Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Critical Care
Published in: Critical Care 3/2013

Open Access 01-06-2013 | Research

Meropenem and piperacillin/tazobactam prescribing in critically ill patients: does augmented renal clearance affect pharmacokinetic/pharmacodynamic target attainment when extended infusions are used?

Authors: Mieke Carlier, Sofie Carrette, Jason A Roberts, Veronique Stove, Alain Verstraete, Eric Hoste, Pieter Depuydt, Johan Decruyenaere, Jeffrey Lipman, Steven C Wallis, Jan J De Waele

Published in: Critical Care | Issue 3/2013

Login to get access

Abstract

Background

Correct antibiotic dosing remains a challenge for the clinician. The aim of this study was to assess the influence of augmented renal clearance on pharmacokinetic/pharmacodynamic target attainment in critically ill patients receiving meropenem or piperacillin/tazobactam, administered as an extended infusion.

Methods

This was a prospective, observational, pharmacokinetic study executed at the medical and surgical intensive care unit at a large academic medical center. Elegible patients were adult patients without renal dysfunction receiving meropenem or piperacillin/tazobactam as an extended infusion. Serial blood samples were collected to describe the antibiotic pharmacokinetics. Urine samples were taken from a 24-hour collection to measure creatinine clearance. Relevant data were drawn from the electronic patient file and the intensive care information system.

Results

We obtained data from 61 patients and observed extensive pharmacokinetic variability. Forty-eight percent of the patients did not achieve the desired pharmacokinetic/pharmacodynamic target (100% f T>MIC), of which almost 80% had a measured creatinine clearance >130 mL/min. Multivariate logistic regression demonstrated that high creatinine clearance was an independent predictor of not achieving the pharmacokinetic/pharmacodynamic target. Seven out of nineteen patients (37%) displaying a creatinine clearance >130 mL/min did not achieve the minimum pharmacokinetic/pharmacodynamic target of 50% f T>MIC.

