title: Efficacy and safety of daptomycin in patients with renal impairment: a multicenter retrospective analysis.
abstract: OBJECTIVE
  Daptomycin is a therapeutic option for patients with underlying renal insufficiency who are vulnerable to nephrotoxicity from vancomycin. We evaluated the efficacy and safety of daptomycin in patients with renal impairment.
  
  
  METHODS
  Multicenter, retrospective, observational, case series analysis.
  
  
  METHODS
  Two academic medical centers.
  
  
  METHODS
  One hundred and sixty adults with creatinine clearance (Clcr ) of 50 ml/minute or less who received daptomycin for at least 72 hours for complicated Gram-positive infections from 2008-2011.
  Clinical and microbiologic outcomes were assessed at the end of daptomycin therapy. Safety evaluations were documented for all patients, and when available, creatine phosphokinase (CPK) levels were recorded. Thirty-eight (23.8%) patients were on hemodialysis, and 122 (76.3%) had a decreased baseline renal clearance not requiring hemodialysis with a median interquartile range (IQR) Clcr of 32.4 ml/minute (24.2-40.4 ml/min). The median (IQR) daptomycin dose was 6.0 mg/kg (5.8-7.8 mg/kg) administered every 24 hours in 68 patients (42.5%) and every 48 hours in 92 patients (57.5%). Daptomycin success, including cure or improvement, (Cure: signs and symptoms resolved and no additional antibiotic therapy required, or infection cleared with negative cultures reported at the end of daptomycin therapy; Improvement: partial resolution of signs and symptoms and additional antibiotic therapy necessary at the end of daptomycin therapy) was achieved in 128 of 160 (80.0%) patients at the end of therapy. Methicillin-resistant Staphylococcus aureus (MRSA) was the most common pathogen (45%) isolated. The most frequent reason for using daptomycin was due to vancomycin-associated nephrotoxicity (20%). Daptomycin therapy was discontinued in six patients (3.8%) because of elevated CPK (median time to onset, 11.5 days). Loss of daptomycin susceptibility occurred in two patients with complex endovascular infections who were on hemodialysis.
  
  
  CONCLUSIONS
  Daptomycin demonstrated clinical and microbiologic success rates comparable with prior studies. Discontinuation of therapy because of elevated CPK levels may have been avoided in some patients with adjustment to every 48-hour dosing for Clcr less than 30 ml/minute. The relatively early time to onset suggests the need for CPK monitoring more frequently than once/week in renally impaired patients receiving daptomycin. The treatment of bacteremia in patients with renal insufficiency warrants further study.
authors.affiliation: Department of Medical Affairs, Cubist Pharmaceuticals, Lexington, Massachusetts; College of Pharmacy, Oregon State University/Oregon Health and Science University, Portland, Oregon.
authors.forename: Ravina
authors.initials: R
authors.lastname: Kullar
authors.forename: Ian
authors.initials: I
authors.lastname: McClellan
authors.forename: Matthew
authors.initials: M
authors.lastname: Geriak
authors.forename: George
authors.initials: G
authors.lastname: Sakoulas
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003402:Creatine Kinase / Q000378:metabolism; D003404:Creatinine / Q000097:blood / Q000652:urine; D017576:Daptomycin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D024881:Drug Resistance, Bacterial; D005260:Female; D006094:Gram-Positive Bacteria / Q000302:isolation & purification; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000150:complications* / Q000503:physiopathology / Q000628:therapy; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D003404:Creatinine; D003402:Creatine Kinase; D017576:Daptomycin
keywords: MRSA infections; daptomycin; renally impaired