今日の臨床サポート

HIV患者のPneumocystis肺炎

著者: 柳澤如樹 ハーバード公衆衛生大学院

監修: 味澤篤 がん・感染症センター 都立駒込病院

著者校正/監修レビュー済:2018/06/06

概要・推奨   

疾患のポイント:
  1. ニューモシスチス肺炎(Pneumocystis pneumonia、PCP)とは、Pneumocystis jiroveciiによって引き起こされる肺炎で、亜急性の経過をたどる労作時の呼吸困難、発熱、乾性咳嗽を来す疾患である。
  1. なお、Pneumocystis jiroveciiは真菌であり、空気感染を来すことが知られている。潜伏期間は4~8週間ほどで4歳までに75%がPneumocystis jiroveciiに不顕性感染しているとの報告もある。
  1. HIV感染者が発症する日和見感染症のなかで最も頻度が高い疾患であり、CD4陽性リンパ球数が200/µl以下で発病するリスクが高くなることが知られている。
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  1. 血ガス所見でPaO2<70mmHg、A-aDO2≧35mmHgを認める場合は重症と判断する。
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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:
柳澤如樹 : 特に申告事項無し[2021年]
監修:味澤篤 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 「抗HIV治療ガイドライン2018」、「HIV感染症「治療の手引き」 第21版」に基づき確認を行った(特に新たな知見なし)。
  1. プリマキンがわが国で2016年に承認されたこと、ニューモシスチス肺炎に対して適用外使用となることにつき追記
  1. 「米国の日和見感染症ガイドライン」に基づき、新たにPCPの一次・二次予防の中止基準を追記した。

病態・疫学・診察

疾患(疫学・病態)  
  1. ニューモシスチス肺炎(Pneumocystis pneumonia、PCP)とは、Pneumocystis jirovecii によって引き起こされる肺炎で、亜急性の経過をたどる労作時の呼吸困難、発熱、乾性咳嗽を来す疾患である。
  1. なお、Pneumocystis jiroveciiは、原虫と評価されていた時期もあるが、現在はリボソームとミトコンドリアDNAの性質により真菌に分類されている菌であり、空気感染を来すことが知られている[1]。潜伏期間は4~8週間ほどである。また、血清による評価をした研究によると4歳までに75%がPneumocystis jiroveciiに不顕性感染しているとの報告もある[2]
  1. HIV感染者が発症する日和見感染症のなかで最も頻度が高い疾患であり、CD4陽性リンパ球数が200/µl以下で発病するリスクが高くなることが知られている。 エビデンス 
  1. PCPは、AIDS関連日和見感染症の代表的疾患であるが、ステロイド長期使用、免疫抑制剤や抗TNFα抗体などの生物学的製剤や抗がん剤の使用中、血液腫瘍・骨髄移植、固形臓器移植後などのさまざまな免疫不全状態でも発症することがある。このコンテンツでは特にHIV患者のニューモシスチス肺炎について記載をする。
  1. 抗ウイルス治療の導入により、サンフランシスコや英国におけるHIV患者のPCPの発症率は、9.1~9.5症例/100症例/年から0.9~1.9症例/100症例・年に減少している[3]
問診・診察のポイント  
HIV感染症のリスク確認:
  1. 性感染症の既往:梅毒、淋菌感染症、クラミジア感染症、性器ヘルペス、尖圭コンジローマ、赤痢アメーバ症、ウイルス性肝炎、疥癬など

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文献 

著者: M N Dohn, M L White, E M Vigdorth, C Ralph Buncher, V S Hertzberg, R P Baughman, A George Smulian, P D Walzer
雑誌名: Am J Respir Crit Care Med. 2000 Nov;162(5):1617-21. doi: 10.1164/ajrccm.162.5.9707101.
Abstract/Text To detect whether there was geographic clustering of Pneumocystis carinii pneumonia cases among patients with human immunodeficiency virus (HIV) infection, we performed a retrospective analysis of a clinical database. The rates of pneumocystosis were analyzed by zip code zones for evidence of geographical clustering. During the study period, 118 patients at our AIDS Treatment Center had a first episode of P. carinii pneumonia. An analysis of the 24 zip code zones for which a P. carinii pneumonia rate was calculated (requiring a denominator of at least 10 known HIV- infected individuals residing in that zone) showed a trend toward geographic clustering (p = 0.07); when all 45 Cincinnati zip code zones were included in the analysis, clustering of cases was observed (p = 0. 02). By contrast, no clustering was observed for 52 HIV-infected control subjects with respiratory disease or for 960 HIV-infected patients treated at our center during the same time period. These data raise intriguing questions about exposure to exogenous sources of P. carinii and suggest the need for prospective studies.

