Predicting the occurrence of embolic events: an analysis of 1456 episodes of infective endocarditis from the Italian Study on Endocarditis (SEI)

Background: Embolic events are a major cause of morbidity and mortality in patients with infective endocarditis. We analyzed the database of the prospective cohort study SEI in order to identify factors associated with the occurrence of embolic events and to develop a scoring system for the assessment of the risk of embolism. Methods: We retrospectively analyzed 1456 episodes of infective endocarditis from the multicenter study SEI. Predictors of embolism were identified. Risk factors identified at multivariate analysis as predictive of embolism in left-sided endocarditis, were used for the development of a risk score: 1 point was assigned to each risk factor (total risk score range: minimum 0 points; maximum 2 points). Three categories were defined by the score: low (0 points), intermediate (1 point), or high risk (2 points); the probability of embolic events per risk category was calculated for each day on treatment (day 0 through day 30).Results: There were 499 episodes of infective endocarditis (34%) that were complicated by 65 1 embolic event. Most embolic events occurred early in the clinical course (first week of therapy: 15.5 episodes per 1000 patient days; second week: 3.7 episodes per 1000 patient days). In the total cohort, the factors associated with the occurrence of embolism at multivariate analysis were prosthetic valve localization (odds ratio, 1.84), right-sided endocarditis (odds ratio, 3.93), Staphylococcus aureus etiology (odds ratio, 2.23) and vegetation size 65 13 mm (odds ratio, 1.86). In left-sided endocarditis, Staphylococcus aureus etiology (odds ratio, 2.1) and vegetation size 65 13 mm (odds ratio, 2.1) were independently associated with embolic events; the 30-day cumulative incidence of embolism varied with risk score category (low risk, 12%; intermediate risk, 25%; high risk, 38%; p < 0.001).Conclusions: Staphylococcus aureus etiology and vegetation size are associated with an increased risk of embolism. In left-sided endocarditis, a simple scoring system, which combines etiology and vegetation size with time on antimicrobials, might contribute to a better assessment of the risk of embolism, and to a more individualized analysis of indications and contraindications for early surgery

Mitochondrial changes during D-drug-containing once-daily therapy in HIV-positive treatment-naive patients

BackgroundAntiviral drugs of the category of nucleoside reverse transcriptase inhibitors (NRTIs), largely used for the treatment of HIV infection, can have toxic effects on mitochondria. We performed a cross-sectional study on mitochondrial toxicity in a randomized group of patients belonging to a larger randomized study on different NRTI-based once-daily regimens by quantifying mitochondrial DNA (mtDNA), three different mitochondrial RNAs (mtRNAs) and functional parameters in highly purified peripheral CD4+and CD8+T-cells.MethodsA total of 49 previously treatment-naive patients treated for a mean of 15 months with efavirenz plus didanosine plus lamivudine (group 1), or tenofovir disoproxil fumarate plus lamivudine (group 2), or didanosine plus abacavir (group 3) were considered. The groups were matched for sex, age, CDC classification, risk factor for HIV, nadir CD4+T-cell count and baseline viral load. mtDNA and mtRNA were quantified by using real-time PCR assays.ResultsNo patient showed any clinical symptom; however, the amount of mtDNA in CD4+and CD8+T-cells was significantly lower in groups 1 and 3; similarly, the expression of different mtRNAs in both CD4+and CD8+T-cells showed significant differences that were dependent upon the drug used. No differences were found in mitochondrial membrane potential and mitochondrial mass in peripheral lymphocytes. The amount of total HIV DNA in CD4+T-cells did not differ among the groups, who displayed a similar immune reconstitution and control of the virus.ConclusionsAn efficient didanosine-containing once-daily therapy can have more mitochondrial toxicity than regimens devoid of this drug

Typing of Enterococcus spp. strains isolated from patients with infective endocarditis by an automated repetitive-sequence-based PCR system

The use of rep-PCR was studied to characterize 32 isolates of Enterococcus spp. from Italian patients with infective endocarditis and determine specific banding patterns associated with antimicrobial resistance phenotypes. The results obtained with rep-PCR were analyzed with respect to the antimicrobial profile by a MIC evaluation (E-test) of all strains tested. The automated rep-PCR technique resulted an easy method for the characterization of Enterococcus spp. It confirmed the eterogenicity of enterococcal strains involved in infective endocarditis. Furthermore results of antimicrobial susceptibility revealed that rep-PCR can not be used as diagnostic tool to characterize and identify difference between resistant and susceptible Enterococcus spp. strains

Antimicrobial susceptibility of enterococci from Italian patients with infective endocarditis

The epidemiological and clinical study “Studio Endocarditi Italiane” (SEI) evaluated 947 cases of infective endocarditis in 2004-2008. Enterococcal aethiology was described in 11% cases.The aim of our study was to evacuate the in vitro activity of twelve antibiotics alone and in association against 20 strains (15 E. faecalis, 5 E. faecium). Results show the in vitro activity of tigecyicline, daptomicine and linezolid. Synergism is appreciated for ceftriaxone-fosfomycin (FICindex50=0.34, FICindex90=0.56) against E. faecalis and for imipenem-fosfomycin against E. faecium.The majority of the tested strains show addition using ampicillin-ceftriaxone (FICindex50=0.85, FICindex90=1.01) and moxifloxacin- tigecycline (FICindex50=0.77, FICindex90=1.96)

