Assessment of microbiological air quality in hemato-oncology units and its relationship with the occurrence of invasive fungal infections: an integrative review

Worldwide aging of the human population has promoted an increase in the incidence of neoplasia, including hematological cancers, which render patients particularly vulnerable to invasive fungal infections. For this reason, air filtration in hemato-oncology units has been recommended. However, scarce literature has assessed the impact of microbiological air quality on the occurrence of fungal infections in this population. We performed an integrative review of studies in the MEDLINE database that were published between January 1980 and October 2012, using the following combinations of keywords: air × quality × HEPA, air × quality × hematology, and airborne fungal infections. The search yielded only 13 articles, suggesting that high-efficiency filtering of the ambient air in hemato-oncology units can prevent the incidence of invasive fungal infections. However, no randomized clinical trial was found to confirm this suggestion. Currently, there is no consensus about the maximum allowable count of fungi in the air, which complicates filtration monitoring, including filter maintenance and replacement, and needs to be addressed in future studies.

Epidemiology of fungal infections in liver transplant recipients: a six-year study of a large Brazilian liver transplantation centre

Liver transplant seems to be an effective option to prolong survival in patients with end-stage liver disease, although it still can be followed by serious complications. Invasive fungal infections (ifi) are related to high rates of morbidity and mortality. The epidemiology of fungal infections in Brazilian liver transplant recipients is unknown. The aim of this observational and retrospective study was to determine the incidence and epidemiology of fungal infections in all patients who underwent liver transplantation at Albert Einstein Israeli Hospital between 2002-2007. A total of 596 liver transplants were performed in 540 patients. Overall, 77 fungal infections occurred in 68 (13%) patients. Among the 77 fungal infections, there were 40 IFI that occurred in 37 patients (7%). Candida and Aspergillus species were the most common etiologic agents. Candida species accounted for 82% of all fungal infections and for 67% of all IFI, while Aspergillus species accounted for 9% of all fungal infections and for 17% of all IFI. Non-albicans Candida species were the predominant Candida isolates. Invasive aspergillosis tended to occur earlier in the post-transplant period. These findings can contribute to improve antifungal prophylaxis and therapy practices in Brazilian centres.

Fungal infections in marrow transplant recipients under antifungal prophylaxis with fluconazole

Fungal infection is one of the most important causes of morbidity and mortality in bone marrow transplant (BMT) recipients. The growing incidence of these infections is related to several factors including prolonged granulocytopenia, use of broad-spectrum antibiotics, conditioning regimens, and use of immunosuppression to avoid graft-versus-host disease (GvHD). In the present series, we report five cases of invasive mold infections documented among 64 BMT recipients undergoing fluconazole antifungal prophylaxis: 1) A strain of Scedosporium prolificans was isolated from a skin lesion that developed on day +72 after BMT in a chronic myeloid leukemic patient. 2) Invasive pulmonary aspergillosis (Aspergillus fumigatus) was diagnosed on day +29 in a patient with a long period of hospitalization before being transplanted for severe aplastic anemia. 3) A tumoral lung lesion due to Rhizopus arrhizus (zygomycosis) was observed in a transplanted patient who presented severe chronic GvHD. 4) A tumoral lesion due to Aspergillus spp involving the 7th, 8th and 9th right ribs and local soft tissue was diagnosed in a BMT patient on day +110. 5) A patient with a history of Ph1-positive acute lymphocytic leukemia exhibited a cerebral lesion on day +477 after receiving a BMT during an episode of severe chronic GvHD. At that time, blood and spinal fluid cultures yielded Fusarium sp. Opportunistic infections due to fungi other than Candida spp are becoming a major problem among BMT patients receiving systemic antifungal prophylaxis with fluconazole.

Fungal infections in neutropenic patients: a 8-year prospective study

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.

Fungal infections in the immunocompromised host

In recent years many remarkable changes occurred in our way of life, producing opportunities for microbes. All these changes are related to the recent emergence of previously unrecognized diseases, or the resurgence of diseases that, at least in developed countries, were thought to be under control. This concept is reviewed regarding fungal infections and their agents in the immunocompromised host. The changing pattern of these infections, the portals of entry of fungi into the human host, fungal pathogenicity and the main predisposing factors are analyzed. Opportunistic fungal infections in cancer, organ transplant and acquired immunodeficiency syndrome patients are reviewed, specially candidiasis and aspergillosis.

New insights on the development of fungal vaccines: from immunity to recent challenges

Fungal infections are emerging as a major problem in part due to high mortality associated with systemic infections, especially in the case of immunocompromised patients. With the development of new treatments for diseases such as cancer and the acquired immune deficiency syndrome pandemic, the number of immunosuppressed patients has increased and, as a consequence, also the number of invasive fungal infections has increased. Several studies have proposed new strategies for the development of effective fungal vaccines. In addition, better understanding of how the immune system works against fungal pathogens has improved the further development of these new vaccination strategies. As a result, some fungal vaccines have advanced through clinical trials. However, there are still many challenges that prevent the clinical development of fungal vaccines that can efficiently immunise subjects at risk of developing invasive fungal infections. In this review, we will discuss these new vaccination strategies and the challenges that they present. In the future with proper investments, fungal vaccines may soon become a reality.

