Gloria Barreiros

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.

Risk Factors for Death Among Cancer Patients with Fungemia

In order to identify prognostic factors for death among cancer patients with fungemia, an 18-month survey of fungemia in patients with cancer was undertaken in three hospitals in Rio de Janeiro. For the assessment of risk factors for death, the following variables were analyzed: age; gender; underlying cancer; last treatment for the underlying disease; previous surgery; use of antibiotics, antifungal agents, steroids, or total parenteral nutrition; use of a central venous catheter; chemotherapy; radiotherapy; presence and duration of neutropenia; etiologic agent of the fungemia; treatment of the fungemia; clinical manifestations; and performance status (Karnofsky score) on the day of the positive blood culture. In multivariate analysis, the variables associated with an increased risk for death were older age, persistent neutropenia, and low performance status. Identifying risk factors for death may help to define a group-risk patients for whom new therapeutic options should be tried.

Nosocomial outbreak of Exophiala jeanselmei fungemia associated with contamination of hospital water.

From December 1996 through September 1997, we diagnosed 19 cases of fungemia due to Exophiala jeanselmei. We conducted a matched case-control study in which we cultured specimens of blood products, intravenous solutions, and water from a hospital water system. Isolates from environmental cultures were compared to those recovered from patients by random amplification of polymorphic DNA (RAPD). Multivariate analysis showed that neutropenia, longer duration of hospitalization, and use of corticosteroids were risk factors for infection. Environmental cultures yielded E. jeanselmei from 3 of 85 sources: deionized water from the hospital pharmacy, 1 water tank, and water from a sink in a non-patient care area. Use of deionized pharmacy water to prepare antiseptic solutions was discontinued, and no additional cases of infection occurred. RAPD typing showed that isolates from case patients and isolates from the pharmacy water were highly related, whereas the patterns of isolates recovered from the 2 other sources of water were distinct.

Nosocomial Fungemia Due to Exophiala jeanselmei var. jeanselmei and a Rhinocladiella Species: Newly Described Causes of Bloodstream Infection

ABSTRACT Fungi have become increasingly important causes of nosocomial bloodstream infections. The major cause of nosocomial fungemia has beenCandida spp, but increasingly molds and other yeasts have caused disease. Exophiala jeanselmei and members of the genus Rhinocladiella are dematiaceous moulds, which have been infrequently associated with systemic infection and have not been described as causes of fungemia. In this paper, the occurrence of 23 cases of fungemia due to these organisms over a 10-month period is reported and the clinical characteristics of patients and outcomes are described. The majority of patients were immunosuppressed; 21 of 23 (91%) had received blood products and 78% had a central venous catheter. All patients had at least one manifestation of fever, but only one patient had signs or symptoms suggesting deep-seated infection. Antifungal therapy was given to 19 of the 23 patients; of those who did not receive therapy, 3 died prior to the culture result and 1 had been discharged without therapy. Antifungal susceptibility of the organisms showed activity of amphotericin B, itraconazole, and the new triazole antifungals voriconazole and posaconazole. E. jeanselmei and Rhinocladiella species are potential causes of nosocomial fungemia and may be associated with systemic infection.

Increased Incidence of Invasive Fusariosis with Cutaneous Portal of Entry, Brazil

Most cases of infection with Fusarium spp. fungi involved primary skin lesions.

Molecular analyses of Fusarium isolates recovered from a cluster of invasive mold infections in a Brazilian hospital

BackgroundInvasive fusariosis (IF) is a rare but often fatal fungal infection in immunosuppressed patients. In 2007, cases of IF above the expected epidemiologic baseline were detected in the hematology ward of a hospital in Rio de Janeiro, Brazil. Possible sources of infection were investigated by performing environmental sampling and patient isolate collection, followed by molecular typing. Isolates from dermatology patients with superficial fusariosis were included in the study for comparison to molecular types found in the community.MethodsEnvironmental sampling focused on water-related sources in and around the hematology ward. Initially, we characterized 166 clinical and environmental isolates using the Fusarium translation elongation factor 1α (EF-1α) genetic locus. Isolates included 68 collected from water-related sources in the hospital environment, 55 from 18 hematology patients, and 43 from the skin/nails of 40 outpatients seen at the hospital dermatology clinic. Multi-locus sequence typing was performed on Fusarium solani species complex (FSSC) species 1 and 2 isolates to investigate their relatedness further.ResultsMost of the hematology samples were FSSC species 2, with species type FSSC 2-d the most commonly isolated from these patients. Most of the outpatient dermatology samples were also FSSC 2, with type 2-d again predominating. In contrast, environmental isolates from water sources were mostly Fusarium oxysporum species complex (FOSC) and those from air samples mostly Fusarium incarnatum-equiseti species complex (FIESC). A third of the environmental samples were FSSC, with species types FSSC 1-a and FSSC 1-b predominating.ConclusionsFusarium isolate species types from hematology patient infections were highly similar to those recovered from dermatology patients in the community. Four species types (FSSC 1-a, 1-b, 2-d and 2-f) were shared between hematology patients and the environment. Limitations in environmental sampling do not allow for nosocomial sources of infection to be ruled out. Future studies will focus on environmental factors that may have influenced the prevalence of FSSC fusariosis in this hematology ward.

