Skip to main content
Top
Published in: Critical Care 1/2019

Open Access 01-12-2019 | Antibiotic | Research

Increased β-Lactams dosing regimens improve clinical outcome in critically ill patients with augmented renal clearance treated for a first episode of hospital or ventilator-acquired pneumonia: a before and after study

Authors: Cédric Carrié, Grégoire Chadefaux, Noémie Sauvage, Hugues de Courson, Laurent Petit, Karine Nouette-Gaulain, Bruno Pereira, Matthieu Biais

Published in: Critical Care | Issue 1/2019

Login to get access

Abstract

Background

Augmented renal clearance (ARC) is recognized as a leading cause of β-lactam subexposure when conventional dosing regimens are used. The main objective was to compare the clinical outcome of ARC patients treated by conventional or increased β-lactam dosing regimens for a first episode of hospital or ventilator-acquired pneumonia (HAP-VAP).

Methods

In this single-center, retrospective study, every ARC patient treated by β-lactam for a first episode of HAP-VAP was included during two 15-month periods, before (Control period) and after (Treatment period) the modification of a local antibiotic therapy protocol. ARC was defined by a 24-h measured creatinine clearance ≥ 150 ml/min. The primary endpoint was defined as a therapeutic failure of the antimicrobial therapy or a HAP-VAP relapse within 28 days. Inverse probability of treatment weight (IPTW) was derived from a propensity score model. Cox proportional hazard models were used to evaluate the association between treatment period and clinical outcome.

Results

During the study period, 177 patients were included (control period, N = 88; treatment period, N = 89). Therapeutic failure or HAP-VAP relapse was significantly lower in the treatment period (10 vs. 23%, p = 0.019). The IPTW-adjusted hazard ratio of poor clinical outcome in the treatment period was 0.35 (95% CI 0.15–0.81), p = 0.014. No antibiotic side effect was reported during the treatment period.

