Activity of Ceftazidime-Avibactam against Isolates from Patients in a Phase 3 Clinical Trial for Treatment of Complicated Intra-abdominal Infections.

The increasing prevalence of multidrug-resistant Gram-negative pathogens has generated a requirement for new treatment options. Avibactam, a novel non-β-lactam-β-lactamase inhibitor, restores the activity of ceftazidime against Ambler class A, C, and some class D β-lactamase-producing strains of and The activities of ceftazidime-avibactam versus comparators were evaluated against 1,440 clinical isolates obtained in a phase 3 clinical trial in patients with complicated intra-abdominal infections (cIAI; ClinicalTrials.gov identifier NCT01499290). Overall, activities were determined for 803 , 70 , 304 Gram-positive aerobic, and 255 anaerobic isolates obtained from 1,066 randomized patients at baseline. Susceptibility was determined by broth microdilution. The most commonly isolated Gram-negative, Gram-positive, and anaerobic pathogens were ( = 549), ( = 130), and ( = 96), respectively. Ceftazidime-avibactam was highly active against isolates of , with an overall MIC of 0.25 mg/liter. In contrast, the MIC for ceftazidime alone was 32 mg/liter. The MIC value for ceftazidime-avibactam (4 mg/liter) was one dilution lower than that of ceftazidime alone (8 mg/liter) against isolates of The ceftazidime-avibactam MIC for 109 ceftazidime-nonsusceptible isolates was 2 mg/liter, and the MIC range for 6 ceftazidime-nonsusceptible isolates was 8 to 32 mg/liter. The MIC values were within the range of susceptibility for the study drugs permitted per the protocol in the phase 3 study to provide coverage for aerobic Gram-positive and anaerobic pathogens. These findings demonstrate the activity of ceftazidime-avibactam against bacterial pathogens commonly observed in cIAI patients, including ceftazidime-nonsusceptible (This study has been registered at ClinicalTrials.gov under identifier NCT01499290.).