Modelled target attainment after meropenem infusion in patients with severe nosocomial pneumonia: the PROMESSE study.

[en] OBJECTIVES: The objective of this study was to propose an optimal treatment regimen of meropenem in critically ill patients with severe nosocomial pneumonia. PATIENTS AND METHODS: Among 55 patients in intensive care treated with 1 g of meropenem every 8 h for severe nosocomial pneumonia, 30 were assigned to intermittent infusion (II; over 0.5 h) and 25 to extended infusion (EI; over 3 h) groups. Based on plasma and epithelial lining fluid (ELF) concentrations determined at steady-state, pharmacokinetic modelling and Monte Carlo simulations were undertaken to assess the probability of attaining drug concentrations above the MIC for 40%-100% of the time between doses (%T > 1-fold and 4-fold MIC), for 1 or 2 g administered by either method. RESULTS: Penetration ratio, measured by the ELF/plasma ratio of AUCs, was statistically higher in the EI group than in the II group (mean +/- SEM: 0.29 +/- 0.030 versus 0.20 +/- 0.033, P = 0.047). Considering a maximum susceptibility breakpoint of 2 mg/L, all dosages and modes of infusions achieved 40%-100% T > 1-fold MIC in plasma, but none did so in ELF, and only the 2 g dose over EI achieved 40%-100% T > 4-fold MIC in plasma. CONCLUSIONS: The optimum regimen to treat severe nosocomial pneumonia was 2 g of meropenem infused over 3 h every 8 h. This regimen achieved the highest pharmacodynamic targets both in plasma and in ELF.

Disciplines :

Immunology & infectious disease

Author, co-author :

FRIPPIAT, Frédéric ; Centre Hospitalier Universitaire de Liège - CHU > Maladies infectieuses et médecine interne générale

Musuamba, Flora Tshinanu

Seidel, Laurence ; Université de Liège - ULiège > Département des sciences de la santé publique > Informatique médicale et biostatistique

Albert, Adelin ; Université de Liège - ULiège > Département des sciences de la santé publique > Département des sciences de la santé publique

DENOOZ, Raphael ; Centre Hospitalier Universitaire de Liège - CHU > Toxicologie clinique

Charlier, Corinne ; Université de Liège - ULiège > Département de pharmacie > Chimie toxicologique

Van Bambeke, Francoise

Wallemacq, Pierre

DESCY, Julie ; Centre Hospitalier Universitaire de Liège - CHU > Microbiologie médicale

LAMBERMONT, Bernard ; Centre Hospitalier Universitaire de Liège - CHU > Frais communs médecine

More authors (3 more)

Language :

English

Title :

Modelled target attainment after meropenem infusion in patients with severe nosocomial pneumonia: the PROMESSE study.

Publication date :

12 September 2014

Journal title :

Journal of Antimicrobial Chemotherapy

ISSN :

0305-7453

eISSN :

1460-2091

Publisher :

Oxford University Press, London, United Kingdom

Volume :

Pages :

207-216

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

(c) The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Available on ORBi :

