今日の臨床サポート

ニューモシスチス肺炎

概要・推奨   

  1. HIV陽性者においてCD4陽性細胞数の減少(<250個/μLまたは<14%)はPCP発症のリスクとなるが、抗ウイルス療法(ART)はそのリスクを減らす可能性がある(推奨度2)。
  1. PCPの患者を入院させる際には病室は個室が望ましい。少なくとも免疫不全者との同室は避けるべきかもしれない(推奨度3)。
  1. 非HIV陽性者のPCPに対する予防内服はリスクが3.5%以上あれば考慮すべきである。しかし個別の悪性腫瘍や膠原病などについての明確なデータは十分ではない(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。
※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:
上原由紀 : 特に申告事項無し[2021年]
監修:上原由紀 : 特に申告事項無し[2021年]

改訂のポイント:
  1.  定期レビューを行い、関連ガイドラインの更新、予防投薬に関する内容の更新を行なった。 

病態・疫学・診察

疾患情報(疫学・病態)  
  1. ニューモシスチス肺炎とは、Pneumocystis jiroveciiが主に免疫不全者に引き起こす重篤な肺炎である。
  1. Pneumocystis属は真菌の一種と考えられており、そのなかでもP. jiroveciiがヒトに感染を起こす(以前はP. cariniiと表現されていたが、この種はネズミに感染する)[1]
  1. P. jiroveciiの主な形態は嚢子(cyst)と栄養体(trophozoite)である。嚢子は直径5~8μmの球形~卵円形を示し、そのなかにスポロゾイト(sporozoite)を認める。また栄養体は2~5μmほどの大きさの楕円形である(染色により不定形になることもある)。現在のところ人工培養は成功していない。
  1. 表面抗原としてMSG(major surface glycoprotein)を持ち、免疫系の反応を回避する役割を果たしている。
  1. ニューモシスチス肺炎は「Pneumocystis Carinii Pneumonia」の略としてPCPと略されていたが、現在でも「Pneumo Cystis Pneumonia」の略称として同様のPCPが使用されている。
  1. P. jiroveciiはヒト-ヒトで飛沫感染を起こす可能性が示されているが、免疫系に異常がない場合には無症候のキャリアとなる。免疫不全者の場合、P. jiroveciiを保菌している率は高い[2][3]
  1. 疾患の予防として患者のリスクに応じた予防内服を行う。また曝露予防のために発症者と免疫不全者の病室を分けることを勧める考えもある。
  1. HIV陽性者と非HIV陽性者とでは同じPCPでも病像がさまざまな点で異なることに留意する。HIV陽性者の発症は緩徐で数週間を経て悪化するが、非HIV陽性者では数日で急激に悪化する。
 
HIV陽性者とHIV非陽性者におけるPCPの違い

PCPはHIV陽性者と非陽性者とでは病態や治療反応など多くの点で異なっている。
 
参考文献:
  1. McKinnell JA, et al. Pneumocystis pneumonia in hospitalized patients; A detailed examination of symptoms, management, and outcomes in HIV-infected and HIV-uninfected persons. Transpl Infect Dis. 2012 Oct;14(5):510-518. doi:10.1111/j.1399-3062.2012.00739.x. PMID:22548840
  1. Sepkowitz KA. Opportunistic infections in patients with and patients without acquired immunodeficiency syndrome. CID 2002;34:1098-107. PMID:11914999
  1. Mansharamani NG, et al. Management and outcome patterns for adult pneumocystis carinii pneumonia, 1985 to 1995. Comparison of HIV-associated cases to other immunocompromised states. Chest 2000;118:701-711. PMID:10988192
  1. Tasaka S, et al. Comparison of clinical and radiological features of Pneumocystis pneumonia between malignancy cases and acquired immunodeficiency syndrome cases: a multicenter study. Inter Med 49: 273-281, 2010. PMID:20154431

出典

img1:  椎木創一先生提供
 
 
問診・診察のポイント  
  1. 免疫不全者に多い疾患である。特にHIV感染症が挙げられるため、そのリスクを評価する。

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文献 

著者: Emilie Catherinot, Fanny Lanternier, Marie-Elisabeth Bougnoux, Marc Lecuit, Louis-Jean Couderc, Olivier Lortholary
雑誌名: Infect Dis Clin North Am. 2010 Mar;24(1):107-38. doi: 10.1016/j.idc.2009.10.010.
Abstract/Text Pneumocystis jirovecii has gained attention during the last decade in the context of the AIDS epidemic and the increasing use of cytotoxic and immunosuppressive therapies. This article summarizes current knowledge on biology, pathophysiology, epidemiology, diagnosis, prevention, and treatment of pulmonary P jirovecii infection, with a particular focus on the evolving pathophysiology and epidemiology. Pneumocystis pneumonia still remains a severe opportunistic infection, associated with a high mortality rate.

Copyright 2010 Elsevier Inc. All rights reserved.
PMID 20171548  Infect Dis Clin North Am. 2010 Mar;24(1):107-38. doi: 1・・・
著者: Alison Morris, Kenneth Wei, Kamyar Afshar, Laurence Huang
雑誌名: J Infect Dis. 2008 Jan 1;197(1):10-7. doi: 10.1086/523814.
Abstract/Text Pneumocystis pneumonia has long been recognized as a cause of morbidity and mortality in immunocompromised populations, particularly those with HIV infection. Pneumocystis colonization-that is, detection of the organism or its DNA, without signs or symptoms of pneumonia-has recently been described, and accumulating evidence suggests that it may be an important clinical phenomenon. Sensitive molecular techniques such as polymerase chain reaction are frequently used to identify Pneumocystis colonization. Low levels of Pneumocystis in the lungs may stimulate pulmonary inflammation and may play a role in the development of lung diseases such as chronic obstructive pulmonary disease. In this review, we discuss evidence for the occurrence of Pneumocystis colonization in animals as well as the epidemiology and risk factors for Pneumocystis colonization in various human populations. We also evaluate the clinical significance of Pneumocystis colonization and its relationship to lung disease.

