2169. A 4-Year Analysis of Antimicrobial Susceptibility to Ceftolozane/Tazobactam in Pseudomonas aeruginosa: How Drug Availability Affects Resistance Rate

BACKGROUND: Antibiotic resistance is associated with a fitness cost and reduced bacterial growth that allows susceptible bacteria to outcompete resistant bacteria, if selective pressure from antibiotics is reduced. Ceftolozane/tazobactam (C/T) approved in 2014, was temporarily withdrawn from December 2020 to February 2022: this forced unavailability created the conditions to study how drug discontinuation might influence resistance reversibility. METHODS: This is a retrospective observational study, including isolates of P. aeruginosa collected between March 1(st) 2019 and February 22(nd) 2023. Isolates collected from swabs (e.g. rectal, skin) or with no C/T susceptibility test were excluded. Antibiotic susceptibility tests were performed with the Vitek-2 assay. Only the first isolate for each patient was included; multiple isolates from the same patient were included if collected at least 5 months apart. Four collection periods were defined (Fig 1). All data were analyzed using JASP. [Figure: see text] RESULTS: From the Hospital microbiology laboratory list, 1768 P. aeruginosa isolates were derived, of which 926 isolates fulfilled the inclusion criteria. A significant (p-value < 0.001) reduction of C/T resistance rate was observed when the antibiotic was unavailable, followed by a subsequent increase with its reintroduction (Tab.1). Evaluating phenotypic susceptibility to other antibiotics, production of GES-variants, suggested by resistance to carbapenem and C/T but retained susceptibility to ceftazidime/avibactam, was most likely the predominant resistance mechanism (Tab. 2); a reduction in GES-like isolates, concurrent with decreasing C/T resistance was observed. 19 patients presented a C/T-resistant isolate after a previous susceptible one, but only 4 patients had received a prior C/T treatment (Tab 3). [Figure: see text] [Figure: see text] [Figure: see text] CONCLUSION: The temporary unavailability of C/T created the condition to analyze the practical application of the theory of fitness cost to maintain resistance. Our data show a significant reduction of resistance in the absence of the antibiotic, but a subsequent increase with its reintroduction, due to the persistence of resistant isolates. Therefore, continuous monitoring of antibiotic use and evolving resistance is essential. DISCLOSURES: All Authors: No reported disclosures