Pneumocystis jirovecii pneumonia diagnosed by next-genetation sequencing after lung transplantation: case report and literature review_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

SHEN Yi ¹ , PAN Yan ² , YIN Chengsheng ³ , LI Feng ³ , ZHOU Wenyong ⁴ , PAN Xufeng ⁴ , CHEN Yuqing ³ ,  ZHANG Hai ³

1. Department of Intensive Care Unit, Shanghai Chest Hospital, Shanghai Chest Hospital of Shanghai Jiao Tong University, Shanghai 200030, P. R. China;
2. Department of Pharmacy, Shanghai Chest Hospital, Shanghai Chest Hospital of Shanghai Jiao Tong University, Shanghai 200030, P. R. China;
3. Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Chest Hospital of Shanghai Jiao Tong University, Shanghai 200030, P. R. China;
4. Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Chest Hospital of Shanghai Jiao Tong University, Shanghai 200030, P. R. China;

Corresponding author：

ZHANG Hai, Email: zhanghai_241@163.com

Keywords：

Pneumocystis jirovecii; Pneumonia; Lung transplantation; Next-generation sequencing

DOI：

10.7507/1671-6205.202104007

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To explore the clinical value of next-generation sequencing (NGS) in the diagnosis of Pneumocystis jirovecii pneumonia (PCP).Methods Two patients with Pneumocystis jirovecii pneumonia after lung transplantation were detected by NGS in the sputum and bronchoalveolar lavage fluid. The clinical data, imaging features, laboratory examination and treatment of the two patients were reported. A systematic literature review was performed for similar published cases in PubMed database, using the keywords "lung transplantation/solid organ transplantation" and "Pneumocystis jirovecii".Results There were six references based on the keywords of "lung transplantation " and " Pneumocystis jirovecii ", of which three were case report. Sixty-six lung transplant patients were complicated with Pneumocystis jirovecii in total. The clinical manifestations of Pneumocystis jirovecii pneumonia were fever and dyspnea of different degrees. The diffuse "ground glass" infiltration could be shown on imaging. Computer tomography scan of chest was a sensitive method to detect PCP. Combined immunofluorescence microscope/PCR/serum 3-β-D-glucan could effectively improve the accuracy of microbiology detection. In addition, NGS could quickly and accurately identify pathogenic bacteria, give guidance for treatment and improve prognosis so as to benefit patients well. Trimethoprim/sulfamethoxazole (TMP/SMZ) was the preferred choice for the treatment of PCP patients.Conclusions Pneumocystis jirovecii pneumonia is more common in patients with immunodeficiency or immunosuppression. NGS can help rapid and accurate diagnosis, and the treatment should be early and sufficient.

Citation： SHEN Yi, PAN Yan, YIN Chengsheng, LI Feng, ZHOU Wenyong, PAN Xufeng, CHEN Yuqing, ZHANG Hai. Pneumocystis jirovecii pneumonia diagnosed by next-genetation sequencing after lung transplantation: case report and literature review. Chinese Journal of Respiratory and Critical Care Medicine, 2021, 20(7): 479-486. doi: 10.7507/1671-6205.202104007 Copy

