| Abstract |
ABSTRACT
Candidaemia: incidence, risk factors, characteristics and outcomes in immunocompetent critically ill patients
The objective of the case-control study was to determine the risk factors for development of candidemia in patients requiring intensive care unit (ICU) treatment for more than 48h and to study the possible role of antifungal prophylaxis in the development and outcome of candidemia. Patients admitted to the medical-surgical ICU who developed candidemia after at least 48h were matched to a control group of ICU patients according to five variables: length of ICU stay until development of candidemia, age, admission department (medical, surgical, and ICU), admission year and sex. Forty-five patients with candidemia were enrolled in the study (incidence of candidemia 0.6 cases/1000 patient-days. Candida albicans was the most commonly isolated yeast followed by C. tropicalis. The risk factors associated with development of candidemia were Candida colonization, duration of mechanical ventilation, gastrointestinal (GIT) surgery, total parenteral nutrition, absolute lymphocyte count <1000/μl at the day of the positive blood culture, and diabetes mellitus. In the regression analysis Candida colonization and GIT surgery were independently associated with candidemia. Prophylactic administration of antifungals was not associated with better outcomes or non-albicans candidemia. ICU and total in-hospital mortality were 40% and 66.7%, respectively. Candidemia related mortality was 20%. Candidemia treatment failure was the only variable associated with in-hospital mortality (p=0.008). Candidemia in the ICU develops mainly in critically ill patients with multiple organ failure and end-stage disease and it is associated with increased morbidity and mortality. Patient populations that may benefit from preventive measures, including the use of antifungal prophylaxis, should be further studied.
Fluconazole versus itraconazole for antifungal prophylaxis in neutropenic patients with haematological malignancies: a meta-analysis of randomised controlled trials
Fluconazole and itraconazole are used as antifungal prophylaxis in neutropenic patients with haematological malignancies. A meta-analysis of randomised-controlled trials (RCTs) was performed in order to compare their safety and effectiveness in this population. Data were obtained from PubMed, Current Contents, Cochrane Central Register for Controlled Trials and references from relevant articles. Five RCTs were included in the analysis. Publication bias and statistically significant heterogeneity was not observed among the analyzed studies. Fewer patients were withdrawn due to the development of adverse effects associated with fluconazole when compared with itraconazole [odds ratio (OR) 0.27, 95% confidence interval (CI):0.18–0.41]. On the contrary, prophylactic use of fluconazole resulted in significantly more fungal infections (documented and suspected infections combined, OR 1.62, 95% CI: 1.06–2.48). There were no statistically significant differences regarding documented fungal infections (OR 1.51, 95% CI: 0.97–2.35), invasive fungal infections (OR 1.44, 95% CI: 0.96–2.17), overall mortality (OR 0.89, 95% CI: 0.63–1.24) and mortality attributed by the authors to fungal infections (OR 1.30, 95% CI: 0.75–2.25) between the two medications. These data suggest that, even though itraconazole is more effective than fluconazole in the prevention of fungal infections in neutropenic patients with haematological malignancies, the development of more adverse effects may limit its use.
Antifungal prophylaxis with azoles in high-risk, surgical intensive care unit patients: A meta-analysis of randomized, placebo-controlled trials
The objective of the second meta-analysis of randomized controlled trials was to evaluate the safety and effectiveness of azoles as antifungal prophylaxis in high-risk patients receiving treatment in the surgical intensive care unit. Data were obtained from PubMed, Current Contents, Cochrane central register of controlled trials, and references from relevant articles. Randomized controlled trials using azoles as antifungal prophylaxis vs placebo were included in the study. Six randomized controlled trials were included in the main analysis. Publication bias and statistically significant heterogeneity were not observed among the analyzed studies. Patients receiving antifungal prophylaxis developed fewer episodes of candidemia (OR 0.28, 95% CI: 0.09–0.86), non-bloodstream invasive fungal infections (OR 0.26, 95% CI: 0.12–0.53), and noninvasive fungal infections (OR 0.22, 95% CI: 0.11–0.43), respectively. No reduction in mortality was observed among patients who received azole prophylaxis (OR 0.74, 95% CI: 0.52–1.05). There was no significant difference in adverse effects (OR 1.28, 95% CI: 0.82–1.98). Despite its limitations, this meta-analysis suggests that the prophylactic use of azoles in high-risk surgical intensive care unit patients is associated with a reduction of fungal infections but not in all-cause mortality. However, although not noted in the analyzed randomized controlled trials, there is concern about the use of azoles due to possible shift toward non-albicans species and development of resistance to azoles.
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