Aerosolised pentamidine for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome

Weinberg, Adriana; Dantonio, Sebastião A.; Duarte, Maria Irma S.; Pedreira Jr., Wilson L.; Barone, Antonio A.; Ishioka, Shinishi

doi:10.1590/S0036-46651990000400009

Abstracts

The goal of this study was to evaluate inhaled pentamidine for the treatment of patients with mild and moderate Pneumocystis carinii pneumonitis. Eight adults with AIDS and pneumocystis pneumonia (4 with a first episode and 4 with a repeat pneumocystosis) received daily inhalations of aerosol pentamidine isethionate for 21 days. Six patients were treated with doses of 300 mg of pentamidine and the remaining 2 received 600 mg every day. In the 300 mg treatment group, 2 individuals showed discrete and transient neutropenia. However, both subjects that received 600 mg of aerosol pentamidine daily developed leukopenia. One of them had major toxicity (overall severe intolerance of 12.5%) that required drug discontinuation and did not allow any analysis of the treatment efficacy. Of the 7 evaluable patients, 6 (88%) completed the treatment successfuly. One subject of the 300 mg regimen experienced an early recurrence. In conclusion, inhaled pentamidine is an effective treatment for mild and moderate cases of P. carinii pneumonia. It is less toxic than standard anti-pneumocystis therapy and is suitable for outpatient use.

Acquired immunodeficiency syndrome; Pneumocystis carinii pneumonia; Pentamidine; Inhalatory therapy

O objetivo deste estudo consistiu em avaliar pentamidina inalatória para o tratamento de pneumonia leve a moderada, causada por Pneumocystis carinii. Oito adultos com a síndrome da imunodeficiência humana e pneumocistose (4 apresentando o primeiro episódio e 4 na vigência de pneumocistose de repetição) receberam inalações diárias de isetionato de pentamidina por 21 dias. Seis pacientes foram tratados com doses de 300 mg de pentamidina e os 2 restantes receberam 600 mg diariamente. No grupo de 300 mg, 2 indivíduos desenvolveram neutropenia leve e transitória. Porém, ambos os pacientes recebendo 600 mg de pentamidina aerosol apresentaram leucopenia. Um deles teve toxicidade importante (intolerância global de 12,5%), que levou a suspensão da droga e impediu a avaliação da sua eficácia. Entre os 7 pacientes que puderam ser avaliados, 6 (86%) completaram o tratamento com sucesso. Um paciente que recebeu 300 mg de pentamidina diariamente teve uma recorrência precoce. Em conclusão, a pentamidina inalatória representa uma modalidade terapêutica eficaz contra a pneumonia por Pneumocystis carinii. E menos tóxica do que as drogas usadas convencionalmente e também pode ser administrada ambulatorialmente.

TREATMENT

Aerosolised pentamidine for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome

Aerosol de pentamidina no tratamento da pneumonia por Pneumocystis carinii em pacientes com a síndrome da imunodeficiência adquirida

Adriana Weinberg^I,II; Sebastião A. Dantonio^III; Maria Irma S. Duarte^IV; Wilson L. Pedreira Jr.^III; Antonio A. Barone^I; Shinishi Ishioka^III

^IDivision of Infectious Diseases of the Hospital das Clínicas of the University of São Paulo School of Medicine. São Paulo, SP, Brazil

^IIVirology laboratory of the Instituto de Medicina Tropical, São Paulo, LIM-52. São Paulo, SP, Brazil

^IIIDivision of Endoscopy of the Hospital das Clínicas of the University of São Paulo School of Medicine. São Paulo, SP, Brazil

^IVDepartment of Pathology of the University of São Paulo School of Medicine. São Paulo, SP, Brazil

^{Address for correspondence} Address for correspondence: A. Weinberg Av. Dr. Enéas C. Aguiar, 470 05403 S. Paulo, Brasil

SUMMARY

The goal of this study was to evaluate inhaled pentamidine for the treatment of patients with mild and moderate Pneumocystis carinii pneumonitis. Eight adults with AIDS and pneumocystis pneumonia (4 with a first episode and 4 with a repeat pneumocystosis) received daily inhalations of aerosol pentamidine isethionate for 21 days. Six patients were treated with doses of 300 mg of pentamidine and the remaining 2 received 600 mg every day. In the 300 mg treatment group, 2 individuals showed discrete and transient neutropenia. However, both subjects that received 600 mg of aerosol pentamidine daily developed leukopenia. One of them had major toxicity (overall severe intolerance of 12.5%) that required drug discontinuation and did not allow any analysis of the treatment efficacy. Of the 7 evaluable patients, 6 (88%) completed the treatment successfuly. One subject of the 300 mg regimen experienced an early recurrence. In conclusion, inhaled pentamidine is an effective treatment for mild and moderate cases of P. carinii pneumonia. It is less toxic than standard anti-pneumocystis therapy and is suitable for outpatient use.

