Background—: The purpose of this study was to assess the incidence of neurological complications in patients with infective endocarditis, the risk factors for their development, their influence on the clinical outcome, and the impact of cardiac surgery. Methods and Results—: This was a retrospective analysis of prospectively collected data on a multicenter cohort of 1345 consecutive episodes of left-sided infective endocarditis from 8 centers in Spain. Cox regression models were developed to analyze variables predictive of neurological complications and associated mortality. Three hundred forty patients (25%) experienced such complications: 192 patients (14%) had ischemic events, 86 (6%) had encephalopathy/meningitis, 60 (4%) had hemorrhages, and 2 (1%) had brain abscesses. Independent risk factors associated with all neurological complications were vegetation size ≥3 cm (hazard ratio [HR] 1.91), Staphylococcus aureus as a cause (HR 2.47), mitral valve involvement (HR 1.29), and anticoagulant therapy (HR 1.31). This last variable was particularly related to a greater incidence of hemorrhagic events (HR 2.71). Overall mortality was 30%, and neurological complications had a negative impact on outcome (45% of deaths versus 24% in patients without these complications; P <0.01), although only moderate to severe ischemic stroke (HR 1.63) and brain hemorrhage (HR 1.73) were significantly associated with a poorer prognosis. Antimicrobial treatment reduced (by 33% to 75%) the risk of neurological complications. In patients with hemorrhage, mortality was higher when surgery was performed within 4 weeks of the hemorrhagic event (75% versus 40% in later surgery). Conclusions—: Moderate to severe ischemic stroke and brain hemorrhage were found to have a significant negative impact on the outcome of infective endocarditis. Early appropriate antimicrobial treatment is critical, and transitory discontinuation of anticoagulant therapy should be considered.

Previous studies have sought to determine the risk factors associated with candidemia caused by non- albicans Candida spp. or with potentially fluconazole-resistant Candida spp. ( C. glabrata and C. krusei ). Non- albicans Candida strains are a heterogeneous group that includes species with different levels of virulence, and only a limited number of C. glabrata isolates are resistant to fluconazole. We set out to identify the risk factors associated with microbiologically proven fluconazole-resistant candidemia. A prospective study including adult patients with candidemia was performed. Data were collected on patient demographics; underlying diseases; exposure to corticosteroids, antibiotics, or fluconazole; and invasive procedures. Risk factors associated either with non- albicans Candida spp. or potentially fluconazole-resistant Candida spp. ( C. glabrata or C. krusei ) or with Candida spp. with microbiologically confirmed fluconazole resistance were assessed using logistic regressions. We included 226 candidemia episodes. Non- albicans Candida isolates accounted for 53.1% of the fungal isolates, but only 18.2% of the cases were caused by potentially fluconazole-resistant organisms. Thirty isolates exhibited microbiologically confirmed fluconazole resistance. The multivariate analysis revealed that independent predictors associated with fluconazole-resistant Candida spp. were neutropenia (odds ratio [OR] = 4.94; 95% confidence interval [CI] = 1.50 to 16.20; P = 0.008), chronic renal disease (OR = 4.82; 95% CI = 1.47 to 15.88; P = 0.01), and previous fluconazole exposure (OR = 5.09; 95% CI = 1.66 to 15.6; P = 0.004). Independently significant variables associated with non- albicans Candida bloodstream infection or with potentially fluconazole-resistant Candida spp. did not include previous fluconazole exposure. We concluded that prior fluconazole treatment is an independent risk factor only for candidemia caused by microbiologically confirmed fluconazole resistant species. Our findings may be of value for selecting empirical antifungal therapy.

We set out to identify the prognostic factors in adult patients with Candida spp. bloodstream infection, assessing the impact on in-hospital mortality of catheter removal and adequacy of antifungal therapy. Patients with positive blood culture for Candida spp. and a central venous catheter in place at the time of candidaemia were included. Data collected included demographics, underlying diseases, severity of illness, clinical presentation, catheter withdrawal and adequacy of empirical therapy. We included 188 patients (mortality 36.7%). The mortality rate was 34.9% (23/66) in patients with early adequate antifungal treatment and 18.9% (7/37) in patients with early adequate antifungal therapy and catheter withdrawal in the first 48 h. The APACHE (Acute Physiology and Chronic Health Evaluation) II score on the day of candidaemia [adjusted hazard ratio (aHR) 1.12; 95% CI 1.06–1.17; P < 0.001] was associated with death whereas early adequate therapy (aHR 0.4; 95% CI 0.23–0.83; P = 0.012) and catheter withdrawal (aHR 0.34; 95% CI 0.16–0.70; P = 0.03) were protective factors. In primary candidaemia, mortality was 28% (14/50) in patients with adequate therapy and decreased to 17.7% (6/34) in patients with both interventions in the first 48 h. Catheter removal was a protective factor and adequacy of antifungal therapy in the first 48 h showed a strong tendency to protection against death (aHR 0.46; 95% CI 0.19–1.08; P = 0.07). In secondary non-catheter-related candidaemia, only early adequate therapy was a protective factor for mortality. Delay in catheter withdrawal and in administration of adequate antifungal therapy was associated with increased mortality in candidaemic patients. Catheter management did not influence the prognosis of secondary non-catheter-related candidaemia.

