Login Register Cart 0
Generic placeholder image

Current Drug Metabolism

Editor-in-Chief

ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Meropenem for the Pharmacological Treatment of Severe Infections in Critically Ill Pediatric Patients: Breakthrough Standard Treatment Strategies Based on PK/PD

Author(s): Xin He, Xiaoyan Liu, Xiaodan Gong, Li Wang* and Feng Chen*

Volume 24, Issue 1, 2023

Published on: 28 March, 2023

Page: [5 - 15] Pages: 11

DOI: 10.2174/1389200224666230325121729

Price: $65

conference banner
Abstract

Meropenem, as a carbapenem antibiotic, is commonly used in critically ill pediatric patients with severe infection because of its broad antimicrobial spectrum, high penetration into tissues, and favorable safety profile. Due to pathophysiological changes in critically ill children, the available evidence has demonstrated that the standard dosage regimens of meropenem could not meet an appropriate pharmacodynamic (PD) target attainment in severely infected children. Therefore, we reviewed the pharmacokinetic (PK) profile of meropenem in critically ill children, therapeutic drug monitoring (TDM), and dose optimization based on PK/PD. Meropenem kills bacteria in a timedependent manner and its efficacy is positively correlated with the percentage of the time of dosing interval during which the free serum concentration of meropenem remains above the minimum inhibitory concentration (MIC) of the pathogen (%fT>MIC), which is related to PK/PD targets. For critically ill children, TDM-based dosage optimization and setting even higher PK/PD targets seem necessary to be considered. The currently available studies have revealed that increasing the dose and the application of the extended or continuous infusion of meropenem were able to achieve better PK/PD targets. According to limited clinical data on efficacy and safety, these treatment measures cannot yet be adopted as routine regimens only when serious infections caused by drug-resistant bacteria or strains with high values of MIC are suspected. Further high-quality randomized controlled trials (RCTs) or observational studies with sufficient sample sizes are required to confirm the efficacy and safety of these modes of administration.

« Previous Next »
Graphical Abstract

[1]
Engel, C.; Brunkhorst, F.M.; Bone, H.G.; Brunkhorst, R.; Gerlach, H.; Grond, S.; Gruendling, M.; Huhle, G.; Jaschinski, U.; John, S.; Mayer, K.; Oppert, M.; Olthoff, D.; Quintel, M.; Ragaller, M.; Rossaint, R.; Stuber, F.; Weiler, N.; Welte, T.; Bogatsch, H.; Hartog, C.; Loeffler, M.; Reinhart, K. Epidemiology of sepsis in Germany: Results from a national prospective multicenter study. Intensive Care Med., 2007, 33(4), 606-618.
[http://dx.doi.org/10.1007/s00134-006-0517-7] [PMID: 17323051]
[2]
Vincent, J.L.; Rello, J.; Marshall, J.; Silva, E.; Anzueto, A.; Martin, C.D.; Moreno, R.; Lipman, J.; Gomersall, C.; Sakr, Y.; Reinhart, K. International study of the prevalence and outcomes of infection in intensive care units. JAMA, 2009, 302(21), 2323-2329.
[http://dx.doi.org/10.1001/jama.2009.1754] [PMID: 19952319]
[3]
Kempker, J.A.; Martin, G.S. The changing epidemiology and definitions of sepsis. Clin. Chest Med., 2016, 37(2), 165-179.
[http://dx.doi.org/10.1016/j.ccm.2016.01.002] [PMID: 27229635]
[4]
Biban, P.; Gaffuri, M.; Spaggiari, S.; Zaglia, F.; Serra, A.; Santuz, P. Early recognition and management of septic shock in children. Pediatr. Rep., 2012, 4(1), e13.
[http://dx.doi.org/10.4081/pr.2012.e13] [PMID: 22690305]
[5]
Niederman, M.S. Use of broad-spectrum antimicrobials for the treatment of pneumonia in seriously ill patients: Maximizing clinical outcomes and minimizing selection of resistant organisms. Clin. Infect. Dis., 2006, 42(S2), S72-S81.
[http://dx.doi.org/10.1086/499405] [PMID: 16355320]
[6]
Kaukonen, K.M.; Bailey, M.; Suzuki, S.; Pilcher, D.; Bellomo, R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. JAMA, 2014, 311(13), 1308-1316.
[http://dx.doi.org/10.1001/jama.2014.2637] [PMID: 24638143]
[7]
Abdulla, A.; Ewoldt, T.M.J.; Hunfeld, N.G.M.; Muller, A.E.; Rietdijk, W.J.R.; Polinder, S.; van Gelder, T.; Endeman, H.; Koch, B.C.P. The effect of therapeutic drug monitoring of beta-lactam and fluoroquinolones on clinical outcome in critically ill patients: The DOLPHIN trial protocol of a multi-centre randomised controlled trial. BMC Infect. Dis., 2020, 20(1), 57.
[http://dx.doi.org/10.1186/s12879-020-4781-x] [PMID: 31952493]
[8]
Kumar, A.; Roberts, D.; Wood, K.E.; Light, B.; Parrillo, J.E.; Sharma, S.; Suppes, R.; Feinstein, D.; Zanotti, S.; Taiberg, L.; Gurka, D.; Kumar, A.; Cheang, M. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit. Care Med., 2006, 34(6), 1589-1596.
[http://dx.doi.org/10.1097/01.CCM.0000217961.75225.E9] [PMID: 16625125]
[9]
Varghese, J.M.; Roberts, J.A.; Lipman, J. Antimicrobial pharmacokinetic and pharmacodynamic issues in the critically ill with severe sepsis and septic shock. Crit. Care Clin., 2011, 27(1), 19-34.
[http://dx.doi.org/10.1016/j.ccc.2010.09.006] [PMID: 21144984]
[10]
Wiseman, L.R.; Wagstaff, A.J.; Brogden, R.N.; Bryson, H.M. Meropenem a review of its antibacterial activity, pharmacokinetic properties and clinical efficacy. Drugs, 1995, 50(1), 73-101.