PMID 18171279  J Infect Dis. 2008 Jan 1;197(1):10-7. doi: 10.1086/5238・・・
著者: Andreas A Rostved, Monica Sassi, Jørgen A L Kurtzhals, Søren Schwartz Sørensen, Allan Rasmussen, Christian Ross, Emile Gogineni, Charles Huber, Geetha Kutty, Joseph A Kovacs, Jannik Helweg-Larsen
雑誌名: Transplantation. 2013 Nov 15;96(9):834-42. doi: 10.1097/TP.0b013e3182a1618c.
Abstract/Text BACKGROUND: An outbreak of 29 cases of Pneumocystis jirovecii pneumonia (PCP) occurred among renal and liver transplant recipients (RTR and LTR) in the largest Danish transplantation centre between 2007 and 2010, when routine PCP prophylaxis was not used.
METHODS: P. jirovecii isolates from 22 transplant cases, 2 colonized RTRs, and 19 Pneumocystis control samples were genotyped by restriction fragment length polymorphism and multilocus sequence typing analysis. Contact tracing was used to investigate transmission. Potential risk factors were compared between PCP cases and matched non-PCP transplant patients.
RESULTS: Three unique Pneumocystis genotypes were shared among 19 of the RTRs, LTRs, and a colonized RTR in three distinct clusters, two of which overlapped temporally. In contrast, Pneumocystis control samples harbored a wide range of genotypes. Evidence of possible nosocomial transmission was observed. Among several potential risk factors, only cytomegalovirus viremia was consistently associated with PCP (P=0.03; P=0.009). Mycophenolate mofetil was associated with PCP risk only in the RTR population (P=0.04).
CONCLUSION: We identified three large groups infected with unique strains of Pneumocystis and provide evidence of an outbreak profile and nosocomial transmission. LTRs may be infected in PCP outbreaks simultaneously with RTRs and by the same strains, most likely by interhuman transmission. Patients are at risk several years after transplantation, but the risk is highest during the first 6 months after transplantation. Because patients at risk cannot be identified clinically and outbreaks cannot be predicted, 6 months of PCP chemoprophylaxis should be considered for all RTRs and LTRs.

PMID 23903011  Transplantation. 2013 Nov 15;96(9):834-42. doi: 10.1097・・・
著者: Yusuke Ainoda, Yuji Hirai, Takahiro Fujita, Noriko Isoda, Kyoichi Totsuka
雑誌名: J Infect Chemother. 2012 Oct;18(5):722-8. doi: 10.1007/s10156-012-0408-5. Epub 2012 Mar 30.
Abstract/Text Pneumocystis jirovecii pneumonia (PCP) is classified as PCP with human immunodeficiency virus (HIV) and non-HIV PCP, and the two forms differ in progression and prognosis. Although early treatment is necessary, the diagnosis of non-HIV PCP is often difficult because of the underlying diseases. However, the outcome with treatment delay remains unclear because there are no concrete data indicating a worsened clinical situation or increased complications related to delayed therapy initiation. We retrospectively examined patients with non-HIV PCP admitted to Tokyo Women's Medical University Hospital from November 2008 to October 2010. The relationship between intubation with mechanical ventilation (within 1 week after starting treatment) and treatment delay was investigated. Treatment delay was defined as the period, in days, from onset to therapy initiation. In total, 24 confirmed non-HIV PCP cases were included. Median treatment delay was 7 ± 4.83 days (1-20 days). Twelve of 24 cases (50 %) were intubated, and 11 (45.8 %) died of their underlying diseases within 90 days. Treatment delay was more than 7 days in the intubation group, but was within 7 days in 9 of 12 nonintubation cases. The difference in treatment delay was significant (p = 0.0071) between the intubation and nonintubation groups, but there were no significant differences in survival rate at 90 days or other findings. We conclude that starting treatment within 7 days after onset is important because intubation and mechanical ventilation may be avoided in many cases.

PMID 22460829  J Infect Chemother. 2012 Oct;18(5):722-8. doi: 10.1007/・・・
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: Ming-Chi Li, Nan-Yao Lee, Ching-Chi Lee, Hsin-Chun Lee, Chia-Ming Chang, Wen-Chien Ko
雑誌名: J Microbiol Immunol Infect. 2014 Feb;47(1):42-7. doi: 10.1016/j.jmii.2012.08.024. Epub 2012 Oct 11.
Abstract/Text BACKGROUND: Pneumocystis jiroveci pneumonia (PJP) is a life-threatening disease in immunocompromised patients. Improved knowledge about the varied characteristics and management in different populations may guide treatment.
METHODS: We evaluated the clinical characteristics, management, and outcomes of patients with PJP diagnosed by nested polymerase chain reaction at a medical center in southern Taiwan from 2008 to 2011. The risk factors of mortality among non-human immunodeficiency virus (HIV)-infected patients were analyzed.
RESULTS: During the study period, there were 43 cases of PJP, and the common underlying diseases were HIV infection (23 patients, median CD4 count: 19/μl) and malignancy. The HIV-infected patients had a younger age (36.9 ± 13.7 vs. 50.2 ± 16.2 years, p = 0.006), a lower body mass index (19.9 ± 2.3 vs. 22.0 ± 3.7 kg/m(2), p = 0.035), a longer duration of symptoms before admission (24 ± 29 vs. 7 ± 15 days, p = 0.035), and a lower pneumonia severity index (56 ± 25 vs. 99 ± 35, p < 0.001) than non-HIV-infected patients. A delay between admission and starting antimicrobial therapy for PJP (10 ± 10 days vs. 1 ± 3 days, p = 0.004) and a high crude mortality (12/20, 60% vs. 2/23, 9%, p = 0.001) were noted in non-HIV-infected patients. In the univariate analysis, the risk factors for mortality were a low lymphocyte count (p < 0.05) and shock during hospitalization (p = 0.004).
CONCLUSION: A delay in the initiation of antimicrobial therapy for PJP and severe pneumonia were more common in the non-HIV-infected patients and were most likely related to the poor prognosis. The utilization of sensitive diagnostic tools to facilitate early diagnosis and treatment may improve the clinical outcomes of non-HIV-infected patients with PJP.

Copyright © 2012. Published by Elsevier B.V.
PMID 23063081  J Microbiol Immunol Infect. 2014 Feb;47(1):42-7. doi: 1・・・
著者: Yasufumi Matsumura, Yuichiro Shindo, Yoshitsugu Iinuma, Masaki Yamamoto, Michinori Shirano, Aki Matsushima, Miki Nagao, Yutaka Ito, Shunji Takakura, Yoshinori Hasegawa, Satoshi Ichiyama
雑誌名: BMC Infect Dis. 2011 Mar 25;11:76. doi: 10.1186/1471-2334-11-76. Epub 2011 Mar 25.
Abstract/Text BACKGROUND: The number of patients with non-HIV Pneumocystis pneumonia (PCP) is increasing with widespread immunosuppressive treatment. We investigated the clinical characteristics of non-HIV PCP and its association with microbiological genotypes.
METHODS: Between January 2005 and March 2010, all patients in 2 university hospitals who had been diagnosed with PCP by PCR were enrolled in this study. Retrospective chart review of patients, microbiological genotypes, and association with 30-day mortality were examined.
RESULTS: Of the 82 adult patients investigated, 50 patients (61%) had inflammatory diseases, 17 (21%) had solid malignancies, 12 (15%) had hematological malignancies, and 6 (7%) had received transplantations. All patients received immunosuppressive agents or antitumor chemotherapeutic drugs. Plasma (1→3) β-D-glucan levels were elevated in 80% of patients, and were significantly reduced after treatment in both survivors and non-survivors. However, β-D-glucan increased in 18% of survivors and was normal in only 33% after treatment. Concomitant invasive pulmonary aspergillosis was detected in 5 patients. Fifty-six respiratory samples were stored for genotyping. A dihydropteroate synthase mutation associated with trimethoprim-sulfamethoxazole resistance was found in only 1 of the 53 patients. The most prevalent genotype of mitochondrial large-subunit rRNA was genotype 1, followed by genotype 4. The most prevalent genotype of internal transcribed spacers of the nuclear rRNA operon was Eb, followed by Eg and Bi. Thirty-day mortality was 24%, in which logistic regression analysis revealed association with serum albumin and mechanical ventilation, but no association with genotypes.
CONCLUSIONS: In non-HIV PCP, poorer general and respiratory conditions at diagnosis were independent predictors of mortality. β-D-glucan may not be useful for monitoring the response to treatment, and genotypes were not associated with mortality.