PMID 11069785  Am J Respir Crit Care Med. 2000 Nov;162(5):1617-21. doi・・・
著者: L L Pifer, W T Hughes, S Stagno, D Woods
雑誌名: Pediatrics. 1978 Jan;61(1):35-41.
Abstract/Text Using Pneumocystis carinii organisms propagated through three passages in embryonic chick epithelial lung cultures, specific antigens and antisera were prepared for use in counterimmunoelectrophoresis and indirect immunofluorescent antibody techniques. These methods proved to be specific and sensitive for the detection of P. carinii antigen and antibody, respectively, in sera, and were applied to the study of cancer patients with P. carinii pneumonitis (PCP), cancer patients without pneumonitis, and normal children. Antigenemia was detected in 95% of patients with PCP, in 15% of cancer patients without pneumonitis, and in none of the normal children tested. In cross-sectional and longitudinal studies of normal infants and children, acquisition of serum antibody to P. carinii was demonstrated to occur progressively with increase in age. By 4 years of age two thirds of the normal children were found to have antibody to P. carinii in titers of 1:16 or greater. These studies indicate that subclinical P. carinii infection is highly prevalent in normal children, analogous to other opportunistic infections where active disease is manifest predominantly in the compromised host.

PMID 400818  Pediatrics. 1978 Jan;61(1):35-41.
著者: Lara Coelho, Valdiléa Gonçalves Veloso, Beatriz Grinsztejn, Paula Mendes Luz
雑誌名: Braz J Infect Dis. 2014 Mar-Apr;18(2):196-210. doi: 10.1016/j.bjid.2013.10.003. Epub 2013 Nov 23.
Abstract/Text BACKGROUND: The natural history of HIV infection has changed dramatically after the introduction of highly active antiretroviral therapy. Currently, opportunistic illnesses still represent a major cause of death and hospitalization in this population. In this study, we review the trends in opportunistic illnesses incidence rates and compare the results observed in high-income settings with that for low/middle-income settings, with special attention given to studies from Brazil.
METHODS: We systematically searched Pubmed, Web of Science, Lilacs and Google scholar for publications on HIV associated opportunistic illness. Studies reporting rates based on person-time for all opportunistic illnesses and/or the three opportunistic infections of interest, namely, Pneumocystis carinii pneumonia, cerebral toxoplasmosis, and Mycobacterium avium complex were included.
RESULTS: Significant reductions in the incidence rates were demonstrated for opportunistic illnesses overall and also for the specific opportunistic infections included in the present study, both in high and low/middle-income settings. Out of the 37 studies included in the present review, almost 70% were from high-income settings. All the studies conducted in low/middle-income settings were single center studies and four were from Brazil. We found no study from Brazil reporting annual incidence rates of opportunistic illnesses.
CONCLUSIONS: Opportunistic illnesses remain an important public health problem. To better guide health policies in low/middle-income settings, multicenter cohort studies should be encouraged. Studies from Brazil are urgently needed to assess the current burden of opportunistic illnesses in our population and to support the planning of HIV/AIDS health care services organization.

Copyright © 2013 Elsevier Editora Ltda. All rights reserved.
PMID 24275372  Braz J Infect Dis. 2014 Mar-Apr;18(2):196-210. doi: 10.・・・
著者: J A McKinnell, A P Cannella, D F Kunz, E W Hook, S A Moser, L G Miller, J W Baddley, P G Pappas
雑誌名: Transpl Infect Dis. 2012 Oct;14(5):510-8. doi: 10.1111/j.1399-3062.2012.00739.x. Epub 2012 May 1.
Abstract/Text BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is a life-threatening infection for immunocompromised individuals. Robust data and clear guidelines are available for prophylaxis and treatment of human immunodeficiency virus (HIV)-related PCP (HIV-PCP), yet few data and no guidelines are available for non-HIV-related PCP (NH-PCP). We postulated that prevention and inpatient management of HIV-PCP differed from NH-PCP.
METHODS: We performed a retrospective case review of all pathologically confirmed cases of PCP seen at the University of Alabama Medical Center from 1996 to 2008. Data on clinical presentation, hospital course, and outcome were collected using a standardized data collection instrument. Bivariate analysis compared prophylaxis, adjunctive corticosteroids, and clinical outcomes between patients with HIV-PCP and NH-PCP.
RESULTS: Our analysis of the cohort included 97 cases of PCP; 65 HIV and 32 non-HIV cases. Non-HIV cases rarely received primary prophylaxis (4% vs. 38%, P = 0.01) and received appropriate antibiotics later in the course of hospitalization (5.2 days vs. 1.1 days, P < 0.005). Among transplant patients, NH-PCP was diagnosed a mean of 1066 days after transplantation and most patients were on low-dose corticosteroids (87%) at the time of disease onset. No significant differences in adjunctive corticosteroid use (69% vs. 77%, P = 0.39) and 90-day mortality (41% vs. 28%, P = 0.20) were detected.
CONCLUSIONS: Patients who have undergone organ or stem cell transplant remain at risk for PCP for many years after transplantation. In our cohort, patients who developed NH-PCP were rarely given prophylaxis, and initiation of appropriate antibiotics was significantly delayed compared to cases of HIV-PCP. Medical providers should be aware of the ongoing risk for NH-PCP, even late after transplantation, and consider more aggressive approaches to both prophylaxis and earlier empirical therapy for PCP.

