Browsing by Author "Baddley, John W"

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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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    Coronavirus Disease 2019-Associated Invasive Fungal Infection.
    (Open forum infectious diseases, 2021-12) Baddley, John W; Thompson, George R; Chen, Sharon C-A; White, P Lewis; Johnson, Melissa D; Nguyen, M Hong; Schwartz, Ilan S; Spec, Andrej; Ostrosky-Zeichner, Luis; Jackson, Brendan R; Patterson, Thomas F; Pappas, Peter G
    Coronavirus disease 2019 (COVID-19) can become complicated by secondary invasive fungal infections (IFIs), stemming primarily from severe lung damage and immunologic deficits associated with the virus or immunomodulatory therapy. Other risk factors include poorly controlled diabetes, structural lung disease and/or other comorbidities, and fungal colonization. Opportunistic IFI following severe respiratory viral illness has been increasingly recognized, most notably with severe influenza. There have been many reports of fungal infections associated with COVID-19, initially predominated by pulmonary aspergillosis, but with recent emergence of mucormycosis, candidiasis, and endemic mycoses. These infections can be challenging to diagnose and are associated with poor outcomes. The reported incidence of IFI has varied, often related to heterogeneity in patient populations, surveillance protocols, and definitions used for classification of fungal infections. Herein, we review IFI complicating COVID-19 and address knowledge gaps related to epidemiology, diagnosis, and management of COVID-19-associated fungal infections.
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    Effect of Algorithm-Based Therapy vs Usual Care on Clinical Success and Serious Adverse Events in Patients with Staphylococcal Bacteremia: A Randomized Clinical Trial.
    (JAMA, 2018-09) Holland, Thomas L; Raad, Issam; Boucher, Helen W; Anderson, Deverick J; Cosgrove, Sara E; Aycock, P Suzanne; Baddley, John W; Chaftari, Anne-Marie; Chow, Shein-Chung; Chu, Vivian H; Carugati, Manuela; Cook, Paul; Corey, G Ralph; Crowley, Anna Lisa; Daly, Jennifer; Gu, Jiezhun; Hachem, Ray; Horton, James; Jenkins, Timothy C; Levine, Donald; Miro, Jose M; Pericas, Juan M; Riska, Paul; Rubin, Zachary; Rupp, Mark E; Schrank, John; Sims, Matthew; Wray, Dannah; Zervos, Marcus; Fowler, Vance G; Staphylococcal Bacteremia Investigators

    Importance

    The appropriate duration of antibiotics for staphylococcal bacteremia is unknown.

    Objective

    To test whether an algorithm that defines treatment duration for staphylococcal bacteremia vs standard of care provides noninferior efficacy without increasing severe adverse events.

    Design, setting, and participants

    A randomized trial involving adults with staphylococcal bacteremia was conducted at 16 academic medical centers in the United States (n = 15) and Spain (n = 1) from April 2011 to March 2017. Patients were followed up for 42 days beyond end of therapy for those with Staphylococcus aureus and 28 days for those with coagulase-negative staphylococcal bacteremia. Eligible patients were 18 years or older and had 1 or more blood cultures positive for S aureus or coagulase-negative staphylococci. Patients were excluded if they had known or suspected complicated infection at the time of randomization.

    Interventions

    Patients were randomized to algorithm-based therapy (n = 255) or usual practice (n = 254). Diagnostic evaluation, antibiotic selection, and duration of therapy were predefined for the algorithm group, whereas clinicians caring for patients in the usual practice group had unrestricted choice of antibiotics, duration, and other aspects of clinical care.

    Main outcomes and measures

    Coprimary outcomes were (1) clinical success, as determined by a blinded adjudication committee and tested for noninferiority within a 15% margin; and (2) serious adverse event rates in the intention-to-treat population, tested for superiority. The prespecified secondary outcome measure, tested for superiority, was antibiotic days among per-protocol patients with simple or uncomplicated bacteremia.

    Results

    Among the 509 patients randomized (mean age, 56.6 [SD, 16.8] years; 226 [44.4%] women), 480 (94.3%) completed the trial. Clinical success was documented in 209 of 255 patients assigned to algorithm-based therapy and 207 of 254 randomized to usual practice (82.0% vs 81.5%; difference, 0.5% [1-sided 97.5% CI, -6.2% to ∞]). Serious adverse events were reported in 32.5% of algorithm-based therapy patients and 28.3% of usual practice patients (difference, 4.2% [95% CI, -3.8% to 12.2%]). Among per-protocol patients with simple or uncomplicated bacteremia, mean duration of therapy was 4.4 days for algorithm-based therapy vs 6.2 days for usual practice (difference, -1.8 days [95% CI, -3.1 to -0.6]).

