Chun Lin, Tsung-Ying Yang, Ming-Cheng Chan, Kuo-Hsuan Hsu, Yen-Hsiang Huang, Jeng-Sen Tseng
Comprehensive Analysis and Risk Identification of Pulmonary Cryptococcosis in Non-HIV Patients.
J Fungi (Basel). 2021 Aug 13;7(8). doi: 10.3390/jof7080657. Epub 2021 Aug 13.
Abstract/Text
Pulmonary cryptococcosis in the non-human immunodeficiency virus-infected population is uncommon. We aimed to explore the relevance between clinical presentations, radiological findings, and comorbidities and identify the outcome predictors. A total of 321 patients at Taichung Veterans General Hospital between 2005 and 2019 were included; of them, 204 (63.6%) had at least one comorbidity, while 67 (20.9%) had two or more. The most common comorbidities were diabetes mellitus (27.4%), malignant solid tumor (19.6%), autoimmune disease (15.6%), and chronic kidney disease (8.4%). Patients experiencing comorbidity, particularly those with multiple comorbidities, had a higher multilobar and extrapulmonary involvement, which could explain these patients being more symptomatic. In the overall population, extrapulmonary involvement independently predicted disease recurrence and death. Amongst patients with isolated pulmonary cryptococcosis, age, cryptococcal antigen (CrAg) titer in blood, and comorbidities not only predicted the extent of disease, but also its outcome. Of note, patients simultaneously with age ≥ 65 years, CrAg test ≥ 1:128, and multiple comorbidities had the lowest disease control of antifungal treatment (76.9%) and the highest rate of disease recurrence or death from any cause (40.0%). In conclusion, approximately two-thirds of patients had at least one underlying comorbidity. In addition to extrapulmonary involvement, old age, high CrAg titer in blood, and multiple comorbidities could act as risk factors for predicting the extent of disease and outcome.
Findra Setianingrum, Riina Rautemaa-Richardson, David W Denning
Pulmonary cryptococcosis: A review of pathobiology and clinical aspects.
Med Mycol. 2019 Feb 1;57(2):133-150. doi: 10.1093/mmy/myy086.
Abstract/Text
Pulmonary cryptococcosis is an important opportunistic invasive mycosis in immunocompromised patients, but it is also increasingly seen in immunocompetent patients. The main human pathogens are Cryptococcus neoformans and C. gattii, which have a worldwide distribution. In contrast to cryptococcal meningitis, pulmonary cryptococcosis is still underdiagnosed because of limitations in diagnostic tools. It can mimic lung cancer, pulmonary tuberculosis, bacterial pneumonia, and other pulmonary mycoses both clinically and radiologically. Pulmonary nodules are the most common radiological feature, but these are not specific to pulmonary cryptococcosis. The sensitivity of culture of respiratory samples for Cryptococcus is poor and a positive result may also reflect colonisation. Cryptococcal antigen (CrAg) with lateral flow device is a fast and sensitive test and widely used on serum and cerebrospinal fluid, but sera from patients with pulmonary cryptococcosis are rarely positive in the absence of disseminated disease. Detection of CrAg from respiratory specimens might assist the diagnosis of pulmonary cryptococcosis but there are very few data. Molecular detection techniques such as multiplex reverse transcription polymerase chain reaction (RT-PCR) could also provide better sensitivity but these still require validation for respiratory specimens. The first line of treatment for pulmonary cryptococcosis is fluconazole, or amphotericin B and flucytosine for those with central nervous system involvement. Pulmonary cryptococcosis worsens the prognosis of cryptococcal meningitis. In this review, we summarize the biological aspects of Cryptococcus and provide an update on the diagnosis and management of pulmonary cryptococcosis.
Li-xuan Xie, You-san Chen, Shi-yuan Liu, Yu-xin Shi
Pulmonary cryptococcosis: comparison of CT findings in immunocompetent and immunocompromised patients.
Acta Radiol. 2015 Apr;56(4):447-53. doi: 10.1177/0284185114529105. Epub 2014 Apr 22.