© 2012 John Wiley & Sons A/S.
PMID 22548840  Transpl Infect Dis. 2012 Oct;14(5):510-8. doi: 10.1111/・・・
著者: J L Davis, D A Welsh, C B Beard, J L Jones, G G Lawrence, M R Fox, K Crothers, A Morris, D Charbonnet, A Swartzman, L Huang
雑誌名: Thorax. 2008 Apr;63(4):329-34. doi: 10.1136/thx.2007.088104. Epub 2007 Nov 16.
Abstract/Text BACKGROUND: When Pneumocystis DNA is recovered from respiratory specimens of patients without Pneumocystis pneumonia (PCP), patients are said to be colonised with Pneumocystis, although the significance of this state is unknown. Understanding risk factors for and outcomes of colonisation may provide insights into the life cycle and transmission dynamics of Pneumocystis jirovecii.
METHODS: We performed a cross sectional study of the prevalence and clinical predictors of Pneumocystis colonisation in 172 HIV infected, PCP negative inpatients undergoing diagnostic evaluation of 183 episodes of pneumonia at either the Medical Center of Louisiana at New Orleans between 2003 and 2005 or San Francisco General Hospital between 2000 and 2005. DNA was extracted from sputum and bronchoalveolar lavage specimens and amplified using a nested PCR assay at the mitochondrial large subunit (18S) ribosomal RNA locus. Colonisation was deemed present if Pneumocystis DNA was identified by both gel electrophoresis and direct DNA sequencing.
RESULTS: 68% (117/172) of all patients were colonised with Pneumocystis. No strong associations with colonisation were identified for any demographic factors. Among clinical factors, having a CD4+ T cell count CONCLUSIONS: The majority of hospitalised HIV infected patients with non-PCP pneumonia are colonised with Pneumocystis. Failure to use co-trimoxazole prophylaxis and severe immunosuppression are associated with an increase in the odds of colonisation. Pneumocystis colonisation among hospitalised patients does not commonly lead to PCP.

PMID 18024536  Thorax. 2008 Apr;63(4):329-34. doi: 10.1136/thx.2007.08・・・
著者: Philippe M Hauser, Jacques Bille, Cornelia Lass-Flörl, Christian Geltner, Marta Feldmesser, Michael Levi, Hitesh Patel, Victoria Muggia, Barbara Alexander, Martin Hughes, Sarah A Follett, Xiaohui Cui, Flora Leung, Gillian Morgan, Adrian Moody, David S Perlin, David W Denning
雑誌名: J Clin Microbiol. 2011 May;49(5):1872-8. doi: 10.1128/JCM.02390-10. Epub 2011 Mar 2.
Abstract/Text Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection. Microscopic diagnosis, including diagnosis using the Merifluor-Pneumocystis direct fluorescent antigen (MP-DFA) test, has limitations. Real-time PCR may assist in diagnosis, but no commercially validated real-time PCR assay has been available to date. MycAssay Pneumocystis is a commercial assay that targets the P. jirovecii mitochondrial large subunit (analytical detection limit, ≤ 3.5 copies/μl of sample). A multicenter trial recruited 110 subjects: 54 with transplants (40 with lung transplants), 32 with nonmalignant conditions, 13 with leukemia, and 11 with solid tumors; 9 were HIV positive. A total of 110 respiratory samples (92% of which were bronchoalveolar lavage [BAL] specimens) were analyzed by PCR. Performance was characterized relative to investigator-determined clinical diagnosis of PCP (including local diagnostic tests), and PCR results were compared with MP-DFA test results for 83 subjects. Thirteen of 14 subjects with PCP and 9/96 without PCP (including 5 undergoing BAL surveillance after lung transplantation) had positive PCR results; sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) were 93%, 91%, 59%, and 99%, respectively. Fourteen of 83 subjects for whom PCR and MP-DFA test results were available had PCP; PCR sensitivity, specificity, PPV, and NPV were 93%, 90%, 65%, and 98%, respectively, and MP-DFA test sensitivity, specificity, PPV, and NPV were 93%, 100%, 100%, and 98%. Of the 9 PCR-positive subjects without PCP, 1 later developed PCP. The PCR diagnostic assay compares well with clinical diagnosis using nonmolecular methods. Additional positive results compared with the MP-DFA test may reflect low-level infection or colonization.