PMID 21439061  BMC Infect Dis. 2011 Mar 25;11:76. doi: 10.1186/1471-23・・・
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: L Huang, F M Hecht, J D Stansell, R Montanti, W K Hadley, P C Hopewell
雑誌名: Am J Respir Crit Care Med. 1995 Jun;151(6):1866-71. doi: 10.1164/ajrccm.151.6.7767533.
Abstract/Text In U.S. patients with the acquired immunodeficiency syndrome (AIDS), Pneumocystis carinii pneumonia is the most frequent AIDS-defining opportunistic infection. Sputum induction and bronchoscopy are effective techniques for obtaining specimens used to identify P. carinii although debate continues over their optimal use, specifically whether to perform bronchoscopy after a negative induced sputum examination for P. carinii. To evaluate the usefulness of bronchoscopy in this situation, we reviewed all cases of suspected P. carinii pneumonia in which sputum induction for P. carinii was performed at San Francisco General Hospital during a 4-yr period. Bronchoscopy, performed after a negative induced sputum examination, yielded a diagnosis in 50.5% of evaluations. The most frequent diagnoses were P. carinii pneumonia (192), tracheobronchial Kaposi's sarcoma (93), tuberculosis (28), and Cryptococcus neoformans pneumonia (9). Bronchoscopy provided either the only or an earlier diagnosis in 64.3% of tuberculosis cases. Bronchoscopy with BAL was free of complications, and, importantly, a negative BAL examination for P. carinii allowed physicians to discontinue empiric P. carinii pneumonia treatment in 95%. In patients with suspected P. carinii pneumonia with a negative induced sputum examination for P. carinii, early bronchoscopy with BAL should be performed.

PMID 7767533  Am J Respir Crit Care Med. 1995 Jun;151(6):1866-71. doi・・・
著者: Yihong Wang, Saryn Doucette, Qinfang Qian, James E Kirby
雑誌名: Arch Pathol Lab Med. 2007 Oct;131(10):1582-4. doi: 10.1043/1543-2165(2007)131[1582:YOPARI]2.0.CO;2.
Abstract/Text CONTEXT: Induced sputum sampling has an approximate 70% sensitivity for detection of Pneumocystis jiroveci in human immunodeficiency virus (HIV) patients. Bronchoalveolar lavage sampling has greater than 90% sensitivity but is a far more invasive procedure. Therefore, bronchoalveolar lavage testing is often recommended as a follow-up after a negative induced sputum. In HIV-negative patients, the utility of induced sputum testing is still not well defined.
OBJECTIVE: To determine whether repeat induced sputum sampling increases diagnostic yield and might thereby reduce the need for follow-up bronchoalveolar lavage sampling. To determine the utility of induced sputum sampling in HIV-negative patients.
DESIGN: A 2-year retrospective review of the utility of repeat induced sputa testing in patients with previous first and/or second negative induced sputa. Retrospective review of induced sputa detection in HIV-negative patients.
RESULTS: Repeat testing of induced sputa for Pneumocystic jirovecii did not significantly increase diagnostic yield. Furthermore, in HIV-negative patients, induced sputum testing was diagnostically insensitive.
CONCLUSIONS: Bronchoalveolar lavage testing should be performed initially in HIV-negative patients and after a first negative induced sputum in HIV-positive patients.

PMID 17922597  Arch Pathol Lab Med. 2007 Oct;131(10):1582-4. doi: 10.1・・・
著者: Pierre Flori, Bahrie Bellete, Fabrice Durand, Hélène Raberin, Céline Cazorla, Jamal Hafid, Frédéric Lucht, Roger Tran Manh Sung
雑誌名: J Med Microbiol. 2004 Jul;53(Pt 7):603-7.
Abstract/Text Between January 2002 and July 2003, 173 bronchoalveolar lavage (BAL) specimens from 150 patients (19 HIV-infected and 131 non-HIV-infected patients) were evaluated for identification of Pneumocystis jiroveci (formerly known as Pneumocystis carinii f. sp. hominis) using staining techniques, conventional PCR (mtLSUrRNA gene) and real-time PCR (MSG gene). Test results were compared to Pneumocystis pneumonia (PCP) confirmed by typical clinical findings and response to treatment. Sensitivity and specificity of the techniques were 60 and 100% for staining (where either one or both techniques were positive), 100 and 87.0% for conventional PCR and 100 and 84.9 % for real-time PCR, respectively. The use of a concentration of 10(3) copies of DNA per capillary of BAL as a cut-off (determined by real-time PCR) increased specificity from 84.9 to 98.6% without reducing the sensitivity of the technique. This technique is rapid (<3 h) and therefore of major interest in differentiating between asymptomatic carriage and PCP. A BAL specimen with <10(3) copies per capillary of Pneumocystis-specific DNA is more likely to indicate a chronic carrier state, but in such cases follow-up is required to ensure that the patient is not in the early stage of an active PCP.

PMID 15184529  J Med Microbiol. 2004 Jul;53(Pt 7):603-7.
著者: Elie Azoulay, Anne Bergeron, Sylvie Chevret, Nicolas Bele, Benoît Schlemmer, Jean Menotti
雑誌名: Chest. 2009 Mar;135(3):655-61. doi: 10.1378/chest.08-1309.
Abstract/Text RATIONALE: Pneumocystis jiroveci polymerase chain reaction (PCR) has higher sensitivity than conventional stains but cannot distinguish colonization from infection.
METHODS: We compared P jiroveci PCR and conventional stains in HIV-uninfected immunocompromised patients.
RESULTS: Among the 448 patients, 296 (66%) patients had hematologic malignancies; 72 (16.1%), bone marrow transplants; 44 (9.8%), solid tumors; 21 (4.7%), renal transplants; and 15 (3.4%) were taking immunosuppressants for systemic diseases. Diagnostic strategy consisted of BAL in 351 patients and induced sputum (IS) in 97 patients. Conventional pneumocystic pneumonia (PCP) stain was positive in 39 (8.7%) patients, including 34 with positive PCR. In addition, PCR was positive in 32 patients, including 21 with complete follow-up, of whom 14 were diagnosed with probable or definitive PCP (a 36% increase). PCR was 87.2% sensitive and 92.2% specific; positive and negative predictive values were 51.5% and 98.7%, respectively. Sensitivity and negative predictive value were 100% on IS.
CONCLUSIONS: In HIV-uninfected immunocompromised patients with acute pulmonary infiltrates, P jiroveci PCR correlates with clinical evidence of PCP. A negative PCR allows withdrawing anti-PCP therapy.

