New Data Suggests Change in Daptomycin Breakpoint for Enterococcal Bacteremia

A ratio of free (unbound) drug area under the concentration-time curve (fAUC) to minimum inhibitory concentration (MIC) for daptomycin, which was >27.43, was associated with an increased likelihood for 30-day survival in low-acuity patients with enterococcal bacteremia, and the probability of target attainment was <90% at the current susceptibility breakpoint for doses ≤12 mg/kg/day, according to findings published in Clinical Infectious Diseases.

Preclinical research has demonstrated that the free (unbound) drug area under the concentration-time curve to MIC ratio (fAUC/MIC) is the pharmacodynamic parameter most predictive of effective bactericide, but the precise ratio needed for the best outcomes in severe enterococcal infections remains unknown. In this study, the researchers pooled data from 7 observational studies that assessed outcomes for 114 patients with enterococcal bacteremia who were treated with daptomycin monotherapy.

Of this cohort, 67 (58.8%) were alive after 30 days, and in low-acuity patients in this group, the median fAUC/MIC was higher (32.9 vs 26.0; P =.085); significantly higher daptomycin doses were prescribed (7.7 vs 6.3 mg/kg/dose; P =.023) in this group. The median daptomycin MIC (2 mg/L) was similar between patients who were alive and those who were deceased at 30 days (P =.607). In contrast, significant relationships with fAUC/MIC thresholds were not identified in high-acuity patients only.

“These data justify a lower breakpoint for enterococci [, and] strategies that employ higher daptomycin doses to maximize fAUC/MIC should be seriously considered in deep-seated enterococcal infections,” concluded the authors.

Reference

Avery LM, Kuti JL, Weisser M, et al. Pharmacodynamic analysis of daptomycin-treated enterococcal bacteremia: it is time to change the breakpoint [published online September 5, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy749