Skip to main content
NCBI home page
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 2012 Oct 30;42(4):628–639. doi: 10.2165/00003495-199142040-00006

Treatment and Prophylaxis of Pneumocystis carinii Pneumonia in AIDS Patients

Don Smith 1, Brian G Gazzard 1,✉
PMCID: PMC7102186  PMID: 1723365

Summary

Pneumocystis carinii pneumonia (PCP) is seen in people with a defect in cell-mediated immunity. Today the most common cause for this is the Acquired Immunodeficiency Syndrome (AIDS). There have been some remarkable advances recently in the development of new drug regimens to combat this otherwise fatal infection. Although cotripoxazole (trimethoprim-sulfamethoxazole) is still the drug of first choice it cannot be tolerated by a significant proportion of patients, and therapies such as pentamidine (pentamidine-isethionate) [intravenous or nebulised], dapsone-trimethoprim, eflornithine (DFMO; difluoromethylornithine), trimetrexate, and clindamycin-primaquine are finding therapeutic niches. The major advantage in these other agents is not improved efficacy but different toxicity profiles, enabling therapy to be most appropriately tailored to individual patients’ conditions. Although the majority of patients should now survive an attack of PCP, relapses will occur if prophylaxis is not used: There is also the capacity to predict accurately which patients are at risk for this pneumonia and prevent it through the use of chemoprophylaxis. These advances in the treatment and prevention of PCP, together with anti-retro viral therapy, mean that this is an area of AIDS management that has resulted in improved long term survival.

Keywords: Dapsone, Pentamidine, Celiprolol, Primaquine, Calcium Folinate

References

  1. Allegra C.J, Chabner B.A, Tuazon C.A, Ogata-Arakai D, Baird B, et al. Trimetrexate for the treatment of pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. New England Journal of Medicine. 1987;317:978–985. doi: 10.1056/NEJM198710153171602. [DOI] [PubMed] [Google Scholar]
  2. Allegra C.J, Kovacs J.A, Drake J.C, Swan J.C, Chabner S.A, et al. Activity of antifolates against pneumocystis carinii dihydrofolate reductase and identification of a potent new agent. Journal of Experimental Medicine. 1987;165:926–931. doi: 10.1084/jem.165.3.926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bacchi C.J, McCann P.P, et al. Parasitic protozoa and polyamines. In: McGann P.P, et al., editors. Inhibition of polyamine metabolism. New York: Academic Press; 1987. pp. 317–344. [Google Scholar]
  4. Bozzette S.A. The use of corticosteroids in Pneumocystis carinii pneumonia. Journal of Infectious Diseases. 1990;162:1365–1369. doi: 10.1093/infdis/162.6.1365. [DOI] [PubMed] [Google Scholar]
  5. Bozzette S.A, Sattler F.R, Chui J, et al. A controlled trial of early adjunctive treatment with corticosteroids for pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. New England Journal of Medicine. 1990;323:1451–1457. doi: 10.1056/NEJM199011223232104. [DOI] [PubMed] [Google Scholar]
  6. Brenner M, Ognibene F.P, Lack E.E, Simmons J.T, Saffredini A.F, et al. Prognostic factors and life expectancy of patients with acquired immunodeficiency syndrome and pneumocystis carinii pneumonia. American Review of Respiratory Disease. 1987;136:1119–1206. doi: 10.1164/ajrccm/136.5.1199. [DOI] [PubMed] [Google Scholar]