Key words: Acquired immunodeficiency syndrome; Pneumocystis carinii pneumonia; Pentamidine; Inhalatory therapy.

RESUMO

O objetivo deste estudo consistiu em avaliar pentamidina inalatória para o tratamento de pneumonia leve a moderada, causada por Pneumocystis carinii. Oito adultos com a síndrome da imunodeficiência humana e pneumocistose (4 apresentando o primeiro episódio e 4 na vigência de pneumocistose de repetição) receberam inalações diárias de isetionato de pentamidina por 21 dias. Seis pacientes foram tratados com doses de 300 mg de pentamidina e os 2 restantes receberam 600 mg diariamente. No grupo de 300 mg, 2 indivíduos desenvolveram neutropenia leve e transitória. Porém, ambos os pacientes recebendo 600 mg de pentamidina aerosol apresentaram leucopenia. Um deles teve toxicidade importante (intolerância global de 12,5%), que levou a suspensão da droga e impediu a avaliação da sua eficácia. Entre os 7 pacientes que puderam ser avaliados, 6 (86%) completaram o tratamento com sucesso. Um paciente que recebeu 300 mg de pentamidina diariamente teve uma recorrência precoce. Em conclusão, a pentamidina inalatória representa uma modalidade terapêutica eficaz contra a pneumonia por Pneumocystis carinii. E menos tóxica do que as drogas usadas convencionalmente e também pode ser administrada ambulatorialmente.

Full text available only in PDF format.

Texto completo disponível apenas em PDF.

Recebido para publicação em 13/10/1989.

This work was supported by a grant from Rhodia Farma Ltda.

