Evaluation of Possible Correlations between Antifungal Susceptibilities of Filamentous Fungi In Vitro and Antifungal Treatment Outcomes in Animal Infection Models

Odds, Frank C.; Gerven, F. Van; Espinel-Ingroff, Ana; Bartlett, Marilyn S.; Ghannoum, Mahmoud A.; Lancaster, M. C.; Pfaller, Michael A.; Rex, John H.; Rinaldi, Michael G.; Walsh, Thomas J.

doi:10.1128/aac.42.2.282

Cited by 136 publications

(53 citation statements)

References 23 publications

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“…Culture-independent detection is needed since Scedosporium strains have reduced susceptibilities to many antifungal agents. Early diagnosis is the key to successful antifungal treatment (8,21,35). At present, no comprehensive data exist on mortality rates attributable to the newly circumscribed Pseudallescheria and Scedosporium species in different patient groups (e.g., transplant recipients or cystic fibrosis pa-tients).…”

Section: Discussionmentioning

confidence: 99%

Rapid Identification of Pseudallescheria and Scedosporium Strains by Using Rolling Circle Amplification

Lackner

Najafzadeh

Sun

et al. 2012

Appl Environ Microbiol

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The Pseudallescheria boydii complex, comprising environmental pathogens with Scedosporium anamorphs, has recently been subdivided into five main species: Scedosporium dehoogii, S. aurantiacum, Pseudallescheria minutispora, P. apiosperma, and P. boydii, while the validity of some other taxa is being debated. Several Pseudallescheria and Scedosporium species are indicator organisms of pollution in soil and water. Scedosporium dehoogii in particular is enriched in soils contaminated by aliphatic hydrocarbons. In addition, the fungi may cause life-threatening infections involving the central nervous system in severely impaired patients. For screening purposes, rapid and economic tools for species recognition are needed. Our aim is to establish rolling circle amplification (RCA) as a screening tool for species-specific identification of Pseudallescheria and Scedosporium. With this aim, a set of padlock probes was designed on the basis of the internal transcribed spacer (ITS) region, differing by up to 13 fixed mutations. Padlock probes were unique as judged from sequence comparison by BLAST search in GenBank and in dedicated research databases at CBS (Centraalbureau voor Schimmelcultures Fungal Biodiversity Centre). RCA was applied as an in vitro tool, tested with pure DNA amplified from cultures. The species-specific padlock probes designed in this study yielded 100% specificity. The method presented here was found to be an attractive alternative to identification by restriction fragment length polymorphism (RFLP) or sequencing. The rapidity (<1 day), specificity, and low costs make RCA a promising screening tool for environmentally and clinically relevant fungi.

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Section: Discussionmentioning

confidence: 99%

Rapid Identification of Pseudallescheria and Scedosporium Strains by Using Rolling Circle Amplification

Lackner

Najafzadeh

Sun

et al. 2012

Appl Environ Microbiol

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“…The response, however, may have been secondary to a recovering neutrophil count [146]. Most in-vitro and animal studies have shown poor efficacy of azoles [51,145,[147][148][149][150]. Azoles were not effective against Rhizopus infection in guinea-pig and murine models [145].…”

Section: Entomophthoramycosismentioning

confidence: 99%

Mucormycosis and entomophthoramycosis: a review of the clinical manifestations, diagnosis and treatment