[http://dx.doi.org/10.2165/00003495-199550010-00007] [PMID: 7588092]
[11]
Pea, F.; Viale, P. Bench-to-bedside review: Appropriate antibiotic therapy in severe sepsis and septic shock – does the dose matter? Crit. Care, 2009, 13(3), 214.
[http://dx.doi.org/10.1186/cc7774] [PMID: 19519961]
[12]
Rello, J.; Ulldemolins, M.; Lisboa, T.; Koulenti, D.; Mañez, R.; Martin-Loeches, I.; De Waele, J.J.; Putensen, C.; Guven, M.; Deja, M.; Diaz, E. Determinants of prescription and choice of empirical therapy for hospital-acquired and ventilator-associated pneumonia. Eur. Respir. J., 2011, 37(6), 1332-1339.
[http://dx.doi.org/10.1183/09031936.00093010] [PMID: 20847075]
[13]
Thalhammer, F.; Hörl, W.H. Pharmacokinetics of meropenem in patients with renal failure and patients receiving renal replacement therapy. Clin. Pharmacokinet., 2000, 39(4), 271-279.
[http://dx.doi.org/10.2165/00003088-200039040-00003] [PMID: 11069213]
[14]
Cies, J.J.; Moore, W.S., II; Dickerman, M.J.; Small, C.; Carella, D.; Chopra, A.; Parker, J. Pharmacokinetics of continuous-infusion meropenem in a pediatric patient receiving extracorporeal life support. Pharmacotherapy, 2014, 34(10), e175-e179.
[http://dx.doi.org/10.1002/phar.1476] [PMID: 25146254]
[15]
Nicolau, D.P. Pharmacokinetic and pharmacodynamic properties of meropenem. Clin. Infect. Dis., 2008, 47(S1), S32-S40.
[http://dx.doi.org/10.1086/590064] [PMID: 18713048]
[16]
Gonçalves-Pereira, J.; Póvoa, P. Antibiotics in critically ill patients: A systematic review of the pharmacokinetics of β-lactams. Crit. Care, 2011, 15(5), R206.
[http://dx.doi.org/10.1186/cc10441] [PMID: 21914174]
[17]
McKinney, C.W.; Pruden, A. Ultraviolet disinfection of antibiotic resistant bacteria and their antibiotic resistance genes in water and wastewater. Environ. Sci. Technol., 2012, 46(24), 13393-13400.
[http://dx.doi.org/10.1021/es303652q] [PMID: 23153396]
[18]
Carlet, J.; Jarlier, V.; Harbarth, S.; Voss, A.; Goossens, H.; Pittet, D. Ready for a world without antibiotics? The pensières antibiotic resistance call to action. Antimicrob. Resist. Infect. Control, 2012, 1(1), 11.
[http://dx.doi.org/10.1186/2047-2994-1-11] [PMID: 22958833]
[19]
Villegas, M.V.; Briceno, D.F.; Ruiz, S.J.; Furtado, G.H.; Nicolau, D.P. Assessing the pharmacodynamic profile of intravenous antibiotics against prevalent Gram-negative organisms collected in] Colombia. Braz. J. Infect. Dis., 2011, 15(5), 413-419.
[http://dx.doi.org/10.1590/S1413-86702011000500001] [PMID: 22230846]
[20]
Pascale, R.; Giannella, M.; Bartoletti, M.; Viale, P.; Pea, F. Use of meropenem in treating carbapenem-resistant Enterobacteriaceae infections. Expert Rev. Anti Infect. Ther., 2019, 17(10), 819-827.
[http://dx.doi.org/10.1080/14787210.2019.1673731] [PMID: 31559876]
[21]
Pinder, M.; Bellomo, R.; Lipman, J. Pharmacological principles of antibiotic prescription in the critically ill. Anaesth. Intens. Care, 2002, 30(2), 134-144.
[http://dx.doi.org/10.1177/0310057X0203000203] [PMID: 12002919]
[22]
Hassan, E.; Ober, J.D. Predicted and measured aminoglycoside pharmacokinetic parameters in critically ill patients. Antimicrob. Agents Chemother., 1987, 31(11), 1855-1858.
[http://dx.doi.org/10.1128/AAC.31.11.1855] [PMID: 3435131]
[23]
Mathew, S.K.; Mathew, B.S.; Neely, M.N.; Naik, G.S.; Prabha, R.; Jacob, G.G. K, S.; Fleming, D.H. A nonparametric pharmacokinetic approach to determine the optimal dosing regimen for 30-minute and 3-hour meropenem infusions in critically Ill patients. Ther. Drug Monit., 2016, 38(5), 593-599.
[http://dx.doi.org/10.1097/FTD.0000000000000323] [PMID: 27454665]
[24]
Zhou, P.; Zhang, Y.; Wang, Z.; Ying, Y.; Xing, Y.; Tong, X.; Zhai, S. Extended or continuous infusion of carbapenems in children with severe infections: A systematic review and narrative synthesis. Antibiotics, 2021, 10(9), 1088.
[http://dx.doi.org/10.3390/antibiotics10091088] [PMID: 34572670]
[25]
Burger, R.; Guidi, M.; Calpini, V.; Lamoth, F.; Decosterd, L.; Robatel, C.; Buclin, T.; Csajka, C.; Marchetti, O. Effect of renal clearance and continuous renal replacement therapy on appropriateness of recommended meropenem dosing regimens in critically ill patients with susceptible life-threatening infections. J. Antimicrob. Chemother., 2018, 73(12), 3413-3422.
[http://dx.doi.org/10.1093/jac/dky370] [PMID: 30304491]
[26]
Furtado, G.H.; Cardinal, L.; Macedo, R.S.; Silva, J.O.; Medeiros, E.A.; Kuti, J.L.; Nicolau, D.P. Pharmacokinetic/pharmacodynamic target attainment of intravenous β-lactam regimens against Gram-negative bacteria isolated in a Brazilian teaching hospital. Rev. Soc. Bras. Med. Trop., 2015, 48(5), 539-545.
[http://dx.doi.org/10.1590/0037-8682-0122-2015] [PMID: 26516962]
[27]
Ellis, J.M.; Kuti, J.L.; Nicolau, D.P. Use of monte carlo simulation to assess the pharmacodynamics of β-lactams against pseudomonas aeruginosa infections in children: A report from the OPTAMA program. Clin. Ther., 2005, 27(11), 1820-1830.
