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Updated: May 26, 2026
Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Subtherapeutic initial β-lactam concentrations in select critically ill patients: association between augmented renal
Andrew A Udy1, Julie M Varghese2, Mahdi Altukroni3
1Department of Intensive Care Medicine, Herston, Brisbane, QLD, Australia; Burns, Trauma, and Critical Care Research Center, University of Queensland, Herston, Brisbane, QLD, Australia.
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.
Insights
High creatinine clearance (CLCR) in critically ill patients often leads to subtherapeutic β-lactam concentrations. This finding highlights the need to monitor renal function to ensure effective antibiotic dosing in the ICU.
Area of Science:
- Pharmacology
- Nephrology
- Critical Care Medicine
Background:
- β-Lactam antibiotics are crucial for empirical therapy in critical illness.
- Achieving adequate drug concentrations above the minimum inhibitory concentration (MIC) is vital for treatment success.
- Altered renal function in critically ill patients can compromise therapeutic drug levels.
Purpose of the Study:
- To investigate the relationship between renal function and β-lactam trough concentrations in critically ill patients.
- To determine if elevated creatinine clearance (CLCR) predicts subtherapeutic antibiotic levels.
Main Methods:
- Analysis of trough plasma β-lactam concentrations and concurrent 8-h creatinine clearance (CLCR) in critically ill patients.
- Drug concentrations measured by high-performance liquid chromatography and corrected for protein binding.
- Therapeutic levels defined as ≥ MIC and ≥ 4x MIC.
Main Results:
- In 58% of patients, trough concentrations were ≥ MIC, and in 31%, they were ≥ 4x MIC.
- Elevated CLCR (≥ 130 mL/min/1.73 m²) was associated with subtherapeutic β-lactam concentrations in 82% of cases (vs. MIC) and 72% (vs. 4x MIC).
- CLCR was a significant independent predictor of subtherapeutic antibiotic concentrations.
Conclusions:
- Elevated CLCR is a key predictor of subtherapeutic β-lactam levels in intensive care unit (ICU) patients.
- Monitoring CLCR is important for identifying critically ill patients at risk of inadequate antibiotic dosing.
- Optimizing β-lactam therapy in critical illness requires consideration of individual renal function.
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