Compare Ceftazidime-Avibactam + Metronidazole vs Meropenem for Hospitalized Adults With Complicated Intra-Abd Infections

• Drug: Ceftazidime-avibactam
  
  Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg
• Drug: metronidazole
  
  Metronidazole 500mg/100ml solution for infusion
• Drug: Meropenem
  
  Meropenem powder for solution for infusion 1000mg

• Experimental: Ceftazidime-Avibactam plus metronidazole
  
  Interventions:
  

  • Drug: Ceftazidime-avibactam
  • Drug: metronidazole
• Active Comparator: Meropenem
  
  Intervention: Drug: Meropenem

• Li J, Lovern M, Green ML, Chiu J, Zhou D, Comisar C, Xiong Y, Hing J, MacPherson M, Wright JG, Riccobene T, Carrothers TJ, Das S. Ceftazidime-Avibactam Population Pharmacokinetic Modeling and Pharmacodynamic Target Attainment Across Adult Indications and Patient Subgroups. Clin Transl Sci. 2019 Mar;12(2):151-163. doi: 10.1111/cts.12585. Epub 2018 Sep 28.
• Nichols WW, Stone GG, Newell P, Broadhurst H, Wardman A, MacPherson M, Yates K, Riccobene T, Critchley IA, Das S. Ceftazidime-Avibactam Susceptibility Breakpoints against Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2018 Oct 24;62(11). pii: e02590-17. doi: 10.1128/AAC.02590-17. Print 2018 Nov.
• Stone GG, Newell P, Gasink LB, Broadhurst H, Wardman A, Yates K, Chen Z, Song J, Chow JW. Clinical activity of ceftazidime/avibactam against MDR Enterobacteriaceae and Pseudomonas aeruginosa: pooled data from the ceftazidime/avibactam Phase III clinical trial programme. J Antimicrob Chemother. 2018 Sep 1;73(9):2519-2523. doi: 10.1093/jac/dky204.
• Qin X, Tran BG, Kim MJ, Wang L, Nguyen DA, Chen Q, Song J, Laud PJ, Stone GG, Chow JW. A randomised, double-blind, phase 3 study comparing the efficacy and safety of ceftazidime/avibactam plus metronidazole versus meropenem for complicated intra-abdominal infections in hospitalised adults in Asia. Int J Antimicrob Agents. 2017 May;49(5):579-588. doi: 10.1016/j.ijantimicag.2017.01.010. Epub 2017 Mar 29.

Inclusion Criteria:

• Patient must be 18 to 90 years of age, inclusive,
• Female patients can participate if they are surgically sterilized or postmenopausal for at least 1 year or her sexual partner has had a vasectomy
• Female of childbearing potential has had normal menstrual periods for 3 months and negative serum pregnancy test and agree to practice highly effective methods of birth control during treatment and for at least 7 days after last dose
• Intraoperative/postoperative enrollment with visual confirmation (presence of pus within the abdominal cavity) of an intra-abdominal infection associated with peritonitis
• Confirmation of infection by surgical intervention within 24 hours of entry: evidence of systemic inflammatory indicators; physical findings consistent with intra-abdominal infection; supportive radiologic imaging findings of intra-abdominal infections

Exclusion Criteria:

• Patient is diagnosed with traumatic bowel perforation undergoing surgery within 12 hours; perforation of gastroduodenal ulcers undergoing surgery within 24 hours. Other intra-abdominal processes in which primary etiology is not likely to be infectious
• Patient has abdominal wall abscess or bowel obstruction without perforation or ischemic bowel without perforation
• Patients whose surgery will include staged abdominal repair, or "open abdomen" technique, or marsupialization
• Patient has suspected intra-abdominal infections due to fungus, parasites, virus or tuberculosis
• Patient is considered unlikely to survive the 6- to 8-week study period or has a rapidly progressive or terminal illness, including septic shock that is associated with a high risk of mortality