Prabhu

Patel

2004

Clinical Microbiology and Infection

501

422

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The class Zygomycetes is divided into two orders, Mucorales and Entomophthorales. These two orders produce dramatically different infections. Genera from the order Mucorales (Rhizopus, Mucor, Rhizomucor, Absidia, Apophysomyces, Cunninghamella and Saksenaea) cause an angioinvasive infection called mucormycosis. Mucormycosis presents with rhino-orbito-cerebral, pulmonary, disseminated, cutaneous, or gastrointestinal involvement. Immunocompromising states such as haematological malignancy, bone marrow or peripheral blood stem cell transplantation, neutropenia, solid organ transplantation, diabetes mellitus with or without ketoacidosis, corticosteroids, and deferoxamine therapy for iron overload predispose patients to infection. Mucormycosis in immunocompetent hosts is rare, and is often related to trauma. Mortality rates can approach 100% depending on the patient's underlying disease and form of mucormycosis. Early diagnosis, along with treatment of the underlying medical condition, surgery, and an amphotericin B product are needed for a successful outcome. Genera from the order Entomophthorales produce a chronic subcutaneous infection called entomophthoramycosis in immunocompetent patients. This infection occurs in tropical and subtropical climates. The genus Basidiobolus typically produces a chronic subcutaneous infection of the thigh, buttock, and/or trunk. Rarely, it has been reported to involve the gastrointestinal tract. The genus Conidiobolus causes a chronic infection of the nasal submucosa and subcutaneous tissue of the nose and face. This paper will review the clinical manifestations, diagnosis and treatment of mucormycosis and entomophthoramycosis.

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“…It is a matter of concern now that amphotericin B resistance in Aspergillus non-fumigatus strains is increasingly being reported. [7][8][9] In addition emerging triazole resistance in A. fumigatus is worrisome, as resistance is correlated with treatment failure. 10 In the Netherlands, azole resistance in A. fumigatus strains was 2% till 2006, but is expected to rise.…”

Section: Introductionmentioning

confidence: 99%

In vitro susceptibility of 188 clinical and environmental isolates of Aspergillus flavus for the new triazole isavuconazole and seven other antifungal drugs

Shivaprakash

Geertsen

Chakrabarti

et al. 2011

Mycoses

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Recently isavuconazole, an experimental triazole agent, was found to be active against Aspergillus species. As Aspergillus flavus is the second-most common Aspergillus species isolated from human infection and the fungus has not been widely tested against the drug, we studied a large collection of clinical (n = 178) and environmental (n = 10) strains of A. flavus against isavuconazole and compared the results with seven other Aspergillus-active antifungal agents (some of them triazoles, others echinocandins or polyene antifungals: voriconazole, posaconazole, itraconazole, caspofungin, anidulafungin, micafungin and amphotericin B) using Clinical and Laboratory Standards Institute methods. Strains with high minimal inhibitory concentrations (MICs) were tested by E-test as well. The strains were collected from two different geographical locations (India and the Netherlands). Three isolates (1.6%) had high MIC (2 mg l(-1) by microbroth dilution and 8 mg l(-1) by E-test) for amphotericin B. Isavuconazole showed good activity against A. flavus strains with MIC(50) and MIC(90) values of 1 mg l(-1). As compared with voriconazole (the drug recommended for primary therapy of aspergillosis), isavuconazole had better activity (99.5% of strains had MIC of ≤ 1 mg l(-1) for isavuconazole, compared to 74% of strains with same MIC for voriconazole). All strains were, following recently proposed clinical breakpoints, susceptible for the triazoles tested except three strains, which had MICs of 4 mg l(-1) for voriconazole. Testing these strains with high MIC by E-test, gave results of 0.5-2 mg l(-1). Posaconazole had the lowest MIC(50) and MIC(90) of 0.125 mg l(-1) and 0.25 mg l(-1), respectively. Among echinocandins, 97% of strains had a minimum effective concentration (MEC) of ≤ 0.5 mg l(-1) for caspofungin, and all strains had a MEC of ≤ 0.016 mg l(-1) and ≤ 0.125 mg l(-1) for anidulafungin and micafungin, respectively.

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Evaluation of Possible Correlations between Antifungal Susceptibilities of Filamentous Fungi In Vitro and Antifungal Treatment Outcomes in Animal Infection Models

Cited by 136 publications

References 23 publications

Rapid Identification of Pseudallescheria and Scedosporium Strains by Using Rolling Circle Amplification

Rapid Identification of Pseudallescheria and Scedosporium Strains by Using Rolling Circle Amplification

Mucormycosis and entomophthoramycosis: a review of the clinical manifestations, diagnosis and treatment

In vitro susceptibility of 188 clinical and environmental isolates of Aspergillus flavus for the new triazole isavuconazole and seven other antifungal drugs

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