Checklist for Oral Antibiotic Treatment of Endocarditis
(Updated Date 25 May 2025)
POET trial (2018)
The POET trial is the largest randomized controlled trial (RCT) investigating oral antibiotics for infective endocarditis (IE). This non-blinded study evaluated oral antibiotics as a step-down treatment for left-sided endocarditis caused by Staphylococcus aureus, coagulase-negative Staphylococci (CoNS), streptococci, or Enterococcus faecalis.
A total of 400 patients who completed at least 10 days of intravenous (IV) antibiotics were randomized to either continue with IV therapy or switch to oral antibiotics, chosen for their good bioavailability. All patients underwent transoesophageal echocardiograms (TOE) before and after treatment.
The primary outcome, which included all-cause mortality, unplanned cardiac surgery, embolic events, and relapse of bacteremia, was assessed over a six-month follow-up. Seven patients in the oral group had below-effective antimicrobial levels, but no adjustments were made to their treatment. The study found that oral antibiotics were non-inferior to IV antibiotics, with the primary endpoint occurring in 24 patients (12.1%) in the IV group and 18 patients (9.0%) in the oral group (P = 0.40). Administering oral antibiotics is non-inferior to IV antibiotics. The primary endpoint occurred in 24 patients (12.1%) in the IV treatment group and in 18 patients (9.0%) in the oral treatment group, with a P-value of 0.40.
Inclusion criteria
Oral regimens recommended in the POET trial (Supplementary Appendix)
Penicillin and methicillin-sensitive Staphylococcus aureus and coagulase-negative staphylococci:
1) Amoxicillin 1 g x 4 and fusidic acid 0.75 g x 2
2) Amoxicillin 1 g x 4 and rifampicin 0.6 g x 2
3) Linezolid 0.6 g x 2 and fusidic acid 0.75 g x 2
4) Linezolid 0.6 g x 2 and rifampicin 0.6 g x 2
Methicillin-sensitive Staphylococcus aureus and coagulase-negative staphylococci
1) Dicloxacillin 1 g x 4 and fusidic acid 0.75 g x 2
2) Dicloxacillin 1 g x 4 and rifampicin 0.6 g x 2
3) Linezolid 0.6 g x 2 and fucidic acid 0.75g x 2
4) Linezolid 0.6 g x 2 and rifampicin 0.6 g x 2
Methicillin-resistant coagulase-negative staphylococci
1) Linezolid 0.6 g x 2 and fusidic acid
2) Linezolid 0.6 g x 2 and rifampicin 0.6 g x2
Enterococcus faecalis:
1) Amoxicillin 1 g x 4 and rifampicin 0.6 g x 2
2) Amoxicillin 1 g x 4 and moxifloxacin 0.4 g x 1
3) Linezolid 0.6 g x 2 and rifampicin 0.6 g x 2
4) Linezolid 0.6 g x 2 and moxifloxacin 0.4 g x 1
Streptococci with a minimal inhibitory concentration for penicillin of <1 mg/L:
1) Amoxicillin 1 g x 4 and rifampicin 0.6 g x 2
2) Linezolid 0.6 g x 2 and rifampicin 0.6 g x 2
3) Linezolid 0.6 g x 2 and moxifloxacin 0.4 g x1
Streptococci with a minimal inhibitory concentration for penicillin of ≥1 mg/L:
1) Linezolid 0,6 g x2 and rifampicin 0.6 g x 2
2) Moxifloxacin 0.4 g x 1 and rifampicin 0.6 g x 2
3) Moxifloxacin 0.4 g x 1 and clindamycin 06 g x3
Pharmacokinetic and pharmacodynamic properties of amoxicillin & flucloxacillin given orally (PO) and IV
Amoxycillin
Amoxycillin IV:
Peak serum concentration: 83–112 mg/L, 1 min after 500 mg IV injection
Duration of effective plasma concentration: after 500 mg IV dose, plasma concentration fell to 1 mg/L after 3.5 h
Amoxycillin PO:
Peak serum concentration: 8–10 mg/L, 2 h after 500 mg PO dose
Duration of effective plasma concentration: after 500 mg PO dose, concentration fell to zero after 6–8 h
Published MIC values
S. aureus (penicillin susceptible) : 0.1 mg/L
α-haemolytic streptococci : 0.01 mg/L
E. faecalis : 0.5 mg/L
Flucloxacillin
Flucloxacillin IV:
Peak serum concentration: 86.8 mg/L after 500 mg IV dose (immediately after injection)
Duration of effective plasma concentration: 6 h after 500 mg IV dose plasma levels fell below 1.0 mg/L
Flucloxacillin PO:
Peak serum concentration: 14.5 mg/L, 1 h after 500 mg PO dose
Duration of effective plasma concentration:
4 h after 500 mg PO dose, plasma level 2.2 mg/L
6 h after 500 mg PO dose, plasma level <1.0 mg/L in non-fasting subjects.
Published MIC values
S. aureus (penicillin susceptible) : 0.1–0.25 mg/L
β-haemolytic streptococci : 0.05–0.1 mg/L
E. faecalis : 25 mg/L
Published MBC values
S. aureus (penicillin susceptible) : 0.2 mg/L
Streptococcus pyogenes : 0.4 mg/L
References
Iversen K, Ihlemann N, Gill SU, Madsen T, Elming H, Jensen KT, Bruun NE, Høfsten DE, Fursted K, Christensen JJ, Schultz M, Klein CF, Fosbøll EL, Rosenvinge F, Schønheyder HC, Køber L, Torp-Pedersen C, Helweg-Larsen J, Tønder N, Moser C, Bundgaard H. Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis. N Engl J Med. 2019 Jan 31;380(5):415-424.
Evelyn Brown, F Kate Gould, Oral antibiotics for infective endocarditis: a clinical review, Journal of Antimicrobial Chemotherapy, Volume 75, Issue 8, August 2020, Pages 2021–2027,