title: 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.
authors.affiliation: United States Army Institute of Surgical Research, Fort Sam Houston, San Antonio, Texas, USA Brooke Army Medical Center, Fort Sam Houston, San Antonio, Texas, USA kevin.s.akers.mil@mail.mil.
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Akers
authors.affiliation: United States Army Institute of Surgical Research, Fort Sam Houston, San Antonio, Texas, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Rowan
authors.affiliation: United States Army Institute of Surgical Research, Fort Sam Houston, San Antonio, Texas, USA.
authors.forename: Krista L
authors.initials: KL
authors.lastname: Niece
authors.affiliation: Brooke Army Medical Center, Fort Sam Houston, San Antonio, Texas, USA.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Stewart
authors.affiliation: Brooke Army Medical Center, Fort Sam Houston, San Antonio, Texas, USA Infectious Diseases Clinical Research Program, Bethesda, Maryland, USA.
authors.forename: Katrin
authors.initials: K
authors.lastname: Mende
authors.affiliation: University of the Incarnate Word, Feik School of Pharmacy, San Antonio, Texas, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Cota
authors.affiliation: Brooke Army Medical Center, Fort Sam Houston, San Antonio, Texas, USA.
authors.forename: Clinton K
authors.initials: CK
authors.lastname: Murray
authors.affiliation: United States Army Institute of Surgical Research, Fort Sam Houston, San Antonio, Texas, USA Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Chung
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy*; D040981:Acinetobacter baumannii / Q000187:drug effects; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002053:Burn Units; D002056:Burns / Q000382:microbiology*; D003091:Colistin / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D024901:Drug Resistance, Multiple, Bacterial; D006440:Hemofiltration; D006801:Humans; D008297:Male
chemical_list: D000900:Anti-Bacterial Agents; D003091:Colistin