cilastatin--imipenem-drug-combination and Skin-Diseases--Bacterial

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.. 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).. 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.. 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.. 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.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cilastatin; Cilastatin, Imipenem Drug Combination; Diabetes Complications; Double-Blind Method; Drug Combinations; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Skin Diseases, Bacterial; Soft Tissue Infections; Thienamycins

Meropenem, a broad-spectrum carbapenem with potent in vitro activity, is postulated to be an effective monotherapy for the treatment of complicated skin and skin structure infections (cSSSI).. This multicenter, international, double-blind, randomized, prospective study of hospitalized patients with cSSSI evaluated the efficacy, safety, and tolerability of meropenem (500 mg IV q8h) versus imipenem-cilastatin (500 mg IV q8h). The primary efficacy endpoint was clinical outcome at follow-up in the clinically evaluable (CE) and modified intent-to-treat populations (MITT; patients who met eligibility criteria and received at least one dose of study drug). The study aimed to demonstrate non-inferiority (delta of 10%, 95% confidence intervals) in clinical response in the CE population. Clinical responses for all pathogens at follow-up were assessed in the fully evaluable population (CE population with baseline pathogen and follow-up cultures).. In total, 1,076 patients were enrolled. Of these, 692 patients comprised the MITT population (334 and 358 patients randomized to meropenem and imipenem-cilastatin, respectively) and 548 the CE population (261 and 287 patients randomized to meropenem and imipenem-cilastatin, respectively). Cure rates were 86.2% (meropenem) and 82.9% (imipenemcilastatin; 95% CI, -2.8, 9.3) in the CE population and 73.1% (meropenem) and 74.9% (imipenem-cilastatin; 95% CI, -8.4, 4.7) in the MITT population. The frequencies of adverse events and drug-related adverse events were similar between treatment groups.. In one of the largest studies conducted to date of hospitalized patients with cSSSI, meropenem, 500 mg IV q8h had comparable safety and efficacy to imipenem-cilastatin, 500 mg IV q8h.

Topics: Adolescent; Adult; Aged; Bacteria, Anaerobic; Cilastatin; Cilastatin, Imipenem Drug Combination; Double-Blind Method; Drug Combinations; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Imipenem; Male; Meropenem; Middle Aged; Skin Diseases, Bacterial; Soft Tissue Infections; Thienamycins; Treatment Outcome

Topics: Adolescent; Adult; Anti-Infective Agents; Bacteria; Cefazolin; Cilastatin; Cilastatin, Imipenem Drug Combination; Ciprofloxacin; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Ofloxacin; Skin Diseases, Bacterial; Soft Tissue Infections