PMID 21367988  J Clin Microbiol. 2011 May;49(5):1872-8. doi: 10.1128/J・・・
著者: M Cruciani, P Marcati, M Malena, O Bosco, G Serpelloni, C Mengoli
雑誌名: Eur Respir J. 2002 Oct;20(4):982-9.
Abstract/Text Sputum induction is a simple and noninvasive procedure for Pneumocystis carinii pneumonia (PCP) diagnosis in human immunodeficiency virus-1-positive patients, although less sensitive than bronchoalveolar lavage (BAL). In order to obtain an overview of the diagnostic accuracy of sputum induction, a systematic review and meta-analysis of studies reporting the comparative sensitivity and specificity of BAL (the "gold standard") and sputum induction was performed. The odds ratio and related 95% confidence interval were calculated using summary receiving operating characteristic curves as well as fixed-effect and random-effect models. Based on pooled data, the negative and positive predictive values were calculated for a range of PCP prevalence using a Bayesian approach. Seven prospective studies assessed the comparative accuracy of BAL and sputum induction. On the whole, sputum induction demonstrated 55.5% sensitivity and 98.6% specificity. The sensitivity of sputum induction was significantly higher with immunofluorescence than with cytochemical staining (67.1 versus 43.1%). In settings of 25-60% prevalence of PCP, the positive and negative predictive values ranged 86-96.7 and 66.2-89.8, respectively, with immunofluorescence, and 79-94.4 and 53-83.5% with cytochemical staining. In conclusion, in a setting of low prevalence of Pneumocystis carinii pneumonia, sputum induction, particularly with immunostaining, appears to be adequate for clinical decision-making.

PMID 12412693  Eur Respir J. 2002 Oct;20(4):982-9.
著者: Paul E Sax, Lauren Komarow, Malcolm A Finkelman, Philip M Grant, Janet Andersen, Eileen Scully, William G Powderly, Andrew R Zolopa, AIDS Clinical Trials Group Study A5164 Team
雑誌名: Clin Infect Dis. 2011 Jul 15;53(2):197-202. doi: 10.1093/cid/cir335.
Abstract/Text UNLABELLED: (See the editorial commentary by Morris and Masur, on pages 203-204.)
BACKGROUND: Improved noninvasive diagnostic tests for Pneumocystis jirovecii pneumonia (PCP) are needed. We evaluated the test characteristics of plasma (1 → 3)-β-D-glucan (β-glucan) for HIV-related PCP among a large group of patients presenting with diverse opportunistic infections (OIs).
METHODS: The study population included all 282 participants in AIDS Clinical Trials Group A5164, a study of early versus deferred antiretroviral therapy in conjunction with initial therapy of acute OIs. Baseline plasma samples were assayed for β-glucan, with standard assay reference values defining ≥ 80 pg/mL as positive. Before this analysis, diagnosis of PCP was independently adjudicated by 2 study investigators after reviewing reports from study sites.
RESULTS: A total of 252 persons had a β-glucan result that could be analyzed, 173 (69%) of whom had received a diagnosis of PCP. Median β-glucan with PCP was 408 pg/mL (interquartile range [IQR], 209-500 pg/mL), compared with 37 pg/mL (IQR, 31-235 pg/mL) without PCP (P < .001). The sensitivity of β-glucan dichotomized at 80 pg/mL for the diagnosis of PCP was 92% (95% confidence interval [CI], 87%-96%), and the specificity was 65% (95% CI, 53%-75%); positive and negative predictive values were 85% (95% CI, 79%-90%) and 80% (95% CI, 68%-89%) respectively, based on the study prevalence of 69% of patients with PCP. Rates of abnormal lactate dehyrogenase levels did not differ significantly between those with and without PCP.
CONCLUSIONS: Blood (1 → 3)-β-D-glucan is strongly correlated with HIV-related PCP. In some clinical centers, this may be a more sensitive test than the induced sputum examination and could reduce the need for both bronchoscopy and empirical therapy of PCP.