  7. Centers for Disease Control Guidelines for prophylaxis against Pneumocystis carinii pneumonia for persons infected with human immunodeficiency virus. Morbidity and Mortality Weekly Report. 1989;38(5):1–9. [PubMed] [Google Scholar]
  8. Centers for Disease Control Guidelines for prophylaxis against Pneumocystis carinii pneumonia for children infected with human immunodeficiency virus. Morbidity and Mortality Weekly Report. 1991;40:1–13. [PubMed] [Google Scholar]
  9. Clolet B, Sirera G, Romeu J, Gimeno J.M, Jou A, et al. Twice-weekly dapsone-pyrimethamine for preventing PCP and cerebral toxoplasmosis. AIDS. 1991;5:601. doi: 10.1097/00002030-199105000-00024. [DOI] [PubMed] [Google Scholar]
  10. Conte J.E, Chernoff D, Feigal D.W, Joseph P, McDonald C, et al. Intravenous or inhaled pentamidine for treating Pneumocystis carinii pneumonia in AIDS: a randomised trial. Annals of Internal Medicine. 1990;113:203–209. doi: 10.7326/0003-4819-113-3-203. [DOI] [PubMed] [Google Scholar]
  11. Conte J.E, Golden J.A. Concentrations of aerosolised pentamidine in bronchoalveolar lavage, systemic absorption and excretion. Antimicrobial Agents and Chemotherapy. 1988;32:1490–1493. doi: 10.1128/AAC.32.10.1490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Corkery K.J, Luce J.M, Montgomery A.B. Aerosolised pentamidine for treatment and prophylaxis of Pneumocystis carinii pneumonia: an update. Respiratory Care. 1988;8:676–685. [Google Scholar]
  13. Cushion M.T, Stanforth D, Linke M.J, Walzer P.D. Method of testing the susceptibility of pneumocystis carinii to antimicrobial agents in vitro. Antimicrobial Agents and Chemotherapy. 1985;28:796–801. doi: 10.1128/AAC.28.6.796. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Debs R.J, Straubinger R.M, Brunette E.N, Lin J.M, Lin E.J, et al. Selective enhancement of pentamidine uptake in the lungs by aerosolisation and delivery in liposomes. American Review of Respiratory Disease. 1987;135:731–737. doi: 10.1164/arrd.1987.135.3.731. [DOI] [PubMed] [Google Scholar]
  15. Donnelly H, Bernard E.M, Rothkotter H, Gold J.W.M, Armstrong D. Distribution of pentamidine in patients with AIDS. Journal of Infectious Diseases. 1988;157:985–989. doi: 10.1093/infdis/157.5.985. [DOI] [PubMed] [Google Scholar]
  16. Finegold I. Oral desensitization to trimethoprim-sulfamethoxazole in a patient with acquired immunodeficiency syndrome. Journal of Allergy and Clinical Immunology. 1986;78:905–908. doi: 10.1016/0091-6749(86)90238-1. [DOI] [PubMed] [Google Scholar]
  17. Fischl M.A, Dickinson G.M. Fansidar prophylaxis of pneumocystis pneumonia in the Acquired Immunodeficiency Syndrome. Correspondence. Annals of Internal Medicine. 1986;105:629–630. doi: 10.7326/0003-4819-105-4-629_1. [DOI] [PubMed] [Google Scholar]
  18. Fischl M.A, Dickinson G.M, La Voie L. Safety and efficacy of sulfamethoxazole and trimethoprim chemoprophylaxis for Pneumocystis carinii pneumonia in AIDS. Journal of the American Medical Association. 1988;259:1185–1189. doi: 10.1001/jama.259.8.1185. [DOI] [PubMed] [Google Scholar]
