URINARY CONCENTRATIONS OF COLISTIMETHATE AND FORMED COLISTIN AFTER INTRAVENOUS ADMINISTRATION IN PATIENTS WITH MULTIDRUG-RESISTANT GRAM-NEGATIVE BACTERIAL INFECTIONS [PublishAheadOfPrint]

Objectives: Limited information is available on the urinary excretion of colistin in infected patients. This study aimed to investigate the pharmacokinetics of colistimethate sodium (CMS) and formed colistin in urine in patients with multidrug-resistant (MDR) Gram-negative infections.

Methods: Pharmacokinetic study conducted in 12 patients diagnosed with an infection caused by an extremely drug-resistant (XDR) P. aeruginosa and treated with intravenous CMS. Freshly urine samples were collected in 2-h interval and blood samples pre-dose (Cmin_ss) and at the end of the CMS infusion (Cmax_ss) for measurement of concentrations of CMS and formed colistin using HPLC. CMS urinary recovery was determined as the summed amount of CMS and formed colistin recovered in urine for each 2-h interval divided by the CMS dose.

Results: Twelve enrolled patients: 9 male (75%), median (range) data: age 65.5 (37-86) years; colistimethate urinary recovery 0-6 h: 42.6% (2.9-72.8); range of concentrations of colistin in urine: < 0.1-95.4 mg/L; Cmin_ss and Cmax_ss of colistin in plasma: 0.9 (<0.2-1.4) and 0.9 (<0.2-1.4) mg/L, respectively. In 6/12 (50%) patients more than 40% of the CMS dose was recovered in the urine within the first 6 hours after CMS administration.

Conclusions: This study demonstrated rapid urinary excretion of CMS within the first 6 hours in patients after the intravenous administration. In all but one patient the concentrations of formed colistin in urine were above the MIC of the most frequent isolate of P. aeruginosa in our hospital. Future studies are warranted for optimising CMS dosage regimens in UTI patients.

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