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Simultaneous infections with Cryptococcus neoformans and Histoplasma capsulatum are rare and typically occur in immunocompromised individuals, particularly AIDS patients. Because both of those fungi can spur the development of latent infections, it is generally unknown which organism was first present. The diagnosis of one fungus can hide the diagnosis of the other, leading to underdiagnoses and poor prognosis. We report a case of C. neoformans and H. capsulatum co-infection. We also performed a systematic review of the literature. Our patient, a 69-year-old HIV-negative man, presented with a 9-month history of a productive cough, dyspnea and wheezing. His history showed chronic obstructive pulmonary disease and type II diabetes mellitus (DM). Pulmonary lesions of unidentified etiology were noted. Cryptococcal involvement of the central nervous system was confirmed, and C. neoformans and H. capsulatum were also isolated from blood cultures. In the literature, we found ten cases of simultaneous histoplasmosis and cryptococcosis. Including our patient, all of the cases were located in North America and Latin America, except for two, one Indian and one African diagnosed in France. AIDS was the main predisposing factor, followed by DM and age >60 years. Several diagnostic methods were employed. A blood culture and bronchoalveolar lavage (BAL) culture resulted in the growth of C. neoformans in most of the cases. H. capsulatum was more often detected in BAL and bone marrow cultures. Although co-infection by these pathogens is severe, it can be cured if it is diagnosed and treated early. We emphasized the importance of clinical suspicion and differential diagnosis of systemic mycoses.

Molecular epidemiology studies on cryptococcemia are limited. This study aimed to describe the clinical features of patients with bloodstream infections by Cryptococcus sp. in a public tertiary hospital in Mato Grosso do Sul, as well as identify the fungus' molecular type and determine its antifungal susceptibility. Molecular typing was performed using URA5 restriction fragment length polymorphism PCR, and antifungal susceptibility was determined by microdilution method standardized by the Clinical and Laboratory Standards Institute. Over 14 years, 48 patients were diagnosed with cryptococcemia. The majority (72.9 %) was male with a median age of 40 years; 81.3 % of the patients had HIV/AIDS and 72.9 % died. Cryptococcus neoformans was the most commonly isolated species (97.9 %). Molecular analysis identified the genotypes C. neoformans VNI (93.7 %), C. neoformans VNII (4.2 %), and Cryptococcus gattii VGII (2.1 %). In vitro, these fungi were not resistant to fluconazole, itraconazole, voriconazole, and amphotericin B. This is the first description of the molecular types of cryptococcemia agents in central-west Brazil. Its high lethality, especially in HIV-negative patients, suggests that early diagnosis and prompt antifungal therapy are crucial for a good clinical outcome.

To describe the incidence and susceptibility profile of Candida bloodstream infections in a tertiary-care hospital, we performed a retrospective observational study from 1998 to 2007. Comorbidities and risk factors were compiled from all cases. In vitro susceptibility testing to fluconazole, itraconazole, voriconazole, and amphotericin B was performed for 100 isolates, and caspofungin was tested for C. parapsilosis complex. In a ten-year evaluation of candidemias, 44 % were caused by C. albicans, and species of the C. parapsilosis complex were the second most frequent agents (37 %). Other species presented lower incidences (C. tropicalis, 13 %, C. glabrata, 5 %, and C. krusei, 1 %). Neither C. dubliniensis nor C. metapsilosis were observed in this study. C. orthopsilosis (3 %) and C. parapsilosis stricto sensu (34 %) were also found. Species distribution was independent of catheterization, mechanical ventilation, or previous use of antifungals or corticoids. Parenteral nutrition administration was strongly related to C. glabrata infection, and the highest mortality (80 %) was observed in patients infected by this species. All C. albicans isolates showed high susceptibility to all tested drugs. However, two C. parapsilosis stricto sensu isolates presented high minimum inhibitory concentration (MIC) (4 mg/L each) to fluconazole, and one exhibited voriconazole MIC of 0.25 mg/L, highlighting the cross-resistance to these azoles. All isolates of C. tropicalis and C. glabrata showed no resistance to any drug tested. No difference was noted between C. parapsilosis and C. orthopsilosis susceptibilities to caspofungin. Our results suggest that resistance to amphotericin B, fluconazole, voriconazole, itraconazole, and caspofungin in Brazilian Candida bloodstream isolates is still uncommon.

The therapeutic efficacy of amphotericin B and voriconazole alone and in combination with one another were evaluated in immunodeficient mice (BALB/c-SCID) infected with a fluconazole-resistant strain of Cryptococcus neoformans var. grubii. The animals were infected intravenously with 3 × 10(5) cells and intraperitoneally treated with amphotericin B (1.5 mg/kg/day) in combination with voriconazole (40 mg/kg/days). Treatment began 1 day after inoculation and continued for 7 and 15 days post-inoculation. The treatments were evaluated by survival curves and yeast quantification (CFUs) in brain and lung tissues. Treatments for 15 days significantly promoted the survival of the animals compared to the control groups. Our results indicated that amphotericin B was effective in assuring longest-term survival of infected animals, but these animals still harbored the highest CFU of C. neoformans in lungs and brain at the end of the experiment. Voriconazole was not as effective alone, but in combination with amphotericin B, it prolonged survival for the second-longest time period and provided the lowest colonization of target organs by the fungus. None of the treatments were effective in complete eradication of the fungus in mice lungs and brain at the end of the experiment.