2,551
Views
23
CrossRef citations to date
0
Altmetric
Review

Pneumocystis jirovecii: a review with a focus on prevention and treatment

, , , & ORCID Icon
Pages 1579-1592 | Received 12 Feb 2021, Accepted 08 Apr 2021, Published online: 19 Apr 2021

References

  • Hawksworth DL. Responsibility in naming pathogens: the case of Pneumocystis jirovecii, the causal agent of Pneumocystis pneumonia. Lancet Infect Dis. 2007;7(1):3–5. discussion 5.
  • Dhami ACZ, Cermakova Z. Pneumocystis jiroveci: its history and emergence as a human pathogen. Reviews in Medical Microbiology. 2015;26(3):91–97.
  • Venek J, Jirovec O, Lukes J. Interstitial plasma cell pneumonia in infants. Ann Paediatr. 1953;180(1):1–21.
  • Hughes WT, Feldman S, Aur RJ, et al. Intensity of immunosuppressive therapy and the incidence of Pneumocystis carinii pneumonitis. Cancer. 1975;36(6):2004–2009.
  • Hughes WT, Kuhn S, Chaudhary S, et al. Successful chemoprophylaxis for Pneumocystis carinii pneumonitis. N Engl J Med. 1977;297(26):1419–1426.
  • Masur H, Michelis MA, Greene JB, et al. An outbreak of community-acquired Pneumocystis carinii pneumonia: initial manifestation of cellular immune dysfunction. N Engl J Med. 1981;305(24):1431–1438.
  • Edman JC, Kovacs JA, Masur H, et al. Ribosomal RNA sequence shows Pneumocystis carinii to be a member of the fungi. Nature. 1988;334(6182):519–522.
  • Skalski JH, Kottom TJ, Limper AH. Pathobiology of Pneumocystis pneumonia: life cycle, cell wall and cell signal transduction. FEMS Yeast Res. 2015;15(6):6.
  • Sokulska M, Kicia M, Wesolowska M, et al. Pneumocystis jirovecii–from a commensal to pathogen: clinical and diagnostic review. Parasitol Res. 2015;114(10):3577–3585.
  • Pifer LL, Hughes WT, Stagno S, et al. Pneumocystis carinii infection: evidence for high prevalence in normal and immunosuppressed children. Pediatrics. 1978;61(1):35–41.
  • Vargas SL, Hughes WT, Santolaya ME, et al. Search for primary infection by Pneumocystis carinii in a cohort of normal, healthy infants. Clin Infect Dis. 2001;32(6):855–861.
  • Morris A, Wei K, Afshar K, et al. Epidemiology and clinical significance of pneumocystis colonization. J Infect Dis. 2008;197(1):10–17.
  • O’Brien KL, Baggett HC, Brooks WA, Pneumonia Etiology Research for Child Health Study G. Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study. Lancet. 2019;394(10200):757–779.
  • GeorgeP M, Gingo MR, Morris A. Pneumocystis (carinii) jirovecii. Antimicrobe. Published 2015. [cited 2020 Dec]. Available from: http://www.antimicrobe.org/f11.asp
  • Kofteridis DP, Valachis A, Velegraki M, et al. Predisposing factors, clinical characteristics and outcome of Pneumonocystis jirovecii pneumonia in HIV-negative patients. J Infect Chemother. 2014;20(7):412–416.
  • Hosseini-Moghaddam SM, Shokoohi M, Singh G, et al. A multicenter case-control study of the effect of acute rejection and cytomegalovirus infection on Pneumocystis pneumonia in solid organ transplant recipients. Clin Infect Dis. 2019;68(8):1320–1326.
  • Mecoli CA, Saylor D, Gelber AC, et al. Pneumocystis jiroveci pneumonia in rheumatic disease: a 20-year single-centre experience. Clin Exp Rheumatol. 2017;35(4):671–673.
  • Wei KC, Sy C, Wu SY, et al. Pneumocystis jirovecii pneumonia in HIV-uninfected, rituximab treated non-Hodgkin lymphoma patients. Sci Rep. 2018;8(1):8321.
