今日の臨床サポート

クリプトコッカス肺炎

著者: 大場雄一郎 大阪急性期・総合医療センター 総合内科

監修: 上原由紀 藤田医科大学医学部感染症科

著者校正/監修レビュー済:2022/03/02
参考ガイドライン:
  1. 米国感染症学会(IDSA):Clinical Practice Guidelines for the Management of Cryptococcal Disease: 2010 Update by the Infectious Diseases Society of America (クリプトコッカス症診療ガイドライン2010年)
患者向け説明資料

概要・推奨   

  1. クリプトコッカス肺炎はHIV患者やその他免疫不全患者に多いが、免疫健常者であっても、クリプトコッカス肺炎を除外することはできない(推奨度1)
  1. クリプトコッカス肺炎で、血清クリプトコッカス抗原陽性の場合は、髄液穿刺を行って、髄膜脳炎併発の有無を確認するほうがよい(推奨度2)
  1. 軽症から中等症のクリプトコッカス肺炎で、肺外病変、中枢神経病変が除外されている場合の治療には、フルコナゾール400mg静注または内服を6~12カ月用いる。重症クリプトコッカス肺炎では、中枢神経が感染している場合と同様に、アムホテリシンB静注を主軸とした初期治療を行う(推奨度2)
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
大場雄一郎 : 特に申告事項無し[2022年]
監修:上原由紀 : 特に申告事項無し[2022年]

改訂のポイント:
  1. クリプトコッカス肺炎(肺クリプトコッカス症)の診療指針について定期レビューを行い、疫学、臨床症状、胸部画像所見、微生物検査のプロセス、血清抗原検査の意義、外科的切除治療の意義などについて、新しく研究報告されているエビデンスに基づく記述を追加した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. クリプトコッカスは、莢膜のある酵母様真菌で、Cryptococcus neoformansと、C.gattiiにヒト病原性がある。
 
Cryptococcus neoformans 気管支肺胞洗浄液・墨汁染色

墨汁染色・インディアインク染色で、菌体周囲の莢膜が白く抜け特徴的なhaloを認める。

出典

img1:  著者提供
 
 
 
Cryptococcus neoformans培養コロニー

a:白~クリーム色、滑らかで光沢のあるコロニーを形成する。
b:グラム染色では、球形~卵円状で、発芽を伴う酵母様真菌の形態を呈する。

出典

img1:  著者提供
 
 
 
  1. ハト・ニワトリなどの腸管に定着し、その糞や、糞に汚染された土壌粉塵を吸入して肺胞に達し感染する。
  1. マクロファージに貪食され、肺実質や所属リンパ節の肉芽腫性病変を形成し、無症状定着、肺病変(気道内定着、結節、浸潤影、すりガラス影、空洞、粟粒状病変、acute respiratory distress syndrome: ARDS、縦隔・肺門リンパ節腫脹、気胸、胸膜炎・膿胸)、髄膜脳炎、全身播種まで、結核に類似した多様な病態を呈する。
  1. 肺クリプトコッカス症は、細胞性免疫不全患者が多いが、免疫健常者も1/3以上を占める[1]
  1. 途上国では頻度が多く、先進国での頻度は比較的まれである。
  1. 免疫健常者の肺病変は1/3が無症状で胸部画像発見とされる。
 
  1. クリプトコッカス肺炎はHIV患者やその他免疫不全患者に多いが、免疫健常者であっても、クリプトコッカス肺炎を除外することはできない(推奨度1)
 
  1. 2005年~2019年の台湾の都市部基幹病院1施設の非HIV患者の肺クリプトコッカス症321例の観察研究では、免疫不全に関与する何らかの基礎疾患が64%に見られ、複数の基礎疾患をもつものが21%いたが、36%には全く基礎疾患がなかった。年齢は20~87歳(中央値59歳)で、基礎疾患は多い順に糖尿病(27%)、固形がん(20%)、自己免疫性疾患(16%)、慢性腎臓病(8.4%)、血液疾患(5.3%)、慢性肺疾患(4.7%)、慢性肝疾患(3.2%)、心血管疾患(2.5%)、臓器移植後(0.9%)などであった[1]
問診・診察のポイント  
  1. クリプトコッカス肺炎の経過は、急性から亜急性・慢性、無症状まで幅がある。

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文献 

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.

PMID 34436197
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.

PMID 30329097
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.
PMID 24757183
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.

PMID 18449582
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.

PMID 18171241
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.

PMID 32000709
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.

PMID 11477526
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.

PMID 20047480
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.
PMID 32010733
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.
PMID 29377368
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.

PMID 12715306

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