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Objectives: Azole resistance among Aspergillus fumigatus isolates is a growing concern worldwide. Induction of mutations during azole therapy, environment-acquired mutations caused by azole fungicides and intrinsic resistance of cryptic Fumigati species all contribute to the burden of resistance. However, there is a lack of data in Canada on this emerging threat.Methods: To gain insights into the magnitude and mechanisms of resistance, a 14 year collection of Aspergillus section Fumigati comprising 999 isolates from 807 patients at a Montreal hospital was screened for azole resistance, and resistance mechanisms were investigated with the combined use of genome sequencing, 3D modelling and phenotypic efflux pump assays.Results: Overall azole resistance was low (4/807 patients; 0.5%). A single azole-resistant A. fumigatus sensu stricto strain, isolated from a patient with pulmonary aspergillosis, displayed efflux-pump-mediated resistance. Three patients were colonized or infected with azole-resistant cryptic Fumigati species (one Aspergillus thermomutatus, one Aspergillus lentulus and one Aspergillus turcosus). Evidence is presented that azole resistance is efflux-pump-mediated in the A. turcosus isolate, but not in the A. lentulus and A. thermomutatus isolates.Conclusions: Azole resistance is rare in our geographic area and currently driven by cryptic Fumigati species. Continued surveillance of emergence of resistance is warranted. [ABSTRACT FROM AUTHOR]

Background. Neonatal invasive candidiasis (IC) presenting in the first week of life is less common and less well described than later-onset IC. Risk factors, clinical features, and disease outcomes have not been studied in early-onset disease (EOD, ⩽7 days) or compared to late-onset disease (LOD, >7 days). Methods. All extremely low birth weight (ELBW, <1000 g) cases with IC and controls from a multicenter study of neonatal candidiasis enrolled from 2001 to 2003 were included in this study. Factors associated with occurrence and outcome of EOD in ELBW infants were determined. Results. Forty-five ELBW infants and their 84 matched controls were included. Fourteen (31%) ELBW infants had EOD. Birth weight <750 g, gestation <25 weeks, chorioamnionitis, and vaginal delivery were all strongly associated with EOD. Infection with Candida albicans, disseminated disease, pneumonia, and cardiovascular disease were significantly more common in EOD than in LOD. The EOD case fatality rate (71%) was higher than in LOD (32%) or controls (15%) (P = .0001). The rate of neurodevelopmental impairment and mortality combined was similar in EOD (86%) and LOD (72%), but higher than in controls (32%; P = .007). Conclusions. ELBW infants with EOD have a very poor prognosis compared to those with LOD. The role of perinatal transmission in EOD is supported by its association with chorioamnionitis, vaginal delivery, and pneumonia. Dissemination and cardiovascular involvement are common, and affected infants often die. Empiric treatment should be considered for ELBW infants delivered vaginally who have pneumonia and whose mothers have chorioamnionitis or an intrauterine foreign body. [ABSTRACT FROM AUTHOR]

The availability of CD4C/HIV&supMutA; transgenic (Tg) mice expressing human immunodeficiency virus type 1 in immune cells and developing an AIDS-like disease has provided the opportunity to devise a model of mucosal candidiasis that closely mimics the clinical and pathologic features of candidal infection in human AIDS. After intraoral infection with Candida albicans, oral burdens were strikingly elevated in the Tg mice, compared with non-Tg littermates (P <.05), during primary infection, a 6-10-week carrier state, and a marked terminal outgrowth preceding death. The chronic carrier state was absent in the non-Tg mice because of clearing of C. albicans. Candida hyphae penetrated the epithelium of the oral cavity, esophagus, and cardial-atrium fold of the stomach, accompanied by a mononuclear cell infiltrate. Immunohistochemical analysis suggested that decreased frequencies of major histocompatibility complex class II-expressing cells, combined with reduced CD4&sup+; cells, may underlie the susceptibility to mucosal candidiasis in these Tg mice. [ABSTRACT FROM AUTHOR]