1.	Brown GD, Denning DW, Gow NA, et al. Hidden killers: human fungal infections. Sci Transl Med, 2012, 4(165): 165rv13.
2.	Maini R, Henderson KL, Sheridan EA, et al. Increasing Pneumocystis pneumonia, England, UK, 2000-2010. Emerg Infect Dis, 2013, 19(3): 386-392.
3.	Wickramasekaran RN, Jewell MP, Sorvillo F, et al. The changing trends and profile of pneumocystosis mortality in the United States, 1999-2014. Mycoses, 2017, 60(9): 607-615.
4.	Delbove A, Alami H, Tissot A, et al. Pneumocystis pneumonia after lung transplantation: a retrospective multicenter study. Resp Med, 2020, 169: 106019.
5.	Wojarski J, Ochman M, Latos M, et al. Immunosuppressive treatment and its effect on the occurrence of Pneumocystis jiroveci, Mycoplasma pneumoniae, Chlamydophila pnemoniae, and Legionella pneumophila infections/colonizations among lung transplant recipients. Transplant Proc, 2018, 50(7): 2053-2058.
6.	Wang EH, Partovi N, Levy RD, et al. Pneumocystis pneumonia in solid organ transplant recipients: not yet an infection of the past. Transpl Infect Dis, 2012, 14(5): 519-525.
7.	Izadi M, Jonaidi Jafari N, Sadraei J, et al. The prevalence of Pneumocystis jiroveci in bronchoalveolar lavage specimens of lung transplant recipients examined by the nested PCR. Jundishapur J Microbiol, 2014, 7(12): e13518.
8.	Zeglen S, Wojarski J, Wozniak-Grygiel E, et al. Procalcitonin Serum Concentration During Pneumocystis Jiroveci Colonization or Pseudomonas Aeruginosa Infection/Colonization in Lung Transplant Recipients. Transplant Proc, 2009, 41(8): 3225-3227.
9.	Lehto JT, Koskinen PK, Anttila VT, et al. Bronchoscopy in the diagnosis and surveillance of respiratory infections in lung and heart-lung transplant recipients. Transpl Int, 2005, 18(5): 562-571.
10.	杨靖波, 刘懿禾, 于立新, 等. 实体器官移植术后重症肺孢子虫肺炎诊治. 实用器官移植电子杂志, 2020, 8(4): 278-281.
11.	Masur H, Brooks JT, Benson CA, et al. Prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Updated Guidelines from the Centers for Disease Control and Prevention, National Institutes of Health, and HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis, 2014, 58(9): 1308-1311.
12.	Smith DE, McLuckie A, Wyatt J, et al. Severe exercise hypoxaemia with normal or near normal X-rays: a feature of Pneumocystis carinii infection. Lancet, 1988, 2(8619): 1049-1051.
13.	Mu XD, Jia P, Gao L, et al. Relationship between radiological stages and prognoses of pneumocystis pneumonia in non-aids immunocompromised patients. Chin Med J (Engl), 2016, 129(17): 2020-2025.
14.	Vogel MN, Brodoefel B, Hierl T, et al. Differences and similarities of cytomegalovirus and pneumocystis pneumonia in HIV-negative immunocompromised patients thin section CT morphology in the early phase of the disease. Br J Radiol, 2007, 80(955): 516-523.
15.	Corpo OD, Laporte GB, Sheppard DC, et al. Diagnostic accuracy of serum (1-3)-β-D-glucan for Pneumocystis jirovecii pneumonia: a systematic review and meta-analysis. Clin Microbiol Infect, 2020, 26(9): 1137-1143.
16.	Li WJ, Guo YL, Liu TJ, et al. Diagnosis of pneumocystis pneumonia using serum (1-3)-β-D-Glucan: a bivariate meta-analysis and systematic review. J Thorac Dis, 2015, 7(12): 2214-2225.
17.	Onishi A, Sugiyama D, Kogata Y, et al. Diagnostic accuracy of serum 1, 3-β-D-glucan for pneumocystis jiroveci pneumonia, invasive candidiasis, and invasive aspergillosis: systematic review and meta-analysis. J Clin Microbol, 2012, 50(1): 7-15.
18.	Karageorgopoulos DE, Qu JM, Korbila IP, et al. Accuracy of β-D-glucan for the diagnosis of Pneumocystis jirovecii pneumonia: a meta-analysis. Clin Microbiol Infect, 2013, 19(1): 39-49.