Over the last decade, an exponential increase in bacterial resistance has been observed worldwide [ 1 x 1 Nicolas-Chanoine, MH, Blanco, J, Leflon-Guibout, V et al. Intercontinental emergence of Escherichia coli clone O25:H4-ST131 producing CTX-M-15. J Antimicrob Chemother. 2008; 61: 273–281 Crossref | PubMed | Scopus (522) | Google Scholar See all References , 2 x 2 Talan, DA, Krishnadasan, A, Gorwitz, RJ et al. Comparison of Staphylococcus aureus from skin and soft-tissue infections in US emergency department patients, 2004 and 2008. Clin Infect Dis. 2011; 53: 144–149 Crossref | PubMed | Scopus (179) | Google Scholar See all References , 3 x 3 Valencia, R, Arroyo, LA, Conde, M et al. Nosocomial outbreak of infection with pan-drug-resistant Acinetobacter baumannii in a tertiary care university hospital. Infect Control Hosp Epidemiol. 2009; 30: 257–263 Crossref | PubMed | Scopus (141) | Google Scholar See all References , 4 x 4 Yong, D, Toleman, MA, Giske, CG et al. Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother. 2009; 53: 5046–5054 Crossref | PubMed | Scopus (1170) | Google Scholar See all References ]. No new antibacterial agents are expected to be on the market until 2018 at the earliest [ 5 x 5 Bartlett, JG. A call to arms: the imperative for antimicrobial stewardship. Clin Infect Dis. 2011; 53: S4–S7 Crossref | PubMed | Scopus (79) | Google Scholar See all References , 6 x 6 European Centre for Disease Prevention and Control EMA. ECDC/EMEA Joint Technical Report: the bacterial challenge: time to react. Available at: http://www.ecdc.europa.eu/en/publications/Publications/0909_TER_The_Bacterial_Challenge_Time_to_React.pdf; 2009. ((last accessed 27 February 2013).) Google Scholar See all References ]. Furthermore, the overall societal costs of antibiotic resistance were estimated to be 1.5 billion €/year in the European Union [ 6 x 6 European Centre for Disease Prevention and Control EMA. ECDC/EMEA Joint Technical Report: the bacterial challenge: time to react. Available at: http://www.ecdc.europa.eu/en/publications/Publications/0909_TER_The_Bacterial_Challenge_Time_to_React.pdf; 2009. ((last accessed 27 February 2013).) Google Scholar See all References 6 ]. Inappropriate use of antibiotics has been shown to be directly related to the increase of bacterial resistances [ 7 x 7 Livermore, DM. Minimising antibiotic resistance. Lancet Infect Dis. 2005; 5: 450–459 Abstract | Full Text | Full Text PDF | PubMed | Scopus (173) | Google Scholar See all References 7 ], as well as to significant increases in morbidity and mortality [ 8 x 8 Davey, PG and Marwick, C. Appropriate vs. inappropriate antimicrobial therapy. Clin Microbiol Infect. 2008; 14: 15–21 Abstract | Full Text | Full Text PDF | PubMed | Scopus (63) | Google Scholar See all References , 9 x 9 Kumar, A, Ellis, P, Arabi, Y et al. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest. 2009; 136: 1237–1248 Crossref | PubMed | Scopus (505) | Google Scholar See all References , 10 x 10 Garnacho-Montero, J, Ortiz-Leyba, C, Herrera-Melero, I et al. Mortality and morbidity attributable to inadequate empirical antimicrobial therapy in patients admitted to the ICU with sepsis: a matched cohort study. J Antimicrob Chemother. 2008; 61: 436–441 Crossref | PubMed | Scopus (119) | Google Scholar See all References ]. It is widespread in most health centres, and up to 50% of antibiotic treatments prescribed have been estimated to be incorrect [ 11 x 11 Dellit, TH, Owens, RC, McGowan, JE et al. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis. 2007; 15: 44 Google Scholar See all References 11 ]. All clinicians are potential antimicrobial prescribers; therefore the generalization of antibiotic misuse is likely to be due to a misbalance between the high level of knowledge required for the appropriate use of antibiotics and the scarce training offered in this respect to the practising clinician.

Listeria monocytogenes is the third most frequent cause of bacterial meningitis. The aim of this study is to know the incidence and risk factors associated with development of acute community-acquired Lm meningitis in adult patients and to evaluate the clinical features, management, and outcome in this prospective case series.