  19. Gagnon S, Boota A.M, Fischl M.A, Baier H, Kirksey O.W, et al. Corticosteroids as adjunctive therapy for severe Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. New England Journal of Medicine. 1990;323:1444–1450. doi: 10.1056/NEJM199011223232103. [DOI] [PubMed] [Google Scholar]
  20. Girard P.M, Landman R, Gaudebout C, Lepretre A, Lottin P, et al. Prevention of pneumocystis carinii pneumonia relapse by pentamidine aerosol in zidovudine-treated AIDS patients. Lancet. 1989;1:1348–1353. doi: 10.1016/S0140-6736(89)92802-X. [DOI] [PubMed] [Google Scholar]
  21. Goa K.L, Campoli-Richards D. Pentamidine isethionate. A review of its antiprotozoal activity, pharmacokinetic properties and therapeutic use in Pneumocystis carinii pneumonia. Drugs. 1987;33:242–258. doi: 10.2165/00003495-198733030-00002. [DOI] [PubMed] [Google Scholar]
  22. Golden J.A, Chernoff D, Hollander H, Feigal D, Conte J.E. Prevention of pneumocystis carinii pneumonia by inhaled pentamidine. Lancet. 1989;2:654–657. doi: 10.1016/S0140-6736(89)92153-3. [DOI] [PubMed] [Google Scholar]
  23. Harris J.E. Improved short term survival of AIDS patients initially diagnosed with pneumocystis carinii pneumonia, 1984 through 1987. Journal of the American Medical Association. 1990;263:397–401. doi: 10.1001/jama.1990.03440030084026. [DOI] [PubMed] [Google Scholar]
  24. Hirschel B, Lazzarin A, Chopard P, Opravil M, Furrer H.J, et al. A controlled study of inhaled pentamidine for primary prevention of pneumocystis carinii pneumonia. New England Journal of Medicine. 1991;324:1079–1083. doi: 10.1056/NEJM199104183241602. [DOI] [PubMed] [Google Scholar]
  25. Hughes W.T, Feldman S, Chaudhary S.C, Ossi M.J, Cox F, et al. Comparison of pentamidine isethionate and trimethoprim-sulfamethoxazole in the treatment of pneumocystis carinii pneumonia. Journal of Pediatrics. 1978;92:285–291. doi: 10.1016/S0022-3476(78)80028-6. [DOI] [PubMed] [Google Scholar]
  26. Hughes W.T, Pivera G.K, Schell M.J, Thornton D, Lott L. Successful intermittent chemoprophylaxis for pneumocystis carinii pneumonitis. New England Journal of Medicine. 1987;316:1627–1632. doi: 10.1056/NEJM198706253162604. [DOI] [PubMed] [Google Scholar]
  27. Jaffe H.S, Abrams D.I, Ammann A.J, Lewis B.J, Golden J.A. Complications of co-trimoxazole in the treatment of AIDS-associated pneumocystis carinii pneumonia in homosexual men. Lancet. 1983;2:1109–1111. doi: 10.1016/S0140-6736(83)90627-X. [DOI] [PubMed] [Google Scholar]
  28. Kay R, DuBois R.E. Clindamycin/primaquine therapy and secondary prophylaxis against pneumocystis carinii pneumonia in patients with AIDS. Southern Medical Journal. 1990;83:403–404. doi: 10.1097/00007611-199004000-00010. [DOI] [PubMed] [Google Scholar]
  29. Kemper C.A, Tucker R.M, Lang O.S, Kessinger J.M, Greene S.I, et al. Low-dose dapsone prophylaxis of pneumocystis carinii pneumonia in AIDS and AIDS-related complex. AIDS. 1990;4:1145–1148. doi: 10.1097/00002030-199011000-00015. [DOI] [PubMed] [Google Scholar]
  30. Kovacs J.A, Masur H. Prophylaxis of Pneumocystis carinii pneumonia: an update. Journal of Infectious Disease. 1989;160:882–886. doi: 10.1093/infdis/160.5.882. [DOI] [PubMed] [Google Scholar]
