#145 – PO-ssibilities Beyond the Drip: IV to PO Antibiotic Transition for Gram-Positive Infections (Part 1)
Chapters
- 0:00IV to PO - Part 1 GPs
- 53:41Marker 2
Episode Notes
Join host Dr. Julie Ann Justo and guests Drs. Nicholas Mercuro and Andrew Haynes for the first installment of a two-part series on IV to PO antibiotic transition. Building on landmark studies such as POET, OVIVA, and SABATO, this episode explores the evidence supporting oral therapy for gram-positive bacterial infections, practical implementation strategies, pharmacokinetic and pharmacodynamic considerations, pediatric perspectives, and areas where clinicians may still have concerns about transitioning from IV to PO therapy.
References:
1. https://sidp.org/SIDPEC, search for on-demand CE course from Drs. Jonathan Ryder & Esther Golnabi entitled, "Breaking Points: Landmark Studies that Shaped Infectious Diseases Pharmacotherapy Part 2: Advancing Oral Therapy" from 9/30/26
2. SABATO: Kaasch AJ, et al. Efficacy and safety of an early oral switch in low-risk Staphylococcus aureus bloodstream infection (SABATO): an international, open-label, parallel-group, randomised, controlled, non-inferiority trial. Lancet Infect Dis. 2024 May;24(5):523-534. doi: 10.1016/S1473-3099(23)00756-9. PMID: 38244557.
3. Wilcox MH, et al. Complicated skin and skin-structure infections and catheter-related bloodstream infections: noninferiority of linezolid in a phase 3 study. Clin Infect Dis. 2009 Jan 15;48(2):203-12. doi: 10.1086/595686. PMID: 19072714.
4. 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.
5. BALANCE: BALANCE Investigators, Daneman N, et al. Antibiotic Treatment for 7 versus 14 Days in Patients with Bloodstream Infections. N Engl J Med. 2025 Mar 13;392(11):1065-1078. doi: 10.1056/NEJMoa2404991. PMID: 39565030.
6. POvIV: Obremskey WT, et al. Oral vs Intravenous Antibiotics for Fracture-Related Infections: The POvIV Randomized Clinical Trial. JAMA Surg. 2025 Mar 1;160(3):276-284. doi: 10.1001/jamasurg.2024.6439. PMID: 39841468.
7. DATIPO: Bernard L, et al. Antibiotic Therapy for 6 or 12 Weeks for Prosthetic Joint Infection. N Engl J Med. 2021 May 27;384(21):1991-2001. doi: 10.1056/NEJMoa2020198. PMID: 34042388.
8. Gariani K, et al. Three Weeks Versus Six Weeks of Antibiotic Therapy for Diabetic Foot Osteomyelitis: A Prospective, Randomized, Noninferiority Pilot Trial. Clin Infect Dis. 2021 Oct 5;73(7):e1539-e1545. doi: 10.1093/cid/ciaa1758. PMID: 33242083.
9. Tone A, et al. Six-week versus twelve-week antibiotic therapy for nonsurgically treated diabetic foot osteomyelitis: a multicenter open-label controlled randomized study. Diabetes Care. 2015 Feb;38(2):302-7. doi: 10.2337/dc14-1514. Epub 2014 Nov 20. Erratum in: Diabetes Care. 2015 Apr;38(4):735. doi: 10.2337/dc15-er04b. PMID: 25414157.
10. 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.
11. Heldman AW, et al. Oral antibiotic treatment of right-sided staphylococcal endocarditis in injection drug users: prospective randomized comparison with parenteral therapy. Am J Med. 1996 Jul;101(1):68-76. doi: 10.1016/s0002-9343(96)00070-8. PMID: 8686718.
12. Bactrim upfront: Paul M, et al. Trimethoprim-sulfamethoxazole versus vancomycin for severe infections caused by meticillin resistant Staphylococcus aureus: randomised controlled trial. BMJ. 2015 May 14;350:h2219. doi: 10.1136/bmj.h2219. PMID: 25977146.
13. Bactrim upfront: Markowitz N, Quinn EL, Saravolatz LD. Trimethoprim-sulfamethoxazole compared with vancomycin for the treatment of Staphylococcus aureus infection. Ann Intern Med. 1992 Sep 1;117(5):390-8. doi: 10.7326/0003-4819-117-5-390. PMID: 1503330.
14. El-Dalati S, et al. Partial Oral Versus Intravenous Antibiotic Therapy for Endocarditis With Management by a Multidisciplinary Team: A Retrospective Cohort Study. Open Forum Infect Dis. 2025 Oct 28;12(10):ofaf625. doi: 10.1093/ofid/ofaf625. PMID: 41164785.
