title: Low flucloxacillin concentrations in a patient with central nervous system infection: the need for plasma and cerebrospinal fluid drug monitoring in the ICU.
abstract: OBJECTIVE
  To report the difficulty in achieving and maintaining target antibiotic exposure in critically ill patients with deep-seeded infections.
  
  
  METHODS
  We present a case of a 36-year-old man who was admitted to the intensive care unit with diffuse central nervous system and peripheral methicillin-sensitive Staphylococcus aureus infection (minimum inhibitory concentration; MIC, 1 µg/mL). Owing to the complicated nature of the infection, sequential concentrations of free flucloxacillin were measured in plasma and cerebrospinal fluid (CSF) and used to direct antibiotic dosing. Unsurprisingly, the trough plasma concentrations of flucloxacillin were below the MIC (0.2-0.4 µg/mL), and the corresponding CSF concentrations were undetectable (<0.1 µg/mL) with standard intermittent bolus dosing of 2 g every 4 hours. By administering flucloxacillin by continuous infusion (CI) and increasing the dose to 20 g daily, the plasma (2.2-5.7 µg/mL) and CSF (0.1 µg/mL) levels were increased, albeit lower than the predefined targets (plasma, 40 µg/mL; CSF, 4 µg/mL).
  
  
  CONCLUSIONS
  The presence of physiological changes associated with critical illness-namely, hypoalbuminemia and augmented renal clearance-may significantly alter antibiotic pharmacokinetics, and this phenomenon may lead to suboptimal antibiotic exposure if they are not accounted for. This case also highlights the value of applying CI in such patient groups and demonstrates the significance of monitoring plasma and CSF drug concentrations in optimizing antibiotic delivery.
  
  
  CONCLUSIONS
  Future research should aim to evaluate the utility of such drug monitoring with regard to patient outcomes and cost-effectiveness.
authors.affiliation: The University of Queensland, Brisbane, Australia mohd.abdulaziz1@uqconnect.edu.au.
authors.forename: Mohd H
authors.initials: MH
authors.lastname: Abdul-Aziz
authors.affiliation: Royal Brisbane and Women's Hospital, Brisbane, Australia.
authors.forename: Craig
authors.initials: C
authors.lastname: McDonald
authors.affiliation: Queensland Pathology, Brisbane, Queensland, Australia.
authors.forename: Brett
authors.initials: B
authors.lastname: McWhinney
authors.affiliation: Queensland Pathology, Brisbane, Queensland, Australia.
authors.forename: Jacobus P J
authors.initials: JP
authors.lastname: Ungerer
authors.affiliation: The University of Queensland, Brisbane, Australia Royal Brisbane and Women's Hospital, Brisbane, Australia.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
authors.affiliation: The University of Queensland, Brisbane, Australia Royal Brisbane and Women's Hospital, Brisbane, Australia.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood* / Q000134:cerebrospinal fluid*; D020806:Central Nervous System Bacterial Infections / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D016638:Critical Illness; D016903:Drug Monitoring; D005436:Floxacillin / Q000008:administration & dosage / Q000097:blood* / Q000134:cerebrospinal fluid*; D006801:Humans; D007262:Infusions, Intravenous; D007362:Intensive Care Units; D008297:Male; D008826:Microbial Sensitivity Tests; D013203:Staphylococcal Infections / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D005436:Floxacillin
keywords: cerebrospinal fluid; intensive care unit; pharmacokinetics; therapeutic drug monitoring; β-lactams