PMID 19265086  Chest. 2009 Mar;135(3):655-61. doi: 10.1378/chest.08-13・・・
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: Hideta Nakamura, Masao Tateyama, Daisuke Tasato, Syusaku Haranaga, Satomi Yara, Futoshi Higa, Yuji Ohtsuki, Jiro Fujita
雑誌名: Intern Med. 2009;48(4):195-202. Epub 2009 Feb 16.
Abstract/Text OBJECTIVE: New serum markers (1-->3) beta-D-glucan (beta-D-glucan) and KL-6 are reported to be useful for the clinical diagnosis of Pneumocystis jirovecii pneumonia (PCP). However, the utility of these markers in PCP with HIV infection (HIV PCP) and without HIV (non-HIV PCP) is unknown. This study was aimed to evaluate the utility of beta-D-glucan and KL-6 for the diagnosis of PCP in patients with HIV infection (HIV PCP) and non-HIV PCP.
METHODS: Retrospective study.
PATIENTS: We reviewed the medical records of consecutive 35 patients. The serum levels of beta-D-glucan and KL-6 in HIV PCP and non-HIV PCP were comparatively evaluated. We evaluated these markers in survivors and non survivors.
RESULTS: The detection rates of serum beta-D-glucan and KL-6 levels in non-HIV PCP were lower than those in HIV PCP (88% vs. 100%, 66% vs. 88%, respectively). The false positive rates of these markers in both groups were similar (12%, 37%, respectively). Oxygenation index, serum albumin, and mechanical ventilation were the variables which were significantly associated with poor outcome in the univariate analysis.
CONCLUSION: In conclusion, beta-D-glucan was a reliable diagnostic marker for PCP. However, the detection rate of beta-D-glucan and KL-6 in non-HIV PCP was lower than in HIV PCP. Neither beta-D-glucan nor KL-6 was associated with the outcome of PCP.

PMID 19218768  Intern Med. 2009;48(4):195-202. Epub 2009 Feb 16.
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: Andrew Zolopa, Janet Andersen, William Powderly, Alejandro Sanchez, Ian Sanne, Carol Suckow, Evelyn Hogg, Lauren Komarow
雑誌名: PLoS One. 2009;4(5):e5575. doi: 10.1371/journal.pone.0005575. Epub 2009 May 18.
Abstract/Text BACKGROUND: Optimal timing of ART initiation for individuals presenting with AIDS-related OIs has not been defined.
METHODS AND FINDINGS: A5164 was a randomized strategy trial of "early ART"--given within 14 days of starting acute OI treatment versus "deferred ART"--given after acute OI treatment is completed. Randomization was stratified by presenting OI and entry CD4 count. The primary week 48 endpoint was 3-level ordered categorical variable: 1. Death/AIDS progression; 2. No progression with incomplete viral suppression (ie HIV viral load (VL) >or=50 copies/ml); 3. No progression with optimal viral suppression (ie HIV VL <50 copies/ml). Secondary endpoints included: AIDS progression/death; plasma HIV RNA and CD4 responses and safety parameters including IRIS. 282 subjects were evaluable; 141 per arm. Entry OIs included Pneumocytis jirovecii pneumonia 63%, cryptococcal meningitis 12%, and bacterial infections 12%. The early and deferred arms started ART a median of 12 and 45 days after start of OI treatment, respectively. THE DIFFERENCE IN THE PRIMARY ENDPOINT DID NOT REACH STATISTICAL SIGNIFICANCE: AIDS progression/death was seen in 20 (14%) vs. 34 (24%); whereas no progression but with incomplete viral suppression was seen in 54 (38%) vs. 44 (31%); and no progression with optimal viral suppression in 67 (48%) vs 63 (45%) in the early vs. deferred arm, respectively (p = 0.22). However, the early ART arm had fewer AIDS progression/deaths (OR = 0.51; 95% CI = 0.27-0.94) and a longer time to AIDS progression/death (stratified HR = 0.53; 95% CI = 0.30-0.92). The early ART had shorter time to achieving a CD4 count above 50 cells/mL (p<0.001) and no increase in adverse events.
CONCLUSIONS: Early ART resulted in less AIDS progression/death with no increase in adverse events or loss of virologic response compared to deferred ART. These results support the early initiation of ART in patients presenting with acute AIDS-related OIs, absent major contraindications.
TRIAL REGISTRATION: ClinicalTrials.gov NCT00055120.

PMID 19440326  PLoS One. 2009;4(5):e5575. doi: 10.1371/journal.pone.00・・・
著者: Charles F Thomas, Andrew H Limper
雑誌名: N Engl J Med. 2004 Jun 10;350(24):2487-98. doi: 10.1056/NEJMra032588.
Abstract/Text
PMID 15190141  N Engl J Med. 2004 Jun 10;350(24):2487-98. doi: 10.1056・・・
著者: Jonathan E Kaplan, Constance Benson, King H Holmes, John T Brooks, Alice Pau, Henry Masur, Centers for Disease Control and Prevention (CDC), National Institutes of Health, HIV Medicine Association of the Infectious Diseases Society of America
雑誌名: MMWR Recomm Rep. 2009 Apr 10;58(RR-4):1-207; quiz CE1-4.
Abstract/Text This report updates and combines earlier versions of guidelines for the prevention and treatment of opportunistic infections (OIs) in HIV-infected adults (i.e., persons aged >/=18 years) and adolescents (i.e., persons aged 13--17 years), last published in 2002 and 2004, respectively. It has been prepared by the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by clinicians and other health-care providers, HIV-infected patients, and policy makers in the United States. These guidelines address several OIs that occur in the United States and five OIs that might be acquired during international travel. Topic areas covered for each OI include epidemiology, clinical manifestations, diagnosis, prevention of exposure; prevention of disease by chemoprophylaxis and vaccination; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment; management of treatment failure; prevention of disease recurrence; discontinuation of secondary prophylaxis after immune reconstitution; and special considerations during pregnancy. These guidelines were developed by a panel of specialists from the United States government and academic institutions. For each OI, a small group of specialists with content-matter expertise reviewed the literature for new information since the guidelines were last published; they then proposed revised recommendations at a meeting held at NIH in June 2007. After these presentations and discussion, the revised guidelines were further reviewed by the co-editors; by the Office of AIDS Research, NIH; by specialists at CDC; and by HIVMA of IDSA before final approval and publication. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments. Major changes in the guidelines include 1) greater emphasis on the importance of antiretroviral therapy for the prevention and treatment of OIs, especially those OIs for which no specific therapy exists; 2) information regarding the diagnosis and management of immune reconstitution inflammatory syndromes; 3) information regarding the use of interferon-gamma release assays for the diagnosis of latent Mycobacterium tuberculosis (TB) infection; 4) updated information concerning drug interactions that affect the use of rifamycin drugs for prevention and treatment of TB; 5) the addition of a section on hepatitis B virus infection; and 6) the addition of malaria to the list of OIs that might be acquired during international travel. This report includes eleven tables pertinent to the prevention and treatment of OIs, a figure that pertains to the diagnois of tuberculosis, a figure that describes immunization recommendations, and an appendix that summarizes recommendations for prevention of exposure to opportunistic pathogens.