  31. Kovacs J.A, Masur H. Are corticosterpids beneficial as adjunctive therapy for pneumocystis pneumonia in AIDS. Annals of Internal Medicine. 1990;113:1–3. doi: 10.7326/0003-4819-113-1-1. [DOI] [PubMed] [Google Scholar]
  32. Kronawitter U, Bogner J.R, Goebel F.D. Pentamide prophylaxis of pneumocystis carinii pneumonia. Annals of Internal Medicine. 1991;115:497–498. doi: 10.7326/0003-4819-115-6-497_2. [DOI] [PubMed] [Google Scholar]
  33. Leen C.L.S, Mandai B.K. Rash due to nebulised pentamidine. Correspondence. Lancet. 1988;2:1250–1251. doi: 10.1016/S0140-6736(88)90841-0. [DOI] [PubMed] [Google Scholar]
  34. Lemp G.F, Payne S.F, Neal D, Temelso T, Rutherford G.W. Survival trends for patients with AIDS. Journal of the American Medical Association. 1990;263:402–406. doi: 10.1001/jama.1990.03440030089027. [DOI] [PubMed] [Google Scholar]
  35. Leoung G.S, Feigal D.W, Montgomery A.B, Corkery K, Wardlaw L, et al. Aerosolized pentamidine for prophylaxis against pneumocystis carinii pneumonia. New England Journal of Medicine. 1990;323:769–775. doi: 10.1056/NEJM199009203231201. [DOI] [PubMed] [Google Scholar]
  36. Leoung G.S, Mills J, Hopewell P.C, Hughes W, Wofsy C. Dapsone-trimethoprim for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Annals of Internal Medicine. 1986;105:45–48. doi: 10.7326/0003-4819-105-1-45. [DOI] [PubMed] [Google Scholar]
  37. Mallory D.L, Parrillo J.E, Bailey K.R, Akin G.L, Brenner M, et al. Cardiovascular effects and safety of intravenous and intramuscular pentamidine isethionate. Critical Care Medicine. 1987;15:503–505. doi: 10.1097/00003246-198705000-00010. [DOI] [PubMed] [Google Scholar]
  38. Martinez C.M, Romanelli A, Mullen M.P, Lee M. Spontaneous pneumothoraces in AIDS patients receiving aerosolised pentamidine. Chest. 1988;94:1317–1318. doi: 10.1378/chest.94.6.1317b. [DOI] [PubMed] [Google Scholar]
  39. Montaner J.S.G, Lawson L.M, Gervais A, Hyland R.H, Chan C.K, et al. Aerosol pentamidine for secondary prophylaxis of AIDS-related pneumocystis carinii pneumonia. Annals of Internal Medicine. 1991;114:948–953. doi: 10.7326/0003-4819-114-11-948. [DOI] [PubMed] [Google Scholar]
  40. Masur H, Michelis M.A, Greene J.B, et al. An outbreak of community acquired Pneumocystis carinii pneumonia: initial manifestation of cellular immune dysfunction. New England Journal of Medicine. 1981;305:1431–1438. doi: 10.1056/NEJM198112103052402. [DOI] [PubMed] [Google Scholar]
  41. Masur H, Meier P, McCatchan J.A, Feinberg J, Bernard G, et al. Consensus statement on the use of corticosteroids as adjunctive therapy for pneumocystis pneumonia in the Acquired Immunodeficiency Syndrome. New England Journal of Medicine. 1990;323:1500–1504. doi: 10.1056/NEJM199011223232131. [DOI] [PubMed] [Google Scholar]
  42. Medina I, Mills J, Leoung G, Hopewell P.C, Lee B, et al. Oral therapy for pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. New England Journal of Medicine. 1990;323:776–782. doi: 10.1056/NEJM199009203231202. [DOI] [PubMed] [Google Scholar]
  43. Monk J.P, Benfield P. Inhaled pentamidine: an overview of its pharmacological properties and a review of its therapeutic use in Pneumocystis carinii pneumonia. Drugs. 1990;39:741–756. doi: 10.2165/00003495-199039050-00008. [DOI] [PubMed] [Google Scholar]
