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Pharmacokinetics of meropenem in critically ill patients in Saudi Arabia
Abdullah Alsultan1,2, Shereen A Dasuqi3, Fadi Aljamaan4,5
1Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Background:
Meropenem is commonly used in the ICU to treat gram-negative infections. Due to various pathophysiological changes, critically ill patients are at higher risk of having subtherapeutic concentrations and hence have a higher risk of treatment failure-especially in regions where gram-negative drug resistance is increasing, such as Saudi Arabia. No studies have evaluated the pharmacokinetics of meropenem in critically ill patients in Saudi Arabia. Our primary objective is to assess the percentage of patients achieving the therapeutic target for meropenem.
Methods:
This prospective observational study was conducted in the ICUs of King Khalid University Hospital. Patient were included if >18 years-of-age and received meropenem for a clinically suspected or proven bacterial infection. The primary outcome was to assess the percentage of patients who achieved the pharmacokinetic/pharmacodynamic (PKPD) therapeutic target of a free trough concentration four times the MIC. The secondary outcome was to estimate the pharmacokinetics of meropenem. Pharmacokinetic analysis was performed using Monolix Suite 2020R1 (Lixoft, France).
Results:
Trough concentrations were highly variable and ranged from <0.5 µg/mL to 39 µg/mL, with a mean ± SD trough concentration of 8.5 ± 8 µg/mL. Only 46% of patients achieved the therapeutic target. The only significant predictor of failing to achieve the PKPD target was augmented renal clearance.
Conclusion:
In conclusion, more than half of our patients did not achieve the PKPD target. Thus, there is a need for better dosing strategies of meropenem in critically ill patients in Saudi Arabia such as extended and continuous infusion.
Insights
Meropenem dosing in Saudi ICUs often fails to reach therapeutic targets. Augmented renal clearance was linked to treatment failure, suggesting a need for adjusted dosing strategies like continuous infusions.
Area of Science:
- Pharmacology
- Critical Care Medicine
- Infectious Diseases
Background:
- Meropenem is crucial for treating Gram-negative infections in intensive care units (ICUs).
- Critically ill patients face higher risks of subtherapeutic meropenem concentrations and treatment failure, particularly in regions with increasing Gram-negative resistance like Saudi Arabia.
- Limited pharmacokinetic data exists for meropenem in Saudi critically ill populations.
Purpose of the Study:
- To determine the percentage of critically ill patients in Saudi Arabia achieving the meropenem pharmacokinetic/pharmacodynamic (PKPD) therapeutic target.
- To investigate the pharmacokinetics of meropenem in this patient population.
Main Methods:
- A prospective observational study was conducted in the ICUs of King Khalid University Hospital.
- Patients over 18 receiving meropenem for bacterial infections were included.
- The primary outcome was achieving a free trough meropenem concentration four times the minimum inhibitory concentration (MIC); pharmacokinetic analysis used Monolix Suite.
Main Results:
- Meropenem trough concentrations exhibited high variability (0.5–39 µg/mL), with a mean of 8.5 ± 8 µg/mL.
- Only 46% of patients achieved the defined PKPD therapeutic target.
- Augmented renal clearance was the sole significant predictor of failing to achieve the target concentration.
Conclusions:
- Over half of the critically ill patients in this Saudi Arabian cohort did not achieve the meropenem PKPD target.
- Current meropenem dosing strategies may be inadequate for critically ill patients in Saudi Arabia.
- Optimized dosing strategies, such as extended or continuous infusions, are recommended to improve therapeutic outcomes.
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