The objective of this study was to investigate predisposing factors and outcomes of infective endocarditis (IE) caused by non-HACEK Gram-negative bacilli (GNB) in a contemporary multicenter cohort. 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 age- and sex-matched controls with IE due to other etiologies. Logistic regression was performed to identify risk factors for IE due to GNB. Factors associated with early and late mortality were assessed by Cox regression analysis. The study group comprised 58 patients with IE due to GNB. We found that was the most common pathogen, followed by and The genitourinary tract as a source of infection (odds ratio [OR], 13.59; 95% confidence interval [CI], 4.63 to 39.93; < 0.001), immunosuppression (OR, 5.16; 95% CI, 1.60 to 16.24; = 0.006), and the presence of a cardiac implantable electronic device (CIED) (OR, 3.57; 95% CI, 1.55 to 8.20; = 0.003) were factors independently associated with IE due to GNB. In-hospital mortality was 13.8%, and mortality rose to 30.6% at 1 year. A multidrug-resistant (MDR) etiology was associated with in-hospital mortality (hazard ratio [HR], 21.849; 95% CI, 2.672 to 178.683; = 0.004) and 1-year mortality (HR, 4.408; 95% CI, 1.581 to 12.287; = 0.005). We conclude that the presence of a genitourinary focus, immunosuppressive therapy, and an indwelling CIED are factors associated with IE due to GNB. MDR etiology is the major determinant of in-hospital and long-term mortality.
BackgroundEmbolic 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.MethodsWe 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).ResultsThere 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).ConclusionsStaphylococcus 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.
Fluconazole (800-1,000 mg i.v.) was administered to 14 consecutive patients with AIDS and cryptococcal meningitis. At 10 weeks the rate of clinical success was 54.5% (six of 11 patients responded to fluconazole); the Kaplan-Meier estimate of the response rate was 67.1%, and the overall mortality rate was 18.2% (two of 11 patients died). At the end of treatment, eight (72.7%) of 11 patients responded to fluconazole. The median time to the first negative cerebrospinal fluid (CSF) culture was 33.5 days (95% confidence interval, 18.3-67.3); the median time for patients with initial CSF cryptococcal antigen titers of > or = 1:1,024 was 66 days compared with 18 days for patients with initial CSF cryptococcal antigen titers of < 1:1,024 (P = .06). The median time to the first negative CSF culture for patients with an isolate for which the minimum inhibitory concentration (MIC) was 4 micrograms/mL was 56 days compared with 16 days for patients with an isolate for which the MIC was < 4 micrograms/mL (P = .11). The mean serum and CSF levels of fluconazole at steady state were 42.47 +/- 26.31 micrograms/mL and 36.63 +/- 21.08 micrograms/mL, respectively (ratio of CSF:serum, 0.86). No treatment was interrupted and no dose was tapered because of side effects. High-dose fluconazole might be an effective and well-tolerated therapeutic option for patients with AIDS and acute cryptococcal meningitis.
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