Clinical implications of varying degrees of vancomycin susceptibility in methicillin-resistant Staphylococcus aureus bacteremia

Abstract

We conducted a retrospective study of the clinical aspects of bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) with heterogeneously reduced susceptibility to vancomycin. Bloodstream MRSA isolates were screened for reduced susceptibility by using brain-heart infusion agar, including 4 mg/L vancomycin with and without 4% NaCl. Patients whose isolates exhibited growth (case-patients) were compared with those whose isolates did not (controls) for demographics, coexisting chronic conditions, hospital events, antibiotic exposures, and outcomes. Sixty-one (41%) of 149 isolates exhibited growth. Subclones from 46 (75%) of these had a higher MIC of vancomycin than did their parent isolates. No isolates met criteria for vancomycin heteroresistance. No differences in potential predictors or in outcomes were found between case-patients and controls. These data show that patients with vancomycin-susceptible MRSA bacteremia have similar baseline clinical features and outcomes whether or not their bacterial isolates exhibit growth on screening media containing vancomycin.

Figure 1

Pulsed-field gel electrophoresis of selected isolates, demonstrating predominant and secondary types. Lane 1, Staphylococcus aureus NCTC 8325, used as DNA molecular weight reference marker; lanes 2 and 3, clinical isolates of type A13; lane 4, clinical isolate of type A1; lane 5, clinical isolate of type B2; lane 6, clinical isolate of type H.

Figure 2

a) Population analysis of parent isolates and reference strains. PC3, vancomycin- intermediate Staphylococcus aureus (VISA) reference strain (published vancomycin MIC 8 mg/L (19); MIC 4 mg/L by our assay); ATCC, methicillin-resistant S. aureus (MRSA) reference strain ATCC 33591 (MIC 1 mg/L by our assay); clinical isolates exhibiting growth on screening media (MIC in parentheses, in mg/L, followed by MIC of subclone)—302 (1, 4), 354 (0.5, 1), 1150 (1,2), 1203 (1,2); clinical isolates with no growth on screening media (MIC in parentheses, in mg/L)—328 (1), 736 (1), 744 (1), 1149 (1). Isolates with growth on screening media are represented by solid lines; isolates with no growth are represented by broken lines. Isolates 354 and 1150 were cultured from the same patient, 14 months apart. b) Population analysis of an MRSA bloodstream isolate exhibiting heterogeneously reduced susceptibility to vancomycin, and its subclone, compared with reference strains. ATCC, MRSA reference strain ATCC 33591 (MIC 1 mg/L by our assay); PC3, VISA reference strain (published MIC 8 mg/L (19); MIC 4 mg/L by our assay); 1337, clinical isolate (MIC 1 mg/L); 1337d, subclone of 1337 grown on screening media (MIC 2 mg/L). While the population curve representing 1337d closely resembles that of PC3, this subclone did not meet MIC criteria for VISA. CFU, colony-forming units.