Oral Switch During Treatment of Left-sided Endocarditis Due to Multi-susceptible Streptococcus

Inclusion Criteria:

• Left-sided IE (Defined according to Duke criteria) on native or prosthetic valve

• due to one isolate of Streptococcus/Enterococcus sp. susceptible to amoxicillin (MCI ≤ 0.5 mg/l)

• in an adult ≥18 year old

• appropriate parenteral antibiotics treatment received for at least 10 days

• in case of valvular surgery, appropriate parenteral antibiotics treatment receivedfor at least 10 days after valvular surgery

• planned duration of antibiotics will extend for at least 14 days at the time ofrandomisation i.e. a potential switch to oral treatment between Day 10 and Day 28thus ensuring to have at least 14 days of oral therapy remaining in the experimentalgroup

• apyrexia (temperature < 38°C) at each time point during the last 48 hours (at leasttwo measures/day) at the time of randomisation

• blood cultures have been sterile for at least 5 days at the time of randomisation

• informed, written consent obtained from patient

• subject covered by or having the rights to French social security

Exclusion Criteria:

• body mass index <15 kg/m² or > 40 kg/m²

• glomerular filtration rate < 30 ml/min/1,73m²

• patient unable or unwilling to take oral treatment (digestive intolerance,significant malabsorption) at the time of randomisation

• expected difficulties regarding compliance with oral antibiotic treatment orfollow-up (e.g. severe cognitive impairment, severe psychiatric disease...)

• patient without entourage to support and watch him at discharge

• valvular surgery planned within the next 6 months

• for patients with cardiac devices (pace-maker, implantable cardiac defibrillator)and suspected device-related IE (vegetation on the leads) if removal of the devicewas not performed

• breast feeding or pregnant women, or women on childbearing age without effectivecontraception

• expected duration of follow-up < 7 months at the time of randomisation (e.g.expected life expectancy < 7 months, patient living abroad...)

• past medical history of IE in the last 3 months

• other infection requiring parenteral antibiotic therapy

• taking of an estrogen-progesterone treatment interacting with rifampicin

• patient with contra-indication to oral antibiotics administered in the experimentalarm (i.e. amoxicillin) - including anticipated non-manageable drug interactions, andallergy.