OPTIMIZING DRUG DOSING IN CRITICALLY ILL PATIENTS WITH AUGMENTED RENAL CLEARANCE: A COMPREHENSIVE REVIEW AND META-ANALYSIS

MIHIR CHACHAR; TALLINI LOKHANDE; ANJALI KUMBHAR; ROHINI CHAVAN; DHANRAJ SHINDE

doi:10.22159/ijpps.2024v16i11.52092

Authors

MIHIR CHACHAR Department of Clinical Pharmacy, Modern College of Pharmacy, Nigdi, Pune, India https://orcid.org/0009-0003-4926-4541
TALLINI LOKHANDE Department of Clinical Pharmacy, Modern College of Pharmacy, Nigdi, Pune, India https://orcid.org/0009-0004-5410-8241
ANJALI KUMBHAR Department of Clinical Pharmacy, Modern College of Pharmacy, Nigdi, Pune, India https://orcid.org/0009-0003-5171-2999
ROHINI CHAVAN Department of Clinical Pharmacy, Modern College of Pharmacy, Nigdi, Pune, India https://orcid.org/0009-0007-4249-2962
DHANRAJ SHINDE Intensive and Pediatric Care Clinical Pharmacist, Deenanath Mangeshkar Hospital and Research Center, Pune, India https://orcid.org/0009-0002-3421-8772

DOI:

https://doi.org/10.22159/ijpps.2024v16i11.52092

Keywords:

Augmented renal clearance, Critically ill patients, Antibiotic dose adjustments, Treatment failure, Increased dose, eGFR, Creatinine clearance

Abstract

Renal clearance plays a pivotal role in eliminating most administered drugs, particularly antibiotics, which is crucial for achieving therapeutic goals by maintaining plasma concentrations within the therapeutic window. Various pre-existing conditions such as renal replacement therapies, kidney or liver impairment, and enhanced excretory organ function can disrupt drug concentrations, leading to treatment failure. Augmented Renal Clearance (ARC) exacerbates this by causing rapid drug elimination, notably in critically ill patients. Consequently, careful monitoring and adjustment of drug dosages tailored to individual patient conditions and comorbidities are imperative to prevent sub-therapeutic outcomes or treatment failures. Our review highlights the necessity of dosage modifications informed by current research to optimize therapeutic outcomes in such cases. We provide a comprehensive table detailing effective antibiotics and their adjustments for ARC.

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References

Hobbs AL, Shea KM, Roberts KM, Daley MJ. Implications of augmented renal clearance on drug dosing in critically ill patients: a focus on antibiotics. Pharmacotherapy. 2015 Nov;35(11):1063-75. doi: 10.1002/phar.1653.

Chen IH, Nicolau DP. Augmented renal clearance and how to augment antibiotic dosing. Antibiotics (Basel). 2020 Jul 9;9(7):393. doi: 10.3390/antibiotics9070393, PMID 32659898.

Huttner A, Von Dach E, Renzoni A, Huttner BD, Affaticati M, Pagani L. Augmented renal clearance low β-lactam concentrations and clinical outcomes in the critically ill: an observational prospective cohort study. Int J Antimicrob Agents. 2015 Apr 1;45(4):385-92. doi: 10.1016/j.ijantimicag.2014.12.017.

Shi AX, QU Q, Zhuang HH, Teng XQ, XU WX, Liu YP. Individualized antibiotic dosage regimens for patients with augmented renal clearance. Front Pharmacol. 2023 Jul 26;14:1137975. doi: 10.3389/fphar.2023.1137975, PMID 37564179.

Bilbao Meseguer I, Rodriguez Gascon A, Barrasa H, Isla A, Solinis MA. Augmented renal clearance in critically ill patients: a systematic review. Clin Pharmacokinet. 2018 Sep;57(9):1107-21. doi: 10.1007/s40262-018-0636-7.

Udy AA, Baptista JP, Lim NL, Joynt GM, Jarrett P, Wockner L. Augmented renal clearance in the ICU: results of a multicenter observational study of renal function in critically ill patients with normal plasma creatinine concentrations. Crit Care Med. 2014 Mar 1;42(3):520-7. doi: 10.1097/CCM.0000000000000029.

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. J Crit Care. 2013 Oct 1;28(5):695-700. doi: 10.1016/j.jcrc.2013.03.003, PMID 23683557.