Abstract/Text
BACKGROUND: Computed tomography (CT) findings in patients with pulmonary cryptococcosis have been reported, however, many reports were limited by the small number of patients, and not taken into account the distinction between immunocompetent and immunocompromised patients.
PURPOSE: To retrospectively evaluate thoracic CT findings in patients with pulmonary cryptococcosis whose immune status ranged from normal to severely compromised, and determine characteristic imaging features of pulmonary cryptococcosis between patients with different immune status.
MATERIAL AND METHODS: CT scan findings of 29 immunocompetent and 43 immunocompromised patients with clinically proven pulmonary cryptococcosis were reviewed retrospectively. Different patterns of CT scan abnormalities between immunocompromised and immunocompetent patients, AIDS and non-AIDS immunocompromised patients were compared by Fisher's exact test.
RESULTS: Pulmonary nodules/masses, either solitary or multiple, were the most common CT finding, present in 65 (90.3%) of the 72 patients; associated findings included CT halo sign (n = 24), cavitation (n = 23), and air bronchogram (n = 17). Areas of consolidation (n = 14), areas of GGO (n = 13), linear opacities (n = 11), lymphadenopathy (n = 5), and pleural effusion (n = 8) were uncommon. The parenchymal abnormalities were peripherally located in 47 (65.2%) of the cases. Cavitations within nodules/masses were more frequently present in immunocompromised patients than in immunocompetent patients (P = 0.009), and in AIDS patients than in non-AIDS immunocompromised patients (P = 0.002). Air bronchograms within nodules/masses were more frequent present in immunocompetent patients than in immunocompromised patients (P = 0.005). Nodules/masses with halo sign were less frequent in AIDS patients than those in non-AIDS immunocompromised patients (P = 0.027).
CONCLUSION: Pulmonary cryptococcosis should be considered in the differential diagnosis of solitary or multiple pulmonary nodules. Cavitations within nodules/masses were more commonly seen in immunocompromised patients, especially AIDS patients, while air bronchograms were more commonly seen in immunocompetent patients.
© The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
J W Baddley, J R Perfect, R A Oster, R A Larsen, G A Pankey, H Henderson, D W Haas, C A Kauffman, R Patel, A K Zaas, P G Pappas
Pulmonary cryptococcosis in patients without HIV infection: factors associated with disseminated disease.
Eur J Clin Microbiol Infect Dis. 2008 Oct;27(10):937-43. doi: 10.1007/s10096-008-0529-z. Epub 2008 May 1.
Abstract/Text
Cryptococcus neoformans is an uncommonly recognized cause of pneumonia in HIV-negative patients. Because of its propensity to disseminate to the meninges and other sites, a lumbar puncture is recommended for patients with pulmonary cryptococcosis, regardless of other risk factors. This study explored clinical and laboratory features to help predict which patients had pulmonary disease alone versus those who had pulmonary plus extrapulmonary disease. A retrospective chart review at 15 medical centers was performed from 1990 to 2000 of all HIV-negative patients who had pulmonary cryptococcosis. Demographic, clinical, radiographic, and laboratory features were evaluated to determine factors that differentiated those patients who had extrapulmonary disease. Among 166 patients who had pulmonary cryptococcosis, 122 had pulmonary infection only and 44 had pulmonary plus extrapulmonary (disseminated) disease. A negative serum cryptococcal antigen titer was more common in patients with pulmonary disease alone (p < 0.01). Multivariate analysis demonstrated that patients who had disseminated disease were more likely than those who only had pulmonary disease to have cirrhosis (p = 0.049), headache (p < 0.001), weight loss (p = 0.003), fever (p = 0.035), altered mental status (p < 0.001), and to be receiving high-dose corticosteroids (p = 0.008). In this large cohort of HIV-negative patients with pulmonary cryptococcosis, there were easily distinguished clinical and laboratory features among patients with pulmonary disease alone versus those with pulmonary plus extrapulmonary disease. These findings may be helpful in the evaluation of HIV-negative patients with pulmonary cryptococcosis with regard to the need for lumbar puncture or to search for disseminated disease.
