#146 – PO-ssibilities Beyond the Drip: IV to PO Antibiotic Transition for Gram-Negative Infections (Part 2)

Episode Notes

Join host Dr. Julie Ann Justo and guests Drs. Conan MacDougall and Majdi Al-Hasan for the second installment of a two-part series on IV to PO antibiotic transition. Turning the focus to gram-negative infections, this episode explores the evidence for oral therapy, how to choose among agents like fluoroquinolones, trimethoprim-sulfamethoxazole, and beta-lactams, key dosing and PK/PD considerations, patient selection and safety, and practical strategies for implementing early IV to PO transition in clinical practice.

References:

1. POET: Iversen K, et al. Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis. N Engl J Med. 2019 Jan 31;380(5):415-424. doi: 10.1056/NEJMoa1808312. PMID: 30152252.

2. OVIVA: Li HK, et al. Oral versus Intravenous Antibiotics for Bone and Joint Infection. N Engl J Med. 2019 Jan 31;380(5):425-436. doi: 10.1056/NEJMoa1710926. PMID: 30699315.

3. Kutob LF, et al. Effectiveness of oral antibiotics for definitive therapy of Gram-negative bloodstream infections. Int J Antimicrob Agents. 2016 Nov;48(5):498-503. doi: 10.1016/j.ijantimicag.2016.07.013. PMID: 27590704.

4. Punjabi C, et al. Oral Fluoroquinolone or Trimethoprim-sulfamethoxazole vs. ß-lactams as Step-Down Therapy for Enterobacteriaceae Bacteremia: Systematic Review and Meta-analysis. Open Forum Infect Dis. 2019 Aug 14;6(10):ofz364. doi: 10.1093/ofid/ofz364. PMID: 31412127.

5. Harris PNA, et al. Proposed primary endpoints for use in clinical trials that compare treatment options for bloodstream infection in adults: a consensus definition. Clin Microbiol Infect. 2017 Aug;23(8):533-541. doi: 10.1016/j.cmi.2016.10.023. Epub 2016 Nov 1. PMID: 27810466.

6. Mponponsuo K, et al. Highly versus less bioavailable oral antibiotics in the treatment of gram-negative bloodstream infections: a propensity-matched cohort analysis. Clin Microbiol Infect. 2023 Apr;29(4):490-497. doi: 10.1016/j.cmi.2022.10.004. PMID: 36216237.

7. Cals JW, et al. Dose timing and patient compliance with two antibiotic treatment regimens for lower respiratory tract infections in primary care. Int J Antimicrob Agents. 2008 Jun;31(6):531-6. doi: 10.1016/j.ijantimicag.2008.01.029. PMID: 18457936.

8. USCAST Presentation: Andes D. Oral cephalosporin STIC against S. aureus and E. coli. 2024 Dec. Accessed at https://www.uscast.org/presentations.

9. Haynes AS, et al. Cephalexin Model-Informed Dosing Recommendations for Severe Infections: A Pooled Pharmacokinetic Analysis From Infancy to Adulthood. Open Forum Infect Dis. 2026 Sep 26;13(10):ofag611. doi: 10.1093/ofid/ofag611. PMID: 42898747.

10. Narayanan N, et al. Amoxicillin-Clavulanate Breakpoints Against Enterobacterales: Rationale for Revision by the Clinical and Laboratory Standards Institute. Clin Infect Dis. 2024 Aug 16;79(2):516-523. doi: 10.1093/cid/ciae201. PMID: 38626241.

11. VanScoy BD, et al. Evaluation of Oral Tebipenem as a Step-Down Therapy following Intravenous Ertapenem against Extended-Spectrum β-Lactamase-Producing Escherichia coli in a Hollow-Fiber In Vitro Infection Model. Antimicrob Agents Chemother. 2023 Mar 16;67(3):e0090822. doi: 10.1128/aac.00908-22. PMID: 36757190.

12. Heil EL, et al. Optimizing the Management of Uncomplicated Gram-Negative Bloodstream Infections: Consensus Guidance Using a Modified Delphi Process. Open Forum Infect Dis. 2021 Oct 11;8(10):ofab434. doi: 10.1093/ofid/ofab434. PMID: 34738022.

13. Early Oral Switch for Uncomplicated Gram-negative Bacteraemia (INVEST). Clinicaltrials.gov. 2026 Aug. NCT05199324.

14. Gram-Negative Bloodstream Infection Oral Antibiotic Therapy Trial (GOAT). Clinicaltrials.gov. 2026 Mar. NCT06080698.

15. Kunz Coyne AJ, et al. Oral β-Lactams for Complicated Urinary Tract Infections: A Systematic Review and Point-Counterpoint Comparison With Trimethoprim/Sulfamethoxazole and Fluoroquinolones. Pharmacotherapy. 2026 Mar;46(3):e70118. doi: 10.1002/phar.70118. PMID: 41693075.

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