Conclusions

Higher than licensed dosing regimens of β-lactams may be safe and effective in reducing the rate of therapeutic failure and HAP-VAP recurrence in critically ill augmented renal clearance (ARC) patients.
Appendix
Available only for authorised users
Literature
1.
go back to reference Leone M, Bouadma L, Bouhemad B, et al. Hospital-acquired pneumonia in ICU. Anaesth Crit Care Pain Med. 2018;37(1):83–98.CrossRef Leone M, Bouadma L, Bouhemad B, et al. Hospital-acquired pneumonia in ICU. Anaesth Crit Care Pain Med. 2018;37(1):83–98.CrossRef
2.
go back to reference Taccone FS, Laupland KB, Montravers P. Continuous infusion of β-lactam antibiotics for all critically ill patients? Intensive Care Med. 2016;42(10):1604–6.CrossRef Taccone FS, Laupland KB, Montravers P. Continuous infusion of β-lactam antibiotics for all critically ill patients? Intensive Care Med. 2016;42(10):1604–6.CrossRef
3.
go back to reference Mc Kinnon PS, Paladino JA, Schentag JJ. Evaluation of area under the inhibitory curve (AUIC) and time above the minimum inhibitory concentration (T>MIC) as predcitors of outcome for cefepime and ceftazidime in serious bacterial infections. Int J Antimicrob Agents. 2008;31(4):345–51.CrossRef Mc Kinnon PS, Paladino JA, Schentag JJ. Evaluation of area under the inhibitory curve (AUIC) and time above the minimum inhibitory concentration (T>MIC) as predcitors of outcome for cefepime and ceftazidime in serious bacterial infections. Int J Antimicrob Agents. 2008;31(4):345–51.CrossRef
4.
go back to reference Roberts JA, Paul SK, Akova M, et al. DALI: defining antibiotic levels in intensive care unit patients: are current β-lactam antibiotic doses sufficient for critically ill patients? Clin Infect Dis. 2014;58:1072–83.CrossRef Roberts JA, Paul SK, Akova M, et al. DALI: defining antibiotic levels in intensive care unit patients: are current β-lactam antibiotic doses sufficient for critically ill patients? Clin Infect Dis. 2014;58:1072–83.CrossRef
5.
go back to reference Udy AA, Varghese JM, Altukroni M, et al. Subtherapeutic initial β-lactam concentrations in select critically ill patients: association between augmented renal clearance and low trough drug concentrations. Chest. 2012;142:30–9.CrossRef Udy AA, Varghese JM, Altukroni M, et al. Subtherapeutic initial β-lactam concentrations in select critically ill patients: association between augmented renal clearance and low trough drug concentrations. Chest. 2012;142:30–9.CrossRef
6.
go back to reference Huttner A, Von Dach E, Renzoni A, et al. Augmented renal clearance, low β-lactam concentrations and clinical outcomes in the critically ill: an observational prospective cohort study. Int J Antimicrob Agents. 2015;45:385–92.CrossRef Huttner A, Von Dach E, Renzoni A, et al. Augmented renal clearance, low β-lactam concentrations and clinical outcomes in the critically ill: an observational prospective cohort study. Int J Antimicrob Agents. 2015;45:385–92.CrossRef
7.
go back to reference 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;28:695–700.CrossRef 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;28:695–700.CrossRef
8.
go back to reference Carrie C, Bentejac M, Cottenceau V, et al. Association between augmented renal clearance and clinical failure of antibiotic treatment in brain-injured patients with ventilator-acquired pneumonia: a preliminary study. Anaesth Crit Care Pain Med. 2018;37:35–41.CrossRef Carrie C, Bentejac M, Cottenceau V, et al. Association between augmented renal clearance and clinical failure of antibiotic treatment in brain-injured patients with ventilator-acquired pneumonia: a preliminary study. Anaesth Crit Care Pain Med. 2018;37:35–41.CrossRef
9.
go back to reference Carrie C, Petit L, d’Houdain N, et al. Association between augmented renal clearance, antibiotic exposure and clinical outcome in critically ill patients receiving high doses of β-lactams administered by continuous infusion: a prospective observational study. Int J Antimicrob Agents. 2018;51(3):443–9.CrossRef Carrie C, Petit L, d’Houdain N, et al. Association between augmented renal clearance, antibiotic exposure and clinical outcome in critically ill patients receiving high doses of β-lactams administered by continuous infusion: a prospective observational study. Int J Antimicrob Agents. 2018;51(3):443–9.CrossRef
10.
go back to reference Carrié C, Legeron R, Petit L, et al. 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;48:66–71.CrossRef Carrié C, Legeron R, Petit L, et al. 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;48:66–71.CrossRef
11.
go back to reference Ollivier J, Carrié C, d'Houdain N, et al. Are standard dosing regimens of ceftriaxone adapted for critically ill patients with augmented creatinine clearance? A prospective observational study. Antimicrob Agents Chemother. 2019;63(3):e02134-18. Ollivier J, Carrié C, d'Houdain N, et al. Are standard dosing regimens of ceftriaxone adapted for critically ill patients with augmented creatinine clearance? A prospective observational study. Antimicrob Agents Chemother. 2019;63(3):e02134-18.
12.
go back to reference Besnard T, Carrié C, Petit L, Biais M. Increased dosing regimens of piperacillin-tazobactam are needed to avoid subtherapeutic exposure in critically ill patients with augmented renal clearance. Crit Care. 2019;23(1):13.CrossRef Besnard T, Carrié C, Petit L, Biais M. Increased dosing regimens of piperacillin-tazobactam are needed to avoid subtherapeutic exposure in critically ill patients with augmented renal clearance. Crit Care. 2019;23(1):13.CrossRef
13.
go back to reference Dhaese SAM, Roberts JA, Carlier M, Verstraete AG, Stove V, De Waele JJ. Population pharmacokinetics of continuous infusion of piperacillin in critically ill patients. Int J Antimicrob Agents. 2018;51(4):594–600.CrossRef Dhaese SAM, Roberts JA, Carlier M, Verstraete AG, Stove V, De Waele JJ. Population pharmacokinetics of continuous infusion of piperacillin in critically ill patients. Int J Antimicrob Agents. 2018;51(4):594–600.CrossRef
14.
go back to reference Austin PC. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivar Behav Res. 2011;46:399–424.CrossRef Austin PC. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivar Behav Res. 2011;46:399–424.CrossRef
15.
go back to reference Austin PC, Stuart EA. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat Med. 2015;34(28):3661–79.CrossRef Austin PC, Stuart EA. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat Med. 2015;34(28):3661–79.CrossRef
16.
go back to reference Austin PC, Schuster T, Platt RW. Statistical power in parallel group point exposure studies with time-to-event outcomes: an empirical comparison of the performance of randomized controlled trials and the inverse probability of treatment weighting (IPTW) approach. BMC Med Res Methodol. 2015;15:87.CrossRef Austin PC, Schuster T, Platt RW. Statistical power in parallel group point exposure studies with time-to-event outcomes: an empirical comparison of the performance of randomized controlled trials and the inverse probability of treatment weighting (IPTW) approach. BMC Med Res Methodol. 2015;15:87.CrossRef
17.
go back to reference Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43:304–77.CrossRef Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43:304–77.CrossRef
18.
go back to reference Sime FB, Udy AA, Roberts JA. Augmented renal clearance in critically ill patients: etiology, definition and implications for beta-lactam dose optimization. Curr Opin Pharmacol. 2015;24:1–6.CrossRef Sime FB, Udy AA, Roberts JA. Augmented renal clearance in critically ill patients: etiology, definition and implications for beta-lactam dose optimization. Curr Opin Pharmacol. 2015;24:1–6.CrossRef
19.
go back to reference Carlier M, Noë M, De Waele JJ, et al. Population pharmacokinetics and dosing simulations of amoxicillin/clavulanic acid in critically ill patients. J Antimicrob Chemother. 2013;68(11):2600–8.CrossRef Carlier M, Noë M, De Waele JJ, et al. Population pharmacokinetics and dosing simulations of amoxicillin/clavulanic acid in critically ill patients. J Antimicrob Chemother. 2013;68(11):2600–8.CrossRef
20.
go back to reference Roberts JA, Ulldemolins M, Roberts MS, et al. Therapeutic drug monitoring of beta-lactams in critically ill patients: proof of concept. Int J Antimicrob Agents. 2010;36:332–9.CrossRef Roberts JA, Ulldemolins M, Roberts MS, et al. Therapeutic drug monitoring of beta-lactams in critically ill patients: proof of concept. Int J Antimicrob Agents. 2010;36:332–9.CrossRef
21.
go back to reference Carlier M, Carrette S, Roberts JA, 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? Crit Care. 2013;17(3):R84.CrossRef Carlier M, Carrette S, Roberts JA, 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? Crit Care. 2013;17(3):R84.CrossRef
22.
go back to reference Andersen MG, Thorsted A, Storgaard M, Kristoffersson AN, Friberg LE, Öbrink-Hansen K. Population pharmacokinetics of piperacillin in sepsis patients: should alternative dosing strategies be considered? Antimicrob Agents Chemother. 2018 Apr;26:62(5). Andersen MG, Thorsted A, Storgaard M, Kristoffersson AN, Friberg LE, Öbrink-Hansen K. Population pharmacokinetics of piperacillin in sepsis patients: should alternative dosing strategies be considered? Antimicrob Agents Chemother. 2018 Apr;26:62(5).
23.
go back to reference Udy AA, Lipman J, Jarrett P, et al. Are standard doses of piperacillin sufficient for critically ill patients with augmented creatinine clearance? Crit Care. 2015;19:28.CrossRef Udy AA, Lipman J, Jarrett P, et al. Are standard doses of piperacillin sufficient for critically ill patients with augmented creatinine clearance? Crit Care. 2015;19:28.CrossRef
24.
go back to reference Haeseker M, Havenith T, Stolk L, Neef C, Bruggeman C, Verbon A. Is the standard dose of amoxicillin-clavulanic acid sufficient? BMC Pharmacol Toxicol. 2014;15:38.CrossRef Haeseker M, Havenith T, Stolk L, Neef C, Bruggeman C, Verbon A. Is the standard dose of amoxicillin-clavulanic acid sufficient? BMC Pharmacol Toxicol. 2014;15:38.CrossRef
