Improvement in the outcome of invasive fusariosis in the last decade.

Invasive fusariosis (IF) has been associated with a poor prognosis. Although recent series have reported improved outcomes, the definition of optimal treatments remains controversial. The objective of this study was to evaluate changes in the outcome of IF. We retrospectively analysed 233 cases of IF from 11 countries, comparing demographics, clinical findings, treatment and outcome in two periods: 1985-2000 (period 1) and 2001-2011 (period 2). Most patients (92%) had haematological disease. Primary treatment with deoxycholate amphotericin B was more frequent in period 1 (63% vs. 30%, p <0.001), whereas voriconazole (32% vs. 2%, p <0.001) and combination therapies (18% vs. 1%, p <0.001) were more frequent in period 2. The 90-day probabilities of survival in periods 1 and 2 were 22% and 43%, respectively (p <0.001). In period 2, the 90-day probabilities of survival were 60% with voriconazole, 53% with a lipid formulation of amphotericin B, and 28% with deoxycholate amphotericin B (p 0.04). Variables associated with poor prognosis (death 90 days after the diagnosis of fusariosis) by multivariable analysis were: receipt of corticosteroids (hazard ratio (HR) 2.11, 95% CI 1.18-3.76, p 0.01), neutropenia at end of treatment (HR 2.70, 95% CI 1.57-4.65, p <0.001), and receipt of deoxycholate amphotericin B (HR 1.83, 95% CI 1.06-3.16, p 0.03). Treatment practices have changed over the last decade, with an increased use of voriconazole and combination therapies. There has been a 21% increase in survival rate in the last decade.

A double-blind, randomized, placebo-controlled trial of itraconazole capsules as antifungal prophylaxis for neutropenic patients.

To evaluate the efficacy of itraconazole capsules in prophylaxis for fungal infections in neutropenic patients, we conducted a prospective, double-blind, placebo-controlled, randomized trial. Patients with hematologic malignancies or those who received autologous bone marrow transplants were assigned either a regimen of itraconazole (100 mg orally twice daily; n=104) or of placebo (n=106). Overall, fungal infections (superficial or systemic) occurred more frequently in the placebo group (15% vs. 6%; P=.03). There were no differences in the empirical use of amphotericin B or systemic fungal infections. Among patients with neutropenia that was profound (<100 neutrophils/mm3) and prolonged (for at least 7 days), those receiving itraconazole used less empirical amphotericin B (22% vs. 61%; P=.0001) and developed fewer systemic fungal infections (6% vs. 19%; P=.04). For patients with profound and prolonged neutropenia, itraconazole capsules at the dosage of 100 mg every 12 h reduce the frequency of systemic fungal infections and the use of empirical amphotericin B.

Predictive value of a positive nasal swab for Aspergillus sp. in the diagnosis of invasive aspergillosis in adult neutropenic cancer patients.

To evaluate the value of a positive nasal swab for Aspergillus in the diagnosis of invasive aspergillosis, we prospectively evaluated nasal colonization in 173 episodes of neutropenia in 92 patients with hematological malignancies. Weekly nasal swabs were taken, and the patients were followed until death or resolution of neutropenia. The outcome variables were the development of invasive aspergillosis, empirical antifungal therapy and death. In 31 episodes of neutropenia (18%) there was at least one positive nasal swab for Aspergillus sp. Only two patients developed invasive aspergillosis, both with a positive nasal swab (p = 0.03). The positive and negative predictive values of a nasal swab were 6.4% and 100%, respectively. There was no difference between patients with positive or negative swabs regarding antifungal therapy or death. In this population of patients, a nasal swab for Aspergillus sp. had a low positive predictive value and a high negative predictive value for invasive aspergillosis.

Risk factors and attributable mortality associated with superinfections in neutropenic patients with cancer.

To identify the risk factors and attributable mortality associated with superinfections in febrile neutropenic patients with hematologic malignancies, we prospectively evaluated 333 episodes of fever and neutropenia by means of univariate and multivariate analyses. Superinfection was defined as any infection either occurring during antibiotic therapy or developing within 1 week after discontinuation of antibiotic therapy. Of 333 episodes, 46 (13.8%) were defined as superinfection; these episodes occurred in 46 patients. The risk factors for superinfection in the multivariate analysis were longer duration of profound neutropenia (P < .0001), lack of use of quinolones as prophylaxis (P < .0001), presence of a central venous catheter (P = .02), and persistence of fever after 3 days of antibiotic therapy (P = .02). The crude mortality rate among patients with superinfection was 48%, and the attributable mortality rate was 24% (95% confidence interval, 3%-45%). Identifying risk factors for superinfections in neutropenic patients might allow clinical practices to reduce the negative impact of this complication.