Evaluation of PK/PD Properties of Recommended Doses of Meropenem in Critically Ill Patients with Augmented Renal Clearance, A Prospective Observational Study Meropenem Dosing in Augmented Renal Clearance
Iranian Journal of Pharmaceutical Sciences,
Vol. 18 No. 4 (2022),
1 Mehr 2022
,
Page 326-335
https://doi.org/10.22037/ijps.v18.43102
Abstract
Augmented renal clearance (ARC) is a common phenomenon among critically ill patients and creates sub-therapeutic concentrations of antibiotics, due to an increase in renal clearance of them. We evaluated the Pharmacokinetic and Pharmacodynamic (PK/PD) properties of recommended doses of meropenem in critically ill patients with ARC. Adult critically ill patients with confirmed ARC, based on 12-hour Creatinine Clearance (CrCl) (≥130 ml/min/1.73 m2), who received standard doses of meropenem enrolled in this study. Two blood samples were gathered from each participant, at the steady-state time, to determination of peak and trough concentrations. Serum concentrations of meropenem were measured by high-performance liquid chromatography (HPLC) with an ultra-violet (UV) detector. From eighteen paired samples (peak and trough concentrations) that were obtained from 16 critically ill patients, peak concentrations were significantly lower in group 1 (received meropenem 1g every 8 hours) than in group 2 (received meropenem 2g every 8 hours) (mean ±SD, 5.95 ±3.39 µg/mL vs. 11.93± 4.18 µg/mL, respectively, p=0.005). Trough concentrations were sub-threshold (< 2 µg/mL) in 10 patients of group 1 (83.3%) and 3 patients of group 2 (50%). ft > MIC ≥ 50% was achieved in 83.3% of patients in both groups whereas 16.6% of patients of group 1 and 33.3% of patients of group 2 had ft> MIC= 100%. Augmented renal clearance is an essential cause of sub-therapeutic concentrations of meropenem in critically ill patients, and higher than the recommended doses of meropenem administered as an intermittent infusion may be necessary to achieve the PD targets and improve efficacy.
- Augmented renal clearance
- Critically ill patients
- High-performance liquid chromatography
- HPLC
- Meropenem
- Pharmacodynamic
- Pharmacokinetic
How to Cite
References
. Udy AA, Jarrett P, Lassig-Smith M, Stuart J, Starr T, Dunlop R, et al. Augmented renal clearance in traumatic brain injury: a single-center observational study of atrial natriuretic peptide, cardiac output, and creatinine clearance. Journal of neurotrauma. 2017;34(1):137-44.
. Baptista JP, Martins PJ, Marques M, Pimentel JM. Prevalence and Risk Factors for Augmented Renal Clearance in a Population of Critically Ill Patients. Journal of Intensive Care Medicine. 2020;35(10):1044-52.
. Mahmoud SH, Shen C. Augmented renal clearance in critical illness: an important consideration in drug dosing. Pharmaceutics. 2017;9(3):36.
. Ruiz S, Minville V, Asehnoune K, Virtos M, Georges B, Fourcade O, et al. Screening of patients with augmented renal clearance in ICU: taking into account the CKD-EPI equation, the age, and the cause of admission. Annals of intensive care. 2015;5(1):49.
. Mulder MB, Eidelson SA, Sussman MS, Schulman CI, Lineen EB, Iyenger RS, et al. Risk Factors and Clinical Outcomes Associated With Augmented Renal Clearance in Trauma Patients. Journal of Surgical Research. 2019;244:477-83.
. Claus BO, Hoste EA, Colpaert K, Robays H, Decruyenaere J, De Waele JJ. Augmented renal clearance is a common finding with worse clinical outcome in critically ill patients receiving antimicrobial therapy. Journal of critical care. 2013;28(5):695-700.
. Cook AM, Hatton‐Kolpek J. Augmented renal clearance. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2019;39(3):346-54.
. Carrie C, Bentejac M, Cottenceau V, Masson F, Petit L, Cochard J-F, et al. Association between augmented renal clearance and clinical failure of antibiotic treatment in brain-injured patients with ventilator-acquired pneumonia: a preliminary study. Anaesthesia Critical Care & Pain Medicine. 2018;37(1):35-41.
. Conil J-M, Georges B, Mimoz O, Dieye E, Ruiz S, Cougot P, et al. Influence of renal function on trough serum concentrations of piperacillin in intensive care unit patients. Intensive care medicine. 2006;32(12):2063-6.
. De Waele JJ, Lipman J, Akova M, Bassetti M, Dimopoulos G, Kaukonen M, et al. Risk factors for target non-attainment during empirical treatment with β-lactam antibiotics in critically ill patients. Intensive care medicine. 2014;40(9):1340-51.
. Wu C-C, Tai C-H, Liao W-Y, Wang C-C, Kuo C-H, Lin S-W, et al. Augmented renal clearance is associated with inadequate antibiotic pharmacokinetic/pharmacodynamic target in Asian ICU population: a prospective observational study. Infection and drug resistance. 2019;12:2531.