[http://dx.doi.org/10.1016/j.clinthera.2005.11.007] [PMID: 16368453]
[28]
Craig, W.A. Pharmacokinetic/pharmacodynamic parameters: Rationale for antibacterial dosing of mice and men. Clin. Infect. Dis., 1998, 26(1), 1-10.
[http://dx.doi.org/10.1086/516284] [PMID: 9455502]
[29]
Roberts, J.A.; Abdul-Aziz, M.H.; Lipman, J.; Mouton, J.W.; Vinks, A.A.; Felton, T.W.; Hope, W.W.; Farkas, A.; Neely, M.N.; Schentag, J.J.; Drusano, G.; Frey, O.R.; Theuretzbacher, U.; Kuti, J.L. Individualised antibiotic dosing for patients who are critically ill: Challenges and potential solutions. Lancet Infect. Dis., 2014, 14(6), 498-509.
[http://dx.doi.org/10.1016/S1473-3099(14)70036-2] [PMID: 24768475]
[30]
Roberts, J.A.; Ulldemolins, M.; Roberts, M.S.; McWhinney, B.; Ungerer, J.; Paterson, D.L.; Lipman, J. Therapeutic drug monitoring of β-lactams in critically ill patients: Proof of concept. Int. J. Antimicrob. Agents, 2010, 36(4), 332-339.
[http://dx.doi.org/10.1016/j.ijantimicag.2010.06.008] [PMID: 20685085]
[31]
Delattre, I.K.; Taccone, F.S.; Jacobs, F.; Hites, M.; Dugernier, T.; Spapen, H.; Laterre, P.F.; Wallemacq, P.E.; Van Bambeke, F.; Tulkens, P.M. Optimizing β-lactams treatment in critically-ill patients using pharmacokinetics/pharmacodynamics targets: Are first conventional doses effective? Expert Rev. Anti Infect. Ther., 2017, 15(7), 677-688.
[http://dx.doi.org/10.1080/14787210.2017.1338139] [PMID: 28571493]
[32]
Abdul-Aziz, M.H.; Alffenaar, J.W.C.; Bassetti, M.; Bracht, H.; Dimopoulos, G.; Marriott, D.; Neely, M.N.; Paiva, J.A.; Pea, F.; Sjovall, F.; Timsit, J.F.; Udy, A.A.; Wicha, S.G.; Zeitlinger, M.; De Waele, J.J.; Roberts, J.A. Antimicrobial therapeutic drug monitoring in critically ill adult patients: A position paper. Intensive Care Med., 2020, 46(6), 1127-1153.
[http://dx.doi.org/10.1007/s00134-020-06050-1] [PMID: 32383061]
[33]
Craig, W.A. The pharmacology of meropenem, a new carbapenem antibiotic. Clin. Infect. Dis., 1997, 24(S2), S266-S275.
[http://dx.doi.org/10.1093/clinids/24.Supplement_2.S266] [PMID: 9126702]
[34]
Hutchison, M.; Faulkner, K.L.; Turner, P.J.; Haworth, S.J.; Sheikh, W.; Nadler, H.; Pitkin, D.H. A compilation of meropenem tissue distribution data. J. Antimicrob. Chemother., 1995, 36, 43-56.
[http://dx.doi.org/10.1093/jac/36.suppl_A.43] [PMID: 8543498]
[35]
Moon, Y.S.K.; Chung, K.C.; Gill, M.A. Pharmacokinetics of meropenem in animals, healthy volunteers, and patients. Clin. Infect. Dis., 1997, 24(S2), S249-S255.
[http://dx.doi.org/10.1093/clinids/24.Supplement_2.S249] [PMID: 9126700]
[36]
Nehus, E.J.; Mouksassi, S.; Vinks, A.A.; Goldstein, S. Meropenem in children receiving continuous renal replacement therapy: Clinical trial simulations using realistic covariates. J. Clin. Pharmacol., 2014, 54(12), 1421-1428.
[http://dx.doi.org/10.1002/jcph.360] [PMID: 25042683]
[37]
Leroy, A.; Fillastre, J.P.; Borsa-Lebas, F.; Etienne, I.; Humbert, G. Pharmacokinetics of meropenem (ICI 194,660) and its metabolite (ICI 213,689) in healthy subjects and in patients with renal impairment. Antimicrob. Agents Chemother., 1992, 36(12), 2794-2798.
[http://dx.doi.org/10.1128/AAC.36.12.2794] [PMID: 1482147]
[38]
Nilsson-Ehle, I.; Hutchison, M.; Haworth, S.J.; Norrby, S.R. Pharmacokinetics of meropenem compared to imipenem-cilastatin in young, healthy males. Eur. J. Clin. Microbiol. Infect. Dis., 1991, 10(2), 85-88.
[http://dx.doi.org/10.1007/BF01964413] [PMID: 1864280]
[39]
Bax, R.P.; Bastain, W.; Featherstone, A.; Wilkinson, D.M.; Hutchison, M.; Haworth, S.J. The pharmacokinetics of meropenem in volunteers. J. Antimicrob. Chemother., 1989, 24(Suppl. A), 311-320.
[http://dx.doi.org/10.1093/jac/24.suppl_A.311] [PMID: 2808215]
[40]
Harrison, M.P.; Moss, S.R.; Featherstone, A.; Fowkes, A.G.; Sanders, A.M.; Case, D.E. The disposition and metabolism of meropenem in laboratory animals and man. J. Antimicrob. Chemother., 1989, 24(Suppl. A), 265-277.
[http://dx.doi.org/10.1093/jac/24.suppl_A.265] [PMID: 2808212]
[41]
Baldwin, C.M.; Lyseng-Williamson, K.A.; Keam, S.J. Meropenem a review of its use in the treatment of serious bacterial infections. Drugs, 2008, 68(6), 803-838.
[http://dx.doi.org/10.2165/00003495-200868060-00006] [PMID: 18416587]
[42]
Hurst, M.; Lamb, H.M. Meropenem: A review of its use in patients in intensive care. Drugs, 2000, 59(3), 653-680.
