title: Multicenter study of high-dose daptomycin for treatment of enterococcal infections.
abstract: Enterococci are among the leading pathogens isolated in hospital-acquired infections. Current antimicrobial options for vancomycin-resistant enterococci (VRE) are limited. Prior data suggest that daptomycin at >6 mg/kg of body weight/day may be used to treat enterococcal infections. We retrospectively evaluated the effectiveness and safety of high-dose daptomycin (HD-daptomycin) therapy (>6 mg/kg) in a multicenter cohort of adult patients with enterococcal infections to describe the characteristics and outcomes. Two hundred forty-five patients were evaluated. Enterococcus faecium was identified in 175 (71%), followed by Enterococcus faecalis in 49 (20%) and Enterococcus spp. in 21 (9%); overall, 204 (83%) isolates were VRE. Enterococcal infections included bacteremia (173, 71%) and intra-abdominal (35, 14%) and bone and joint (25, 10%) infections. The median dosage and duration of HD-daptomycin were 8.2 mg/kg/day (interquartile range [IQR], 7.7 to 9.7) and 10 days (IQR, 6 to 15), respectively. The overall clinical success rate was 89% (193/218), and microbiological eradication was observed in 93% (177/191) of patients. The median time to clearance of blood cultures on HD-daptomycin was 3 days (IQR, 2 to 5). The 30-day all-cause mortality rate was 27%, and 5 (2%) patients developed daptomycin-nonsusceptible enterococcal strains while on HD-daptomycin. Seven patients (3%) had creatine phosphokinase (CPK) elevation, yet no HD-daptomycin regimen was discontinued due to an elevated CPK and all patients were asymptomatic. Overall, there was a high frequency of clinical success and microbiological eradication in patients treated with HD-daptomycin for enterococcal infections, even in patients with complicated and difficult-to-treat infections. No adverse event-related discontinuation of HD-daptomycin was noted. HD-daptomycin may be an option for the treatment of enterococcal infections.
authors.affiliation: Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Casapao
authors.forename: Ravina
authors.initials: R
authors.lastname: Kullar
authors.forename: Susan L
authors.initials: SL
authors.lastname: Davis
authors.forename: Donald P
authors.initials: DP
authors.lastname: Levine
authors.forename: Jing J
authors.initials: JJ
authors.lastname: Zhao
authors.forename: Brian A
authors.initials: BA
authors.lastname: Potoski
authors.forename: Debra A
authors.initials: DA
authors.lastname: Goff
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Crank
authors.forename: John
authors.initials: J
authors.lastname: Segreti
authors.forename: George
authors.initials: G
authors.lastname: Sakoulas
authors.forename: Sara E
authors.initials: SE
authors.lastname: Cosgrove
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rybak
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D003402:Creatine Kinase / Q000097:blood; D017576:Daptomycin / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D016983:Enterococcus / Q000187:drug effects* / Q000254:growth & development; D013293:Enterococcus faecalis / Q000187:drug effects* / Q000254:growth & development; D016984:Enterococcus faecium / Q000187:drug effects* / Q000254:growth & development; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D003402:Creatine Kinase; D017576:Daptomycin