Determine the PK and Safety and Tolerability of ATM-AVI for the Treatment of cIAIs in Hospitalized Adults (REJUVENATE)

Inclusion Criteria

• Provision of informed consent
• Male or female from 18 to 90 years
• Female patients are authorized to participate in this clinical study if criteria concerning pregnancy avoidance stated in the protocol are met
• Diagnosis of cIAI

EITHER:

Intra-operative/postoperative enrolment with visual confirmation of cIAI. OR Preoperative enrollment with evidence of systemic inflammatory response, physical and radiological findings consistent with cIAI; confirmation of cIAI at time of surgery within 24 hours of study entry

• Patients who failed prior antibacterial treatment for their current cIAI can be enrolled but must:
• Have a known or suspected pathogen causing cIAI that is resistant to the prior therapy
• Require surgical intervention.
• Patient must have or will have a surgical intervention within 24 hours (before or after) the administration of the first dose of study drug

Exclusion criteria

• Involvement in the planning and/or conduct of the study
• Patient has been previously enrolled in this study, previously treated with ATM-AVI or previously participated in an investigational study containing AVI
• Patient has participated or intends to participate in any other clinical study that involves the administration of a study drug during the course of the study, or during the 30 days prior to study start.
• History of serious allergy, hypersensitivity (eg, anaphylaxis), or any serious reaction to aztreonam, carbapenem,monobactam or other β-lactam antibiotics, avibactam, nitroimidazoles or metronidazole, or any of the excipients of the study drugs
• Diagnosis of abdominal wall abscess; small bowel obstruction or ischemic bowel disease without perforation; traumatic bowel perforation with surgery within 12 hours of diagnosis; perforation of gastroduodenal ulcer with surgery within 24 hours of diagnosis primary etiology is not likely to be infectious
• Simple cholecystitis, gangrenous cholecystitis without rupture, simple appendicitis, acute suppurative cholangitis, infected necrotizing pancreatitis, pancreatic abscess or ischaemic/necrotic intestine without perforation
• Staged abdominal repair (STAR), open abdomen technique or where infection source control is not likely to be achieved; unlikely to solely respond to antimicrobial therapy
• Infection due to a pathogen that is unlikely to respond to ATM-AVI plus metronidazole
• Rapidly progressive or terminal illness
• Systemic antibacterial agents received within the 72- hour period prior to study entry, unless:
• A new infection and no more than 24 hours of prior antibiotic treatment received within the 72 hour period prior to study entry or
• Patient is considered to have failed the previous treatment
• Concurrent infection that may interfere with the evaluation of clinical cure for the study therapy
• requirement for effective concomitant systemic antibacterials or antifungals
• Creatinine clearance ≤30 ml/min or requirement for renal replacement therapy
• Acute hepatitis in the prior 6 months, chronic hepatitis, cirrhosis, acute hepatic failure, or acute decompensation of chronic hepatic failure
• Hepatic disease as indicated by AST or ALT >3 × ULN. Patients with AST and/or ALT >3 × ULN and 3 × ULN, unless isolated hyperbilirubinemia is directly related to cIAI or due to known Gilbert's disease
• ALP >3 × ULN. Patients with values >3 × ULN and <5 x ULN are eligible if acute and directly related to the infectious process being treated.
• Immunocompromising illness
• Active Clostridium difficile associated diarrhoea
• Any other condition that may confound the results of the study or pose additional risks
• Do not resuscitate order
• Absolute neutrophil count <1000/μL
• Hematocrit <25% or hemoglobin <8 gm/dL.
• Platelet count <75,000/μL.
• Currently receiving probenecid.
• Pregnant or breastfeeding or if of child bearing potential, not using a medically accepted effective method of birth control.
• Unli