DISSEMINATED FUNGAL INFECTION WITH ADRENAL INVOLVEMENT: REPORT OF TWO HIV NEGATIVE BRAZILIAN PATIENTS

Paracoccidioidomycosis and histoplasmosis are systemic fungal infections endemic in Brazil. Disseminated clinical forms are uncommon in immunocompetent individuals. We describe two HIV-negative patients with disseminated fungal infections, paracoccidioidomycosis and histoplasmosis, who were diagnosed by biopsies of suprarenal lesions. Both were treated for a prolonged period with oral antifungal agents, and both showed favorable outcomes.

Invasive candidosis: contrasting the perceptions of infectious disease physicians and intensive care physicians

Introduction We analyze how infectious disease physicians perceive and manage invasive candidosis in Brazil, in comparison to intensive care unit specialists. Methods A 38-question survey was administered to 56 participants. Questions involved clinicians' perceptions of the epidemiology, diagnosis, treatment and prophylaxis of invasive candidosis. P < 0.05 was considered statistically significant. Results The perception that candidemia not caused by Candida albicans occurs in less than 10% of patients is more commonly held by intensive care unit specialists (p=0.018). Infectious disease physicians almost always use antifungal drugs in the treatment of patients with candidemia, and antifungal drugs are not as frequently prescribed by intensive care unit specialists (p=0.006). Infectious disease physicians often do not use voriconazole when a patient's antifungal treatment has failed with fluconazole, which also differs from the behavior of intensive care unit specialists (p=0.019). Many intensive care unit specialists use fluconazole to treat candidemia in neutropenic patients previously exposed to fluconazole, in contrast to infectious disease physicians (p=0.024). Infectious disease physicians prefer echinocandins as a first choice in the treatment of unstable neutropenic patients more frequently than intensive care unit specialists (p=0.013). When candidemia is diagnosed, most infectious disease physicians perform fundoscopy (p=0.015), whereas intensive care unit specialists usually perform echocardiograms on all patients (p=0.054). Conclusions This study reveals a need to better educate physicians in Brazil regarding invasive candidosis. The appropriate management of this disease depends on more drug options being available in our country in addition to global coverage in private and public hospitals, thereby improving health care.

Comparative performance of two air samplers for monitoring airborne fungal propagules

Many studies have attempted to evaluate the importance of airborne fungi in the development of invasive fungal infection, especially for immunocompromised hosts. Several kinds of instruments are available to quantitate fungal propagule levels in air. We compared the performance of the most frequently used air sampler, the Andersen sampler with six stages, with a portable one, the Reuter centrifugal sampler (RCS). A total of 84 samples were analyzed, 42 with each sampler. Twenty-eight different fungal genera were identified in samples analyzed with the Andersen instrument. In samples obtained with the RCS only seven different fungal genera were identified. The three most frequently isolated genera in samples analyzed with both devices were Penicillium, Aspergillus and Cladophialophora. In areas supplied with a high efficiency particulate air filter, fungal spore levels were usually lower when compared to areas without these filters. There was a significant correlation between total fungal propagule measurements taken with both devices on each sampling occasion (Pearson coefficient = 0.50). However, the Andersen device recovered a broader spectrum of fungi. We conclude that the RCS can be used for quantitative estimates of airborne microbiological concentrations. For qualitative studies, however, this device cannot be recommended.

Basidiomycosis: a review of the literature

The basidiomycosis, fungal infections provoked by basidiomycetes or agaric fungi have been recorded at growing frequencies in the medical literature, especially after the advent of AIDS in 1991. The basidiospores of these fungi, scattered in the atmosphere and transported by winds or air currents, reach the maxillary sinuses through the nasal route, most of the times causing signs and symptoms of chronic sinusitis. Basidiomycetes have also been isolated from sputum, especially Schizophyllum commune. Lesions of the buccal mucosa, brain abscesses, onychomycosis and endocarditis have been described, with a growing interest in this type of deep mycosis on the part of mycologists and infectologists. The present paper reports descriptions of mycetism as well as infectious processes caused by basidiomycetes, such as Schizophyllum commune, Ustilago maydis (= Ustilago zeae) and Coprinus cinereus

Cerebrospinal fluid profiles in acquired immunodeficiency syndrome with and without neurocryptococcosis