Conclusions

In this large patient cohort, we observed significant variability in pharmacokinetic/pharmacodynamic target attainment in critically ill patients. A large proportion of the patients without renal dysfunction, most of whom displayed a creatinine clearance >130 mL/min, did not achieve the desired pharmacokinetic/pharmacodynamic target, even with the use of alternative administration methods. Consequently, these patients may be at risk for treatment failure without dose up-titration.
Appendix
Available only for authorised users
Literature
1.
Vincent J-L, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, Moreno R, Lipman J, Gomersall C, Sakr Y, Reinhart K, EPICII Group of Investigators: International study of the prevalence and outcomes of infection in intensive care units. JAMA 2009, 302: 2323-2329. 10.1001/jama.2009.1754CrossRefPubMed
2.
Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M, Early Goal-Directed Therapy Collaborative Group: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001, 345: 1368-1377. 10.1056/NEJMoa010307CrossRefPubMed
3.
Leibovici L, Shraga I, Drucker M, Konigsberger H, Samra Z, Pitlik SD: The benefit of appropriate empirical antibiotic treatment in patients with bloodstream infection. J Intern Med 1998, 244: 379-386. 10.1046/j.1365-2796.1998.00379.xCrossRefPubMed
4.
Roberts JA, Ulldemolins M, Roberts MS, McWhinney B, Ungerer J, Paterson DL, Lipman J: Therapeutic drug monitoring of beta-lactams in critically ill patients: proof of concept. Int J Antimicrob Agents 2010, 36: 332-339. 10.1016/j.ijantimicag.2010.06.008CrossRefPubMed
5.
Taccone FS, Laterre P-F, Dugernier T, Spapen H, Delattre I, Wittebole X, De Backer D, Layeux B, Wallemacq P, Vincent JL, Jacobs F: Insufficient beta-lactam concentrations in the early phase of severe sepsis and septic shock. Crit Care 2010, 14: R126. 10.1186/cc9091PubMedCentralCrossRefPubMed
6.
Navas D, Caillon J, Batard E, Le Conte P, Kergueris MF, Moreau P, Potel G: Trough serum concentrations of beta-lactam antibiotics in cancer patients: inappropriateness of conventional schedules to pharmacokinetic/pharmacodynamic properties of beta-lactams. Int J Antimicrob Agents 2006, 27: 102-107. 10.1016/j.ijantimicag.2005.09.016CrossRefPubMed
7.
Roberts DM, Roberts JA, Roberts MS, Liu X, Nair P, Cole L, Lipman J, Bellomo R: Variability of antibiotic concentrations in critically ill patients receiving continuous renal replacement therapy: A multicentre pharmacokinetic study*. Crit Care Med 2012, 40: 1523-1528. 10.1097/CCM.0b013e318241e553CrossRefPubMed
8.
Roberts JA, Lipman J: Pharmacokinetic issues for antibiotics in the critically ill patient. Crit Care Med 2009, 37: 840-851. 10.1097/CCM.0b013e3181961bffCrossRefPubMed
9.
Udy AA, Putt MT, Boots RJ, Lipman J: ARC - Augmented Renal Clearance. Curr Pharm Biotechnol 2011, 12: 2020-2029. 10.2174/138920111798808446CrossRefPubMed
10.
Udy AA, Roberts JA, Boots RJ, Paterson DL, Lipman J: Augmented renal clearance implications for antibacterial dosing in the critically ill. Clin Pharmacokinet 2010, 49: 1-16. 10.2165/11318140-000000000-00000CrossRefPubMed
11.
Fuster-Lluch O, Geronimo-Pardo M, Peyro-Garcia R, Lizan-Garcia M: Glomerular hyperfiltration and albuminuria in critically ill patients. Anaesth Intensive Care 2008, 36: 674-680.PubMed
12.
Udy A, Boots R, Senthuran S, Stuart J, Deans R, Lassig-Smith M, Lipman J: Augmented creatinine clearance in traumatic brain injury. Anesth Analg 2010, 111: 1505-1510. 10.1213/ANE.0b013e3181f7107dCrossRefPubMed
13.
Conil JM, Georges B, Lavit M, Seguin T, Tack I, Samil K, Chabanon G, Houin G, Saivin S: Pharmacokinetics of ceftazidime and cefepime in burn patients: The importance of age and creatinine clearance. Int J Clin Pharmacol Ther 2007, 45: 529-538. 10.5414/CPP45529CrossRefPubMed
14.
Udy AA, Varghese JM, Altukroni M, Briscoe S, McWhinney BC, Ungerer JP, Lipman J, Roberts JA: Subtherapeutic initial beta-lactam concentrations in select critically ill patients association between augmented renal clearance and low trough drug concentrations. Chest 2012, 142: 30-39. 10.1378/chest.11-1671CrossRefPubMed
15.
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. Int J Antimicrob Agents 2008, 31: 345-351. 10.1016/j.ijantimicag.2007.12.009CrossRefPubMed
16.
McWhinney BC, Wallis SC, Hillister T, Roberts JA, Lipman J, Ungerer JPJ: Analysis of 12 beta-lactam antibiotics in human plasma by HPLC with ultraviolet detection. J Chromatogr B 2010, 878: 2039-2043. 10.1016/j.jchromb.2010.05.027CrossRef
17.
18.
Zeitlinger MA, Erovic BM, Sauermann R, Georgopoulos A, Muller M, Joukhadar C: Plasma concentrations might lead to overestimation of target site activity of piperacillin in patients with sepsis. J Antimicrob Chemother 2005, 56: 703-708. 10.1093/jac/dki284CrossRefPubMed
19.
Kitzes-Cohen R, Farin D, Piva G, De Myttenaere-Bursztein SA: Pharmacokinetics and pharmacodynamics of meropenem in critically ill patients. Int J Antimicrob Agents 2002, 19: 105-110. 10.1016/S0924-8579(01)00474-5CrossRefPubMed
