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Ceftazidime-Avibactam Antimicrobial Activity and Spectrum When Tested against Gram-negative Organisms from Pediatric Patients: Results from the INFORM Surveillance Program (United States, 2011-2015)

Sader Helio S. MD PhD; Huband, Michael D. BS; Duncan, Leonard R. PhD; Flamm, Robert K. PhD
The Pediatric Infectious Disease Journal: Post Acceptance: December 04, 2017
doi: 10.1097/INF.0000000000001859
Antimicrobial Reports: PDF Only

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, 8,461 (15.9%) were from pediatric (≤17 years-old [yo]) 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 yo (3,671 isolates); 2-5 (1,900); 6-12 (1,644) and 13-17 (1,246). 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 breakpoint 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 4,724 Enterobacteriaceae (0.02%) isolates was nonsusceptible to ceftazidime-avibactam, an E. aerogenes with a ceftazidime-avibactam 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 [S]), including isolates nonsusceptible to meropenem (94.0%S to ceftazidime-avibactam) or piperacillin-tazobactam (91.7%S) or ceftazidime (89.6%S). Ceftazidime-avibactam activity against P. aeruginosa did not vary substantially among age groups (98.8-99.3%S) or year of isolation (98.5-100.0%S).

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/or resistant to carbapenems.

Source of support: This study was supported by Allergan.

acknowledgements: The authors would like to thank all participants of the International Network for Optimal Resistance Monitoring (INFORM) program for providing bacterial isolates.

FUNDING: This study was supported by Allergan. Allergan was involved in the design and decision to present these results and JMI Laboratories received compensation fees for services in relation to preparing the manuscript. Allergan had no involvement in the collection, analysis, and interpretation of data.

Contact Information: Helio S. Sader, MD, PhD, JMI Laboratories, 345 Beaver Kreek Ctr, Suite A, North Liberty, IA, 52317, USA. Phone: 319-665-3370; Fax: 319-665-3371; helio-sader@jmilabs.com

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