Pneumocystis jiroveci Prophylaxis with Rituximab

Authors

  • Margarida Lampreia Gomes Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal https://orcid.org/0009-0000-1688-9463
  • Iolanda Nunes Godinho Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal; Nephrology Department, Centro Hospitalar Universitário Lisboa Norte EPE, Lisbon, Portugal https://orcid.org/0000-0003-3254-9404
  • Joana Luísa Pereira Estrela Gameiro Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal; Nephrology Department, Centro Hospitalar Universitário Lisboa Norte EPE, Lisbon, Portugal https://orcid.org/0000-0001-6143-461X
  • José António Machado Lopes Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal; Nephrology Department, Centro Hospitalar Universitário Lisboa Norte EPE, Lisbon, Portugal https://orcid.org/0000-0001-5563-5132

DOI:

https://doi.org/10.71749/pkj.78

Keywords:

Pneumonia, Pneumocystis/drug therapy, Rituximab/therapeutic use, Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use

Abstract

Introduction: Pneumocystis jiroveci pneumonia (PJP) prophylaxis is highly effective in HIV patients. The objective of this study was to examine the efficacy and adverse effects of PJP prophylaxis among rituximab treated non–HIV patients.

Methods: We performed a systematic review based on the Preferred Reporting Items for Systematic Review and Meta‑Analyses (PRISMA) model.

Results: Eight retrospective studies were included with a combined cohort of 6048 patients. The most common prophylaxis drug used was trimethoprim/sulfamethoxazole (TMP‑SMX). There were 17 PJP infections in the prophylaxis arm against 147 in the control arm (incidence 0.3% vs 2.4%; OR, 0.35; 95% CI, 0.19‑0.64). The number needed to treat (NNT) to prevent 1 PJP episode was 36 patients (CER, 3.6%). The mortality rate due to PJP was 25%. All ADRs (adverse drug reactions) resolved with TMP‑SMX discontinuation.

Conclusion: Prophylaxis with TMP‑SMX seems justifiable in combined therapies with rituximab. But in monotherapy, the results are not robust. The decision should be patient‑based. The optimal duration of prophylaxis is also unclear.

Downloads

Download data is not yet available.

References

Maertens J, Cesaro S, Maschmeyer G, Einsele H, Donnelly JP, Alanio A, et al. ECIL guidelines for preventing Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients. J Antimicrob Chemother. 2016;71:2397-404. doi: 10.1093/jac/dkw157.

Cartin-Ceba R, Golbin JM, Keogh KA, Peikert T, Sanchez-Menendez M, Ytterberg R, et al. Rituximab for remission induction and maintenance in refractory granulomatosis with polyangiitis (Wegener's): ten-year experience at a single center. Arthritis Rheum. 2012;64:3770-8. doi: 10.1002/art.34584.

Grimwade K, Swinger GH. Cotrimoxazole prophylaxis for opportunistic infections in adults with HIV. Cochrane Database Syst Rev. 2003;2003:CD003108. doi: 10.1002/14651858.CD003108.

Benson CA, Kaplan JE, Masur H, Pau A, Holmes K. (2004). Treating opportunistic infections among HIV-exposed and infected children. CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2004;53:1-92. Erratum in: MMWR Morb Mortal Wkly Rep. 2006;55:824.

Bozzette SA, Finkelstein DM, Spector SA, Frame P, Powderly WG, He W, et al. A randomized trial of three antineuromycosis agents in patients with advanced human immunodeficiency virus infection. N Engl J Med. 1995;332:693-9.

Bucher HC, Griffith L, Guyatt GH, Opravil M. Meta-analysis of prophylactic treatments against Pneumocystis carinii pneumonia and toxoplasma encephalitis in HIV-infected patients. J Acquir Immune Defic Syndr. 1997;15:104-14.

BC Renal. Pneumocystis jirovecii Pneumonia Prophylaxis Guidelines in Patients with Glomerulonephritis. [accessed Jan 2025] Available at: https://www.bcrenal.ca/resource-gallery/Documents/GN-Pneumonia%20_Prophylaxis_Guidelines_GN_Pts.pdf

Chung JB, Armstrong K, Schwartz JS, Albert D. Cost-effectiveness of prophylaxis against Pneumocystis carinii pneumonia in patients with Wegner's granulomatosis undergoing immunosuppressive therapy. Arthritis Rheum. 2000;43:1841-8. doi: 10.1002/1529-0131(200008)43:8<1841-ADAN-R21>3.0.CO;2-Q.

