Ceftriaxone: Pharmacokinetics and Effect on the Intestinal Microflora in Patients with Acute Bacterial Infections

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Abstract
12 patients with acute bacterial infections were treated with ceftriaxone, 1.5 g intravenously twice daily for 7–13 days. Pharmacokinetic variables were studied in 11 patients. In older subjects, serum half-lives were longer and serum clearances lower than in younger individuals. After the last dose, a larger increase in AUC compared to the first dose was observed in older patients and a biphasic elimination curve appeared in all patients but 2, with a terminal half-life of 15.6 h and 11.4 h in old and young subjects, respectively. Estimated biliary clearances showed large individual variation, with a range of 0–16 ml/min 1.73 m2. Changes in the colonic microflora were pronounced. Almost total disappearance of staphylococci, streptococci and enterobacteria was found, and there was a marked tendency to overgrowth of yeasts and enterococci. One patient with the highest estimated biliary clearance of ceftriaxone developed diarrhoea after 7 days of therapy. A toxin-producing Clostridium difficile was isolated from the stool.

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