title: Differences in pharmacokinetics and pharmacodynamics of colistimethate sodium (CMS) and colistin between three different CMS dosage regimens in a critically ill patient infected by a multidrug-resistant Acinetobacter baumannii.
abstract: Use of colistin has re-emerged for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria, but information on its pharmacokinetics and pharmacodynamics is limited, especially in critically ill patients. Recent data from pharmacokinetic/pharmacodynamic (PK/PD) population studies have suggested that this population could benefit from administration of higher than standard doses of colistimethate sodium (CMS), but the relationship between administration of incremental doses of CMS and corresponding PK/PD parameters as well as its efficacy and toxicity have not yet been investigated in a clinical setting. The objective was to study the PK/PD differences of CMS and colistin between three different CMS dosage regimens in the same critically ill patient. A critically ill patient with nosocomial pneumonia caused by a MDR Acinetobacter baumannii received incremental doses of CMS. During administration of the different CMS dosage regimens, CMS and colistin plasma concentrations were determined and PK/PD indexes were calculated. With administration of the highest CMS dose once daily (720 mg every 24h), the peak plasma concentration of CMS and colistin increased to 40.51 mg/L and 1.81 mg/L, respectively, and the AUC0-24/MIC of colistin was 184.41. This dosage regimen was efficacious, and no nephrotoxicity or neurotoxicity was observed. In conclusion, a higher and extended-interval CMS dosage made it possible to increase the exposure of CMS and colistin in a critically ill patient infected by a MDR A. baumannii and allowed a clinical and microbiological optimal response to be achieved without evidence of toxicity.
authors.affiliation: Pharmacy Department, Hospital del Mar-IMIM, Parc de Salut Mar, Universitat Autònoma de Barcelona, Paseo Marítimo 25-29, Barcelona, Spain.
authors.forename: Sònia
authors.initials: S
authors.lastname: Luque
authors.forename: Santiago
authors.initials: S
authors.lastname: Grau
authors.forename: Marta
authors.initials: M
authors.lastname: Valle
authors.forename: Luisa
authors.initials: L
authors.lastname: Sorlí
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Horcajada
authors.forename: Concha
authors.initials: C
authors.lastname: Segura
authors.forename: Francisco
authors.initials: F
authors.lastname: Alvarez-Lerma
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects*; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D003091:Colistin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D016638:Critical Illness; D003428:Cross Infection / Q000188:drug therapy / Q000382:microbiology; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D010949:Plasma / Q000737:chemistry; D018410:Pneumonia, Bacterial / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; C004691:colistinmethanesulfonic acid; D003091:Colistin
keywords: Colistin; Critical care; Dosage regimens; Pharmacodynamics; Pharmacokinetics; Polymyxins