19.	Damiani C, Gal SL, Costa CD, et al. Combined quantification of pulmonary Pneumocystis jirovecii DNA and serum (1-> 3)-β-D-glucan for differential diagnosis of pneumocystis pneumonia and Pneumocystis colonization. J Clin Microbiol, 2013, 51(10): 3380-3388.
20.	Rose SR, Vallabhajosyula S, Velez MG, et al. The utility of bronchoalveolar lavage beta-D-glucan testing for the diagnosis of invasive fungal infections. J Infect, 2014, 69(3): 278-283.
21.	Salerno D, Mushatt D, Myers L, et al. Serum and bal beta-D-glucan for the diagnosis of Pneumocystis pneumonia in HIV positive patients. Respir Med, 2014, 108(11): 1688-1695.
22.	Salzer HJF, Schäfer G, Hoenigl M, et al. Clinical, diagnostic, and treatment disparities between HIV-infected and non-HIV-infected immunocompromised patients with Pneumocystis jirovecii pneumonia. Respiration, 2018, 96(1): 52-65.
23.	Vogel M, Weissgerber P, Goeppert B, et al. Accuracy of serum LDH elevation for the diagnosis of Pneumocystis jiroveci pneumonia. Swiss Med Wkly, 2011, 141: w13184.
24.	Nyamande K, Lalloo UG. Serum procalcitonin distinguishes CAP due to bacteria, Mycobacterium tuberculosis and PJP. Int J Tuberc Lung Dis, 2006, 10(5): 510-515.
25.	Ma L, Cissé OH, Kovacs JA. A molecular window into the biology and epidemiology of Pneumocystis spp. Clin Microbiol Rev, 2018, 31(3): e00009-18.
26.	Desoubeaux G, Franck-Martel C, Caille A, et al. Use of calcofluor-blue brightener for the diagnosis of Pneumocystis jirovecii pneumonia in bronchial-alveolar lavage fluids: a single-center prospective study. Med Mycol, 2017, 55(3): 295-301.
27.	Roblot F, Moal GL, Kauffmann-Lacroix C, et al. Pneumocystis jirovecii pneumonia in HIV-negative patients: a prospective study with focus on immunosuppressive drugs and markers of immune impairment. Scand J Infect Dis, 2014, 46(3): 210-214.
28.	Cruciani M, Marcati P, Malena M, et al. Meta-analysis of diagnostic procedures for Pneumocystis carinii pneumonia in HIV-1-infected patients. Eur Respir J, 2002, 20(4): 982-989.
29.	Summah H, Zhu YG, Falagas ME, et al. Use of real-time polymerase chain reaction for the diagnosis of Pneumocystis pneumonia in immunocompromised patients: a meta-analysis. Chin Med J (Engl), 2013, 126(10): 1965-1973.
30.	Fan LC, Lu HW, Cheng KB, et al. Evaluation of PCR in bronchoalveolar lavage fluid for diagnosis of Pneumocystis jirovecii pneumonia: a bivariate meta-analysis and systematic review. PLoS One, 2013, 8(9): e73099.
31.	Lu Y, Ling G, Qiang C, et al. PCR diagnosis of Pneumocystis pneumonia: a bivariate meta-analysis. J Clin Microbiol, 2011, 49(12): 4361-4363.
32.	Sasso M, Chastang-Dumas E, Bastide S, et al. Performances of four real-time PCR assays for diagnosis of Pneumocystis jirovecii pneumonia. J Clin Microbiol, 2016, 54(3): 625-630.
33.	Gazaignes S, Bergeron A, Menotti J, et al. [Pneumocystis jirovecii and quantitative PCR: pneumonia or colonization?]. Rev Mal Respir, 2020, 37(4): 299-307.
34.	Barbier F, Mer M, Szychowiak P, et al. Management of HIV-infected patients in the intensive care unit. Intensive Care Med, 2020, 46(2): 329-342.
35.	Tu GW, Ju MJ, Xu M, et al. Combination of caspofungin and low‐dose trimethoprim/sulfamethoxazole for the treatment of severe Pneumocystis jirovecii pneumonia in renal transplant recipients. Nephrology (Carlton), 2013, 18(11): 736-742.
36.	Simner PJ, Miller S, Carroll KC. Understanding the promises and hurdles of metagenomic next-generation sequencing as a diagnostic tool for infectious diseases. Clin Infect Dis, 2018, 66(5): 778-788.