PMID 21690628  Clin Infect Dis. 2011 Jul 15;53(2):197-202. doi: 10.109・・・
著者: Brian R Wood, Lauren Komarow, Andrew R Zolopa, Malcolm A Finkelman, William G Powderly, Paul E Sax
雑誌名: AIDS. 2013 Mar 27;27(6):967-72. doi: 10.1097/QAD.0b013e32835cb646.
Abstract/Text OBJECTIVE: The objective of this study was to define the test characteristics of plasma beta-glucan for diagnosis of Pneumocystis jirovecii pneumonia (PCP) in AIDS patients with respiratory symptoms.
DESIGN: Analysis of baseline blood samples in a randomized strategy study of patients with acute opportunistic infections, limited to participants with respiratory symptoms.
METHODS: Participants in the 282-person ACTG A5164 trial had baseline plasma samples assayed for beta-glucan testing. As part of A5164 trial, two study investigators independently adjudicated the diagnosis of PCP. Respiratory symptoms were identified by investigators from a list of all signs and symptoms with an onset or resolution in the 21 days prior to or 14 days following study entry. Beta-glucan was defined as positive if at least 80 pg/ml and negative if less than 80 pg/ml.
RESULTS: Of 252 study participants with a beta-glucan result, 159 had at least one respiratory symptom, 139 of whom had a diagnosis of PCP. The sensitivity of beta-glucan for PCP in participants with respiratory symptoms was 92.8% [95% confidence interval (CI) 87.2-96.5], and specificity 75.0% (95% CI 50.9-91.3). Among 134 individuals with positive beta-glucan and respiratory symptoms, 129 had PCP, for a positive predictive value of 96.3% (95% CI 91.5-98.8). Fifteen of 25 patients with a normal beta-glucan did not have PCP, for a negative predictive value of 60% (95% CI 38.7-78.9).
CONCLUSION: Elevated plasma beta-glucan has a high predictive value for diagnosis of PCP in AIDS patients with respiratory symptoms. We propose an algorithm for the use of beta-glucan as a diagnostic tool on the basis of the pretest probability of PCP in such patients.

PMID 23698062  AIDS. 2013 Mar 27;27(6):967-72. doi: 10.1097/QAD.0b013e・・・
著者: V L Ng, D M Yajko, W K Hadley
雑誌名: Clin Microbiol Rev. 1997 Jul;10(3):401-18.
Abstract/Text Extrapulmonary pneumocystosis is an exceedingly rare complication of Pneumocystis carinii pneumonia (PCP). Prior to the advent of the human immunodeficiency virus type 1 (HIV-1) epidemic, only 16 cases of extrapulmonary pneumocystosis in individuals who were immunocompromised by a variety of underlying diseases had been reported. Since the beginning of the HIV-1 and related PCP epidemic, at least 90 cases of extrapulmonary pneumocystosis have been reported. This review briefly presents a history of the discovery of P. carinii and its recognition as a human pathogen, the controversy regarding its taxonomy, and the epidemiology of this organism. A more detailed analysis of the incidence of extrapulmonary pneumocystosis in HIV-1-infected individuals and its occurrence despite widespread prophylaxis for PCP with either aerosolized pentamidine or systemic dapsone-trimethoprim is presented. The clinical features of published cases of extrapulmonary pneumocystosis in non-HIV-1-infected individuals are summarized and contrasted with those in HIV-1 infected individuals. The diagnosis of extrapulmonary pneumocystosis is discussed, and because clinical microbiologists and pathologists are the key individuals in establishing the diagnosis, the characteristic microscopic morphology of P. carinii as its appears when stained with a variety of stains is presented and reviewed. The review concludes with a brief discussion of treatments for extrapulmonary pneumocystosis.

