Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · May 1988
Effect of cardiopulmonary bypass on vancomycin and netilmicin disposition.
The effect of cardiopulmonary bypass (CPB) on the disposition of vancomycin (15 mg/kg) and of netilmicin (3 mg/kg) was studied in 10 adults. The concentration-time profile of the drug in serum and renal clearance were characterized pre-CPB, during CPB, and post-CPB. Vancomycin and netilmicin exhibited initial decreases in mean concentrations in serum of 4.0 mg/liter (16.8%) and 2.2 mg/liter (29.1%), respectively, upon initiation of CPB. ⋯ Vancomycin concentrations in serum demonstrated a rebound increase of 2.3 mg/liter (23.5%) at the end of CPB when the aorta was unclamped. Mean renal clearance throughout CPB was decreased for vancomycin (58.4 to 43.4 ml/min per m2) and netilmicin (53.4 to 31.5 ml/min per m2). The rebound in vancomycin concentration in serum strongly correlated with the length of time between unclamping the aorta and coming off CPB (r = 0.94), as well as with the increase in temperature upon rewarming (r = 0.92).
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Antimicrob. Agents Chemother. · May 1988
Comparative StudyComparison of dosages, intervals, and drugs in the prevention of Pneumocystis carinii pneumonia.
The efficacies of trimethoprim (TMP)-sulfamethoxazole (SMZ), TMP-dapsone, dapsone, and pentamidine were compared for the prevention of Pneumocystis carinii pneumonia in the corticosteroid-treated-rat model. While 11 (73%) of 15 untreated control animals had P. carinii pneumonia after 10 weeks of immunosuppression, none of the animals given 125 mg of dapsone per kg daily, weekly, biweekly, or monthly had evidence of infection. Of the 10 rats given a single dose of dapsone 23 and 50 days after immunosuppression was started, 5 (50%) had P. carinii pneumonia. ⋯ The experiments showed that dapsone is highly effective in chemoprophylaxis for P. carinii pneumonia when given at monthly intervals or more frequently and that dapsone and TMP-dapsone are more effective than is TMP-SMZ when given at biweekly intervals. It seems reasonable to expect that biweekly doses of dapsone or TMP-dapsone would provide an effective and reasonably safe chemoprophylaxis regimen for patients at high risk for P. carinii pneumonia, and studies to test such a scheme are justifiable. Biweekly doses are preferred over monthly doses to allow for occasional inadvertent omission of doses expected from patients.