To comprehensively assess the in vivo expression of Candida albicans hydrolytic enzyme genes during oropharyngeal candidiasis (OPC), a controlled sequential analysis of the temporal expression of individual members of the SAP (secretory aspartyl proteinase) gene family and PLB1 (phospholipase B) in a murine model of OPC was conducted. Acute infections in intact C3H and DBA/2 mice were terminated by clearance of C. albicans within 7 days after oral inoculation, but transgenic (Tg) mice expressing human immunodeficiency virus type 1 were persistently colonized until a final outgrowth before death. In contrast to the sustained expression of other SAP genes and PLB1, SAP7 and SAP8 were conspicuously distinguished by their transient expression in both intact and Tg mice. SAP5 and SAP9 were most strongly expressed throughout the course of infection in the Tg mice. These findings indicate that expression of individual members of the C. albicans SAP gene family is differentially regulated during experimental OPC. [ABSTRACT FROM AUTHOR]

One-hundred and five Candida albicans isolates from various anatomic sites of 28 patients, obtained at the onset of two consecutive episodes of well-documented recurrent vulvovaginitis, were typed by methods relying on physiologic or genomic markers. The isolates represented a wide variety of types, and neither a single biotype nor genotype was associated with recurrent vaginitis or a particular body site. Patients generally carried similar strains at various anatomic sites that persisted over time. Genomic methods indicated an 86% rate of relapse, which suggested that most recurrent vaginal infections are of endogenous origin. A similar evaluation with biotyping methods was inconclusive because of a lack of reproducibility, resulting from clonal variation or switching, and difficulties in establishing the number ofphenotypic tests necessary to distinguish between identical and different strains. Therefore, Southern hybridization was considered the ideal reference method to study the epidemiology of C. albicans infections. [ABSTRACT FROM PUBLISHER]

Theantibody response to Aspergillus fumigatus proteins was studied by the immunoblot technique in a rabbit model of invasive aspergillosis. Components of an A. fumigatus mycelial homogenate unbound by concanavalin A-Sepharose 4B chromatography were fractionated using SDS-PAGE and transferred to nitrocellulose papers. The protein fraction was probed with serial sera obtained from immunosuppressed or nonimmunosuppressed rabbits inoculated intravenously with saline or gradedinocula of A. fumigatus conidia. Seroconversion against antigens of 41, 54,and 71 kDa was demonstrated in 7 (50%),3 (21%), and 3 (21%) of 14 infected animals that survived ⩾10 days. Antibodies against the three antigens were detected in 4 (12.5%), 19(59%), and 14(44%) of 32 rabbits before immunosuppression or infection. Two-dimensional immuno-blotting revealed that the 41-, 54-, and 71-kDa antigens were derived in denaturing conditions from a single component resolved in nondenaturing polyacrylamide gel electrophoresis. [ABSTRACT FROM PUBLISHER]

During the past decade, substantial progress has been made in the development of new approaches and methods for the serological diagnosis of the mycoses. Clinically relevant antigens have been adapted for use in immunoassays for the detection of specific antibodies, and methods that detect fungal antigens in body fluids have been progressively refined. Nevertheless, few of the novel serological techniques have as yet found widespread clinical use. Reasons for this apparent discrepancy include the paucity of clinical data that substantiate improved predictive value for disease of antibody tests that use specific immunodominant antigens. The usefulness of detection of antigenemia in invasive candidiasis and invasive aspergillosis has been limited by the rapid clearance of Candida mannan and Aspergillus galactomannan from serum, which results in only moderate sensitivity for disease. False-negative results are especially frequent when single serum samples are tested in cases where fungal infection is clinically suspected. The detection of antigen in samples of urine collected serially may circumvent this problem in the future. The limited dissemination of methods for the detection of fungal antigens is also due to the slow development of simple and reliable commercial kits. [ABSTRACT FROM PUBLISHER]