PMID 9227859  Clin Microbiol Rev. 1997 Jul;10(3):401-18.
著者: M W Fei, E J Kim, C A Sant, L G Jarlsberg, J L Davis, A Swartzman, L Huang
雑誌名: Thorax. 2009 Dec;64(12):1070-6. doi: 10.1136/thx.2009.117846. Epub 2009 Oct 12.
Abstract/Text BACKGROUND: Although the use of antiretroviral therapy has led to dramatic declines in AIDS-associated mortality, Pneumocystis pneumonia (PCP) remains a leading cause of death in HIV-infected patients.
OBJECTIVES: To measure mortality, identify predictors of mortality at time of illness presentation and derive a PCP mortality prediction rule that stratifies patients by risk for mortality.
METHODS: An observational cohort study with case note review of all HIV-infected persons with a laboratory diagnosis of PCP at San Francisco General Hospital from 1997 to 2006.
RESULTS: 451 patients were diagnosed with PCP on 524 occasions. In-hospital mortality was 10.3%. Multivariate analysis identified five significant predictors of mortality: age (adjusted odds ratio (AOR) per 10-year increase, 1.69; 95% CI 1.08 to 2.65; p = 0.02); recent injection drug use (AOR 2.86; 95% CI 1.28 to 6.42; p = 0.01); total bilirubin >0.6 mg/dl (AOR 2.59; 95% CI 1.19 to 5.62; p = 0.02); serum albumin <3 g/dl (AOR 3.63; 95% CI 1.72-7.66; p = 0.001); and alveolar-arterial oxygen gradient >or=50 mm Hg (AOR 3.02; 95% CI 1.41 to 6.47; p = 0.004). Using these five predictors, a six-point PCP mortality prediction rule was derived that stratifies patients according to increasing risk of mortality: score 0-1, 4%; score 2-3, 12%; score 4-5, 48%.
CONCLUSIONS: The PCP mortality prediction rule stratifies patients by mortality risk at the time of illness presentation and should be validated as a clinical tool.

PMID 19825785  Thorax. 2009 Dec;64(12):1070-6. doi: 10.1136/thx.2009.1・・・
著者: M S Dworkin, D L Hanson, T R Navin
雑誌名: J Infect Dis. 2001 May 1;183(9):1409-12. doi: 10.1086/319866. Epub 2001 Apr 10.
Abstract/Text To examine survival after diagnosis of Pneumocystis carinii pneumonia (PCP) and factors associated with early death (during the month of or the month after diagnosis of PCP), data were analyzed from the Adult and Adolescent Spectrum HIV Disease project. Among 4412 patients with 5222 episodes of PCP during follow-up (1992-1998), survival at >1 month after diagnosis was 82%, and survival at > or =12 months after diagnosis was 47%; 12-month survival increased from 40% in 1992-1993 to 63% in 1996-1998. By multiple logistic regression analysis, early death was associated with history of PCP (odds ratio [OR], 1.4), age 45-59 years (OR, 1.9) or > or =60 years (OR, 3.7), and CD4 cell count of 0-24 cells/microL (< or =5 months before PCP; OR, 1.8) or 25-49 cells/microL (OR, 1.4) (P<.05). Concurrent prescription of combination antiretroviral therapy (OR, 0.2) and other antiretroviral therapy (OR, 0.4) was associated with surviving the early period. This study shows improved survival after diagnosis of PCP in recent years, despite emergence of antibiotic-resistant mutant P. carinii strains.

PMID 11294675  J Infect Dis. 2001 May 1;183(9):1409-12. doi: 10.1086/3・・・
著者: S H Yale, A H Limper
雑誌名: Mayo Clin Proc. 1996 Jan;71(1):5-13.
Abstract/Text OBJECTIVE: To determine the clinical spectrum of immunosuppressive conditions and systemic corticosteroid therapy associated with the development of Pneumocystis carinii pneumonia in a consecutive series of patients without acquired immunodeficiency syndrome (AIDS).
DESIGN: We retrospectively analyzed a consecutive series of 116 patients without AIDS who were assessed at Mayo Medical Center for a first episode of P. carinii pneumonia between 1985 and 1991.
METHODS: Medical records were examined to determine underlying immunosuppressive disorders, premorbid corticosteroid dosage and duration of therapy, associated infections, and subsequent respiratory failure and in-hospital mortality.
RESULTS: Conditions associated with a first episode of P. carinii pneumonia were hematologic malignant disorders (30.2%), organ transplantation (25.0%), inflammatory disorders (22.4%), solid tumors (12.9%), and miscellaneous conditions (9.5%). Regardless of the associated underlying disease, corticosteroids had been administered systemically in 105 patients (90.5%) within 1 month before the diagnosis of P. carinii pneumonia. The median daily corticosteroid dose was equivalent to 30 mg of prednisone; however, 25% of patients had received as little as 16 mg of prednisone daily. The median duration of corticosteroid therapy was 12 weeks before the development of pneumonia; however, P. carinii pneumonia developed after 8 weeks or less of corticosteroid therapy in 25% of these patients. Respiratory failure occurred in 43%, and in-hospital mortality was 34% for patients with P. carinii pneumonia in conditions other than AIDS.
CONCLUSION: Although these results do not suggest that premorbid administration of corticosteroids is the only factor that contributes to the development of P. carinii pneumonia in these patients, they show that, in this large consecutive series, systemic corticosteroid therapy, even in moderate doses, was administered to most patients during the month preceding the onset of P. carinii pneumonia. Consideration should be given to instituting P. carinii prophylaxis (when not contra-indicated) in patients for whom prolonged systemic corticosteroid therapy is prescribed.