[http://dx.doi.org/10.2165/00003495-200059030-00016] [PMID: 10776838]
[43]
Ljungberg, B.; Nilsson-Ehle, I. Pharmacokinetics of meropenem and its metabolite in young and elderly healthy men. Antimicrob. Agents Chemother., 1992, 36(7), 1437-1440.
[http://dx.doi.org/10.1128/AAC.36.7.1437] [PMID: 1510440]
[44]
Braune, S.; König, C.; Roberts, J.A.; Nierhaus, A.; Steinmetz, O.; Baehr, M.; Kluge, S.; Langebrake, C. Pharmacokinetics of meropenem in septic patients on sustained low-efficiency dialysis: A population pharmacokinetic study. Crit. Care, 2018, 22(1), 25.
[http://dx.doi.org/10.1186/s13054-018-1940-1] [PMID: 29382394]
[45]
Blumer, J.L.; Reed, M.D.; Kearns, G.L.; Jacobs, R.F.; Gooch, W.M., III; Yogev, R.; Willims, K.; Ewing, B.J. Sequential, single-dose pharmacokinetic evaluation of meropenem in hospitalized infants and children. Antimicrob. Agents Chemother., 1995, 39(8), 1721-1725.
[http://dx.doi.org/10.1128/AAC.39.8.1721] [PMID: 7486908]
[46]
Parker, E.M.; Hutchison, M.; Blumer, J.L. The pharmacokinetics of meropenem in infants and children: A population analysis. J. Antimicrob. Chemother., 1995, 36, 63-71.
[http://dx.doi.org/10.1093/jac/36.suppl_A.63] [PMID: 8543500]
[47]
Cies, J.J.; Moore, W.S., II; Enache, A.; Chopra, A. Population pharmacokinetics and pharmacodynamic target attainment of meropenem in critically Ill young children. J. Pediatr. Pharmacol. Ther., 2017, 22(4), 276-285.
[http://dx.doi.org/10.5863/1551-6776-22.4.276] [PMID: 28943823]
[48]
Binder, L.; Schwörer, H.; Hoppe, S.; Streit, F.; Neumann, S.; Beckmann, A.; Wachter, R.; Oellerich, M.; Walson, P.D. Pharmacokinetics of meropenem in critically ill patients with severe infections. Ther. Drug Monit., 2013, 35(1), 63-70.
[http://dx.doi.org/10.1097/FTD.0b013e31827d496c] [PMID: 23318279]
[49]
Blot, S.I.; Pea, F.; Lipman, J. The effect of pathophysiology on pharmacokinetics in the critically ill patient — Concepts appraised by the example of antimicrobial agents. Adv. Drug Deliv. Rev., 2014, 77, 3-11.
[http://dx.doi.org/10.1016/j.addr.2014.07.006] [PMID: 25038549]
[50]
Honore, P.M.; Jacobs, R.; Hendrickx, I.; De Waele, E.; Van Gorp, V.; Spapen, H.D. Meropenem therapy in extracorporeal membrane oxygenation patients: An ongoing pharmacokinetic challenge. Crit. Care, 2015, 19(1), 263.
[http://dx.doi.org/10.1186/s13054-015-0953-2] [PMID: 26095659]
[51]
Béranger, A.; Oualha, M.; Urien, S.; Genuini, M.; Renolleau, S.; Aboura, R.; Hirt, D.; Heilbronner, C.; Toubiana, J.; Tréluyer, J.M.; Benaboud, S. Population pharmacokinetic model to optimize cefotaxime dosing regimen in critically Ill children. Clin. Pharmacokinet., 2018, 57(7), 867-875.
[http://dx.doi.org/10.1007/s40262-017-0602-9] [PMID: 28980166]
[52]
Rhodin, M.M.; Anderson, B.J.; Peters, A.M.; Coulthard, M.G.; Wilkins, B.; Cole, M.; Chatelut, E.; Grubb, A.; Veal, G.J.; Keir, M.J.; Holford, N.H.G. Human renal function maturation: A quantitative description using weight and postmenstrual age. Pediatr. Nephrol., 2009, 24(1), 67-76.
[http://dx.doi.org/10.1007/s00467-008-0997-5] [PMID: 18846389]
[53]
Rapp, M.; Urien, S.; Foissac, F.; Béranger, A.; Bouazza, N.; Benaboud, S.; Bille, E.; Zheng, Y.; Gana, I.; Moulin, F.; Lesage, F.; Renolleau, S.; Tréluyer, J.M.; Hirt, D.; Oualha, M. Population pharmacokinetics of meropenem in critically ill children with different renal functions. Eur. J. Clin. Pharmacol., 2020, 76(1), 61-71.
[http://dx.doi.org/10.1007/s00228-019-02761-7] [PMID: 31654149]
[54]
Scaglione, F.; Paraboni, L. Pharmacokinetics/pharmacodynamics of antibacterials in the Intensive Care Unit: Setting appropriate dosing regimens. Int. J. Antimicrob. Agents, 2008, 32(4), 294-301.e7.
[http://dx.doi.org/10.1016/j.ijantimicag.2008.03.015] [PMID: 18621508]
[55]
Mehrotra, R.; De Gaudio, R.; Palazzo, M. Antibiotic pharmacokinetic and pharmacodynamic considerations in critical illness. Intensive Care Med., 2004, 30(12), 2145-2156.
[http://dx.doi.org/10.1007/s00134-004-2428-9] [PMID: 15536528]
[56]
Du, X.; Li, C.; Kuti, J.L.; Nightingale, C.H.; Nicolau, D.P. Population pharmacokinetics and pharmacodynamics of meropenem in pediatric patients. J. Clin. Pharmacol., 2006, 46(1), 69-75.
[http://dx.doi.org/10.1177/0091270005283283] [PMID: 16397286]
[57]
Bradley, J.S.; Sauberan, J.B.; Ambrose, P.G.; Bhavnani, S.M.; Rasmussen, M.R.; Capparelli, E.V. Meropenem pharmacokinetics, pharmacodynamics, and Monte Carlo simulation in the neonate. Pediatr. Infect. Dis. J., 2008, 27(9), 794-799.
