Modelled target attainment after temocillin treatment in severe pneumonia: systemic and epithelial lining fluid pharmacokinetics of continuous versus intermittent infusions.
Layios, Nathalie; Visée, C.; Mistretta, V.et al.
2022 • In Antimicrobial Agents and Chemotherapy, p. 0205221
temocillin; pharmacokinetics; pneumonia; Epithelial lining fluid; Monte Carlo; breakpoints
Abstract :
[en] Objectives: To describe the population pharmacokinetics of temocillin administered via continuous versus intermittent infusion in critically ill patients with pneumonia. Secondary objectives included characterization of epithelial lining fluid (ELF)/plasma penetration ratios and determination of the probability of target attainment (PTA) for a range of MICs. Methods: Thirty-two mechanically ventilated patients who were treated for pneumonia with 6g of temocillin daily for in vitro sensitive pathogens were assigned either to the II (2g every 8h over 0.5h) or to the CI (6g over 24h after a loading dose of 2g) group. A population pharmacokinetic model was developed using unbound plasma and total ELF concentrations of temocillin and related Monte Carlo simulations were performed to assess PTAs. Results: The AUC(0-24) ELF/plasma penetration ratio was 0.73, at steady-state, for both modes of infusion and whatever the level of creatinine clearance. Monte Carlo simulations showed for the minimal pharmacodynamic (PD) targets of 50% T> 1X MIC (II group) and 100% T > 1X MIC (CI group), PK/PD breakpoints of 4 mg/L in plasma and 2 mg/L in ELF and 4mg/L in plasma and ELF, respectively. The breakpoint was 8 mg/L in ELF for both modes of infusion in patients with CL(CR)<60mL/min. Conclusion: While CI provides better PKPD indexes, the latter remain below available recommendations for systemic infections, except in case of moderate renal impairment, thereby warranting future clinical studies in order to determine the efficacy of temocillin in severe pneumonia.
Denooz, Raphaël ; Université de Liège - ULiège > Département de pharmacie > Pharmacocintéique et pharmacovigilence
Maes, Nathalie ; Centre Hospitalier Universitaire de Liège - CHU > > Service des informations médico économiques (SIME)
Descy, Julie ; Université de Liège - ULiège University Hospital of Liège Service de Microbiologie Clinique
Frippiat, Frédéric ; Université de Liège - ULiège University Hospital of Liège
Marchand, S.
Grégoire, N.
Language :
English
Title :
Modelled target attainment after temocillin treatment in severe pneumonia: systemic and epithelial lining fluid pharmacokinetics of continuous versus intermittent infusions.
Publication date :
2022
Journal title :
Antimicrobial Agents and Chemotherapy
ISSN :
0066-4804
eISSN :
1098-6596
Publisher :
American Society for Microbiology, Washington, United States - District of Columbia
Pages :
AAC0205221
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
FIRS - CHU Liège. Fonds d'Investissement de Recherche Scientifique [BE]
Livermore DM, Hope R, Fagan EJ, Warner M, Woodford N, Potz N. 2006. Activity of temocillin against prevalent ESBL- and AmpC-producing Enterobacteriaceae from south-east England. J Antimicrob Chemother 57: 1012-1014. https://doi.org/10.1093/jac/dkl043.
Gupta ND, Smith RE, Balakrishnan I. 2009. Clinical efficacy of temocillin. J Antimicrob Chemother 64:431-433. https://doi.org/10.1093/jac/dkp208.
Balakrishnan I, Awad-El-Kariem FM, Aali A, Kumari P, Mulla R, Tan B, Brudney D, Ladenheim D, Ghazy A, Khan I, Virgincar N, Iyer S, Carryn S, Van de Velde S. 2011. Temocillin use in England: clinical and microbiological efficacies in infections caused by extended-spectrum and/or derepressed AmpC b-lactamase-producing Enterobacteriaceae. J Antimicrob Chemother 66:2628-2631. https://doi.org/10.1093/jac/dkr317.
