Low flucloxacillin concentrations in a patient with central nervous system infection: the need for plasma and cerebrospinal fluid drug monitoring in the ICU

Abdul-Aziz, Mohd H., McDonald, Craig, McWhinney, Brett, Ungerer, Jacobus P. J., Lipman, Jeffrey and Roberts, Jason A. (2014) Low flucloxacillin concentrations in a patient with central nervous system infection: the need for plasma and cerebrospinal fluid drug monitoring in the ICU. Annals of Pharmacotherapy, 48 10: 1380-1384. doi:10.1177/1060028014540610


Author Abdul-Aziz, Mohd H.
McDonald, Craig
McWhinney, Brett
Ungerer, Jacobus P. J.
Lipman, Jeffrey
Roberts, Jason A.
Title Low flucloxacillin concentrations in a patient with central nervous system infection: the need for plasma and cerebrospinal fluid drug monitoring in the ICU
Journal name Annals of Pharmacotherapy   Check publisher's open access policy
ISSN 1542-6270
1060-0280
Publication date 2014-10
Year available 2014
Sub-type Article (original research)
DOI 10.1177/1060028014540610
Open Access Status
Volume 48
Issue 10
Start page 1380
End page 1384
Total pages 5
Place of publication Thousand Oaks, CA, United States
Publisher SAGE Publications
Collection year 2015
Language eng
Formatted abstract
Objective: To report the difficulty in achieving and maintaining target antibiotic exposure in critically ill patients with deep-seeded infections. Case Summary: 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). Discussion: 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.
Keyword β-lactams
Cerebrospinal fluid
Intensive care unit
Pharmacokinetics
Therapeutic drug monitoring
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
 
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