1. ALLEGRA, C.J.; CHABNER, B.A.; TUAZON, C.U.; OGATA-ARAKAKI, D.; BAIRD, B.; DRAKE, J.C.; SIMMONS, J.T.; LACK, E.E.; SHELHAMER, J.H.; BALIS, F.; WALKER, R.; KOVACS, J.A.; LANE, H.C. & MASUR, H. Trimetrexate for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. New Engl. J. Med., 317: 978-985, 1987.
2. BIGBY, T.D.; MARGOLESKEE, D.; CURTIS, J.L.; MICHAEL, P.F.; SHEPPARD, D.; HADLEY, W.K. & HOPEWELL, P.C. The usefulness of induced sputum in the diagnosis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. Amer. Rev. resp. Dis., 133: 515-518, 1986.
3. BROADDUS, C.; DAKE, M.D.; STULBARG, M.S.; BLUMENFELD, W.; HADLEY, W.K.; GOLDEN, J.A. & HOPEWELL, P.C. Bronchoalveolar lavage and transbronchial biopsy for the diagnosis of pulmonary infections in the acquired immunodeficiency syndrome. Ann. intern. Med., 102: 747-752, 1985.
4. CHEQUER, P.; LOURES, L.R.; CASTILHO, E. & BERGAMASHI, D. Epidemiological approach of tuberculosis in AIDS patients Brazil 1982-1988. In: INTERNATIONAL CONFERENCE ON AIDS, 5., Montreal, 1988. Abstract. p. 197.
5. CONTE, J.E.; HOLLANDER, H. & GOLDEN, J.A. Inhaled or reduced dose intravenous pentamidine for Pneumocystis carinii pneumonia. A pilot study. Ann. intern. Med., 107: 495-498, 1987.
6. FISCHL, M.A. & DICKINSON, G.M. Fansidar prophylaxis of Pneumocystis carinii in the acquired immunodeficiency syndrome. Ann. intern. Med., 105: 629, 1986.
7. FISCHL, M.A.; DICKINSON, G.M. & LA VOIE, L. Safety and efficacy of trimethoprim-sulfamethoxazole chemoprophylaxis for Pneumocystis carinii pneumonia in AIDS. J. Amer. med. Ass., 259: 1185-1189, 1988.
8. FLANIGAN, T.; SHAPIRO, E. & GRAHAM, R. Prophylaxis against Pneumocystis carinii pneumonia in patients receiving azidothymidine. New Engl. J. Med., 317: 1155, 1987.
9. GLATT, A.E.; CHIRGWIN, K. & LANDESMAN, S.H. Treatment of infections associated with human immunodeficiency virus. New Engl. J. Med., 318: 1439-1448, 1988.
10. GODFREY-FAUSETT, P.; MILLER, R.F. & SEMPLE, S.J.G. Nebulized pentamidine (letter). Lancet, 1: 645-646, 1988.
11. GOLDEN, J.A.; HOLLANDER, H.; CHERNOFF, D.; FEIGAL, D. & CONTE, J.E. Prevention of Pneumocystis carinii pneumonia by inhaled pentamidine. Lancet, 1: 654-657, 1989.
12. GORDIN, F.M.; SIMON, G.L.; WOFSY, C.B. & MILLS, J. Adverse reactions with trimethoprin-sulfamethoxazole in patients with the acquired immunodeficiency syndrome. Ann. intern. Med., 100: 495-499, 1984.
13. GOTTLIEB, M.S.; KNIGHT, S.; MITSUYASU, R.; WEISMAN, J.; ROTH, M. & YOUNG, L.S. Prophylaxis of Pneumocystis carinii infection in AIDS with pyrimethamine-sulfadoxine. Lancet, 2: 398-399, 1984.
14. HOPEWELL, P.C. Pneumocystis carinii pneumonia: diagnosis. J. infect. Dis., 157: 1115-1119, 1988.
15. HUGHES, W.T. Pneumocystis carinii pneumonitis. New Engl. J. Med., 317: 1021-1023, 1987.
16. KOVACS, J.A.; HIEMENZ, J.W.; MACHER, A.M.; STOVER, D.; MURRAY, H.W.; SHELHANEN, J.; LANE, C.; URMACHER, C.; HONIG, C.; LONGO, D.C.; PARKER, M.M.; NATHANSON, C.; PARRILLO, J.E.; FAUCI, A.S.; PIZZO, P.A. & MASUR, H. Pneumocystis carinii pneumonia: a comparison between patients with acquired immunodeficiency syndrome and patients with other immunodeficiencies. Ann. intern. Med., 100: 663-671, 1984.
17. LEOUNG, G.S.; MILLS, J.; HOPEWELL, P.C. & WOOFSY, C.B. Dapsone-trimethoprim for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Ann. intern. Med., 105: 45-48, 1986.
18. METROKA, C.E.; LANGE, M.; BRAUN, N.; O'SULIVAN, M.; JOSEFBERG, H. & JACOBSON, D. Successful chemoprophylaxis for Pneumocystis carinii pneumonia with dapsone in patients with AIDS and ARC. In: INTERNATIONAL CONFERENCE ON AIDS, 3., Washington, 1987. Abstract. p. 45.
19. MICHALANY, J.; MATTOS, A.L.A.; FILIE, A.C. & MONTEZZO, L.C. Acquired immune deficiency syndrome (AIDS) in Brazil. Necropsy findings. Ann. Path. (Paris), 7: 15-24, 1987.
20. MILLS, J. Pneumocystis carinii and toxoplasmosis in patients with AIDS. Rev. infect. Dis., 8: 1001-1011, 1986.
21. MONTGOMERY, A.B.; LUCE, J.M.; TURNER, J.; LIN, E.T.; DEBS, R.J.; CORKERY, K.J.; BRUNETTE, E.N. & HOPEWELL, P.C. Aerosolized pentamidine as sole therapy for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. Lancet, 2: 480-483, 1986.
22. MURRAY, J.F.; FELTON, C.P.; GARAY, S.M.; GOTTLIEB, M.S.; HOPEWELL, P.C.; STOVER, D.E. & TEIRSTEIN, A.S. Pulmonary complications of the acquired immunodeficiency syndrome. Report of a National Heart, Lung and Blood Institute Workshop. New Engl. J. Med., 310: 1682-1688, 1984.
23. MURRAY, J.F.; GARAY, S.M.; HOPEWELL, P.C.; MILLS, J.; SNIDER G.L. & STOVER, D.E. NHLBI workshop summary. Pulmonary complications of the acquired immunodeficiency syndrome: an update. Report of the second National Heart, Lung and Blood Institute Workshop. Amer. Rev. resp. Dis., 135: 504-509, 1987.
24. O'DOHERTY, M.J.; PAGE, C.; BRADBEER, C.; THOMAS, S.; BARLOW, D.; NUNAN, T.O. & BATEMAN, N.T. Differences in relative efficiency of nebulisers for pentamidine administration. Lancet, 2: 1283-1286, 1988.
25. PEARSON, R.D. & HEWLETT, E.L. Pentamidine for the treatment of Pneumocystis carinii pneumonia and other protozoan disease. Ann. intern. Med., 103: 782-786, 1985.
26. PITCHENIK, A.E.; GANJEI, P.; TORRES, A.; EVANS, D.A.; RUBIN, E. & BAIER, H. Sputum examination for the diagnosis of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Amer. Rev. resp. Dis., 133: 226-229, 1986.
27. RAINER, C.A.; FEIGAL, A.W.; LEOUNG, G.; CLEMENT, M. & WOFSY, C. Prognosis and natural history of Pneumocystis carinii pneumonia: indicators for early and late survival. In: INTERNATIONAL CONFERENCE ON AIDS, 3., Washington D. C., 1987. Abstract. p. 48.
28. SATTLER, F.R.; COWAN, R.; NIELSEN, D.M. & RUSKIN, J. Trimethoprim-sulfamethoxazole compared with pentamidine for the treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A prospective noncrossover study. Ann. intern. Med., 109: 280-287, 1988.
29. SMITH, D.E.; OWEN, S.; NELSON, M. & GAZZARD, B.G. Eflornithine in PCP cases resistant to conventional therapy. In: INTERNATIONAL CONFERENCE ON AIDS, 3., Montreal, 1988. Abstract. p. 201.
30. TOMA, E.; FOURNIER, S.; POISSON, M.; MORRISSET, R.; PHANEUF, D. & VEGA, C. Clindamycin/primaquine for P. carinii pneumonia (PCP) in AIDS. In: INTERNATIONAL CONFERENCE ON AIDS, 3., Montreal, 1988. Abstract. p. 201.
31. WALDMAN, R.H.; PEARCE, D.E. & MARTIN, R.A. Pentamidine isethionate levels in lungs, livers and kidneys of rats after aersol or intramuscular administration. Amer. Rev. resp. Dis., 108: 1004-1006, 1973.
32. WEINBERG, A. & DUARTE, M.I.S. Respiratory complications in Brazilian patients infected with human immunodeficiency virus. (Submitted for publication)
33. WHARTON, J.M.; COLEMAN, D.L.; WOFSY, C.B.; LUCE, J.M.; BLUMENFELD, W.; HADLEY, W.K.; INGRAM-DRAKE, L.; VOLBERDING, P.A. & HOPEWELL, P.C. Trimethoprim-sulfamethoxazole or pentamidine for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Ann. intern. Med., 105: 37-44, 1986.

