-
Views
-
Cite
Cite
Jeff Alder, Barry I. Eisenstein, The Clinical Relevance and Correct Designation of Isolates Nonsusceptible to Daptomycin, Clinical Infectious Diseases, Volume 41, Issue 3, 1 August 2005, Pages 411–412, https://doi.org/10.1086/431765
Close - Share Icon Share
Extract
SIR—We read with interest the article by Mangili et al. [1] that described “daptomycin resistance” in Staphlycoccus aureus bacteremia during prolonged therapy. The isolate labeled as “resistant” had a daptomycin MIC value of 2 µg/mL, which is only 1 dilution over the breakpoint of 1 µg/mL. Daptomycin MIC values of 2 µg/mL are found, although uncommonly, in the wild-type distribution of S. aureus [2]. Although the baseline isolate tested as “susceptible” by disk diffusion (and was unavailable for MIC testing), a shift of as little as 2 mm in zone size (or a 1-dilution tube increase in MIC value) could have caused the interpretation to change from susceptible to nonsusceptible.
Importantly, daptomycin does not have a “resistant” category, according to the US Food and Drug Administration or Clinical Laboratory Standards Institute criteria; the correct designation is “nonsusceptible”—which is the designation applied when there is insufficient clinical information on resistance, as is typically the case with new classes of antibiotics. The daptomycin S. aureus breakpoints were set at 1 µg/mL, which abuts the MIC90 value of 0.5 µg/mL in a unimodal distribution curve [2]. In contrast, vancomycin susceptibility is designated as intermediate at 8 and 16 µg/mL and resistant at ⩾32 µg/mL, values that are placed well above the MIC90 value of 1 µg/mL, despite the fact that vancomycin is not as bactericidal as daptomycin and has a lower maximum serum concentration and a shorter half-life than daptomycin. The high breakpoint values for vancomycin, relative to its MIC90 value, undoubtedly have contributed to the dearth of resistance reports (n = 4). Vancomycin breakpoints were set in a different era. Additional data on the relationship between isolate MIC values and clinical outcomes, along with surveillance, pharmacokinetic, and pharmacodynamic data, can lead to the assignment of true intermediate and resistant breakpoints. Thus, it is a misnomer at this stage to designate a strain of S. aureus as “resistant” to daptomycin.
