Correlation of OXA-1 and TEM-1 genes with antibiotic resistance to piperacillin/tazobactam in ESBL-producing Enterobacterales: insights from a multi-center analysis

Background The emergence of extended-spectrum β-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 and additional antimicrobial resistance genes. Methods Clinical 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. Results OXA-1 and TEM-1 β-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. Conclusions The 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.