RÉSUMÉ
BACKGROUND: The indications of daptomycin have been extended to off-label indications including prosthesis-related infection, and bone and joint infection (BJI). However, efficacy and safety have not been thoroughly demonstrated compared with the standard of care. This systematic review and meta-analysis aimed to compare the treatment effect of daptomycin and glycopeptides for complicated infections. MATERIALS AND METHODS: MEDLINE, Embase and Web of Science were searched for randomized controlled trials (RCTs) comparing daptomycin and standard of care for Gram-positive infections, published until 30 June 2021. The primary outcome was defined as all-cause mortality. Secondary outcomes were clinical and microbiological success. The main safety outcome was any severe adverse event (SAE) (grade â≥3). RESULTS: Overall, eight RCTs were included in the meta-analysis, totalling 1095 patients. Six (75%) were in complicated skin and soft-structure infections, one (12.5%) in bacteraemia and one (12.5%) in a BJI setting. Six RCTs used vancomycin as a comparator and two used either vancomycin or teicoplanin. All-cause mortality and clinical cure were not different between groups. The microbiological cure rate was superior in patients who received daptomycin [risk ratio (RR)â=â1.17 (95% CI: 1.01-1.35)]. The risk of SAEs [RRâ=â0.57 (95% CI: 0.36-0.90)] was lower in the daptomycin arm. CONCLUSIONS: While daptomycin is associated with a significantly lower risk of SAEs and a better microbiological eradication, substantial uncertainty remains about the best treatment strategy in the absence of good-quality evidence, especially in bacteraemia and endocarditis where further RCTs should be conducted.