Antimicrobial Activity of Aztreonam-Avibactam and Other β-Lactamase Inhibitor Combinations Tested Against Enterobacterales Isolates from Pediatric Patients from United States Medical Centers (2019–2023)

TL;DR

This study found that certain antibiotic combinations are highly effective against bacteria causing infections in children, with lower resistance rates compared to adults.

Contribution

The study provides new insights into the antimicrobial susceptibility of pediatric Enterobacterales isolates and evaluates the effectiveness of β-lactamase inhibitor combinations.

Findings

Aztreonam–avibactam, ceftazidime–avibactam, and meropenem–vaborbactam showed high activity against resistant pediatric isolates.

Carbapenem resistance was significantly lower in pediatric isolates compared to adults.

ESBL-producing bacteria in children were mostly CTX-M +/− OXA-1/30 gene carriers, similar to adults.

Abstract

Objective: To evaluate the antimicrobial susceptibility of Enterobacterales isolated from pediatric patients. Methods: A total of 5723 isolates were consecutively collected (1/patient) from pediatric patients (<18 years old [yo]) from 82 United States medical centers in 2019–2023 and susceptibility-tested by broth microdilution method. Susceptibility was stratified by infection type and patient age: ≤1 yo (n = 2275), 2–5 yo (n = 1130), 6–12 yo (n = 1213), and 13–17 yo (n = 1105) and compared to adults (18–64 yo; n = 17,712). Results: Pediatric isolates were mainly from pneumonia (21.8%), bloodstream (BSI; 15.3%), and urinary tract infection (UTI; 51.8%). Aztreonam–avibactam, ceftazidime–avibactam, and meropenem–vaborbactam were active against ≥99.4% of ceftriaxone-nonsusceptible (99.4–100.0% susceptible), multidrug-resistant (MDR; 99.7–100.0% susceptible), and ESBL producer (99.7–100.0% susceptible) isolates from pediatric patients. Susceptibility to imipenem–relebactam varied from 97.1% (ceftriaxone-nonsusceptible) to 100.0% (ESBL producers). Ceftolozane–tazobactam showed good activity against ESBL producers (91.8% susceptible), but limited activity against ceftriaxone-nonsusceptible (75.8% susceptible) and MDR isolates (80.9% susceptible). The MDR phenotype varied from 14.3% (13–17 yo) to 19.7% (6–12 yo) among pediatric isolates (15.8% overall) and was 20.7% among adult Enterobacterales. Carbapenem resistance rates were markedly lower in pediatric (0.1%) isolates compared to adult isolates (1.3%). The ESBL profiles were similar among pediatric and adult isolates; 90.1% of ESBL producers from pediatric patients and 88.5% from adults carried a CTX-M +/− an OXA-1/30 gene. Conclusions: Antimicrobial resistance was generally lower among Enterobacterales from pediatric patients compared to adults. ESBL-producing Enterobacterales, mainly CTX-M, remain an important cause of infection in children. Aztreonam–avibactam, ceftazidime–avibactam, and meropenem–vaborbactam were highly active against isolates from both pediatric and adult population.

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