De Jongh R, Hens R, Basma V, Mouton JW, Tulkens PM, Carryn S. 2008. Continuous versus intermittent infusion of temocillin, a directed spectrum penicillin for intensive care patients with nosocomial pneumonia: stability, compatibility, population pharmacokinetic studies and breakpoint selection. J Antimicrob Chemother 61:382-388. https://doi.org/10 .1093/jac/dkm467.
Laterre P-F, Wittebole X, Van de Velde S, Muller AE, Mouton JW, Carryn S, Tulkens PM, Dugernier T. 2015. Temocillin (6 g daily) in critically ill patients: continuous infusion versus three times daily administration. J Antimicrob Chemother 70:891-898. https://doi.org/10.1093/jac/dku465.
Roberts JA, Paratz J, Paratz E, Krueger WA, Lipman J. 2007. Continuous infusion of beta-lactam antibiotics in severe infections: a review of its role. Int J Antimicrob Agents 30:11-18. https://doi.org/10.1016/j.ijantimicag.2007.02 .002.
Vardakas KZ, Voulgaris GL, Maliaros A, Samonis G, Falagas ME. 2018. Prolonged versus short-term intravenous infusion of antipseudomonal betalactams for patients with sepsis: a systematic review and meta-analysis of randomised trials. Lancet Infect Dis 18:108-120. https://doi.org/10.1016/ S1473-3099(17)30615-1.
Lee YR, Miller PD, Alzghari SK, Blanco DD, Hager JD, Kuntz KS. 2018. Continuous infusion versus intermittent bolus of beta-lactams in critically ill patients with respiratory infections: a systematic review and metaanalysis. Eur J Drug Metab Pharmacokinet 43:155-170. https://doi.org/10 .1007/s13318-017-0439-5.
Alexandre K, Fantin B. 2018. Pharmacokinetics and pharmacodynamics of temocillin. Clin Pharmacokinet 57:287-296. https://doi.org/10.1007/s40262 -017-0584-7.
CraigWA. 2003. Basic pharmacodynamics of antibacterials with clinical applications to the use of beta-lactams, glycopeptides, and linezolid. Infect Dis Clin North Am17:479-501. https://doi.org/10.1016/S0891-5520(03)00065-5.
European Committee on Antimicrobial Susceptibility Testing. 2021. Temocillin: rationale for the clinical breakpoints, version 1.0. https://www .eucast.org/publications_and_documents/consultations/#c18518.
Udy AA, Roberts JA, Boots RJ, et al. 2010. Augmented renal clearance: implications for antibacterial dosing in the critically ill. Clin Pharmacokinet 49:1-16.
Boselli E, Breilh D, Saux MC, Gordien JB, Allaouchiche B. 2006. Pharmacokinetics and lung concentrations of ertapenem in patients with ventilator-associated pneumonia. Intensive Care Med 32:2059-2062. https://doi .org/10.1007/s00134-006-0401-5.
Frippiat F, Musuamba FT, Seidel L, Albert A, Denooz R, Charlier C, Van Bambeke F, Wallemacq P, Descy J, Lambermont B, Layios N, Damas P, Moutschen M. 2015. Modelled target attainment after meropenem infusion in patients with severe nosocomial pneumonia: the PROMESSE study. J Antimicrob Chemother 70:207-216. https://doi.org/10.1093/jac/ dku354.
Rodvold KA, George JM, Yoo L. 2011. Penetration of anti-infective agents into pulmonary epithelial lining fluid: focus on antibacterial agents. Clin Pharmacokinet 50:637-664. https://doi.org/10.2165/11594090-000000000 -00000.
Boselli E, Breilh D, Duflo F, Saux M-C, Debon R, Chassard D, Allaouchiche B. 2003. Steady-state plasma and intrapulmonary concentrations of cefepime administered in continuous infusion in critically ill patients with severe nosocomial pneumonia. Crit Care Med 31:2102-2106. https://doi .org/10.1097/01.CCM.0000069734.38738.C8.
Heffernan AJ, Sime FB, Lipman J, Dhanani J, Andrews K, Ellwood D, Grimwood K, Roberts JA. 2019. Intrapulmonary pharmacokinetics of antibiotics used to treat nosocomial pneumonia caused by Gram-negative bacilli: a systematic review. Int J Antimicrob Agents 53:234-245. https:// doi.org/10.1016/j.ijantimicag.2018.11.011.
