Vancomycin MICs and risk of complicated bacteremia by glycopeptide-susceptible Staphylococcus aureus

Abstract

Vancomycin (VAN) minimum inhibitory concentrations (MICs) at the upper end of the susceptible range for Staphylococcus aureus (S. aureus), as measured by the Etest method, have been associated with poor clinical outcomes of S. aureus bloodstream infections, as has the isolate's genetic background. Here, we assessed the impact of VAN MICs, as determined by a broth microdilution method (BMD) that incorporates incremental VAN concentrations between the conventional log₂ dilutions, isolate susceptibility to killing by human phagocytes, acting as a surrogate marker for bacterial cell wall thickness, and S. aureus genetic composition, on the development of complicated S. aureus bacteremia (SAB). We carried out a retrospective, observational single-center cohort study of 148 consecutive patients with SAB caused by methicillin-susceptible (MSSA) isolates (n = 113) or methicillin-resistant (MRSA) isolates (n = 35). S. aureus isolates were genotyped using a commercially available DNA microarray. Overall, VAN MICs of S. aureus isolates taken from complicated and uncomplicated SAB were comparable, irrespective of the testing method (P = 0.19 with BMD, and P = 0.94 with Etest). Likewise, S. aureus isolates in both comparison groups had the same susceptibility to killing by human phagocytes (P = 0.5). Among the genes screened by the S. aureus DNA array, only Sec and Sel were differentially present among S. aureus isolates in both groups (overrepresented in those causing complications) and their presence was associated independently with complicated SAB in multivariate models adjusted for potentially relevant clinical covariates. Separate analysis of MSSA SAB episodes yielded similar results.

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