. Abdul-Aziz MH, Alffenaar J-WC, Bassetti M, Bracht H, Dimopoulos G, Marriott D, et al. Antimicrobial therapeutic drug monitoring in critically ill adult patients: a Position Paper#. Intensive Care Medicine. 2020;46(6):1127-53.
. Kees MG, Minichmayr IK, Moritz S, Beck S, Wicha SG, Kees F, et al. Population pharmacokinetics of meropenem during continuous infusion in surgical ICU patients. Journal of clinical pharmacology. 2016;56(3):307-15.
. Nicolau DP. Pharmacokinetic and pharmacodynamic properties of meropenem. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2008;47 Suppl 1:S32-40.
. Taccone FS, Laterre P-F, Dugernier T, Spapen H, Delattre I, Wittebole X, et al. Insufficient β-lactam concentrations in the early phase of severe sepsis and septic shock. Critical Care. 2010;14(4):R126.
. Jaruratanasirikul S, Sriwiriyajan S. Comparison of the pharmacodynamics of meropenem in healthy volunteers following administration by intermittent infusion or bolus injection. The Journal of antimicrobial chemotherapy. 2003;52(3):518-21.
. Yu Z, Pang X, Wu X, Shan C, Jiang S. Clinical outcomes of prolonged infusion (extended infusion or continuous infusion) versus intermittent bolus of meropenem in severe infection: A meta-analysis. PloS one. 2018;13(7).
. Craig WA. Basic pharmacodynamics of antibacterials with clinical applications to the use of β-lactams, glycopeptides, and linezolid. Infectious Disease Clinics. 2003;17(3):479-501.
. Udy AA, Roberts JA, Shorr AF, Boots RJ, Lipman J. Augmented renal clearance in septic and traumatized patients with normal plasma creatinine concentrations: identifying at-risk patients. Critical Care. 2013;17(1):R35.
. Elkhaïli H, Niedergang S, Pompei D, Linger L, Leveque D, Jehl F. High-performance liquid chromatographic assay for meropenem in serum. Journal of Chromatography B: Biomedical Sciences and Applications. 1996;686(1):19-26.
. Carlier M, Carrette S, Roberts JA, Stove V, Verstraete A, Hoste E, et al. Meropenem and piperacillin/tazobactam prescribing in critically ill patients: does augmented renal clearance affect pharmacokinetic/pharmacodynamic target attainment when extended infusions are used? Critical care. 2013;17(3):R84.
. Ehmann L, Zoller M, Minichmayr IK, Scharf C, Maier B, Schmitt MV, et al. Role of renal function in risk assessment of target non-attainment after standard dosing of meropenem in critically ill patients: a prospective observational study. Critical care. 2017;21(1):263.
. Roberts JA, Paul SK, Akova M, Bassetti M, De Waele JJ, Dimopoulos G, et al. DALI: Defining Antibiotic Levels in Intensive Care Unit Patients: Are Current β-Lactam Antibiotic Doses Sufficient for Critically Ill Patients? Clinical Infectious Diseases. 2014;58(8):1072-83.
. Li C, Du X, Kuti JL, Nicolau DP. Clinical Pharmacodynamics of Meropenem in Patients with Lower Respiratory Tract Infections. Antimicrobial Agents and Chemotherapy. 2007;51(5):1725-30.
. McKinnon PS, Paladino JA, Schentag JJ. Evaluation of area under the inhibitory curve (AUIC) and time above the minimum inhibitory concentration (T>MIC) as predictors of outcome for cefepime and ceftazidime in serious bacterial infections. International Journal of Antimicrobial Agents. 2008;31(4):345-51.
. Wiseman LR, Wagstaff AJ, Brogden RN, Bryson HM. Meropenem. Drugs. 1995;50(1):73-101.
. Mattioli F, Fucile C, Del Bono V, Marini V, Parisini A, Molin A, et al. Population pharmacokinetics and probability of target attainment of meropenem in critically ill patients. European journal of clinical pharmacology. 2016;72(7):839-48.
. Gonçalves-Pereira J, Póvoa P. Antibiotics in critically ill patients: a systematic review of the pharmacokinetics of β-lactams. Critical Care. 2011;15(5):R206.
. Petersson J, Giske C, Eliasson E. Standard dosing of piperacillin and meropenem fail to achieve adequate plasma concentrations in ICU patients. Acta Anaesthesiologica Scandinavica. 2016;60(10):1425-36.
. Tröger U, Drust A, Martens-Lobenhoffer J, Tanev I, Braun-Dullaeus RC, Bode-Böger SM. Decreased meropenem levels in Intensive Care Unit patients with augmented renal clearance: benefit of therapeutic drug monitoring. International Journal of Antimicrobial Agents. 2012;40(4):370-2.
. Kothekar AT, Divatia JV, Myatra SN, Patil A, Krishnamurthy MN, Maheshwarappa HM, et al. Clinical pharmacokinetics of 3-h extended infusion of meropenem in adult patients with severe sepsis and septic shock: implications for empirical therapy against Gram-negative bacteria. Annals of Intensive Care. 2020;10(1):4.
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