Udy AA, Dulhunty JM, Roberts JA, Davis JS, Webb SA, Bellomo R. Association between augmented renal clearance and clinical outcomes in patients receiving β-lactam antibiotic therapy by continuous or intermittent infusion: a nested cohort study of the BLING-II randomised placebo-controlled clinical trial. Int J Antimicrob Agents. 2017;49(5):624-30. doi: 10.1016/j.ijantimicag.2016.12.022, PMID 28286115.

Kamidani R, Okada H, Kawasaki Y, Shimada T, Tamaoki Y, Nakashima Y. Impact of augmented renal clearance on anticoagulant therapy in critically ill patients with coronavirus disease 2019: a retrospective cohort study. J Infect Chemother. 2024 Feb 1;30(2):111-7. doi: 10.1016/j.jiac.2023.09.017.

Cook AM, Arora S, Davis J, Pittman T. Augmented renal clearance of vancomycin and levetiracetam in a traumatic brain injury patient. Neurocrit Care. 2013 Oct;19(2):210-4. doi: 10.1007/s12028-013-9837-y, PMID 23907742.

Udy AA, Roberts JA, Boots RJ, Paterson DL, Lipman J. Augmented renal clearance: implications for antibacterial dosing in the critically ill. Clin Pharmacokinet. 2010 Jan;49(1):1-16. doi: 10.2165/11318140-000000000-00000, PMID 20000886.

Expert opinion. Senior Renal Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sci, FSHP, FISAC; Michael Heung, MD, MS; 2022.

Cies JJ, LA Coursiere RJ, Moore WS, Chopra A. Therapeutic drug monitoring of prolonged infusion aztreonam for multi-drug resistant pseudomonas aeruginosa: a case report. J Pediatr Pharmacol Ther. 2017 Dec 1;22(6):467-70. doi: 10.5863/1551-6776-22.6.467, PMID 29290748.

Roberts JA, Udy AA, Jarrett P, Wallis SC, Hope WW, Sharma R. Plasma and target site subcutaneous tissue population pharmacokinetics and dosing simulations of cefazolin in post-trauma critically ill patients. J Antimicrob Chemother. 2015 May;70(5):1495-502. doi: 10.1093/jac/dku564.

Wong G, Briscoe S, McWhinney B, Ally M, Ungerer J, Lipman J. Therapeutic drug monitoring of β-lactam antibiotics in the critically ill: direct measurement of unbound drug concentrations to achieve appropriate drug exposures. J Antimicrob Chemother. 2018;73(11):3087-94. doi: 10.1093/jac/dky314, PMID 30137377.

Shionogi Inc. FETROJA®(cefiderocol) prescribing information; 2020.

Zasowski E, Bland CM, Tam VH, Lodise TP. Identification of optimal renal dosage adjustments for high dose extended infusion cefepime dosing regimens in hospitalized patients. J Antimicrob Chemother. 2015 Mar 1;70(3):877-81. doi: 10.1093/jac/dku435, PMID 25381169.

Exblifep(R) intravenous injection cefepime hydrochloride enmetazobactam intravenous injection. Advyzom LLC (per FDA). Berkeley Heights, NJ; 2024.

Das S, LI J, Riccobene T, Carrothers TJ, Newell P, Melnick D. Dose selection and validation for ceftazidime avibactam in adults with complicated intra-abdominal infections complicated urinary tract infections and nosocomial pneumonia. Antimicrob Agents Chemother. 2019 Apr;63(4):10-128. doi: 10.1128/AAC.02187-18, PMID 30670413.

Gatti M, Pea F. Pharmacokinetic/pharmacodynamic target attainment in critically ill renal patients on antimicrobial usage: focus on novel beta-lactams and beta-lactams/beta-lactamase inhibitors. Expert Rev Clin Pharmacol. 2021 May 4;14(5):583-99. doi: 10.1080/17512433.2021.1901574, PMID 33687300.

LI J, Lovern M, Riccobene T, Carrothers TJ, Newell P, Das S. Considerations in the selection of renal dosage adjustments for patients with serious infections and lessons learned from the development of ceftazidime-avibactam. Antimicrob Agents Chemother. 2020 Mar 24;64(4):10-128. doi: 10.1128/AAC.02105-19, PMID 32015049.

