Background: 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).
Methods: 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).
Results: 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.
Conclusion: 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.