37.	Gu W, Miller S, Chiu CY. Clinical metagenomic next-generation sequencing for pathogen detection. Annu Rev Pathol, 2019, 14: 319-338.
38.	Chiu CY, Miller SA. Clinical metagenomics. Nat Rev Genet, 2019, 20(6): 341-355.
39.	Wang J, Han Y, Feng J. Metagenomic next-generation sequencing for mixed pulmonary infection diagnosis. BMC Pulm Med, 2019, 19(1): 252.
40.	Irinyi L, Hu Y, Hoang MTV, et al. Long-read sequencing based clinical metagenomics for the detection and confirmation of Pneumocystis jirovecii directly from clinical specimens: a paradigm shift in mycological diagnostics. Med Mycol, 2020, 58(5): 650-660.
41.	Camargo JF, Ahmed AA, Lindner MS, et al. Next-generation sequencing of microbial cell-free DNA for rapid noninvasive diagnosis of infectious diseases in immunocompromised hosts. F1000Res, 2019, 8: 1194.
42.	Li Y, Sun B, Tang X, et al. Application of metagenomic next-generation sequencing for bronchoalveolar lavage diagnostics in critically ill patients. Eur J Clin Microbiol Infect Dis, 2020, 39(2): 369-374.
43.	Fonseca Brito L, Brune W, Stahl FR. Cytomegalovirus (CMV) pneumonitis: cell tropism, inflammation, and immunity. Int J Mol Sci, 2019, 20(16): 3865.
44.	Kotton CN. CMV: prevention, diagnosis and therapy. Am J Transplant, 2013, 13 Suppl 3: 24-40.
45.	Alvarez B, Arcos J, Fernández-Guerrero ML. Pulmonary infectious diseases in patients with primary immunodeficiency and those treated with biologic immunomodulating agents. Curr Opin Pulm Med, 2011, 17(3): 172-179.
46.	Baddley JW, Winthrop KL, Chen L, et al. Non-viral opportunistic infections in new users of tumour necrosis factor inhibitor therapy: results of the SAfety Assessment of Biologic ThERapy (SABER) study. Ann Rheum Dis, 2014, 73(11): 1942-1948.
47.	Park JW, Curtis JR, Moon J, et al. Prophylactic effect of trimethoprim-sulfamethoxazole for pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoids. Ann Rheum Dis, 2018, 77(5): 644-649.
48.	Green H, Paul M, Vidal L, et al. Prophylaxis of Pneumocystis pneumonia in immunocompromised non-HIV-infected patients: systematic review and meta-analysis of randomized controlled trials. Mayo Clin Proc, 2007, 82(9): 1052-1059.
49.	Maschmeyer G, Helweg-Larsen J, Pagano L, et al. ECIL guidelines for treatment of Pneumocystis jirovecii pneumonia in non-HIV-infected haematology patients. J Antimicrob Chemoth, 2016, 71(9): 2405-2413.
50.	倪蓓文, 黄洪辉, 王婷, 等. 卡泊芬净联合治疗急性红白血病并发卡氏肺孢子虫肺炎1例. 世界临床药物, 2013, 34(8): 480-482.
51.	Armstrong-James D, Stebbing J, John L, et al. A trial of caspofungin salvage treatment in PCP pneumonia. Thorax, 2011, 66(6): 537-538.
52.	Simonds RJ, Hughes WT, Feinberg J, et al. Preventing Pneumocystis carinii pneumonia in persons infected with human immunodeficiency virus. Clin Infect Dis, 1995, 21 Suppl 1: S44-S48.
53.	Dao BD, Barreto JN, Wolf RC, et al. Serum peak sulfamethoxazole concentrations demonstrate difficulty in achieving a target range: a retrospective cohort study. Curr Ther Res Clin Exp, 2014, 76: 104-109.
54.	Ice LL, Barreto JN, Dao BD, et al. Relationship of sulfamethoxazole therapeutic drug monitoring to clinical efficacy and toxicity: a retrospective cohort study. Ther Drug Monit, 2016, 38(3): 319-326.
55.	Chang HM, Tsai HC, Lee SS, et al. High daily doses of trimethoprim/sulfamethoxazole are an independent risk factor for adverse reactions in patients with pneumocystis pneumonia and AIDS. J Chin Med Assoc, 2016, 79(6): 314-319.