Risk factors and outcomes of endocarditis due to non-HACEK gram-negative bacilli: Data from the prospective multicenter Italian endocarditis study cohort

Objective: To investigate predisposing factors and outcomes of non-HACEK Gram-negative bacilli (GNB) infective endocarditis (IE) in a multicenter, contemporary cohort.Patients and Methods:Patients with IE due to GNB prospectively observed in 26 Italian centers from 2004 to 2011 were analyzed. Using a case-control design, each case was compared to three controls with IE by other etiologies matched for age and sex. Logistic regression was performed to identify risk factors for GNB IE. Factors associated with early and late mortality were assessed by Cox regression analysis.Results:The study group comprised 58 patients with GNB IE.Escherichia coliwas the most common pathogen followed byPseudomonas aeruginosaandKlebsiella pneumoniaeGenitourinary tract as source of infection (OR 13.59, 95% CI 4.63-39.93, p<.001), immunosuppression (OR 5.16, 95% CI 1.60-16.24, p=.006) and presence of a cardiac implantable electronic device (CIED) (OR 3.57, 95% CI 1.55-8.20, p=.003) were factors independently associated with GNB IE. The in-hospital mortality was 13.8%, and rose up to 30.6% at 1 year. A multidrug-resistant etiology was associated with in-hospital (HR 21.849, 95% CI 2.672-178.683, p=0.004) and 1-year mortality (HR 4.408, 95% CI 1.581-12.287, p=0.005).Conclusions:The presence of a genitourinary focus, immunosuppressive therapy and an indwelling CIED are factors associated with GNB IE. MDR etiology is the major determinant of in-hospital and long-term mortality

Candida endocarditis: systematic literature review from 1997 to 2014 and analysis of 29 cases from the Italian Study of Endocarditis

Candida Endocarditis (CE) is a deadly disease. It is of paramount importance to assess risk factors for acquisition of both Candida native (NVE) and prosthetic (PVE) valve endocarditis and relate clinical features and treatment strategies with the outcome of the disease. Areas covered: We searched the literature using the Pubmed database. Cases of CE from the Italian Study on Endocarditis (SEI) were also included. Overall, 140 cases of CE were analyzed. Patients with a history of abdominal surgery and antibiotic exposure had higher probability of developing NVE than PVE. In the PVE group, time to onset of CE was significantly lower for biological prosthesis compared to mechanical prosthesis. In the whole population, greater age and longer time to diagnosis were associated with increased likelihood of death. Patients with effective anti-biofilm treatment, patients who underwent cardiac surgery and patients who were administered chronic suppressive antifungal treatment showed increased survival. For PVE, moderate active anti-biofilm and highly active anti-biofilm treatment were associated with lower mortality. Expert commentary: Both NVE and PVE could be considered biofilm-related diseases, pathogenetically characterized by Candida intestinal translocation and initial transient candidemia. Cardiac surgery, EAB treatment and chronic suppressive therapy might be crucial in increasing patient survival

Bactericidal activity of oxacillin and glycopeptides against <it>Staphylococcus aureus </it>in patients with endocarditis: Looking for a relationship between tolerance and outcome

Abstract Background There is no clear relationship between in vitro bactericidal activity tests and clinical outcome. We studied bactericidal activity of oxacillin, vancomycin and teicoplanin against Staphylococcus aureus isolates in patients with endocarditis and then we sought to determine if there was a relationship between in vitro bactericidal activity and clinical outcome. Methods Minimal bacteriostatic and minimal bactericidal concentrations were determined for Staphylococcus aureus strains isolated from patients with endocarditis following standardized methods. Medical records were reviewed retrospectively to collect data on antimicrobial susceptibility at admission, antimicrobial therapy, need for surgery, embolic events and outcome. Results and Discussion Sixty-two Staphylococcus aureus strains were studied in 62 patients with endocarditis. Overall, 91.9% definite, 21% methicillin resistant and 72.6% cured. Surgery was performed in 32.3% and embolic events were documented in 64.5%. Tolerance to oxacillin and teicoplanin was more common than vancomycin tolerance among methicillin susceptible Staphylococcus aureus. Among methicillin resistant Staphylococcus aureus teicoplanin was shown to have a higher rate of tolerance than vancomycin. No statistically significant differences on clinical outcome between oxacillin tolerant and oxacillin non tolerant Staphylococcus aureus infections were observed. Tolerance to oxacillin did not adversely affect clinical outcomes of patients with methicillin susceptible Staphylococcus aureus endocarditis treated with a combination of antimicrobials including oxacillin. The cure rate was significantly lower among patients with methicillin resistant Staphylococcus aureus endocarditis. Conclusions In vitro bactericidal test results were not valid predictors of clinical outcome. Physicians need to use additional parameters when treating patients with staphylococcal endocarditis.</p

Candida Infective Endocarditis Report of 15 Cases From a Prospective Multicenter Study