  • Lopez-Sanchez C, Falco V, Burgos J, et al. Epidemiology and long-term survival in HIV-infected patients with Pneumocystis jirovecii pneumonia in the HAART era: experience in a university hospital and review of the literature. Medicine (Baltimore). 2015;94(12):e681.
  • Rodriguez M, Fishman JA. Prevention of infection due to Pneumocystis spp. in human immunodeficiency virus-negative immunocompromised patients. Clin Microbiol Rev. 2004;17(4):770–782.
  • Williams KM, Ahn KW, Chen M, et al. The incidence, mortality and timing of Pneumocystis jiroveci pneumonia after hematopoietic cell transplantation: a CIBMTR analysis. Bone Marrow Transplant. 2016;51(4):573–580.
  • Wang EHZ, 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.
  • Neofytos D, Hirzel C, Boely E, et al. Pneumocystis jirovecii pneumonia in solid organ transplant recipients: a descriptive analysis for the Swiss Transplant Cohort. Transpl Infect Dis. 2018;20(6):e12984.
  • Liu Y, Su L, Jiang SJ, et al. Risk factors for mortality from pneumocystis carinii pneumonia (PCP) in non-HIV patients: a meta-analysis. Oncotarget. 2017;8(35):59729–59739.
  • Walzer PD, Evans HE, Copas AJ, et al. Early predictors of mortality from Pneumocystis jirovecii pneumonia in HIV-infected patients: 1985-2006. Clin Infect Dis. 2008;46(4):625–633.
  • 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):1204–1209.
  • Kovacs JA, Hiemenz JW, Macher AM, et al. Pneumocystis carinii pneumonia: a comparison between patients with the acquired immunodeficiency syndrome and patients with other immunodeficiencies. Ann Intern Med. 1984;100(5):663–671.
  • 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;12:1457–1467.
  • Schildgen V, Mai S, Khalfaoui S, et al., Pneumocystis jirovecii can be productively cultured in differentiated CuFi-8 airway cells. mBio. 5(3): e01186–01114. 2014.
  • 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.
  • Fishman JA, Gans H; Practice ASTIDCo. Pneumocystis jiroveci in solid organ transplantation: guidelines from the American society of transplantation infectious diseases community of practice. Clin Transplant. 2019;33(9):e13587.
  • Kaplan JE, Benson C, Holmes KK, et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009;58(RR–4):1–207. quiz CE201-204.
  • Alanio A, Hauser PM, Lagrou K, et al. ECIL guidelines for the diagnosis of Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients. J Antimicrob Chemother. 2016;71(9):2386–2396.
  • Marr KA, Datta K, Mehta S, et al. Urine antigen detection as an aid to diagnose invasive aspergillosis. Clin Infect Dis. 2018;67(11):1705–1711.
  • Tasaka S, Kobayashi S, Yagi K, et al. Serum (1 –> 3) beta-D-glucan assay for discrimination between Pneumocystis jirovecii pneumonia and colonization. J Infect Chemother. 2014;20(11):678–681.
  • Sax PE, Komarow L, Finkelman MA, et al. Blood (1->3)-beta-D-glucan as a diagnostic test for HIV-related Pneumocystis jirovecii pneumonia. Clin Infect Dis. 2011;53(2):197–202.
  • Kovacs Z, Simon-Sarkadi L, Szucs A, et al. Differential effects of cold, osmotic stress and abscisic acid on polyamine accumulation in wheat. Amino Acids. 2010;38(2):623–631.
  • Ng VL, Yajko DM, Hadley WK. Extrapulmonary pneumocystosis. Clin Microbiol Rev. 1997;10(3):401–418.
  • Nollstadt KH, Powles MA, Fujioka H, et al. Use of beta-1,3-glucan-specific antibody to study the cyst wall of Pneumocystis carinii and effects of pneumocandin B0 analog L-733,560. Antimicrob Agents Chemother. 1994;38(10):2258–2265.
  • Ricks DM, Chen K, Zheng M, et al. Dectin immunoadhesins and pneumocystis pneumonia. Infect Immun. 2013;81(9):3451–3462.
