Safety and Efficacy Study to Compare IV CXA 101/Tazobactam and Metronidazole With Meropenem in Complicated Intraabdominal Infections

Inclusion Criteria

• •Male or female, from 18 to 90 years of age, inclusive
• •One of the following diagnoses (in which there is evidence of intraperitoneal infection) including:(a) Cholecystitis (including gangrenous cholecystitis) with rupture, perforation, or progression of the infection beyond the gallbladder wall;(b)Diverticular disease with perforation or abscess; (c) Appendiceal perforation or periappendiceal abscess; (d) Acute gastric or duodenal perforation, only if operated on \>24 hours after perforation occurs; (e) Traumatic perforation of the intestine, only if operated on \> 12 hours after perforation occurs; (f) Peritonitis due to perforated viscus, postoperative or spread from other focus of infection (but not spontaneous \[primary\] bacterial peritonitis or peritonitis associated with cirrhosis and chronic ascites).Subjects with inflammatory bowel disease or ischemic bowel disease are eligible provided there is bowel perforation; or (g) Intraabdominal abscess (including liver and spleen).
• •Subject requires surgical intervention (e.g. laparotomy, laparoscopic surgery, or percutaneous draining of an abscess) within 24 hours of (before or after) the first dose of study drug
• •If subject is to be enrolled preoperatively, the subject must have radiographic evidence of bowel perforation or intraabdominal abscess
• •Subjects who failed prior antibacterial treatment for the current cIAI can be enrolled but must: (a) have a positive culture (from an intraabdominal site) and (b) require surgical intervention. Such subjects can be enrolled before the results of the culture are known; however, if the culture is negative, study drug administration must be discontinued.
• •Willing and able to comply with all study procedures and restrictions
• •Willing and able to provide written informed consent
• •Subjects with acute hepatic failure or acute decompensation of chronic hepatic failure
• •Hematocrit \< 25% or hemoglobin \< 8 gm/dL
• •Neutropenia with absolute neutrophil count \< 1000/mm3
• •Platelet count \< 75,000 /mm3. Subjects with a platelet count as low as 50,000 /mm3 are permitted if the reduction is historically stable.
• •Immunocompromising illness, including known human immunodeficiency virus (HIV) positivity or AIDS, organ (including bone marrow) transplant recipients, and hematological malignancy. Immunosuppressive therapy, including use of high-dose corticosteroid therapy (e.g. \>40 mg prednisone or equivalent per day for greater than 2 weeks).
• •History of hypersensitivity reactions to cephalosporins, carbapenems, penicillins, ß-lactamase inhibitors, metronidazole, or nitroimidazole derivatives. Subjects with a history of mild skin rash, not documented to be caused by previous ß-lactam use, may be enrolled.
• •Any condition or circumstance that, in the opinion of the Investigator, would compromise the safety of the subject or the quality of study data
• •Clinically significant abnormality in baseline electrocardiogram (ECG)
• •Participation in any investigational drug or device study within 30 days prior to study entry
• •Use of systemic antibiotic therapy for IAI for 24 or more hours in the 48-hour period prior to the first dose of study drug, unless there is a documented treatment failure with such therapy
• •More than one dose of an active non-study antibacterial regimen was given postoperatively. For subjects enrolled preoperatively, no postoperative non-study antibacterial therapy is allowed
• •who previously participated in a study with CXA-101
• •Subjects who previously received imipenem, meropenem, doripenem or cefepime for the current intraabdominal infection
• •Subjects who have received disulfiram in the past 14 days or who are currently receiving probenecid.