There was no significant difference in the length of MRSA bacteremia. Variables independently associated with treatment failure included vancomycin therapy (adjusted odds ratio [aOR] = 2.16, 95% confidence interval [CI] = 1.24 to 3.76), intensive care unit admission (aOR = 2.46, 95% CI = 1.34 to 4.54), and infective endocarditis as the primary source (aOR = 2.33, 95% CI = 1.16 to 4.68). Treatment of MRSA BSIs with daptomycin was associated with reduced clinical failure and 30-day mortality; these findings were independent of vancomycin BMD MIC.

Project description:IntroductionA one-time vancomycin loading dose of 25-30 mg/kg is recommended in the current iteration of the vancomycin consensus guidelines in order to more rapidly achieve target serum concentrations and hasten clinical improvement. However, there are few clinical data to support this practice, and the extents of its benefits are largely unknown.MethodsA multicenter, retrospective, cohort study was performed to assess the impact of a vancomycin loading dose (≥ 20 mg/kg) on clinical outcomes and rates of nephrotoxicity in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. The study matched patients in a 1:1 fashion based on age, Pitt bacteremia score, and bacteremia source. The primary outcome was composite treatment failure (30-day mortality, bacteremia duration ≥ 7 days after vancomycin initiation, persistent signs and symptoms of infection ≥ 7 days after vancomycin initiation, or switch to an alternative antimicrobial agent). Secondary outcomes included duration of bacteremia, length of stay post-bacteremia onset, and nephrotoxicity.ResultsA total of 316 patients with MRSA bacteremia were included. Median first doses in the loading dose and non-loading dose groups were 23.0 mg/kg and 14.3 mg/kg, respectively (P < 0.001). No difference was found in composite failure rates between the non-loading dose and loading dose groups (40.5% vs. 36.7%; P = 0.488) or in the incidence of nephrotoxicity (12.7% vs. 16.5%; P = 0.347). While multivariable regression modeling showed receipt of a vancomycin loading dose on a mg/kg basis was not significantly associated with composite failure [aOR 0.612, 95% CI (0.368-1.019)]; post hoc analyses demonstrated that initial doses ≥ 1750 mg were independently protective against failure [aOR 0.506, 95% CI (0.284-0.902)] without increasing the risk for nephrotoxicity [aOR 0.909, 95% CI (0.432-1.911)].ConclusionThese findings suggest that initial vancomycin doses above a certain threshold may decrease clinical failures without increasing toxicity and that weight-based dosing might not be the optimal strategy.

Dataset Information

Relationship between vancomycin exposure and outcomes among patients with MRSA bloodstream infections with vancomycin Etest® MIC values of 1.5mg/L: A pilot study.

Publications

Relationship between vancomycin exposure and outcomes among patients with MRSA bloodstream infections with vancomycin Etest® MIC values of 1.5mg/L: A pilot study.

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