Cryptococcosis is one of the most common fungal infections of the central nervous system (CNS) in AIDS patients and meningoencephalitis or meningitis is a frequently observed manifestation. However, systematic studies of cerebrospinal fluid (CSF) composition from AIDS patients with CNS cryptococcosis have been few. CSF samples from 114 HIV seropositive patients whose clinical complaint suggested CNS involvement, were analyzed; 32 samples from patients diagnosed as having neurocryptococcosis (Group 1) and 82 samples from patients with no identified neurological disfunction (Group 2). Based on cytological and biochemical results, two distinct profiles were observed: Normal (Group 1 = 31%, Group 2 = 39%); Abnormal (Group 1 = 69%, Group 2 = 61%). Lymphocytes were the most frequent cells in both groups. Our CSF cytological and biochemical findings showed that in AIDS patients liquoric abnormalities are quite frequent, non-specific and difficult to interpret. In these circumstances a systematic search to identify the etiologic agent using microbiological and/or immunological assays must be routinely performed

Pyogenic abscesses and parasitic diseases

Parasitic diseases which during their course in the host switch the immune system from a T helper 1 to a T helper 2 response may be detrimental to the host, contributing to granuloma formation, eosinophilia, hyper-IgE, and increased susceptibility to bacterial and fungal infections. Patients and animals with acute schistosomiasis and hyper-IgE in their serum develop pyogenic liver abscess in the presence of bacteremia caused by Staphylococcus aureus. The Salmonella-S. mansoni association has also been well documented. The association of tropical pyomyositis (pyogenic muscle abscess) and pyogenic liver abscess with Toxocara infection has recently been described in the same context. In tropical countries that may be an interesting explanation for the great morbidity of bacterial diseases. If the association of parasitic infections and pyogenic abscesses and/or fungal diseases are confirmed, there will be a strong case in favor of universal treatment for parasitic diseases to prevent or decrease the morbidity of superinfection with bacteria and fungi.

Dermatophytoses in children: study of 137 cases

Dermatophytoses are common fungal infections caused by dermatophytes but there are few data about this condition in the childhood. 137 children below the age of 12 and clinically diagnosed as tineas were investigated prospectively at Instituto de Puericultura e Pediatria, Rio de Janeiro, from 1994 to 1999. Hair, skin/nails scraping and pus swabs were collected from lesions and processed for fungus. Male children from 2 to 12 years were mostly affected; tinea capitis (78 cases) mainly caused by Microsporum canis (46 cases) was the most common clinical form. Tinea corporis (43 cases) mainly caused by Trichophyton rubrum (17 cases) accounted for the second most frequent clinical form. Tinea cruris (10 cases) with Trichophyton rubrum (5 cases) as the most common etiologic agent accounted for the third most frequent clinical form. Tinea pedis and tinea unguium were much less frequent (3 cases each). Trichophyton rubrum was the most common etiologic agent isolated in these cases (3 cases).

Posaconazole treatment of refractory eumycetoma and chromoblastomycosis

Eumycetoma and chromoblastomycosis are chronic, disfiguring fungal infections of the subcutaneous tissue that rarely resolve spontaneously. Most patients do not achieve sustained long-term benefits from available treatments; therefore, new therapeutic options are needed. We evaluated the efficacy of posaconazole, a new extended-spectrum triazole antifungal agent, in 12 patients with eumycetoma or chromoblastomycosis refractory to existing antifungal therapies. Posaconazole 800 mg/d was given in divided doses for a maximum of 34 months. Complete or partial clinical response was considered a success; stable disease or failure was considered a nonsuccess. All 12 patients had proven infections refractory to standard therapy. Clinical success was reported for five of six patients with eumycetoma and five of six patients with chromoblastomycosis. Two patients were reported to have stable disease. As part of a treatment-use extension protocol, two patients with eumycetoma who initially had successful outcome were successfully retreated with posaconazole after a treatment hiatus of > 10 months. Posaconazole was well tolerated during long-term administration (up to 1015 d). Posaconazole therapy resulted in successful outcome in most patients with eumycetoma or chromoblastomycosis refractory to standard therapies, suggesting that posaconazole may be an important treatment option for these diseases.

Histopathology, serology and cultures in the diagnosis of cryptococcosis

Cryptococcosis is one of the most common opportunistic fungal infections in patients with acquired immunodeficiency syndrome (AIDS). We report 13 cases of cryptococcal infection based on histopathology, serology and cultures. Epidemiological analysis, histochemical techniques of hematoxilin and eosin (HE) and Grocot's silver (GMS), as well special histochemical techniques such as Mayer's mucicarmine (MM) and Fontana-Masson (FM), cryptococcal antigen test (CrAg) and isolation on fungal media: Sabouraud's (SAB), brain-heart infusion agar (BHI) and canavanine-glycine-bromothymol blue (CGB) agar were analyzed. Unsatisfactory staining results by MM stain associated to negative titers by CrAg test, which FM stain confirmed that capsule-deficient Cryptococcus infections were observed in four cases. Eight isolated cases were identified as follows: six cases were infection with Cryptococcus neoformans and two cases were Cryptococcus gattii.