Antimold Prophylaxis May Reduce the Risk of Invasive Fusariosis in Hematologic Patients with Superficial Skin Lesions with Positive Culture for Fusarium

ABSTRACT Hematologic patients with superficial skin lesions on admission growing Fusarium spp. are at a high risk for developing invasive fusariosis during neutropenia. We evaluated the impact of primary prophylaxis with a mold-active azole in preventing invasive fusariosis in these patients. Between August 2008 and December 2014, patients with acute leukemia or aplastic anemia and recipients of hematopoietic cell transplants were screened on admission with dermatologic and direct exams and fungal cultures of superficial skin lesions. Until November 2009, no interventions were made. Beginning in December 2009, patients with baseline skin lesions and a direct exam and/or culture suggestive of the presence of Fusarium spp. received prophylaxis with voriconazole or posaconazole. Skin lesions in the extremities (mostly onychomycosis and interdigital intertrigo) were present on admission in 88 of 239 episodes (36.8%); 44 lesions had hyaline septate hyphae identified by direct exam, and cultures from 11 lesions grew Fusarium spp. Antimold prophylaxis was given for 20 episodes (voriconazole for 17 and posaconazole for 3). Invasive fusariosis was diagnosed in 14 episodes (5.8%). Among patients with baseline skin lesions with positive cultures for Fusarium spp., 4 of 5 without antimold prophylaxis developed invasive fusariosis versus 0 of 6 with antimold prophylaxis (P = 0.01; 95% confidence interval for the difference between proportions, 22% to 96%). Primary antifungal prophylaxis with an antimold azole may prevent the occurrence of invasive fusariosis in high-risk hematologic patients with superficial skin lesions on admission growing Fusarium spp.

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.

Effect of the implosion and demolition of a hospital building on the concentration of fungi in the air

Building renovations increase the concentration of Aspergillus conidia in the air. In 2010, one wing of the hospital building was imploded due to structural problems. To evaluate the impact of building implosion on the concentration of fungi in the air, the demolition was performed in two phases: mechanical demolition of 30 m of the building, followed by implosion of the wing. Patients at high risk for aspergillosis were placed in protected wards. Air sampling was performed during mechanical demolition, on the day of implosion and after implosion. Total and specific fungal concentrations were compared in the different areas and periods of sampling, using the anova test. The incidence of IA in the year before and after implosion was calculated. The mean concentration of Aspergillus increased during mechanical demolition and on the day of implosion. However, in the most protected areas, there was no significant difference in the concentration of fungi. The incidence of invasive aspergillosis (cases per 1000 admissions) was 0.9 in the 12 months before, 0.4 during, and 0.5 in the 12 months after mechanical demolition (P > 0.05). Continuous monitoring of the quality of air and effective infection control measures are important to minimize the impact of building demolition.

Cutaneous Nocardiosis Simulating Cutaneous Lymphatic Sporotrichosis

Sporotrichosis is the subcutaneous mycosis caused by several species of the Sporothrix genus. With worldwide occurrence, the State of Rio de Janeiro is presently undergoing a zoonotic sporotrichosis epidemic. The form of lymphocutaneous nocardiosis is rare, being caused especially by Nocardia brasiliensis. It appears as a nodular or ulcerated lesion, with multiple painful erythematous nodules or satellite pustules distributed along the lymphatic tract, similar to the lymphocutaneous variant of sporotrichosis. We present a 61-year-old man who, after an insect bite in the left leg, developed an ulcerated lesion associated with ascending lymphangitis, nonresponsive to previous antibiotic therapies. The patient was admitted for investigation, based on the main diagnostic hypothesis of lymphatic cutaneous sporotrichosis entailed by the highly suggestive morphology, associated with the epidemiologic information that he is a resident of the city of Rio de Janeiro. While culture results were being awaited, the patient was medicated with sulfamethoxazole-trimethoprim to cover CA-MRSA and evolved with total healing of the lesions. After hospital discharge, using an ulcer fragment, an Actinomyces sp. was cultivated and N. brasiliensis was identified by molecular biology. The objective of this report is to demonstrate a case of lymphocutaneous nocardiosis caused by N. brasiliensis after a probable insect bite. Despite the patient being a resident of the State of Rio de Janeiro (endemic region for sporotrichosis), it is highlighted that it is necessary to be aware of the differential diagnoses of an ulcerated lesion with lymphangitis, favoring an early diagnosis and appropriate treatment of the illness.