Pneumocystis jirovecii Positivity and Empirical Treatment Approach in Bronchoalveolar Lavage Samples

Year 2020, Volume: 34 Issue: 2, 57 - 64, 31.08.2020

Buket Erturk Sengel , Özlem Alhan , Rabia Can Sarinoğlu , Elif Tükenmez Tigen , Zekaver Odabaşı

https://doi.org/10.5222/ankem.2020.065

Abstract

Pneumocystis jirovecii (PJ) is an opportunistic yeast-like fungus that causes pneumonia in immunosuppressed patients. The most risky group is HIV-positive patients, but in recent years it has been more common in HIV-negative immunosuppressed patients. In this study, PJ polymerase chain reaction (PCR) positivity rate, patient risk factors, clinical and laboratory findings were evaluated retrospectively in patients with suspected Pneumocystis jirovecii pneumonia (PJP) and other opportunistic respiratory pathogens at Marmara University Pendik Training and Research Hospital. Pneumocystis jirovecii PCR was studied from the bronchoalveolar lavage sample of a total of 133 patients, and 13 % (17/133) were positive. Forty one % of PCR positive patients were HIV-positive, and 59 % were HIV-negative immunosuppressed patients. Empirical trimethoprim/sulfamethoxazole was initiated in 72 of the patients whose specimens were sent, and treatment was continued in 38 including PCR positive patients. Clinical response was obtained in 9 of 21 PJ PCR negative patients, and no other infectious agents were shown. A total of 66 patients were given steroids because they were hypoxic. Twenty four % of patients who started empirical treatment had positive PJ PCR, and 36 % responded to the treatment. In HIV-negative immunosuppressed patients, PJP should be considered, and treatment can be continued if no other factor could be shown and there is high suspicion after taking the required specimen and starting empirical treatment.

Keywords

HIV, immunosupression, Pneumocystis jirovecii, polymerase chain reaction

Ethical Statement

Marmara University Faculty of Medicine Clinical Research Ethics Committee approval was obtained (09.2020.661).

Bronkoalveolar Lavaj Örneklerinde Pneumocystis jirovecii Pozitifliği ve Ampirik Tedavi Yaklaşımı

Abstract

Pneumocystis jirovecii (PJ) immünosupresif hastalarda pnömoniye sebep olan fırsatçı bir maya benzeri fungustur. En riskli grup HIV-pozitif hastalardır ancak son yıllarda HIV-negatif immünosuprese hastalarda daha sık görülmektedir. Bu çalışmada Marmara Üniversitesi Pendik Eğitim ve Araştırma Hastanesinde Pneumocystis jirovecii pnömonisi (PJP) ve diğer fırsatçı solunum yolu patojenleri şüphesi ile bronkoskopik örnekleri değerlendirilen hastalarda PJ polimeraz zincir reaksiyonu (PZR) pozitiflik oranı, hasta risk faktörleri, klinik ve laboratuvar bulgularını retrospektif olarak değerlendirilmiştir.
Toplam 133 hastanın bronkoalveolar lavaj örneğinden PJ-PZR çalışılmış ve % 13 (17/133) oranında pozitiflik bulunmuştur. PZR pozitif hastaların % 41’inin HIV-pozitif ve % 59’unun HIV-negatif immünosuprese hastalar olduğu görülmüştür. Örnek gönderilen hastaların 72’sine ampirik trimetroprim/sülfametoksazol başlanmış, PZR pozitif hastalarla beraber toplam 38 hastada tedaviye devam edilmiştir. PJ-PZR negatif 21 hastanın dokuzunda klinik yanıt alınmıştır ve başka bir enfeksiyon etkeni gösterilememiştir.
Toplam 66 hastaya hipoksik olmaları nedeniyle steroid verilmiştir. Ampirik tedavi baş- lanan hastaların % 24’ünde PJ-PZR pozitifliği ve % 36’sının tedaviye yanıt verdiği görülmüştür. HIV-negatif immün suprese hastalarda PJP akla gelmeli ve gerekli örnek alındıktan ve ampirik tedaviye başlandıktan sonra başka bir etken gösterilemiyorsa ve yüksek klinik şüphe varsa tedaviye devam edilebilir.

Keywords

HIV, immünsupresyon, Pneumocystis jirovecii, polimeraz zincir reaksiyonu

Ethical Statement

Marmara Üniversitesi Tıp Fakültesi Klinik Araştırmalar Etik Kurulu’nun onayı alınmıştır (09.2020.661).

