title: Standard dosing of piperacillin and meropenem fail to achieve adequate plasma concentrations in ICU patients.
abstract: BACKGROUND
  Controversies remain regarding optimal dosing and the need for plasma concentration measurements when treating intensive care patients with beta-lactam antibiotics.
  
  
  METHODS
  We studied ICU patients treated with either antibiotic, excluding patients on renal replacement therapy. Antibiotic concentrations were measured at the mid and end of the dosing interval, and repeated after 2-3 days when feasible. Glomerular filtration rate (GFR) was estimated from plasma creatinine and cystatin C, GFR calculated from cystatin C (eGFR) and measured creatinine clearance (CrCl). Measured concentrations were compared to the clinical susceptible breakpoints for Pseudomonas aeruginosa, 16 and 2 mg/l for piperacillin and meropenem respectively.
  
  
  RESULTS
  We analysed 33 and 31 paired samples from 20 and 19 patients treated with piperacillin-tazobactam and meropenem respectively. Antibiotic concentrations at the mid and end of the dosing interval were for piperacillin, 27.0 (14.7-52.9) and 8.6 (2.7-30.3); and for meropenem, 7.5 (4.7-10.2) and 2.4 (1.0-3.5). All values median (interquartile range) and concentrations in mg/l. The percentage of measured concentrations below the breakpoint at the mid and end of the dosing interval were for piperacillin, 27% and 61%; and for meropenem, 6% and 48%. Lower estimates of GFR were associated with higher concentrations but concentrations varied greatly between patients with similar GFR. The correlation with terminal concentration half-life was similar for eGFR and CrCl.
  
  
  CONCLUSIONS
  With standard doses of meropenem and piperacillin-tazobactam, plasma concentrations in ICU patients vary > 10-fold and are suboptimal in a significant percentage of patients. The variation is large also between patients with similar renal function.
authors.affiliation: Function Perioperative Medicine and Intensive Care, Karolinska University hospital Solna, Stockholm, Sweden. johan.petersson@karolinska.se.|Section of Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. johan.petersson@karolinska.se.
authors.forename: J
authors.initials: J
authors.lastname: Petersson
authors.affiliation: Clinical Microbiology, Karolinska University Hospital Solna, Stockholm, Sweden.|Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: C G
authors.initials: CG
authors.lastname: Giske
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.|Clinical Pharmacology, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Eliasson
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D010878:Piperacillin / Q000008:administration & dosage / Q000097:blood; D000077725:Piperacillin, Tazobactam Drug Combination; D011446:Prospective Studies; D013845:Thienamycins / Q000008:administration & dosage* / Q000097:blood
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D000077731:Meropenem; D010878:Piperacillin