PMID 19357635  MMWR Recomm Rep. 2009 Apr 10;58(RR-4):1-207; quiz CE1-4・・・
著者: M Briel, H C Bucher, R Boscacci, H Furrer
雑誌名: Cochrane Database Syst Rev. 2006 Jul 19;(3):CD006150. doi: 10.1002/14651858.CD006150. Epub 2006 Jul 19.
Abstract/Text BACKGROUND: Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Among patients with HIV infection and PCP the mortality rate is 10 to 20% during the initial infection and increases substantially with the need for mechanical ventilation. It was suggested that in these patients corticosteroids adjunctive to standard treatment for PCP could prevent the need for mechanical ventilation and decrease mortality.
OBJECTIVES: To assess the effects of adjunctive corticosteroids on overall mortality and the need for mechanical ventilation in HIV-infected patients with PCP and substantial hypoxemia (arterial oxygen partial pressure <70 mmHg or alveolar-arterial gradient >35 mmHg on room air).
SEARCH STRATEGY: We searched Medline (January 1980-December 2004), EMBASE (January 1985-December 2004) and The Cochrane Library (Issue 4, 2004) without language restrictions to identify randomised controlled trials that compared adjunctive corticosteroids to control in HIV-infected patients with PCP. We further reviewed the reference lists from previously published overviews, we searched UptoDate version 2005 and Clinical Evidence Concise (Issue 12, 2004), contacted experts of the field, and searched reference lists of identified publications for citations of additional relevant articles.
SELECTION CRITERIA: Trials were considered eligible for this review if they compared corticosteroids to placebo or usual care in HIV-infected patients with PCP in addition to baseline treatment with trimethoprim-sulfamethoxazole, pentamidine or dapsone-trimethoprim, used random allocation, and reported mortality data. We excluded trials in patients with no or mild hypoxemia (arterial oxygen partial pressure >70 mmHg or an alveolar-arterial gradient <35 mmHg on room air) and trials with a follow-up of less than 30 days.
DATA COLLECTION AND ANALYSIS: Two teams of reviewers independently evaluated the methodology and extracted data from each primary study. We pooled treatment effects across studies and calculated a weighted average risk ratio of overall mortality in the treatment and control groups by using a random effects model.
MAIN RESULTS: Six studies were included in the review and meta-analysis. Risk ratios for overall mortality for adjunctive corticosteroids were 0.56 (95% confidence interval [CI], 0.32-0.98) at 1 month and 0.68 (95% CI, 0.50-0.94) at 3-4 months of follow-up. To prevent 1 death, numbers needed to treat are 9 patients in a setting without highly active antiretroviral therapy (HAART) available, and 23 patients with HAART available. Only the 3 largest trials provided data on the need for mechanical ventilation with a risk ratio of 0.38 (95% CI, 0.20-0.73) in favour of adjunctive corticosteroids.
AUTHORS' CONCLUSIONS: The number and size of trials investigating adjunctive corticosteroids for HIV-infected patients with PCP is small, but evidence from this review suggests a beneficial effect for patients with substantial hypoxemia.

PMID 16856118  Cochrane Database Syst Rev. 2006 Jul 19;(3):CD006150. d・・・
著者: Song Mi Moon, Tark Kim, Heungsup Sung, Mi-Na Kim, Sung-Han Kim, Sang-Ho Choi, Jin-Yong Jeong, Jun Hee Woo, Yang Soo Kim, Sang-Oh Lee
雑誌名: Antimicrob Agents Chemother. 2011 Oct;55(10):4613-8. doi: 10.1128/AAC.00669-11. Epub 2011 Jul 25.
Abstract/Text While it is well-known that adjunctive corticosteroid use improves the outcome of moderate-to-severe Pneumocystis jirovecii pneumonia (PcP) in patients with human immunodeficiency virus (HIV), there are limited data on its efficacy in non-HIV-infected patients with PcP. Patients undergoing fiber-optic bronchoscopy with bronchoalveolar lavage for suspected PcP from January 2007 through December 2010 were reviewed retrospectively. We compared demographics, clinical characteristics, and outcomes in 88 non-HIV-infected patients with moderate-to-severe PcP with (n = 59) and without (n = 29) adjunctive corticosteroid use. Outcomes of PcP were assessed by respiratory failure and 30-day and 90-day all-cause mortality. Survival curves were analyzed by the Kaplan-Meier method and estimated by the log rank test. All-cause mortality of moderate-to-severe PcP at 90 days was lower in the solid-organ transplant recipients than in all other patients (6/26 [23%] versus 34/62 [55%], respectively; P = 0.006), and mortality at 30 days was lower in patients with hematologic malignancies than in all other patients (4/26 [15%] versus 24/62 [39%], respectively; P = 0.03). The outcomes of PcP were not significantly different in moderate-to-severe PcP patients with and without adjunctive corticosteroid use, regardless of recent corticosteroid use. Survival analysis of PcP patients with and without corticosteroid use by the Kaplan-Meier method also did not reveal any difference (log rank test; P = 0.81). There again was no difference within the subgroup of PcP patients with solid-organ transplants. Adjunctive corticosteroid use may not improve the outcome of moderate-to-severe PcP in non-HIV-infected patients.

PMID 21788460  Antimicrob Agents Chemother. 2011 Oct;55(10):4613-8. do・・・
著者: C Delclaux, J R Zahar, G Amraoui, G Leleu, F Lebargy, L Brochard, B Schlemmer, C Brun-Buisson
雑誌名: Clin Infect Dis. 1999 Sep;29(3):670-2.
Abstract/Text The aim of this retrospective study was to assess whether corticosteroid adjunctive therapy (CAT) could prevent death in immunocompromised patients with severe Pneumocystis carinii pneumonia (PCP) who do not have human immunodeficiency virus (HIV) infection, similarly to what has been demonstrated for HIV-infected patients. The charts of all non-HIV-infected patients who were admitted to two medical intensive care units between 1988 and 1996 because of severe PCP, defined by an arterial oxygen pressure (determined while the patient was breathing room air) of <70 mm Hg, and who were treated with trimethoprim-sulfamethoxazole were analyzed retrospectively. Thirty-one patients met the study criteria, of whom 23 received CAT (within 72 hours of antibiotic therapy) and eight did not receive CAT. The need for mechanical ventilation (10 [43%] of 23 vs. 4 [50%] of 8) and the mortality rate (9 [39%] of 23 vs. 4 [50%] of 8) were similar for the two groups. Although this small study does not have a statistical power high enough to rule out the possibility of a difference, the results suggest that CAT does not improve the survival of non-HIV-infected patients as has been described for HIV-infected patients with severe PCP.