Address for correspondence:

A. Weinberg

Av. Dr. Enéas C. Aguiar, 470

05403 S. Paulo, Brasil

Publication Dates

Publication in this collection
12 Sept 2006
Date of issue
Aug 1990

History

Received
13 Oct 1989

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. ALLEGRA, C.J.; CHABNER, B.A.; TUAZON, C.U.; OGATA-ARAKAKI, D.; BAIRD, B.; DRAKE, J.C.; SIMMONS, J.T.; LACK, E.E.; SHELHAMER, J.H.; BALIS, F.; WALKER, R.; KOVACS, J.A.; LANE, H.C. & MASUR, H. Trimetrexate for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. New Engl. J. Med., 317: 978-985, 1987.

[2] 2. BIGBY, T.D.; MARGOLESKEE, D.; CURTIS, J.L.; MICHAEL, P.F.; SHEPPARD, D.; HADLEY, W.K. & HOPEWELL, P.C. The usefulness of induced sputum in the diagnosis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. Amer. Rev. resp. Dis., 133: 515-518, 1986.

[3] 3. BROADDUS, C.; DAKE, M.D.; STULBARG, M.S.; BLUMENFELD, W.; HADLEY, W.K.; GOLDEN, J.A. & HOPEWELL, P.C. Bronchoalveolar lavage and transbronchial biopsy for the diagnosis of pulmonary infections in the acquired immunodeficiency syndrome. Ann. intern. Med., 102: 747-752, 1985.

