2236. Effectiveness of TBP-PI-HBr in Patients with Instrumentation, Anatomic or Functional Abnormalities: Secondary Analysis from ADAPT-PO. (15th December 2022)

• Record Type: Journal Article
• Authors: Talley, Angela K; Eckburg, Paul B; Critchley, Ian A; Critchley, Ian A; Moore, Gary E; Bhatt, Nivedita; Muir, Lori A; Muir, Lori A; Melnick, David
• 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/ofac492.1854
• Languages: English
• ISSNs: 2328-8957

Abstract

Abstract: Background: Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is an oral carbapenem with activity against Enterobacterales uropathogens, including drug resistant strains. The ADAPT-PO trial demonstrated the non-inferiority of oral TBP-PI-HBr vs. intravenous (IV) ertapenem (ERT) in treating patients with cUTI and/or acute pyelonephritis (AP). Patients with certain anatomical disorders, functional (metabolic or neurological) disorders and/or urinary tract instrumentation (i.e., indwelling catheters) are at increased risk for poor outcomes and recurrent bacteriuria. This secondary analysis of ADAPT-PO evaluated outcomes in patients with various cUTI risk factors. Methods: ADAPT-PO was a Phase 3 multinational, double-blind, double-dummy trial evaluating oral TBP-PI-HBr vs. IV ERT in 1372 hospitalized adult patients with cUTI/AP. Patients were randomized 1:1 to oral TBP-PI-HBr or IV ERT for 7-10 days. The primary efficacy endpoint was overall response (composite favorable clinical and microbiologic response) in the microbiological intent-to-treat (micro-ITT) population. Overall outcomes were assessed among patients with identified with at least one cUTI risk factor at baseline. Results: At baseline, 382/449 (85.1%) and 361/449(86.2%) of patients in the TBP-PI-HBr and ERT arms, respectively had ≥1 risk factor and 289 (64.4%) and 268 (64.2%) had ≥2 risk factors. Anatomical abnormalities and/or urinary track instrumentation were present in 252 (56.1%) TBP-PI-HBr and 242 (57.8%) ERT patients; functional abnormalities were present in 90 (20.0%) and 85(20.3%) respectively). Among patients with ≥1 risk factor, overall response at TOC was 56.3% and 59.6% with TBP-PI-HBr and ERT, respectively, vs. 73.1% and 74.1% among those with no risk factors. Clinical response rates at TOC were high and similar in both arms in patients with (≥92.9%) and without (≥91.4%) risk factors whereas microbiologic responses were more variable between the 2 subsets. Conclusion: In cUTI patients with ≥1 risk factor for complicated disease at baseline, outcomes were comparable between oral TBP-PI-HBr and IV ERT. As expected, these patients were at higher risk for recurrent bacteriuria. Overall responses in both groups were higher among patients without these risk factors. Disclosures: Angela K. Talley, MD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Paul B. Eckburg, MD, AN2 Therapeutics: Stocks/Bonds|Spero Therapeutics: Advisor/Consultant Ian A. Critchley, PhD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Ian A. Critchley, PhD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Gary E. Moore, PhD, Spero Therapeutics: Advisor/Consultant Nivedita Bhatt, PhD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Lori A. Muir, B.Sc., Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Lori A. Muir, B.Sc., Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds David Melnick, MD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds.