Daptomycin for serious enterococcal infection: a case for higher, MIC-informed dosing

The edition in brief

A Lancet Infectious Diseases review notes that daptomycin has no FDA or EMA licence, no randomised trials and no harmonised breakpoints for enterococcal bacteraemia or endocarditis, yet is widely used. CLSI treats Enterococcus faecium as susceptible dose-dependent at MIC 4 mg/L or less with 8–12 mg/kg daily, while EUCAST sets no breakpoint. Observational data link 10–12 mg/kg daily with lower mortality in vancomycin-resistant E faecium. The authors propose at least 8 mg/kg for E faecium, 10–12 mg/kg in vancomycin-resistant disease, MIC-informed dosing, a β-lactam partner in endocarditis and weekly creatine kinase checks. A meta-analysis of 23 studies and 5,734 patients with MDR-TB in low- and lower-middle-income countries put depression prevalence at 41.9%, with stigma, comorbidity, drug side effects, financial hardship and female sex linked to higher odds; heterogeneity was very high. A meta-analysis of 59 studies identified advanced HIV stage, low baseline and nadir CD4, hepatitis C, tuberculosis, injecting drug use, older age and male sex as predictors of poor CD4 recovery despite viral suppression.