222. Clinical and microbiological outcomes for Enterobacterales uropathogens in the Phase 3 ADAPT-PO Study of oral tebipenem pivoxil hydrobromide. (15th December 2022)

• Record Type: Journal Article
• Authors: Critchley, Ian A; Critchley, Ian A; Eckburg, Paul B; Muir, Lori A; Muir, Lori A; Dane, Aaron; Moore, Gary E; Melnick, David; Talley, Angela K
• Is Part Of: Open forum infectious diseases. Volume 9:(2022)Supplement 2
• Publication Date: 2022-12-15
• Subjects: Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofac492.300
• Languages: English
• ISSNs: 2328-8957

Abstract

Abstract: Background: Enterobacterales (ENT) are frequently implicated in complicated urinary tract infection, including acute pyelonephritis (cUTI/AP), with Escherichia coli (EC) being the most prevalent. Extended-spectrum β-lactamase (ESBL)-producing organisms are increasing and often coresistant to existing oral antibiotics such as the fluoroquinolones (FQ) and trimethoprim-sulfamethoxazole (TMP-SMX). Tebipenem pivoxil hyrdrobromide (TBP-PI-HBr) — a novel oral carbapenem under development — was shown to be non-inferior to IV ertapenem (ETP) in the treatment of cUTI/AP in the ADAPT-PO trial. The goal of this analysis was to assess clinical response (CR) and by-pathogen microbiological responses (MR) for ENT pathogens, including those with resistant phenotypes. Methods: ADAPT-PO was a Phase 3 multinational, double-blind trial evaluating oral TBP-PI-HBr vs. IV ertapenem in 1372 hospitalized adult patients with cUTI/AP. Patients were randomized 1:1 to oral TBP-PI-HBr or IV ertapenem for 7-10 days. CR and MR at the test-of-cure (TOC) for patients with ENT including resistant phenotypes were assessed in the microbiological intent-to-treat population (micro-ITT). Results: 90.2% of patients in the micro-ITT population were infected with ENT; EC was the most prevalent (64.2%), followed by Klebsiella pneumoniae (14.3%), Proteus mirabilis (6.7%) and Enterobacter cloacae (2.2%). ESBL-positive, FQ non-susceptible (NS) and TMP-SMX-R phenotypes were 23.5%, 38.4% and 41.8% of ENT, respectively. MIC90 vales for both TBP and ETP against ENT were 0.12 µg/mL. At TOC, the CR for TBP-PI-HBr and ETP and all ENT were 92.7% and 94.0%, respectively, and MR was 59.7% and 65.9%, respectively. CR at TOC for ESBL positive ENT was 87.6% and 95.3%, respectively and MR was 54.7% and 61.6%, respectively. Similar MR rates were observed among EC and resistant EC phenotypes. Conclusion: At TOC CR rates for ENT pathogens were high and similar between treatment groups, including resistant subsets. MR rates for all pathogens were lower in both treatment groups, translating to to a phenomenon consistent with other cUTI trials representing asymptomatic bacteriuria. TBP-PI-HBr and ETP showed similar MR rates for EC, the most prevalent uropathogens, including resistant phenotypes. Disclosures: Ian A. Critchley, PhD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Ian A. Critchley, PhD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Paul B. Eckburg, MD, AN2 Therapeutics: Stocks/Bonds|Spero Therapeutics: Advisor/Consultant Lori A. Muir, B.Sc., Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Lori A. Muir, B.Sc., Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Aaron Dane, MSc, Amplyx: Advisor/Consultant|AN2 therapeutics: Advisor/Consultant|Artizan: Advisor/Consultant|Cidara: Advisor/Consultant|ContraFect: Advisor/Consultant|Correvio: Advisor/Consultant|Davolterra: Advisor/Consultant|Destiny Pharma: Advisor/Consultant|Entasis: Advisor/Consultant|F2G Limited: Advisor/Consultant|GSK: Advisor/Consultant|Humanigen: Advisor/Consultant|Kymab: Advisor/Consultant|Modis: Advisor/Consultant|Orca: Advisor/Consultant|Pfizer: Advisor/Consultant|Phico: Advisor/Consultant|Pled Pharma: Advisor/Consultant|Rare Thyroid: Advisor/Consultant|Roche: Advisor/Consultant|Scynexis: Advisor/Consultant|Sinovent: Advisor/Consultant|Spero Therapeutics: Advisor/Consultant|Transcrip: Advisor/Consultant|Venatorx: Advisor/Consultant Gary E. Moore, PhD, Spero Therapeutics: Advisor/Consultant David Melnick, MD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Angela K. Talley, MD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds.