The recommended treatment of Pneumocystis jirovecii pneumonia (PCP) is high-dose trimethoprim–sulfamethoxazole (TMP–SMX) in an equivalent of TMP 15–20 mg/kg/day and SMX 75–100 mg/kg/day for 2 or 3 weeks. High rates of adverse events are reported with this dose, which raises the question if lower doses are possible.
All adult patients diagnosed with PCP in various immune dysfunctions and treated with TMP–SMX between January 1, 2003 and July 1, 2013 in a tertiary university hospital were included. Per institutional protocol, patients initiated treatment on intermediate-dose TMP–SMX (TMP 10–15 mg/kg/day) and could be stepped down to low-dose TMP–SMX (TMP 4–6 mg/kg/day) during treatment. Clinical variables at presentation, relapse rate and mortality rates were compared between intermediate- and step-down treatment groups by uni- and multivariate analyses.
A total of 104 patients were included. Twenty-four patients (23 %) were switched to low-dose TMP–SMX after a median of 4.5 days (IQR 2.8–7.0 days). One relapse (4 %) occurred in the step-down group versus none in the intermediate-dose group. The overall 30-day mortality was 13 %. There was 1 death in the step-down group (4 %) compared to 13 deaths (16 %) in the intermediate-dose group.
We observed high cure rates of PCP by treatment with intermediate-dose TMP–SMX. In addition, a step-down strategy to low-dose TMP–SMX during treatment in selected patients appears to be safe and does not compromise the outcome of treatment.
Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed 18 June 2014.
Walzer PD, Smulian AG. Pneumocystis species. In: Mandell GL, Bennett JE, Dolin R, editors. Mandell, Douglas, and Bennett’s principles and practice of infectious diseases, 7th ed. Philadelphia; 2010. p. 3377–90.
Hughes WT, Feldman S, Sanyal SK. Treatment of Pneumocystis carinii pneumonitis with trimethoprim–sulfamethoxazole. Can Med Assoc J. 1975;112:47S–50S.
Wharton JM, Coleman DL, Wofsy CB, Luce JM, Blumenfeld W, Hadley WK, Ingram-Drake L, Volberding PA, Hopewell PC. Trimethoprim–sulfamethoxazole or pentamidine for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A prospective randomized trial. Ann Intern Med. 1986;105:37–44. CrossRefPubMed
Sattler FR, Frame P, Davis R, Nichols L, Shelton B, Akil B, Baughman R, Hughlett C, Weiss W, Boylen CT, van der Horst C, Black J, Powderly W, Steigbigel RT, Leedom JM, Masur H, Feinberg J. 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;170:165–72. CrossRefPubMed
Klein NC, Duncanson FP, Lenox TH, Forszpaniak C, Sherer CB, Quentzel H, Nunez M, Suarez M, Kawwaff O, Pitta-Alvarez A, Freeman K, Wormser GP. Trimethoprim–sulfamethoxazole versus pentamidine for Pneumocystis carinii pneumonia in AIDS patients: results of a large prospective randomized treatment trial. AIDS. 1992;6:301–5. CrossRefPubMed
Safrin S, Finkelstein DM, Feinberg J, Frame P, Simpson G, Wu A, Cheung T, Soeiro R, Hojczyk P, Black JR. 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;124:792–802. CrossRefPubMed
Hughes W, Leoung G, Kramer F, Bozzette SA, Safrin S, Frame P, Clumeck N, Masur H, Lancaster D, Chan C, Lavelle J, Rosenstock J, Falloon J, Feinberg J, Lafon S, Rogers M, Sattler F. Comparison of atovaquone (566C80) with trimethoprim–sulfamethoxazole to treat Pneumocystis carinii pneumonia in patients with AIDS. N Engl J Med. 1993;328:1521–7. CrossRefPubMed
Bowden FJ, Stewart K, Mashford L, Lucas CR. A randomised, double blind trial of low dose versus high dose cotrimoxazole in the treatment of aids-related Pneumocystis carinii pneumonia. Aust N Z J Med. 1991;21:593.
Linssen CF, Jacobs JA, Beckers P, Templeton KE, Bakkers J, Kuijper EJ, Melchers WJ, Drent M, Vink C. Inter-laboratory comparison of three different real-time PCR assays for the detection of Pneumocystis jirovecii in bronchoalveolar lavage fluid samples. J Med Microbiol. 2006;55:1229–35. CrossRefPubMed
Rahdi S, Alexander T, Ukwu M, Saleh S, Morris A. Outcome of HIV-associated Pneumocystis pneumonia in hospitalized patients from 2000 through 2003. BMC Infect Dis. 2008;8:118–9. CrossRef
Arend SM, Kroon FP, van’t Wout JW. Pneumocystis carinii pneumonia in patients without AIDS, 1980 through 1993. An analysis of 78 cases. Arch Intern Med. 1995;1995:2436–41. CrossRef
Roblot F, Godet C, Le Moal G, Garo B, Faouzi Souala M, Dary M, De Gentile L, Gandji JA, Guimard Y, Lacroix C, Roblot P, Becq-Giraudon B. Analysis of underlying diseases and prognosis factors associated with Pneumocystis carinii pneumonia in immunocompromised HIV-negative patients. Eur J Clin Microbiol Infect Dis. 2002;21:523–31. CrossRefPubMed
Bergan T, Brodwall EK. The pharmacokinetic profile of co-trimoxazole. Scand J Infect Dis Suppl. 1976;8:42–9. PubMed
- Treatment of Pneumocystis pneumonia with intermediate-dose and step-down to low-dose trimethoprim–sulfamethoxazole: lessons from an observational cohort study
Frank P. Kroon
Ed. J. Kuijper
Mark G. J. de Boer
- Springer Berlin Heidelberg
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