Tigecycline is efficacious in the treatment of complicated intra-abdominal infections

Abstract

Background

Empiric treatment of complicated intra-abdominal infections (cIAI) represents a clinical challenge because of the diverse bacteriology and the emergence of bacterial resistance. The efficacy and safety of tigecycline (TGC), a first-in-class, expanded broad-spectrum glycylcycline antibiotic, were compared with imipenem/cilastatin (IMI/CIS) in patients with cIAI. Methods

In this prospective, double-blind, phase 3, multinational trial, patients were randomly assigned to intravenous (IV) TGC (100 mg initial dose, then 50 mg every 12 h) or IV IMI/CIS (500/500 mg every 6 h) for 5–14 days. Clinical response was assessed at the test-of-cure (TOC) visit (14–35 days after therapy) for microbiologically evaluable (ME) and microbiologically modified intent-to-treat (m-mITT) populations (co-primary efficacy endpoint populations in which cure/failure response rates were determined). Results

Of 817 mITT patients (i.e., received ≥ 1 dose of study drug), 641 (78%) comprised the m-mITT cohort (322 TGC, 319 IMI/CIS) and 523 (64%) were ME (266 TGC, 256 IMI/CIS). Patients were predominantly white (88%) and male (59%) with a mean age of 49 years. The primary diagnoses for the mITT group were complicated appendicitis (41%), cholecystitis (22%), and intra-abdominal abscess (11%). For the ME population, clinical cure rates at TOC were 91.3% (242/265) for TGC versus 89.9% (232/258) for IMI/CIS (95% CI −4.0, 6.8; P < 0.001). Corresponding clinical cure rates within the m-mITT population were 86.6% (279/322) for TGC versus 84.6% (270/319) for IMI/CIS (95% CI −3.7, 7.5; P < 0.001 for noninferiority TGC versus IMI/CIS). The most commonly reported adverse events for TGC and IMI/CIS were nausea (17.6% TGC versus 13.3% IMI/CIS; P = 0.100) and vomiting (12.6% TGC versus 9.2% IMI/CIS; P = 0.144). Conclusions

TGC is efficacious in the treatment of patients with cIAIs and TGC met per the protocol-specified statistical criteria for noninferiority to the comparator, IMI/CIS.