Predictors of long-term mortality in left-sided infective endocarditis: an historical cohort study in 414 patients.

INTRODUCTION: Very limited data are available on the long-term outcome of infective endocarditis (IE) and its determinants. The aim of this study was to identify the predictors of long-term mortality in patients affected by left sided IE (LSIE). METHODS: This was an historical retrospective observational study on prospectively collected data from patients with LSIE hospitalized in our Unit (January 2000-December 2017). Multiple variables relevant to history, physical examination, laboratory tests, echocardiography, comorbidities, complications and outcome were analysed by Cox regression to identify predictors of long-term mortality. RESULTS: 414 patients were included, and followed up for a median of 39 months [IQR 11-74]. Median age was 59 years [range 3-89], and most patients were male. Over 50% showed at least one comorbidity. Hyperglycaemia, increased creatinine and an indication for surgery predicted in-hospital mortality, while a prior myocardial infarction, chronic kidney disease (CKD) on hemodialysis and a larger vegetation were independent predictors of 1-year mortality. At multivariate analysis, peripheral arterial disease (p= 0.017), hyperglycemia on admission (p=0.013) and a higher BMI (p=0.009) were independent predictors of long-term mortality in 1-year survivors. At multivariable Cox proportional hazard regression, peripheral arterial disease (p=0.002), hyperglycemia (p=0.041) and CKD on hemodialysis (p=0.025) confirmed to be independently associated with an increased risk of long-term mortality in the overall 414 patient cohort. CONCLUSIONS: Cardiovascular and metabolic risk signals, specifically peripheral arterial disease and hyperglicemia, affect long-term mortality of LSIE. An active and long-term follow up seems warranted in IE survivors showing these conditions at outset.

Safety of treatment with high-dose daptomycin in 102 patients with infective endocarditis.

Daptomycin is commonly used at doses >6 mg/kg/day for various indications, including infective endocarditis (IE). A systematic assessment of skeletal muscle, renal, haematological, hepatic and pulmonary toxicity of high-dose daptomycin (HDD) in IE is lacking. A total of 102 IE patients treated with HDD were included in this non-comparative, observational, single-centre cohort study conducted from 2007 to 2014. The incidence, timing, severity and evolution of adverse events (AEs) were assessed. Patients had a median age of 61.5 years and a high prevalence of co-morbidities. Staphylococci were cultured in 87.2% of cases (62.2% meticillin-resistant). The median daptomycin dose was 8.2 mg/kg/day for a median of 20 days (range, 1-60 days). HDD was withdrawn due to AEs in 12 patients (11.8%). On-treatment death occurred in 4 cases (3.9%, none HDD-related). Muscle toxicity occurred in 15 patients in a median of 15 days after HDD starts, which was largely mild and reversible with ongoing HDD use. Mild renal toxicity was observed in 9 patients (8.8%) after a median of 12 days of HDD (RIFLE-Risk in 8, Injury in 1). A rise of peripheral blood eosinophils occurred in 16 patients (15.7%). There were three cases of eosinophilic interstitial pneumonia. Four patients (3.9%) had mild allergic or idiosyncratic reactions. No other hepatic or haematological AEs were observed. Our current experience with 102 patients suggests that HDD is safe in significantly ill IE patients with multiple co-morbidities. Muscle toxicity was clinically negligible. Most importantly, there was no significant renal toxicity. Eosinophils should be carefully monitored.