title: Multicenter evaluation of the clinical outcomes of daptomycin with and without concomitant β-lactams in patients with Staphylococcus aureus bacteremia and mild to moderate renal impairment.
abstract: Patients with underlying renal disease may be vulnerable to vancomycin-mediated nephrotoxicity and Staphylococcus aureus bacteremia treatment failure. In light of recent data demonstrating the successful use of β-lactam plus daptomycin in very difficult cases of S. aureus bacteremia, we examined safety and clinical outcomes for patients who received daptomycin with or without concomitant β-lactams. We identified 106 patients who received daptomycin for S. aureus bacteremia, had mild or moderate renal insufficiency according to FDA criteria, and enrolled in the Cubicin Outcomes Registry and Experience (CORE), a multicenter registry, from 2005 to 2009. Daptomycin treatment success was 81%. Overall treatment efficacy was slightly enhanced with the addition of a β-lactam (87% versus 78%; P = 0.336), but this trend was most pronounced for bacteremia associated with endocarditis or bone/joint infection or bacteremia from an unknown source (90% versus 57%; P = 0.061). Factors associated with reduced daptomycin efficacy (by logistic regression) were an unknown source of bacteremia (odds ratio [OR] = 7.59; 95% confidence interval [CI] = 1.55 to 37.2), moderate renal impairment (OR = 9.11; 95% CI = 1.46 to 56.8), and prior vancomycin failure (OR = 11.2; 95% CI = 1.95 to 64.5). Two patients experienced an increase in creatine phosphokinase (CPK) that resolved after stopping daptomycin. No patients developed worsening renal insufficiency related to daptomycin. In conclusion, daptomycin appeared to be effective and well tolerated in patients with S. aureus bacteremia and mild to moderate renal insufficiency. Daptomycin treatment efficacy might be enhanced with β-lactam combination therapy in primary endovascular and bone/joint infections. Additional studies will be necessary to confirm these findings.
authors.affiliation: Department of Medical Affairs, Cubist Pharmaceuticals, Lexington, MA, USA. pamela.moise@cubist.com
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Moise
authors.forename: Maria
authors.initials: M
authors.lastname: Amodio-Groton
authors.forename: Mohamad
authors.initials: M
authors.lastname: Rashid
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Lamp
authors.forename: Holly L
authors.initials: HL
authors.lastname: Hoffman-Roberts
authors.forename: George
authors.initials: G
authors.lastname: Sakoulas
authors.forename: Min J
authors.initials: MJ
authors.lastname: Yoon
authors.forename: Suzanne
authors.initials: S
authors.lastname: Schweitzer
authors.forename: Anjay
authors.initials: A
authors.lastname: Rastogi
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016470:Bacteremia / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D003402:Creatine Kinase / Q000378:metabolism; D017576:Daptomycin / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004697:Endocarditis, Bacterial / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D006801:Humans; D008297:Male; D012042:Registries; D051437:Renal Insufficiency / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D016896:Treatment Outcome; D047090:beta-Lactams / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D003402:Creatine Kinase; D017576:Daptomycin