Efficacy and safety of daptomycin for the treatment of infectious disease: a meta-analysis based on randomized controlled trials

A systematic review and meta-analysis based on randomized controlled trials (RCTs) of the efficacy and safety of daptomycin versus comparators. Electronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials and clinical registered trials) were searched to identify RCTs that assessed the efficacy and safety of daptomycin versus therapy with comparators. Two reviewers independently applied selection criteria, performed a quality assessment and extracted the data. The I-2 statistic was calculated for heterogeneity, and a random-effects or fixed-effects model was used for estimates of risk ratio (RR). The primary outcome assessed was clinical treatment success among the intention-to-treat (ITT) population. Thirteen trials fulfilled the inclusion criteria. Daptomycin was as efficacious as comparator regimens among the ITT population (RRaEuroS=aEuroS0.98, 95% CI 0.93-1.03) but had a lower efficacy among the clinically evaluable (CE) population (RRaEuroS=aEuroS0.96, 95% CI 0.93-1.00). Subgroup analyses according to the quality of the trial, the type of antibiotic and the type of infection did not alter the outcomes. No significant difference was identified for all-cause mortality between the daptomycin and comparator groups (RRaEuroS=aEuroS1.17, 95% CI 0.76-1.79) but daptomycin therapy did reduce the duration of treatment. Daptomycin caused a significantly lower incidence of renal impairment, nausea and headache but caused a reversible increase in creatine phosphokinase (CPK). Subgroup analysis indicated that daptomycin was significantly associated with a higher incidence of CPK elevation and fewer renal impairments among the population with a mean age a parts per thousand currency sign60 years and a dose of daptomycin a parts per thousand yen6 mg/kg/24 h. Daptomycin showed efficacy similar to the comparator regimens among the ITT population but lower efficacy among the CE population. Fewer adverse effects in total, but more CPK elevation effects, were observed in patients treated with daptomycin.