Efficacy and Safety of Ceftazidime-Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-abdominal Infection: Results From a Randomized, Controlled, Double-Blind, Phase 3 Program

Clin Infect Dis. 2016 Jun 1;62(11):1380-1389. doi: 10.1093/cid/ciw133. Epub 2016 Mar 8.


Background: When combined with ceftazidime, the novel non-β-lactam β-lactamase inhibitor avibactam provides a carbapenem alternative against multidrug-resistant infections. Efficacy and safety of ceftazidime-avibactam plus metronidazole were compared with meropenem in 1066 men and women with complicated intra-abdominal infections from 2 identical, randomized, double-blind phase 3 studies (NCT01499290 and NCT01500239).

Methods: The primary end point was clinical cure at test-of-cure visit 28-35 days after randomization, assessed by noninferiority of ceftazidime-avibactam plus metronidazole to meropenem in the microbiologically modified intention-to-treat (mMITT) population (in accordance with US Food and Drug Administration guidance), and the modified intention-to-treat and clinically evaluable populations (European Medicines Agency guidance). Noninferiority was considered met if the lower limit of the 95% confidence interval for between-group difference was greater than the prespecified noninferiority margin of -12.5%.

Results: Ceftazidime-avibactam plus metronidazole was noninferior to meropenem across all primary analysis populations. Clinical cure rates with ceftazidime-avibactam plus metronidazole and meropenem, respectively, were as follows: mMITT population, 81.6% and 85.1% (between-group difference, -3.5%; 95% confidence interval -8.64 to 1.58); modified intention-to-treat, 82.5% and 84.9% (-2.4%; -6.90 to 2.10); and clinically evaluable, 91.7% and 92.5% (-0.8%; -4.61 to 2.89). The clinical cure rate with ceftazidime-avibactam plus metronidazole for ceftazidime-resistant infections was comparable to that with meropenem (mMITT population, 83.0% and 85.9%, respectively) and similar to the regimen's own efficacy against ceftazidime-susceptible infections (82.0%). Adverse events were similar between groups.

Conclusions: Ceftazidime-avibactam plus metronidazole was noninferior to meropenem in the treatment of complicated intra-abdominal infections. Efficacy was similar against infections caused by ceftazidime-susceptible and ceftazidime-resistant pathogens. The safety profile of ceftazidime-avibactam plus metronidazole was consistent with that previously observed with ceftazidime alone.

Clinical trials registration: NCT01499290 and NCT01500239.

Keywords: ceftazidime-avibactam plus metronidazole; complicated intra-abdominal infection; meropenem; noninferiority; phase 3.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents* / administration & dosage
  • Anti-Bacterial Agents* / adverse effects
  • Anti-Bacterial Agents* / therapeutic use
  • Azabicyclo Compounds* / administration & dosage
  • Azabicyclo Compounds* / adverse effects
  • Azabicyclo Compounds* / therapeutic use
  • Ceftazidime* / administration & dosage
  • Ceftazidime* / adverse effects
  • Ceftazidime* / therapeutic use
  • Drug Combinations
  • Female
  • Humans
  • Intraabdominal Infections / drug therapy*
  • Intraabdominal Infections / epidemiology
  • Male
  • Meropenem
  • Metronidazole* / administration & dosage
  • Metronidazole* / adverse effects
  • Metronidazole* / therapeutic use
  • Middle Aged
  • Thienamycins* / administration & dosage
  • Thienamycins* / adverse effects
  • Thienamycins* / therapeutic use
  • Treatment Outcome
  • Young Adult


  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • Drug Combinations
  • Thienamycins
  • avibactam, ceftazidime drug combination
  • Metronidazole
  • Ceftazidime
  • Meropenem

Associated data

  • ClinicalTrials.gov/NCT01499290
  • ClinicalTrials.gov/NCT01500239