  • Kovacs JA, Powell F, Edman JC, et al. Multiple genes encode the major surface glycoprotein of Pneumocystis carinii. J Biol Chem. 1993;268(8):6034–6040.
  • Maertens J, Cesaro S, Maschmeyer G, et al. ECIL guidelines for preventing Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients. J Antimicrob Chemother. 2016;71(9):2397–2404.
  • Wolfe RM, Beekmann SE, Polgreen PM, et al. Practice patterns of Pneumocystis pneumonia prophylaxis in connective tissue diseases: a survey of infectious disease physicians. Open Forum Infect Dis. 2019;6(9):ofz315.
  • Phair J, Munoz A, Detels R, et al. The risk of Pneumocystis carinii pneumonia among men infected with human immunodeficiency virus type 1. Multicenter AIDS cohort study group. N Engl J Med. 1990;322(3):161–165.
  • Stansell JD, Osmond DH, Charlebois E, et al. Predictors of Pneumocystis carinii pneumonia in HIV-infected persons. Pulmonary complications of HIV infection study group. Am J Respir Crit Care Med. 1997;155(1):60–66.
  • Chaiwarith R, Praparattanapan J, Nuntachit N, et al. Discontinuation of primary and secondary prophylaxis for opportunistic infections in HIV-infected patients who had CD4+ cell count <200 cells/mm(3) but undetectable plasma HIV-1 RNA: an open-label randomized controlled trial. AIDS Patient Care STDS. 2013;27(2):71–76.
  • D’Egidio GE, Kravcik S, Cooper CL, et al. Pneumocystis jiroveci pneumonia prophylaxis is not required with a CD4+ T-cell count < 200 cells/microl when viral replication is suppressed. AIDS. 2007;21(13):1711–1715.
  • Cervera C, Yaskina M, Kabbani D. Targeted prophylaxis to prevent late-onset Pneumocystis jirovecii pneumonia in kidney transplantation. Are we there yet? Clin Infect Dis. 2020. https://doi.org/10.1093/cid/ciaa1619
  • Wolfe RM, Peacock JE Jr. Pneumocystis pneumonia and the rheumatologist: which patients are at risk and how can PCP be prevented? Curr Rheumatol Rep. 2017;19(6):35.
  • Ognibene FP, Shelhamer JH, Hoffman GS, et al. Pneumocystis carinii pneumonia: a major complication of immunosuppressive therapy in patients with Wegener’s granulomatosis. Am J Respir Crit Care Med. 1995;151(3 Pt 1):795–799.
  • 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.
  • Castro JG, Morrison-Bryant M. Management of Pneumocystis Jirovecii pneumonia in HIV infected patients: current options, challenges and future directions. HIV AIDS (Auckl). 2010;2:123–134.
  • Ioannidis JP, Cappelleri JC, Skolnik PR, et al. A meta-analysis of the relative efficacy and toxicity of Pneumocystis carinii prophylactic regimens. Arch Intern Med. 1996;156(2):177–188.
  • Schneider MM, Nielsen TL, Nelsing S, et al. Efficacy and toxicity of two doses of trimethoprim-sulfamethoxazole as primary prophylaxis against Pneumocystis carinii pneumonia in patients with human immunodeficiency virus. Dutch AIDS treatment group. J Infect Dis. 1995;171(6):1632–1636.
  • Velazquez H, Perazella MA, Wright FS, et al. Renal mechanism of trimethoprim-induced hyperkalemia. Ann Intern Med. 1993;119(4):296–301.
  • Smilack JD. Trimethoprim-sulfamethoxazole. Mayo Clin Proc. 1999;74(7):730–734.
  • Leoung GS, Stanford JF, Giordano MF, et al. Trimethoprim-sulfamethoxazole (TMP-SMZ) dose escalation versus direct rechallenge for Pneumocystis Carinii pneumonia prophylaxis in human immunodeficiency virus-infected patients with previous adverse reaction to TMP-SMZ. J Infect Dis. 2001;184(8):992–997.
