Dapsone-Trimethoprim for Pneumocystis carinii Pneumonia in the Acquired Immunodeficiency Syndrome

Abstract

All patients with the acquired immunodeficiency syndrome and a first episode of Pneumocystis carinii pneumonia seen at the San Francisco General Hospital between November 1984 and April 1985 were evaluated for oral treatment with dapsone (100 mg/d) plus trimethoprim (20 mg/kg body weight X d). All 15 patients who met the entry criteria improved clinically and radiographically within 3 to 10 days after starting treatment. Repeat pulmonary function tests and gallium lung scans after 3 weeks of therapy also showed improvement. Although side effects occurred in 14 patients, in only 2 were they severe enough to require stopping therapy. Both of these patients had worsening skin rash, and dapsone-trimethoprim therapy was stopped after 10 days. When compared with trimethoprim-sulfamethoxazole or pentamidine used to treat P. carinii pneumonia in similar patients, oral dapsone-trimethoprim is at least as effective, seems to be better tolerated, and may have a lower frequency of serious side effects.

Comparison of dosages, intervals, and drugs in the prevention of Pneumocystis carinii pneumonia

“…The corticosteroid-tetracycline-treated-rat model has been highly predictive of the effects of prophylactic and therapeutic interventions in human disease (8,10,13). The data from this study clearly indicate that dapsone given as infrequently as monthly is totally effective in the prevention of P. carinii pneumonia when started at the time of immunosuppression.…”

“…In a search for new drugs for the management of P. carinii infections, we recently found that dapsone (diaminodiphenylsulfone) administered daily was as effective as TMP-SMZ in the prevention and treatment of murine P. carinii pneumonia and that its effect was enhanced by combination with trimethoprim (10). Subsequently, a similar response was reported in AIDS patients with P. carinii pneumonia (13). Although dapsone may also cause adverse effects in AIDS and non-AIDS patients, Edelson et al (3) recently administered the drug daily to 14 AIDS patients known to have suffered adverse effects from TMP-SMZ.…”

“…In a search for new drugs for the management of P. carinii infections, we recently found that dapsone (diaminodiphenylsulfone) administered daily was as effective as TMP-SMZ in the prevention and treatment of murine P. carinii pneumonia and that its effect was enhanced by combination with trimethoprim (10). Subsequently, a similar response was reported in AIDS patients with P. carinii pneumonia (13 In considering modifications of dapsone administration to optimize safety and efficacy, it occurred to us that the remarkably long plasma half-life of the drug might provide a decided advantage in prophylaxis. In human studies, the half-lives have ranged between 14 and 53 h, with an average of about 28 h (15).…”

AIDS‐related Pneumocystis carinii pneumonia successfully treated with dapsone‐trimethoprim [letter]

“…This particular patient sustained no side effects from his treatment with dapsone/ trimethoprim and although Leoung et al (1986) in the USA reported mild nausea and vomiting, erythematous maculo-papular rashes, a degree of neutropenia or thrombocytopenia and a mild hepatic transaminitis as possible side-effects, those workers concluded that the oral dapsone/ trimethoprim combination is a safe regimen for the treatment of PCP in patients with AIDS. We would endorse that view that a combination of dapsone and trimethoprim is a useful addition to the therapeutic armamentarium in the treatment of PCP.…”

Pneumocystis carinii, an opportunist in immunocompromised patients

“…Patients treated with trimetrexate required concurrent leucovorin rescue, making the regimen costly. Dapsone has been used both alone and in combination with SMX or TMP (43,108). The dapsone combinations are effective, but some problems with adverse reactions remain (153).…”