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Meropenem pharmacokinetic/pharmacodynamic target attainment and clinical response in ICU patients: A prospective
Elin Helset1, Vesa Cheng2,3, Hilde Sporsem4
1Division of Emergencies and Critical care, Oslo University Hospital, Oslo, Norway.
Background:
Several studies report lack of meropenem pharmacokinetic/pharmacodynamic (PK/PD) target attainment (TA) and risk of therapeutic failure with intermittent bolus infusions in intensive care unit (ICU) patients. The aim of this study was to describe meropenem TA in an ICU population and the clinical response in the first 72 h after therapy initiation.
Methods:
A prospective observational study of ICU patients ≥18 years was conducted from 2014 to 2017. Patients with normal renal clearance (NRC) and augmented renal clearance (ARC) and patients on continuous renal replacement therapy (CRRT) were included. Meropenem was administered as intermittent bolus infusions, mainly at a dose of 1 g q6h. Peak, mid, and trough levels were sampled at 24, 48, and 72 h after therapy initiation. TA was defined as 100% T > 4× MIC or trough concentration above 4× MIC. Meropenem PK was estimated using traditional calculation methods and population pharmacokinetic modeling (P-metrics®). Clinical response was evaluated by change in C-reactive protein (CRP), Sequential Organ Failure Assessment (SOFA) score, leukocyte count, and defervescence.
Results:
Eighty-seven patients were included, with a median Simplified Acute Physiology (SAPS) II score 37 and 90 days mortality rate of 32%. Median TA was 100% for all groups except for the ARC group with 45.5%. Median CRP fell from 175 (interquartile range [IQR], 88-257) to 70 (IQR, 30-114) (p < .001) in the total population. A reduction in SOFA score was observed only in the non-CRRT groups (p < .001).
Conclusion:
Intermittent meropenem bolus infusion q6h gives satisfactory TA in an ICU population with variable renal function and CRRT modality, except for ARC patients. No consistent relationship between TA and clinical endpoints were observed.
Insights
Intermittent meropenem infusions achieved target attainment in most intensive care unit patients, but not those with augmented renal clearance. Clinical response varied, with no clear link to meropenem pharmacokinetic/pharmacodynamic targets.
Area of Science:
- Pharmacology
- Critical Care Medicine
- Infectious Diseases
Background:
- Meropenem intermittent bolus infusions may not achieve pharmacokinetic/pharmacodynamic (PK/PD) targets in intensive care unit (ICU) patients.
- This can lead to a risk of therapeutic failure in critically ill patients.
Purpose of the Study:
- To evaluate meropenem target attainment (TA) in ICU patients with varying renal function.
- To assess the clinical response within 72 hours of meropenem therapy initiation.
Main Methods:
- Prospective observational study of 87 ICU patients (≥18 years) from 2014-2017.
- Included patients with normal renal clearance (NRC), augmented renal clearance (ARC), and continuous renal replacement therapy (CRRT).
- Meropenem administered as 1g q6h intermittent bolus infusions; PK/PD targets assessed via drug levels and modeling. Clinical response evaluated using CRP, SOFA score, leukocyte count, and defervescence.
Main Results:
- Median TA was 100% for NRC and CRRT groups, but only 45.5% for the ARC group.
- Significant reduction in C-reactive protein (CRP) observed in the total population (p < .001).
- Sequential Organ Failure Assessment (SOFA) score improved only in non-CRRT groups (p < .001).
Conclusions:
- Intermittent meropenem bolus infusions achieve satisfactory target attainment in most ICU patients, except those with ARC.
- No consistent correlation was found between meropenem target attainment and clinical outcomes.
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