Stein GE, Smith CL, Scharmen A, Kidd JM, Cooper C, Kuti J. Pharmacokinetic and pharmacodynamic analysis of ceftazidime/avibactam in critically ill patients. Surg Infect. 2019 Jan 1;20(1):55-61. doi: 10.1089/sur.2018.141.

Hahn MM, Triplett CA, Anderson MS, Smart JI, Litherland K, Keech S. Ceftobiprole medocaril is an effective post-exposure treatment in the Fischer 344 rat model of pneumonic tularemia. Antibiotics. 2023 Aug 19;12(8):1337. doi: 10.3390/antibiotics12081337.

Ollivier J, Carrie C, D Houdain N, Djabarouti S, Petit L, Xuereb F. Are standard dosing regimens of ceftriaxone adapted for critically ill patients with augmented creatinine clearance? Antimicrob Agents Chemother. 2019 Mar;63(3):10-128. doi: 10.1128/AAC.02134-18, PMID 30602511.

Carlier M, Noe M, Roberts JA, Stove V, Verstraete AG, Lipman J. Population pharmacokinetics and dosing simulations of cefuroxime in critically ill patients: non-standard dosing approaches are required to achieve therapeutic exposures. J Antimicrob Chemother. 2014 Oct 1;69(10):2797-803. doi: 10.1093/jac/dku195, PMID 24917580.

Roberts JA, Alobaid AS, Wallis SC, Perner A, Lipman J, Sjovall F. Defining optimal dosing of ciprofloxacin in patients with septic shock. J Antimicrob Chemother. 2019 Jun 1;74(6):1662-9. doi: 10.1093/jac/dkz069.

Hobbs AL, Shea KM, Roberts KM, Daley MJ. Implications of augmented renal clearance on drug dosing in critically ill patients: a focus on antibiotics. Pharmacotherapy. 2015 Nov;35(11):1063-75. doi: 10.1002/phar.1653.

Falcone M, Russo A, Venditti M, Novelli A, Pai MP. Considerations for higher doses of daptomycin in critically ill patients with methicillin-resistant staphylococcus aureus bacteremia. Clin Infect Dis. 2013 Dec 1;57(11):1568-76. doi: 10.1093/cid/cit582, PMID 24046298.

Parker SL, Frantzeskaki F, Wallis SC, Diakaki C, Giamarellou H, Koulenti D. Population pharmacokinetics of fosfomycin in critically ill patients. Antimicrob Agents Chemother. 2015 Oct;59(10):6471-6. doi: 10.1128/AAC.01321-15, PMID 26239990.

Parker S, Lipman J, Koulenti D, Dimopoulos G, Roberts JA. What is the relevance of fosfomycin pharmacokinetics in the treatment of serious infections in critically ill patients? A systematic review. Int J Antimicrob Agents. 2013 Oct 1;42(4):289-93. doi: 10.1016/j.ijantimicag.2013.05.018, PMID 23880170.

Roberts JA, Cotta MO, Cojutti P, Lugano M, Rocca GD, Pea F. Does critical illness change levofloxacin pharmacokinetics? Antimicrob Agents Chemother. 2016 Mar;60(3):1459-63. doi: 10.1128/AAC.02610-15.

Cojutti P, Pai MP, Pea F. Population pharmacokinetics and dosing considerations for the use of linezolid in overweight and obese adult patients. Clin Pharmacokinet. 2018 Aug;57(8):989-1000. doi: 10.1007/s40262-017-0606-5, PMID 29080937.

Crass RL, Cojutti PG, Pai MP, Pea F. Reappraisal of linezolid dosing in renal impairment to improve safety. Antimicrob Agents Chemother. 2019 Aug;63(8):10-128. doi: 10.1128/AAC.00605-19.

Cojutti PG, PEA F, Baraldo M. A 10 y experience of therapeutic drug monitoring (TDM) of linezolid in a hospital-wide population of patients receiving conventional dosing: is there enough evidence for suggesting TDM in the majority of patients? Basic Clin Pharmacol Toxicol. 2017 Oct;121(4):303-8. doi: 10.1111/bcpt.12797.

Tamatsukuri T, Ohbayashi M, Kohyama N, Kobayashi Y, Yamamoto T, Fukuda K. The exploration of population pharmacokinetic model for meropenem in augmented renal clearance and investigation of optimum setting of dose. J Infect Chemother. 2018 Oct 1;24(10):834-40. doi: 10.1016/j.jiac.2018.07.007, PMID 30087007.