[4] 4. CHEQUER, P.; LOURES, L.R.; CASTILHO, E. & BERGAMASHI, D. Epidemiological approach of tuberculosis in AIDS patients Brazil 1982-1988. In: INTERNATIONAL CONFERENCE ON AIDS, 5., Montreal, 1988. Abstract. p. 197.

[5] 5. CONTE, J.E.; HOLLANDER, H. & GOLDEN, J.A. Inhaled or reduced dose intravenous pentamidine for Pneumocystis carinii pneumonia. A pilot study. Ann. intern. Med., 107: 495-498, 1987.

[6] 6. FISCHL, M.A. & DICKINSON, G.M. Fansidar prophylaxis of Pneumocystis carinii in the acquired immunodeficiency syndrome. Ann. intern. Med., 105: 629, 1986.

[7] 7. FISCHL, M.A.; DICKINSON, G.M. & LA VOIE, L. Safety and efficacy of trimethoprim-sulfamethoxazole chemoprophylaxis for Pneumocystis carinii pneumonia in AIDS. J. Amer. med. Ass., 259: 1185-1189, 1988.

[8] 8. FLANIGAN, T.; SHAPIRO, E. & GRAHAM, R. Prophylaxis against Pneumocystis carinii pneumonia in patients receiving azidothymidine. New Engl. J. Med., 317: 1155, 1987.

[9] 9. GLATT, A.E.; CHIRGWIN, K. & LANDESMAN, S.H. Treatment of infections associated with human immunodeficiency virus. New Engl. J. Med., 318: 1439-1448, 1988.

[10] 10. GODFREY-FAUSETT, P.; MILLER, R.F. & SEMPLE, S.J.G. Nebulized pentamidine (letter). Lancet, 1: 645-646, 1988.

[11] 11. GOLDEN, J.A.; HOLLANDER, H.; CHERNOFF, D.; FEIGAL, D. & CONTE, J.E. Prevention of Pneumocystis carinii pneumonia by inhaled pentamidine. Lancet, 1: 654-657, 1989.

[12] 12. GORDIN, F.M.; SIMON, G.L.; WOFSY, C.B. & MILLS, J. Adverse reactions with trimethoprin-sulfamethoxazole in patients with the acquired immunodeficiency syndrome. Ann. intern. Med., 100: 495-499, 1984.

[13] 13. GOTTLIEB, M.S.; KNIGHT, S.; MITSUYASU, R.; WEISMAN, J.; ROTH, M. & YOUNG, L.S. Prophylaxis of Pneumocystis carinii infection in AIDS with pyrimethamine-sulfadoxine. Lancet, 2: 398-399, 1984.

[14] 14. HOPEWELL, P.C. Pneumocystis carinii pneumonia: diagnosis. J. infect. Dis., 157: 1115-1119, 1988.

[15] 15. HUGHES, W.T. Pneumocystis carinii pneumonitis. New Engl. J. Med., 317: 1021-1023, 1987.

[16] 16. KOVACS, J.A.; HIEMENZ, J.W.; MACHER, A.M.; STOVER, D.; MURRAY, H.W.; SHELHANEN, J.; LANE, C.; URMACHER, C.; HONIG, C.; LONGO, D.C.; PARKER, M.M.; NATHANSON, C.; PARRILLO, J.E.; FAUCI, A.S.; PIZZO, P.A. & MASUR, H. Pneumocystis carinii pneumonia: a comparison between patients with acquired immunodeficiency syndrome and patients with other immunodeficiencies. Ann. intern. Med., 100: 663-671, 1984.

[17] 17. LEOUNG, G.S.; MILLS, J.; HOPEWELL, P.C. & WOOFSY, C.B. Dapsone-trimethoprim for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Ann. intern. Med., 105: 45-48, 1986.

[18] 18. METROKA, C.E.; LANGE, M.; BRAUN, N.; O'SULIVAN, M.; JOSEFBERG, H. & JACOBSON, D. Successful chemoprophylaxis for Pneumocystis carinii pneumonia with dapsone in patients with AIDS and ARC. In: INTERNATIONAL CONFERENCE ON AIDS, 3., Washington, 1987. Abstract. p. 45.