[http://dx.doi.org/10.1097/INF.0b013e318170f8d2] [PMID: 18645546]
[58]
Smith, P.B.; Cohen-Wolkowiez, M.; Castro, L.M.; Poindexter, B.; Bidegain, M.; Weitkamp, J.H.; Schelonka, R.L.; Ward, R.M.; Wade, K.; Valencia, G.; Burchfield, D.; Arrieta, A.; Bhatt-Mehta, V.; Walsh, M.; Kantak, A.; Rasmussen, M.; Sullivan, J.E.; Finer, N.; Brozanski, B.S.; Sanchez, P.; van den Anker, J.; Blumer, J.; Kearns, G.L.; Capparelli, E.V.; Anand, R.; Benjamin, D.K., Jr Population pharmacokinetics of meropenem in plasma and cerebrospinal fluid of infants with suspected or complicated intra-abdominal infections. Pediatr. Infect. Dis. J., 2011, 30(10), 844-849.
[http://dx.doi.org/10.1097/INF.0b013e31822e8b0b] [PMID: 21829139]
[59]
Wang, Z.M.; Chen, X.Y.; Bi, J.; Wang, M.Y.; Xu, B.P.; Tang, B.H.; Li, C.; Zhao, W.; Shen, A.D. Reappraisal of the optimal dose of meropenem in critically ill infants and children: A developmental pharmacokinetic-pharmacodynamic analysis. Antimicrob. Agents Chemother., 2020, 64(8), e00760-e20.
[http://dx.doi.org/10.1128/AAC.00760-20] [PMID: 32513801]
[60]
Saito, J.; Shoji, K.; Oho, Y.; Kato, H.; Matsumoto, S.; Aoki, S.; Nakamura, H.; Ogawa, T.; Hasegawa, M.; Yamatani, A.; Miyairi, I. Population pharmacokinetics and pharmacodynamics of meropenem in critically Ill pediatric patients. Antimicrob. Agents Chemother., 2021, 65(2), e01909-20.
[http://dx.doi.org/10.1128/AAC.01909-20] [PMID: 33199385]
[61]
Kongthavonsakul, K.; Lucksiri, A.; Eakanunkul, S.; Roongjang, S. na Ayuthaya, I.S.; Oberdorfer, P. Pharmacokinetics and pharmacodynamics of meropenem in children with severe infection. Int. J. Antimicrob. Agents, 2016, 48(2), 151-157.
[http://dx.doi.org/10.1016/j.ijantimicag.2016.04.025] [PMID: 27345269]
[62]
Steffens, N.A.; Zimmermann, E.S.; Nichelle, S.M.; Brucker, N. Meropenem use and therapeutic drug monitoring in clinical practice: A literature review. J. Clin. Pharm. Ther., 2021, 46(3), 610-621.
[http://dx.doi.org/10.1111/jcpt.13369] [PMID: 33533509]
[63]
Wong, G.; Brinkman, A.; Benefield, R.J.; Carlier, M.; De Waele, J.J.; El Helali, N.; Frey, O.; Harbarth, S.; Huttner, A.; McWhinney, B.; Misset, B.; Pea, F.; Preisenberger, J.; Roberts, M.S.; Robertson, T.A.; Roehr, A.; Sime, F.B.; Taccone, F.S.; Ungerer, J.P.J.; Lipman, J.; Roberts, J.A. An international, multicentre survey of -lactam antibiotic therapeutic drug monitoring practice in intensive care units. J. Antimicrob. Chemother., 2014, 69(5), 1416-1423.
[http://dx.doi.org/10.1093/jac/dkt523] [PMID: 24443514]
[64]
Touw, D.J.; van den Anker, J.N. Therapeutic drug monitoring of antimicrobial drugs in neonates. An opinion paper. Ther. Drug Monit., 2022, 44(1), 65-74.
[http://dx.doi.org/10.1097/FTD.0000000000000919] [PMID: 34369442]
[65]
Lonsdale, D.O.; Baker, E.H.; Kipper, K.; Barker, C.; Philips, B.; Rhodes, A.; Sharland, M.; Standing, J.F. Scaling beta‐lactam antimicrobial pharmacokinetics from early life to old age. Br. J. Clin. Pharmacol., 2019, 85(2), 316-346.
[http://dx.doi.org/10.1111/bcp.13756] [PMID: 30176176]
[66]
Scharf, C.; Liebchen, U.; Paal, M.; Taubert, M.; Vogeser, M.; Irlbeck, M.; Zoller, M.; Schroeder, I. The higher the better? Defining the optimal beta-lactam target for critically ill patients to reach infection resolution and improve outcome. J. Intensive Care, 2020, 8(1), 86.
[http://dx.doi.org/10.1186/s40560-020-00504-w] [PMID: 33292582]
[67]
Donadello, K.; Antonucci, E.; Cristallini, S.; Roberts, J.A.; Beumier, M.; Scolletta, S.; Jacobs, F.; Rondelet, B.; de Backer, D.; Vincent, J.L.; Taccone, F.S. β-Lactam pharmacokinetics during extracorporeal membrane oxygenation therapy: A case–control study. Int. J. Antimicrob. Agents, 2015, 45(3), 278-282.
[http://dx.doi.org/10.1016/j.ijantimicag.2014.11.005] [PMID: 25542059]
[68]
Kearns, G.L.; Abdel-Rahman, S.M.; Alander, S.W.; Blowey, D.L.; Leeder, J.S.; Kauffman, R.E. Developmental pharmacology--drug disposition, action, and therapy in infants and children. N. Engl. J. Med., 2003, 349(12), 1157-1167.
[http://dx.doi.org/10.1056/NEJMra035092] [PMID: 13679531]
[69]
Guilhaumou, R.; Benaboud, S.; Bennis, Y.; Dahyot-Fizelier, C.; Dailly, E.; Gandia, P.; Goutelle, S.; Lefeuvre, S.; Mongardon, N.; Roger, C.; Scala-Bertola, J.; Lemaitre, F.; Garnier, M. Optimization of the treatment with beta-lactam antibiotics in critically ill patients—guidelines from the French Society of Pharmacology and Therapeutics (Société Française de Pharmacologie et Thérapeutique—SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (Société Française d’Anesthésie et Réanimation—SFAR). Crit. Care, 2019, 23(1), 104.