    Conclusions and relevance

    Among patients with staphylococcal bacteremia, the use of an algorithm to guide testing and treatment compared with usual care resulted in a noninferior rate of clinical success. Rates of serious adverse events were not significantly different, but interpretation is limited by wide confidence intervals. Further research is needed to assess the utility of the algorithm.

    Trial registration

    ClinicalTrials.gov Identifier: NCT01191840.
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    Factors associated with mortality in transplant patients with invasive aspergillosis.
    (Clin Infect Dis, 2010-06-15) Baddley, John W; Andes, David R; Marr, Kieren A; Kontoyiannis, Dimitrios P; Alexander, Barbara D; Kauffman, Carol A; Oster, Robert A; Anaissie, Elias J; Walsh, Thomas J; Schuster, Mindy G; Wingard, John R; Patterson, Thomas F; Ito, James I; Williams, O Dale; Chiller, Tom; Pappas, Peter G
    BACKGROUND: Invasive aspergillosis (IA) is an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. The purpose of this study was to evaluate factors associated with mortality in transplant patients with IA. METHODS: Transplant patients from 23 US centers were enrolled from March 2001 to October 2005 as part of the Transplant Associated Infection Surveillance Network. IA cases were identified prospectively in this cohort through March 2006, and data were collected. Factors associated with 12-week all-cause mortality were determined by logistic regression analysis and Cox proportional hazards regression. RESULTS: Six-hundred forty-two cases of proven or probable IA were evaluated, of which 317 (49.4%) died by the study endpoint. All-cause mortality was greater in HSCT patients (239 [57.5%] of 415) than in SOT patients (78 [34.4%] of 227; P<.001). Independent poor prognostic factors in HSCT patients were neutropenia, renal insufficiency, hepatic insufficiency, early-onset IA, proven IA, and methylprednisolone use. In contrast, white race was associated with decreased risk of death. Among SOT patients, hepatic insufficiency, malnutrition, and central nervous system disease were poor prognostic indicators, whereas prednisone use was associated with decreased risk of death. Among HSCT or SOT patients who received antifungal therapy, use of an amphotericin B preparation as part of initial therapy was associated with increased risk of death. CONCLUSIONS: There are multiple variables associated with survival in transplant patients with IA. Understanding these prognostic factors may assist in the development of treatment algorithms and clinical trials.
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    Fungal Endocarditis: Pathophysiology, Epidemiology, Clinical Presentation, Diagnosis, and Management.
    (Clinical microbiology reviews, 2023-07) Thompson, George R; Jenks, Jeffrey D; Baddley, John W; Lewis, James S; Egger, Matthias; Schwartz, Ilan S; Boyer, Johannes; Patterson, Thomas F; Chen, Sharon C-A; Pappas, Peter G; Hoenigl, Martin
    Fungal endocarditis accounts for 1% to 3% of all infective endocarditis cases, is associated with high morbidity and mortality (>70%), and presents numerous challenges during clinical care. Candida spp. are the most common causes of fungal endocarditis, implicated in over 50% of cases, followed by Aspergillus and Histoplasma spp. Important risk factors for fungal endocarditis include prosthetic valves, prior heart surgery, and injection drug use. The signs and symptoms of fungal endocarditis are nonspecific, and a high degree of clinical suspicion coupled with the judicious use of diagnostic tests is required for diagnosis. In addition to microbiological diagnostics (e.g., blood culture for Candida spp. or galactomannan testing and PCR for Aspergillus spp.), echocardiography remains critical for evaluation of potential infective endocarditis, although radionuclide imaging modalities such as 18F-fluorodeoxyglucose positron emission tomography/computed tomography are increasingly being used. A multimodal treatment approach is necessary: surgery is usually required and should be accompanied by long-term systemic antifungal therapy, such as echinocandin therapy for Candida endocarditis or voriconazole therapy for Aspergillus endocarditis.
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    Global guideline for the diagnosis and management of the endemic mycoses: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology.
