This study evaluates the antimicrobial activity of aztreonam–avibactam and other β-lactamase inhibitor combinations against Enterobacterales isolates from pediatric patients, showing that aztreonam–avibactam, ceftazidime–avibactam, and meropenem–vaborbactam demonstrate high sensitivity against drug-resistant strains, including ESBL and MDR isolates. These findings provide important guidance for the treatment of drug-resistant Gram-negative bacterial infections in the pediatric population.
Literature Overview
This article, titled '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)', published in the journal Antibiotics, reviews and summarizes recent antimicrobial resistance trends in Enterobacterales bacteria among pediatric patients. Based on 5,723 pediatric isolates collected from 82 U.S. medical institutions, the study evaluates the antimicrobial activity of various β-lactamase inhibitor combinations against these isolates and compares the findings with adult data. The study highlights the prevalence and treatment impact of ESBL (particularly CTX-M genotypes) and MDR in the pediatric population.
Background Knowledge
Enterobacterales bacteria are important pathogens in both hospital- and community-acquired infections, and the emergence of ESBL and MDR strains has complicated treatment approaches in the pediatric population. The rise of resistance to third-generation cephalosporins and carbapenems, primarily mediated by ESBL and carbapenemase genes, has become a global health threat. Although newer β-lactamase inhibitor combinations (e.g., aztreonam–avibactam, ceftazidime–avibactam) have been approved for adult infection treatments, data on their activity in pediatric patients remain limited. This study provides up-to-date antimicrobial susceptibility data for pediatric populations through nationwide surveillance with a large sample size, offering critical insights for empirical antimicrobial therapy in clinical settings.
Research Methods and Experiments
The study collected 5,723 Enterobacterales isolates from pediatric patients across 82 U.S. medical centers between 2019 and 2023, using the INFORM (International Network for Optimal Resistance Monitoring) surveillance program. Antimicrobial susceptibility testing was performed using the broth microdilution method. An adult control group (aged 18–64 years, n=17,712) was also included in the analysis. The tested antimicrobials included aztreonam–avibactam, ceftazidime–avibactam, meropenem–vaborbactam, imipenem–relebactam, ceftolozane–tazobactam, piperacillin–tazobactam, ceftriaxone, cefepime, meropenem, levofloxacin, gentamicin, and amikacin. All MIC determinations were performed according to CLSI, US FDA, and EUCAST standards.
Key Conclusions and Perspectives
Research Significance and Prospects
This study provides critical antimicrobial susceptibility data for guiding pediatric infection treatment, demonstrating the high efficacy of novel β-lactamase inhibitor combinations, such as aztreonam–avibactam, ceftazidime–avibactam, and meropenem–vaborbactam, against drug-resistant Enterobacterales. These findings highlight the potential for rational use of these agents in pediatric clinical settings and offer empirical support for future antimicrobial treatment guidelines targeting drug-resistant pathogens in children. Additionally, the study underscores the need for ongoing surveillance of molecular epidemiological trends in pediatric antimicrobial resistance to anticipate and respond to emerging resistance gene variants and transmission dynamics.
Conclusion
This study systematically evaluated the in vitro antimicrobial activity of several novel β-lactamase inhibitor combinations against Enterobacterales isolates in pediatric infections. The results indicate that aztreonam–avibactam, ceftazidime–avibactam, and meropenem–vaborbactam exhibit excellent antimicrobial activity in vitro against ESBL, MDR, and carbapenem-resistant strains. The study also found that while carbapenem resistance rates are low in pediatric patients, ESBL-producing isolates, predominantly carrying the CTX-M genotype, remain a significant cause of infection. Moreover, the highest prevalence of MDR phenotypes was observed in children aged 6–12 years, suggesting this age group may be at higher risk for drug-resistant infections. These findings provide evidence-based guidance for the development of antimicrobial treatment strategies in pediatric clinical settings and emphasize the importance of continuous monitoring of drug-resistant pathogens in children.
