Pharmacokinetics of meropenem in critically ill patients in Saudi Arabia

Abdullah Alsultan; Shereen A Dasuqi; Fadi Aljamaan; Rasha A Omran; Saeed Ali Syed; Turki AlJaloud; Abdullah AlAhmadi; Saeed Alqahtani; Mohammed A Hamad

doi:10.1016/j.jsps.2021.09.017

Pharmacokinetics of meropenem in critically ill patients in Saudi Arabia

Saudi Pharm J. 2021 Nov;29(11):1272-1277. doi: 10.1016/j.jsps.2021.09.017. Epub 2021 Oct 8.

Authors

Abdullah Alsultan^{1

2}, Shereen A Dasuqi³, Fadi Aljamaan^{4

5}, Rasha A Omran⁶, Saeed Ali Syed⁷, Turki AlJaloud¹, Abdullah AlAhmadi¹, Saeed Alqahtani^{1

2}, Mohammed A Hamad⁴

Affiliations

¹ Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
² Clinical Pharmacokinetics and Pharmacodynamics Unit, King Saud University Medical City, Riyadh, Saudi Arabia.
³ Department of Pharmacy, King Khalid University Hospital, King Saudi University Medical City, Riyadh, Saudi Arabia.
⁴ Critical Care Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
⁵ Critical Care Department, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia.
⁶ Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, University of Jordan, Amman Jordan.
⁷ Department of Pharmaceutical; Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Abstract

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.

Keywords: ICU; Meropenem; Pharmacokinetics; Saudi Arabia; Sepsis.