Candida species are an uncommon cause of infective endocarditis (IE). Given the rarity of this infection, the epidemiology, prognosis, and optimal therapy of Candida IE are poorly defined. We conducted a prospective, observational study at 18 medical centers in Italy, including all consecutive patients with a definite diagnosis of IE admitted front January 2004 through December 2007. A Candida species was the causative organism in 8 cases of prosthetic valve endocarditis (PVE), 5 cases of native valve endocarditis (NVE), I case of pacemaker endocarditis, and I case of left ventricular patch infection. Candida species accounted for 1.8% of total cases, and for 3.4% of PVE cases. Most patients (86.6%) had a health care-associated infection. PVE associated with a health care contact occurred after a median of 225 days from valve implantation. Ten patients (66.6%) were treated with caspofungin alone or in combination with other antifungal drugs. The overall mortality rate was 46.6%. Mortality was higher in patients with PVE (5 of 8 cases, 62.5%) than in patients with NVE (2 of 5 patients, 40%). A better outcome was observed in patients treated with a combined medical and surgical therapy. Candida IE should be classified as an emerging infectious disease, usually involving patients with intravascular prosthetic devices, and associated with substantial related morbidity and mortality. Candida PVE usually is a late-onset disease, which becomes clinically evident even several months after an initial episode of transient candidemia. (Medicine 2009;88: 160-168

Current features of infective endocarditis in persons on hemodialysis: a prevalence study with case control design from the prospective multicenter SEI cohort

Purpose: Persons on hemodialysis (HD) are at high risk of infective endocarditis (IE). In non-comparative retrospective studies, a higher rate of mortality was reported in IE on HD. We assessed risk factors, clinical characteristics, and outcomes of IE in HD. Methods: This was a prevalence study with a case control methodology on a set of data from the prospectively followed cohort of the Studio Endocarditi Italiano (SEI), conducted between 2004 and 2011. Included were 42 consecutive cases of IE HD subjects and 126 controls not on HD, matched for age, sex, type of IE, and heart side involved. Clinical, echocardiographic, microbiological features, and disease complications and therapeutic modalities were assessed. Results: HD patients were more often diabetics (42.9 vs 18.2 % in no-HD; p = 0.007) and immune-suppressed (16.7 vs 3.2 %; p = 0.02), and had a higher rate of predisposing cardiac conditions (45 vs 25 %; p = 0.031). A higher prevalence of health care-related acquisition and a shorter diagnostic delay was observed in IE on HD, that was more likely to be caused by staphylococci and less by streptococci (p < 0.002). Cardiac surgery was performed in 38 % of HD patients and 36.5 % of no-HD patients (p = 0.856). Complications were similar and in-hospital mortality did not differ significantly (26.2 % in HD vs 15.9 % in no-HD; p = 0.168). Conclusions: IE in persons on HD is characterized by distinctive clinical features, including a higher prevalence of some important comorbidities. Inconsistent with prior studies, we could not confirm a higher rate of complications and mortality in HD patients with IE

Predicting the occurrence of embolic events: an analysis of 1456 episodes of infective endocarditis from the Italian Study on Endocarditis (SEI)

BACKGROUND: Embolic events are a major cause of morbidity and mortality in patients with infective endocarditis. We analyzed the database of the prospective cohort study SEI in order to identify factors associated with the occurrence of embolic events and to develop a scoring system for the assessment of the risk of embolism. METHODS: We retrospectively analyzed 1456 episodes of infective endocarditis from the multicenter study SEI. Predictors of embolism were identified. Risk factors identified at multivariate analysis as predictive of embolism in left-sided endocarditis, were used for the development of a risk score: 1 point was assigned to each risk factor (total risk score range: minimum 0 points; maximum 2 points). Three categories were defined by the score: low (0 points), intermediate (1 point), or high risk (2 points); the probability of embolic events per risk category was calculated for each day on treatment (day 0 through day 30). RESULTS: There were 499 episodes of infective endocarditis (34%) that were complicated by ≥ 1 embolic event. Most embolic events occurred early in the clinical course (first week of therapy: 15.5 episodes per 1000 patient days; second week: 3.7 episodes per 1000 patient days). In the total cohort, the factors associated with the occurrence of embolism at multivariate analysis were prosthetic valve localization (odds ratio, 1.84), right-sided endocarditis (odds ratio, 3.93), Staphylococcus aureus etiology (odds ratio, 2.23) and vegetation size ≥ 13 mm (odds ratio, 1.86). In left-sided endocarditis, Staphylococcus aureus etiology (odds ratio, 2.1) and vegetation size ≥ 13 mm (odds ratio, 2.1) were independently associated with embolic events; the 30-day cumulative incidence of embolism varied with risk score category (low risk, 12%; intermediate risk, 25%; high risk, 38%; p < 0.001). CONCLUSIONS: Staphylococcus aureus etiology and vegetation size are associated with an increased risk of embolism. In left-sided endocarditis, a simple scoring system, which combines etiology and vegetation size with time on antimicrobials, might contribute to a better assessment of the risk of embolism, and to a more individualized analysis of indications and contraindications for early surgery