[http://dx.doi.org/10.1186/s13054-019-2378-9] [PMID: 30925922]
[70]
Heffernan, A.J.; Sime, F.B.; Taccone, F.S.; Roberts, J.A. How to optimize antibiotic pharmacokinetic/pharmacodynamics for Gram-negative infections in critically ill patients. Curr. Opin. Infect. Dis., 2018, 31(6), 555-565.
[http://dx.doi.org/10.1097/QCO.0000000000000494] [PMID: 30299354]
[71]
Casu, G.S.; Hites, M.; Jacobs, F.; Cotton, F.; Wolff, F.; Beumier, M.; De Backer, D.; Vincent, J.L.; Taccone, F.S. Can changes in renal function predict variations in β-lactam concentrations in septic patients? Int. J. Antimicrob. Agents, 2013, 42(5), 422-428.
[http://dx.doi.org/10.1016/j.ijantimicag.2013.06.021] [PMID: 23993066]
[72]
De Waele, J.J.; Carrette, S.; Carlier, M.; Stove, V.; Boelens, J.; Claeys, G.; Leroux-Roels, I.; Hoste, E.; Depuydt, P.; Decruyenaere, J.; Verstraete, A.G. Therapeutic drug monitoring-based dose optimisation of piperacillin and meropenem: A randomised controlled trial. Intensive Care Med., 2014, 40(3), 380-387.
[http://dx.doi.org/10.1007/s00134-013-3187-2] [PMID: 24356862]
[73]
Liebchen, U.; Paal, M.; Scharf, C.; Schroeder, I.; Grabein, B.; Zander, J.; Siebers, C.; Zoller, M. The ONTAI study – a survey on antimicrobial dosing and the practice of therapeutic drug monitoring in German intensive care units. J. Crit. Care, 2020, 60, 260-266.
[http://dx.doi.org/10.1016/j.jcrc.2020.08.027] [PMID: 32932111]
[74]
Wu, Y.E.; Xu, H.Y.; Shi, H.Y.; van den Anker, J.; Chen, X.Y.; Zhao, W. Carbapenem-resistant enterobacteriaceae bloodstream infection treated successfully with high-dose meropenem in a preterm neonate. Front. Pharmacol., 2020, 11, 566060.
[http://dx.doi.org/10.3389/fphar.2020.566060] [PMID: 33041807]
[75]
Schoenenberger-Arnaiz, J.A.; Ahmad-Diaz, F.; Miralbes-Torner, M.; Aragones-Eroles, A.; Cano-Marron, M.; Palomar-Martinez, M. Usefulness of therapeutic drug monitoring of piperacillin and meropenem in routine clinical practice: A prospective cohort study in critically ill patients. Eur. J. Hosp. Pharm. Sci. Pract., 2020, 27(e1), e30-e35.
[http://dx.doi.org/10.1136/ejhpharm-2018-001713] [PMID: 32296502]
[76]
Roberts, J.A.; Lipman, J. Pharmacokinetic issues for antibiotics in the critically ill patient. Crit. Care Med., 2009, 37(3), 840-851.
[http://dx.doi.org/10.1097/CCM.0b013e3181961bff] [PMID: 19237886]
[77]
Drusano, G.L. Antimicrobial pharmacodynamics: Critical interactions of ‘bug and drug’. Nat. Rev. Microbiol., 2004, 2(4), 289-300.
[http://dx.doi.org/10.1038/nrmicro862] [PMID: 15031728]
[78]
Mattoes, H.M.; Kuti, J.L.; Drusano, G.L.; Nicolau, D.P. Optimizing antimicrobial pharmacodynamics: Dosage strategies for meropenem. Clin. Ther., 2004, 26(8), 1187-1198.
[http://dx.doi.org/10.1016/S0149-2918(04)80001-8] [PMID: 15476901]
[79]
Ikawa, K.; Morikawa, N.; Ikeda, K.; Miki, M.; Kobayashi, M. Population pharmacokinetics and pharmacodynamics of meropenem in Japanese pediatric patients. J. Infect. Chemother., 2010, 16(2), 139-143.
[http://dx.doi.org/10.1007/s10156-009-0025-0] [PMID: 20094749]
[80]
Cies, J.J.; Moore, W.S., II; Calaman, S.; Brown, M.; Narayan, P.; Parker, J.; Chopra, A. Pharmacokinetics of continuous-infusion meropenem for the treatment of Serratia marcescens ventriculitis in a pediatric patient. Pharmacotherapy, 2015, 35(4), e32-e36.
[http://dx.doi.org/10.1002/phar.1567] [PMID: 25884534]
[81]
Cies, J.J.; Moore, W.S., II; Conley, S.B.; Dickerman, M.J.; Small, C.; Carella, D.; Shea, P.; Parker, J.; Chopra, A. Pharmacokinetics of continuous infusion meropenem with concurrent extracorporeal life support and continuous renal replacement therapy: A case report. J. Pediatr. Pharmacol. Ther., 2016, 21(1), 92-97.
[http://dx.doi.org/10.5863/1551-6776-21.1.92] [PMID: 26997934]
[82]
Courter, J.D.; Kuti, J.L.; Girotto, J.E.; Nicolau, D.P. Optimizing bactericidal exposure for β-lactams using prolonged and continuous infusions in the pediatric population. Pediatr. Blood Cancer, 2009, 53(3), 379-385.
[http://dx.doi.org/10.1002/pbc.22051] [PMID: 19422028]
[83]
Udy, A.A.; Varghese, J.M.; Altukroni, M.; Briscoe, S.; McWhinney, B.C.; Ungerer, J.P.; Lipman, J.; Roberts, J.A. Subtherapeutic initial β-lactam concentrations in select critically ill patients: Association between augmented renal clearance and low trough drug concentrations. Chest, 2012, 142(1), 30-39.
[http://dx.doi.org/10.1378/chest.11-1671] [PMID: 22194591]
[84]
McKinnon, P.S.; Paladino, J.A.; Schentag, J.J. 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(4), 345-351.
