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 (< or =0.5 microg/ml versus 1.0 to 2.0 microg/ml; P = 0.02) and degree of killing (reduction in log(10) CFU/milliliter) by
vancomycin over 72 h of incubation in vitro (P = 0.03). For MRSA isolates with
vancomycin MICs < or = 0.5 microg/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 microg/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) < 4.71 [n = 9], 0%; log(10) 4.71 to 6.26 [n = 13], 23.1%; log(10) > 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.