PurposeIn this multicentre, retrospective, matched cohort study we aimed to evaluate the outcomes of neutropenic fever cases that were treated with daptomycin or a glycopeptide (vancomycin or teicoplanin).MethodsData and outcomes of adult (aged>18-years old) patients with neutropenic fever [(1) without clinical and radiological evidence of pneumonia, (2) who were treated with daptomycin or a glycopeptide (teicoplanin or vancomycin) for any reason and for at least 72 h] were extracted from the hospital databases. Matching was performed with all of the three following criteria: (1) underlying disease, (2) reason for starting daptomycin or glycopeptide (microbiologic evidence vs. microbiologic evidence, clinical infection vs. clinical infection and empirical therapy vs. empirical therapy) and (3) neutropenic status.ResultsOverall 128 patients [(69/123) (56.1%) in the daptomycin cohort (D) and 59/123 (48%) in the glycopeptide cohort (G)] had a resolution of fever at the end of 72h antibiotic treatment (p=0.25). There was no significant difference in cured, improved and (cured+improved) rates between (D) and (G) cohorts as well as fever of unknown origin cases or microbiologically confirmed infections or clinically defined infections subgroups (p>0.05). There was also no significant difference (p>0.05), in terms of persistent response in the (D) versus (G) cohorts,ConclusionsThese findings suggest that although not better, daptomycin efficacy is comparable to vancomycin if used as empiric therapy in the treatment of adult febrile neutropenia. We conclude that daptomycin may be used at least as a salvage therapy alternative to glycopeptides in the treatment of adult febrile neutropenia cases. A large, randomized-controlled trial may further consolidate the evidence related to this question.