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.
H. S. Sader,
L. R. Duncan, Allergan: Research Contractor , Research grant
R. K. Flamm, Allergan: Research Contractor , Research grant
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