PMID 8538233  Mayo Clin Proc. 1996 Jan;71(1):5-13.
著者: A M Morris, L Huang, P Bacchetti, J Turner, P C Hopewell, J M Wallace, P A Kvale, M J Rosen, J Glassroth, L B Reichman, J D Stansell
雑誌名: Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):612-6. doi: 10.1164/ajrccm.162.2.9912058.
Abstract/Text Human immunodeficiency virus (HIV)-associated respiratory infections, most notably Pneumocystis carinii pneumonia (PCP), but also bacterial pneumonia (BP), result in reductions in lung function that have been studied mainly during the course of acute infection. Whether HIV-associated pneumonias also cause permanent changes in pulmonary function is unknown. In this study we investigated the long-term effects of PCP and BP on pulmonary function in a cohort of HIV-infected persons. One thousand, one hundred forty-nine HIV-infected persons were followed in a prospective, observational cohort study at six centers in the United States. Study participants had pulmonary function testing performed at regular preset intervals. PCP and BP diagnoses were verified with defined criteria. Longitudinal multivariate analysis was used to model pulmonary function in terms of demographic data and occurrence of PCP or BP. We found that PCP or BP was associated with permanent decreases in FEV(1), FVC, FEV(1)/FVC, and the diffusing capacity of carbon monoxide. Neither infection resulted in statistically significant changes in TLC. We conclude that PCP and BP result in expiratory airflow reductions that persist after the acute infection resolves. The clinical implications of these changes are unknown, but they may contribute to prolonged respiratory complaints in HIV-infected patients who have had pneumonia.

PMID 10934095  Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):612-6. ・・・
著者: A M Morris, M Swanson, H Ha, L Huang
雑誌名: Am J Respir Crit Care Med. 2000 Nov;162(5):1622-6. doi: 10.1164/ajrccm.162.5.2002065.
Abstract/Text The epidemiology of Pneumocystis carinii pneumonia (PCP) and its geographic distribution are incompletely understood. We examined the influence of geographic location as a risk factor for PCP through a retrospective case-control study of HIV-infected persons evaluated for PCP at San Francisco General Hospital. Subjects had microscopically confirmed PCP diagnosed between January 1996 and June 1999. Control subjects had a presentation suggestive of PCP, but had bronchoalveolar lavage examination that did not reveal P. carinii. Medical chart review was performed to obtain demographic and clinical characteristics of the subjects as well as their addresses at time of PCP evaluation. Multivariate analyses were performed in order to identify variables associated with PCP. Lack of P. carinii prophylaxis and a CD4 cell count
PMID 11069786  Am J Respir Crit Care Med. 2000 Nov;162(5):1622-6. doi:・・・
著者: Firas Choukri, Jean Menotti, Claudine Sarfati, Jean-Christophe Lucet, Gilles Nevez, Yves J F Garin, Francis Derouin, Anne Totet
雑誌名: Clin Infect Dis. 2010 Aug 1;51(3):259-65. doi: 10.1086/653933.
Abstract/Text BACKGROUND: Airborne transmission of Pneumocystis has been demonstrated in animal models and is highly probable in humans. However, information concerning burdens of Pneumocystis jirovecii (human-derived Pneumocystis) in exhaled air from infected patients is lacking. Our objective is to evaluate P. jirovecii air diffusion in patients with Pneumocystis pneumonia.
METHODS: Patients admitted with Pneumocystis pneumonia were prospectively enrolled from 9 January 2008 to 21 July 2009. Air samples (1.5 m(3)) were collected on liquid medium with a commercial sampler at 1-, 3-, 5-, and 8-m distances from patients' heads. Air control samples were collected away from Pneumocystis pneumonia patient wards and outdoors. Samples were examined for P. jirovecii detection and quantification using a real-time polymerase chain reaction assay targeting the mitochondrial large subunit ribosomal RNA gene.
RESULTS: Forty patients were diagnosed as having Pneumocystis pneumonia. Air sampling was performed in the environment for 19 of them. At a 1-m distance from patients' heads, P. jirovecii DNA was detected in 15 (79.8%) of 19 patients, with fungal burdens ranging from 7.5 X 10³ to 4.5 X 10⁶ gene copies/m(3). These levels decreased with distance from the patients (P < .002). Nevertheless, 4 (33.3%) of the 12 samples taken at 8 m, in the corridor adjacent to their room, were still positive. Forty control samples were collected and remained negative.
CONCLUSION: This study provides the first quantitative data on the spread of P. jirovecii in exhaled air from infected patients. It sustains the risk of P. jirovecii direct transmission in close contact with patients with Pneumocystis pneumonia and leads the way for initiating a quantitative risk assessment for airborne transmission of P. jirovecii.

