Tigecycline compared with imipenem/cilastatin in the treatment of complicated intra-abdominal infections
Abstract number: 1134_03_87
Ellis-Grosse E.J., Loh E.
Due to their diverse bacteriology and emergence of bacterial resistance, treatment of complicated intra-abdominal infections (cIAI) represents a clinical challenge. The efficacy of tigecycline (TGC) monotherapy, a novel, expanded broad-spectrum glycylcycline, was compared with imipenem/cilastatin (IMI/CIS) in adult hospitalized patients with cIAI.
In this double-blind, phase 3, multinational trial, patients were stratified by disease severity (APACHE II score <=15 vs >15 but <31), and randomly assigned to IV TGC (100 mg loading, then 50 mg q12h) or IV IMI/CIS adjusted for body weight (500/500 mg q6h for >=70 kg) for 514 days. Clinical response at test-of-cure (TOC, 1244 days after therapy) for microbiological evaluable (ME) and microbiological modified intent-to-treat (m-mITT) populations were co-primary efficacy endpoints in which cure/failure responses were determined.
Of 825 mITT patients who received more than 1 dose of study drug, 621 (75%) comprised the m-mITT cohort (309 TGC, 312 IMI/CIS) and 502 (61%) were ME (247 TGC, 255 IMI/CIS). Treatment groups were balanced with respect to demographic/baseline medical characteristics. Patients were predominately males (65%) with a mean age of 44 years. The primary diagnoses for the mITT group were complicated appendicitis (52%), perforation of intestine (10%), gastric/duodenal perforation (10%), cholecystitis (8%), and intraabdominal abscess (8%). The median duration of therapy was 7 days. For the ME group, clinical cure rates at TOC were 80.6% (199/247) for TGC vs 82.4% (210/255) for IMI/CIS (95% CI = 8.4, 5.1; p < 0.001). Corresponding clinical cure rates for the m-mITT cohort were 73.5% (227/309) for TGC vs 78.2% (244/312) for IMI/CIS (95% CI = 11.0, 2.5; p < 0.001). The most commonly reported adverse events for TGC and IMI/CIS were nausea (31.0% and 24.8%) and vomiting (25.7% and 19.4%).
TGC is an expanded-broad-spectrum IV glycylcycline with activity against gram-positive, gram-negative and anaerobic pathogens, including strains resistant to commonly used antibiotics. TGC met statistical criteria for non-inferiority to the comparator IMI/CIS and appears to be safe and effecacious in the treatment of hospitalized patients with cIAI.
|Session name:||XXIst ISTH Congress|
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