Meropenem versus imipenem-cilastatin for the treatment of hospitalized patients with complicated skin and skin structure infections: results of a multicenter, randomized, double-blind comparative study.
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.


CONCLUSIONS
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.
Fabian
Timothy C
TC
University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. tfabian@utmem.edu
File
Thomas M
TM
Embil
John M
JM
Krige
Jacobus E J
JE
Klein
Stanley
S
Rose
Andrea
A
Melnick
David
D
Soto
Norberto E
NE
D000293:Adolescent; D000328:Adult; D000368:Aged; D001421:Bacteria, Anaerobic / Q000302:isolation & purification; D015377:Cilastatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000077728:Cilastatin, Imipenem Drug Combination; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006090:Gram-Negative Bacteria / Q000302:isolation & purification; D006094:Gram-Positive Bacteria / Q000302:isolation & purification; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D000077731:Meropenem; D008875:Middle Aged; D017192:Skin Diseases, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D018461:Soft Tissue Infections / Q000188:drug therapy* / Q000382:microbiology; D013845:Thienamycins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D004338:Drug Combinations; D013845:Thienamycins; D015377:Cilastatin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination; D000077731:Meropenem