    (The Lancet. Infectious diseases, 2021-12) Thompson, George R; Le, Thuy; Chindamporn, Ariya; Kauffman, Carol A; Alastruey-Izquierdo, Ana; Ampel, Neil M; Andes, David R; Armstrong-James, Darius; Ayanlowo, Olusola; Baddley, John W; Barker, Bridget M; Lopes Bezerra, Leila; Buitrago, Maria J; Chamani-Tabriz, Leili; Chan, Jasper FW; Chayakulkeeree, Methee; Cornely, Oliver A; Cunwei, Cao; Gangneux, Jean-Pierre; Govender, Nelesh P; Hagen, Ferry; Hedayati, Mohammad T; Hohl, Tobias M; Jouvion, Grégory; Kenyon, Chris; Kibbler, Christopher C; Klimko, Nikolai; Kong, David CM; Krause, Robert; Lee Lee, Low; Meintjes, Graeme; Miceli, Marisa H; Rath, Peter-Michael; Spec, Andrej; Queiroz-Telles, Flavio; Variava, Ebrahim; Verweij, Paul E; Schwartz, Ilan S; Pasqualotto, Alessandro C
    The global burden of the endemic mycoses (blastomycosis, coccidioidomycosis, emergomycosis, histoplasmosis, paracoccidioidomycosis, sporotrichosis, and talaromycosis) continues to rise yearly and these infectious diseases remain a leading cause of patient morbidity and mortality worldwide. Management of the associated pathogens requires a thorough understanding of the epidemiology, risk factors, diagnostic methods and performance characteristics in different patient populations, and treatment options unique to each infection. Guidance on the management of these infections has the potential to improve prognosis. The recommendations outlined in this Review are part of the "One World, One Guideline" initiative of the European Confederation of Medical Mycology. Experts from 23 countries contributed to the development of these guidelines. The aim of this Review is to provide an up-to-date consensus and practical guidance in clinical decision making, by engaging physicians and scientists involved in various aspects of clinical management.
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    Invasive non-Aspergillus mold infections in transplant recipients, United States, 2001-2006.
    (Emerging infectious diseases, 2011-10) Park, Benjamin J; Pappas, Peter G; Wannemuehler, Kathleen A; Alexander, Barbara D; Anaissie, Elias J; Andes, David R; Baddley, John W; Brown, Janice M; Brumble, Lisa M; Freifeld, Alison G; Hadley, Susan; Herwaldt, Loreen; Ito, James I; Kauffman, Carol A; Lyon, G Marshall; Marr, Kieren A; Morrison, Vicki A; Papanicolaou, Genovefa; Patterson, Thomas F; Perl, Trish M; Schuster, Mindy G; Walker, Randall; Wingard, John R; Walsh, Thomas J; Kontoyiannis, Dimitrios P
    Recent reports describe increasing incidence of non-Aspergillus mold infections in hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients. To investigate the epidemiology of infections with Mucorales, Fusarium spp., and Scedosporium spp. molds, we analyzed data from the Transplant-Associated Infection Surveillance Network, 23 transplant centers that conducted prospective surveillance for invasive fungal infections during 2001-2006. We identified 169 infections (105 Mucorales, 37 Fusarium spp., and 27 Scedosporium spp.) in 169 patients; 124 (73.4%) were in HCT recipients, and 45 (26.6%) were in SOT recipients. The crude 90-day mortality rate was 56.6%. The 12-month mucormycosis cumulative incidence was 0.29% for HCT and 0.07% for SOT. Mucormycosis incidence among HCT recipients varied widely, from 0.08% to 0.69%, with higher incidence in cohorts receiving transplants during 2003 and 2004. Non-Aspergillus mold infections continue to be associated with high mortality rates. The incidence of mucormycosis in HCT recipients increased substantially during the surveillance period.
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    Needles in a haystack: Extremely rare invasive fungal infections reported in FungiScopeⓇ-Global Registry for Emerging Fungal Infections.
    (The Journal of infection, 2020-11) Salmanton-García, Jon; Koehler, Philipp; Kindo, Anupma; Falces-Romero, Iker; García-Rodríguez, Julio; Ráčil, Zdeněk; Chen, Sharon C-A; Klimko, Nikolai; Desoubeaux, Guillaume; Thompson, George R; Benítez-Peñuela, Miguel-Ángel; Rodríguez, José-Yesid; Sheppard, Donald C; Hoenigl, Martin; Le Govic, Yohann; Badali, Hamid; Baddley, John W; Chander, Jagdish; Ingram, Paul R; Pakstis, Diana L; Mellinghoff, Sibylle C; Atıcı, Serkan; Cesaro, Simone; Chakrabarti, Arunaloke; Dupont, Damien; González, Gloria M; Hatvani, Lóránt; Herbrecht, Raoul; Klyasova, Galina; Lass-Flörl, Cornelia; Mareș, Mihai; Mullane, Kathleen; Vinh, Donald C; Wisplinghoff, Hilmar; Lackner, Michaela; Cornely, Oliver A; Seidel, Danila; ECMM/ISHAM working group

