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. 1991 Sep;35(9):1705–1709. doi: 10.1128/aac.35.9.1705

Use of low-dose trimethoprim-sulfamethoxazole thrice weekly for primary and secondary prophylaxis of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients.

D S Stein 1, R C Stevens 1, D Terry 1, S C Laizure 1, S Palte 1, D J Lancaster 1, J J Weems 1, C L Williams 1
PMCID: PMC245254  PMID: 1952835

Abstract

We conducted an open prospective clinical trial to evaluate the efficacy and toxicity of trimethoprim-sulfamethoxazole given as one double-strength tablet thrice weekly for primary and secondary prophylaxis of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus-infected (HIV+) patients. A total of 104 HIV+ patients were evaluated, with 74 being in the primary prophylaxis group and 30 being in the secondary prophylaxis group. All except six patients received concomitant zidovudine; five patients on primary prophylaxis and one patient on secondary prophylaxis refused zidovudine. There were 70 patients evaluated for the efficacy of primary prophylaxis. The mean CD4 count was 124.4 +/- 110.1 cells per microliter. The mean follow-up time was 11.8 +/- 5.8 months (median, 12 months; range, 1 to 32 months). Two noncompliant patients developed PCP after 1 and 3 months of chemoprophylaxis. The failure rate (under the intention to treat principle) was 2 of 70 patients (2.9%; 95% confidence interval, 0.35 to 10%), or 1 per 413 patient-months of observation. There were 27 patients evaluated for the efficacy of secondary prophylaxis. The mean follow-up time was 12.4 +/- 7.2 months (median, 11 months; range, 1 to 29 months). Two patients, one of whom was noncompliant, were treatment failures, developing PCP after 14 and 15 months of chemoprophylaxis; this gave a failure rate of 2 of 27 patients (7.4%; 95% confidence interval, 0.9 to 24.3%), or 1 per 167 patient-months of observation. Adverse reactions sufficient to permanently terminate therapy occurred in 9 of 104 patients (8.7%; 95% confidence interval, 4 to 15.7%) overall. The serum trimethoprim, sulfamethoxazole, and N4-acetyl-sulfamethoxazole concentrations measured by high-pressure liquid chromatography were uniformly low. One double-strength tablet of trimethoprim-sulfamethoxazole taken weekly on Monday, Wednesday, and Friday appeared to be well tolerated and efficacious for the prophylaxis of PCP in HIV+ patients at high risk and deserves further investigation.

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Selected References

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  1. Davey R. T., Jr, Masur H. Recent advances in the diagnosis, treatment, and prevention of Pneumocystis carinii pneumonia. Antimicrob Agents Chemother. 1990 Apr;34(4):499–504. doi: 10.1128/aac.34.4.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Fischl M. A., Dickinson G. M., La Voie L. Safety and efficacy of sulfamethoxazole and trimethoprim chemoprophylaxis for Pneumocystis carinii pneumonia in AIDS. JAMA. 1988 Feb 26;259(8):1185–1189. doi: 10.1001/jama.259.8.1185. [DOI] [PubMed] [Google Scholar]
  3. Fischl M. A., Richman D. D., Grieco M. H., Gottlieb M. S., Volberding P. A., Laskin O. L., Leedom J. M., Groopman J. E., Mildvan D., Schooley R. T. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987 Jul 23;317(4):185–191. doi: 10.1056/NEJM198707233170401. [DOI] [PubMed] [Google Scholar]
  4. Hirschel B., Lazzarin A., Chopard P., Opravil M., Furrer H. J., Rüttimann S., Vernazza P., Chave J. P., Ancarani F., Gabriel V. A controlled study of inhaled pentamidine for primary prevention of Pneumocystis carinii pneumonia. N Engl J Med. 1991 Apr 18;324(16):1079–1083. doi: 10.1056/NEJM199104183241602. [DOI] [PubMed] [Google Scholar]
  5. Hughes W. T., Rivera G. K., Schell M. J., Thornton D., Lott L. Successful intermittent chemoprophylaxis for Pneumocystis carinii pneumonitis. N Engl J Med. 1987 Jun 25;316(26):1627–1632. doi: 10.1056/NEJM198706253162604. [DOI] [PubMed] [Google Scholar]
  6. Laizure S. C., Holden C. L., Stevens R. C. Ion-paired high-performance liquid chromatographic separation of trimethoprim, sulfamethoxazole and N4-acetylsulfamethoxazole with solid-phase extraction. J Chromatogr. 1990 Jun 8;528(1):235–242. doi: 10.1016/s0378-4347(00)82381-6. [DOI] [PubMed] [Google Scholar]
  7. Leoung G. S., Feigal D. W., Jr, Montgomery A. B., Corkery K., Wardlaw L., Adams M., Busch D., Gordon S., Jacobson M. A., Volberding P. A. Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia. The San Francisco community prophylaxis trial. N Engl J Med. 1990 Sep 20;323(12):769–775. doi: 10.1056/NEJM199009203231201. [DOI] [PubMed] [Google Scholar]
  8. Montaner J. S., Lawson L. M., Gervais A., Hyland R. H., Chan C. K., Falutz J. M., Renzi P. M., MacFadden D., Rachlis A. R., Fong I. W. Aerosol pentamidine for secondary prophylaxis of AIDS-related Pneumocystis carinii pneumonia. A randomized, placebo-controlled study. Ann Intern Med. 1991 Jun 1;114(11):948–953. doi: 10.7326/0003-4819-114-11-948. [DOI] [PubMed] [Google Scholar]
  9. Phair J., Muñoz A., Detels R., Kaslow R., Rinaldo C., Saah A. 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 Jan 18;322(3):161–165. doi: 10.1056/NEJM199001183220304. [DOI] [PubMed] [Google Scholar]
  10. Ruskin J., LaRiviere M. Low-dose co-trimoxazole for prevention of Pneumocystis carinii pneumonia in human immunodeficiency virus disease. Lancet. 1991 Feb 23;337(8739):468–471. doi: 10.1016/0140-6736(91)93402-u. [DOI] [PubMed] [Google Scholar]
  11. Siber G. R., Gorham C. C., Ericson J. F., Smith A. L. Pharmacokinetics of intravenous trimethoprim-sulfamethoxazole in children and adults with normal and impaired renal function. Rev Infect Dis. 1982 Mar-Apr;4(2):566–578. doi: 10.1093/clinids/4.2.566. [DOI] [PubMed] [Google Scholar]
  12. Volberding P. A., Lagakos S. W., Koch M. A., Pettinelli C., Myers M. W., Booth D. K., Balfour H. H., Jr, Reichman R. C., Bartlett J. A., Hirsch M. S. Zidovudine in asymptomatic human immunodeficiency virus infection. A controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter. The AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. N Engl J Med. 1990 Apr 5;322(14):941–949. doi: 10.1056/NEJM199004053221401. [DOI] [PubMed] [Google Scholar]

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