By Hira Ilyas, PharmD

Dr. Pak and colleagues have recently published their early experience using intravenous to oral transition in pediatric endocarditis at Seattle Children’s hospital, which raises the question of whether this approach is ready for broader use.^1,2 They reported on the use of intravenous to oral antibiotic transition in pediatric endocarditis from December 2022 to June 2024 (control: Dec 22-Nov 23; intravenous to oral protocol group Dec 23 – Jun 24). Patients were excluded from the study if they were diagnosed with fungal infective endocarditis or endovascular infection without vegetation.^1,2

In the oral transitioned group (n=8), patients were 10 months to 20 years old and had antibiotics transitioned to oral as early as 7 days (n=4), 21 days (n=3), and 35 days (n=1), with an 88 percent success rate.^1,2 Patients had primarily gram-positive pathogens, except for two cases: Serratia marcescens and Enterococcus faecalis (n=1) and Haemophilus parainfluenzae (n=1). Oral regimens included amoxicillin plus rifampin plus trimethoprim/sulfamethoxazole (n=1), amoxicillin (n=2), linezolid plus levofloxacin (n=2), levofloxacin (n=2), and trimethoprim/sulfamethoxazole plus ciprofloxacin (n=1).² One patient failed to achieve clinical success, which was attributed to oncologic progression and death. In the control group (n=14), all patients were noted to have clinical success, but importantly 4 patients also received an oral transition despite the absence of a formal protocol at that time.^1,2

What Can We Learn from Adult Intravenous to Oral Recommendations?

The Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis trial (also known as the POET trial) was published in 2019 looking to see if oral step-down therapy in patients with stable endocarditis would be safe and efficacious.³ This was a noninferiority, multicenter trial, with 400 adults who had stable left-sided endocarditis where 199 patients were randomized to continue intravenous treatment and 201 patients were switched to oral therapy.³ This trial targeted Streptococcus species, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci associated endocarditis. Additionally, the most common antibiotic regimens used included dicloxacillin and rifampicin (n=15) or amoxicillin and rifampicin (n=13) for S. aureus, amoxicillin and moxifloxacin (n=24) or amoxicillin and linezolid (n=13) for E. faecalis, amoxicillin and rifampicin (n=47) or amoxicillin and moxifloxacin (n=12) for Streptococcus species, and fusidic acid and linezolid (n=5) or rifampicin and linezolid (n=4) for coagulase-negative Staphylococcus species.³ Changing to the oral antibiotic treatment was noninferior to continued intravenous antibiotics treatment.³

There are multiple adult studies that further support intravenous to oral transition, primarily in patients with gram positive endocarditis.^4-6 All but one required intravenous therapy for at least 10 days. The majority of the trials recommended dual oral therapy, although they noted some issues with this as well.

Guided by the POET trial, the ESC guidelines recommend switching patients to home oral antibiotic regimens for up to 6 weeks in the outpatient setting.⁷ To mimic the recommendation of the adult population, these guidelines suggest that before considering oral antibiotic therapy, stable patients are recommended to get a Transesophageal echocardiography.⁷  This differs from common pediatric practice, where transthoracic echocardiography is often preferred because it is noninvasive and performs well in children, particularly those weighing less than 60 kg, with reported sensitivity of 97% for detecting findings of infective endocarditis.⁸

A Promising Strategy, but Not Yet Routine Practice

Following the POET trial, intravenous-to-oral conversion for adult patients with left-sided endocarditis has increasingly become a standard of care. While oral step-down therapy for pediatric infective endocarditis remains preliminary, the early experience from Seattle Children’s hospital suggests this approach may be feasible in carefully selected patients. Pharmacists will be essential in evaluating oral bioavailability, organism-specific susceptibility, drug interactions, tolerability, adherence barriers, and monitoring needs as pediatric experience with this strategy evolves.