  44. Montgomery A.B, Debs R.J, Luce J.M, Corkery K.J, Turner J, et al. Aerosolised pentamidine as sole therapy for Pneumocystis carinii pneumonia in patients with Acquired Immunodeficiency Syndrome. Lancet. 1987;2:480–483. doi: 10.1016/S0140-6736(87)91794-6. [DOI] [PubMed] [Google Scholar]
  45. Newman S.P. Aerosol deposition considerations in inhalation therapy. Chest. 1985;88:152–160. doi: 10.1378/chest.88.1.160-a. [DOI] [PubMed] [Google Scholar]
  46. Northfelt D.W. Extrapulmonary pneumocystis in patients taking aerosolised pentamidine. Correspondence/Lancet. 1989;2:1454. doi: 10.1016/s0140-6736(89)92060-6. [DOI] [PubMed] [Google Scholar]
  47. O’Doherty M.J, Page C, Bradbeer C, Thomas S, Barlow D, et al. Differences in relative efficiency of nebulisers for pentamidine administration. Lancet. 1988;2:1283–1286. doi: 10.1016/S0140-6736(88)92894-2. [DOI] [PubMed] [Google Scholar]
  48. Ogata-Arakaki D, Fallon J, Lavelle J, Bryne A, Kovacs J, et al. The safety of weekly dapsone and weekly dapsone + pyrimethamine as pneumocystis prophylaxis. Abstract Th.B.411, p. 224, 6th International Conference on AIDS, San Francisco, 1990
  49. Phair J, Munoz A, Detels R, Kaslow R, Rinaldo C, et al. The risk of Pneumocystis carinii pneumonia among men infected with Human Immunodeficiency Virus type 1. New England Journal of Medicine. 1990;322:161–165. doi: 10.1056/NEJM199001183220304. [DOI] [PubMed] [Google Scholar]
  50. Rainer CA, Feigal DW, Leoung G, Clement M, Wofsy CB. Prognosis and natural history of Pneumocystis carinii pneumonia: indicators for early and late survival, p. 189. Abstracts of the third International Conference on AIDS, Washington, DC, 1987
  51. Rashbridge M.R, Scott G.L. The haemolytic action of dapsone: the effect on red cell glycolysis. British Journal of Haematology. 1973;24:169–181. doi: 10.1111/j.1365-2141.1973.tb05737.x. [DOI] [PubMed] [Google Scholar]
  52. Raviglione M.C, Nsah E.N, Cortes H, Mariuz P, Sanjana V. Intermittent co-trimoxazole prophylaxis against pneumocystis carinii pneumonia. Correspondence. Lancet. 1990;2:180. doi: 10.1016/0140-6736(90)91701-B. [DOI] [PubMed] [Google Scholar]
  53. Ruf B, Pohle H.D. Clindamycin/primaquine for pneumocystis carinii pneumonia. Correspondence. Lancet. 1989;2:626–627. doi: 10.1016/S0140-6736(89)90755-1. [DOI] [PubMed] [Google Scholar]
  54. Ruskin J, La Riviere M. Low dose co-trimoxazole for prevention of pneumocystis carinii pneumonia in human immunodeficiency virus disease. Lancet. 1991;337:468–471. doi: 10.1016/0140-6736(91)93402-U. [DOI] [PubMed] [Google Scholar]
  55. Sattler F.R. Who should receive corticosteroids as adjunctive treatment for Pneumocystis carinii pneumonia? Chest. 1991;99:1058–1060. doi: 10.1378/chest.99.5.1058. [DOI] [PubMed] [Google Scholar]
  56. Sattler F.R, Cowan R, Nielsen D.M, Ruskin J. Trimethoprim-sulphamethoxazole compared with pentamidine for treatment of Pneumocystis carinii pneumonia in the Acquired Immunodeficiency Syndrome. Annals of Internal Medicine. 1988;109:280–287. doi: 10.7326/0003-4819-109-4-280. [DOI] [PubMed] [Google Scholar]