  • Blum RN, Miller LA, Gaggini LC, et al. Comparative trial of dapsone versus trimethoprim/sulfamethoxazole for primary prophylaxis of Pneumocystis carinii pneumonia. 1992;5(4):341–347. J Acquir Immune Defic Syndr (1988).
  • Bozzette SA, Finkelstein DM, Spector SA, et al., A randomized trial of three antipneumocystis agents in patients with advanced human immunodeficiency virus infection. NIAID AIDS Clinical Trials Group. N Engl J Med. 332(11): 693–699. 1995.
  • Mallolas J, Zamora L, Gatell JM, et al., Primary prophylaxis for Pneumocystis carinii pneumonia: a randomized trial comparing cotrimoxazole, aerosolized pentamidine and dapsone plus pyrimethamine. AIDS. 7(1): 59–64. 1993.
  • Souza JP, Boeckh M, Gooley TA, et al. High rates of Pneumocystis carinii pneumonia in allogeneic blood and marrow transplant recipients receiving dapsone prophylaxis. Clin Infect Dis. 1999;29(6):1467–1471.
  • Sangiolo D, Storer B, Nash R, et al. Toxicity and efficacy of daily dapsone as Pneumocystis jiroveci prophylaxis after hematopoietic stem cell transplantation: a case-control study. Biol Blood Marrow Transplant. 2013;27(2):521–529.
  • Wozel G, Wozel G, Schmitt J. Hypersensitivity reactions to dapsone: a systematic review. Acta Derm Venereol. 2007;21(13):194–199.
  • Baggish AL, Hill DR. Antiparasitic agent atovaquone. Antimicrob Agents Chemother. 2002;46(5):1163–1173.
  • Argy N, Le Gal S, Coppee R, et al. Pneumocystis cytochrome b mutants associated with atovaquone prophylaxis failure as the cause of Pneumocystis infection outbreak among heart transplant recipients. Clin Infect Dis. 2018;67(6):913–919.
  • El-Sadr WM, Murphy RL, Yurik TM, et al. Atovaquone compared with dapsone for the prevention of Pneumocystis carinii pneumonia in patients with HIV infection who cannot tolerate trimethoprim, sulfonamides, or both. Community Program for Clinical Research on AIDS and the AIDS Clinical Trials Group. N Engl J Med. 1998;339(26):1889–1895.
  • Chan C, Montaner J, Lefebvre EA, et al. Atovaquone suspension compared with aerosolized pentamidine for prevention of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected subjects intolerant of trimethoprim or sulfonamides. J Infect Dis. 1999;180(2):369–376.
  • John E, Bennett RD, Blaser MJ. Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. 9th ed. Philadelphia, PA: Elsevier; 2020.
  • Coker RJ, Clark D, Claydon EL, et al. Disseminated pneumocystis carinii infection in AIDS. J Clin Pathol. 1991;44(10):820–823.
  • Fichera ME, Roos DS. A plastid organelle as a drug target in apicomplexan parasites. Nature. 1997;390(6658):407–409.
  • Vale N, Moreira R, Gomes P. Primaquine revisited six decades after its discovery. Eur J Med Chem. 2009;44(3):937–953.
  • Kay R, DuBois RE. Clindamycin/primaquine therapy and secondary prophylaxis against Pneumocystis carinii pneumonia in patients with AIDS. South Med J. 1990;83(4):403–404.
  • Barber BA, Pegram PS, High KP. Clindamycin/primaquine as prophylaxis for Pneumocystis carinii pneumonia. Clin Infect Dis. 1996;23(4):718–722.
  • Lyman WD, Tricoche M, Hatch WC, et al. Human fetal central nervous system organotypic cultures. Brain Res Dev Brain Res. 1991;60(2):155–160.
  • Falagas ME, Gorbach SL. Clindamycin and metronidazole. Med Clin North Am. 1995;79(4):845–867.
  • Owens RC Jr., Donskey CJ, Gaynes RP, et al. Antimicrobial-associated risk factors for clostridium difficile infection. Clin Infect Dis. 2008;46(Suppl 1):S19–31.
