Multicenter Population Pharmacokinetic Study of Unbound Ceftriaxone in Critically III Patients

被引:15
作者
Heffernan, Aaron J. [1 ,2 ]
Sime, Fekade B. [1 ]
Kumta, Nilesh [1 ]
Wallis, Steven C. [1 ]
McWhinney, Brett [3 ]
Ungerer, Jacobus [3 ,4 ]
Wong, Gloria [1 ]
Joynt, Gavin M. [6 ]
Lipman, Jeffrey [1 ,5 ,7 ]
Roberts, Jason A. [1 ,7 ,8 ]
机构
[1] Univ Queensland, Ctr Clin Res, Fac Med, Herston, Qld, Australia
[2] Griffith Univ, Sch Med, Southport, Qld, Australia
[3] Pathol Queensland, Dept Chem Pathol, Herston, Qld, Australia
[4] Univ Queensland, Fac Biomed Sci, St Lucia, Qld, Australia
[5] Royal Brisbane & Womens Hosp, Jamieson Trauma Inst, Brisbane, Qld, Australia
[6] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Anaesthesia & Intens Care, Hong Kong, Peoples R China
[7] Univ Montpellier, Nimes Univ Hosp, Div Anaesthesiol Crit Care Emergency & Pain Med, Nimes, France
[8] Royal Brisbane & Womens Hosp, Dept Pharm, Brisbane, Qld, Australia
基金
英国医学研究理事会; 澳大利亚国家健康与医学研究理事会;
关键词
ceftriaxone; pharmacokinetics; dose; intensive care; intensive care unit; pharmacodynamics; population pharmacokinetics; INTENSIVE-CARE-UNIT; BETA-LACTAM ANTIBIOTICS; PROTEIN-BINDING; RENAL-FUNCTION; ILL PATIENTS; HYPOALBUMINEMIA;
D O I
10.1128/aac.02189-21
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The objective of this study was to describe the total and unbound population pharmacokinetics of ceftriaxone in critically ill adult patients and to define optimized dosing regimens. Total and unbound ceftriaxone concentrations were obtained from two pharmacokinetic studies and from a therapeutic drug monitoring (TDM) program at a tertiary hospital intensive care unit. Population pharmacokinetic analysis and Monte Carlo simulations were used to assess the probability of achieving a free trough concentration/MIC ratio of >= 1 using Pmetrics for R. A total of 474 samples (267 total and 207 unbound) were available from 36 patients. A two-compartment model describing ceftriaxone-albumin binding with both nonrenal and renal elimination incorporating creatinine clearance to explain the between-patient variability best described the data. An albumin concentration of <= 20 g/L decreased the probability of target attainment (PTA) by up to 20% across different dosing regimens and simulated creatinine clearances. A ceftriaxone dose of 1 g twice daily is likely therapeutic in patients with creatinine clearance of <100 mL/min infected with susceptible isolates (PTA, similar to 90%). Higher doses administered as a continuous infusion (4 g/day) are needed in patients with augmented renal clearance (creatinine clearance, >130 mL/min) who are infected by pathogens with a MIC of >= 0.5 mg/L The ceftriaxone dose should be based on the patient's renal function and albumin concentration, as well as the isolate MIC. Hypoalbuminemia decreases the PTA in patients receiving intermittent dosing by up to 20%.
引用
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页数:15
相关论文
共 34 条
[1]   Antimicrobial therapeutic drug monitoring in critically ill adult patients: a Position Paper# [J].
Abdul-Aziz, Mohd H. ;
Alffenaar, Jan-Willem C. ;
Bassetti, Matteo ;
Bracht, Hendrik ;
Dimopoulos, George ;
Marriott, Deborah ;
Neely, Michael N. ;
Paiva, Jose-Artur ;
Pea, Federico ;
Sjovall, Fredrik ;
Timsit, Jean F. ;
Udy, Andrew A. ;
Wicha, Sebastian G. ;
Zeitlinger, Markus ;
De Waele, Jan J. ;
Roberts, Jason A. .
INTENSIVE CARE MEDICINE, 2020, 46 (06) :1127-1153
[2]   A method for determining the free (unbound) concentration of ten beta-lactam antibiotics in human plasma using high performance liquid chromatography with ultraviolet detection [J].
Briscoe, Scott E. ;
McWhinney, Brett C. ;
Lipman, Jeffrey ;
Roberts, Jason A. ;
Ungerer, Jacobus P. J. .
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2012, 907 :178-184
[3]   Population pharmacokinetics of total and unbound teicoplanin concentrations and dosing simulations in patients with haematological malignancy [J].
Byrne, Catherine J. ;
Parton, Ted ;
McWhinney, Brett ;
Fennell, Jerome P. ;
O'Byrne, Philomena ;
Deasy, Evelyn ;
Egan, Sean ;
Enright, Helen ;
Desmond, Ronan ;
Ryder, Sheila A. ;
D'Arcy, Deirdre M. ;
McHugh, Johnny ;
Roberts, Jason A. .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2018, 73 (04) :995-1003
[4]  
Carr DR, 2018, OPEN FORUM INFECT DI, V5, DOI [10.1093/ofid/ofy89, 10.1093/ofid/ofy089]
[5]   Pharmacokinetic/pharmacodynamic parameters: Rationale for antibacterial dosing of mice and men [J].
Craig, WA .
CLINICAL INFECTIOUS DISEASES, 1998, 26 (01) :1-10
[6]  
European Committee on Antimicrobial Susceptibility Testing, 2018, BREAKPOINT TABLES IN
[7]   Effect of baseline serum albumin concentration on outcome of resuscitation with albumin or saline in patients in intensive care units: analysis of data from the saline versus albumin fluid evaluation (SATE) study [J].
Finfer, Simon ;
Bellomo, Rinaldo .
BRITISH MEDICAL JOURNAL, 2006, 333 (7577) :1044-1046
[8]   Population pharmacokinetics of ceftriaxone in critically ill septic patients: a reappraisal [J].
Garot, Denis ;
Respaud, Renaud ;
Lanotte, Philippe ;
Simon, Nicolas ;
Mercier, Emmanuelle ;
Ehrmann, Stephan ;
Perrotin, Dominique ;
Dequin, Pierre-Francois ;
Le Guellec, Chantal .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2011, 72 (05) :758-767
[9]   High-Dose Ceftriaxone for Bacterial Meningitis and Optimization of Administration Scheme Based on Nomogram [J].
Gregoire, Matthieu ;
Dailly, Eric ;
Le Turnier, Paul ;
Garot, Denis ;
Guimard, Thomas ;
Bernard, Louis ;
Tattevin, Pierre ;
Vandamme, Yves-Marie ;
Hoff, Jerome ;
Lemaitre, Florian ;
Verdier, Marie-Clemence ;
Deslandes, Guillaume ;
Bellouard, Ronan ;
Sebille, Veronique ;
Chiffoleau, Anne ;
Boutoille, David ;
Navas, Dominique ;
Asseray, Nathalie .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2019, 63 (09)
[10]   Intrapulmonary pharmacokinetics of antibiotics used to treat nosocomial pneumonia caused by Gram-negative bacilli: A systematic review [J].
Heffernan, Aaron J. ;
Sime, Fekade B. ;
Lipman, Jeffrey ;
Dhanani, Jayesh ;
Andrews, Katherine ;
Ellwood, David ;
Grimwood, Keith ;
Roberts, Jason A. .
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2019, 53 (03) :234-245