Colistin pharmacokinetics in burn patients during continuous venovenous hemofiltration

Abstract

While colistin is considered a last resort for the treatment of multidrug-resistant Gram-negative bacterial infections, there has been an increase in its use due to the increasing prevalence of drug-resistant infections worldwide. The pharmacology of colistin is complex, and pharmacokinetic data are limited, especially in patients requiring renal replacement therapy. As a result, dosing for patients who require renal replacement remains a challenge. Here, we present pharmacokinetic data for colistin from two burn patients (37 and 68 years old) infected with colistin-susceptible isoclonal Acinetobacter baumannii and receiving continuous venovenous hemofiltration (CVVH). To our knowledge, we are the first to examine data from before and during CVVH (for one patient), allowing analysis of the effect of CVVH on colistin pharmacokinetics. Pharmacokinetic/pharmacodynamic analysis indicated that a dose increase from 1.5 to 2.2 mg/kg of body weight colistin base activity on CVVH was insufficient to satisfy the target parameter of an AUC24/MIC (area under the concentration-time curve over 24 h in the steady state divided by the MIC) of ≥ 60 at an MIC of ≥ 1 μg/ml in one patient with residual endogenous renal function. Plasma concentrations of colistin ranged from 0 to 15 μg/ml, with free colistin levels ranging from 0.4 to 2.2 μg/ml. While both patients resolved their clinical infections and survived to discharge, colistin-resistant colonizing isolates resulted from therapy in one patient. The variabilities observed in colistin concentrations and pharmacokinetic characteristics highlight the importance of pharmacokinetic monitoring of antibiotics in patients undergoing renal replacement therapy.

FIG 1

Time-concentration curves for CMS and colistin in patients undergoing CVVH. Concentrations over time in prefilter plasma samples for total and free colistin and ultrafiltrate fluid for patient 1 (A) and patient 2 (B). Additionally, colistin concentrations over time before CVVH are shown for patient 2. For patient 2, 12-h sampling was not performed during CVVH due to filter clotting.

FIG 2

Achievement of the pharmacodynamic target of total colistin AUC₂₄/MIC of ≥60 (dashed line) versus hypothetical MIC using plasma AUC values in two burn patients, one of whom was sampled before and during CVVH therapy. Filled squares, patient 1 treated with 2.2 mg CBA/kg with a delivered CVVH dose of 38.1 ± 11.0 ml/kg/h over 12 h; filled circles, patient 2 treated with 1.5 mg CBA/kg without CVVH; open circles, patient 2 treated with 2.2 mg CBA/kg with a delivered CVVH dose of 28.0 ± 3.7 ml/kg/h over 8 h. Both patients also received nebulized CMS (75 mg every 8 h) during sampling.