since 07 October 2014

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Niederman MS, Craven DE, Bonten MJ et al. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388-416.
Bartlett JG, Barie PS, Niederman MS et al. Workshop on clinical trials of antibacterial agents for hospital-acquired pneumonia and ventilatorassociated pneumonia. Clin Infect Dis 2010; 51 Suppl 1: 1-3.
Craig WA. Pharmacokinetic/pharmacodynamics parameters: rational for antibacterial dosing of mices and men. Clin Infect Dis 1998; 26: 1-12.
Nicolau DP. Pharmacokinetic and pharmacodynamics properties of meropenem. Clin Infect Dis 2008; 47 Suppl 1: 32-40.
Gonçalves-Pereira J, Póvoa P. Antibiotics in critically ill patients: a systematic review of the pharmacokinetics of β-lactams. Crit Care 2011; 15: R206.
Chytra I, Stepan M, Benes J et al. Clinical and microbiological efficacy of continuous versus intermittent application of meropenem in critically ill patients: a randomized open-label controlled trial. Crit Care 2012; 28: R113.
Roberts JA, Ulldemolins M, Roberts MS et al. Therapeutic drugmonitoring of β-lactams in critically ill patients: proof of concept. Int J Antimicrob Agents 2010; 36: 332-9.
Dulhunty JM, Roberts JA, Davis JS et al. Continuous infusion of β-lactam antibiotics in severe sepsis: a multicenter double-blind, randomized controlled trial. Clin Infect Dis 2013; 56: 236-44.
Falagas ME, Tansarli GS, Ikawa K et al. Clinical outcomes with extended or continuous versus short-termintravenous infusion of carbapenems and piperacillin/tazobactam: a systematic review and meta-analysis. Clin Infect Dis 2013; 56: 272-82.
Jaruratanasirikul S, Sriwiriyajan S, Punyo J. Comparison of the pharmacodynamics of meropenem in patients with ventilator-associated pneumonia following administration by 3-hour infusion or bolus injection. Antimicrob Agents Chemother 2005; 49: 1337-9.
Thalhammer F, Traunmüller F, El Menyawi I et al. Continuous infusion versus intermittent administration of meropenem in critically ill patients. J Antimicrob Chemother 1999; 43: 523-7.
Roberts JA, Kirkpatrick CM, Roberts MS et al. Meropenem dosing in critically ill patients with sepsis and without renal dysfunction: intermittent bolus versus continuous administration? Monte Carlo dosing simulations and subcutaneous tissue distribution. J Antimicrob Chemother 2009; 64: 142-50.
Nicasio AM, Eagye KJ, Nicolau DP et al. Pharmacodynamic-based clinical pathway for empiric antibiotic choice in patients with ventilatorassociated pneumonia. J Crit Care 2010; 25: 69-77.
Baldwin DR, Honeybourne D, Wise R. Pulmonary disposition of antimicrobial agents: methodological considerations. Antimicrob Agents Chemother 1992; 36: 1171-5.
Boselli E, Breilh D, Saux MC et al. Pharmacokinetics and lung concentrations of ertapenem in patients with ventilator-associated pneumonia. Intensive Care Med 2006; 32: 2059-62.
Rodvold KA, George JM, Yoo L. Penetration of anti-infective agents into pulmonary epithelial lining fluid. Clin Pharmacokinetic 2011; 50: 637-64.
Kiem S, Schentag JJ. Interpretation of antibiotic concentration ratios measured in epithelial lining fluid. Antimicrob Agents Chemother 2008; 52: 24-36.
Roberts JA, Kirkpatrick CM, Lipman J. Monte Carlo simulations: maximizing antibiotic pharmacokinetic data to optimize clinical practice for critically ill patients. J Antimicrob Chemother 2011; 66: 227-31.
Levey AS, Coresh J, Balk E et al. National Kidney Foundation: National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 2003; 139: 137-47.
Ferrer M, Liapikou A, Valencia M et al. Validation of the American Thoracic Society-Infectious Diseases Society of America guidelines for hospital-acquired pneumonia in the intensive care unit. Clin Infect Dis 2010; 50: 945-52.
Luna CM, Blanzaco D, Niederman MS et al. Resolution of ventilatorassociated pneumonia: prospective evaluation of the clinical pulmonary infection score as an early clinical predictor of outcome. Crit Care Med 2003; 31: 676-82.
Claus B, Buyle F, Robays H et al. Importance of infusion volume and pump characteristics in extended administration of β-lactam antibiotics. Antimicrob Agents Chemother 2010; 54: 4950.
Denooz R, Charlier C. Simultaneous determination of five β-lactam antibiotics (cefepim, ceftazidim, cefuroxim, meropenem and piperacillin) in human plasma by high-performance liquid chromatography with ultraviolet detection. J Chromatogr B Analyt Technol Biomed Life Sci 2008; 864: 161-7.
Allegranzi B, Cazzadori A, Di Perri G et al. Concentration of single-dose meropenem (1 g iv) in bronchoalveolar lavage and epithelial lining fluid. J Antimicrob Chemother 2000; 46: 319-22.
Conte JE, Golden JA, Kelley MG et al. Intrapulmonary pharmacokinetics and pharmacodynamics of meropenem. Int J Antimicrob Agents 2005; 26: 449-56.
Lodise TP, Sorgel F, Melnick D et al. Penetration of meropenem into epithelial lining fluid of patients with ventilator-associated pneumonia. Antimicrob Agents Chemother 2011; 55: 1606-10.
Lindbom L, Pihlgren P, Jonsson EN. PsN-toolkit-a collection of computer intensive statistical methods for non-linear mixed effect modeling using NONMEM. Comput Meth Programs Biomed 2005; 79: 241-57.
The R project for statistical computing. http://www.r-project.org/(17 july 2014, date last accessed).
Ette EI, Ludden TM. Population pharmacokinetic modeling: The importance of informative graphics. Pharm Res 1995; 12: 1845-55.
Clinical Breakpoints-Bacteria. http://www.eucast.org/clinical_breakpoints/.
Li C, Du X, Kuti JL et al. Clinical pharmacodynamics of meropenem in patients with lower respiratory tract infections. Antimicrob Agents Chemother 2007; 51: 1725-30.
Mouton JW, Theuretzbacher U, Craig WA et al. Tissue concentrations: do we ever learn ?. J Antimicrob Chemother 2008; 61: 235-7.
Kikuchi E, Kikuchi J, Nasuhara Y et al. Comparison of the pharmacodynamics of biapenem in bronchial epithelial lining fluid in healthy volunteers given half-hour and three-hour intravenous infusions. Antimicrob Agents Chemother 2009; 53: 2799-803.
Tomaselli F, Maier A, Matzi V et al. Penetration of meropenem into pneumonic human lung tissue as measured by in vivo microdialysis. Antimicrob Agents Chemother 2004; 48: 2228-32.
Ambrose P, Bhavnani SM, Ellis-Grosse EJ et al. Pharmacokineticpharmacodynamic considerations in the design of hospital-acquired or ventilator-associated bacterial pneumonia studies: look before you leap! Clin Infect Dis 2010; 51 Suppl 1: 103-10.
Zhou QT, He B, Zhang C, Zhai SD et al. Pharmacokinetics and pharmacodynamics of meropenem in elderly Chinese with lower respiratory tract infections. Drugs Aging 2011; 28: 903-12.
Jaruratanasirikul S, Limapichat T, Jullangkoon M et al. Pharmacodynamics of meropenem in critically ill patients with febrile neutropenia and bacteraemia. Int J Antimicrob Agents 2011; 38: 231-6.
Kitzes-Cohen R, Farin D, Piva G et al. Pharmacokinetics and pharmacodynamics of meropenem in critically ill patients. Int J Antimicrob Agents 2002; 19: 105-10.
Binder L, Schwörer H, Hoppe S et al. Pharmacokinetics of meropenem in critically ill patients with severe infections. The Drug Monit 2013; 35: 67-70.
Drusano GL, Hutchison M. The pharmacokinetics of meropenem. Scand J Infect Dis 1995; 96: 11-6.