    Objectives

    Emerging invasive fungal infections (IFI) have become a notable challenge. Apart from the more frequently described fusariosis, lomentosporiosis, mucormycosis, scedosporiosis, and certain dematiaceae or yeasts, little is known about extremely rare IFI.

    Methods

    Extremely rare IFI collected in the FungiScopeⓇ registry were grouped as Dematiaceae, Hypocreales, Saccharomycetales, Eurotiales, Dermatomycetes, Agaricales, and Mucorales.

    Results

    Between 2003 and June 2019, 186 extremely rare IFI were documented in FungiScopeⓇ. Dematiaceae (35.5%), Hypocreales (23.1%), Mucorales (11.8%), and Saccharomycetales (11.3%) caused most IFI. Most patients had an underlying malignancy (38.7%) with acute leukemia accounting for 50% of cancers. Dissemination was observed in 26.9% of the patients. Complete or partial clinical response rate was 68.3%, being highest in Eurotiales (82.4%) and in Agaricales (80.0%). Overall mortality rate was 29.3%, ranging from 11.8% in Eurotiales to 50.0% in Mucorales.

    Conclusions

    Physicians are confronted with a complex variety of fungal pathogens, for which treatment recommendations are lacking and successful outcome might be incidental. Through an international consortium of physicians and scientists, these cases of extremely rare IFI can be collected to further investigate their epidemiology and eventually identify effective treatment regimens.
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    Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001-2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database.
    (Clin Infect Dis, 2010-04-15) Kontoyiannis, Dimitrios P; Marr, Kieren A; Park, Benjamin J; Alexander, Barbara D; Anaissie, Elias J; Walsh, Thomas J; Ito, James; Andes, David R; Baddley, John W; Brown, Janice M; Brumble, Lisa M; Freifeld, Alison G; Hadley, Susan; Herwaldt, Loreen A; Kauffman, Carol A; Knapp, Katherine; Lyon, G Marshall; Morrison, Vicki A; Papanicolaou, Genovefa; Patterson, Thomas F; Perl, Trish M; Schuster, Mindy G; Walker, Randall; Wannemuehler, Kathleen A; Wingard, John R; Chiller, Tom M; Pappas, Peter G
    BACKGROUND: The incidence and epidemiology of invasive fungal infections (IFIs), a leading cause of death among hematopoeitic stem cell transplant (HSCT) recipients, are derived mainly from single-institution retrospective studies. METHODS: The Transplant Associated Infections Surveillance Network, a network of 23 US transplant centers, prospectively enrolled HSCT recipients with proven and probable IFIs occurring between March 2001 and March 2006. We collected denominator data on all HSCTs preformed at each site and clinical, diagnostic, and outcome information for each IFI case. To estimate trends in IFI, we calculated the 12-month cumulative incidence among 9 sequential subcohorts. RESULTS: We identified 983 IFIs among 875 HSCT recipients. The median age of the patients was 49 years; 60% were male. Invasive aspergillosis (43%), invasive candidiasis (28%), and zygomycosis (8%) were the most common IFIs. Fifty-nine percent and 61% of IFIs were recognized within 60 days of neutropenia and graft-versus-host disease, respectively. Median onset of candidiasis and aspergillosis after HSCT was 61 days and 99 days, respectively. Within a cohort of 16,200 HSCT recipients who received their first transplants between March 2001 and September 2005 and were followed up through March 2006, we identified 718 IFIs in 639 persons. Twelve-month cumulative incidences, based on the first IFI, were 7.7 cases per 100 transplants for matched unrelated allogeneic, 8.1 cases per 100 transplants for mismatched-related allogeneic, 5.8 cases per 100 transplants for matched-related allogeneic, and 1.2 cases per 100 transplants for autologous HSCT. CONCLUSIONS: In this national prospective surveillance study of IFIs in HSCT recipients, the cumulative incidence was highest for aspergillosis, followed by candidiasis. Understanding the epidemiologic trends and burden of IFIs may lead to improved management strategies and study design.
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    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.