[19] 19. MICHALANY, J.; MATTOS, A.L.A.; FILIE, A.C. & MONTEZZO, L.C. Acquired immune deficiency syndrome (AIDS) in Brazil. Necropsy findings. Ann. Path. (Paris), 7: 15-24, 1987.

[20] 20. MILLS, J. Pneumocystis carinii and toxoplasmosis in patients with AIDS. Rev. infect. Dis., 8: 1001-1011, 1986.

[21] 21. MONTGOMERY, A.B.; LUCE, J.M.; TURNER, J.; LIN, E.T.; DEBS, R.J.; CORKERY, K.J.; BRUNETTE, E.N. & HOPEWELL, P.C. Aerosolized pentamidine as sole therapy for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. Lancet, 2: 480-483, 1986.

[22] 22. MURRAY, J.F.; FELTON, C.P.; GARAY, S.M.; GOTTLIEB, M.S.; HOPEWELL, P.C.; STOVER, D.E. & TEIRSTEIN, A.S. Pulmonary complications of the acquired immunodeficiency syndrome. Report of a National Heart, Lung and Blood Institute Workshop. New Engl. J. Med., 310: 1682-1688, 1984.

[23] 23. MURRAY, J.F.; GARAY, S.M.; HOPEWELL, P.C.; MILLS, J.; SNIDER G.L. & STOVER, D.E. NHLBI workshop summary. Pulmonary complications of the acquired immunodeficiency syndrome: an update. Report of the second National Heart, Lung and Blood Institute Workshop. Amer. Rev. resp. Dis., 135: 504-509, 1987.

[24] 24. O'DOHERTY, M.J.; PAGE, C.; BRADBEER, C.; THOMAS, S.; BARLOW, D.; NUNAN, T.O. & BATEMAN, N.T. Differences in relative efficiency of nebulisers for pentamidine administration. Lancet, 2: 1283-1286, 1988.

[25] 25. PEARSON, R.D. & HEWLETT, E.L. Pentamidine for the treatment of Pneumocystis carinii pneumonia and other protozoan disease. Ann. intern. Med., 103: 782-786, 1985.

[26] 26. PITCHENIK, A.E.; GANJEI, P.; TORRES, A.; EVANS, D.A.; RUBIN, E. & BAIER, H. Sputum examination for the diagnosis of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Amer. Rev. resp. Dis., 133: 226-229, 1986.

[27] 27. RAINER, C.A.; FEIGAL, A.W.; LEOUNG, G.; CLEMENT, M. & WOFSY, C. Prognosis and natural history of Pneumocystis carinii pneumonia: indicators for early and late survival. In: INTERNATIONAL CONFERENCE ON AIDS, 3., Washington D. C., 1987. Abstract. p. 48.

[28] 28. SATTLER, F.R.; COWAN, R.; NIELSEN, D.M. & RUSKIN, J. Trimethoprim-sulfamethoxazole compared with pentamidine for the treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A prospective noncrossover study. Ann. intern. Med., 109: 280-287, 1988.

[29] 29. SMITH, D.E.; OWEN, S.; NELSON, M. & GAZZARD, B.G. Eflornithine in PCP cases resistant to conventional therapy. In: INTERNATIONAL CONFERENCE ON AIDS, 3., Montreal, 1988. Abstract. p. 201.

[30] 30. TOMA, E.; FOURNIER, S.; POISSON, M.; MORRISSET, R.; PHANEUF, D. & VEGA, C. Clindamycin/primaquine for P. carinii pneumonia (PCP) in AIDS. In: INTERNATIONAL CONFERENCE ON AIDS, 3., Montreal, 1988. Abstract. p. 201.

[31] 31. WALDMAN, R.H.; PEARCE, D.E. & MARTIN, R.A. Pentamidine isethionate levels in lungs, livers and kidneys of rats after aersol or intramuscular administration. Amer. Rev. resp. Dis., 108: 1004-1006, 1973.

[32] 32. WEINBERG, A. & DUARTE, M.I.S. Respiratory complications in Brazilian patients infected with human immunodeficiency virus. (Submitted for publication)

[33] 33. WHARTON, J.M.; COLEMAN, D.L.; WOFSY, C.B.; LUCE, J.M.; BLUMENFELD, W.; HADLEY, W.K.; INGRAM-DRAKE, L.; VOLBERDING, P.A. & HOPEWELL, P.C. Trimethoprim-sulfamethoxazole or pentamidine for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Ann. intern. Med., 105: 37-44, 1986.

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