Oral Transition Therapies^1,2,7

Condition or Organism	Adult Oral Guideline Recommendations	Pediatric Oral Antibiotic Transitions Used by Pak and Colleagues
Penicillin susceptible Streptococcus species	amoxicillin + rifampin amoxicillin + moxifloxacin amoxicillin + linezolid linezolid + rifampin linezolid + moxifloxacin	amoxicillin
Penicillin resistant  Streptococcus species	linezolid + rifampin moxifloxacin + rifampin linezolid + moxifloxacin	linezolid + levofloxacin
Penicillin and Methicillin susceptible S. aureus and coagulase-negative Staphylococcus species	amoxicillin + rifampin amoxicillin + fusidic acid moxifloxacin + rifampin linezolid + rifampin linezolid + fusidic acid	linezolid + levofloxacin levofloxacin
Methicillin susceptible S. aureus and coagulase-negative Staphylococcus species	dicloxacillin + rifampin dicloxacillin + fusidic acid moxifloxacin + rifampin linezolid + rifampin linezolid + fusidic acid
Methicillin resistant coagulase-negative Staphylococcus species	linezolid + fusidic acid linezolid + rifampin	linezolid
Enterococcus faecalis	amoxicillin + moxifloxacin amoxicillin + linezolid amoxicillin + rifampin linezolid + moxifloxacin linezolid + rifampin	amoxicillin + rifampin +  sulfamethoxazole/trimethoprim
Coagulase-negative Staphylococcus species	fusidic acid + linezolid rifampicin + linezolid amoxicillin + linezolid	–

*Positive blood cultures for Serratia marcescens and E. faecalis

Treatment duration of infective endocarditis varies by organism but is at least 4-6 weeks long. Enteral intervention in infective endocarditis patients can help reduce the risk associated with central line placement.

Hira Ilyas was a Doctor of Pharmacy candidate at the University of Connecticut. This post was written as part of her Advanced Pharmacy Practice Experience under the guidance of her professor, Jennifer Girotto PharmD, BCPPS, BCIDP, who also reviewed and edited the piece.

References:

1. Pak D, McDonald DR, Brothers AW, et al. Switch to Oral Antibiotics for Infective Endocarditis in Children. Hosp Pediatr. 2025;16(1):e31–e35. doi:10.1542/hpeds.2025-008463
2. Pak D, McDonald DR, Brothers AW, et al. Partial Oral Therapy for Pediatric Infective Endocarditis. 2025;14(Supplement_1):S12. https://10.1093/jpids/piaf072.021
3. Iversen K, Ihlemann N, Gill SU, et al. Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis. New England Journal of Medicine. 2019;380(5):415–424. doi:10.1056/NEJMoa1808312
4. Freling S, Wald-Dickler N, Banerjee J, et al. Real-World Application of Oral Therapy for Infective Endocarditis: A Multicenter, Retrospective, Cohort Study. Clin Infect Dis. 2023;77(5):672–679. doi:10.1093/cid/ciad119
5. Pries-Heje MM, Hjulmand JG, Lenz IT, et al. Clinical implementation of partial oral treatment in infective endocarditis: the Danish POETry study. Eur Heart J. 2023;44(48):5095–5106. doi:10.1093/eurheartj/ehad715
6. Rallet B, Pouy R, Coutureau C, et al. Should We Extend the Use of Oral Antibiotics in Infective Endocarditis? The ENDO-ORAL Study. Clin Infect Dis. 2026;82(3):e462–e470. doi:10.1093/cid/ciaf452
7. Delgado V, Ajmone Marsan N, de Waha S, et al. 2023 ESC Guidelines for the management of endocarditis. Eur Heart J. 2023;44(39):3948–4042. doi:10.1093/eurheartj/ehad193
8. Aldrich JB, Madsen N, Armstrong AK, et al. Evaluation and treatment of infective endocarditis in children and adolescents with underlying CHD: a Paediatric Acute Care Cardiology Collaborative Clinical Practice Guideline. Cardiology in the Young. 2025;35(12):2422–2440. doi:10.1017/S1047951125110561