20.
Roos JF, Lipman J, Kirkpatrick CMJ: Population pharmacokinetics and pharmacodynamics of cefpirome in critically ill patients against Gram-negative bacteria. Intensive Care Med 2007, 33: 781-788. 10.1007/s00134-007-0573-7CrossRefPubMed
21.
Angus BJ, Smith MD, Suputtamongkol Y, Mattie H, Walsh AL, Wuthiekanun V, Chaowagul W, White NJ: Pharmacokinetic-pharmacodynamic evaluation of ceftazidime continuous infusion vs intermittent bolus injection in septicaemic melioidosis. Br J Clin Pharmacol 2000, 49: 445-452.PubMedCentralCrossRefPubMed
22.
Li C, Kuti JL, Nightingale CH, Mansfield DL, Dana A, Nicolau DP: Population pharmacokinetics and pharmacodynamics of piperacillin/tazobactam in patients with complicated intra-abdominal infection. J Antimicrob Chemother 2005, 56: 388-395. 10.1093/jac/dki243CrossRefPubMed
23.
Young RJ, Lipman J, Gin T, Gomersall CD, Joynt GM, Oh TE: Intermittent bolus dosing of ceftazidime in critically ill patients. J Antimicrob Chemother 1997, 40: 269-273. 10.1093/jac/40.2.269CrossRefPubMed
24.
Tam VH, McKinnon PS, Akins RL, Drusano GL, Rybak MJ: Pharmacokinetics and pharmacodynamics of cefepime in patients with various degrees of renal function. Antimicrob Agents Chemother 2003, 47: 1853-1861. 10.1128/AAC.47.6.1853-1861.2003PubMedCentralCrossRefPubMed
25.
Lipman J, Wallis SC, Rickard C: Low plasma cefepime levels in critically ill septic patients: Pharmacokinetic modeling indicates improved troughs with revised dosing. Antimicrob Agents Chemother 1999, 43: 2559-2561.PubMedCentralPubMed
26.
Lipman J, Wallis SC, Rickard CM, Fraenkel D: Low cefpirome levels during twice daily dosing in critically ill septic patients: pharmacokinetic modelling calls for more frequent dosing. Intensive Care Med 2001, 27: 363-370. 10.1007/s001340000741CrossRefPubMed
27.
28.
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. Int J Antimicrob Agents 2008, 31: 345-351. 10.1016/j.ijantimicag.2007.12.009CrossRefPubMed
29.
Vogelman B, Craig WA: Kinetics of antimicrobial activity. J Pediatr 1986, 108: 835-840. 10.1016/S0022-3476(86)80754-5CrossRefPubMed
30.
Li C, Du X, Kuti JL, Nicolau DP: Clinical pharmacodynamics of meropenem in patients with lower respiratory tract infections. Antimicrob Agents Chemother 2007, 51: 1725-1730. 10.1128/AAC.00294-06PubMedCentralCrossRefPubMed
31.
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. Int J Antimicrob Agents 2012, 40: 370-372. 10.1016/j.ijantimicag.2012.05.010CrossRefPubMed
32.
Udy AA, Putt MT, Shanmugathasan S, Roberts JA, Lipman J: Augmented renal clearance in the Intensive Care Unit: an illustrative case series. Int J Antimicrob Agents 2010, 35: 606-608. 10.1016/j.ijantimicag.2010.02.013CrossRefPubMed
33.
Baptista JP, Sousa E, Martins PJ, Pimentel JM: Augmented renal clearance in septic patients and implications for vancomycin optimisation. Int J Antimicrob Agents 2012, 39: 420-423. 10.1016/j.ijantimicag.2011.12.011CrossRefPubMed
34.
Martin JH, Fay MF, Udy A, Roberts J, Kirkpatrick C, Ungerer J, Lipman J: Pitfalls of using estimations of glomerular filtration rate in an intensive care population. Intern Med J 2011, 41: 537-543. 10.1111/j.1445-5994.2009.02160.xCrossRefPubMed
35.
Baptista JP, Udy AA, Sousa E, Pimentel J, Wang L, Roberts JA, Lipman J: A comparison of estimates of glomerular filtration in critically ill patients with augmented renal clearance. Crit Care 2011, 15: R139. 10.1186/cc10262PubMedCentralCrossRefPubMed
36.
Roberts JA, Hope WW, Lipman J: Therapeutic drug monitoring of beta-lactams for critically ill patients: unwarranted or essential? Int J Antimicrob Agents 2010, 35: 419-420. 10.1016/j.ijantimicag.2010.01.022CrossRefPubMed
Metadata
Title
Meropenem and piperacillin/tazobactam prescribing in critically ill patients: does augmented renal clearance affect pharmacokinetic/pharmacodynamic target attainment when extended infusions are used?
Authors
Mieke Carlier
Sofie Carrette
Jason A Roberts
Veronique Stove
Alain Verstraete
Eric Hoste
Pieter Depuydt
Johan Decruyenaere
Jeffrey Lipman
Steven C Wallis
Jan J De Waele
Publication date
01-06-2013
Publisher
BioMed Central
Published in
Critical Care / Issue 3/2013
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc12705

Other articles of this Issue 3/2013

Critical Care 3/2013 Go to the issue

Research

The peripheral perfusion index and transcutaneous oxygen challenge test are predictive of mortality in septic patients after resuscitation

Research

Effect of tyrosine kinase inhibitors, imatinib and nilotinib, in murine lipopolysaccharide-induced acute lung injury during neutropenia recovery

Review

Clinical review: Can we predict which patients are at risk of complications following surgery?

Research

Plasma levels of mitochondrial and nuclear DNA in patients with massive pulmonary embolism in the emergency department: a prospective cohort study

Letter

Target blood pressure in sepsis: between a rock and a hard place

Review

Clinical review: Respiratory failure in HIV-infected patients - a changing picture