  57. Simonds A.K, Newman S.P, Johnson M.A, Talaee N, Lee C.A, et al. Simple modification to enhance alveolar deposition of pentamidine. Lancet. 1989;2:953. doi: 10.1016/S0140-6736(89)90957-4. [DOI] [PubMed] [Google Scholar]
  58. Sjoerdsma A, Schechter P.J. Chemotherapeutic implications of polyamine biosynthesis inhibition. Clinical Pharmacology and Therapeutics. 1984;35:287–300. doi: 10.1038/clpt.1984.33. [DOI] [PubMed] [Google Scholar]
  59. Smalldone G.C, Perry R.J, Deutsch D.G. Characteristics of nebulisers used in the treatment of AIDS-related Pneumocystis carinii pneumonia. Journal of Aerosol Medicine. 1988;1:113–125. doi: 10.1089/jam.1988.1.113. [DOI] [Google Scholar]
  60. Smith D, Davies S, Nelson M, Youle M, Gleeson J, et al. Pneumocystis carinii pneumonia treated with eflornithine in AIDS patients resistant to conventional therapy. AIDS. 1990;4:1019–1021. doi: 10.1097/00002030-199010000-00012. [DOI] [PubMed] [Google Scholar]
  61. Smith D, Smithson J, Harding I, Gazzard B, Nelson M. Eflornithine versus co-trimoxazole in the treatment of pneumocystis carinii pneumonia. Abstract Th.B.398. 6th International Conference on AIDS, San Francisco, 1990b
  62. Smith D.E, Herd D.A, Gazzard B.G. Reversible bronchocon-striction with nebulised pentamidine. Lancet. 1988;2:905. doi: 10.1016/S0140-6736(88)92500-7. [DOI] [PubMed] [Google Scholar]
  63. Smith D.E, Hills D.A, Harman C, Hawkins D.A, Gazzard B.G. Nebulised pentamidine for the prevention of pneumocystis carinii pneumonia in AIDS patients: experience of 173 patients and a review of the literature. Quarterly Journal of Medicine. 1991;78:619–629. [PubMed] [Google Scholar]
  64. Soo Hoo G.W, Mohsenifar Z, Meyer R.D. Inhaled or intravenous pentamidine therapy for Pneumocystis carinii pneumonia in AIDS: a randomised trial. Annals of Internal Medicine. 1990;113:195–202. doi: 10.7326/0003-4819-113-3-195. [DOI] [PubMed] [Google Scholar]
  65. Stahlhofen W, Gebhart J, Heyder J. Experimental determination of the regional deposition of aerosol particles in the human respiratory tract. American Industrial Hygiene Association Journal. 1980;41:385–398. doi: 10.1080/15298668091424933. [DOI] [PubMed] [Google Scholar]
  66. Toma E, Fournier S, Poisson M, Morisset R, Phaneuf D, et al. Clindamycin with primaquine for pneumocystis carinii pneumonia. Lancet. 1989;1:1046–1048. doi: 10.1016/S0140-6736(89)92446-X. [DOI] [PubMed] [Google Scholar]
  67. Thomas S, O’Doherty M, Bateman N. Pneumocystis carinii pneumonia. Editorial. British Medical Journal. 1990;300:211–212. doi: 10.1136/bmj.300.6719.211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Waskin H, Stehr-Green J.K, Heimick C.G, Sattler F.R. Risk factors for hypoglycaemia associated with pentamidine therapy for pneumocystis pneumonia. Journal of the American Medical Association. 1988;260:345–347. doi: 10.1001/jama.1988.03410030061029. [DOI] [PubMed] [Google Scholar]
  69. Wharton J.M, Coleman D.L, Wofsy C.B, Luce J.M, Blumenfeld W, et al. Trimethoprim-sulfamethoxole or pentamidine for pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome: a prospective randomised trial. Annals of Internal Medicine. 1986;105:37–44. doi: 10.7326/0003-4819-105-1-37. [DOI] [PubMed] [Google Scholar]

Articles from Drugs are provided here courtesy of Nature Publishing Group

RESOURCES