Nina Singh, Barbara D Alexander, Olivier Lortholary, Françoise Dromer, Krishan L Gupta, George T John, Ramon del Busto, Goran B Klintmalm, Jyoti Somani, G Marshall Lyon, Kenneth Pursell, Valentina Stosor, Patricia Muñoz, Ajit P Limaye, Andre C Kalil, Timothy L Pruett, Julia Garcia-Diaz, Atul Humar, Sally Houston, Andrew A House, Dannah Wray, Susan Orloff, Lorraine A Dowdy, Robert A Fisher, Joseph Heitman, Marilyn M Wagener, Shahid Husain
Pulmonary cryptococcosis in solid organ transplant recipients: clinical relevance of serum cryptococcal antigen.
Clin Infect Dis. 2008 Jan 15;46(2):e12-8. doi: 10.1086/524738.
Abstract/Text
BACKGROUND: The role of serum cryptococcal antigen in the diagnosis and determinants of antigen positivity in solid organ transplant (SOT) recipients with pulmonary cryptococcosis has not been fully defined.
METHODS: We conducted a prospective, multicenter study of SOT recipients with pulmonary cryptococcosis during 1999-2006.
RESULTS: Forty (83%) of 48 patients with pulmonary cryptococcosis tested positive for cryptococcal antigen. Patients with concomitant extrapulmonary disease were more likely to have a positive antigen test result (P=.018), and antigen titers were higher in patients with extrapulmonary disease (P=.003) or fungemia (P=.045). Patients with single nodules were less likely to have a positive antigen test result than were those with all other radiographic presentations (P=.053). Among patients with isolated pulmonary cryptococcosis, lung transplant recipients were less likely to have positive cryptococcal antigen test results than were recipients of other types of SOT (P=.003). In all, 38% of the patients were asymptomatic or had pulmonary cryptococcosis detected as an incidental finding. Nodular densities or mass lesions were more likely to present as asymptomatic or incidentally detected pulmonary cryptococcosis than as pleural effusions and infiltrates (P=.008).
CONCLUSIONS: A positive serum cryptococcal antigen test result in SOT recipients with pulmonary cryptococcosis appears to reflect extrapulmonary or more advanced radiographic disease.
Jingqi Min, Kunlun Huang, Chanmei Shi, Laifu Li, Fuye Li, Tao Zhu, Huojin Deng
Pulmonary Cryptococcosis: comparison of Cryptococcal antigen detection and radiography in Immunocompetent and Immunocompromised patients.
BMC Infect Dis. 2020 Jan 30;20(1):91. doi: 10.1186/s12879-020-4818-1. Epub 2020 Jan 30.
Abstract/Text
BACKGROUND: We compared the cryptococcal antigen detection and imaging findings between immunocompetent and immunocompromised patients in whom pulmonary cryptococcosis had been diagnosed. The aim of our study was to determine whether the patient's immune status and radiography affect the detection of cryptococcal antigen.
METHODS: According to whether they took immunosuppressive drugs or not, seventy and eight adult patients with pulmonary cryptococcosis were divided into two groups: the immunocompetent group and the immunocompromised group. According to the detection of CrAg, each group was divided into the CrAg+ group and the CrAg- group. Then, clinical records, laboratory examinations and computed tomography findings were collected and analyzed.
RESULTS: No difference was found in baseline characteristics, clinical symptoms, and laboratory investigations. By comparing CrAg detection in these two groups, it was found that the number of CrAg+ cases in the immunocompetent group was more than that in the immunocompromised group. And in the immunocompetent group, diffuse lesions were more common in CrAg+ group and limited lesions were more frequently observed in CrAg- group.
CONCLUSIONS: The patient's immune status and radiography would affect the detection of cryptococcal antigen. And serum CrAg could be a useful tool for the diagnosis of pulmonary cryptococcosis in immunocompetent patients with extensive lung involvement.
