title: Colistin serum concentrations after intravenous administration in critically ill patients with serious multidrug-resistant, gram-negative bacilli infections: a prospective, open-label, uncontrolled study.
abstract: BACKGROUND
  The emergence of multidrug-resistant nosocomial pathogens, such as Pseudomonas aeruginosa and Acinetobacter baumannii, has led to the revival of the systemic use of antimicrobial agent colistin in critically ill patients, but only limited data are available to define its pharmacokinetic profile in these patients.
  
  
  OBJECTIVE
  The aim of this study was to assess steady-state serum concentrations of colistin after i.v. administration of colistin methanesulfonate (CMS) in critically ill patients with stable kidney function.
  
  
  METHODS
  This prospective, open-label, uncontrolled study was conducted at 2 intensive care units in the Athens Trauma Hospital, KAT, Athens, Greece. Adult patients were nonconsecutively enrolled if they were critically ill and had stable kidney function (<0.5 mg/dL change in serum creatinine prior to and until the day of sample collection) and had been receiving CMS as part of a treatment regimen for sepsis irrespective of site of infection with multidrug-resistant, gram-negative bacilli. After i.v. administration of 225-mg CMS (with the exception of 1 patient who received 150 mg) every 8 or 12 hours for at least 2 days, blood samples were collected just before and at 10 minutes and 1, 2, 4, 6, and 8 hours after i.v. infusion (duration, 30 minutes) of the colistin dose on the sampling day.
  
  
  RESULTS
  Fourteen nonconsecutive patients were enrolled in the study (13 male, 1 female; mean [SD] age, 62.0 [19.2] years; mean [SD] estimated weight, 72.5 [8.5] kg; mean [SD] Acute Physiology And Chronic Health Evaluation II score on admission, 17.1 [6.0]). At steady state, mean (SD) colistin maximum and minimum concentrations were 2.93 (1.24) and 1.03 (0.44) mg/L, respectively, while mean (SD) apparent total body clearance, apparent volume of distribution, and t(1/2) were 13.6 (5.8) L/h, 139.9 (60.3) L, and 7.4 (1.7) hours, respectively. Colistin-related nephrotoxicity was not observed in the study patients.
  
  
  CONCLUSIONS
  CMS dosage regimens administered to these critically ill adult patients were associated with suboptimal Cmax/MIC ratios for many strains of gram-negative bacilli currently reported as sensitive (MIC, < or = 2 microg/mL).
authors.affiliation: Intensive Care Unit B, KAT Hospital, Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Markou
authors.forename: Sophia L
authors.initials: SL
authors.lastname: Markantonis
authors.forename: Efthimios
authors.initials: E
authors.lastname: Dimitrakis
authors.forename: Dimitris
authors.initials: D
authors.lastname: Panidis
authors.forename: Eleni
authors.initials: E
authors.lastname: Boutzouka
authors.forename: Stylianos
authors.initials: S
authors.lastname: Karatzas
authors.forename: Petros
authors.initials: P
authors.lastname: Rafailidis
authors.forename: Haralampos
authors.initials: H
authors.lastname: Apostolakos
authors.forename: George
authors.initials: G
authors.lastname: Baltopoulos
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy*; D040981:Acinetobacter baumannii; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000097:blood* / Q000627:therapeutic use; D003091:Colistin / Q000097:blood* / Q000627:therapeutic use; D016638:Critical Illness; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000188:drug therapy*; D018805:Sepsis / Q000188:drug therapy
chemical_list: D000900:Anti-Bacterial Agents; D003091:Colistin