Abstract
BACKGROUND: Management of complicated urinary tract infections (cUTIs) is increasingly difficult due to rising antimicrobial resistance. There is an unmet need for oral treatment options for antimicrobial-resistant cUTIs. Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is an investigational oral carbapenem with activity against antimicrobial-resistant Enterobacterales, including extended-spectrum β-lactamase–positive (ESBL+) pathogens. [Figure: see text] [Figure: see text] METHODS: PIVOT-PO (NCT06059846) was a global, randomized, double-blind, non-inferiority (10% margin) Phase 3 study comparing the efficacy and safety of oral TBP-PI-HBr with intravenous (IV) imipenem-cilastatin (IMI-CIL) in hospitalized adult patients with cUTI or acute pyelonephritis (AP) (Figure 1). The primary endpoint of overall response (clinical cure plus microbiological eradication) at test-of-cure (TOC) was assessed in the microbiological intent-to-treat (micro-ITT) population. An interim analysis to assess efficacy and futility was reviewed by an Independent Data Monitoring Committee and the study was stopped for efficacy. [Figure: see text] [Figure: see text] RESULTS: Baseline characteristics were balanced between treatment groups (Table 1). Overall response at TOC was 58.5% in 261/446 participants who received TBP-PI-HBr versus 60.2% in 291/483 participants who received IMI-CIL (adjusted treatment difference: −1.3%; 95% CI: −7.5%, 4.8%). Treatment effects were comparable in participants with ESBL+ Enterobacterales (Table 2). The safety profile of TBP-PI-HBr was overall consistent with IMI-CIL; the two most frequent treatment-emergent adverse events were diarrhea and headache (Table 3). CONCLUSION: Oral TBP-PI-HBr was non-inferior to IV IMI-CIL in the treatment of cUTI or AP and showed comparable efficacy in participants with ESBL+ Enterobacterales. No new safety signals were identified. TBP-PI-HBr may provide an effective oral treatment option for cUTI or AP. Funding: PIVOT-PO was funded by Spero Therapeutics, Inc. The development of TBP-PI-HBr is supported in part with federal funds from the U.S. Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA), under contract number HHSO100201800015C. DISCLOSURES: All Authors: No reported disclosures