Abstract

Abstract Background Resistance to β-lactams amongst PSA is common with roughly 20% of isolates demonstrating resistance to TZP. This can lead to delays in the time to appropriate empiric therapy. While rapid diagnostics can identify PSA at earlier time points, they fail to detect common β-lactam resistance mechanisms in this pathogen. Though risk factors for TZP resistance (TZP-R) amongst PSA have been identified, co-resistance amongst traditional anti-PSA β-lactams is common, so decisions to turn to other traditional anti-PSA or novel agents in the presence of such predictors are unclear. This study aims to find predictors unique to varying degrees of β-lactam resistance amongst TZP-R PSA to inform these decisions. Methods This was a retrospective case-case-case-control study of all non-cystic fibrosis patients with PSA isolated from a culture from 2015-2021 at Michigan Medicine. Four study groups were created based on the susceptibility profile of PSA: TZP susceptible (TZP-S), resistance to TZP only (TZP-R ONLY), resistance to TZP in addition to 1 or 2 other traditional anti-PSA β-lactams (TZP-R PLUS), and resistance to all traditional anti-PSA β-lactams (pan β-lactam resistance, PBR). Bivariate and multivariate analyses were performed to compare each degree of TZP resistance to the TZP-S group. Results were then compared across models to assess uniqueness to a given resistant phenotype. Results 2365 patients were included, and results of the multivariate analyses are listed in the table. The sole predictor of TZP-R ONLY was recent ceftriaxone or cefotaxime use. Independent predictors unique to TZP-R PLUS were community acquired infection, recent ICU residence, and recent exposure to TZP or aztreonam. Most risk factors identified were either unique to PBR or shared between PBR and TZP-R PLUS including history of PSA, history of TZP-R PSA, and recent exposure to multiple antibiotics. Multivariate Models for TZP-R ONLY, TZP-R PLUS, and PBR Conclusion This analysis demonstrates that previously identified risk factors for TZP-R P. aeruginosa are predictors of PSA with greater degrees of resistance. Given these findings, consideration needs to be given to escalation to novel agents in the presence of risk factors at the time of PSA isolation, rather than to other traditional anti-PSA β-lactams. Disclosures Owen Albin, MD, Charles River Laboratory: Advisor/Consultant|Cipla Pharmaceuticals: Advisor/Consultant|Shionogi Inc: Advisor/Consultant Keith S. Kaye, MD, GSK: Advisor/Consultant|merck: Advisor/Consultant|merck: Stocks/Bonds|Qpex: Advisor/Consultant|Shionogi: Advisor/Consultant|Spero: Advisor/Consultant jason M. Pogue, PharmD, consultant to Venatorx, Merck, Shionogi, QPex Biopharma, Utility, GSK, and Entasis.: Advisor/Consultant.

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