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Introduction: long term suppressive antibiotic treatment may be the only feasible option for patients with infective endocarditis (IE) not suitable for surgery., Case Reports: we present three cases of prosthetic valve endocarditis (PVE) caused by Enterococcus faecalis and Streptococcus gallolyticus which could not undergo surgical intervention due to high risk. Despite this, patients were successfully managed only by medical approach. Following intravenous targeted antimicrobial therapy, patients received chronic suppressive antimicrobial therapy (SAT) for at least twelve months with oral amoxicillin. In all cases, no further febrile episodes nor bacteraemia were observed and in two cases a complete positron emission tomography (PET) response was achieved. Due to a priori uncertainty about antimicrobial exposure during oral SAT, serum bactericidal titres (SBTs) were obtained and compared to those obtained during parenteral therapy., Conclusions: long term oral amoxicillin was effective and well-tolerated. SBTs after switch to oral therapy were quite heterogeneous, in some cases not reaching the conventionally established titre to assess bactericidal effect (1:8).Key pointsendovascular infection in non-suitable-for-surgery patients can be managed with long-term oral suppressive therapy.serum bactericidal assay confirmed high effectiveness of parenteral antibiotic therapy.serum bactericidal assay showed highly variable titres during oral therapy.