In Vitro Activity of Ceftazidime-Avibactam Against Isolates from Patients in a Phase 3 Clinical Trial for the Treatment of Complicated Intra-Abdominal Infections [PublishAheadOfPrint]

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 activity of ceftazidime against Ambler class A, C and some class D β-lactamase-producing strains of Enterobacteriaceae and Pseudomonas aeruginosa. In vitro activity of ceftazidime-avibactam versus comparators was evaluated against 1,440 clinical isolates obtained in a phase 3 clinical trial in patients with complicated intra-abdominal infections (cIAI; NCT01499290).

Overall, in vitro activity was determined for 803 Enterobacteriaceae, 70 P. aeruginosa, 304 Gram-positive aerobes and 255 anaerobes isolated at baseline from 1,066 randomized patients. Susceptibility was determined by broth microdilution.

The most commonly isolated Gram-negative, Gram-positive and anaerobic pathogens were Escherichia coli (n = 549), Streptococcus anginosus (n = 130) and Bacteroides fragilis (n = 96), respectively. Ceftazidime-avibactam was highly active against isolates of Enterobacteriaceae, with an overall MIC₉₀ of 0.25 mg/l. In contrast, the MIC₉₀ for ceftazidime alone was 32 mg/l. The MIC₉₀ value for ceftazidime-avibactam (4 mg/l) was one dilution lower than that of ceftazidime alone (8 mg/l) against isolates of Pseudomonas aeruginosa. The ceftazidime-avibactam MIC₉₀ for 109 ceftazidime-non-susceptible Enterobacteriaceae isolates was 2 mg/l and the MIC range for 6 ceftazidime-non-susceptible P. aeruginosa isolates was 8 to 32 mg/l. MIC₉₀ values were within the range of susceptibility for the study drugs permitted per protocol in the phase 3 study to provide coverage for aerobic Gram-positive and anaerobic pathogens.

These findings demonstrate the in vitro activity of ceftazidime-avibactam against bacterial pathogens commonly observed in cIAI patients, including ceftazidime-non-susceptible Enterobacteriaceae.

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