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: 具芳明 東京医科歯科大学大学院医歯学総合研究科 統合臨床感染症学分野

著者校正/監修レビュー済:2016/06/30
患者向け説明資料

概要・推奨   

疾患のポイント:
  1. クリプトコッカス肺炎とは、莢膜を有する酵母のCryptococcus neoformansで汚染された土壌の吸入により罹患する肺感染症である。免疫能正常者に対しては無症候性かつ自己限定性の一次肺病変を示すが、エイズ患者などのcompromised hostに対しては急性呼吸困難など重度の症状を伴う進行性肺炎を呈することがある。
  1. クリプトコッカス肺炎は比較的まれな疾患であるが、免疫不全者でも免疫健常者でも発症し、多彩な画像所見をとる。難治性下気道感染症の鑑別診断の1つにいつも挙げておくように心がけたい。
 
診断:
  1. 下気道検体で、グラム染色、H-E染色、塗銀染色などで莢膜を持つ酵母様真菌を認めるか、培養でクリプトコッカスを同定する。
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  1. Cryptococcus neoformans 気管支肺胞洗浄液・墨汁染色:
  1. Cryptococcus neoformans培養コロニー:
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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。
※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、実際の保険適用の査定において保険適用及び保険適用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用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 : 未申告[2021年]
監修:具芳明 : 特に申告事項無し[2021年]

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。<図表> <図表>
  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. 感染症は、細胞性免疫不全患者が多いが、免疫健常者も20%を占める[1]。 エビデンス 
  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。
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 

著者: 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
雑誌名: 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  Clin Infect Dis. 2001 Sep 1;33(5):690-9. doi: 10.1086/3・・・
著者: 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
雑誌名: 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  Eur J Clin Microbiol Infect Dis. 2008 Oct;27(10):937-43・・・
著者: 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
雑誌名: 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  Clin Infect Dis. 2008 Jan 15;46(2):e12-8. doi: 10.1086/・・・
著者: 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
雑誌名: 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  Clin Infect Dis. 2010 Feb 1;50(3):291-322. doi: 10.1086・・・
著者: Hassan F Nadrous, Vera S Antonios, Christine L Terrell, Jay H Ryu
雑誌名: Chest. 2003 Dec;124(6):2143-7.
Abstract/Text BACKGROUND: Cryptococcus neoformans can cause serious systemic infections requiring systemic antifungal therapy in immunocompromised hosts. However, isolated pulmonary cryptococcosis in nonimmunocompromised hosts has been reported to resolve spontaneously without treatment.
STUDY OBJECTIVE: s: To determine the role of antifungal therapy in the management of isolated pulmonary cryptococcosis in nonimmunocompromised hosts.
DESIGN: Retrospective study.
SETTING: Tertiary care, referral medical center
PATIENTS: Thirty-six nonimmunocompromised subjects with isolated pulmonary cryptococcosis who received diagnoses at the Mayo Clinic (Rochester, MN) from 1976 to 2001.
INTERVENTIONS: None.
MEASUREMENTS AND RESULTS: Of 42 nonimmunocompromised subjects with cryptococcal infections, 36 (86%) had isolated pulmonary cryptococcosis. The mean (+/- SD) age of these 36 patients was 61 +/- 15 years (range, 14 to 88 years), and the groups included 17 men (47%) and 19 women (53%). Twenty-four patients (67%) were symptomatic, and 12 patients (33%) were asymptomatic. The most common presenting symptoms were cough, dyspnea, and fever. Cultures of sputum and bronchial washings most commonly yielded the diagnosis. Cerebrospinal fluid examination was performed in 11 patients (31%) and was negative in all of them. Follow-up information was available on 25 patients (69%) with a median duration of 19 months (range, 1 to 330 months). Twenty-three of these patients (92%) had resolution of their disease (no treatment, 8 patients; surgical resection only, 6 patients; and antifungal therapy, 9 patients). The condition of the two remaining patients had improved. There was no documented treatment failure, relapse, dissemination, or death in any of these 25 patients.
CONCLUSIONS: Our findings suggest that an initial period of observation without the administration of antifungal therapy is a reasonable option for nonimmunocompromised subjects with pulmonary cryptococcosis in the absence of systemic symptoms or evidence of dissemination, as well as after surgical resection for focal cryptococcal pneumonia.

PMID 14665493  Chest. 2003 Dec;124(6):2143-7.
著者: 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
雑誌名: 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  Clin Infect Dis. 2003 May 1;36(9):1122-31. doi: 10.1086・・・

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