Warnock AC, Rimland D. Comparison of trimethoprim-sulfamethoxazole, dapsone, and pentamidine in the prophylaxis of Pneumocystis carinii pneumonia. Pharmacotherapy. 1996;16:1030-8.

Martin-Garrido I, Carmona EM, Specks U, Limper AH. Pneumocystis pneumonia in patients treated with rituximab. Chest. 2013;144:258-65. doi: 10.1378/chest.12-0477.

Li MC, Lee NY, Lee CC, Lee HC, Chang CM, Ko WC. Pneumocystis jirovecii pneumonia in immunocompromised patients: delayed diagnosis and poor outcomes in non-HIV-infected individuals. J Microbiol Immunol Infect. 2014;47:42-7. doi: 10.1016/j.jmii.2012.08.024.

Yale SH, Limper AH. Pneumocystis carinii pneumonia in patients without acquired immunodeficiency syndrome: associated illness and prior corticosteroid therapy. Mayo Clin Proc. 1996;71:5-13.

Green H, Paul M, Vidal L, Leibovici L. Prophylaxis of Pneumocystis pneumonia in immunocompromised non-HIV-infected patients: systematic review and meta-analysis of randomized controlled trials. Mayo Clin Proc. 2007;82:1052-9. doi: 10.4065/82.9.1052.

Stern A, Green H, Paul M, Vidal L, Leibovici L. Prophylaxis for Pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients. Cochrane Database Syst Rev. 2014;2014:CD005590. doi: 10.1002/14651858.CD005590.pub3.

Park JW, Curtis JR, Moon J, Song YW, Kim S, Lee EB. Prophylactic effect of trimethoprim-sulfamethoxazole for pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoids. Ann Rheum Dis. 2018;77:644-9. doi: 10.1136/annrheumdis-2017-211796.

Park JW, Curtis R, Moon J, Song Y, Kim S, Lee E. Pneumocystis pneumonia in patients with rheumatic diseases receiving prolonged, nonhigh-dose steroids- of primary prophylaxis clinical implication of primary prophylaxis using trimethoprim-sulfamethoxazole. Arthritis Res Ther. 2019;21:207. doi: 10.1186/s13075-019-1996-6.

Wei KC, Sy C, Wu SY, Chuang TI, Huang WC, Lai PC. Pneumocystis jirovecii pneumonia in HIV-uninfected, rituximab treated non-Hodgkin lymphoma patients. Sci Rep. 2018;8:8321. doi: 10.1038/s41598-018-26743-4.

Alexandre K, Ingen-Housz-Oro S, Versini M, Sailler L, Benhamou Y. Pneumocystis jirovecii pneumonia in patients treated with rituximab for systemic diseases: Report of 11 cases and review of the literature. Eur J Intern Med. 2018;50:e23-4. doi: 10.1016/j.ejim.2017.11.014.

Brusamolino E, Rusconi C, Montalbetti L, Gargantini L, Uziel I, Pinotti G, et al. Dose-dense R-CHOP-14 supported by pegfilgrastim in patients with diffuse large B-cell lymphoma: a phase II study of feasibility and toxicity. Haematologica. 2006;91:496-502.

Kolstad A, Holte H, Fosså A, Lauritzsen GF, Gaustad P, Torfoss D. Pneumocystis jirovecii pneumonia in B-cell lymphoma patients treated with the rituximab-CHOP-14 regimen. Haematologica. 2007;92:139-40. doi: 10.3324/haematol.10564.

Hardak E, Oren I, Dann EJ, Yigal M, Faibish T, Rowe JM, et al. The increased risk for pneumocystis pneumonia in patients receiving rituximab-CHOP-14 can be prevented by the administration of trimethoprim/sulfamethoxazole: a single-center experience. Acta Haematol. 2012;127:110-4. doi: 10.1159/000334113.

Ennishi D, Terui Y, Yokoyama M, Mishima Y, Takahashi S, Takeuchi K, et al. Increased incidence of interstitial pneumonia by CHOP combined with rituximab. Int J Hematol. 2008;87:393-7. doi: 10.1007/s12185-008-0066-7.

Jiang X, Mei X, Feng D, Wang X. Prophylaxis and treatment of pneumocystis jirovecii pneumonia in lymphoma patients subjected to rituximab-contained therapy: a systemic review and meta-analysis. PLoS One. 2015;10:e0122171. doi: 10.1371/journal.pone.0122171.

