The safety and efficacy of high versus low vancomycin trough levels in the treatment of patients with infections caused by methicillin-resistant Staphylococcus aureus: a meta-analysis

Abstract

BackgroundRecent guidelines have recommended vancomycin trough levels of 15–20 mg/L for treatment of serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA). However, high trough levels may increase risk of nephrotoxicity and mortality, and high vancomycin trough levels have not been well studied. This study was designed to combine safety and efficacy results from independent studies and to compare between high and low vancomycin trough levels in the treatment of MRSA-infected patients using meta-analysis.MethodsFrom 19 eligible studies, 9 studies were included in meta-analysis to compare clinical success between high and low vancomycin trough levels, while 10 and 11 studies met criteria for comparing trough levels and nephrotoxicity and trough levels and mortality, respectively. The PubMed/Medline, Web of Science, and Scopus databases, and hand searching were used to identify eligible studies dated up to March 2016. Of 2344 subjects with MRSA infection, 1036 were assigned to trough levels ≥15 mg/L and 1308 to trough levels <15 mg/L.ResultsHigh vancomycin trough levels were found to be associated with risk of nephrotoxicity (odds ratio [OR] 2.14, 95 % confidence interval [CI] 1.42–3.23 and adjusted OR 3.33, 95 % CI 1.91–5.79). There was no evidence of difference between high and low vancomycin trough levels for mortality (OR; 1.09; 95 % CI 0.75–1.60) or clinical success (OR 1.07; 95 % CI 0.68–1.68).ConclusionIn this study, high vancomycin trough levels were identified as an independent factor associated with risk of nephrotoxicity in MRSA-infected patients. Association between vancomycin trough levels and both adverse effects and clinical outcomes requires further study.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-016-2252-7) contains supplementary material, which is available to authorized users.

Sustained improvement in vancomycin dosing and monitoring post-implementation of guidelines: Results of a three-year follow-up after a multifaceted intervention in an Australian teaching hospital

“…In this study we demonstrated that a multifaceted intervention improved guideline-adherent vancomycin prescribing, resulting in hospital inpatients more rapidly attaining target concentrations, which have been associated with improved clinical outcomes and reduced risk of nephrotoxicity [34][35]. The findings observed in the current study were generally consistent with our pilot [26], and we showed meaningful reductions in the duration of vancomycin treatment and nephrotoxicity.…”

The Nephrotoxicity of Vancomycin

“…A meta‐analysis of these trials found no significant benefit of higher trough concentration on mortality or treatment failure, but there was a higher rate of microbiologic failure in the low trough group . Another meta‐analysis evaluated only trials involving patients with documented MRSA infections: nine studies compared troughs ≥15 mg/L vs. <15 mg/L with regard to clinical success, and 11 studies compared such troughs to mortality . There was no significant difference with levels ≥15 mg/L in clinical success (odds ratio (OR) 1.07, 95% confidence interval (CI) 0.68–1.68) or mortality (OR 1.09, 95% CI 0.75–1.60), unless accounting for publication bias by the trim‐and‐fill method for clinical success (OR 1.71, 95% CI 1.04–2.81).…”

“…This finding persisted if restricted to studies evaluating only initial troughs . More recently, Tongsai and Koomanachai analyzed 10 studies involving only patients with MRSA infection and found an OR of 2.14 (95% CI 1.42–3.23) for nephrotoxicity with troughs ≥15 mg/L and an adjusted OR of 3.33 (95% CI 1.91–5.79) in three studies providing sufficient data for combining adjusted ORs . Hence, the evidence for potential harm with attaining troughs ≥15 mg/L is more compelling than the evidence for potential benefit.…”

Daptomycin treatment in patients with resistant staphylococcal periprosthetic joint infection

“…Furthermore, a risk of vancomycin-induced nephrotoxicity in the population with chronic kidney disease has also been reported [ 25 ]. In a recent meta-analysis study related to MRSA-infected patients, high vancomycin trough levels were recognized as an independent factor associated with risk of nephrotoxicity [ 26 ]. For the above reasons, vancomycin is not optimal for the treatment of resistant staphylococcal PJI in patients with CKD.…”

“…For example, Rao et al used daptomycin at a median dosage of 4 mg∕kg per day in 11 cases, and achieved a lower success rate of 54.5% [ 21 ]. Antony et al reported a 38% success rate among patients treated with 4 mg∕kg per 24 or 48 h as compared with a 77% success rate among patients who received daptomycin at 6 mg∕kg per day [ 26 ]. Byren et al [ 17 ] used daptomycin at 6 or 8 mg∕kg per day for 6 weeks in a randomized trial during the two-stage reimplantation process, and found that the higher-dose group (8 mg∕kg per day) exhibited a higher treatment success rate than the lower-dose (6 mg∕kg per day) group.…”