Four weeks versus six weeks of ampicillin plus ceftriaxone in Enterococcus faecalis native valve endocarditis: A prospective cohort study.

Antonio Ramos-Martínez,M Carmen Fariñas,Maricela Valerio,Guillermo Ojeda-Burgos,Antonio Plata,Martha Kestler,Fernando Domínguez,Ana Fernández-Cruz,José María Miró,Dolores Sousa,Miguel Montejo,Patricia Muñoz,Juan Manuel Pericàs,Laura Vidal,Cécile Oury

doi:10.1371/journal.pone.0237011

Abstract

Enterococcus faecalis infective endocarditis (EFIE) is a severe disease of increasing incidence. The objective was to analyze whether the outcome of patients with native valve EFIE (NVEFIE) treated with a short course of ampicillin plus ceftriaxone (4wAC) was similar to patients treated according to international guidelines (6wAC). Between January 2008 and June 2018, 1,978 consecutive patients with definite native valve IE were prospectively included in a national registry. Outcomes of patients with NVEFIE treated with 4wAC were compared to those of patients who received 6wAC. Three hundred and twenty-two patients (16.3%) had NVEFIE. One hundred and eighty-three (56.8%) received AC. Thirty-nine patients (21.3%) were treated with 4wAC for four weeks and 70 patients (38.3%) with 6wAC. There were no differences in age or comorbidity. Patients treated 6wAC presented a longer duration of symptoms before diagnosis (21 days, IQR 7-60 days vs. 7 days, IQR 1-22 days; p = 0.002). Six patients presented perivalvular abscess and all of these received 6wAC. Surgery was performed on 14 patients (35.9%) 4wAC and 34 patients (48.6%) 6wAC (p = 0.201). In-hospital mortality, one-year mortality and relapses among 4wAC and 6wAC patients were 10.3% vs. 11.4% (p = 0.851); 17.9% vs. 21.4% (p = 0.682) and 5.1% vs. 4.3% (p = 0.833), respectively. In conclusion, a four-week course of AC may be considered as an alternative regimen in NVEFIE, notably in patients with shorter duration of symptoms and those without perivalvular abscess. These results support the performance of a randomized clinical trial to evaluate the efficacy of this short regimen.

Highlights

Enterococcus faecalis is the third most common cause of infective endocarditis (IE) [1]
Mortality during admission was 5.5% (2 patients), mortality during the first year was 22.2% (8 patients) and no cases of recurrence were recorded. This is the first cohort study to primarily focus on the prognosis of patients with E. faecalis infective endocarditis (EFIE) treated with a short course of ampicillin plus ceftriaxone (AC)
The study by Fernandez-Hidalgo et al confirmed that AC given for a median of six weeks was an effective therapy for EFIE and safer than four to six weeks of ampicillin plus gentamicin

Summary

Introduction

Enterococcus faecalis is the third most common cause of infective endocarditis (IE) [1]. The combination of ampicillin plus ceftriaxone (AC) is the antibiotic treatment of choice for EFIE in several settings, and especially so in Spain [4,5,6,7]. With respect to treatment duration, international guidelines recommend a 6 week-course of AC for native valve EFIE [8, 9]. These same guidelines accept the use of other antibiotic combinations (e.g. a beta-lactam plus gentamicin) for four weeks when the duration of symptoms is shorter than 3 months. Evidence is lacking from studies comparing the efficacy of shorter courses of AC with respect to the recommended duration of 6 weeks for the treatment of EFIE. The use of a shortened course of AC is relatively common for treating non-complicated native EFIE

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