1687. Antimicrobial Activity of Ceftibuten-Avibactam against a Global Collection of Enterobacterales from Patients with Complicated Urinary Tract Infections (2021)
Authors: Sader Helio S , Carvalhaes Cecilia G , Huband Michael D , Mendes Rodrigo E , Castanheira Mariana 
Published: December 2022

Abstract

Background
Limited therapeutic options are currently available for oral treatment of complicated urinary tract infections (cUTIs) caused by resistant Enterobacterales (ENT). Ceftibuten (CTB) is an oral cephalosporin active against ENT approved by the US FDA in 1995. Avibactam (AVI) is a potent inhibitor of extended-spectrum β-lactamases (ESBLs), serine carbapenemases, and AmpC that can be administered orally. We evaluated the in vitro activity of CTB-AVI against ENT causing cUTI.

Methods
3,216 isolates (1/patient) were consecutively collected from patients with cUTI in 72 hospitals from 25 countries in 2021 then susceptibility (S) tested by CLSI broth microdilution. Isolates were mainly from the US (n=1,584; 29 centers) and Europe (n=1,411; 33 centers in 18 countries), but included E. coli isolates from Latin America (LATAM; n=121; 6 centers in 5 countries) and Japan (n=100). A proposed CTB-AVI breakpoint (≤ 2 mg/L) and the current CLSI breakpoint for CTB (≤ 8 mg/L) were applied for comparison.

Results
The most active agents against ENT were CTB-AVI (99.1%/99.6% inhibited at ≤ 2/≤ 8 mg/L), ceftazidime (CAZ)-AVI (99.6%S), amikacin (AMK; 99.1%S), and meropenem (MEM; 98.2%S; Table). CTB-AVI was 4-fold more potent than CAZ-AVI based on MIC50/90 values. The most active oral agents were CTB (89.3%S; 82.9% inhibited at ≤ 2 mg/L), levofloxacin (LEV; 75.4%S), and trimethoprim-sulfamethoxazole (TMP-SMX; 73.4%S). Only CTB-AVI, CAZ-AVI, MEM, and AMK were active against &gt;90% of ESBL-phenotype isolates; only CTB-AVI, CAZ-AVI, and AMK were active against &gt; 70% of CRE isolates. CRE rates were 1.8%/1.9% in US/EU; CTB-AVI inhibited 79.3%/81.5% of CRE isolates from US/EU at ≤ 8 mg/L (75.9%/77.8% at ≤ 2 mg/L). The second most active oral agent against CRE was TMP-SMX (24.6%S). Only 17 isolates (0.5%) showed CTB-AVI MICs ≥8 mg/L; these were from the US (n=9; 0.6% of US isolates), EU (n=6; 0.4%), and LATAM (n=2; 1.7%). Among these 17 isolates, 23.5% were MEM-S, 41.2% were TMP-SMX-S, and 82.4% were AMK-S.

Conclusion
CTB-AVI was highly active against a large collection of contemporary ENT isolated from patients with cUTIs and exhibited a similar spectrum to CAZ-AVI. CTB-AVI may represent a valuable option for oral treatment of cUTI caused by resistant ENT.

Disclosures
Helio S. Sader, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Pfizer: Grant/Research Support Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Michael D. Huband, BS, Pfizer: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Office for Assistant Secretary of Defense for Health Affairs: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Spero Therapeutics: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.