(496) Extended-Spectrum Gram-Negative Antibiotic Prescribing Around a Ceftolozane/Tazobactam Shortage

Introduction: Drug shortages may lead to the use of agents that have a broader range of activity, are more expensive, have a higher toxicity profile, and contribute to the development of antimicrobial resistance. The aim of this study is to evaluate shifts in antimicrobial prescribing trends around a ceftolozane/tazobactam shortage that occurred from December 2020 to December 2021.

Methods: A retrospective, single-center, interrupted-time series analysis was performed from January 2020 to June 2022 at The University of Kansas Health System. Patients included in the study were 18 years of age or older, had a culture-confirmed infection due to a Gram-negative organism, and treated with one of the following: ceftolozane/tazobactam, ceftazidime/avibactam, cefiderocol, imipenem/cilastatin/relebactam, or meropenem/vaborbactam. The three time periods include January 2020 to December 2020 (before shortage), December 2020 to December 2021 (shortage), and January 2022 to June 2022 (after shortage). The primary outcome was antimicrobial utilization as days of therapy (DOT) per 1000 patient-days.

Results: A total of 100 patients were included in the study across the 3 timeframes. Length of hospital stay, length of antimicrobial therapy, and infectious disease consults were similar for the three study periods. All five of the study drugs had varying rates of use between the three periods. Ceftolozane/tazobactam use decreased by 46% (7.36 vs 3.39 DOT per 1000 patient-days) after the shortage compared to its use before. Four of the five antimicrobials decreased in utilization after the shortage compared to before, with the only increase in use being imipenem/cilastatin/relebactam. Two antimicrobials with the overall lowest utilization were imipenem/cilastatin/relebactam and meropenem/vaborbactam. Rates of hospital onset C. difficle infection and antimicrobial cost were not statistically different across the three time periods.

Conclusions: An overall reduction in DOT per 1000 patient-days for 4 of the 5 study antibiotics was identified after the shortage. Ceftolozane/tazobactam utilization, while not statistically significant, was reduced by 46% from baseline. This study may indicate that shortages do not result in permanent prescribing changes once a shortage resolves.