Volume 17, Number 11—November 2011
Reduced Susceptibility to Vancomycin in Staphylococcus aureus
To the Editor: I read with interest the article by Aguado et al. (1). I congratulate the authors for their high-quality research and would like to make 2 brief comments.
My first point regards the mechanism by which methicillin-susceptible Staphylococcus aureus (MSSA) with reduced susceptibility to vancomycin would also acquire decreased susceptibility to β-lactams. The authors “hypothesize that certain structural modifications might also occur in the cell wall of strains with high vancomycin MIC, including a thicker cell wall as it has been described in MRSA [methicillin-resistant S. aureus].” In addition to cell wall thickening, possible mechanisms could include reduction in autolysis (2,3) and in the cell wall content of penicillin binding protein 4 (PBP4) (3). A study of MSSA isolates has shown a reduction in autolysis and in the bactericidal activity of oxacillin after development of intermediate vancomycin susceptibility (2). Lower content of PBP4 and decreased autolysis were reported in MRSA isolates after reduced susceptibility to vancomycin developed after exposure to this antimicrobial drug (3). Decreased PBP4 has been associated with reduced methicillin susceptibility in S. aureus (4).
Second, knowing whether the authors had the exact vancomycin MIC of the isolates by broth microdilution to compare with the Etest results would be interesting. In the article, they only state that “all 99 MSSA strains were susceptible to vancomycin (MIC <2 μg/mL) by the broth microdilution method.” Although difficult to compare (because Etest dilution progression is arithmetic and broth microdilution is performed with a geometric dilution), some authors have found substantial differences between the vancomycin MIC results given by these 2 methods (5). These differences could have major laboratory and clinical implications.
- Aguado JM, San-Juan R, Lalueza A, Sanz F, Rodríguez-Otero J, Gómez-Gonzalez C, High vancomycin MIC and complicated methicillin-susceptible Staphylococcus aureus bacteremia. Emerg Infect Dis. 2011;17:1099–102.
- Pillai SK, Wennersten C, Venkataraman L, Eliopoulos G, Moellering R, Karchmer A. Development of reduced vancomycin susceptibility in methicillin-susceptible Staphylococcus aureus. Clin Infect Dis. 2009;49:1169–74.
- Sieradzki K, Tomasz A. Alterations of cell wall structure and metabolism accompany reduced susceptibility to vancomycin in an isogenic series of clinical isolates of Staphylococcus aureus. J Bacteriol. 2003;185:7103–10.
- Wyke AW, Ward JB, Hayes MV, Curtis NA. A role in vivo for penicillin-binding protein-4 of Staphylococcus aureus. Eur J Biochem. 1981;119:389–93.
- Mason EO, Lamberth LB, Hammerman WA, Hulten KG, Versalovic J, Kaplan SL. Vancomycin MICs for Staphylococcus aureus vary by detection method and have subtly increased in a pediatric population since 2005. J Clin Microbiol. 2009;47:1628–30.
In Response: We appreciate the comments by M. J. Mimica (1). We agree that mechanisms other than increased cell wall thickness, such as decreased autolysis, metabolic changes, and reduction in the cell wall content of penicillin binding protein 4, characterize Staphylococcus aureus isolates, and they could explain this reduced susceptibility not only to vancomycin but also to β-lactam antimicrobial drugs. A recently published report by Holmes et al. (2) confirms this hypothesis. That study showed that S. aureus vancomycin MIC >1.5 μg/mL, determined by Etest, was associated with a significantly higher death rate for patients with methicillin-susceptible S. aureus bacteremia irrespective of the type of antimicrobial drug used.
Unfortunately, the vancomycin MIC determined by broth microdilution could not be compared with the Etest results because all our isolates had a MIC by broth microdilution that oscillated between 0.5 and 1.0 µg/mL. No isolate had a MIC of 2 µg/mL. In the study by Holmes et al., vancomycin MICs were higher by Etest than by broth microdilution (1); however, all isolates were considered vancomycin susceptible by Clinical and Laboratory Standards Institute broth microdilution methods. The authors pointed out that they also found that increased mortality rate was associated with increased broth microdilution MIC (data not shown), although the trend was not so prominent (2).
A prospective study would be required to specifically investigate the relationship between vancomycin MIC and outcome of S. aureus bacteremia. Our group is performing such a prospective study that we hope will enable us to shed light on this relevant topic.
- Mimica MJ. Reduced susceptibility to vancomycin in Staphylococcus aureus [letter]. Emerg Infect Dis. 2011;17:2083–4.
- Holmes NE, Turnidge JD, Munckhof WJ, Robinson JO, Korman TM, O'Sullivan MV, Antibiotic choice may not explain poorer outcomes in patients with Staphylococcus aureus bacteremia and high vancomycin minimum inhibitory concentrations. J Infect Dis. 2011;204:340–7.