B. Joos et al., MONITORING OF COTRIMOXAZOLE CONCENTRATIONS IN SERUM DURING TREATMENT OF PNEUMOCYSTIS-CARINII PNEUMONIA, Antimicrobial agents and chemotherapy, 39(12), 1995, pp. 2661-2666
The purpose of this prospective randomized open trial was to investiga
te the impact of monitoring concentrations in;serum on the efficacy an
d 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 bf trimethoprim a
nd 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 sulfamethoxazo
le levels in serum (target, 150 to 200 mu g/ml) for a total of 21 days
, Only 7 of 19 (group A) and 11 of 21 (group B) patients tolerated a f
ull S-week course, Adverse effects were observed in 33 patients (83%).
Patients who mere treated for the full period and patients for whom c
o-trimoxazole was prematurely stopped had similar concentrations of su
lfamethoxazole (157 +/- 52 versus 155 +/- 47 mu g/ml) and trimethoprim
(5.0 +/- 1.4 versus 5.6 +/- 1.9 mu g/ml). Concentrations of sulfameth
oxazole and trimethoprim in group A (158 +/- 39 and 5.6 +/- 1.8 mu g/m
l, respectively) did not differ from those in group B (153 +/- 57 and
5.1 +/- 1.6 mu g/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 sulfamethoxaz
ole concentrations were maintained within the target zone in the monit
oring group (day 5, 160 +/- 44 mu g/ml; day 10, 160 +/- 41 mu g/ml; da
y 15, 168 +/- 61 mu g/ml; and day 21, 157 +/- 95 mu g/ml), only 28% of
the individual sulfamethoxazole levels were within the target range o
f 150 to 200 mu g/ml after the dose adjustments (32% in group B withou
t intervention), Response rates were similar in both groups, Complete
response or improvement was observed in 18 of 19 (group A) and 19;of 2
1 (group B) patients, The method used for monitoring sulfamethoxazole
levels with subsequent dose adjustment did not allow us to reliably ac
hieve the target concentrations and did not significantly alter the in
cidence of side effects or the efficacy of the therapy.