Daptomycin-Containing Regimens for Treatment of Gram-Positive Endocarditis

Abstract

Background: Infective endocarditis (IE) is a severe infection and a leading cause of mortality and morbidity. In clinical practice, daptomycin is routinely used in IE for its favorable microbiological and pharmacological characteristics. Methods: A prospective study was conducted in a large tertiary-care hospital in Italy over an 8-year period (January 2010 - January 2018) on all patients with native- (NVE) or prosthetic-valve endocarditis (PVE) caused by gram-positive bacteria. Patients with NVE and PVE treated with regimens that included daptomycin at different dosages (daptomycin-containing regimens, DCR) were compared with those treated with non-DCR. The primary endpoints of the study were 30-day mortality and clinical treatment failure. Findings: During the study period, we analyzed 327 patients with gram-positive NVE (n=224, 68.8%) or PVE (n=103, 31.2%). Eighty-four (37.5%) NVE patients were treated with daptomycin, alone (59.9%) or with other antimicrobials. Most PVE patients (n=61, 58%) were treated with a DCR, which always consisted of daptomycin plus other drugs. Among PVE patients, treatment with a DCR was associated with lower 30-day mortality than treatment with a non-DCR (6.5% vs. 38%, p<0.001). Among NVE patients treated with DCRs, risk factors for 30-day mortality were streptococcal infections, persistent bacteremia, and standard-dose (4-6 mg/kg) rather than high-dose daptomycin therapy. Overall, surgical treatment of IE was associated with clinical success. Interpretation: Compared with non-DCRs, use of single- or multiple-drug DCRs is associated with lower 30-day mortality in PVE, but with higher 30-day mortality in NVE at approved doses and in the subgroup of streptococcal IE. Funding Statement: The authors state: No funding. Declaration of Interests: The authors state: None to declare. Ethics Approval Statement: The study was pre-approved by the local ethics committee and conducted in accordance with the principles of the Declaration of Helsinki.