1. Brown GD, Denning DW, Gow NA, et al. Hidden killers: human fungal infections. Sci Transl Med, 2012, 4(165): 165rv13.
2. Maini R, Henderson KL, Sheridan EA, et al. Increasing Pneumocystis pneumonia, England, UK, 2000-2010. Emerg Infect Dis, 2013, 19(3): 386-392.
3. Wickramasekaran RN, Jewell MP, Sorvillo F, et al. The changing trends and profile of pneumocystosis mortality in the United States, 1999-2014. Mycoses, 2017, 60(9): 607-615.
4. Delbove A, Alami H, Tissot A, et al. Pneumocystis pneumonia after lung transplantation: a retrospective multicenter study. Resp Med, 2020, 169: 106019.
5. Wojarski J, Ochman M, Latos M, et al. Immunosuppressive treatment and its effect on the occurrence of Pneumocystis jiroveci, Mycoplasma pneumoniae, Chlamydophila pnemoniae, and Legionella pneumophila infections/colonizations among lung transplant recipients. Transplant Proc, 2018, 50(7): 2053-2058.
6. Wang EH, Partovi N, Levy RD, et al. Pneumocystis pneumonia in solid organ transplant recipients: not yet an infection of the past. Transpl Infect Dis, 2012, 14(5): 519-525.
7. Izadi M, Jonaidi Jafari N, Sadraei J, et al. The prevalence of Pneumocystis jiroveci in bronchoalveolar lavage specimens of lung transplant recipients examined by the nested PCR. Jundishapur J Microbiol, 2014, 7(12): e13518.
8. Zeglen S, Wojarski J, Wozniak-Grygiel E, et al. Procalcitonin Serum Concentration During Pneumocystis Jiroveci Colonization or Pseudomonas Aeruginosa Infection/Colonization in Lung Transplant Recipients. Transplant Proc, 2009, 41(8): 3225-3227.
9. Lehto JT, Koskinen PK, Anttila VT, et al. Bronchoscopy in the diagnosis and surveillance of respiratory infections in lung and heart-lung transplant recipients. Transpl Int, 2005, 18(5): 562-571.
10. 杨靖波, 刘懿禾, 于立新, 等. 实体器官移植术后重症肺孢子虫肺炎诊治. 实用器官移植电子杂志, 2020, 8(4): 278-281.
11. Masur H, Brooks JT, Benson CA, et al. Prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Updated Guidelines from the Centers for Disease Control and Prevention, National Institutes of Health, and HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis, 2014, 58(9): 1308-1311.
12. Smith DE, McLuckie A, Wyatt J, et al. Severe exercise hypoxaemia with normal or near normal X-rays: a feature of Pneumocystis carinii infection. Lancet, 1988, 2(8619): 1049-1051.
13. Mu XD, Jia P, Gao L, et al. Relationship between radiological stages and prognoses of pneumocystis pneumonia in non-aids immunocompromised patients. Chin Med J (Engl), 2016, 129(17): 2020-2025.
14. Vogel MN, Brodoefel B, Hierl T, et al. Differences and similarities of cytomegalovirus and pneumocystis pneumonia in HIV-negative immunocompromised patients thin section CT morphology in the early phase of the disease. Br J Radiol, 2007, 80(955): 516-523.
15. Corpo OD, Laporte GB, Sheppard DC, et al. Diagnostic accuracy of serum (1-3)-β-D-glucan for Pneumocystis jirovecii pneumonia: a systematic review and meta-analysis. Clin Microbiol Infect, 2020, 26(9): 1137-1143.
16. Li WJ, Guo YL, Liu TJ, et al. Diagnosis of pneumocystis pneumonia using serum (1-3)-β-D-Glucan: a bivariate meta-analysis and systematic review. J Thorac Dis, 2015, 7(12): 2214-2225.
17. Onishi A, Sugiyama D, Kogata Y, et al. Diagnostic accuracy of serum 1, 3-β-D-glucan for pneumocystis jiroveci pneumonia, invasive candidiasis, and invasive aspergillosis: systematic review and meta-analysis. J Clin Microbol, 2012, 50(1): 7-15.
18. Karageorgopoulos DE, Qu JM, Korbila IP, et al. Accuracy of β-D-glucan for the diagnosis of Pneumocystis jirovecii pneumonia: a meta-analysis. Clin Microbiol Infect, 2013, 19(1): 39-49.
