Study confirms high prevalence of Methicillin-resistant Staphylococcus aureus with reduced susceptibility to vancomycin

Methicillin-resistant Staphylococcus aureus (MRSA) strains showing reduced susceptibility to vancomycin (minimum inhibitory concentration [MIC] of 2 mcg/mL) and requiring aggressive empiric vancomycin dosing are highly prevalent among those that cause invasive infections, according to a prospective cohort study.

In the study, published in the Archives of Internal Medicine, researchers sought to determine the distribution of vancomycin MICs among MRSA isolates and to evaluate the efficacy and safety of more aggressive vancomycin dosing to achieve an unbound target trough concentration of 4 or more times the MIC of the infecting strain (corresponding to a trough target of ≥15 mcg/mL).

To conduct the study, researchers used their institution's microbiology laboratory computer records to identify all patients receiving vancomycin from whom a strain of MRSA was isolated from August 1, 2004, through June 30, 2005. Medical records were then retrospectively reviewed to assess rates of patient response (resolution of fever, leukocytosis, and local signs of infection), mortality and nephrotoxicity (increase in serum creatinine of 0.5 mg/dL, or 50% or more from baseline).

Conversely, even in patients achieving target vancomycin trough levels, response rates at end of treatment were significantly lower in patients with high MIC strains compared with those with low MIC strains (62% vs 85%, respectively; P=.02). Upon multivariate logistic regression analysis, only higher APACHE II scores and having a high MIC strain were found to be independent predictors of poor patient response. While not reaching statistical significance, a trend toward higher mortality (26% vs 10%; P=.20) was observed in patients with high MIC strains being treated with vancomycin.

In a separate safety analysis, multivariate logistic regression analysis revealed that the risk of nephrotoxicity from vancomycin was associated with a patients' duration of therapy at high (15 to 20 mcg/mL) trough levels, with an observed 6.3% increase in risk when exposure was ≤7 days, a 21.1% increase for 8 to 14 days, and 30% increase when exposure was >2 weeks. However, it is important to note that of the 11 patients who developed nephrotoxicity, 10 were receiving concomitant nephrotoxic agents (eg, aminoglycosides, amphotericin B) and 4 had pre-existing renal disease.

Based upon their findings, Levita K. Hidayat, MD, and colleagues from the University of Southern California and Western University emphasized that the "suboptimal response associated with vancomycin therapy not attaining the trough target underscores the importance of aggressive initial dosing to achieve a trough of 15 mcg/mL or more until culture and sensitivity results are known." In addition, they suggested that combination or alternative therapy should be considered for invasive infections caused by these strains.

SOURCE Hidayat LK, Hsu DI, Quist R, Shriner KA, Wong-Beringer A. High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections. Arch Intern Med. 2006;166:2138–2144.