Abstract
Ceftazidime-avibactam, a combination of ceftazidime and the non–β-lactam β-lactamase inhibitor avibactam, is in advanced clinical development. In this study, we report results of in vitro testing of ceftazidime-avibactam and comparator agents against a collection of urinary tract infection (UTI) isolates from the United States (USA), Europe and Mediterranean region (EMR), Latin America (LATAM), and the Asia-Pacific/South Africa regions (APAC). Clinical isolates (1 per patient episode) were collected from patients with a UTI during 2011. A total of 1797 isolates were collected from 159 medical centers. Isolates were processed at the medical centers and forwarded to a central monitoring laboratory for confirmatory identification and reference susceptibility testing. Ceftazidime-avibactam was highly active against Enterobacteriaceae and Pseudomonas aeruginosa. The MIC90 values for ceftazidime-avibactam against Enterobacteriaceae in the USA, EMR, and LATAM regions ranged from 0.25 to 0.5μg/mL. The MIC90 in the APAC was slightly elevated at 1μg/mL. A total of 6.1% (8/131) of Escherichia coli in the USA, 23.5% (43/183) in the EMR, 61.2% (30/49) in LATAM, and 75.0% (9/12) in APAC exhibited an extended-spectrum β-lactamase (ESBL) screen–positive phenotype. A total of 1.6% (2/129) of Klebsiella pneumoniae isolates in the USA were meropenem-non-susceptible (MIC ≥2μg/mL), but a rate of 10.3% (10/97) was observed in the EMR. All ESBL screen–positive phenotype and meropenem-non-susceptible E. coli and K. pneumoniae isolates exhibited a ceftazidime-avibactam MIC ≤4μg/mL. All isolates of P. aeruginosa in the USA and 80.9% (38/47) in the EMR were inhibited at a ceftazidime-avibactam MIC of ≤8μg/mL compared to 88.2% (15/17) and 61.7% (29/47) for ceftazidime alone. Ceftazidime-avibactam demonstrated wide in vitro activity against Gram-negative bacteria from patients with UTI including high potencies against multidrug-resistant organisms.
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