International guidelines on IE2,3 recommend 4–6 weeks of penicillin or ampicillin plus an aminoglycoside for treating β-lactam– and gentamicin-susceptible enterococcal IE. However, the results of previous studies2 led to a change in the Danish Society of Cardiology guidelines in 20073, when the course of gentamicin was reduced from 4 to 6 weeks to 2 weeks to reduce nephrotoxicity caused by prolonged treatment with aminoglycosides.
The evaluation of the impact of new recommendations in gentamicin duration on mortality, IE relapses and renal function has not been evaluated.
Aim of the Study
The objective was to evaluate the efficacy and safety of ampicilin plus short-course gentamicin for treating non-high level aminoglycoside resistance (non-HLAR) EFIE in Denmark.
The present study was designed as a non-randomized, non-controlled clinical trial that included a prospectively collected consecutive cohort (after 2007; n=43) and a historical control group (before 2007; n=41) of patients with non-HALR EFIE from tertiary centers.
The primary outcome was 12-month event-free survival (mortality, IE relapses). Secondary outcomes were in-hospital mortality and change in renal function during treatment.
Baseline characteristics (including Charlson comorbidity index, duration of symptoms, basal renal function and rates of prosthetic valve endocarditis) were similar in both groups. The historical control group received gentamicin for a significantly longer period (28 vs 14 days; p<0.001). No statistically significant differences were detected in the primary end point, event-free 1-year survival (66% vs 69;p=0.75), even after stratification by prosthetic valve endocarditis. No differences were found in heart failure, stroke or other embolisms, in-hospital surgery, in-hospital mortality, or relapses. Nonetheless; patients treated before 2007 had a significantly greater loss in renal function (median loss in estimated glomerular filtration rate, 11 vs 1ml/min; p=0.009) compared with those treated after 2007.
The recommended 2-week treatment with gentamicin seems adequate and preferable in treating non–HLAR EFIE. The longer duration of gentamicin treatment is associated with worse renal function.
This study represents the largest investigation so far of the relationship between gentamicin treatment and 1-year outcome in EFIE, providing novel data on non-HLAR EFIE and amynoglycoside use. A short-course gentamicin strategy of 2 weeks seems as efficacious and less nephrotoxic than 4 to 6 weeks.
Some strengths of the study included the evidence that nephrotoxicity was associated with the duration of gentamicin therapy, given that at 2 weeks the decrease on glomerular filtration rate was very small and similar in both cohort (p=0.65). This finding is especially relevant because the typical EFIE patient is older with high rates of chronic renal failure and a high risk of renal impairment.
However, the study suffered from certain limitations. It is a not randomized, controlled trial, with a small sample size of both cohorts and restricted to tertiary centers. Moreover, it does not account for adverse events other than renal failure secondary to aminoglycoside treatment
Corresponding author from original paper
Dr. Anders Dahl, MD, Niels Andersens Vej 65, 2900 Hellerup, Denmark.
1.- Danish Society of Cardiology. Infective endocarditis: diagnosis and treatment: Danish Society of Cardiology guidelines. 2007.
http://cardio.dk/component/docman/doc_download/129infektiosendokardit?Itemid=247. Accessed May 17, 2013
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Citation: Circulation. 2013;127:1810-1817