Summary:epidemiology and risk factors for IFI is important in identifying subsets of BMT recipients for clinical trials investigating the effects of novel preventive measures, as In order to analyze the incidence and risk factors for invasive fungal infection (IFI) after allogeneic BMT, 142 well as clinical decision-making on the management of patients after allogeneic BMT. consecutive adult BMT recipients (131 sibling donors, 11 unrelated donors) transplanted in 1989-1993 wereIn most previous studies, the role of GVHD and especially the effects of regimens used for GVHD prophyretrospectively analyzed. There were 21 cases with definite or probable IFI (incidence 15%) (Aspergillus, laxis or treatment, have not been evaluated as risk factors for IFI. Due to the increasing age of BMT recipients, wider 15; Candida, four; Fusarium, one; Absidia, one). The median time to the diagnosis of IFI was 136 days after use of unrelated donors, modifications in pre-and posttransplant immunosuppression and antifungal prophylaxis, BMT (range 6-466 days). Only 14% of the IFIs were found during the neutropenic period post-BMT. Of the the incidence of fungal infections, as well as the spectrum of causative agents, may change. We therefore investigated pretransplant characteristics, hematological disease (MDS vs other) (P = 0.001) and unrelated donor (P = the incidence and risk factors for IFI and especially the effects of acute and chronic GVHD and their treatment with 0.01) were risk factors for IFI. Acute GVHD grade III-IV (P = 0.03) and extensive chronic GVHD (P = 0.0002) steroids and antithymocyte globulin, on the risk of IFI in allogeneic BMT recipients transplanted between 1989 and were also found to be significant risk factors. Only three patients with IFI (14%) became long-term survivors.1993. Invasive fungal infections tended to develop late after BMT, were usually caused by Aspergillus sp., and were strongly associated with GVHD and its treatment. BetPatients and methods ter prophylaxis and treatment of IFI are needed. More effective prophylaxis for GVHD might decrease the risk Patients of IFI after allogeneic BMT.One hundred and forty-two adult patients received their first Keywords: invasive fungal infection; BMT; GVHD; risk allogeneic BMT (131 HLA-identical sibling donors, 11 factors; incidence unrelated donors) in the Department of Medicine, Helsinki University Central Hospital between 1989 and 1993. All patient charts were screened for relevant baseline data, Invasive fungal infections (IFI) mainly caused by Candida post-transplant course, occurrence and treatment of GVHD, and Aspergillus species constitute a major problem after as well as invasive fungal infections and their management. allogeneic BMT. Invasive Candida infections have beenThe patients had a median follow-up of 26 months postreported in 10-15% of patients, 1-4 and the incidence of BMT (range 1-82 months). The main pretransplant characAspergillus infections has varied between 3 and 7% in teristics are presented in Table 1. recent series. 2,[5][6][7] ...

Candida parapsilosis is an increasing cause of bloodstream infections (BSIs) in neonatal intensive care units (NICUs).During the last decades the incidence of candidemia in neonatal intensive care units (NICUs) has increased, and the most prevalent Candida species that cause candidemias have shifted over time from Candida albicans to Candida parapsilosis (12,16,23). The known risk factors for candidemia are prematurity; the use of central venous lines, intubation, parenteral nutrition, and broad-spectrum antibiotics; and prolonged hospitalization (16,18,20,26,35). In addition, in some reports colonization with Candida spp. was associated with an increased risk for candidemia, especially in very low birth weight (VLBW; Ͻ1,500 g) infants (4,25,26).In VLBW infants, prevention of fungal colonization by fluconazole prophylaxis has been shown to be effective (10, 11). The efficacy of this drug in preventing infections is, however, controversial (1, 3). In addition, selection of Candida species with primary resistance to fluconazole and development of resistance to azoles are potential threats (14,19). Two studies on fluconazole prophylaxis previously conducted in NICUs (10, 11) found no difference in the rates of fluconazole susceptibility among Candida isolates before and after a relatively short study period. Global surveillance studies also indicate that reduced susceptibility to fluconazole is extremely uncommon among bloodstream infection (BSI) isolates of C. parapsilosis (21).The NICU of the Hospital for Children and Adolescents (HCA), Helsinki University Central Hospital, Helsinki, Finland, has had problems with nosocomial C. parapsilosis infections for years. Fluconazole prophylaxis seemed to control the problem (27), but later, the number of infected or colonized patients in the NICU started to increase again.We describe a clonal outbreak caused by C. parapsilosis in the NICU during a 12-year period and the development of fluconazole resistance of the causative clone during the longterm use of fluconazole prophylaxis. MATERIALS AND METHODSSetting and surveillance. The 18-bed NICU of HCA serves a population of 1.4 million people with 470 annual admissions, including 150 VLBW infants. The NICU consists of five rooms. Sinks are available in each room, and handdisinfectant dispensers are available at each bed. Alcohol-based hand rub is used before and after any patient contact, and gloves are routinely used during aseptic procedures. Blood samples for culture are drawn from a peripheral vessel by venipuncture. Endotracheal aspirates are taken weekly from every patient in the NICU for surveillance culture, and other samples of other specimens are taken for culture whenever an infection is suspected. The empirical antimicrobial treatment for a suspected case of septicemia is a combination of ampicillin and netilmicin. All patients with either suspected or verified candidemia are treated with amphotericin B; since June 1999, liposomal amphotericin B has been used routinely.An in-house system of surveillance for noso...

