Oral therapy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A controlled trial of trimethoprim-sulfamethoxazole versus trimethoprim-dapsone.
BACKGROUND
Antimicrobial drugs that can be taken orally are needed for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). Preliminary data indicate that dapsone with trimethoprim may be an effective alternative to trimethoprim-sulfamethoxazole, which is frequently toxic.


METHODS
In a double-blind trial, 60 patients with AIDS and mild-to-moderately-severe first episodes of P. carinii pneumonia (partial pressure of oxygen in arterial blood, greater than 60 mm Hg while breathing room air) were randomly assigned to 21 days of treatment with either trimethoprim-sulfamethoxazole (20 and 100 mg per kilogram of body weight per day, respectively) or trimethoprim-dapsone (20 mg per kilogram per day and 100 mg per day).


RESULTS
The orally administered treatment failed because of progressive pneumonitis in 3 of the 30 patients assigned to trimethoprim-sulfamethoxazole and in 2 of the 30 assigned to trimethoprim-dapsone (P greater than 0.3). Major toxic effects required a switch to intravenous pentamidine for 17 patients (57 percent) in the trimethoprim-sulfamethoxazole group, as compared with 9 (30 percent) in the trimethoprim-dapsone group (P less than 0.025). With trimethoprim-sulfamethoxazole, there were more instances of severe chemical hepatitis (six, as compared with one in the trimethoprim-dapsone group) and marked neutropenia (five vs. one). Intolerable rash (three in each treatment group) and severe nausea and vomiting (two in each group) occurred with equal frequency with both drug combinations. Methemoglobinemia occurred in most of the patients treated with trimethoprim-dapsone, but it was asymptomatic and the level exceeded 20 percent in only one patient. Mild hyperkalemia (serum potassium level, 5.1 to 6.1 mmol per liter) also occurred in 53 percent of the patients treated with trimethoprim-dapsone.


CONCLUSIONS
In patients with AIDS, oral therapy with trimethoprim-sulfamethoxazole and with trimethoprim-dapsone are equally effective for mild-to-moderate first episodes of P. carinii pneumonia, but with trimethoprim-dapsone there are fewer serious adverse reactions than with trimethoprim-sulfamethoxazole.
Medina
I
I
Medical Service, San Francisco General Hospital, CA 94110.
Mills
J
J
Leoung
G
G
Hopewell
P C
PC
Lee
B
B
Modin
G
G
Benowitz
N
N
Wofsy
C B
CB
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000284:Administration, Oral; D000328:Adult; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D003622:Dapsone / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D010419:Pentamidine / Q000627:therapeutic use; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy* / Q000401:mortality; D011897:Random Allocation; D015996:Survival Rate; D014295:Trimethoprim / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects / Q000627:therapeutic use*
D004338:Drug Combinations; D010419:Pentamidine; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D003622:Dapsone; D014295:Trimethoprim