Summary
The efficacy and safety of pentamidine aerosol versus intravenous cotrimoxazole (trimethoprim-sulfamethoxazole) [TMP/SMX] in the treatment of slight to moderate Pneumocystis carinii pneumonia in HIV-infected patients were investigated in a comparative study. The study was designed as an open, randomised, multicentre, prospective study for a collective of 60 patients. Pentamidine aerosol (600 mg/day) was tested against intravenous cotrimoxazole (TMP 20mg/SMX 100mg per kg). Major inclusion criteria were: arterial partial oxygen pressure (pO2) >60mm Hg and forced vital capacity (FVC1) >2L or >50%. 24-hour urine and serum samples were used to evaluate the pharmacokinetics of the tested medications in selected patients. A statistical evaluation was performed according to the ‘intent to treat’ principle after a 4-week follow-up.
Case reports of 22 patients treated with pentamidine and 24 treated with TMP/SMX were evaluated. Because of a high frequency of side effects in the TMP/SMX group, the study was discontinued after 46 patients had completed the treatment cycles. However, the response rate in the 2 groups was virtually identical. Complete remission occurred in 16 pentamidine patients and in 10 TMP/SMX patients who received the full course of treatment. In the pentamidine group, 3 patients showed slight side effects; no severe side effects occurred. In the TMP/SMX group, slight side effects were observed in 9 patients, and severe side effects in 7 patients. The difference in the frequency of side effects, the main target variable, was statistically significant (p = 0.0003; 2-tailed, Fisher’s exact test; power of comparison = 95%). Treatment success in the absence of side effects was observed in 15 pentamidine patients and in 3 TMP/SMX patients.
The study suggests that pentamidine aerosol has advantages over standard intravenous TMP/SMX treatment in slight to moderate Pneumocystis carinii pneumonia.
Similar content being viewed by others
References
Montgomery AB, Debs RJ, Luce JM, et al. Aerosolized pen-tamidine as second line therapy in patients with AIDS and Pneumocystis carinii pneumonia. Chest 1989; 95: 747–50
Montgomery AB, Debs RJ, Luce JM, et al. Aerosolised pen-tamidine as sole therapy for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. Lancet 1987; 2: 480–3
Waldmann RH, Pearce DE, Martin RA. Pentamidine isethion-ate levels in lungs, livers, and kidneys of rats after aerosol or intramuscular administration. Am Rev Respir Dis 1979; 108: 1004–6
Leoung GS, Feigal DW Jr, Montgomery AB, et al. Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia. The San Francisco community prophylaxis trial. New Engl J Med 1990; 323: 769–75
Lin J, Shi R, Lin E. High performance liquid Chromatographic determination of pentamidine in plasma. J Liq Chromatogr 1986; 9: 2035–46
Fleiss J. Statistical methods for rates and proportions. 2nd ed. New York: John Wiley, 1973
Wharton JM, Coleman DL, Wofsy CB, et al. Trimethoprim-sul-famethoxazole or pentamidine for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A prospective randomized trial. Ann Intern Med 1986; 105: 37–44
Klein NC, Duncanson FP, Lenox TH, et al. Trimethoprim-sul-famethoxazole versus pentamidine for Pneumocystis carinii pneumonia in AIDS patients. Results of a large prospective randomized treatment trial. AIDS 1992; 6: 301–5
Sattler FR, Cowan R, Nielsen DM, et al. Trimethoprim-sul-famethoxazole compared with pentamidine for treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A prospective, noncrossover study. Ann Intern Med 1988; 109: 280–7
Pearson RD, Hewlett EL. Diagnosis and treatment. Pentamidine for the treatment of Pneumocystis carinii pneumonia and other protozoal diseases. Ann Intern Med 1985; 103: 782–6
Jaffe HS, Abrams DI, Ammann AJ, et al. Complications of co-trimoxazole in treatment of AIDS-associated Pneumocystis carinii pneumonia in homosexual men. Lancet 1983; 2: 1109–11
