The Impact of Linezolid versus Vancomycin on Surgical Interventions for Complicated Skin and Skin Structure Infections Caused by Methicillin-ResistantStaphylococcus aureus

Abstract

We conducted a study with the primary objective of assessing whether a difference existed in the frequency and type of surgical interventions (SIs) implemented in patients treated with linezolid versus vancomycin for the management of complicated skin and skin structure infections (cSSSIs) caused by methicillin-resistant Staphylococcus aureus (MRSA). We analyzed data from a phase IV clinical trial evaluating the safety and efficacy of linezolid and vancomycin, given for 7-14 d, to treat cSSSIs other than cellulitis that were caused by MRSA. The study included patients who received ≥1 dose of drug, had a cSSSI caused by culture-proved MRSA, and underwent ≥1 SI after commencement of the study. The types and frequencies of SIs were assessed on a per-patient basis during the following three time periods: (1) study days 0-3: the estimated time to reach steady-state serum drug concentrations; (2) study days 4-14: the drug-treatment period (days 4-14) during which steady state drug concentrations are likely reached; and (3) study days 15-28: the post-treatment period through end of the study (EOS). Independent predictors of ≥2 SIs during the drug-treatment period were identified by logistic regression. Clinical and microbiologic outcomes were assessed at the end of treatment (EOT), and at EOS for the SI population. The data analysis included 323 patients (linezolid, n=167; vancomycin, n=156). The majority of patients (81% in the linezolid group and 83% in the vancomycin group) underwent an initial SI or source control procedure within 72 h of study initiation. The most common cSSSIs among patients having SIs were abscesses (59%) and infected ulcers (20%). Independent predictors of ≥2 SIs during study days 4-14 included treatment with vancomycin (OR 5.97; 95% CI 1.97-18.03), polymicrobial infection (OR 2.84; 95% CI 1.13-7.12), and degree of wound induration (OR 1.06; 95% CI 1.02-1.10). Clinical success rates in the SI population were 88% in the linezolid group and 80% in the vancomycin group (p=0.14) at EOT and 80% in the linezolid group and 68% in the vancomycin group (p=0.04) at EOS. Microbiologic success rates were 83% in the linezolid group and 68% in the vancomycin group (p=0.004) at EOT and 71% in the linezolid group and 60% in the vancomycin group (p=0.05) at EOS. Patients who received linezolid had a lower probability of undergoing ≥2 SIs during drug treatment. Type of antibiotic received was the only modifiable predictor of a greater rate of SI during the drug-treatment period. In the patient population of the study, with cSSSIs other than cellulitis that were caused by MRSA, and in which at least one SI per patient was done within 72 h of the commencement of drug treatment, linezolid was associated with a higher rate of clinical success at EOS than was vancomycin, as well as with a higher rate of microbiologic success at both EOT and EOS.