P G Pappas, J R Perfect, G A Cloud, R A Larsen, G A Pankey, D J Lancaster, H Henderson, C A Kauffman, D W Haas, M Saccente, R J Hamill, M S Holloway, R M Warren, W E Dismukes
Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy.
Clin Infect Dis. 2001 Sep 1;33(5):690-9. doi: 10.1086/322597. Epub 2001 Jul 26.
Abstract/Text
We conducted a case study of human immunodeficiency virus (HIV)-negative patients with cryptococcosis at 15 United States medical centers from 1990 through 1996 to understand the demographics, therapeutic approach, and factors associated with poor prognosis in this population. Of 306 patients with cryptococcosis, there were 109 with pulmonary involvement, 157 with central nervous system (CNS) involvement, and 40 with involvement at other sites. Seventy-nine percent had a significant underlying condition. Patients with pulmonary disease were usually treated initially with fluconazole (63%); patients with CNS disease generally received amphotericin B (92%). Fluconazole was administered to approximately two-thirds of patients with CNS disease for consolidation therapy. Therapy was successful for 74% of patients. Significant predictors of mortality in multivariate analysis included age > or =60 years, hematologic malignancy, and organ failure. Overall mortality was 30%, and mortality attributable to cryptococcosis was 12%. Cryptococcosis continues to be an important infection in HIV-negative patients and is associated with substantial overall and cause-specific mortality.
John R Perfect, William E Dismukes, Francoise Dromer, David L Goldman, John R Graybill, Richard J Hamill, Thomas S Harrison, Robert A Larsen, Olivier Lortholary, Minh-Hong Nguyen, Peter G Pappas, William G Powderly, Nina Singh, Jack D Sobel, Tania C Sorrell
Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america.
Clin Infect Dis. 2010 Feb 1;50(3):291-322. doi: 10.1086/649858.
Abstract/Text
Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous Infectious Diseases Society of America guidelines from 2000 and include new sections. There is a discussion of the management of cryptococcal meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)-infected individuals, (2) organ transplant recipients, and (3) non-HIV-infected and nontransplant hosts. There are specific recommendations for other unique risk populations, such as children, pregnant women, persons in resource-limited environments, and those with Cryptococcus gattii infection. Recommendations for management also include other sites of infection, including strategies for pulmonary cryptococcosis. Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas. Three key management principles have been articulated: (1) induction therapy for meningoencephalitis using fungicidal regimens, such as a polyene and flucytosine, followed by suppressive regimens using fluconazole; (2) importance of early recognition and treatment of increased intracranial pressure and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in patients with renal impairment. Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies. However, if the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients.
Shuo Wei, Xin Su, Yun-Hu Pan, Yuan-Yuan Zheng, Xiao-Wen Dong, Xiao-Hua Hu, Fan Wu, Yi Shi
Postoperative Antifungal Treatment of Pulmonary Cryptococcosis in Non-HIV-Infected and Non-Transplant-Recipient Patients: A Report of 110 Cases and Literature Review.
Open Forum Infect Dis. 2020 Jan;7(1):ofaa004. doi: 10.1093/ofid/ofaa004. Epub 2020 Jan 13.
Abstract/Text
Background: To explore the efficacy of postoperative antifungal treatment for preventing the recurrence of pulmonary cryptococcosis (PC) and occurrence of cryptococcal meningitis (CM), a retrospective study was conducted in 112 hospitalized PC patients with or without antifungal treatment following surgery.
Methods: The treatment failure rate, PC recurrence rate, and CM incidence were compared. Additionally, the effectiveness of postoperative antifungal therapy was assessed by gathering and analyzing the published literature.
Results: The failure rate (P = .054) and recurrence rate (P = .178) were similar in the 2 groups, but the incidence of CM was lower in the group that received postoperative antifungal treatment (P = .039).
Conclusions: This study did not show any difference in the PC recurrence rate or failure rate in the different treatment duration groups. Thus, a shorter antifungal treatment course of 2 months may be an optional treatment. In addition, upon review of the literature, no case of CM occurrence was reported among the 169 cases given postoperative antifungal treatment.
© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
Felix Bongomin, Rita O Oladele, Sara Gago, Caroline B Moore, Malcolm D Richardson
A systematic review of fluconazole resistance in clinical isolates of Cryptococcus species.
Mycoses. 2018 May;61(5):290-297. doi: 10.1111/myc.12747. Epub 2018 Feb 14.
Abstract/Text
Fluconazole is the most commonly used antifungal agent for both the treatment of cryptococcal meningitis, and for prophylaxis against the disease. However, its prolonged use has the potential to exert selection pressure in favour of fluconazole-resistant strains. We evaluated the prevalence of fluconazole resistance in Cryptococcus spp. clinical isolates in 29 studies from 1988 to May 2017 included in EMBASE and MEDLINE databases. A total of 4995 Cryptococcus isolates from 3210 patients constituted this study; 248 (5.0%) of the isolates from relapsed episodes of cryptococcosis were included in this analysis. Eleven (38%) of the studies used minimum inhibitory concentrations (MICs) breakpoints of ≥64 μg/mL to define fluconazole resistance, 6 (21%) used ≥32 μg/mL, 11 (38%) used ≥16 μg/mL and 1 (3%) used ≤20 μg/mL. Overall, mean prevalence of fluconazole resistance was 12.1% (95% confidence interval [CI]: 6.7-17.6) for all isolates (n = 4995). Mean fluconazole resistance was 10.6% (95% CI: 5.5-15.6) for the incident isolates (n = 4747) and 24.1% (95% CI: -3.1-51.2) for the relapse isolates (n = 248). Of the 4995 isolates, 936 (18.7%) had MICs above the ecological cut-off value. Fluconazole resistance appears to be an issue in Cryptococcus isolates from patients with relapses. It remains unclear whether relapses occur due to resistance or other factors. There is an urgent need to establish antifungal breakpoints for Cryptococcus spp.
© 2018 Blackwell Verlag GmbH.
John R Perfect, Kieren A Marr, Thomas J Walsh, Richard N Greenberg, Bertrand DuPont, Juliàn de la Torre-Cisneros, Gudrun Just-Nübling, Haran T Schlamm, Irja Lutsar, Ana Espinel-Ingroff, Elizabeth Johnson
Voriconazole treatment for less-common, emerging, or refractory fungal infections.
Clin Infect Dis. 2003 May 1;36(9):1122-31. doi: 10.1086/374557. Epub 2003 Apr 22.
Abstract/Text
Treatments for invasive fungal infections remain unsatisfactory. We evaluated the efficacy, tolerability, and safety of voriconazole as salvage treatment for 273 patients with refractory and intolerant-to-treatment fungal infections and as primary treatment for 28 patients with infections for which there is no approved therapy. Voriconazole was associated with satisfactory global responses in 50% of the overall cohort; specifically, successful outcomes were observed in 47% of patients whose infections failed to respond to previous antifungal therapy and in 68% of patients whose infections have no approved antifungal therapy. In this population at high risk for treatment failure, the efficacy rates for voriconazole were 43.7% for aspergillosis, 57.5% for candidiasis, 38.9% for cryptococcosis, 45.5% for fusariosis, and 30% for scedosporiosis. Voriconazole was well tolerated, and treatment-related discontinuations of therapy or dose reductions occurred for <10% of patients. Voriconazole is an effective and well-tolerated treatment for refractory or less-common invasive fungal infections.
James S Lewis, Nathan P Wiederhold, Morgan Hakki, George R Thompson
New Perspectives on Antimicrobial Agents: Isavuconazole.
Antimicrob Agents Chemother. 2022 Sep 20;66(9):e0017722. doi: 10.1128/aac.00177-22. Epub 2022 Aug 15.
