Reduced Vancomycin Susceptibility in MSSA Increases Complicated Infection

Summary and Comment |
July 13, 2017

Reduced Vancomycin Susceptibility in MSSA Increases Complicated Infection

  1. George Sakoulas, MD

Methicillin-susceptible Staphylococcus aureus infections with reduced susceptibility to vancomycin were more virulent, if not more lethal.

  1. George Sakoulas, MD

Staphylococcus aureus bloodstream infections remain a clinical challenge, particularly in patients with complicated bacteremia (endovascular focus, duration ≥72 hours on antibiotics, metastatic spread). Isolates with reduced vancomycin susceptibility have repeatedly but not consistently been associated with increased mortality and worse clinical outcomes in patients with either methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-susceptible S. aureus (MSSA) bacteremia (the latter treated with beta-lactams), suggesting a collateral intrinsic virulence phenotype with reduced vancomycin susceptibility. Now, researchers have examined outcomes in 252 patients with MSSA bacteremia according to presence of reduced vancomycin susceptibility.

The 84 patients with reduced susceptibility to vancomycin (vancomycin minimum inhibitory concentration [MIC] ≥2 mg/L) were more than twice as likely as the other cases to meet criteria for complicated infection (36% vs. 17%). Genotyping demonstrated a clonal association with reduced vancomycin susceptibility (Spa-CC002 and Spa-CC008). The reduced vancomycin susceptibility phenotype was not associated with increased mortality. In multivariate analysis, vancomycin MIC ≥2 mg/L remained a significant predictor of complicated infection (odds ratio, 2.35; 95% confidence interval, 1.26–4.37), as did Charlson score ≥3 (OR, 2.63; 95% CI, 1.09–6.37).

Comment

The precise clinical impact of reduced vancomycin susceptibility among MRSA and MSSA is heterogeneous, varying among individual hospitals and countries. However, the current findings add to mounting evidence that organisms with this microbiological phenotype differ in the host–pathogen interaction compared with more-susceptible S. aureus strains. The study also shows that the clinical consequences of reduced vancomycin susceptibility extend beyond pharmacokinetic and pharmacodynamic effects of glycopeptides to the beta-lactams used for MSSA. Reduced vancomycin susceptibility confers increased resistance to host cationic peptides produced by the innate immune system to fight bacterial infection, a phenotype associated with metastatic infection.

Editor Disclosures at Time of Publication

  • Disclosures for George Sakoulas, MD at time of publication Consultant / Advisory board: Allergan Pharmaceuticals; The Medicines Company Speaker’s bureau: Allergan Pharmaceuticals Grant / Research support: NIH Editorial boards: Antimicrobial Agents and Chemotherapy

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