PMID 20572759  Clin Infect Dis. 2010 Aug 1;51(3):259-65. doi: 10.1086/・・・
著者: Laurence Huang, Adithya Cattamanchi, J Lucian Davis, Saskia den Boon, Joseph Kovacs, Steven Meshnick, Robert F Miller, Peter D Walzer, William Worodria, Henry Masur, International HIV-associated Opportunistic Pneumonias (IHOP) Study, Lung HIV Study
雑誌名: Proc Am Thorac Soc. 2011 Jun;8(3):294-300. doi: 10.1513/pats.201009-062WR.
Abstract/Text During the past 30 years, major advances have been made in our understanding of HIV/AIDS and Pneumocystis pneumonia (PCP), but significant gaps remain. Pneumocystis is classified as a fungus and is host-species specific, but an understanding of its reservoir, mode of transmission, and pathogenesis is incomplete. PCP remains a frequent AIDS-defining diagnosis and is a frequent opportunistic pneumonia in the United States and in Europe, but comparable epidemiologic data from other areas of the world that are burdened with HIV/AIDS are limited. Pneumocystis cannot be cultured, and bronchoscopy with bronchoalveolar lavage is the gold standard procedure to diagnose PCP, but noninvasive diagnostic tests and biomarkers show promise that must be validated. Trimethoprim-sulfamethoxazole is the recommended first-line treatment and prophylaxis regimen, but putative trimethoprim-sulfamethoxazole drug resistance is an emerging concern. The International HIV-associated Opportunistic Pneumonias (IHOP) study was established to address these knowledge gaps. This review describes recent advances in the pathogenesis, epidemiology, diagnosis, and management of HIV-associated PCP and ongoing areas of clinical and translational research that are part of the IHOP study and the Longitudinal Studies of HIV-associated Lung Infections and Complications (Lung HIV).

PMID 21653531  Proc Am Thorac Soc. 2011 Jun;8(3):294-300. doi: 10.1513・・・
著者: Bryan J Krajicek, Andrew H Limper, Charles F Thomas
雑誌名: Curr Opin Pulm Med. 2008 May;14(3):228-34. doi: 10.1097/MCP.0b013e3282f94abc.
Abstract/Text PURPOSE OF REVIEW: Pneumocystis pneumonia remains the most prevalent opportunistic infection in patients with AIDS. It is also a common devastating infection in patients with other causes of altered immunity. Though scientific study of this fungal pathogen is challenging given the inability to propagate the organism outside of the host lung, studies utilizing advanced molecular techniques and genomic analysis have broadened our understanding of the epidemiology and pathogenesis of Pneumocystis and will be described herein.
RECENT FINDINGS: Results from advanced molecular techniques suggest that Pneumocystis organisms not only cause infection in patients with impaired immunity but also colonize mammals with normal immune systems. Advanced technology has also identified acquired Pneumocystis genetic mutations that confer resistance to currently utilized therapeutics. Though not yet widely utilized in clinical medicine, advanced polymerase chain reaction techniques improve the diagnostic yield of respiratory specimen analysis. Preliminary results from serum beta-glucan testing suggest that a noninvasive marker of Pneumocystis pneumonia infection and response to therapy may be on the horizon.
SUMMARY: Recent scientific advances suggest opportunities for improving the diagnosis and treatment surveillance of Pneumocystis pneumonia. Further investigations are necessary to define the optimal characteristics of these laboratory tests and to develop therapeutics directed at novel Pneumocystis genomic targets.

PMID 18427246  Curr Opin Pulm Med. 2008 May;14(3):228-34. doi: 10.1097・・・

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