Partial oral versus intravenous antibiotic treatment of endocarditis

1. JOURNAL CLUB
- DR. MOTE SRIKANTH

3. BACKGROUND
• Patients with infective endocarditis on the left side of the heart are
typically treated with intarvenous antibiotic agents up to 6 weeks
,whether a shift from intravenous to oral antibiotics once the patient
is stable condition would result in efficacy and safety .

4. 1. NAME OF THE JOURNAL: The NEW ENGLAND JOURNAL of
MEDICINE
2. IMPACT FACTOR: 79.258
• RANKING: First of 153 journals in the category ”General & Internal
Medicine”

5. 1. TYPE OF ARTICLE: RANDOMISED CONTROLLED TRIAL
2. NAME OF THE AUTHORS: Kasper Iversen, M.D., D.M.Sc., Nikolaj Ihlemann, M.D., Ph.D.,
Sabine U. Gill, M.D., Ph.D., Trine Madsen, M.D., Ph.D., Hanne Elming, M.D., Ph.D., Kaare
T. Jensen, M.D., Ph.D., Niels E. Bruun, M.D., D.M.Sc.,
Dan E. Høfsten, M.D., Ph.D., Kurt Fursted, M.D., D.M.Sc.,
Jens J. Christensen, M.D., D.M.Sc., Martin Schultz, M.D., Christine F. Klein, M.D., Emil L.
Fosbøll, M.D., Ph.D., Flemming Rosenvinge, M.D.,
Henrik C. Schønheyder, M.D., D.M.Sc., Lars Køber, M.D., D.M.Sc., Christian
Torp‐Pedersen, M.D., D.M.Sc., Jannik Helweg‐Larsen, M.D., D.M.Sc., Niels Tønder, M.D.,
D.M.Sc., Claus Moser, M.D., Ph.D.,
and Henning Bundgaard, M.D., D.M.Sc

6. 1. STUDY DESIGN: Open label Randomised Controlled Trial
interventional, non-inferiority. (POET – PARTIAL ORAL TREATMENT
OF ENDOCARDITIS)
2. STUDY CENTRE: Multicentre
3. PLACE OF STUDY: Denmark
4. TIME OF STUDY: 15 June 2011– 30 August 2017
5. TRIAL SPONSOR: Danish Heart Foundation, Capital Regions Research
Council, Hartmann’s Foundation, Svend Aage Andersens Foundation,
Novo Nordisk Foundation

7. AIM OF THE STUDY
• AIM: To study if treatment with oral antibiotics instead of
intravenous antibiotics safe in stable patients with infective
endocarditis.

8. RESEARCH QUESTION ?
• Is treatment with oral antibiotics instead of intravenous antibiotics safe in stable
patients with endocarditis?

9. MATERIALS & METHODS:
1. POET TRIAL : The POET study is a Danish multicenter, prospective,
randomized, open label study. The primary aim is to show non-inferiority of
partial oral treatment with antibiotics of endocarditis compared to full
parenteral treatment.
2. 400 participants

10. • Study variables: The following data are collected for the included patients:
• Demographics, vitals, clinical status and results of clinical, biochemical,
microbiological and imaging examinations.
• Personal Identification number (Danish Civil Registration number )
• Results of the routine blood tests at admission and at randomization. Routine
biomarkers: Hemoglobin, Leukocytes, thrombocytes, sodium, potassium, C-
reactive protein, e GFR, Creatinine, Albumin.

12. ANTIBIOTICS USED
• Intravenous : It was administered in accordance with guidelines of the European
Society of cardiology .
• POET : Amoxicillin, Linezolid, Fusidic acid, Linezolid, rifampicin,
dicoxallin,Moxifloxacin,clindamycin

13. • Oral regimens recommended in the POET trial
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

14. • 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

15. • 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

16. • 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

17. • Streptococci with a minimal inhibitory concentration for penicillin of <1 mg/L: 17
• 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

18. • 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 0.6 g x3

21. SAMPLE SIZE:
• SAMPLE SIZE – 400
• Patient receiving intravenous antibiotics :199
• Patient receiving oral antibiotics: 201

22. RANDOMIZATION:

23. INCLUSION CRITERIA
• Left-sided endocarditis based on the Duke criteria
• Infected with one of the following microorganisms:
• Streptococci
• Enterococcus faecalis
• Staphylococcus aureus
• Coagulase-negative staphylococci
• ≥ 18 years

24. • ≥ 10 days of appropriate parenteral antibiotic treatment overall, and at least 1
week of appropriate parenteral treatment after valve surgery .
• T<38.0°C)>2days .
• C-reactive protein dropped to less than 25% of peak value or < 20 mg/L, and
white blood cell count < 15 x 109/L during antibiotic treatment .
• No sign of abscess formation revealed by echocardiography .
• Transthoracic and transesophageal echocardiography performed within 48 hours
of randomization .

25. EXCLUSION CRITERIA:
1. Body mass index > 40.
2. Concomitant infection requiring intravenous antibiotic therapy.
3. Inability to give informed consent to participation.
4. Suspicion of reduced absorption of oral treatment due to abdominal disorder.
5. Reduced compliance .

26. STATISTICAL METHODS
• Variables presented as means /standard deviation/median/interquartile ranges
• Mann-Whitney U test
• Chi-square test
• SPSS software
• Yates’s correction for continuity

27. PRIMARY OUTCOMES

28. RESULTS

37. LIMITATIONS
• Endocarditis on the left side of heart
• Patient with endocarditis caused by certain bacterial species were eligible .
• Patient with simultaneous infection of cardiovascular implantable electronic
device or endocarditis on the right side side of the heart were not excluded .
• Discharge of patients who were receiving oral treatment to outpatient treatment
was not mandatory .

38. CONCLUSION
• The patients who have endocarditis on the lest side of the heart caused by
streptococcus ,E faecalis ,S.aureus, or Couglase-negative staphylococci and who
were in stable condition , a shift from intravenously administred to orally
administered antibiotic treatment was noninferior to continued itravenous
antibiotic treatment .

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