#9: Frequency and Antimicrobial Susceptibility of Gram-Negative Organisms Causing Bloodstream Infections in Pediatric Patients from United States (US) Medical Centers (2014–2018)

Abstract

Abstract Background 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. Methods 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. Results 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). Conclusions 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.