PMID 10530464  Clin Infect Dis. 1999 Sep;29(3):670-2.
著者: J C Lopez Bernaldo de Quiros, J M Miro, J M Peña, D Podzamczer, J C Alberdi, E Martínez, J Cosin, X Claramonte, J Gonzalez, P Domingo, J L Casado, E Ribera, Grupo de Estudio del SIDA 04/98
雑誌名: N Engl J Med. 2001 Jan 18;344(3):159-67. doi: 10.1056/NEJM200101183440301.
Abstract/Text BACKGROUND: Prophylaxis against Pneumocystis carinii pneumonia is indicated in patients with human immunodeficiency virus (HIV) infection who have less than 200 CD4 cells per cubic millimeter and in those with a history of P. carinii pneumonia. However, it is not clear whether prophylaxis can be safely discontinued after CD4 cell counts increase in response to highly active antiretroviral therapy.
METHODS: We conducted a randomized trial of the discontinuation of primary or secondary prophylaxis against P. carinii pneumonia in HIV-infected patients with a sustained response to antiviral therapy, defined by a CD4 cell count of 200 or more per cubic millimeter and plasma HIV type 1 (HIV-1) RNA level of less than 5000 copies per milliliter for at least three months. Prophylactic treatment was restarted if the CD4 cell count declined to less than 200 per cubic millimeter.
RESULTS: The 474 patients receiving primary prophylaxis had a median CD4 cell count at entry of 342 per cubic millimeter, and 38 percent had detectable HIV-1 RNA. After a median follow-up period of 20 months (758 person-years), there had been no episodes of P. carinii pneumonia in the 240 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 0.85 episode per 100 person-years). For the 113 patients receiving secondary prophylaxis, the median CD4 cell count at entry was 355 per cubic millimeter, and 24 percent had detectable HIV-1 RNA. After a median follow-up period of 12 months (123 person-years), there had been no episodes of P. carinii pneumonia in the 60 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 4.5 episodes per 100 person-years).
CONCLUSIONS: In HIV-infected patients receiving highly active antiretroviral therapy, primary and secondary prophylaxis against P. carinii pneumonia can be safely discontinued after the CD4 cell count has increased to 200 or more per cubic millimeter for more than three months.

PMID 11172138  N Engl J Med. 2001 Jan 18;344(3):159-67. doi: 10.1056/N・・・
著者: C Mussini, P Pezzotti, A Govoni, V Borghi, A Antinori, A d'Arminio Monforte, A De Luca, N Mongiardo, M C Cerri, F Chiodo, E Concia, L Bonazzi, M Moroni, L Ortona, R Esposito, A Cossarizza, B De Rienzo
雑誌名: J Infect Dis. 2000 May;181(5):1635-42. doi: 10.1086/315471. Epub 2000 May 15.
Abstract/Text A multicenter open, randomized, controlled trial was conducted to determine whether primary prophylaxis for Pneumocystis carinii pneumonia and toxoplasmic encephalitis can be discontinued in patients infected with human immunodeficiency virus type 1 (HIV-1) whose CD4+ T cell counts have increased to >200 cells/mm3 (and who have remained at this level for at least 3 months) as a result of highly active antiretroviral therapy (HAART). Patients were randomized to either the discontinuation arm (i.e., those who discontinued prophylaxis; n=355) or to the continuation arm (n=353); the 2 arms of the study were similar in terms of demographic, clinical, and immunovirologic characteristics. During the median follow-ups of 6.4 months (discontinuation arm) and 6.1 months (continuation arm) and with a total of 419 patient-years, no patient developed P. carinii pneumonia or toxoplasmic encephalitis. The results of this study strongly indicate that primary prophylaxis for P. carinii pneumonia and toxoplasmic encephalitis can be safely discontinued in patients whose CD4+ T cell counts increase to >200 cells/mm3 during HAART.

PMID 10823763  J Infect Dis. 2000 May;181(5):1635-42. doi: 10.1086/315・・・
著者: Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE), Amanda Mocroft, Peter Reiss, Ole Kirk, Cristina Mussini, Enrico Girardi, Philippe Morlat, Christoph Stephan, Stephane De Wit, Katja Doerholt, Jade Ghosn, Heiner C Bucher, Jens D Lundgren, Genevieve Chene, Jose M Miro, Hansjakob Furrer
雑誌名: Clin Infect Dis. 2010 Sep 1;51(5):611-9. doi: 10.1086/655761.
Abstract/Text BACKGROUND: Current guidelines suggest that primary prophylaxis for Pneumocystis jiroveci pneumonia (PcP) can be safely stopped in human immunodeficiency virus (HIV)-infected patients who are receiving combined antiretroviral therapy (cART) and who have a CD4 cell count >200 cells/microL. There are few data regarding the incidence of PcP or safety of stopping prophylaxis in virologically suppressed patients with CD4 cell counts of 101-200 cells/microL.
METHODS: The Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) included data from 23,412 patients from 12 European cohorts who started taking cART after 1997. Poisson regression was used to model incidence rate ratios (IRRs) of primary PcP.
RESULTS: There were 253 PcP cases during 107,016 person-years of follow-up (PYFU). Prophylaxis significantly reduced the incidence of PcP among patients with current CD4 cell counts 100 cells/microL (adjusted IRR, 0.41; 95% confidence interval [CI], 0.27-0.60) but not significantly among those with current CD4 cell counts of 101-200 cells/microL (adjusted IRR, 0.63; 95% CI, 0.34-1.17). The incidence of PcP among patients who had a current CD4 cell count of 100-200 cells/microL, who had a viral load <400 copies/mL, and who were receiving prophylaxis was 2.1 cases per 1000 PYFU (95% CI, 0.8-4.3 cases per 1000 PYFU; 7 events occurred during 3363 PYFU), whereas 1.2 cases per 1000 PYFU (95% CI, 0.2-4.5 cases per 1000 PYFU; 2 events occurred during 1614 PYFU) occurred among persons who were not receiving prophylaxis (adjusted IRR, 1.65; 95% CI, 0.33-8.15). Among patients who discontinued PcP prophylaxis after starting cART, the incidence of primary PcP was 0 cases per 1000 PYFU (95% CI, 0.0-2.7 cases per 1000 PYFU; 0 events occurred during 1363 PYFU) for patients who had a current CD4 cell count of 101-200 cells/microL and who were receiving cART.
CONCLUSIONS: The incidence of primary PcP among patients who had virologically suppressed HIV infection, were receiving cART, and who had CD4 cell counts >100 cells/microL was low irrespective of prophylaxis use. Discontinuation of prophylaxis may be safe in patients with CD4 counts of 101-200 cells/microL and suppressed viral load.