Bowden FJ, Harman PJ, Lucas CR. Serum trimethoprim and sulphamethoxazole levels in AIDS. Lancet 1986; 1: 853
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: 495–8
McLean I, Lucas CR, Mashford ML, et al. Modified trimetho-prim-sulphamethoxazole doses in Pneumocystis carinii pneumonia. Lancet 1987; 2: 857–8
Donnelly H, Bernard EM, Rothkotter H, et al. Distribution of pentamidine in patients with AIDS. J Infect Dis 1988; 157: 985–9
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: 203–9
Girard PM, Lecompte T, Lazzarin A. Aerosolized pentamidine (AP) in the treatment of PCP episodes. An open multinational trial, preliminary results on 70 patients [abstract]. International Conference on AIDS 1989; 5: 290
Arasteh K, Heise W, L’age M. Treatment of mild to moderately severe Pneumocystis carinii pneumonia with cotrimoxazole versus pentamidine aerosol. Preliminary results of a prospective randomized therapy study. Med Klin 1990; 2: 260–3
Meyer A, Dörlemann A, Dietrich M. Treatment of HIV associated mild to moderate Pneumocystis carinii pneumonia by pentamidine aerosol 600 mg/d. Results of a multicenter study. Med Klin 1990; 2: 260–3
Wordell CJ, Hauptman SP. Treatment of Pneumocystis carinii pneumonia in patients with AIDS. Clin Pharm 1988; 7: 514–27
Toma E. Clindamycin/primaquine for treatment of Pneumocystis carinii pneumonia in AIDS. Eur J Clin Microbiol Infect Dis 1991; 10: 210–3
Black JR, Feinberg J, Murphy RL, et al. Clindamycin and pri-maquine as primary treatment for mild and moderately severe Pneumocystis carinii pneumonia in patients with AIDS. Eur J Clin Microbiol Infect Dis 1991; 10: 204–7
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. New Engl J Med 1990; 323: 776–82
Falloon J, Kovacs J, Hughes W, et al. A preliminary evaluation of 566C80 for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. New Engl J Med 1991; 325: 1534–8
Hughes WT, Leoung G, Kramer F, et al. Comparison of atovaquone (566C80) with trimethoprim-sulfamethoxazole to treat Pneumocystis carinii pneumonia in patients with AIDS. New Engl J Med 1993; 328: 1512–7
Smith D, Davies S, Nelson M, et al. Pneumocystis carinii pneumonia treated with eflornithine in AIDS patients resistant to conventional therapy. AIDS 1990; 4: 1019–21
Smith D, Smithson J, Harding I, et al. Eflornithine versus cotrimoxazole in the treatment of Pneumocystis carinii pneumonia [abstract]. International Conference on AIDS 1990; 6: 221
Sattler FR, Feinberg J. New developments in the treatment of Pneumocystis carinii pneumonia. Chest 1992; 101: 451–7
Sattler FR, Allegra CJ, Verdegem TD, et al. Trimetrexate-leucovorin dosage evaluation study for treatment of Pneumocystis carinii pneumonia. J Infect Dis 1990; 161: 91–6
Vöhringer H, Arastéh K, Hardtmann I, et al. Pharmacological investigation of pentamidine aerosol in HIV-patients. Med Klin 1990; 2: 260–3
Conte JE Jr, Upton RA, Lin ET. Pentamidine pharmacokinetics in patients with AIDS with impaired renal function. J Infect Dis 1987; 15: 885–90
Matthys A, Herceg R. Lung deposition of 300 and 600mg pentamidine by inhalation using three different nebulizers. Med Klin 1990; 2: 260–3
O’Doherty MJ, Thomas S, Page C, et al. Differences in relative efficiency of nebulisers for pentamidine administration. Lancet 1988; 2: 1283–6
Nichols L, Black J, Sattler F, et al. A quantitative scoring system for evaluating the response to therapy of Pneumocystis carinii pneumonia (PCP) [abstract]. International Conference on AIDS 1989; 5: 290
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Arastéh, K.N., Vöhringer, H.F., Heise, W.S. et al. Pentamidine Aerosol vs Cotrimoxazole in the Treatment of Slight to Moderate Pneumocystis carinii Pneumonia. Drug Invest 8, 321–330 (1994). https://doi.org/10.1007/BF03257446
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03257446