Abstract/Text
Isavuconazole is the newest of the clinically available advanced generation triazole antifungals and is active against a variety of yeasts, molds, and dimorphic fungi. Its current FDA-approved indications include the management of invasive aspergillosis as well as mucormycosis, though the latter indication is supported by limited clinical data. Isavuconazole did not achieve noninferiority to caspofungin for the treatment of invasive candidiasis and therefore lacks an FDA-approved indication for this invasive disease. Significant advantages of isavuconazole, primarily over voriconazole but in some circumstances posaconazole as well, make it an appealing option for the management of complex patients with invasive fungal infections. These potential advantages include lack of QTc interval prolongation, more predictable pharmacokinetics, a less complicated drug interaction profile, and improved tolerability, particularly when compared to voriconazole. This review discusses these topics in addition to addressing the in vitro activity of the compound against a variety of fungi and provides insight into other distinguishing factors among isavuconazole, voriconazole, and posaconazole. The review concludes with an opinion section in which the authors provide the reader with a framework for the current role of isavuconazole in the antifungal armamentarium and where further data are required.
John R Perfect, Oliver A Cornely, Markus Heep, Luis Ostrosky-Zeichner, Kathleen M Mullane, Rochelle Maher, Rodney Croos-Dabrera, Christopher Lademacher, Marc Engelhardt, Caroline Chen, Francisco M Marty
Isavuconazole treatment for rare fungal diseases and for invasive aspergillosis in patients with renal impairment: Challenges and lessons of the VITAL trial.
Mycoses. 2018 Jul;61(7):420-429. doi: 10.1111/myc.12769. Epub 2018 Apr 19.
Abstract/Text
Invasive fungal disease (IFD) confers a substantial risk for morbidity and mortality to immunocompromised patients. Invasive aspergillosis (IA) is the most common IFD caused by moulds but the prevalence of other rare mould diseases, such as mucormycosis, hyalohyphomycosis and phaeohyphomycosis, may be increasing. Treatments are available for IA, but evidence to support efficacy and safety of antifungal agents for rare IFDs, or for IFDs in special patient populations, is limited or lacking. The VITAL trial was conducted to assess the efficacy and safety of isavuconazole for the treatment of patients with IA and renal impairment, or with IFDs caused by rare moulds, yeasts or dimorphic fungi. These patients stand to benefit most from a new treatment option but are unlikely to be included in a randomised, controlled trial. In this article, we review the challenges faced in the design and conduct of the VITAL trial. We also review the findings of VITAL, which included evidence of the efficacy and safety of isavuconazole. Finally, we consider the importance of trials such as VITAL to inform therapeutic decision making for clinicians faced with the challenge of treating patients with rare IFDs and as one paradigm of how to determine efficacy and safety of new drugs for rare and resistant infections without a suitable comparator.
© 2018 The Authors. Mycoses Published by Blackwell Verlag GmbH.
George R Thompson, Adrian Rendon, Rodrigo Ribeiro Dos Santos, Flavio Queiroz-Telles, Luis Ostrosky-Zeichner, Nkechi Azie, Rochelle Maher, Misun Lee, Laura Kovanda, Marc Engelhardt, Jose A Vazquez, Oliver A Cornely, John R Perfect
Isavuconazole Treatment of Cryptococcosis and Dimorphic Mycoses.
Clin Infect Dis. 2016 Aug 1;63(3):356-62. doi: 10.1093/cid/ciw305. Epub 2016 May 11.
Abstract/Text
BACKGROUND: Invasive fungal diseases (IFD) caused by Cryptococcus and dimorphic fungi are associated with significant morbidity and mortality. Isavuconazole (ISAV) is a novel, broad-spectrum, triazole antifungal agent (IV and by mouth [PO]) developed for the treatment of IFD. It displays potent activity in vitro against these pathogens and in this report we examine outcomes of patients with cryptococcosis or dimorphic fungal infections treated with ISAV.
METHODS: The VITAL study was an open-label nonrandomized phase 3 trial conducted to evaluate the efficacy and safety of ISAV treatment in management of rare IFD. Patients received ISAV 200 mg 3 times daily for 2 days followed by 200 mg once-daily (IV or PO). Proven IFD and overall response at end of treatment (EOT) were determined by an independent, data-review committee. Mortality and safety were also assessed.