Overbosch D, van Gulpen C, Mattie H. 1985. Renal clearance of temocillin in volunteers. Drugs 29(Suppl 5):128-134. https://doi.org/10.2165/00003495 -198500295-00027.
Casu GS, Hites M, Jacobs F, Cotton F, Wolff F, Beumier M, De Backer D, Vincent J-L, Taccone FS. 2013. Can changes in renal function predict variations in beta-lactam concentrations in septic patients?. Int J Antimicrob Agents 42:422-428. https://doi.org/10.1016/j.ijantimicag.2013.06.021.
Carlier M, Carrette S, Roberts JA, Stove V, Verstraete A, Hoste E, Depuydt P, Decruyenaere J, Lipman J, Wallis SC, DeWaele JJ. 2013. Meropenemand piperacillin/ tazobactam prescribing in critically ill patients: does augmented renal clearance affect pharmacokinetic/pharmacodynamic target attainment when extended infusions are used?. Crit Care 17:R84. https://doi.org/10.1186/cc12705.
Huttner A, Von Dach E, Renzoni A, Huttner BD, Affaticati M, Pagani L, Daali Y, Pugin J, Karmime A, Fathi M, Lew D, Harbarth S. 2015. Augmented renal clearance, low beta-lactam concentrations and clinical outcomes in the critically ill: an observational prospective cohort study. Int J Antimicrob Agents 45:385-392. https://doi.org/10.1016/j.ijantimicag.2014.12.017.
Sime FB, Udy AA, Roberts JA. 2015. Augmented renal clearance in critically ill patients: etiology, definition and implications for beta-lactam dose optimization. Curr Opin Pharmacol 24:1-6. https://doi.org/10.1016/j .coph.2015.06.002.
European Committee on Antimicrobial Susceptibility Testing. 2021. Addendum: temocillin breakpoints and AST methods. https://www.eucast.org/ fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/Addenda/ Addendum_Temocillin_breakpoints_and_AST_2020.pdf.
Alobaid A, Hites M, Lipman J, Taccone FS, Roberts JA. 2016. Effects of obesity on the pharmacokinetics of antimicrobials in critically ill patients: a structured review. Int J Antimicrob Agents 47:259-268. https://doi.org/10 .1016/j.ijantimicag.2016.01.009.
Carryn S, Couwenbergh N, Tulkens PM. 2010. Long-term stability of temocillin in elastomeric pumps for outpatient antibiotic therapy in cystic fibrosis patients. J Antimicrob Chemother 65:2045-2046. https://doi.org/ 10.1093/jac/dkq229.
Rennard SI, Basset G, Lecossier D, O'Donnell KM, Pinkston P, Martin PG, Crystal RG. 1986. Estimation of volume of epithelial lining fluid recovered by lavage using urea as marker of dilution. J Appl Physiol (1985) 60:532-538. https://doi.org/10.1152/jappl.1986.60.2.532.
Rennard SI, Ghafouri M, Thompson AB, Linder J, Vaughan W, Jones K, Ertl RF, Christensen K, Prince A, Stahl MG. 1990. Fractional processing of sequential bronchoalveolar lavage to separate bronchial and alveolar samples. Am Rev Respir Dis 141:208-217. https://doi.org/10.1164/ajrccm/141 .1.208.
LindbomL, Pihlgren P, Jonsson EN, Jonsson N. 2005. PsN-Toolkit-a collection of computer intensive statistical methods for non-linear mixed effect modeling using NONMEM. Comput Methods Programs Biomed 79:241-257. https://doi.org/10.1016/j.cmpb.2005.04.005.
Dosne A-G, Bergstrand M, Harling K, Karlsson MO. 2016. Improving the estimation of parameter uncertainty distributions in nonlinear mixed effects models using sampling importance resampling. J Pharmacokinet Pharmacodyn 43:583-596. https://doi.org/10.1007/s10928-016-9487-8
