A multicenter trial of the efficacy and safety of tigecycline versus imipenem/cilastatin in patients with complicated intra-abdominal infections [Study ID Numbers: 3074A1-301-WW; ClinicalTrials.gov Identifier: NCT00081744].
BACKGROUND
Complicated intra-abdominal infections (cIAI) remain challenging to treat because of their polymicrobial etiology including multi-drug resistant bacteria. The efficacy and safety of tigecycline, an expanded broad-spectrum glycylcycline antibiotic, was compared with imipenem/cilastatin (IMI/CIS) in patients with cIAI.


METHODS
A prospective, double-blind, multinational trial was conducted in which patients with cIAI randomly received intravenous (IV) tigecycline (100 mg initial dose, then 50 mg every 12 hours [q12h]) or IV IMI/CIS (500/500 mg q6h or adjusted for renal dysfunction) for 5 to14 days. Clinical response at the test-of-cure (TOC) visit (14-35 days after therapy) for microbiologically evaluable (ME) and microbiological modified intent-to-treat (m-mITT) populations were the co-primary efficacy endpoint populations.


RESULTS
A total of 825 patients received >or= 1 dose of study drug. The primary diagnoses for the ME group were complicated appendicitis (59%), and intestinal (8.8%) and gastric/duodenal perforations (4.6%). For the ME group, clinical cure rates at TOC were 80.6% (199/247) for tigecycline versus 82.4% (210/255) for IMI/CIS (95% CI -8.4, 5.1 for non-inferiority tigecycline versus IMI/CIS). Corresponding clinical cure rates within the m-mITT population were 73.5% (227/309) for tigecycline versus 78.2% (244/312) for IMI/CIS (95% CI -11.0, 2.5). Nausea (31.0% tigecycline, 24.8% IMI/CIS [P = 0.052]), vomiting (25.7% tigecycline, 19.4% IMI/CIS [P = 0.037]), and diarrhea (21.3% tigecycline, 18.9% IMI/CIS [P = 0.435]) were the most frequently reported adverse events.


CONCLUSIONS
This study demonstrates that tigecycline is as efficacious as imipenem/cilastatin in the treatment of patients with cIAI.
Oliva
María E
ME
Hospital San Martin, Provincia de Entre Rios, Argentina. mariaeugeniaoliva@yahoo.com.ar
Rekha
Arcot
A
Yellin
Albert
A
Pasternak
Jacyr
J
Campos
Maria
M
Rose
Gilbert M
GM
Babinchak
Timothy
T
Ellis-Grosse
Evelyn J
EJ
Loh
Evan
E
D000005:Abdomen / Q000382:microbiology*; D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000494:pharmacology*; D001064:Appendicitis / Q000150:complications; D001424:Bacterial Infections / Q000188:drug therapy* / Q000209:etiology; D002764:Cholecystitis / Q000150:complications / Q000188:drug therapy; D015377:Cilastatin / Q000009:adverse effects / Q000494:pharmacology; D000077728:Cilastatin, Imipenem Drug Combination; D004238:Diverticulitis / Q000150:complications / Q000188:drug therapy; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D015378:Imipenem / Q000009:adverse effects / Q000494:pharmacology; D007416:Intestinal Perforation / Q000150:complications; D008297:Male; D008875:Middle Aged; D008911:Minocycline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D010439:Peptic Ulcer Perforation / Q000150:complications; D010538:Peritonitis / Q000150:complications / Q000188:drug therapy; D000078304:Tigecycline
D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D015377:Cilastatin; D000078304:Tigecycline; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination; D008911:Minocycline