| Eligibility Criteria: |
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
Exclusion Criteria:
- Women who are pregnant, nursing, or - if of child bearing potential - not using a
medically accepted, effective method of birth control (e.g. condom, oral
contraceptive, indwelling intrauterine device, or sexual abstinence)
- Diagnosis of abdominal wall abscess; small bowel obstruction or ischemic bowel disease
without perforation; traumatic bowel perforation with surgery within 12 hours;
perforation of gastroduodenal ulcer with surgery within 24 hours (these are considered
situations of peritoneal soiling before infection has become established); another
intraabdominal process in which the primary etiology is not likely to be infectious.
- Simple cholecystitis, gangrenous cholecystitis without rupture, simple appendicitis,
acute suppurative cholangitis, infected, necrotizing pancreatitis, or pancreatic
abscess
- cIAI managed by staged abdominal repair (STAR), open abdomen technique or any
situation where infection source control is not likely to be achieved
- Known prior to randomization to have an IAI or postoperative infection caused by
pathogen(s) resistant to meropenem
- Considered unlikely to survive the 4- to 5-week study period
- Any rapidly-progressing disease or immediately life-threatening illness (including
acute hepatic failure, respiratory failure and septic shock)
- The need for concomitant systemic antibacterial agents (other than vancomycin or
linezolid) in addition to study drug(s)
- Moderate or severe impairment of renal function (estimated CrCl < 50 mL/min), or
requirement for peritoneal dialysis, hemodialysis or hemofiltration, or oliguria (< 20
mL/h urine output over 24 hours)
- The presence of hepatic disease defined as: (a) ALT or AST > 4 x ULN; (b)Total
bilirubin >2 x ULN, unrelated to cholecystitis (c) Alkaline phosphatase >4 x ULN.
Subjects with a value >4 x ULN and <5 x ULN are eligible if this value is historically
stable.
- 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.
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