Kieren A Marr

..Availability of new antifungal drugs has led to creative attempts to prevent infections caused by both yeasts and molds with new antifungal prophylaxis strategies; these studies will be reviewed...

..This review discusses invasive fungal infections in hematopoietic stem cell transplant recipients, with a focus on the host and the two most common infections, candidiasis and those caused by moulds...

..The purpose of this study was to evaluate factors associated with mortality in transplant patients with IA...

..Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among organ transplant recipients. Multicenter prospective surveillance data to determine disease burden and secular trends are lacking...

..As enrollment continues, additional data will be analyzed and published, which will provide valuable information concerning the epidemiology, therapy, and outcomes of IFIs...

..61; P = 0.065). Significant relationships of in vitro MIC to all-cause mortality at 6 and 12 weeks for VOR or AMB were not found...

..HSCT recipients often have multiple co-morbidities, and understanding the current outcomes and prognostic variables is therefore important for overall management. This paper reviews historical trends and current data...

..Given their superior safety profiles, these preparations can now be considered suitable replacements for AmBD for primary therapy for many invasive fungal infections in clinical practice and research...

..Minimal inhibitory concentrations were > or =1 microg/mL for all available isolates. Yeasts and molds with decreased susceptibility to voriconazole may cause invasive infection in patients treated successfully for aspergillosis...

..The results of in vitro studies and animal models suggest that combination therapy with azoles and echinocandins may have additive activity against Aspergillus species...

..An understanding of design issues can help explain current controversies and can assist in development of future prophylaxis studies...

..We have investigated the use of a viability dye, chloromethylfluorescein di-acetate (CMFDA), for antifungal susceptibility testing in a fluorescence microplate (FM) assay format...

..GM EIA and qPCR assay add to the sensitivity of BAL for diagnosing IPA in high-risk patients, with excellent specificity. Adjunctive use of these tests may reduce dependence on invasive diagnostic procedures...

..No difference in relapsed malignancy was apparent. These data support the hypothesis that fluconazole, when coadministered with CY, decreases CY-related toxicities by inhibiting cytochrome P450 2C9 metabolism...

..Reported sensitivity of the galactomannan enzyme immunoassay as an early diagnostic test for invasive aspergillosis (IA) has been widely variable, ranging from 29% to 100% in earlier clinical studies...

..Accurate identification of these organisms may be clinically meaningful, given their potential differences in antifungal susceptibilities...

..Caution is advised when considering voriconazole therapy for C. glabrata candidemia that occurs in patients with extensive prior azole drug exposure...

..Based on the clustering of cases in space and time and molecular data, common-source acquisition of this unusual drug-resistant species is possible...

..The actuarial survival was 13% (median, 13 days). Persistent neutropenia was the single prognostic factor for death identified by multivariate analysis...

..albicans, but not A. fumigatus. The differential role of MyD88 may represent one mechanism by which macrophages regulate innate responses specific to different pathogenic fungi...

..Voriconazole is a broad-spectrum triazole that is active against aspergillus species. We conducted a randomized trial to compare voriconazole with amphotericin B for primary therapy of invasive aspergillosis...

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..Further studies are necessary to define appropriate preventative strategies, and to determine whether patients with ongoing infections might benefit from nonmyeloablative hematopoietic stem cell transplantation...

..This murine model provided evidence of the efficacy of amphotericin B and caspofungin but not of fluconazole against C. glabrata infection...

..This article focuses on the pathogenesis and clinical manifestations of diseases caused by Aspergillus species, with more detailed discussion on therapy of the most morbid manifestation, invasive aspergillosis...

..More effective strategies are needed to prevent invasive mold infections, which currently account for a notable proportion of nonrelapse mortality after nonmyeloablative allogeneic HCT...

..Voriconazole is an effective and well-tolerated treatment for refractory or less-common invasive fungal infections...

..This review will describe these most recent developments with the goal of evaluating new approaches to prevent, diagnose, and treat invasive fungal infections...

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..94 [1.0-3.8], P = .05), but not for overall mortality or NRM. We propose that intensified strategies to prevent infections should be implemented in MDS patients with preexisting neutropenia who undergo HSCT...

..The aim of this study was to determine the probability of survival and prognostic factors associated with outcomes over a long period of time...

..Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies...

..This review focuses on current and future methods of identifying aspergilli, and implications regarding Aspergillus species/strain identification...

..e., NCCLS) method. The results of these studies illustrate a method by which AMB susceptibility can be rapidly and reproducibly determined by measuring conidial viability...

..We examined the role of TLR polymorphisms in conferring a risk of invasive aspergillosis among recipients of allogeneic hematopoietic-cell transplants...

..Resolution of abnormalities within a 3-day window demonstrates the importance of redundant signaling pathways in mediating pulmonary inflammatory responses to fungi...

..We sought to determine clinical and biological risk factors for different IMIs during each period (early and late) after allogeneic HSCT...

..Because the risk for infections approaches that seen in allogeneic transplant recipients, infection surveillance, diagnostic work-up, and prevention strategies similar to those used in allogeneic recipients are warranted...

..Furthermore, we demonstrated that plasminogen directly binds to Aspergillus fumigatus. We propose that genetic variation within the plasminogen pathway influences the pathogenesis of this invasive fungal infection...

..fumigatus and is not able to survive at 48 degrees C. Our findings suggest the presence of a previously unrecognized, potentially drug-resistant Aspergillus species that we designate A. lentulus...

..The Microascus genus rarely causes invasive fungal infection in humans and can be very difficult to treat because of the resistance to available antifungal agents...

..This may indicate that several secondary metabolites are involved in A. fumigatus virulence...

..This article examines the range of infections caused by Aspergillus species, the challenges of diagnosis, and current treatment options...

..The rapidity and regularity of the rising resistance indicated that C. glabrata is able to upregulate drug efflux without losing the ability to maintain colonization...

..Agar dilution is simple and reproducible, and results were consistent with the results of more technically demanding techniques. This method may be appropriate for use in the clinical laboratory...

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..The 0.5 cutoff may allow for better performance as an early diagnostic test...

..29; 95% CI, 0.15-0.56). Voriconazole is likely to be a better treatment choice for A. terreus infection than is a polyene...

..69). There was no difference in overall or fungal-free survival. Itraconazole appears to prevent IMI in the subset of patients who tolerate the drug; however, toxicities and poor tolerability limit its success as prophylactic therapy...

..These data suggest that azole antifungals, through differential inhibition of hepatic cytochrome P-450 isoenzymes, affect CY metabolism and conditioning-related toxicities...

..Here, issues in trial design will be reviewed to address the question: Can (and should) new antifungals be evaluated for treatment of fever during neutropenia?..

..Increasing evidence underscores the need to carefully evaluate antifungal treatment options, according to both host and therapeutic risks for drug resistance...

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..The widespread availability of a standardized assay may now allow us to address the multiple sources of variability and bias via large, cooperative studies...

..However, changes in GMI levels when different kit lots are used, and single samples with low-positive (GMI of 0.5 to 0.7) indices, should be interpreted with caution...

..This study evaluated the safety and efficacy of micafungin in patients with proven or probable invasive aspergillosis (IA)...

..This risk is an important consideration for the future development of preventive strategies...

..001]). These findings may help in the interpretation and design of future studies on secondary prophylaxis of IA after an allo-HSCT...

..Reduced microbial susceptibility to all three echinocandins (caspofungin, anidulafungin, and micafungin) was noted but was not associated with mutations in FKS1...

..These data suggest the potential presence of a genetically unique, poorly sporulating variant of A. fumigatus that demonstrates decreased susceptibilities to several antifungals...

..These two aims have been developed to take is closer to the overall goal of decreasing Aspergillus associated mortality by developing more effective, laboratory directed therapeutic strategies. ..

..This information will be valuable for development of strategies to prevent and treat fungal infections in immunocompromised people. ..

..This project is enabled by the cooperative activities of FHCRC investigators, Bio-Rad Laboratories, and several multicenter networks supported by the CDC, NIAID, and NHLBI. ..

..fumigatus is coordinated. As this organism is a model lung commensal and pathogen, knowledge generated from these studies will also increase our understanding of mechanisms of specificity of innate host defense. ..

..and will develop a stringent molecular typing method that will enhance our knowledge of the biology and population structure of the fungal pathogen A. fumigatus. ..