Should a Minimum Daptomycin 24-Hour Area Under the Curve of 666 mg × hour/L Be the Target in Staphylococcus aureus Infections?

Le résumé fourni par la source

To the Editor—We read with interest the study by Garreau et al published in Clinical Infectious Diseases describing the relation between daptomycin exposure and myotoxicity and daptomycin-induced eosinophilic pneumonia, which provided valuable data [1]. However, the claim that a 24-hour area under the curve (AUC24h) of at least 666 mg × hour/L is required for Staphylococcus aureus infections is unsubstantiated. While the authors rightly suggest targeting an AUC24h/minimum inhibitory concentration (MIC) ratio ≥666, they proceed to suggest that a minimum AUC24h >666 mg × hour/L is to be aimed at, apparently assuming that MIC is equal to 1 mg/L. However, according to data collected by the European Committee on Antimicrobial Susceptibility Testing, the wild-type distribution of MICs of daptomycin for S. aureus has its mode at 0.25 mg/L and the MIC90 is 0.5 mg/L [2]. Indeed, of 36 227 isolates, less than 2% have MIC of 1 mg/mL. Only for methicillin-resistant S. aureus isolates is the MIC90 1 mg/mL, and even in this case, 87% of the isolates have MIC of ≤0.5 mg/L [2]. Moreover, the authors cite 2 studies to support this minimum target [3, 4]. The first, by Falcone et al, does not establish this minimum target but cites another study conducted by Canut et al [5], which also assumes this target based on the work by Safdar et al in which it was found that a mean AUC24h /MIC ratio of 666 is required for 1-log killing for S. aureus [4]. This is based on 4 strains of S. aureus, all of which have an MIC of 0.5 mg/mL [4]. Other investigators reported an AUC24h/MIC ratio of 512 for 80% maximal kill and that this target would be exceeded in most patients receiving 6 mg/kg of daptomycin [6]. Similarly, Sader et al reported an MIC90 of 0.5 mg/L in 2 different studies, 1 of which included data on 4640 strains from 23 medical centers located in 10 European countries, Turkey, and Israel [7, 8]. Unfortunately, Garreau et al did not provide microbiological data on the isolates as well as data on daptomycin MICs. Unlike the case with the vancomycin revised consensus guideline [9], in which an MIC of 1 mg/L was assumed based on extensive data, in the case of daptomycin, most published data point to an MIC90 of 0.5 mg/L, thus making the assumption of an MIC of 1 mg/mL doubtful. Hence, a higher than needed and even potentially harmful target was recommended, based on an unlikely assumption. Targeting an AUC24h/MIC ratio of 666 when the MIC90 is 0.5 mg/L suggests that clinicians should target an AUC24h of 333 mg × hour/L in most cases of S. aureus infections and that higher exposure is needed only if MIC exceeds 0.5 mg/mL. We conclude that the assumption of MIC of 1 mg/L needs to be proved before a minimum AUC24h >666 mg × hour/L of daptomycin is recommended, and that the daptomycin MIC should be taken into consideration when planning the daptomycin dosage.

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