19. Damiani C, Gal SL, Costa CD, et al. Combined quantification of pulmonary Pneumocystis jirovecii DNA and serum (1-> 3)-β-D-glucan for differential diagnosis of pneumocystis pneumonia and Pneumocystis colonization. J Clin Microbiol, 2013, 51(10): 3380-3388.
20. Rose SR, Vallabhajosyula S, Velez MG, et al. The utility of bronchoalveolar lavage beta-D-glucan testing for the diagnosis of invasive fungal infections. J Infect, 2014, 69(3): 278-283.
21. Salerno D, Mushatt D, Myers L, et al. Serum and bal beta-D-glucan for the diagnosis of Pneumocystis pneumonia in HIV positive patients. Respir Med, 2014, 108(11): 1688-1695.
22. Salzer HJF, Schäfer G, Hoenigl M, et al. Clinical, diagnostic, and treatment disparities between HIV-infected and non-HIV-infected immunocompromised patients with Pneumocystis jirovecii pneumonia. Respiration, 2018, 96(1): 52-65.
23. Vogel M, Weissgerber P, Goeppert B, et al. Accuracy of serum LDH elevation for the diagnosis of Pneumocystis jiroveci pneumonia. Swiss Med Wkly, 2011, 141: w13184.
24. Nyamande K, Lalloo UG. Serum procalcitonin distinguishes CAP due to bacteria, Mycobacterium tuberculosis and PJP. Int J Tuberc Lung Dis, 2006, 10(5): 510-515.
25. Ma L, Cissé OH, Kovacs JA. A molecular window into the biology and epidemiology of Pneumocystis spp. Clin Microbiol Rev, 2018, 31(3): e00009-18.
26. Desoubeaux G, Franck-Martel C, Caille A, et al. Use of calcofluor-blue brightener for the diagnosis of Pneumocystis jirovecii pneumonia in bronchial-alveolar lavage fluids: a single-center prospective study. Med Mycol, 2017, 55(3): 295-301.
27. Roblot F, Moal GL, Kauffmann-Lacroix C, et al. Pneumocystis jirovecii pneumonia in HIV-negative patients: a prospective study with focus on immunosuppressive drugs and markers of immune impairment. Scand J Infect Dis, 2014, 46(3): 210-214.
28. Cruciani M, Marcati P, Malena M, et al. Meta-analysis of diagnostic procedures for Pneumocystis carinii pneumonia in HIV-1-infected patients. Eur Respir J, 2002, 20(4): 982-989.
29. Summah H, Zhu YG, Falagas ME, et al. Use of real-time polymerase chain reaction for the diagnosis of Pneumocystis pneumonia in immunocompromised patients: a meta-analysis. Chin Med J (Engl), 2013, 126(10): 1965-1973.
30. Fan LC, Lu HW, Cheng KB, et al. Evaluation of PCR in bronchoalveolar lavage fluid for diagnosis of Pneumocystis jirovecii pneumonia: a bivariate meta-analysis and systematic review. PLoS One, 2013, 8(9): e73099.
31. Lu Y, Ling G, Qiang C, et al. PCR diagnosis of Pneumocystis pneumonia: a bivariate meta-analysis. J Clin Microbiol, 2011, 49(12): 4361-4363.
32. Sasso M, Chastang-Dumas E, Bastide S, et al. Performances of four real-time PCR assays for diagnosis of Pneumocystis jirovecii pneumonia. J Clin Microbiol, 2016, 54(3): 625-630.
33. Gazaignes S, Bergeron A, Menotti J, et al. [Pneumocystis jirovecii and quantitative PCR: pneumonia or colonization?]. Rev Mal Respir, 2020, 37(4): 299-307.
34. Barbier F, Mer M, Szychowiak P, et al. Management of HIV-infected patients in the intensive care unit. Intensive Care Med, 2020, 46(2): 329-342.
35. Tu GW, Ju MJ, Xu M, et al. Combination of caspofungin and low‐dose trimethoprim/sulfamethoxazole for the treatment of severe Pneumocystis jirovecii pneumonia in renal transplant recipients. Nephrology (Carlton), 2013, 18(11): 736-742.
36. Simner PJ, Miller S, Carroll KC. Understanding the promises and hurdles of metagenomic next-generation sequencing as a diagnostic tool for infectious diseases. Clin Infect Dis, 2018, 66(5): 778-788.
37. Gu W, Miller S, Chiu CY. Clinical metagenomic next-generation sequencing for pathogen detection. Annu Rev Pathol, 2019, 14: 319-338.