  • 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):2405–2413.
  • Hughes WT, Feldman S, Chaudhary SC, et al. Comparison of pentamidine isethionate and trimethoprim-sulfamethoxazole in the treatment of Pneumocystis carinii pneumonia. J Pediatr. 1978;92(2):285–291.
  • Wharton JM, Coleman DL, Wofsy CB, et al. Trimethoprim-sulfamethoxazole or pentamidine for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A prospective randomized trial. Ann Intern Med. 1986;105(1):37–44.
  • Klein NC, Duncanson FP, Lenox TH, et al., Trimethoprim-sulfamethoxazole versus pentamidine for Pneumocystis carinii pneumonia in AIDS patients: results of a large prospective randomized treatment trial. AIDS. 6(3): 301–305. 1992.
  • Sattler FR, Cowan R, Nielsen DM, et al. Trimethoprim-sulfamethoxazole compared with pentamidine for treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A prospective, noncrossover study. Ann Intern Med. 1988;109(4):280–287.
  • Thomas M, Rupali P, Woodhouse A, et al. Good outcome with trimethoprim 10 mg/kg/day-sulfamethoxazole 50 mg/kg/day for Pneumocystis jirovecii pneumonia in HIV infected patients. Scand J Infect Dis. 2009;41(11–12):862–868.
  • Nakashima K, Aoshima M, Nakashita T, et al. Low-dose trimethoprim-sulfamethoxazole treatment for pneumocystis pneumonia in non-human immunodeficiency virus-infected immunocompromised patients: a single-center retrospective observational cohort study. J Microbiol Immunol Infect. 2018;51(6):810–820.
  • Creemers-Schild D, Kroon FP, Kuijper EJ, et al. Treatment of Pneumocystis pneumonia with intermediate-dose and step-down to low-dose trimethoprim-sulfamethoxazole: lessons from an observational cohort study. Infection. 2016;44(3):291–299.
  • Safrin S, Finkelstein DM, Feinberg J, et al. Comparison of three regimens for treatment of mild to moderate Pneumocystis carinii pneumonia in patients with AIDS. A double-blind, randomized, trial of oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine. ACTG 108 study group. Ann Intern Med. 1996;124(9):792–802.
  • Hughes WT, LaFon SW, Scott JD, et al. Adverse events associated with trimethoprim-sulfamethoxazole and atovaquone during the treatment of AIDS-related Pneumocystis carinii pneumonia. J Infect Dis. 1995;171(5):1295–1301.
  • Meyer C, Behm N, Brown E, et al. An adverse drug reaction to Trimethoprim-sulfamethoxazole revealing primary hiv: a case report and literature review. Case Rep Infect Dis. 2015;2015:691010.
  • Huang L, Crothers K, Atzori C, et al. Dihydropteroate synthase gene mutations in Pneumocystis and sulfa resistance. Emerg Infect Dis. 2004;10(10):1721–1728.
  • Queener SF, Cody V, Pace J, et al. Trimethoprim resistance of dihydrofolate reductase variants from clinical isolates of Pneumocystis jirovecii. Antimicrob Agents Chemother. 2013;57(10):4990–4998.
  • Crothers K, Beard CB, Turner J, et al. Severity and outcome of HIV-associated Pneumocystis pneumonia containing Pneumocystis jirovecii dihydropteroate synthase gene mutations. AIDS. 2005;19(8):801–805.
  • Valerio A, Tronconi E, Mazza F, et al. Genotyping of Pneumocystis jiroveci pneumonia in Italian AIDS patients. Clinical outcome is influenced by dihydropteroate synthase and not by internal transcribed spacer genotype. J Acquir Immune Defic Syndr. 2007;45(5):521–528.
  • Alvarez-Martinez MJ, Moreno A, Miro JM, et al. Pneumocystis jirovecii pneumonia in Spanish HIV-infected patients in the combined antiretroviral therapy era: prevalence of dihydropteroate synthase mutations and prognostic factors of mortality. Diagn Microbiol Infect Dis. 2008;62(1):34–43.