Kim T, Choi SH, Kim SH, Jeong JY, Woo JH, Kim YS, et al. Point prevalence of Pneumocystis pneumonia in patients with non-Hodgkin lymphoma according to the number of cycles of R-CHOP chemotherapy. Ann Hematol. 2013;92:231-8. doi: 10.1007/s00277-012-1592-1.

Katsuya H, Suzumiya J, Sasaki H, Ishitsuka K, Shibata T, Takamatsu Y, et al. Addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy has a high risk of developing interstitial pneumonia in patients with non-Hodgkin lymphoma. Leuk Lymphoma. 2009;50:1818-23. doi: 10.3109/10428190903258780.

Hashimoto K, Kobayashi Y, Asakura Y, Mori M, Azuma T, Maruyama D, et al. Pneumocystis jirovecii pneumonia in relation to CD4+ lymphocyte count in patients with B-cell non-Hodgkin lymphoma treated with chemotherapy. Leuk Lymphoma. 2010;51:1816-21.

Elsegeiny W, Eddens T, Chen K, Kolls JK. Anti-CD20 antibody therapy and susceptibility to Pneumocystis pneumonia. Infect Immun. 2015;83:2043-52. doi: 10.1128/IAI.03099-14.

Lund FE, Schuer K, Hollifield M, Randall TD, Garvy BA. Clearance of Pneumocystis carinii in mice is dependent on B cells but not on P carinii-specific antibody. J Immunol. 2003;171:1423-30. doi: 10.4049/jimmunol.171.3.1423.

Roberts DM, Jones RB, Smith RM, Alberici F, Kumaratne DS, Burns S, et al. Rituximab-associated hypogammaglobulinemia: incidence, predictors and outcomes in patients with multi-system autoimmune disease. J Autoimmun. 2015;57:60-5. doi: 10.1016/j.jaut.2014.11.009.

Park JW, Curtis JR, Jun KI, Kim TM, Heo DS, Ha J, et al. Primary prophylaxis for Pneumocystis jirovecii pneumonia in patients receiving rituximab. Chest. 2022;161:1201-10. doi: 10.1016/j.chest.2021.11.007.

Park JW, Curtis JR, Choi SR, Kim MJ, Ha YJ, Kang EH, et al. Risk-benefit analysis of primary prophylaxis against Pneumocystis jirovecii pneumonia in patients with rheumatic diseases receiving rituximab. Arthritis Rheumatol. 2023;75:2036-44. doi: 10.1002/art.42541.

Hsu HC, Huang PW, Cho YT, Chu CY. Cotrimoxazole as a preventative intervention for pneumocystis pneumonia in pemphigus patients treated with rituximab: a retrospective study. Dermatol Ther. 2023;13:1561-76. doi: 10.1007/s13555-023-00953-9.

Lee JY, Kang M, Suh KJ, Kim JW, Kim SH, Kim JW, et al. Pneumocystis jirovecii pneumonia in diffuse large B-cell lymphoma treated with R-CHOP. Mycoses. 2021;64:60-5. doi: 10.1111/myc.13184.

Raso S, Napolitano M, Arrigo G, Reale F, Lucchesi A, Silimbani P, et al. Antimicrobial prophylaxis in patients with immune thrombocytopenia treated with rituximab: a retrospective multicenter analysis. Ann Hematol. 2021;100:653-9. doi: 10.1007/s00277-021-04438-7.

Catroux M, Lauda-Mailen M, Pathe M, De Boisgrollier de Ruolz AC, Cazenave-Roblot F, Roblot P, et al. Evénements infectieux survenus au cours des maladies auto-immunes traitées par rituximab: à partir d'une étude rétrospective de 93 cas Rev Med Interne. 2017;38:160-6. doi: 10.1016/j.remmed.2016.09.010.

Faraji H, Daneshpazhooh M, Ehsani AH, Mahmoudi H, Tavakolpour S, Aryanian Z, et al. Evaluating the risk-to-benefit ratio of using cotrimoxazole as a pneumocystis pneumonia preventative intervention among pemphigus patients treated with rituximab: A retrospective study with 494 patients. Dermatol Ther. 2022;35:e15257. doi: 10.1111/dth.15257.

Downloads

Published

22-01-2026

Issue

Section

Systematic Review

How to Cite

Pneumocystis jiroveci Prophylaxis with Rituximab. (2026). Portuguese Kidney Journal. https://doi.org/10.71749/pkj.78

Most read articles by the same author(s)

<< < 3 4 5 6 7 8 

Similar Articles

1-10 of 34

You may also start an advanced similarity search for this article.