409. Temporal Trends in Antibiotic Use of New β-lactams for Gram-Negative Bacteria with Difficult-to-Treat Resistance in the Southeastern United States
Authors: Vivian Tsai Y , Brandon Bookstaver P , Kohn Joseph , Ann Justo Julie , Ann Justo Julie , Childress Darrell , Stramel Stefanie , Slain Douglas , Tu Patrick , Wingler Mary Joyce B , Jones Bruce M , Anderson Daniel , Seddon Megan M , Gibson Geneen , Cretella David A , Eudy Joshua , Winders Hana R , Antosz Kayla , Bailey Pamela , Al-Hasan Majdi N , Al-Hasan Majdi N 
Published: December 2022

Abstract

Background
Several new β-lactam antibiotics were recently developed for treatment of serious infections due to gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR). This multicenter retrospective cohort study examined temporal trends in prevalence of GNB with DTR and the use of new β-lactams in the southeastern United States.

Methods
The prevalence of GNB with DTR, including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter species was determined in 9 hospitals geographically spread within the Southeastern Research Group Endeavor (SERGE-45) between 2015 to 2020. Antibiotic use (AU) of new β-lactams was also obtained from the 9 hospitals during the study period. New β-lactams included ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilastatin/relebactam, and cefiderocol. Logistic regression analysis was utilized to examine temporal trends in prevalence of GNB with DTR and cumulative AU of new β-lactams.

Results
The overall prevalence of GNB with DTR in the 9 hospitals was 0.78% with a numerical increase from 0.67% to 0.97% between 2015 and 2020 (p=0.067) [Figure]. DTR was more prevalent among Acinetobacter spp., followed by P. aeruginosa, and Enterobacterales (11.8%, 3.5%, and 0.2%, respectively). There was a significant increase in the prevalence of DTR isolates among Acinetobacter spp. from 2.7% to 20.7% (p&lt; 0.001) and Enterobacterales from 0.07% to 2.6% (p=0.025), but not P. aeruginosa (p=0.46) between 2015 and 2020. The cumulative AU of new β-lactams in the 9 hospitals was 2 days of therapy per 1000 patient-days. There was numerical increase in AU of these agents from 0.03 to 2.22 days of therapy per 1000 patient days during the 6-year study period (p=0.096) [Figure].

Conclusion
The overall prevalence of GNB with DTR and cumulative use of new β-lactams remain relatively low in the southeastern United States. However, the upward trend in prevalence of DTR isolates, particularly among Acinetobacter spp. and Enterobacterales, is concerning and may drive future increased use of β-lactams. Additional efforts to benchmark the use and appropriateness of new β-lactams are crucial to preserve their efficacy against bacteria with DTR.

Disclosures
P. Brandon Bookstaver, PharmD, Spero Therapeutics: Advisor/Consultant Julie Ann Justo, PharmD, MS, FIDSA, BCPS-AQ ID, bioMerieux: Honoraria|bioMerieux: Honoraria|Entasis Therapeutics: Advisor/Consultant|Entasis Therapeutics: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Merck & Co: Advisor/Consultant|Merck & Co: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi Inc.: Advisor/Consultant|Spero Therapeutics: Honoraria|Spero Therapeutics: Honoraria|Vaxart: Stocks/Bonds Julie Ann Justo, PharmD, MS, FIDSA, BCPS-AQ ID, bioMerieux: Honoraria|bioMerieux: Honoraria|Entasis Therapeutics: Advisor/Consultant|Entasis Therapeutics: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Merck & Co: Advisor/Consultant|Merck & Co: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi Inc.: Advisor/Consultant|Spero Therapeutics: Honoraria|Spero Therapeutics: Honoraria|Vaxart: Stocks/Bonds Bruce M. Jones, Pharm.D., FIDSA, BCPS, AbbVie: Advisor/Consultant|AbbVie: Honoraria|La Jolla: Honoraria|Melinta: Advisor/Consultant|Paratek: Honoraria|Regeneron: Honoraria.