Browsing by Author "Lockhart, Shawn R"

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    ItemOpen Access
    A Mycoses Study Group International Prospective Study of Phaeohyphomycosis: An Analysis of 99 Proven/Probable Cases.
    (Open forum infectious diseases, 2017-01) Revankar, Sanjay G; Baddley, John W; Chen, Sharon C-A; Kauffman, Carol A; Slavin, Monica; Vazquez, Jose A; Seas, Carlos; Morris, Michele I; Nguyen, M Hong; Shoham, Shmuel; Thompson, George R; Alexander, Barbara D; Simkins, Jacques; Ostrosky-Zeichner, Luis; Mullane, Kathleen; Alangaden, George; Andes, David R; Cornely, Oliver A; Wahlers, Kerstin; Lockhart, Shawn R; Pappas, Peter G

    Background

    Phaeohyphomycosis is infection caused by dematiaceous, or darkly pigmented, fungi. The spectrum of disease is broad, and optimal therapy remains poorly defined. The Mycoses Study Group established an international case registry of patients with proven/probable phaeohyphomycosis with the goal of improving the recognition and management of these infections.

    Methods

    Patients from 18 sites in 3 countries were enrolled from 2009-2015. Cases were categorized as local superficial, local deep (pulmonary, sinus, osteoarticular infections), and disseminated infections. End points were clinical response (partial and complete) and all-cause mortality at 30 days and end of follow-up.

    Results

    Of 99 patients, 32 had local superficial infection, 41 had local deep infection, and 26 had disseminated infection. The most common risk factors were corticosteroids, solid organ transplantation, malignancy, and diabetes. Cultures were positive in 98% of cases. All-cause mortality was 16% at 30 days and 33% at end of follow-up, and 18 of 26 (69%) with dissemination died. Itraconazole was most commonly used for local infections, and voriconazole was used for more severe infections, often in combination with terbinafine or amphotericin B.

    Conclusions

    Phaeohyphomycosis is an increasingly recognized infection. Culture remains the most frequently used diagnostic method. Triazoles are currently the drugs of choice, often combined with other agents. Further studies are needed to develop optimal therapies for disseminated infections.
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    ItemOpen Access
    Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance.
    (Nature communications, 2016-03) Healey, Kelley R; Zhao, Yanan; Perez, Winder B; Lockhart, Shawn R; Sobel, Jack D; Farmakiotis, Dimitrios; Kontoyiannis, Dimitrios P; Sanglard, Dominique; Taj-Aldeen, Saad J; Alexander, Barbara D; Jimenez-Ortigosa, Cristina; Shor, Erika; Perlin, David S
    The fungal pathogen Candida glabrata has emerged as a major health threat since it readily acquires resistance to multiple drug classes, including triazoles and/or echinocandins. Thus far, cellular mechanisms promoting the emergence of resistance to multiple drug classes have not been described in this organism. Here we demonstrate that a mutator phenotype caused by a mismatch repair defect is prevalent in C. glabrata clinical isolates. Strains carrying alterations in mismatch repair gene MSH2 exhibit a higher propensity to breakthrough antifungal treatment in vitro and in mouse models of colonization, and are recovered at a high rate (55% of all C. glabrata recovered) from patients. This genetic mechanism promotes the acquisition of resistance to multiple antifungals, at least partially explaining the elevated rates of triazole and multi-drug resistance associated with C. glabrata. We anticipate that identifying MSH2 defects in infecting strains may influence the management of patients on antifungal drug therapy.
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    ItemOpen Access
    Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.
    (Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2020-09) Donnelly, J Peter; Chen, Sharon C; Kauffman, Carol A; Steinbach, William J; Baddley, John W; Verweij, Paul E; Clancy, Cornelius J; Wingard, John R; Lockhart, Shawn R; Groll, Andreas H; Sorrell, Tania C; Bassetti, Matteo; Akan, Hamdi; Alexander, Barbara D; Andes, David; Azoulay, Elie; Bialek, Ralf; Bradsher, Robert W; Bretagne, Stephane; Calandra, Thierry; Caliendo, Angela M; Castagnola, Elio; Cruciani, Mario; Cuenca-Estrella, Manuel; Decker, Catherine F; Desai, Sujal R; Fisher, Brian; Harrison, Thomas; Heussel, Claus Peter; Jensen, Henrik E; Kibbler, Christopher C; Kontoyiannis, Dimitrios P; Kullberg, Bart-Jan; Lagrou, Katrien; Lamoth, Frédéric; Lehrnbecher, Thomas; Loeffler, Jurgen; Lortholary, Olivier; Maertens, Johan; Marchetti, Oscar; Marr, Kieren A; Masur, Henry; Meis, Jacques F; Morrisey, C Orla; Nucci, Marcio; Ostrosky-Zeichner, Luis; Pagano, Livio; Patterson, Thomas F; Perfect, John R; Racil, Zdenek; Roilides, Emmanuel; Ruhnke, Marcus; Prokop, Cornelia Schaefer; Shoham, Shmuel; Slavin, Monica A; Stevens, David A; Thompson, George R; Vazquez, Jose A; Viscoli, Claudio; Walsh, Thomas J; Warris, Adilia; Wheat, L Joseph; White, P Lewis; Zaoutis, Theoklis E; Pappas, Peter G

    Background

    Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential.

    Methods

    To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved.

    Results

    There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses.

    Conclusions

    These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.