[http://dx.doi.org/10.1016/j.ijantimicag.2007.12.009] [PMID: 18313273]
[85]
Pea, F.; Viale, P.; Cojutti, P.; Furlanut, M. Dosing nomograms for attaining optimum concentrations of meropenem by continuous infusion in critically ill patients with severe gram-negative infections: A pharmacokinetics/pharmacodynamics-based approach. Antimicrob. Agents Chemother., 2012, 56(12), 6343-6348.
[http://dx.doi.org/10.1128/AAC.01291-12] [PMID: 23045356]
[86]
Roberts, J.A.; Paul, S.K.; Akova, M.; Bassetti, M.; De Waele, J.J.; Dimopoulos, G.; Kaukonen, K.M.; Koulenti, D.; Martin, C.; Montravers, P.; Rello, J.; Rhodes, A.; Starr, T.; Wallis, S.C.; Lipman, J.; Roberts, J.A.; Lipman, J.; Starr, T.; Wallis, S.C.; Paul, S.K.; Margarit Ribas, A.; De Waele, J.J.; De Crop, L.; Spapen, H.; Wauters, J.; Dugernier, T.; Jorens, P.; Dapper, I.; De Backer, D.; Taccone, F.S.; Rello, J.; Ruano, L.; Afonso, E.; Alvarez-Lerma, F.; Gracia-Arnillas, M.P.; Fernandez, F.; Feijoo, N.; Bardolet, N.; Rovira, A.; Garro, P.; Colon, D.; Castillo, C.; Fernado, J.; Lopez, M.J.; Fernandez, J.L.; Arribas, A.M.; Teja, J.L.; Ots, E.; Carlos Montejo, J.; Catalan, M.; Prieto, I.; Gonzalo, G.; Galvan, B.; Blasco, M.A.; Meyer, E.; Del Nogal, F.; Vidaur, L.; Sebastian, R.; Garde, P.M.; Martin Velasco, M.M.; Zaragoza Crespo, R.; Esperatti, M.; Torres, A.; Montravers, P.; Baldesi, O.; Dupont, H.; Mahjoub, Y.; Lasocki, S.; Constantin, J.M.; Payen, J.F.; Martin, C.; Albanese, J.; Malledant, Y.; Pottecher, J.; Lefrant, J-Y.; Jaber, S.; Joannes-Boyau, O.; Orban, C.; Ostermann, M.; McKenzie, C.; Berry, W.; Smith, J.; Lei, K.; Rubulotta, F.; Gordon, A.; Brett, S.; Stotz, M.; Templeton, M.; Rhodes, A.; Ebm, C.; Moran, C.; Kaukonen, K-M.; Pettila, V.; Dimopoulos, G.; Koulenti, D.; Xristodoulou, A.; Theodorou, V.; Kouliatsis, G.; Sertaridou, E.; Anthopoulos, G.; Choutas, G.; Rantis, T.; Karatzas, S.; Balla, M.; Papanikolaou, M.; Myrianthefs, P.; Gavala, A.; Fildisis, G.; Koutsoukou, A.; Kyriakopoulou, M.; Petrochilou, K.; Kompoti, M.; Michalia, M.; Clouva-Molyvdas, F-M.; Gkiokas, G.; Nikolakopoulos, F.; Psychogiou, V.; Malliotakis, P.; Akoumianaki, E.; Lilitsis, E.; Koulouras, V.; Nakos, G.; Kalogirou, M.; Komnos, A.; Zafeiridis, T.; Chaintoutis, C.; Arvaniti, K.; Matamis, D.; Chaintoutis, C.; Kydona, C.; Gritsi-Gerogianni, N.; Giasnetsova, T.; Giannakou, M.; Soultati, I.; Chytas, I.; Antoniadou, E.; Antipa, E.; Lathyris, D.; Koukoubani, T.; Paraforou, T.; Spiropoulou, K.; Bekos, V.; Spring, A.; Kalatzi, T.; Nikolaou, H.; Laskou, M.; Strouvalis, I.; Aloizos, S.; Kapogiannis, S.; Soldatou, O.; Bassetti, M.; Adembri, C.; Villa, G.; Giarratano, A.; Maurizio Raineri, S.; Cortegiani, A.; Montalto, F.; Strano, M.T.; Ranieri, V.M.; Sandroni, C.; De Pascale, G.; Molin, A.; Pelosi, P.; Montagnani, L.; Urbino, R.; Mastromauro, I.; De Rosa, F.G.; Ranieri, V.M.; Cardoso, T.; Afonso, S.; Goncalves-Pereira, J.; Baptista, J.P.; Akova, M.; Ozveren, A. 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(8), 1072-1083.
[http://dx.doi.org/10.1093/cid/ciu027] [PMID: 24429437]
[87]
Lutsar, I.; Metsvaht, T. Understanding pharmacokinetics/pharmacodynamics in managing neonatal sepsis. Curr. Opin. Infect. Dis., 2010, 23(3), 201-207.
[http://dx.doi.org/10.1097/QCO.0b013e328337bb42] [PMID: 20179595]
[88]
Saito, J.; Shoji, K.; Oho, Y.; Aoki, S.; Matsumoto, S.; Yoshida, M.; Nakamura, H.; Kaneko, Y.; Hayashi, T.; Yamatani, A.; Capparelli, E.; Miyairi, I. Meropenem pharmacokinetics during extracorporeal membrane oxygenation and continuous haemodialysis: A case report. J. Glob. Antimicrob. Resist., 2020, 22, 651-655.
[http://dx.doi.org/10.1016/j.jgar.2020.04.029] [PMID: 32417590]
[89]
van den Anker, J.N.; Pokorna, P.; Kinzig-Schippers, M.; Martinkova, J.; de Groot, R.; Drusano, G.L.; Sorgel, F. Meropenem pharmacokinetics in the newborn. Antimicrob. Agents Chemother., 2009, 53(9), 3871-3879.