38. Chiu CY, Miller SA. Clinical metagenomics. Nat Rev Genet, 2019, 20(6): 341-355.
39. Wang J, Han Y, Feng J. Metagenomic next-generation sequencing for mixed pulmonary infection diagnosis. BMC Pulm Med, 2019, 19(1): 252.
40. Irinyi L, Hu Y, Hoang MTV, et al. Long-read sequencing based clinical metagenomics for the detection and confirmation of Pneumocystis jirovecii directly from clinical specimens: a paradigm shift in mycological diagnostics. Med Mycol, 2020, 58(5): 650-660.
41. Camargo JF, Ahmed AA, Lindner MS, et al. Next-generation sequencing of microbial cell-free DNA for rapid noninvasive diagnosis of infectious diseases in immunocompromised hosts. F1000Res, 2019, 8: 1194.
42. Li Y, Sun B, Tang X, et al. Application of metagenomic next-generation sequencing for bronchoalveolar lavage diagnostics in critically ill patients. Eur J Clin Microbiol Infect Dis, 2020, 39(2): 369-374.
43. Fonseca Brito L, Brune W, Stahl FR. Cytomegalovirus (CMV) pneumonitis: cell tropism, inflammation, and immunity. Int J Mol Sci, 2019, 20(16): 3865.
44. Kotton CN. CMV: prevention, diagnosis and therapy. Am J Transplant, 2013, 13 Suppl 3: 24-40.
45. Alvarez B, Arcos J, Fernández-Guerrero ML. Pulmonary infectious diseases in patients with primary immunodeficiency and those treated with biologic immunomodulating agents. Curr Opin Pulm Med, 2011, 17(3): 172-179.
46. Baddley JW, Winthrop KL, Chen L, et al. Non-viral opportunistic infections in new users of tumour necrosis factor inhibitor therapy: results of the SAfety Assessment of Biologic ThERapy (SABER) study. Ann Rheum Dis, 2014, 73(11): 1942-1948.
47. Park JW, Curtis JR, Moon J, et al. Prophylactic effect of trimethoprim-sulfamethoxazole for pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoids. Ann Rheum Dis, 2018, 77(5): 644-649.
48. Green H, Paul M, Vidal L, et al. Prophylaxis of Pneumocystis pneumonia in immunocompromised non-HIV-infected patients: systematic review and meta-analysis of randomized controlled trials. Mayo Clin Proc, 2007, 82(9): 1052-1059.
49. Maschmeyer G, Helweg-Larsen J, Pagano L, et al. ECIL guidelines for treatment of Pneumocystis jirovecii pneumonia in non-HIV-infected haematology patients. J Antimicrob Chemoth, 2016, 71(9): 2405-2413.
50. 倪蓓文, 黄洪辉, 王婷, 等. 卡泊芬净联合治疗急性红白血病并发卡氏肺孢子虫肺炎1例. 世界临床药物, 2013, 34(8): 480-482.
51. Armstrong-James D, Stebbing J, John L, et al. A trial of caspofungin salvage treatment in PCP pneumonia. Thorax, 2011, 66(6): 537-538.
52. Simonds RJ, Hughes WT, Feinberg J, et al. Preventing Pneumocystis carinii pneumonia in persons infected with human immunodeficiency virus. Clin Infect Dis, 1995, 21 Suppl 1: S44-S48.
53. Dao BD, Barreto JN, Wolf RC, et al. Serum peak sulfamethoxazole concentrations demonstrate difficulty in achieving a target range: a retrospective cohort study. Curr Ther Res Clin Exp, 2014, 76: 104-109.
54. Ice LL, Barreto JN, Dao BD, et al. Relationship of sulfamethoxazole therapeutic drug monitoring to clinical efficacy and toxicity: a retrospective cohort study. Ther Drug Monit, 2016, 38(3): 319-326.
55. Chang HM, Tsai HC, Lee SS, et al. High daily doses of trimethoprim/sulfamethoxazole are an independent risk factor for adverse reactions in patients with pneumocystis pneumonia and AIDS. J Chin Med Assoc, 2016, 79(6): 314-319.

Chinese Journal of Respiratory and Critical Care Medicine

Pneumocystis jirovecii pneumonia diagnosed by next-genetation sequencing after lung transplantation: case report and literature review

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