Association of vancomycin serum concentrations with efficacy in patients with MRSA infections: a systematic review and meta-analysis

Abstract

Recent Infectious Diseases Society of America guidelines for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections recommend maintaining vancomycin trough concentrations of 15-20 mg/L for serious infections. We conducted a systematic review and meta-analysis of all studies assessing the impact of low (<15 mg/L) vs. high (≥ 15 mg/L) vancomycin trough level on the efficacy of MRSA infections treatment. Four prospective and 12 retrospective studies were included (2003 participants). No significant difference was demonstrated between low and high vancomycin trough level for the outcome of all-cause mortality (odds ratio (OR) 1.07, 95% confidence interval (CI) 0.78-1.46, I(2) = 28%). In studies evaluating mainly MRSA pneumonia, there was significantly higher mortality with low vancomycin level (OR 1.78, 95% CI 1.11-2.84). No significant difference was demonstrated in treatment failure rates (OR 1.25, 95% CI 0.88-1.78, I(2) = 51%). However, excluding one outlier study from the analysis, treatment failure became significantly higher in patients with low vancomycin trough level (OR 1.46, 95% CI 1.12-1.91, I(2) = 16%). Microbiologic failure rates were significantly higher in patients with low vancomycin levels (OR 1.56, 95% CI 1.08-2.26, I(2) = 0%). Nephrotoxicity was significantly higher with vancomycin levels of ≥ 15 mg/L. However, no cases of irreversible renal damage were reported. Current data on the effectiveness of higher vancomycin trough levels in the treatment of MRSA infections are limited to few prospective and mainly retrospective studies. Our findings support the current recommendations for maintaining vancomycin trough levels of ≥ 15 mg/L in the treatment of severe MRSA infections, although no difference in all-cause mortality was observed.

Retrospective analysis of vancomycin treatment outcomes in Chinese paediatric patients with suspected Gram-positive infection

“…A recent study of Chinese adults with Gram‐positive infection did not find any association between the vancomycin trough concentration and the clinical and microbiological responses . In addition, several meta‐analyses have shown that higher vancomycin trough levels (15 mg/L or greater) were not associated with significantly reduced treatment failure, persistent bacteraemia or mortality . In contrast, Kullar et al .…”

Vancomycin Trough Concentration as a Predictor of Clinical Outcomes in Patients withStaphylococcus aureusBacteremia: A Meta-analysis of Observational Studies

“…The results of this study are consistent with similar recently published meta‐analyses attempting to determine the appropriateness of trough level–based dosing for S. aureus infections . One analysis included 2003 patients from 16 studies and found no association between low vancomycin trough level and treatment failure or all‐cause mortality, but it was associated with microbiologic failure. Another analysis included 17 studies involving patients with any gram‐positive infection.…”

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

“…Dosing to a trough target of 15-20 mg/L is recommended by several authorities to maximize the probability of achieving appropriate pharmacodynamic targets, improve tissue penetration, and optimize clinical outcomes [145][146][147]. Pre-dose monitoring of trough concentrations is recommended.…”