We analyzed 79 bulk samples of moldy interior finishes from Finnish buildings with moisture problems for 17 mycotoxins, as well as for fungi that could be isolated using one medium and one set of growth conditions. We found the aflatoxin precursor, sterigmatocystin, in 24% of the samples and trichothecenes in 19% of the samples. Trichothecenes found included satratoxin G or H in five samples; diacetoxyscirpenol in five samples; and 3-acetyl-deoxynivalenol, deoxynivalenol, verrucarol, or T-2-tetraol in an additional five samples. Citrinine was found in three samples. Aspergillus versicolor was present in most sterigmatocystin-containing samples, and Stachybotrys spp. were present in the samples where satratoxins were found. In many cases, however, the presence of fungi thought to produce the mycotoxins was not correlated with the presence of the expected compounds. However, when mycotoxins were found, some toxigenic fungi usually were present, even if the species originally responsible for producing the mycotoxin was not isolated. We conclude that the identification and enumeration of fungal species present in bulk materials are important to verify the severity of mold damage but that chemical analyses are necessary if the goal is to establish the presence of mycotoxins in moldy materials.

Summary:To investigate diagnostic aspects of invasive aspergillosis (IA) in allogeneic BMT recipients, the charts of 22 consecutive patients with IA transplanted in 1989-1995 were reviewed. IA was diagnosed 69-466 days (median 131 days) post BMT. In 16 patients (73%), a definite or probable diagnosis of IA was made during life. Respiratory symptoms were the presenting feature in half of the patients followed by neurological symptoms (27%). Chest X-ray revealed single or multiple nodular lesions in 10 patients; cavitation was observed in five patients. Tissue biopsy was the most common method of diagnosis (nine patients: lungs 6, liver 1, subcutaneous tissue 1, brain 1). Five IA cases were detected by nine guided fine needle lung biopsies in eight patients and without complications. Bronchoalveolar lavage was performed in 14 patients with findings suggestive of invasive pulmonary aspergillosis in eight cases. Lungs were the most common organ affected (90%) followed by central nervous system (41%). The diagnosis of IA is still difficult, and a large number of patients have advanced infection at diagnosis. Methods for early diagnosis are needed. Patients with a clinical suspicion of IA should be treated vigorously with antifungal agents during the diagnostic work-up. Bone Marrow Transplantation (2000) 25, 867-871. Keywords: Aspergillus infection; allogeneic BMT; diagnosis; radiology; biopsy; bronchoalveolar lavage Invasive aspergillosis (IA) is an important clinical problem in allogeneic BMT recipients. In previous studies, the incidence of IA has ranged from 4 to 10% 1-5 and may be increasing. 6 Aspergillus infections have been considered difficult to diagnose. 7-9 They often present with non-specific symptoms and signs. In the allogeneic setting other opportunistic infections may make the diagnosis of IA even more difficult. Due to frequent colonization of the upper respiratory tract with Aspergillus sp, tissue biopsy is needed for definitive diagnosis. Knowledge of the spectrum of clinical presentation of IA is essential both for raising clinical suspicion and for guiding diagnostic attempts. Furthermore, information on the yield of different diagnostic methods is needed in choosing rational diagnostic strategies. We have therefore analyzed our experience on the diagnostic aspects of IA in a recent cohort of allogeneic BMT recipients. Patients and methods

We determined differences in the expression of certain virulence factors between oral Candida dubliniensis and Candida albicans species. In addition, clonal differences were sought among C. albicans isolates recovered from patients with and without compromised immune system. The material comprised 93 clinical yeast isolates originated in 40 subjects (1-5 isolates per subject). All 26 C. dubliniensis isolates and 46 C. albicans isolates originated from healthy routine dental clinic patients. Additionally, 21 C. albicans isolates were collected from patients with autoimmune polyendocrinopathy-candidosis-ectodermal dystrophy (APECED), who have chronic candidosis as one manifestation of their immunocompromising disease. Polymerase chain reaction amplification using the random sequence primer OPE-03 enabled grouping of the C. dubliniensis isolates in 2 genotypes (I and II) and C. albicans isolates in 15 genotypes (I-XV). No significant difference was found in the distribution of genotypes between the patients with APECED and the healthy subjects. C. dubliniensis isolates exhibited high-frequency phenotypic switching significantly more frequently than did C. albicans isolates, and vice versa regarding phospholipase and proteinase production. Proteinase production was significantly more frequent among C. albicans genotype V than genotype IX isolates. No significant difference was found in expression of virulence factors of C. albicans isolates between the patients with APECED and the healthy subjects.