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3204153 
Journal Article 
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 
Mazuski, JE; Gasink, LB; Armstrong, J; Broadhurst, H; Stone, GG; Rank, D; Llorens, L; Newell, P; Pachl, J 
2016 
Yes 
Clinical Infectious Diseases
ISSN: 1058-4838
EISSN: 1537-6591 
English 
26962078 
BACKGROUND:  When combined with ceftazidime, the novel non-β-lactam β-lactamase inhibitor avibactam provides a carbapenem alternative against multi-drug-resistant infections. Efficacy and safety of ceftazidime-avibactam plus metronidazole were compared with meropenem in 1066 men and women with complicated intra-abdominal infections (cIAI) from 2 identical, randomized, double-blind phase 3 studies (NCT01499290 and NCT01500239).

METHODS:  Primary endpoint was clinical cure at test-of-cure visit 28-35 days after randomization, assessed by non-inferiority 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 MITT and clinically evaluable (CE) populations (European Medicines Agency guidance). Non-inferiority was considered met if the lower-limit of the 95% CI for between-group difference was greater than the pre-specified non-inferiority margin -12.5%.

FINDINGS:  Ceftazidime-avibactam plus metronidazole was non-inferior to meropenem across all primary analysis populations. Clinical cure rates (between-group difference, 95% CI) with ceftazidime-avibactam plus metronidazole and meropenem, respectively, were: mMITT population, 81.6% and 85.1% (-3.5%, -8.64 to 1.58); MITT, 82.5% and 84.9% (-2.4%, -6.90 to 2.10); CE, 91.7% and 92.5% (-0.8%, -4.61 to 2.89). Clinical cure with ceftazidime-avibactam plus metronidazole against ceftazidime-resistant infections was comparable with meropenem (mMITT population, 83.0% and 85.9%, respectively) and similar to its own efficacy against ceftazidime-susceptible infections (82.0%). Adverse events were similar between groups.

INTERPRETATION:  Ceftazidime-avibactam plus metronidazole was non-inferior to meropenem in the treatment of cIAI. 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.