Daptomycin-containing regimens for treatment of Gram-positive endocarditis

Abstract

Infective endocarditis (IE) is a severe infection, and a leading cause of mortality and morbidity. Due to its favourable microbiological and pharmacological characteristics, daptomycin is routinely used in clinical practice for treating IE. A prospective study was conducted at a large tertiary-care hospital in Italy over an 8-year period (January 2010-January 2018) on all patients with native-valve endocarditis (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. Primary endpoints of the study were 30-day mortality and clinical treatment failure. During the study period, 327 patients with Gram-positive NVE (n = 224, 68.8%) or PVE (n = 103, 31.2%) were analysed. 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 bacteraemia, and standard-dose (4-6 mg/kg) rather than high-dose daptomycin therapy. Overall, surgical treatment of IE and DCR were associated with clinical success and 30-day survival. Compared with non-DCRs, using single-drug 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 a subgroup of streptococcal IE.