PMID 20645862  Clin Infect Dis. 2010 Sep 1;51(5):611-9. doi: 10.1086/6・・・
著者: J E Kaplan, D L Hanson, T R Navin, J L Jones
雑誌名: J Infect Dis. 1998 Oct;178(4):1126-32.
Abstract/Text Risk factors for the development of a first episode of Pneumocystis carinii pneumonia (PCP) were investigated in the Adult and Adolescent Spectrum of Disease Project, a medical record review study involving longitudinal follow-up of human immunodeficiency virus-infected adults in 9 US cities. Risk factors included decreasing CD4 lymphocyte count and history of AIDS-defining illness, non-P. carinii pneumonia, oral thrush, or unexplained fever for > or = 2 days; PCP prophylaxis was protective. PCP incidence/100 person-years of observation among persons not prescribed PCP prophylaxis was higher in those with CD4 lymphocyte counts < 250 cells/microL or CD4 cell percent < 14% (8.3; 95% confidence interval [CI], 7.7-9.0) than in persons with CD4 cell counts < 200 or history of thrush or fever, which constitute current criteria for prophylaxis against PCP (5.9; 95% CI, 5.5-6.4). Because of increased efficiency in capturing persons at highest risk, CD4 cell count < 250 or CD4 cell percent < 14% should be considered as criteria for prophylaxis against first episodes of PCP.

PMID 9806044  J Infect Dis. 1998 Oct;178(4):1126-32.
著者: Daria Podlekareva, Amanda Mocroft, Ulrik B Dragsted, Bruno Ledergerber, Marek Beniowski, Adriano Lazzarin, Jonathan Weber, Nathan Clumeck, Norbert Vetter, Andrew Phillips, Jens D Lundgren, EuroSIDA study group
雑誌名: J Infect Dis. 2006 Sep 1;194(5):633-41. doi: 10.1086/506366. Epub 2006 Jul 24.
Abstract/Text BACKGROUND: Limited data exist on factors predicting the development of opportunistic infections (OIs) at higher-than-expected CD4(+) cell counts in human immunodeficiency virus (HIV) type 1-infected adults.
METHODS: Multivariate Poisson regression models were used to determine factors related to the development of groups of OIs above their respective traditional upper CD4(+) cell count thresholds: group 1 (>or=100 cells/ microL), OIs caused by cytomegalovirus, Mycobacterium avium complex, and Toxoplasma gondii; group 2 (>or=200 cells/ microL), Pneumocystis pneumonia and esophageal candidiasis; and group 3 (>or=300 cells/ microL), pulmonary and extrapulmonary tuberculosis.
RESULTS: In groups 1, 2, and 3, 71 of 9,219, 125 of 7,934, and 36 of 7,838 patients, respectively, developed >or=1 intragroup OI. The strongest predictor of an OI in groups 1 and 2 was current CD4(+) cell count (for group 1, incidence rate ratio [IRR] per 50% lower CD4(+) cell count, 5.37 [95% confidence interval {CI}, 3.71-7.77]; for group 2, 4.28 [95% CI, 2.98-6.14]). Injection drug use but not current CD4(+) cell count predicted risk in group 3. Use of antiretroviral treatment was associated with a lower incidence of OIs in all groups, likely by reducing HIV-1 RNA levels (IRR per 1-log(10) copies/mL higher HIV-1 RNA levels for group 1, 1.50 [95% CI, 1.15-1.95]; for group 2, 1.68 [95% CI, 1.40-2.02]; and for group 3, 1.89 [95% CI, 1.40-2.54]).
CONCLUSION: Although the absolute incidence is low, the current CD4(+) cell count and HIV-1 RNA level are strong predictors of most OIs in patients with high CD4(+) cell counts.

PMID 16897662  J Infect Dis. 2006 Sep 1;194(5):633-41. doi: 10.1086/50・・・
著者: S I Martin, J A Fishman, AST Infectious Diseases Community of Practice
雑誌名: Am J Transplant. 2013 Mar;13 Suppl 4:272-9. doi: 10.1111/ajt.12119.
Abstract/Text
PMID 23465020  Am J Transplant. 2013 Mar;13 Suppl 4:272-9. doi: 10.111・・・
著者: Hefziba Green, Mical Paul, Liat Vidal, Leonard Leibovici
雑誌名: Mayo Clin Proc. 2007 Sep;82(9):1052-9. doi: 10.4065/82.9.1052.
Abstract/Text OBJECTIVE: To assess the efficacy of prophylaxis for Pneumocystis pneumonia (PCP), caused by Pneumocystis jirovecii (formerly Pneumocystis carinii), for immunocompromised non-HIV-infected patients by conducting a systematic review and meta-analysis.
METHODS: We searched for randomized controlled trials that compared prophylaxis using antibiotics effective against P jirovecii, given orally or intravenously, vs placebo, no intervention, or antibiotics with no activity against P jirovecii. In addition, we included trials that compared different PCP prophylactic regimens or administration schedules. The search included the Cochrane Central Register of Controlled Trials, PubMed, Latin American and Caribbean Health Sciences Literature, and conference proceedings. No language, year, or publication restrictions were applied. Two reviewers (H.G. and M.P.) independently searched, selected trials, extracted data, and performed methodological quality assessment. Relative risks (RRs) with 95% confidence intervals (CIs) are reported. Meta-analysis was performed using the random-effects model.
RESULTS: Twelve randomized trials were identified, including 1245 patients (50% children) who had undergone autologous bone marrow or solid organ transplant or who had hematologic cancer. When trimethoprim-sulfamethoxazole was administered, a 91% reduction was observed in the occurrence of PCP (RR, 0.09; 95% CI, 0.02-0.32); the number needed to treat was 15 (95% CI, 13-20) patients, with no heterogeneity. Pneumocystis pneumonia-related mortality was significantly reduced (RR, 0.17; 95% CI, 0.03-0.94), whereas all-cause mortality did not differ significantly (RR, 0.79; 95% CI, 0.18-3.46). Adverse events that required discontinuation occurred in 3.1% of adults and none of the children, and all were reversible. No differences between once-daily and thrice-weekly administration schedules were found.
CONCLUSION: Balanced against severe adverse events, PCP prophylaxis is warranted when the risk for PCP is higher than 3.5% for adults. Adverse events are less frequent in children, for whom prophylaxis might be warranted at lower PCP incidence rates.

PMID 17803871  Mayo Clin Proc. 2007 Sep;82(9):1052-9. doi: 10.4065/82.・・・
著者: S Neumann, S W Krause, G Maschmeyer, X Schiel, M von Lilienfeld-Toal, Infectious Diseases Working Party (AGIHO), German Society of Hematology and Oncology (DGHO)
雑誌名: Ann Hematol. 2013 Apr;92(4):433-42. doi: 10.1007/s00277-013-1698-0. Epub 2013 Feb 15.
Abstract/Text Bacterial infections are the most common cause for treatment-related mortality in patients with neutropenia after chemotherapy. Here, we discuss the use of antibacterial prophylaxis against bacteria and Pneumocystis pneumonia (PCP) in neutropenic cancer patients and offer guidance towards the choice of drug. A literature search was performed to screen all articles published between September 2000 and January 2012 on antibiotic prophylaxis in neutropenic cancer patients. The authors assembled original reports and meta-analysis from the literature and drew conclusions, which were discussed and approved in a consensus conference of the Infectious Disease Working Party of the German Society of Hematology and Oncology (AGIHO). Antibacterial prophylaxis has led to a reduction of febrile events and infections. A significant reduction of overall mortality could only be shown in a meta-analysis. Fluoroquinolones are preferred for antibacterial and trimethoprim-sulfamethoxazole for PCP prophylaxis. Due to serious concerns about an increase of resistant pathogens, only patients at high risk of severe infections should be considered for antibiotic prophylaxis. Risk factors of individual patients and local resistance patterns must be taken into account. Risk factors, choice of drug for antibacterial and PCP prophylaxis and concerns regarding the use of prophylactic antibiotics are discussed in the review.