15. IV to PO Algorithms: El-Dalati S, et al. Shared Decision-Making for Partial Oral Antibiotic Treatment of Infective Endocarditis: A Case Series. Open Forum Infect Dis. 2024 Mar 19;11(4):ofae166. doi: 10.1093/ofid/ofae166. PMID: 38585184.
16. Freling S, et al. Real-World Application of Oral Therapy for Infective Endocarditis: A Multicenter, Retrospective, Cohort Study. Clin Infect Dis. 2023 Sep 11;77(5):672-679. doi: 10.1093/cid/ciad119. PMID: 36881940.
17. DeSimone DC, et al. Infective Endocarditis: Diagnosis, Antibiotic Therapy, and Management: A Scientific Statement From the American Heart Association. Circulation. 2026 Oct 13;154(15):e593-e619. doi: 10.1161/CIR.0000000000001466. PMID: 42708190.
18. 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.
19. Bock M, et al. Attainment of Target Antibiotic Levels by Oral Treatment of Left-Sided Infective Endocarditis: A POET Substudy. Clin Infect Dis. 2023 Jul 26;77(2):242-251. doi: 10.1093/cid/ciad168. PMID: 36947131.
20. USCAST Presentation: Andes D. Oral cephalosporin STIC against S. aureus and E. coli. 2024 Dec. Accessed at https://www.uscast.org/presentations.
21. 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.
22. Woods CR, et al. Clinical Practice Guideline by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America: 2021 Guideline on Diagnosis and Management of Acute Hematogenous Osteomyelitis in Pediatrics. J Pediatric Infect Dis Soc. 2021 Sep 23;10(8):801-844. doi: 10.1093/jpids/piab027. PMID: 34350458.
23. Hikmat S, et al. Efficacy and tolerability of high-dose cefalexin 45 mg/kg/dose (maximum 1.5 g) three times daily in children with bone and joint infections. J Antimicrob Chemother. 2025 Feb 3;80(2):409-412. doi: 10.1093/jac/dkae423. PMID: 39568056.
24. Ongoing BEST trial of high-dose oral cephalexin among pediatric patients with bone and joint infections in Australia and New Zealand: BonE and Joint Infections - Simplifying Treatment in Children Trial (BEST). Clinicaltrials.gov. 2026 Oct. NCT04538053.
25. Breakpoints Episode #61 – Dosing Consult – Linezolid Therapeutic Drug Monitoring. 2022 Aug 22. Accessed at https://breakpoints-sidp.org/61-dosing-consult-linezolid-therapeutic-drug-monitoring/.
26. Walls G, et al. Patient-reported Perceptions, Experiences, and Preferences Around Intravenous and Oral Antibiotics for the Treatment of Staphylococcus aureus Bacteremia: A Descriptive Qualitative Study. Clin Infect Dis. 2026 Apr 30;82(4):e635-e642. doi: 10.1093/cid/ciaf522. PMID: 40988120.
27. Nursing time for IV vs. PO: Jenkins A. IV to oral switch: a novel viewpoint. J Antimicrob Chemother. 2023 Oct 3;78(10):2603-2604. doi: 10.1093/jac/dkad239. PMID: 37549305.
28. Antibiotic Waste Calculator. Accessed at https://ecorxchoice.com.
29. Juskowich JJ, et al. Using the Comparing Oral versus Parenteral Antimicrobial Therapy (COPAT) Clinical Trial to Influence Institutional Practice Transformation Towards Earlier Transition to Oral Antibiotics. Clin Infect Dis. 2026 Apr 30;82(4):e674-e681. doi: 10.1093/cid/ciaf707. PMID: 41419216.
30. Hawkins MR, et al. Implementing Oral Antibiotics for Bone and Joint Infections: Lessons Learned and Opportunities for Improvement. Open Forum Infect Dis. 2024 Nov 16;11(12):ofae683. doi: 10.1093/ofid/ofae683. PMID: 39660026.
31. MaineHealth Oral Switch Guideline: Schulz J, et al. Unlocked PO-tential: Impact of an Oral Switch Guideline for Osteomyelitis. 2026 MAD-ID & SIDP Annual Meeting. 2026 May 14-17, Orlando, FL. For a pdf of the poster, please email Nicholas Mercuro, PharmD at [email protected]
32. Ongoing VA INTREPID Trial: Investigation of Rifampin to Reduce Pedal Amputations for Osteomyelitis in Diabetics (VA INTREPID). Clinicaltrials.gov. 2026 Apr. NCT03012529.
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