title: Can changes in renal function predict variations in β-lactam concentrations in septic patients?
abstract: This study investigated whether variations in creatinine clearance (CLCr) are correlated with changes in β-lactam concentrations or pharmacokinetics in septic patients. Data for 56 adult patients admitted to the ICU in whom routine therapeutic drug monitoring (TDM) of broad-spectrum β-lactams (ceftazidime, cefepime, piperacillin or meropenem) was performed were reviewed. Patients were included if they had at least two TDM during their ICU stay for the same antibiotic and were not concomitantly treated with any extracorporeal replacement therapy. Serum drug concentrations were measured by HPLC-UV. Antibiotic pharmacokinetics were calculated using a one-compartment model and the percentage of time spent above four times the MIC (%T>4×MIC) for Pseudomonas aeruginosa and the antibiotic clearance (ATB-CL) were obtained. CLCr was measured on the same day as the TDM using 24-h urine collection. The %T>4×MIC and ATB-CL were significantly correlated with CLCr at the first (r=-0.41, P=0.002; r=0.56, P<0.001, respectively) and second (r=-0.61, P<0.001; r=0.63, P<0.001, respectively) TDM. However, changes in ATB-CL were only weakly correlated with changes in CLCr (r=0.34, P=0.01). The proportion of patients with insufficient β-lactam concentrations at the first and second TDM were 39% and 30%, respectively, and increased proportionally to CLCr. Although CLCr was significantly correlated with concentrations and clearance of broad-spectrum β-lactams, changes in CLCr did not reliably predict variations in drug pharmacokinetics/pharmacodynamics. Routine TDM should be considered to adapt β-lactam doses in this setting.
authors.affiliation: Department of Intensive Care, Hôpital Erasme, Université Libre de Bruxelles, route de Lennik 808, 1070 Brussels, Belgium.
authors.forename: Giuseppe Stefano
authors.initials: GS
authors.lastname: Casu
authors.forename: Maya
authors.initials: M
authors.lastname: Hites
authors.forename: Frederique
authors.initials: F
authors.lastname: Jacobs
authors.forename: Frederic
authors.initials: F
authors.lastname: Cotton
authors.forename: Fleur
authors.initials: F
authors.lastname: Wolff
authors.forename: Marjorie
authors.initials: M
authors.lastname: Beumier
authors.forename: Daniel
authors.initials: D
authors.lastname: De Backer
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vincent
authors.forename: Fabio Silvio
authors.initials: FS
authors.lastname: Taccone
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007668:Kidney / Q000502:physiology*; D007677:Kidney Function Tests; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011552:Pseudomonas Infections / Q000188:drug therapy; D018805:Sepsis / Q000188:drug therapy*; D044967:Serum / Q000737:chemistry; D047090:beta-Lactams / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D003404:Creatinine
keywords: Creatinine clearance; Critically ill; Pharmacokinetics; Sepsis; β-Lactams