Ehmann L, Zoller M, Minichmayr IK, Scharf C, Huisinga W, Zander J. Development of a dosing algorithm for meropenem in critically ill patients based on a population pharmacokinetic/pharmacodynamic analysis. Int J Antimicrob Agents. 2019 Sep 1;54(3):309-17. doi: 10.1016/j.ijantimicag.2019.06.016, PMID 31229669.

Venugopalan V, Manigaba K, Borgert SJ, Cope J, Peloquin CA, Klinker KP. Training a drug to do new tricks: insights on stability of meropenem administered as a continuous infusion. Microbiol Insights. 2018 Oct 14;11:1178636118804549. doi: 10.1177/1178636118804549, PMID 30349291.

Carrie C, Legeron R, Petit L, Ollivier J, Cottenceau V, D Houdain N. Higher than standard dosing regimen are needed to achieve optimal antibiotic exposure in critically ill patients with augmented renal clearance receiving piperacillin-tazobactam administered by continuous infusion. J Crit Care. 2018 Dec 1;48:66-71. doi: 10.1016/j.jcrc.2018.08.026, PMID 30172963.

Xacduro(R) intravenous kit, sulbactam, durlobactam intravenous kit. La Jolla Pharmaceutical Company (per manufacturer). Waltham, MA; 2023.

Kim BK, Kim JH, Sohn KH, Kim JY, Chang YS, Kim SH. Incidence of teicoplanin adverse drug reactions among patients with vancomycin-associated adverse drug reactions and its risk factors. Korean J Intern Med. 2020 May;35(3):714-22. doi: 10.3904/kjim.2018.404.

Lin WU FL, Liu SS, Yang TY, Win MF, Lin SW, Huang CF. A larger dose of vancomycin is required in adult neurosurgical intensive care unit patients due to augmented clearance. Ther Drug Monit. 2015 Oct 1;37(5):609-18. doi: 10.1097/FTD.0000000000000187, PMID 25627406.

Tomasa Irriguible TM, Martinez Vega S, Mor Marco E, Herraiz Ruiz A, Raguer Pardo L, Cubells Larrosa C. Low molecular weight heparins in COVID-19 patients: beware of augmented renal clearance. Crit Care. 2020 Jun 10;24(1):325. doi: 10.1186/s13054-020-03058-3.

Mahmoud SH, Shen C. Augmented renal clearance in critical illness: an important consideration in drug dosing. Pharmaceutics. 2017 Sep 16;9(3):36. doi: 10.3390/pharmaceutics9030036, PMID 28926966.

Hefny F, Stuart A, Kung JY, Mahmoud SH. Prevalence and risk factors of augmented renal clearance: a systematic review and meta-analysis. Pharmaceutics. 2022 Feb 19;14(2):445. doi: 10.3390/pharmaceutics14020445, PMID 35214177.

HE CY, YE PP, Liu B, Song L, Van Den Anker J, Zhao W. Population pharmacokinetics and dosing optimization of vancomycin in infants children and adolescents with augmented renal clearance. Antimicrob Agents Chemother. 2021 Sep 17;65(10):10-128. doi: 10.1128/AAC.00897-21.

Luo Y, Wang Y, MA Y, Wang P, Zhong J, Chu Y. Augmented renal clearance: what have we known and what will we do? Front Pharmacol. 2021 Nov 2;12:723731. doi: 10.3389/fphar.2021.723731.

Schwartz GJ, Mun A, Schneider MF, Mak RH, Kaskel F, Warady BA. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009 Mar 1;20(3):629-37. doi: 10.1681/ASN.2008030287.

Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976 Nov 28;16(1):31-41. doi: 10.1159/000180580, PMID 1244564.

Silva CM, Baptista JP, Santos I, Martins P. Recommended antibiotic dosage regimens in critically ill patients with augmented renal clearance: a systematic review. Int J Antimicrob Agents. 2022 May 1;59(5):106569. doi: 10.1016/j.ijantimicag.2022.106569, PMID 35288259.

DE Waele JJ, Dumoulin A, Janssen A, Hoste EA. Epidemiology of augmented renal clearance in mixed ICU patients. Minerva Anestesiol. 2015 Oct 1;81(10):1079-85. PMID 25697881.