title: A post hoc subgroup analysis of meropenem versus imipenem/cilastatin in a multicenter, double-blind, randomized study of complicated skin and skin-structure infections in patients with diabetes mellitus.
abstract: BACKGROUND
  In a multicenter, international, double-blind, randomized clinical trial involving hospitalized patients with complicated skin and skin-structure infections (cSSSIs), meropenem and imipenem/cilastatin (both administered 500 mg intravenously every 8 hours) were not significantly different in their efficacy and safety profiles.
  
  
  OBJECTIVE
  The objective of the post hoc subgroup analysis discussed in the current article was to report the efficacy and tolerability of meropenem and imipenem/cilastatin for the treatment of cSSSIs in patients with or without underlying diabetes mellitus (DM).
  
  
  METHODS
  Hospitalized patients aged > or =13 years with evidence of cSSSIs were eligible for inclusion. Patients were randomized to receive meropenem or imipenem/cilastatin, each 500 mg intravenously every 8 hours, for at least 3 days and up to a maximum of 14 days. Patients were analyzed according to the presence or absence of DM and by the pathogen(s) isolated from wound cultures at baseline, end of N treatment, and test-of-cure visits. The primary efficacy end point was clinical outcome at the posttreatment follow-up (test-of-cure) visit in the clinically evaluable and modified intent-to-treat (intent-to-treat [ITT] subjects who met all eligibility criteria) populations; this was defined as 7 to 14 days after final administration of antibiotics. The secondary efficacy end points included clinical response at the test-of-cure visit in the ITT population (ie, those who received >1 dose of study drug) and at the end of N treatment visit in the clinically evaluable and fully evaluable populations. At baseline, the end of N treatment, and the test-of-cure visits, specimens were obtained from the most extensive site of skin and skin-structure infection and were cultured for bacteria. Adverse events were monitored daily during treatment and for 30 days after the completion of all antibiotic treatment.
  
  
  RESULTS
  Of the 1076 patients enrolled in the original study, 398 had DM. The mean ages of patients with and without DM were 55 and 45 years, respectively; 17.3% of patients with DM and 6.1% of patients without DM had impaired renal function at study entry. Complex abscess was the most common infection diagnosis in both groups (patients with DM, 30.0%; patients without DM, 48.8%). The other top infections per group (patients with and without DM, respectively) were as follows: cellulitis, 24.6% and 12.4%; and ischemic/diabetic ulcers, 20.9% and 1.9%. Gram-negative aerobic and anaerobic pathogens accounted for >40% of bacterial isolates from both groups, with polymicrobial infections reported in 44.2% of patients with DM and 34.0% of patients without DM. In the clinically evaluable population, the satisfactory clinical response rate was 85.6% for patients with DM receiving meropenem and 72.4% for those receiving imipenem/cilastatin; for patients without DM, those rates were 86.6% and 89.0%, respectively. Meropenem and imipenem/cilastatin were generally well tolerated. Reported adverse events were similar between groups.
  
  
  CONCLUSIONS
  This subgroup analysis found that 500 mg every 8 hours intravenously of meropenem or imipenem/cilastatin appeared efficacious and well tolerated for the treatment of cSSSIs among these patients with and without DM.
authors.affiliation: Infection Prevention and Control Unit, Health Sciences Centre, Winnipeg, Manitoba, Canada. Electronic address: JEmbil@exchange.hsc.mb.ca.
authors.forename: John M
authors.initials: JM
authors.lastname: Embil
authors.affiliation: AstraZeneca Pharmaceuticals LP, Wilmington, Delaware, USA.
authors.forename: Norberto E
authors.initials: NE
authors.lastname: Soto
authors.affiliation: AstraZeneca Pharmaceuticals LP, Wilmington, Delaware, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Melnick
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015377:Cilastatin / Q000627:therapeutic use; D000077728:Cilastatin, Imipenem Drug Combination; D048909:Diabetes Complications / Q000188:drug therapy*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D015378:Imipenem / Q000627:therapeutic use; D008297:Male; D000077731:Meropenem; D008875:Middle Aged; D017192:Skin Diseases, Bacterial / Q000188:drug therapy*; D018461:Soft Tissue Infections / Q000188:drug therapy*; D013845:Thienamycins / Q000627:therapeutic use*
chemical_list: D004338:Drug Combinations; D013845:Thienamycins; D015377:Cilastatin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination; D000077731:Meropenem