  • Montgomery AB, Feigal DW Jr., Sattler F, et al. Pentamidine aerosol versus trimethoprim-sulfamethoxazole for Pneumocystis carinii in acquired immune deficiency syndrome. Am J Respir Crit Care Med. 1995;151(4):1068–1074.
  • Conte JE Jr., Hollander H, Golden JA. Inhaled or reduced-dose intravenous pentamidine for Pneumocystis carinii pneumonia. A pilot study. Ann Intern Med. 1987;107(4):495–498.
  • Conte JE Jr., Chernoff D, Feigal DW Jr., et al. Intravenous or inhaled pentamidine for treating Pneumocystis carinii pneumonia in AIDS. A randomized trial. Ann Intern Med. 1990;113(3):203–209.
  • Qiu W, Liu JJ, Carstens EB. Studies of Choristoneura fumiferana nuclear polyhedrosis virus gene expression in insect cells. Virology. 1996;217(2):564–572.
  • Toma E, Thorne A, Singer J, et al. Clindamycin with primaquine vs. Trimethoprim-sulfamethoxazole therapy for mild and moderately severe Pneumocystis carinii pneumonia in patients with AIDS: a multicenter, double-blind, randomized trial (CTN 004). CTN-PCP Study Group. Clin Infect Dis. 1998;27(3):524–530.
  • Kim T, Kim SH, Park KH, et al. Clindamycin-primaquine versus pentamidine for the second-line treatment of pneumocystis pneumonia. J Infect Chemother. 2009;15(5):343–346.
  • Helweg-Larsen J, Benfield T, Atzori C, et al. Clinical efficacy of first- and second-line treatments for HIV-associated Pneumocystis jirovecii pneumonia: a tri-centre cohort study. J Antimicrob Chemother. 2009;64(6):1282–1290.
  • Hughes W, Leoung G, Kramer F, et al., Comparison of atovaquone (566C80) with trimethoprim-sulfamethoxazole to treat Pneumocystis carinii pneumonia in patients with AIDS. N Engl J Med. 328(21): 1521–1527. 1993.
  • Dohn MN, Weinberg WG, Torres RA, et al. Oral atovaquone compared with intravenous pentamidine for Pneumocystis carinii pneumonia in patients with AIDS. Atovaquone Study Group. Ann Intern Med. 1994;121(3):174–180.
  • Kazanjian P, Armstrong W, Hossler PA, et al. Pneumocystis carinii cytochrome b mutations are associated with atovaquone exposure in patients with AIDS. J Infect Dis. 2001;183(5):819–822.
  • Walker DJ, Wakefield AE, Dohn MN, et al. Sequence polymorphisms in the Pneumocystis carinii cytochrome b gene and their association with atovaquone prophylaxis failure. J Infect Dis. 1998;178(6):1767–1775.
  • Medina I, Mills J, Leoung G, et al. Oral therapy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A controlled trial of trimethoprim-sulfamethoxazole versus trimethoprim-dapsone. N Engl J Med. 1990;323(12):776–782.
  • Powles MA, Liberator P, Anderson J, et al. Efficacy of MK-991 (L-743,872), a semisynthetic pneumocandin, in murine models of Pneumocystis carinii. Antimicrob Agents Chemother. 2001;183(5):1985–1989.
  • Cushion MT, Linke MJ, Ashbaugh A, et al. Echinocandin treatment of pneumocystis pneumonia in rodent models depletes cysts leaving trophic burdens that cannot transmit the infection. PLoS One. 2010;5(1):e8524.
  • Kamboj M, Weinstock D, Sepkowitz KA. Progression of Pneumocystis jiroveci pneumonia in patients receiving echinocandin therapy. Clin Infect Dis. 2006;431(9):e92–94.
  • Kim T, Hong HL, Lee YM, et al. Is caspofungin really an effective treatment for Pneumocystis jirovecii pneumonia in immunocompromised patients without human immunodeficiency virus infection? Experiences at a single center and a literature review. Scand J Infect Dis. 2013;45(6):484–488.