RESULTS: Thirty-eight patients received ISAV for IFD caused by Cryptococcus spp. (n = 9), Paracoccidioides spp. (n = 10), Coccidioides spp. (n = 9), Histoplasma spp. (n = 7) and Blastomyces spp. (n = 3). The median length of therapy was 180 days (range 2-331 days). At EOT 24/38 (63%) patients exhibited a successful overall response. Furthermore, 8 of 38 (21%) had stable IFD at the end of therapy without progression of disease, and 6 (16%) patients had progressive IFD despite this antifungal therapy. Thirty-three (87%) patients experienced adverse events.
CONCLUSIONS: ISAV was well tolerated and demonstrated clinical activity against these endemic fungi with a safety profile similar to that observed in larger studies, validating its broad-spectrum in vitro activity and suggesting it may be a valuable alternative to currently available agents.
CLINICAL TRIALS REGISTRATION: NCT00634049.
© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.
Christina C Chang, Thomas S Harrison, Tihana A Bicanic, Methee Chayakulkeeree, Tania C Sorrell, Adilia Warris, Ferry Hagen, Andrej Spec, Rita Oladele, Nelesh P Govender, Sharon C Chen, Christopher H Mody, Andreas H Groll, Yee-Chun Chen, Michail S Lionakis, Alexandre Alanio, Elizabeth Castañeda, Jairo Lizarazo, José E Vidal, Takahiro Takazono, Martin Hoenigl, Jan-Willem Alffenaar, Jean-Pierre Gangneux, Rajeev Soman, Li-Ping Zhu, Alexandro Bonifaz, Joseph N Jarvis, Jeremy N Day, Nikolai Klimko, Jon Salmanton-García, Grégory Jouvion, David B Meya, David Lawrence, Sebastian Rahn, Felix Bongomin, Brendan J McMullan, Rosanne Sprute, Tinashe K Nyazika, Justin Beardsley, Fabianne Carlesse, Christopher H Heath, Olusola O Ayanlowo, Olga M Mashedi, Flavio Queiroz-Telles Filho, Mina C Hosseinipour, Atul K Patel, Elvis Temfack, Nina Singh, Oliver A Cornely, David R Boulware, Olivier Lortholary, Peter G Pappas, John R Perfect
Global guideline for the diagnosis and management of cryptococcosis: an initiative of the ECMM and ISHAM in cooperation with the ASM.
Lancet Infect Dis. 2024 Feb 9;. doi: 10.1016/S1473-3099(23)00731-4. Epub 2024 Feb 9.
Abstract/Text
Cryptococcosis is a major worldwide disseminated invasive fungal infection. Cryptococcosis, particularly in its most lethal manifestation of cryptococcal meningitis, accounts for substantial mortality and morbidity. The breadth of the clinical cryptococcosis syndromes, the different patient types at-risk and affected, and the vastly disparate resource settings where clinicians practice pose a complex array of challenges. Expert contributors from diverse regions of the world have collated data, reviewed the evidence, and provided insightful guideline recommendations for health practitioners across the globe. This guideline offers updated practical guidance and implementable recommendations on the clinical approaches, screening, diagnosis, management, and follow-up care of a patient with cryptococcosis and serves as a comprehensive synthesis of current evidence on cryptococcosis. This Review seeks to facilitate optimal clinical decision making on cryptococcosis and addresses the myriad of clinical complications by incorporating data from historical and contemporary clinical trials. This guideline is grounded on a set of core management principles, while acknowledging the practical challenges of antifungal access and resource limitations faced by many clinicians and patients. More than 70 societies internationally have endorsed the content, structure, evidence, recommendation, and pragmatic wisdom of this global cryptococcosis guideline to inform clinicians about the past, present, and future of care for a patient with cryptococcosis.
Copyright © 2024 Elsevier Ltd. All rights reserved.
