Subtherapeutic Initial beta-Lactam Concentrations in Select Critically Ill Patients Association Between Augmented Renal Clearance and Low Trough Drug Concentrations

Udy, Andrew A., Varghese, Julie M., Altukroni, Mahdi, Briscoe, Scott, McWhinney, Brett C., Ungerer, Jacobus P., Lipman, Jeffrey and Roberts, Jason A. (2012) Subtherapeutic Initial beta-Lactam Concentrations in Select Critically Ill Patients Association Between Augmented Renal Clearance and Low Trough Drug Concentrations. Chest, 142 1: 30-39. doi:10.1378/chest.11-1671


Author Udy, Andrew A.
Varghese, Julie M.
Altukroni, Mahdi
Briscoe, Scott
McWhinney, Brett C.
Ungerer, Jacobus P.
Lipman, Jeffrey
Roberts, Jason A.
Title Subtherapeutic Initial beta-Lactam Concentrations in Select Critically Ill Patients Association Between Augmented Renal Clearance and Low Trough Drug Concentrations
Formatted title
Subtherapeutic initial β-lactam concentrations in select critically Ill patients: Association between augmented renal clearance and low trough drug concentrations
Journal name Chest   Check publisher's open access policy
ISSN 0012-3692
1931-3543
Publication date 2012-07-01
Sub-type Article (original research)
DOI 10.1378/chest.11-1671
Volume 142
Issue 1
Start page 30
End page 39
Total pages 10
Place of publication Northbrook, IL, United States
Publisher American College of Chest Physicians
Collection year 2013
Language eng
Formatted abstract
Background:
β-Lactams are routinely used as empirical therapy in critical illness, with extended concentrations above the minimum inhibitory concentration (MIC) of the infecting organism required for effective treatment. Changes in renal function in this setting can significantly impact the probability of achieving such targets.

Methods:
Analysis was made of trough plasma drug concentrations obtained via therapeutic drug monitoring, compared with renal function, in critically ill patients receiving empirical β-lactam therapy. Drug concentrations were measured by means of high-performance liquid chromatography and corrected for protein binding. Therapeutic levels were defined as greater than or equal to MIC and greater than or equal to four times MIC (maximum bacterial eradication), respectively. Renal function was assessed by means of an 8-h creatinine clearance (CLCR).

Results:
Fifty-two concurrent trough concentrations and CLCR measures were used in analysis. Piperacillin was the most frequent β-lactam prescribed (48%), whereas empirical cover and Staphylococcus species were the most common indications for therapy (62%). Most patients were mechanically ventilated on the day of study (85%), although only 25% were receiving vasopressors. In only 58% (n = 30) was the trough drug concentration greater than or equal to MIC, falling to 31% (n = 16) when using four times MIC as the target. CLCR values ≥ 130 mL/min/1.73 m2 were associated with trough concentrations less than MIC in 82% (P < .001) and less than four times MIC in 72% (P < .001). CLCR remained a significant predictor of subtherapeutic concentrations in multivariate analysis.

Conclusion:

Elevated CLCR appears to be an important predictor of subtherapeutic β-lactam concentrations and suggests an important role in identifying such patients in the ICU.
Keyword Intensive-care units
Organ blood-flow
Creatinine clearance
Septic shock
Population pharmacokinetics
Pseudomonas-aeruginosa
Hyperdynamic sepsis
Dosing strategy
Pharmacodynamics
Ceftazidime
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 129 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 139 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Fri, 03 Aug 2012, 00:35:36 EST by Matthew Lamb on behalf of School of Medicine