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

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.