PMID 23412562  Ann Hematol. 2013 Apr;92(4):433-42. doi: 10.1007/s00277・・・
著者: Anat Stern, Hefziba Green, Mical Paul, Liat Vidal, Leonard Leibovici
雑誌名: Cochrane Database Syst Rev. 2014 Oct 1;(10):CD005590. doi: 10.1002/14651858.CD005590.pub3. Epub 2014 Oct 1.
Abstract/Text BACKGROUND: Pneumocystis pneumonia (PCP) is a disease affecting immunocompromised patients. PCP among these patients is associated with significant morbidity and mortality.
OBJECTIVES: To assess the effectiveness of PCP prophylaxis among non-HIV immunocompromised patients; and to define the type of immunocompromised patient for whom evidence suggests a benefit for PCP prophylaxis.
SEARCH METHODS: Electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 1), MEDLINE and EMBASE (to March 2014), LILACS (to March 2014), relevant conference proceedings; and references of identified trials.
SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing prophylaxis with an antibiotic effective against PCP versus placebo, no intervention, or antibiotic(s) with no activity against PCP; and trials comparing different antibiotics effective against PCP among immunocompromised non-HIV patients. We only included trials in which Pneumocystis infections were available as an outcome.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed risk of bias in each trial and extracted data from the included trials. We contacted authors of the included trials to obtain missing data. The primary outcome was documented PCP infections. Risk ratios (RR) with 95% confidence intervals (CI) were estimated and pooled using the random-effects model.
MAIN RESULTS: Thirteen trials performed between the years 1974 and 2008 were included, involving 1412 patients. Four trials included 520 children with acute lymphoblastic leukemia and the remaining trials included adults with acute leukemia, solid organ transplantation or autologous bone marrow transplantation. Compared to no treatment or treatment with fluoroquinolones (inactive against Pneumocystis), there was an 85% reduction in the occurrence of PCP in patients receiving prophylaxis with trimethoprim/sulfamethoxazole, RR of 0.15 (95% CI 0.04 to 0.62; 10 trials, 1000 patients). The evidence was graded as moderate due to possible risk of bias. PCP-related mortality was also significantly reduced, RR of 0.17 (95% CI 0.03 to 0.94; nine trials, 886 patients) (low quality of evidence due to possible risk of bias and imprecision), but in trials comparing PCP prophylaxis against placebo or no treatment there was no significant effect on all-cause mortality (low quality of evidence due to imprecision). Occurrence of leukopenia or neutropenia and their duration were not reported consistently. No significant differences in overall adverse events or events requiring discontinuation were seen comparing trimethoprim/sulfamethoxazole to no treatment or placebo (four trials, 470 patients, moderate quality evidence). No differences between once daily versus thrice weekly trimethoprim/sulfamethoxazole were seen (two trials, 207 patients).
AUTHORS' CONCLUSIONS: Given an event rate of 6.2% in the control groups of the included trials, prophylaxis for PCP using trimethoprim/sulfamethoxazole is highly effective among non-HIV immunocompromised patients, with a number needed to treat to prevent PCP of 19 patients (95% CI 17 to 42). Prophylaxis should be considered for patients with a similar baseline risk of PCP.

PMID 25269391  Cochrane Database Syst Rev. 2014 Oct 1;(10):CD005590. d・・・
著者: Masayoshi Harigai, Ryuji Koike, Nobuyuki Miyasaka, Pneumocystis Pneumonia under Anti-Tumor Necrosis Factor Therapy (PAT) Study Group
雑誌名: N Engl J Med. 2007 Nov 1;357(18):1874-6. doi: 10.1056/NEJMc070728.
Abstract/Text
PMID 17978303  N Engl J Med. 2007 Nov 1;357(18):1874-6. doi: 10.1056/N・・・
著者: Yukiko Komano, Masayoshi Harigai, Ryuji Koike, Haruhito Sugiyama, Jun Ogawa, Kazuyoshi Saito, Naoya Sekiguchi, Masayuki Inoo, Ikuko Onishi, Hiroyuki Ohashi, Fujio Amamoto, Masayuki Miyata, Hideo Ohtsubo, Kazuko Hiramatsu, Masahiro Iwamoto, Seiji Minota, Naoki Matsuoka, Goichi Kageyama, Kazuyoshi Imaizumi, Hitoshi Tokuda, Yasumi Okochi, Koichiro Kudo, Yoshiya Tanaka, Tsutomu Takeuchi, Nobuyuki Miyasaka
雑誌名: Arthritis Rheum. 2009 Mar 15;61(3):305-12. doi: 10.1002/art.24283.
Abstract/Text OBJECTIVE: To establish proper management of Pneumocystis jiroveci pneumonia (PCP) in rheumatoid arthritis (RA) patients treated with infliximab. PCP has been observed in 0.4% of patients with RA treated with infliximab in Japan.
METHODS: Data from patients with RA (n = 21) who were diagnosed with PCP during infliximab treatment and from 102 patients with RA who did not develop PCP during infliximab therapy were collected from 14 rheumatology referral centers in Japan. A retrospective review of these patients and a case-control study to compare patients with and without PCP were performed.
RESULTS: The median length of time from the first infliximab infusion to the development of PCP was 8.5 weeks. At the onset of PCP, the median dosages of prednisolone and methotrexate were 7.5 mg/day and 8 mg/week, respectively. Pneumocystis jiroveci was microscopically identified in only 2 patients, although the polymerase chain reaction test for the organism was positive in 20 patients. The patients with PCP had significantly lower serum albumin levels (P < 0.001) and lower serum IgG levels (P < 0.001) than the patients without PCP. Computed tomography of the chest in all patients with PCP revealed ground-glass opacity either with sharp demarcation by interlobular septa or without interlobular septal boundaries. Sixteen of the 21 patients with PCP developed acute respiratory failure, but all survived.
CONCLUSION: PCP is a serious complication that may occur early in the course of infliximab therapy in patients with RA. For the proper clinical management of this infectious disease, physicians need to be aware of the possibility of PCP developing during infliximab therapy.

PMID 19248121  Arthritis Rheum. 2009 Mar 15;61(3):305-12. doi: 10.1002・・・

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