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

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• 作者：Peter Fomin ; Mircea Beuran ; Audrius Gradauskas ; Giedrius Barauskas ; Alexey Datsenko ; Nathalie Dartois ; Evelyn Ellis-Grosse ; Evan Loh ; on behalf of the 306 Study Group
• 关键词：Complicated intra-abdominal infections ; Tigecycline ; Glycylcycline ; Imipenem/cilastatin ; Efficacy ; Safety ; In vitro activity
• 刊名：International Journal of Surgery
• 出版年：2005
• 出版时间：2005
• 年：2005
• 卷：3
• 期：1
• 页码：35-47
• 全文大小：274 K

文摘

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.