Changes in the treatment of Enterococcus faecalis infective endocarditis in Spain in the last 15 years: from ampicillin plus gentamicin to ampicillin plus ceftriaxone

Abstract

The aim of this study was to assess changes in antibiotic resistance, epidemiology and outcome among patients with Enterococcus faecalis infective endocarditis (EFIE) and to compare the efficacy and safety of the combination of ampicillin and gentamicin (A+G) with that of ampicillin plus ceftriaxone (A+C). The study was a retrospective analysis of a prospective cohort of EFIE patients treated in our centre from 1997 to 2011. Thirty patients were initially treated with A+G (ampicillin 2 g/4 h and gentamicin 3 mg/kg/day) and 39 with A+C (ampicillin 2 g/4 h and ceftriaxone 2 g/12 h) for 4-6 weeks. Increased rates of high-level aminoglycoside resistance (HLAR; gentamicin MIC ≥512 mg/L, streptomycin MIC ≥1024 mg/L or both) were observed in recent years (24% in 1997-2006 and 49% in 2007-2011; p 0.03). The use of A+C increased over time: 1997-2001, 4/18 (22%); 2002-2006, 5/16 (31%); 2007-2011, 30/35 (86%) (p <0.001). Renal failure developed in 65% of the A+G group and in 34% of the A+C group (p 0.014). Thirteen patients (43%) in the A+G group had to discontinue treatment, whereas only one patient (3%) treated with A+C had to discontinue treatment (p<0.001). Only development of heart failure and previous chronic renal failure were independently associated with 1-year mortality, while the individual antibiotic regimen (A+C vs. A+G) did not affect outcome (OR, 0.7; 95% CI, 0.2-2.2; p 0.549). Our study shows that the prevalence of HLAR EFIE has increased significantly in recent years and that alternative treatment with A+C is safer than A+G, with similar clinical outcomes, although the sample size is too small to draw firm conclusions. Randomized controlled studies are needed to confirm these results.

A Review of Combination Antimicrobial Therapy for Enterococcus faecalis Bloodstream Infections and Infective Endocarditis

“…However, patients treated with AG had significantly higher rates of adverse events (ie, renal impairment) requiring therapy withdrawal [11]. These findings coincide with a retrospective study of prospectively collected data that evaluated 69 episodes of IE caused by E. faecalis (30 subjects in AG group; 39 subjects in AC group) [12]. Similar to Fernández-Hidalgo and colleagues, the authors did not observe a difference in in-hospital mortality or 1-year mortality between the AG and AC groups, and found that patients on AG had higher rates of treatment-induced renal failure than patients receiving AC.…”

“…Clinical data have since evaluated the combination of AC against HLAR and non-HLAR E. faecalis IE [6,11,12]. In 2007, Gavaldà et al assessed the efficacy and safety of AC in 21 patients with HLAR, and 22 patients with non-HLAR E. faecalis IE in a multicenter, open-label clinical trial [6].…”

2015 ESC Guidelines for the management of infective endocarditis

“…Po pierwsze, w kilku badaniach kohortowych dotyczących IZW wywołanego E. faecelis, obejmujących setki przypadków, wykazano, że w przypadkach szczepów E. faecalis bez HLAR, ampicylina zastosowana łącznie z ceftriaksonem wykazuje podobną skuteczność co ampicylina podawana łącznie z gentamicyną. Leczenie jest również bezpieczniejsze, pozbawione ryzyka nefrotoksyczności [183][184][185]. Ponadto jest to schemat terapii z wyboru w leczeniu IZW wywołanego przez E. faecalis z HLAR.…”

Infective Endocarditis

“…Recent data suggest that the combination of ampicillin and ceftriaxone may be effective for IE due to ampicillin-susceptible E. faecalis, particularly in patients with aminoglycoside resistance, or in whom there is concern for nephrotoxicity with an aminoglycoside 164,165 . Vancomycin-resistant enterococcal IE is fortunately rare, but has been successfully treated with linezolid 166 and daptomycin 152 ; If daptomycin is used, high dose therapy may be considered 101 .…”