Monitoring of co-trimoxazole concentrations in serum during treatment of pneumocystis carinii pneumonia.
The purpose of this prospective randomized open trial was to investigate the impact of monitoring concentrations in serum on the efficacy and side effects of high-dose co-trimoxazole therapy. Forty consecutive patients with microscopically confirmed Pneumocystis carinii pneumonia were enrolled. Therapy was started with 5 and 25 mg of trimethoprim and sulfamethoxazole, respectively, per kg of body weight given every 6 h for 2 days and continued every 8 h either with (group A) or without (group B) monitoring and dose adjustments according to sulfamethoxazole levels in serum (target, 150 to 200 micrograms/ml) for a total of 21 days. Only 7 of 19 patients (83%). Patients who were treated for the full period and patients for whom co-trimoxazole was prematurely stopped had similar concentrations of sulfamethoxazole (157 +/- 52 versus 155 +/- 47 micrograms/ml) and trimethoprim (5.0 +/- 1.4 versus 5.6 +/- 1.0 microgram/ml). Concentrations of sulfamethoxazole and trimethoprim in group A (158 +/- 39 and 5.6 +/- 1.8 micrograms/ml, respectively) did not differ from those in group B (153 +/- 57 and 5.1 +/- 1.6 micrograms/ml, respectively), and the average daily maintenance doses for groups A (75.4 mg/kg plus 15.1 mg/kg) and B (76.4 mg/kg plus 15.3 mg/kg) were nearly identical. Although the average sulfamethoxazole concentrations were maintained within the target zone in the monitoring group (day 5, 160 +/- 44 micrograms/ml; day 10, 160 +/- 41 micrograms/ml; day 15, 168 +/- micrograms/ml; and day 21, 157 +/- 95 micrograms/ml), only 28% of the individual sulfamethoxazole levels were within the target range of 150 to 200 micrograms/ml after the dose adjustments (32% in group B without intervention). Response rates were similar in both groups. Complete response or improvement was observed in 18 of 19 (group A) and 19 of 21 (group B) patients. The method used for monitoring sulfamethoxazole levels with subsequent dose adjustment did not allow us to reliably achieve the target concentrations and did not significantly alter the incidence of side effects or the efficacy of the therapy.
Joos
B
B
Division of Infectious Diseases, University Hospital, Zürich, Switzerland.
Blaser
J
J
Opravil
M
M
Chave
J P
JP
Lüthy
R
R
D000386:AIDS-Related Complex / Q000150:complications; D017088:AIDS-Related Opportunistic Infections / Q000097:blood / Q000188:drug therapy; D000293:Adolescent; D000328:Adult; D000935:Antifungal Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D011020:Pneumonia, Pneumocystis / Q000097:blood* / Q000188:drug therapy*; D011446:Prospective Studies; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*
D000935:Antifungal Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination