Τίτλος:
Colistin serum concentrations after intravenous administration in critically ill patients with serious multidrug-resistant, gram-negative bacilli infections: A prospective, open-label, uncontrolled study
Περίληψη:
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 IV 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 IV 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 IV 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 t1/2 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. Conclusion: 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, ≤2 μg/mL). © 2008 Excerpta Medica Inc. All rights reserved.
Συγγραφείς:
Markou, N.
Markantonis, S.L.
Dimitrakis, E.
Panidis, D.
Boutzouka, E.
Karatzas, S.
Rafailidis, P.
Apostolakos, H.
Baltopoulos, G.
Λέξεις-κλειδιά:
colistimethate, Acinetobacter baumannii; adult; aged; area under the curve; article; clinical article; clinical trial; critically ill patient; drug blood level; drug clearance; drug distribution; drug effect; drug efficacy; drug half life; female; Gram negative infection; Greece; human; male; multidrug resistance; nephrotoxicity; open study; prospective study; Pseudomonas aeruginosa; steady state, Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Humans; Infusions, Intravenous; Intensive Care Units; Male; Middle Aged; Prospective Studies; Pseudomonas Infections; Sepsis
