Background: Ceftazidime-avibactam was approved by the US Food and Drug Administration in 2015 to treat complicated intra-abdominal and urinary tract infections in adults and is under clinical development for treating pediatric patients.
Methods: Among 53,381 Gram-negative organisms (1 per patient) collected in 2011-2015, 8461 (15.9%) were from pediatric (≤17 years old) patients. The isolates were collected from 82 US medical centers and susceptibility tested against ceftazidime-avibactam (avibactam at fixed 4 μg/mL) and comparators by reference broth microdilution methods. Susceptibility results were stratified by patient age: ≤1 (3671 isolates); 2-5 (1900); 6-12 (1644) and 13-17 years old (1246). Enterobacteriaceae with an extended-spectrum β-lactamase (ESBL) screening-positive phenotype were evaluated by microarray-based assay for genes encoding ESBLs, KPC, NDM and transferable AmpC enzymes.
Results: Ceftazidime-avibactam inhibited >99.9% of all Enterobacteriaceae at the ≤8 μg/mL susceptible break point and was highly active against ESBL screening-positive phenotype Escherichia coli and Klebsiella pneumoniae. Overall, 83.6% of ESBL screening-positive phenotype K. pneumoniae were susceptible to meropenem. Only 1 of 4724 Enterobacteriaceae (0.02%) isolates was nonsusceptible to ceftazidime-avibactam, an Enterobacter aerogenes with a ceftazidime-avibactam minimum inhibitory concentration (MIC) value of 16 μg/mL and negative results for all β-lactamase tested. Ceftazidime-avibactam was very active against Pseudomonas aeruginosa (MIC50/90, 1/4 μg/mL; 99.1% susceptible), including isolates nonsusceptible to meropenem (94.0% susceptible to ceftazidime-avibactam) or piperacillin-tazobactam (91.7% susceptible) or ceftazidime (89.6% susceptible). Ceftazidime-avibactam activity against P. aeruginosa did not vary substantially among age groups (98.8%-99.3% susceptible) or year of isolation (98.5%-100.0% susceptible).
Conclusions: Ceftazidime-avibactam was very active against a large collection of Gram-negative bacilli isolated from pediatric patients, including P. aeruginosa and Enterobacteriaceae with an ESBL screening-positive phenotype and resistant to carbapenems.