  • Armstrong-James D, Stebbing J, John L, et al. A trial of caspofungin salvage treatment in PCP pneumonia. Thorax. 2011;66(6):537–538.
  • Wang M, Lang G, Chen Y, et al. A pilot study of echinocandin combination with trimethoprim/sulfamethoxazole and clindamycin for the treatment of AIDS patients with Pneumocystis pneumonia. J Immunol Res. 2019;2019:8105075.
  • Huang YS, Liu CE, Lin SP, et al. Echinocandins as alternative treatment for HIV-infected patients with Pneumocystis pneumonia. AIDS. 2019;33(8):1345–1351.
  • Deresinski SC, Stevens DA, Stevens DA. Caspofungin. Clin Infect Dis. 2003;36(11):1445–1457.
  • Huang ZB, Eden E. Effect of corticosteroids on IL1 beta and TNF alpha release by alveolar macrophages from patients with AIDS and Pneumocystis carinii pneumonia. Chest. 1993;104(3):751–755.
  • Bozzette SA, Sattler FR, Chiu J, et al., A controlled trial of early adjunctive treatment with corticosteroids for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. California Collaborative Treatment Group. N Engl J Med. 323(21): 1451–1457. 1990.
  • Gagnon S, Boota AM, Fischl MA, et al. Corticosteroids as adjunctive therapy for severe Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A double-blind, placebo-controlled trial. N Engl J Med. 1990;323(21):1444–1450.
  • 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.
  • Pareja JG, Garland R, Koziel H. Use of adjunctive corticosteroids in severe adult non-HIV Pneumocystis carinii pneumonia. Chest. 1998;113(5):1215–1224.
  • 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):636–644.
  • Lemiale V, Debrumetz A, Delannoy A, et al. Adjunctive steroid in HIV-negative patients with severe Pneumocystis pneumonia. Respir Res. 2013;14(1):87.
  • Fujikura Y, Manabe T, Kawana A, et al. Adjunctive corticosteroids for Pneumocystis jirovecii pneumonia in Non-HIV-infected patients: a systematic review and meta-analysis of observational studies. Arch Bronconeumol. 2017;53(2):55–61.
  • 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.
  • Kasiske BL, Zeier MG, Chapman JR, et al. KDIGO clinical practice guideline for the care of kidney transplant recipients: a summary. Kidney Int. 2010;77(4):299–311.
  • Vogel MN, Vatlach M, Weissgerber P, et al. HRCT-features of Pneumocystis jiroveci pneumonia and their evolution before and after treatment in non-HIV immunocompromised patients. Eur J Radiol. 2012;81(6):1315–1320.
  • Ahmad H, Mehta NJ, Manikal VM, et al. Pneumocystis carinii pneumonia in pregnancy. Chest. 2001;120(2):666–671.
  • Sattler FR, Frame P, Davis R, et al. Trimetrexate with leucovorin versus trimethoprim-sulfamethoxazole for moderate to severe episodes of Pneumocystis carinii pneumonia in patients with AIDS: a prospective, controlled multicenter investigation of the AIDS clinical trials group protocol 029/031. J Infect Dis. 1994;170(1):165–172.
  • Czeizel AE, Rockenbauer M, Sorensen HT, et al. The teratogenic risk of trimethoprim-sulfonamides: a population based case-control study. Reprod Toxicol. 2001;15(6):637–646.
  • Hernandez-Diaz S, Werler MM, Walker AM, et al. Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med. 2000;343(22):1608–1614.
  • Safrin S, Lee BL, Sande MA. Adjunctive folinic acid with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia in AIDS patients is associated with an increased risk of therapeutic failure and death. J Infect Dis. 1994;170(4):912–917.
  • Harstad TW, Little BB, Bawdon RE, et al. Embryofetal effects of pentamidine isethionate administered to pregnant Sprague-Dawley rats. Am J Obstet Gynecol. 2013;14(1):912–916.
  • Park-Wyllie L, Mazzotta P, Pastuszak A, et al. Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Teratology. 2000;62(6):385–392.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.