25.
go back to reference Petit L, Carrié C, Hisz Q, d’Houdain N, Breilh D, Sztark F. Are standard doses of cefazolin adapted for methicillin-susceptible Staphylococcus aureus respiratory infections in critically ill patients with augmented renal clearance? Ann Intensive Care. 2018;8(Suppl 1):13. Petit L, Carrié C, Hisz Q, d’Houdain N, Breilh D, Sztark F. Are standard doses of cefazolin adapted for methicillin-susceptible Staphylococcus aureus respiratory infections in critically ill patients with augmented renal clearance? Ann Intensive Care. 2018;8(Suppl 1):13.
26.
go back to reference Tamatsukuri T, Ohbayashi M, Kohyama N, et al. The exploration of population pharmacokinetic model for meropenem in augmented renal clearance and investigation of optimum setting of dose. J Infect Chemother. 2018;24(10):834–40.CrossRef Tamatsukuri T, Ohbayashi M, Kohyama N, et al. The exploration of population pharmacokinetic model for meropenem in augmented renal clearance and investigation of optimum setting of dose. J Infect Chemother. 2018;24(10):834–40.CrossRef
27.
go back to reference Baptista JP, Udy AA, Sousa E, et al. A comparison of estimates of glomerular filtration in critically ill patients with augmented renal clearance. Crit Care. 2011;15(3):R139.CrossRef Baptista JP, Udy AA, Sousa E, et al. A comparison of estimates of glomerular filtration in critically ill patients with augmented renal clearance. Crit Care. 2011;15(3):R139.CrossRef
28.
go back to reference Carrié C, Rubin S, Sioniac P, Breilh D, Biais M. The kinetic glomerular filtration rate is not interchangeable with measured creatinine clearance for prediction of piperacillin underexposure in critically ill patients with augmented renal clearance. Crit Care. 2018;22(1):177.CrossRef Carrié C, Rubin S, Sioniac P, Breilh D, Biais M. The kinetic glomerular filtration rate is not interchangeable with measured creatinine clearance for prediction of piperacillin underexposure in critically ill patients with augmented renal clearance. Crit Care. 2018;22(1):177.CrossRef
29.
go back to reference Barletta JF, Mangram AJ, Byrne M, et al. Identifying augmented renal clearance in trauma patients: validation of the augmented renal clearance in trauma intensive care scoring system. J Trauma Acute Care Surg. 2017;82(4):665–71.CrossRef Barletta JF, Mangram AJ, Byrne M, et al. Identifying augmented renal clearance in trauma patients: validation of the augmented renal clearance in trauma intensive care scoring system. J Trauma Acute Care Surg. 2017;82(4):665–71.CrossRef
31.
go back to reference Jacobs A, Taccone FS, Roberts JA, Jacobs F, Cotton F, Wolff F, et al. β-Lactam dosage regimens in septic patients with augmented renal clearance. Antimicrob Agents Chemother. 2018;62(9). Jacobs A, Taccone FS, Roberts JA, Jacobs F, Cotton F, Wolff F, et al. β-Lactam dosage regimens in septic patients with augmented renal clearance. Antimicrob Agents Chemother. 2018;62(9).
32.
go back to reference Felton TW, Roberts JA, Lodise TP, Van Guilder M, Boseli E, Neely MN, et al. Individualization of piperacillin dosing for critically ill patients: dosing software to optimize antimicrobial therapy. Antimicrob Agents Chemother. 2018;58(7):4094–102.CrossRef Felton TW, Roberts JA, Lodise TP, Van Guilder M, Boseli E, Neely MN, et al. Individualization of piperacillin dosing for critically ill patients: dosing software to optimize antimicrobial therapy. Antimicrob Agents Chemother. 2018;58(7):4094–102.CrossRef
33.
go back to reference Beumier M, Casu GS, Hites M, Wolff F, Cotton F, Vincent JL, et al. Elevated β-lactam concentrations associated with neurological deterioration in ICU septic patients. Minerva Anestesiol. 2015;81:497–506.PubMed Beumier M, Casu GS, Hites M, Wolff F, Cotton F, Vincent JL, et al. Elevated β-lactam concentrations associated with neurological deterioration in ICU septic patients. Minerva Anestesiol. 2015;81:497–506.PubMed
34.
go back to reference Imani S, Buscher H, Marriott D, Gentili S, SAndaradura I. Too much of a good thing: a retrospective study of β-lactam concentration-toxicity relationships. J Antimicrob Chemother. 2017;72:2891–7.CrossRef Imani S, Buscher H, Marriott D, Gentili S, SAndaradura I. Too much of a good thing: a retrospective study of β-lactam concentration-toxicity relationships. J Antimicrob Chemother. 2017;72:2891–7.CrossRef
Metadata
Title
Increased β-Lactams dosing regimens improve clinical outcome in critically ill patients with augmented renal clearance treated for a first episode of hospital or ventilator-acquired pneumonia: a before and after study
Authors
Cédric Carrié
Grégoire Chadefaux
Noémie Sauvage
Hugues de Courson
Laurent Petit
Karine Nouette-Gaulain
Bruno Pereira
Matthieu Biais
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2019
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-019-2621-4

Other articles of this Issue 1/2019

Critical Care 1/2019 Go to the issue