Short-course Antibiotic Treatment in Gram-positive Cocci Infective Endocarditis
Short-course Antibiotic Treatment in Gram-positive Cocci Infective Endocarditis
Background: it is well known that most serious complications of infective endocarditis (IE)
 appear in the so-called "critical phase" of the disease, which are the first days after
 diagnosis. Subsequently, the vast majority of patients who overcome this acute phase has a
 favourable evolution, and usually stay in the hospital for a long time only to complete
 antibiotic therapy.

 In stable patients with adequate response to antibiotic treatment, without signs of
 persistent infection or metastatic foci such as spondylodiscitis, it is likely that a shorter
 antibiotic regimen would be an efficient and safe alternative, as has already been confirmed
 in patients with IE on tricuspid valves caused by a microorganism considered virulent such as
 S. aureus. This attractive alternative would improve patients' quality of life, save costs,
 and decrease the risk of complications related to the adverse effects of prolonged antibiotic
 treatment.

 Objectives: to compare the incidence of the composite endpoint of all-cause mortality,
 unplanned cardiac surgery, symptomatic embolisms and relapses within 6 months after the
 inclusion between patients with IE caused by gram-positive cocci receiving a short-course of
 2 weeks of antibiotic therapy and those patients receiving conventional antibiotic therapy
 (4-6 weeks).

 Methodology: multicenter, prospective, randomized, controlled open-label, phase IV clinical
 trial. Sample: patients with IE caused by gram-positive cocci, having received at least 10
 days of conventional antibiotic treatment, and at least 7 days after surgery when indicated,
 without clinical, analytical, microbiological or echocardiographic signs of persistent
 infection. Estimated sample size: 298 patients. Intervention: Control group: standard
 antibiotic therapy, according to ESC guidelines recommendations, for 4 to 6 weeks.
 Experimental group: short-course antibiotic therapy for 2 weeks. The prevalence of previously
 known risk factors for adverse events will be compared between the two groups to confirm that
 randomization have worked properly. The incidence of the composite endpoint of all-cause
 mortality, unplanned cardiac surgery, symptomatic embolisms and relapses within 6 months
 after the inclusion in the study will be prospectively registered and compared.
Inclusion Criteria:

 -  Definite IE, according to modified ESC 2015 criteria, caused by gram-positive cocci
 (staphylococci, streptococci and enterococci), including native, prosthetic valve IE
 and cardiac device-related IE.

 -  18 years old or older.

 -  Patients treated for at least 10 days of appropriate parenteral antibiotic therapy
 overall (according to guidelines and microbiology sensitivity testing), and at least 7
 days of parenteral antibiotic therapy after valve surgery when indicated.

 -  Absence of fever, microbiological or analytical findings suggesting persistent
 infection at randomization.

 -  Absence of locally uncontrolled infection signs (abscess, pseudoaneurysm, fistula,
 enlarging vegetation) at randomization, confirmed by recent transesophageal
 echocardiography (performed within 48 h of randomization).

 -  Women of childbearing potential who will agree to the use of effective contraceptive
 methods while on antibiotic treatment.

 Exclusion Criteria:

 -  Patients who have received appropriate parenteral antibiotic therapy for infective
 endocarditis for more than 12 days.

 -  Patients not suitable to be discharged after 10 days of conventional treatment, due to
 clinical reasons (sequels of stroke that prevent discharge, progressive renal failure,
 hepatic failure).

 -  Patients receiving chemotherapy or immunosuppressive therapy.

 -  Pregnant or breastfeeding women.

 -  Need of prolonged antibiotic therapy due to spondylodiscitis or other septic
 complication.

 -  Absence of patient's ability or commitment to continue follow-up after being
 discharged from hospital.

 -  Inability to give informed consent to participation.

 -  Cognitive impairment or lack of language skills needed to complete the questionnaires.

 -  Patients who meet urgent cardiac surgery ESC criteria but are considered inoperable
 due to high surgical risk.