703. Ceftazidime-Avibactam Antimicrobial Activity and Spectrum when Tested Against Gram-negative Organisms from Pediatric Patients: Results from the INFORM Surveillance Program (USA, 2011-2015)
Session: Poster Abstract Session: They've Been Here a Billion Years! Pediatric Bacterial and Viral Infections
Thursday, October 27, 2016
Room: Poster Hall
  • IDWeek16 CAZ-AVI Peds 703.pdf (387.4 kB)

    Background: Avibactam (AVI) is a synthetic non-β-lactam, β-lactamase (BL) inhibitor that inhibits Ambler classes A (e.g., ESBL and KPC), C and some D enzymes. Ceftazidime (CAZ)-AVI was approved by the US-FDA in 2015 for treatment of complicated intra-abdominal and urinary tract infections in adults and is under clinical development for treatment of pneumonia.

    Methods: Among 53,381 Gram-negative (GN) organisms (1/patient) collected by the CAZ-AVI INFORM surveillance program in 2011-2015, 8,461 (15.9%) were from pediatric (17 years old [yo]) patients. The isolates were collected from 82 USA medical centers and susceptibility (S) tested against CAZ-AVI (AVI at fixed 4 µg/mL) and comparators by reference broth microdilution methods. S results were stratified by patient age as follows: ≤1 yo (3,671 isolates); 2-5 (1,900); 6-12 (1,644) and 13-17 (1,246). Enterobacteriaceae (ENT) with an ESBL-phenotype were evaluated for the presence of genes encoding ESBLs, KPC, NDM and transferable AmpC enzymes using a microarray-based assay.

    Results: An ESBL-phenotype was observed among 8.9 and 8.4% of E. coli (EC) and K. pneumoniae (KPN), respectively, and rates were highest for the 2-5 yo group (11.9 and 13.1%, respectively). CAZ-AVI inhibited >99.9% of all ENT at the S breakpoint of ≤8 µg/mL, and was highly active against ESBL-phenotype EC and KPN (Table). Overall, 83.6% of ESBL-phenotype KPN were meropenem (MEM)-S. All E. cloacae isolates, including CAZ-non-S strains, were CAZ-AVI-S. Only 1 of 4,724 ENT (0.02%) was CAZ-AVI-non-S: an E. aerogenes with CAZ-AVI MIC value of 16 μg/mL and negative results for all BL tested. CAZ-AVI was very active against P. aeruginosa (PSA; 99.1% S), including isolates non-S to MEM (94.0% S to CAZ-AVI) or piperacillin/tazobactam (PT; 91.7% S) or CAZ (89.6% S). Further, 77.8% of PSA isolates non-S to MEM, PT and CAZ were CAZ-AVI-S. CAZ-AVI activity against PSA did not vary substantially among age groups (98.8-99.3% S) or year of isolation (98.5-100.0% S).

    Conclusion: CAZ-AVI demonstrated potent activity against a large collection of GN bacilli isolated from pediatric patients, including PSA and ESBL-phenotype and/or carbapenem-resistant ENT. These results support further evaluation of CAZ-AVI for treatment of pediatric patients.


    Helio S. Sader, MD, PhD, Michael D. Huband, BS, Leonard R. Duncan, Ph.D. and Robert K. Flamm, Ph.D., JMI Laboratories, Inc., North Liberty, IA


    H. S. Sader, Allergan: Research Contractor , Research grant

    M. D. Huband, Allergan: Research Contractor , Research grant

    L. R. Duncan, Allergan: Research Contractor , Research grant

    R. K. Flamm, Allergan: Research Contractor , Research grant

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.