Abstract
BackgroundThe 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.MethodsWe 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 [AUC0–24], and AUC0–24/MIC) and efficacy/nephrotoxicity were assessed in MRSA pneumonia patients using univariate logistic regression or Cox proportional hazards regression analysis approach.ResultsAfter 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]).ConclusionsIn non-dialysis patients, baseline renal function did not impact the differences in efficacy or nephrotoxicity with treatment of linezolid versus vancomycin in MRSA pneumonia.
Highlights
The primary objective of this study is to assess whether baseline renal function impacts treatment outcomes of linezolid and vancomycin for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia
It may be postulated that differences in outcomes existing in MRSA pneumonia patients treated with linezolid and vancomycin may be driven by differences in renal function since it may affect vancomycin exposure
Baseline renal function did not modify the relationships between vancomycin exposures and acute kidney injury (AKI) occurrence. We conducted this retrospective analysis of a subpopulation of patients from a prospective, randomized, controlled clinical trial to determine whether baseline renal function impacted treatment efficacy and nephrotoxicity of linezolid and vancomycin in MRSA pneumonia patients
Summary
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. Plasma concentrations of linezolid are not affected in patients with advanced renal impairment [3], while renal dysfunction impairs excretion of vancomycin resulting in a higher systemic exposure with the same dosing regimen [4]. In the face of “MIC creep” in MRSA isolates, a shift of Cmin from the traditional target of 5–15 μg/ml to a higher range of 15–20 μg/ml has been proposed in order to achieve vancomycin exposure in sufficient excess of the minimum concentration required to inhibit the organism [1, 7]. The authors concluded that aggressive dosing strategies for vancomycin (e.g., trough concentrations exceeding 15 μg/ml) may not offer any advantage over traditional targets of 5 to 15 μg/ml [8,9,10,11,12]
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