References

• Alshahrani MY, Alfaifi M, Ahmad I, et al. Pneumocystis Jirovecii detection and comparison of multiple diagnostic methods with quantitative real-time PCR in patients with respiratory symptoms. Saudi J Biol Sci. 2020;27(6):1423-7. https://doi.org/10.1016/j.sjbs.2020.04.032
• Bollee G, Sarfati C, Thiery G, et al. Clinical picture of Pneumocystis jiroveci pneumonia in cancer patients. Chest. 2007;132(4):1305-10. https://doi.org/10.1378/chest.07-0223
• Delclaux C, Zahar JR, Amraoui G, et al. Corticosteroids as adjunctive therapy for severe Pneumocystis carinii pneumonia in non-human immunodeficiency virusinfected patients: retrospective study of 31 patients. Clin Infect Dis. 1999;29(3):670-2. https://doi.org/10.1086/598651
• Ding L, Huang H, Wang H, et al. Adjunctive corticosteroids may be associated with better outcome for non-HIV Pneumocystis pneumonia with respiratory failure: a systemic review and meta-analysis of observational studies. Ann Intensive Care. 2020;10(1):34. https://doi.org/10.1186/s13613-020-00649-9
• Ewald H, Raatz H, Boscacci R, et al. Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV infection. Cochrane Database Syst Rev. 2015(4):CD006150. https://doi.org/10.1002/14651858.CD006150.pub2
• Ide H, Yamaji Y, Tobino K, et al. Pneumocystis jirovecii pneumonia in an immunocompetent Japanese man: a case report and literature review. Case Rep Pulmonol. 2019;2019:3981681. https://doi.org/10.1155/2019/3981681
• Jacobs JL, Libby DM, Winters RA, et al. A cluster of Pneumocystis carinii pneumonia in adults without predisposing illnesses. N Engl J Med. 1991;324(4):246-50. https://doi.org/10.1056/NEJM199101243240407
• Kato H, Samukawa S, Takahashi H, et al. Diagnosis and treatment of Pneumocystis jirovecii pneumonia in HIV-infected or non-HIV-infected patientsdifficulties in diagnosis and adverse effects of trimethoprim-sulfamethoxazole. J Infect Chemother. 2019;25(11):920-4. https://doi.org/10.1016/j.jiac.2019.06.007
• Lemiale V, Debrumetz A, Delannoy A, et al. Adjunctive steroid in HIV-negative patients with severe Pneumocystis pneumonia. Respir Res. 2013;14:87. https://doi.org/10.1186/1465-9921-14-87
• Limper AH, Offord KP, Smith TF, et al. Pneumocystis carinii pneumonia. Differences in lung parasite number and inflammation in patients with and without AIDS. Am Rev Respir Dis. 1989;140(5):1204-9. https://doi.org/10.1164/ajrccm/140.5.1204
• Limper AH, Knox KS, Sarosi GA, et al. An official American Thoracic Society statement: treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med. 2011;183(1):96- 128. https://doi.org/10.1164/rccm.2008-740ST
• Liu CJ, Lee TF, Ruan SY, et al. Clinical characteristics, treatment outcomes, and prognostic factors of Pneumocystis pneumonia in non-HIV-infected patients. Infect Drug Resist. 2019;12:1457-67. https://doi.org/10.2147/IDR.S199761
• 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 Chemother. 2016;71(9):2405-13. https://doi.org/10.1093/jac/dkw158
• Matsumura Y, Ito Y, Yamamoto M, et al. Pneumocystis polymerase chain reaction and blood (1-->3)-beta-Dglucan assays to predict survival with suspected Pneumocystis jirovecii pneumonia. J Infect Chemother. 2014;20(2):109-14. https://doi.org/10.1016/j.jiac.2013.09.004
• Mirani G, Williams PL, Chernoff M, et al. Changing trends in complications and mortality rates among US youth and young adults with HIV infection in the era of combination antiretroviral therapy. Clin Infect Dis. 2015;61(12):1850-61. https://doi.org/10.1093/cid/civ687
• Otahbachi M, Nugent K, Buscemi D. Granulomatous Pneumocystis jiroveci pneumonia in a patient with chronic lymphocytic leukemia: a literature review and hypothesis on pathogenesis. Am J Med Sci. 2007;333(2):131-5. https://doi.org/10.1097/00000441-200702000-00014
• Salzer HJF, Schafer G, Hoenigl M, et al. Clinical, diagnostic, and treatment disparities between HIVinfected and non-HIV-infectedi patients with Pneumocystis jirovecii pneumonia. Respiration. 2018;96(1):52-65. https://doi.org/10.1159/000487713
• Tasaka S, Tokuda H, Sakai F, et al. Comparison of clinical and radiological features of pneumocystis pneumonia between malignancy cases and acquired immunodeficiency syndrome cases: a multicenter study. Intern Med. 2010;49(4):273-81. https://doi.org/10.2169/internalmedicine.49.2871
• Theel ES, Jespersen DJ, Iqbal S, et al. Detection of (1,3)-beta-D-glucan in bronchoalveolar lavage and serum samples collected from immunocompromised hosts. Mycopathologia. 2013;175(1-2):33-41. https://doi.org/10.1007/s11046-012-9579-y
• Thomas CF Jr., Limper AH. Current insights into the biology and pathogenesis of Pneumocystis pneumonia. Nat Rev Microbiol. 2007;5(4):298-308. https://doi.org/10.1038/nrmicro1621
• White PL, Backx M, Barnes RA. Diagnosis and management of Pneumocystis jirovecii infection. Expert Rev Anti Infect Ther. 2017;15(5):435-47. https://doi.org/10.1080/14787210.2017.1305887
• Wieruszewski PM, Barreto JN, Frazee E, et al. Early corticosteroids for Pneumocystis pneumonia in adults without HIV are not associated with better outcome. Chest. 2018;154(3):636-44. https://doi.org/10.1016/j.chest.2018.04.026
• Wilson JW, Limper AH, Grys TE, et al. Pneumocystis jirovecii testing by real-time polymerase chain reaction and direct examination among immunocompetent and immunosuppressed patient groups and correlation to disease specificity. Diagn Microbiol Infect Dis. 2011;69(2):145-52. https://doi.org/10.1016/j.diagmicrobio.2010.10.021
• Yale SH, Limper AH. Pneumocystis carinii pneumonia in patients without acquired immunodeficiency syndrome: associated illness and prior corticosteroid therapy. Mayo Clin Proc. 1996;71(1):5-13. https://doi.org/10.4065/71.1.5
• Zompatori M, Rimondi MR. Diffuse ground-glass opacity of the lung. A guide to interpreting the highresolution computed tomographic (HRCT) picture. Radiol Med. 1994;88(5):576-81.