LAUSR

Ceftazidime–avibactam is US FDA approved for the treatment of pneumonia and complicated intra-abdominal and urinary tract infections in adults, and it is in late-stage clinical development for the treatment of pediatric patients. Organisms were consecutively collected from pediatric patients (≤17 years old) with bloodstream infections in 33 US medical centers in 2014–2018. Enterobacterales, P. aeruginosa, and H. influenzae isolates (n = 976) were susceptibility (S) tested against ceftazidime–avibactam and comparators by reference broth microdilution methods; 42.9% of isolates tested were from patients <1 year old, and 70.7% from patients ≤5 years old. Isolates with an ESBL–phenotype were screened for β-lactamase genes. Overall, 40.1% of organisms were Gram-negative bacteria (GNB), 57.0% Gram-positives, and 2.8% Candida spp. The five most common GNB were E. coli (32.4% of GNB), K. pneumoniae (17.3%), E. cloacae (9.8%), P. aeruginosa (9.2%), and S. marcescens (5.5%; Table). Enterobacterales, P. aeruginosa, and H. influenzae isolates combined represented 89% of GNB and all isolates (100.0%) were susceptible to ceftazidime–avibactam. Among Enterobacterales (n = 845; MIC50/90, 0.12/0.25 mg/L), the highest ceftazidime–avibactam MIC value was only 4 mg/L and 99.2% of isolates were inhibited at ≤1 mg/L. Enterobacterales susceptibility to ceftriaxone, piperacillin–tazobactam, ceftolozane–tazobactam, and meropenem were 88.2%, 93.1%, 97.5%, and 99.5%, respectively. Forty-four Enterobacterales isolates (5.2%) produced an ESBL, including CTX-M-type (n = 35 [79.5% of ESBL producers], 21 being CTX-M-15), SHV-type (12; 27.3%), and OXA-1/30 (9; 20.5%). Twelve isolates (27.3%) produced >1 ESBL. No carbapenemase gene was detected. Among ESBL producers, highest ceftazidime–avibactam MIC was 2 mg/L, and susceptibility rates for ceftolozane–tazobactam and meropenem were 92.9% and 100.0%, respectively. Ceftazidime–avibactam exhibited complete activity against P. aeruginosa (MIC50/90, 2/4 mg/L; 100.0% susceptible). P. aeruginosa susceptibility rates for meropenem, piperacillin–tazobactam, and ceftolozane–tazobactam were 82.5%, 85.6%, and 100.0%, respectively; and 10.3% of isolates exhibited multidrug-resistance phenotype (not susceptible to ≥3 classes). Ceftazidime–avibactam was highly active against H. influenzae (n = 34; MIC50/90, ≤0.015/0.03 mg/L; highest MIC, 0.06 m/L). Ceftazidime–avibactam exhibited potent activity against a large collection of GNB isolated from pediatric patients with bacteremia and showed complete coverage (100.0% susceptibility) against P. aeruginosa, Enterobacterales, and H. influenzae.