[http://dx.doi.org/10.1128/AAC.00351-09] [PMID: 19581463]
[90]
Germovsek, E.; Lutsar, I.; Kipper, K.; Karlsson, M.O.; Planche, T.; Chazallon, C.; Meyer, L.; Trafojer, U.M.T.; Metsvaht, T.; Fournier, I.; Sharland, M.; Heath, P.; Standing, J.F.; Auriti, C.; Esposito, S.; Lorenza, P.; Ilmoja, M-L.; Drazdiene, N.; Sarafidis, K.; Mitsiakos, G.; van der Flier, M.; Clarke, P.; Collinson, A.; Gupta, S.; Anthony, M.; Thomas, M.; Pattnayak, S.; Davis, J.; Rabe, H.; Pilling, E.; Bandi, S.; Sinha, A. Plasma and CSF pharmacokinetics of meropenem in neonates and young infants: Results from the NeoMero studies. J. Antimicrob. Chemother., 2018, 73(7), 1908-1916.
[http://dx.doi.org/10.1093/jac/dky128] [PMID: 29684147]
[91]
Fawaz, S.; Barton, S.; Whitney, L.; Swinden, J.; Nabhani-Gebara, S. Stability of meropenem after reconstitution for administration by prolonged infusion. Hosp. Pharm., 2019, 54(3), 190-196.
[http://dx.doi.org/10.1177/0018578718779009] [PMID: 31205331]
[92]
Salmon-Rousseau, A.; Martins, C.; Blot, M.; Buisson, M.; Mahy, S.; Chavanet, P.; Piroth, L. Comparative review of imipenem/] cilastatin versus meropenem. Med. Mal. Infect., 2020, 50(4), 316-322.
[http://dx.doi.org/10.1016/j.medmal.2020.01.001] [PMID: 32035719]
[93]
Cojutti, P.; Maximova, N.; Pea, F. Pharmacokinetics and pharmacodynamics of continuous-infusion meropenem in pediatric hematopoietic stem cell transplant patients. Antimicrob. Agents Chemother., 2015, 59(9), 5535-5541.
[http://dx.doi.org/10.1128/AAC.00787-15] [PMID: 26124157]
[94]
Soman, R.; Gupta, N.; Shetty, A.; Rodrigues, C. Are prolonged/continuous infusions of β-lactams for all? Clin. Infect. Dis., 2013, 57(2), 323.
[http://dx.doi.org/10.1093/cid/cit200] [PMID: 23547168]
[95]
Yonwises, W.; Wacharachaisurapol, N.; Anugulruengkitt, S.; Maimongkol, P.; Treyaprasert, W. Population pharmacokinetics of meropenem in critically ill infant patients. Int. J. Infect. Dis., 2021, 111, 58-64.
[http://dx.doi.org/10.1016/j.ijid.2021.08.031] [PMID: 34419581]
[96]
Shabaan, A.E.; Nour, I.; Elsayed Eldegla, H.; Nasef, N.; Shouman, B.; Abdel-Hady, H. Conventional versus prolonged infusion of meropenem in neonates with gram-negative late-onset sepsis. Pediatr. Infect. Dis. J., 2017, 36(4), 358-363.
[http://dx.doi.org/10.1097/INF.0000000000001445] [PMID: 27918382]
[97]
Ohata, Y.; Tomita, Y.; Nakayama, M.; Kozuki, T.; Sunakawa, K.; Tanigawara, Y. Optimal dosage regimen of meropenem for pediatric patients based on pharmacokinetic/pharmacodynamic considerations. Drug Metab. Pharmacokinet., 2011, 26(5), 523-531.
[http://dx.doi.org/10.2133/dmpk.DMPK-11-RG-027] [PMID: 21747200]
[98]
Padari, H.; Metsvaht, T.; Kõrgvee, L.T.; Germovsek, E.; Ilmoja, M.L.; Kipper, K.; Herodes, K.; Standing, J.F.; Oselin, K.; Lutsar, I. Short versus long infusion of meropenem in very-low-birth-weight neonates. Antimicrob. Agents Chemother., 2012, 56(9), 4760-4764.
[http://dx.doi.org/10.1128/AAC.00655-12] [PMID: 22733063]
[99]
Pettit, R.S.; Neu, N.; Cies, J.J.; Lapin, C.; Muhlebach, M.S.; Novak, K.J.; Nguyen, S.T.; Saiman, L.; Nicolau, D.P.; Kuti, J.L. Population pharmacokinetics of meropenem administered as a prolonged infusion in children with cystic fibrosis. J. Antimicrob. Chemother., 2016, 71(1), 189-195.
[http://dx.doi.org/10.1093/jac/dkv289] [PMID: 26416780]
[100]
Hassan, H.E.; Ivaturi, V.; Gobburu, J.; Green, T.P. Dosage regimens for meropenem in children with pseudomonas infections do not meet serum concentration targets. Clin. Transl. Sci., 2020, 13(2), 301-308.
[http://dx.doi.org/10.1111/cts.12710] [PMID: 31692264]
[101]
Tan, W.W.; Watt, K.M.; Boakye-Agyeman, F.; Cohen-Wolkowiez, M.; Mok, Y.H.; Yung, C.F.; Chan, Y.H. Optimal dosing of meropenem in a small cohort of critically ill children receiving continuous renal replacement therapy. J. Clin. Pharmacol., 2021, 61(6), 744-754.
[http://dx.doi.org/10.1002/jcph.1798] [PMID: 33314163]
[102]
Wang, Y.; Chen, W.; Huang, Y.; Wang, G.; Li, Z.; Yan, G.; Chen, C.; Lu, G. Optimized dosing regimens of meropenem in septic children receiving extracorporeal life support. Front. Pharmacol., 2021, 12, 699191.
[http://dx.doi.org/10.3389/fphar.2021.699191] [PMID: 34504424]
[103]
Falagas, M.E.; Siempos, I.I.; Tsakoumis, I. Cure of persistent, post-appendectomy Klebsiella pneumoniae septicaemia with continuous intravenous administration of meropenem. Scand. J. Infect. Dis., 2006, 38(9), 807-810.
[http://dx.doi.org/10.1080/00365540500504125] [PMID: 16938737]
[104]
Zobell, J.T.; Ferdinand, C.; Young, D.C. Continuous infusion meropenem and ticarcillin-clavulanate in pediatric cystic fibrosis patients. Pediatr. Pulmonol., 2014, 49(3), 302-306.
[http://dx.doi.org/10.1002/ppul.22820] [PMID: 23775821]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy