Relationship of MIC and Bactericidal Activity to Efficacy of Vancomycin for Treatment of Methicillin-Resistant <i>Staphylococcus aureus</i> Bacteremia

TLDR

MRSA bacteremia refractory to conventional vancomycin therapy has been studied in multicenter prospective trials. The study aimed to determine whether microbiological characteristics of MRSA bloodstream isolates—specifically vancomycin MICs and in‑vitro bactericidal activity—predict clinical success with vancomycin and to elucidate mechanisms of intermediate‑level glycopeptide resistance. Thirty MRSA isolates from 30 patients were subjected to vancomycin susceptibility testing and 72‑hour in‑vitro bactericidal assays, with clinical and microbiological outcomes recorded. Logistic regression revealed that lower vancomycin MICs (≤0.5 µg/mL versus 1–2 µg/mL) and greater in‑vitro killing were significantly associated with higher treatment success (55.6 % versus 9.5 % and increasing success rates with greater killing), indicating that vancomycin failure risk rises within the susceptible range and that in‑vitro bactericidal potency can serve as prognostic information.

Abstract

ABSTRACT We attempted to find a relationship between the microbiological properties of bloodstream isolates of methicillin-resistant Staphylococcus aureus (MRSA) and the efficacy of vancomycin in the treatment of bacteremia. Vancomycin susceptibility testing was performed, and bactericidal activity was determined for 30 isolates from 30 different patients with MRSA bacteremia for whom clinical and microbiological outcome data were available. The majority of these patients had been previously enrolled in multicenter prospective studies of MRSA bacteremia refractory to conventional vancomycin therapy. Logistic regression found a statistically significant relationship between treatment success with vancomycin and decreases in both vancomycin MICs (≤0.5 μg/ml versus 1.0 to 2.0 μg/ml; P = 0.02) and degree of killing (reduction in 1og 10 CFU/milliliter) by vancomycin over 72 h of incubation in vitro ( P = 0.03). For MRSA isolates with vancomycin MICs ≤ 0.5 μg/ml, vancomycin was 55.6% successful in the treatment of bacteremia whereas vancomycin was only 9.5% effective in cases in which vancomycin MICs for MRSA were 1 to 2 μg/ml. Patients with MRSA that was more effectively killed at 72 h by vancomycin in vitro had a higher clinical success rate with vancomycin therapy in the treatment of bacteremia (log 10 &lt; 4.71 [ n = 9], 0%; log 10 4.71 to 6.26 [ n = 13], 23.1%; log 10 &gt; 6.27 [ n = 8], 50%). We conclude that a significant risk for vancomycin treatment failure in MRSA bacteremia begins to emerge with increasing vancomycin MICs well within the susceptible range. Elucidating the mechanisms involved in intermediate-level glycopeptide resistance in S. aureus should begin by examining bacteria that begin to show changes in vancomycin susceptibility before the development of obvious resistance. Prognostic information for vancomycin treatment outcome in MRSA bacteremia may also be obtained by testing the in vitro bactericidal potency of vancomycin.