A New Era for Treating Enterococcus faecalis Endocarditis

Abstract

Enterococci are the third most common etiologic agent of infective endocarditis worldwide after staphylococci and streptococci and cause 10% to 15% of cases.1 Enterococcal infections are increasingly relevant, especially among the elderly and patients with comorbid conditions in the healthcare setting.2,3 Approximately 90% of cases of enterococcal endocarditis are caused by Enterococcus faecalis , with <5% caused by E. faecium .2,3 The morbidity and mortality of enterococcal endocarditis are high. The percentage of patients requiring cardiac surgery (42%) and the 1-year mortality rate (29%) have remained almost unchanged for the last 30 years; recent data show that they may even be increasing.3 Article see p 1810 This worrying picture is worsened by the increase in resistance to classic antimicrobials, especially high-level aminoglycoside resistance (HLAR). However, American Heart Association guidelines4 have not modified their antibiotic recommendations on non-HLAR strains for almost 6 decades, and no randomized clinical trials support current evidence. Because the empirical use of ampicillin plus streptomycin has proven efficacious5 and synergistic (increased cell membrane permeability to aminoglycosides induced by β-lactams in vitro with enterococci),6 the efficacy of combining a β-lactam with an aminoglycoside is unquestionable. The latest AHA guidelines maintain penicillin or ampicillin (or vancomycin in case of allergy to β-lactams) plus gentamicin as the combination of choice for E. faecalis infective endocarditis (EFIE) caused by non-HLAR strains.4 Recommendations on length of treatment have also remained unchanged since the 1980s,7 namely 4 weeks for patients with uncomplicated native valve endocarditis and 6 weeks for patients with prosthetic valve endocarditis and patients with a >3-month history of symptoms before diagnosis.4 The gentamicin dose schedule (3 mg/kg per 24 hours IV …