An Association between Reduced Susceptibility to Daptomycin and Reduced Susceptibility to Vancomycin in Staphylococcus aureus

To THE EDITOR—Daptomycin, a novel lipopeptide antimicrobial agent, is being used with increasing frequency for managing infections caused by drug-resistant, gram-positive bacteria with reduced susceptibility to vancomycin (including Staphylococcus aureus) [1]. Daptomycin has a unique mechanism of action, which includes Ca2+-dependent insertion of the agent into bacterial cytoplasmic membranes. Because the mechanism of action is unique, it was predicted that daptomycin would not exhibit cross-resistance with other antimicrobial agents. However, it appears that S. aureus with reduced susceptibility to vancomycin (i.e., isolates for which the vancomycin MICs are 4–16 µg/mL) also exhibit reduced susceptibility to daptomycin. This was initially described by Jevitt et al. [2], who reported a daptomycin MIC50 of 2 µg/mL and an MIC90 of 8 µg/mL for 19 isolates of S. aureus for which the vancomycin MICs were 4 µg/mL (16 isolates) or 8 µg/mL (3 isolates). S. aureus with daptomycin MICs of ⩽1 µg/mL are considered to be susceptible according to the Clinical and Laboratory Standards Institute [3]. In reviewing results for a larger number of independent S. aureus isolates submitted to the Centers for Disease Control and Prevention for antimicrobial susceptibility testing, we noted an association between a vancomycin MIC of 4 µg/mL or 8 µg/mL and a daptomycin MIC of ⩾2 µg/mL (P < .0001; χ2 test for trend) (table 1). Exceptions to this include glycopeptide intermediate S. aureus–992, a vancomycin-intermediate S. aureus isolate from New Jersey reported by Akins et al. [4], for which the vancomycin MIC was 8 µg/mL and the daptomycin MIC was 1 µg/mL. Results of susceptibility tests performed at the Centers for Disease Control and Prevention are consistent with those results. However, for the majority of other S. aureus isolates from the United States for which the vancomycin MICs are 4–16 µg/mL, the daptomycin MICs were ⩾2 µg/mL (i.e., nonsusceptible). Effect of increasing vancomycin MICs on daptomycin susceptibility for Staphylococcus aureus isolates. It is conceivable that the changes mediating reduced susceptibility to vancomycin in S. aureus, including a thickened cell wall, changes in cellular metabolism, and enhanced cell wall turnover, interfere with the antimicrobial action of daptomycin [5, 6]. However, the 5 vancomycin-resistant S. aureus isolates (MICs ⩾32 µg/mL) reported in the United States that contain the vanA resistance determinant [7–9, unpublished data] have all been susceptible to daptomycin (MICs ⩽1 µg/mL). Thus, vanA-mediated resistance does not appear to affect daptomycin susceptibility. On the basis of these observations, we suggest that clinicians exercise caution when considering daptomycin for treatment of an S. aureus infection when reduced susceptibility to vancomycin is suspected or documented. In such cases, the S. aureus isolate should be tested for susceptibility to daptomycin by either a broth microdilution or gradient diffusion method (e.g., Etest; AB Biodisk) prior to initiating therapy. Potential conflicts of interest. All authors: no conflicts.