title: Prospective, non-comparative study of daptomycin for the treatment of superficial and deep incisional surgical site infections.
abstract: BACKGROUND
  Skin infections, including surgical site infections (SSIs), usually involve gram-positive pathogens and continue to be a leading cause of morbidity and death among hospital patients. The increasing prevalence of methicillin-resistant Staphylococcus aureus and other resistant strains accentuates the need for effective and safe therapies for such infections. This exploratory study evaluated the efficacy and safety of daptomycin in patients with gram-positive SSI according to wound classification.
  
  
  METHODS
  Eligible patients had an SSI with onset < 30 days after surgery, positive gram stain or culture at least three days before daptomycin therapy began, and three or more clinical signs and symptoms of infection. The incisional SSI was classified as superficial or deep according to the U.S. Centers for Disease Control and Prevention criteria. Patients with organ-space infections were excluded, as were those with major concomitant infections, foreign material in the incision that could not be removed, previous systemic antimicrobial therapy, or creatinine clearance < 30 mL/min. Daptomycin 4 mg/kg was administered intravenously once daily for 7-14 days. The primary efficacy endpoint was clinical response at the end of daptomycin therapy, and the safety assessment was based on adverse events (AEs).
  
  
  RESULTS
  Sixty-nine patients were enrolled, 60 of whom were evaluable for efficacy. Extremity wounds predominated among superficial incisional SSIs (n = 30), whereas abdominal wounds predominated among deep SSIs (n = 30). Patients with deep incisional SSI were more likely to be young, male, white, and febrile and to weigh more than patients with superficial SSIs. The overall clinical success rate was 92% (95% confidence interval [CI] 82-97%); the success rate was 100% in superficial incisional SSI and 83% in deep SSI (17% difference; 95% CI 0-33%). Staphylococcus aureus (28/36 methicillin-resistant) was the pathogen isolated most frequently. In 10 patients who were febrile at baseline, the median time to defervescence was five days, and the mean duration of treatment in the series was 11.2 days. Daptomycin was well tolerated. In most patients, AEs were mild or moderate in intensity; in two patients (one superficial, one deep), daptomycin was discontinued because of AEs.
  
  
  CONCLUSIONS
  The results of this exploratory study of SSI are consistent with those of previous studies of daptomycin in the treatment of diverse complicated skin and skin-structure infections, and suggest that wound classification should be treated as an important covariate in future studies of daptomycin and other antibiotics.
authors.affiliation: Cubist Pharmaceuticals Inc, Lexington, Massachusetts 02421, USA. andy.knapp@cubist.com
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Knapp
authors.forename: Ravi K
authors.initials: RK
authors.lastname: Kamepalli
authors.forename: William J
authors.initials: WJ
authors.lastname: Martone
authors.forename: Sara
authors.initials: S
authors.lastname: Yankelev
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D017576:Daptomycin / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006094:Gram-Positive Bacteria / Q000302:isolation & purification; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017192:Skin Diseases, Bacterial / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus; D013530:Surgical Wound Infection / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D016896:Treatment Outcome; D014481:United States
chemical_list: D000900:Anti-Bacterial Agents; D017576:Daptomycin