title: Colistin loading dose: evaluation of the published pharmacokinetic and clinical data.
abstract: Colistin (polymyxin E) has been widely used since the beginning of the century as a last-option antibiotic for the treatment of patients with multidrug-resistant and extensively-drug resistant bacterial infections. However, colistin dosing is troublesome because each batch of the drug contains a mixture of components and because it is administered as the inactive pro-drug colistimethate sodium (CMS), which has different pharmacokinetic (PK) properties from the active drug. Significant inter-individual and intra-individual variability in colistin plasma concentrations have been observed in all available studies. Low plasma concentrations of the drug during the first hours from initiation of administration suggested that a loading dose would be appropriate. However, other PK studies challenge this approach. Clinical data from randomised controlled trials are not available, whilst data from observational studies do not support higher effectiveness of a loading dose. In this review, we summarise the available data regarding the administration of a loading dose and discuss the issues surrounding the potential advantages and disadvantages as well as the context within which such an approach could be beneficial to patients.
authors.affiliation: Alfa Institute of Biomedical Sciences (AIBS), Athens, Greece; Department of Internal Medicine-Infectious Diseases, IASO General Hospital, IASO Group, Athens, Greece.
authors.forename: Konstantinos Z
authors.initials: KZ
authors.lastname: Vardakas
authors.affiliation: Department of Anesthesiology, Central Clinic, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Rellos
authors.affiliation: Alfa Institute of Biomedical Sciences (AIBS), Athens, Greece; Department of Internal Medicine-Infectious Diseases, IASO General Hospital, IASO Group, Athens, Greece.
authors.forename: Nikolaos A
authors.initials: NA
authors.lastname: Triarides
authors.affiliation: Alfa Institute of Biomedical Sciences (AIBS), Athens, Greece; Department of Internal Medicine-Infectious Diseases, IASO General Hospital, IASO Group, Athens, Greece; Tufts University School of Medicine, Boston, MA, USA. Electronic address: m.falagas@aibs.gr.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Falagas
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003091:Colistin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D064887:Observational Studies as Topic; D010949:Plasma / Q000737:chemistry; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D003091:Colistin
keywords: Acinetobacter; Gram-negative; Klebsiella; Polymyxin; Pseudomonas