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bioRxiv · 10.1101/2025.04.18.649505

Association of OXA-1 and TEM-1 Genes with Antibiotic Resistance to Piperacillin/Tazobactam in ESBL-Producing Pathogens: Insights from a Multi-Center Analysis

Kamau, E.·Wong, B.·MacArthur, J.·Dombach, J. L.
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Abstract

BackgroundThe emergence of extended-spectrum {beta}-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae presents significant challenges in treating infections caused by these pathogens. This multi-center retrospective study investigated the prevalence of OXA-1 and TEM-1 genes in ESBL-producing E. coli and K. pneumoniae, along with their association with piperacillin/tazobactam susceptibility. MethodsClinical isolates were collected from three institutions as part of routine patient care: Tripler Army Medical Center (TAMC) in Hawaii, Madigan Army Medical Center (MAMC) in Washington, and Brooke Army Medical Center (BAMC) in Southern Texas. A total of 416 isolates were analyzed through genome sequencing and CLSI-guided susceptibility testing. ResultsOXA-1 and TEM-1 {beta}-lactamase enzymes were present in 20.9% (73/349) and 38.7% (135/349) of the E. coli isolates, respectively. Relative risk analysis of non-susceptibility to piperacillin/tazobactam across isolates from the three study sites revealed a highly significant association for OXA-1 (P < 0.001), whereas no significant associations were observed for TEM-1 (P = 0.424) or the combination of OXA-1 and TEM-1 (P = 0.082). When analyzed by institution, the relative risk of non-susceptibility to piperacillin/tazobactam remained highly significant for OXA-1 at TAMC and MAMC (P < 0.001 for both) but was not significant at BAMC (P = 0.21). OXA-1 and TEM-1-positive variants showed a significant association with genes conferring resistance to other antibiotics. ConclusionsThe OXA-1 gene plays a key role in resistance to piperacillin/tazobactam in ESBL-producing organisms, with geographic differences in non-susceptibility observed. Genetic profiling and localized data are crucial for optimizing antibiotic therapy and improving treatment outcomes.

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Kamau, E., Wong, B., MacArthur, J., Dombach, J. L.. 2025-04-18. Association of OXA-1 and TEM-1 Genes with Antibiotic Resistance to Piperacillin/Tazobactam in ESBL-Producing Pathogens: Insights from a Multi-Center Analysis. https://doi.org/10.1101/2025.04.18.649505

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