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We evaluated the impact of applying the Infectious Diseases Society of America guidelines for febrile neutropenic patients in reducing the use of glycopeptides. Forty-five prior episodes of febrile neutropenia were compared to 97 episodes seen after application of the guidelines. Glycopeptide use was reduced from 73% to 43% of episodes (P=.0008), without changes in outcome.

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.

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.

A prospective randomized trial was performed to compare teicoplanin to vancomycin as part of the empirical antibiotic therapy of febrile neutropenic cancer patients. Fifty-three patients were randomized to receive ceftazidime (100 mg/kg daily every 8 h), amikacin (15 mg/kg daily every 8 h) and teicoplanin (6 mg/kg once a day) and 53 other patients received ceftazidime, amikacin (same dosages) and vancomycin (30 mg/kg/day every 6 h). In 99 evaluable episodes, the success rates were 54% for patients receiving teicoplanin and 52% for patients receiving vancomycin (p=0.76, 95% CI-18-23). The response rates were similar for patients with unexplained fever and for patients with documented infections. There were no differences in renal toxicity or cutaneous side effects between the two groups. The overall death rate was 18.9%, with 10 deaths in each group. The most important factor associated with death was the diagnosis of a fungal infection (p=0.001). Teicoplanin seems to be well tolerated and as effective as vancomycin in the empirical antibiotic therapy of fever in neutropenic cancer patients.

We conducted a retrospective review of 125 patients undergoing high-dose therapy and stem cell rescue in order to evaluate the incidence of documented infection and the utility of the administration of vancomycin empirically. All patients received prophylactic oral quinolone therapy. Because neutropenia in this setting is relatively brief, 21 patients never manifested fever, and no patient died of infection. Of the remaining 104 patients, positive blood cultures were obtained in only 10, nine with a gram stain positive and one with a gram stain negative organism. Sixty-two patients without any evidence of gram positive infection received vancomycin according to the existing algorithm for care of neutropenic fevers. In this population of patients, empiric administration of vancomycin for neutropenic fevers without culture documentation appears to be unnecessary, could be discontinued safely and at substantial cost savings, and might slow the appearance of vancomycin-resistant organisms.

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.

In this paper we report a eight-year prospective study designed to further characterize incidence, epidemiology, specific syndromes, treatment and prognosis associated with fungal infections in neutropenic patients. During the study period 30 fungal infections were diagnosed in 30 patients among 313 episodes of fever and neutropenia (10%). There were 15 cases of candidiasis, 5 pulmonary aspergillosis, 3 sinusitis by Aspergillus fumigatus, 5 infections by Fusarium sp., one infection by Trichosporon sp., and one infection due to Rhodotorula rubra. Blood cultures were positive in 18 cases (60%). The predisposing factors for fungal infection in multivariate analysis were the presence of central venous catheter (p < 0.001), longer duration of profound (< 100/mm3) neutropenia (p < 0.001), the use of corticosteroids (p < 0.001), gram-positive bacteremia (p = 0.002) and younger age (p = 0.03). In multivariate analysis only recovery of the neutropenia (p < 0.001) was associated with good prognosis whereas the diagnosis of infection by Fusarium sp. (p = 0.006) was strongly associated with a poor outcome. The death rate was 43%. There was no statistically significant difference in the death rate between patients who did receive (52%) or did not receive (50%) antifungal treatment. Identifying patients at risk, specific syndromes and prognostic factors may help to reduce the high mortality associated with disseminated fungal infections in neutropenic patients.

In a cohort of 79 febrile episodes in 50 consecutive neutropenic patients seen at the University Hospital, Federal University of Rio de Janeiro, Brazil, between 1987 and 1991, it was observed that the cumulative incidence of disseminated fungal infections rose from 3% to 19% after the introduction of a new empirical antibiotic regimen. In order to identify risk factors, as well as to assess the impact of the new antibiotic regimen on the emergence of fungal infections, a nested case-control study was undertaken, in which 10 cases of disseminated fungal infections were compared with 30 randomly chosen controls, drawn from the same cohort. In a multiple logistic regression analysis, the predictive factors for disseminated fungal infection were younger age (odds ratio 0.85, 95% confidence interval 0.75-0.97) and use of the new antibiotic regimen (odds ratio 14.18, 95% confidence interval 1.05-191.80) The probable explanation for the emergence of fungal infections is that the new antibiotic regimen, by lowering the incidence of bacteraemia-related deaths, allowed patients to be at risk for the development of disseminated fungal infections.

Three cases are reported of disseminated infection due to Fusarium species in severely neutropenic patients. The clinical findings in all patients included fever, painful disseminated nodular skin lesions and severe myalgia. The outcome was fatal despite early administration of amphotericin B. The portal of entry of the organism was probably the nasal sinus in two cases.

Skin nodules can be the first evidence of a disseminated fungal infection in febrile neutropenic patients. We present our experience in the diagnosis of this clinical problem in five patients treated for serious hematologic conditions in our Service. There were two cases of Candida sp., two of Fusarium sp., and one of Trichosporon sp.. The immediate assessment of any suspicious lesion, including a biopsy of the lesion for microbiological and histopathologic examinations, will usually lead to the correct diagnosis.