Abstract：The rational use of carbapenem is challenged in critically ill patients by the emergence of drug-resistant pathogens, the alterations of drug pharmacokinetics and the controversy over the pharmacokinetic/pharmacodynamic targets. Therefore, the optimization of carbapenem dosage regimen is imperative. This paper reviewed the research progress on the clinical application and dosage regimen of carbapenem in critically ill patients by reviewing the relevant domestic and international literatures. In order to improve clinical efficacy and reduce adverse reactions, the administration of carbapenem can be optimized by adjusting dosage, changing the administration interval, adjusting infusion time, performing therapeutic drug monitoring, combining with other drugs and using individual administration software, which is based on the physiological and pathological of critically ill patients and the pharmacokinetic/pharmacodynamic of carbapenem.
滕蒙蒙, 孙丹, 韩瑞英, 董亚琳. 碳青霉烯类在抗感染治疗中给药方案优化研究进展[J]. 中国药学杂志, 2020, 55(21): 1762-1767.
TENG Meng-meng, SUN Dan, HAN Rui-ying, DONG Ya-lin. Research Progress on Optimization of Carbapenem Dosage Regimen in Critically Ill Patients. Chinese Pharmaceutical Journal, 2020, 55(21): 1762-1767.
RHODES A, EVANS L E, ALHAZZANI W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016[J]. Intens Care Med, 2017, 43 (3):304-377.
[2]
ABE K, WADA T, UEDA M, et al. A case of effective endotoxin adsorption therapy for septic shock due to acute pyelonephritis[J]. Hinyokika Kiyo, 2000, 46 (11):803-805.
[3]
LEONE M, BOURGOIN A, CAMBON S, et al. Empirical antimicrobial therapy of septic shock patients: adequacy and impact on the outcome[J]. Crit Care Med, 2003, 31 (2):462-467.
[4]
IREGUI M, WARD S, SHERMAN G, et al. Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia[J]. Chest, 2002, 122 (1):262-268.
[5]
DE MAIO CARRILHO C M, DE OLIVEIRA L M, GAUDERETO J, et al. A prospective study of treatment of carbapenem-resistant enterobacteriaceae infections and risk factors associated with outcome[J]. BMC Infect Dis, 2016, 16 (1):629.
[6]
CHRISTOFF J, TOLENTINO J, MAWDSLEY E, et al. Optimizing empirical antimicrobial therapy for infection due to gram-negative pathogens in the intensive care unit: utility of a combination antibiogram[J]. Infect Control Hosp Epidemiol, 2010, 31 (3):256-261.
[7]
KAUKONEN K M, BAILEY M, SUZUKI S, et al. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012[J]. JAMA, 2014, 311 (13):1308-1316.
[8]
GARNACHO-MONTERO J, AMAYA-VILLAR R, FERRANDIZ-MILLON C, et al. Optimum treatment strategies for carbapenem-resistant Acinetobacter baumannii bacteremia[J]. Expert Rev Anti Infect Ther, 2015, 13 (6):769-777.
[9]
PEREZ F, BONOMO R A. Editorial commentary: bloodstream infection caused by extended-spectrum beta-lactamase-producing gram-negative bacteria: how to define the best treatment regimen?[J]. Clin Infect Dis, 2015, 60 (9):1326-1329.
[10]
XU A, ZHENG B, XU Y C, et al. National epidemiology of carbapenem-resistant and extensively drug-resistant gram-negative bacteria isolated from blood samples in China in 2013[J]. Clin Microbiol Infect, 2016, 22 (suppl 1):1-8.
[11]
MUNTEAN D, HORHAT F G, BADITOIU L,et al. Multidrug-resistant gram-negative bacilli: a retrospective study of trends in a tertiary healthcare unit[J]. Medicina, 2018, 54 (6):92.
[12]
GÓMEZ-ZORRILLA S, CAMOEZ M, TUBAU F, et al. Antibiotic pressure is a major risk factor for rectal colonization by multidrug-resistant pseudomonas aeruginosa in critically ill patients[J]. Antimicrob Agents Chemother, 2014, 58 (10):5863-5870.
[13]
JARURATANASIRIKUL S, TRERAYAPIWAT K, NAWAKITRANGSON M, et al. Meropenem pharmacokinetics during the initial phase of life-threatening infections in critically ill patients in intensive care units[J]. Pharm Sci Asia, 2019, 46 (2):129-134.
[14]
ROBERTS J A, LIPMAN J. Pharmacokinetic issues for antibiotics in the critically ill patient[J]. Crit Care Med, 2009, 37 (3):840-851.
[15]
ZHANG J, LU Y, YU K J, et al. Expert consensus on the clinical application of antimicrobial pharmacokinetics/pharmacodynamics [J]. Chin J Tuberc Respir Dis(中华结核和呼吸杂志), 2018, 41(6):409-446.
[16]
GUILHAUMOU R, BENABOUD S, BENNIS Y, et al. 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) [J]. Crit Care, 2019, 23 (1):104.
[17]
HALBACH J L, WANG A W, HAWISHER D, et al. Why antibiotic treatment is not enough for sepsis resolution: an evaluation in an experimental animal model[J]. Infect Immun, 2017, 85 (12):e00664-17.
[18]
PERROTT J, MABASA V H, ENSOM M H. Comparing outcomes of meropenem administration strategies based on pharmacokinetic and pharmacodynamic principles: a qualitative systematic review[J]. Ann Pharmacother, 2010, 44(3):557-564.
[19]
DRUSANO G L. Prevention of resistance: a goal for dose selection for antimicrobial agents[J]. Clin Infect Dis, 2003, 36 (suppl 1):S42-50.
[20]
EGUCHI K, KANAZAWA K, SHIMIZUDANI T, et al. Experimental verification of the efficacy of optimized two-step infusion therapy with meropenem using an in vitro pharmacodynamic model and Monte Carlo simulation[J]. J Infect Chemother, 2010, 16 (1):1-9.
[21]
PERROTT J, MABASA V H, ENSOM M H. Comparing outcomes of meropenem administration strategies based on pharmacokinetic and pharmacodynamic principles: a qualitative systematic review[J]. Ann Pharmacother, 2010, 44 (3):557-564.
[22]
BRANKA B, HARIS C, DOMAGOJ S, et al. In vitro synergy and postantibiotic effect of colistin combinations with meropenem and vancomycin against Enterobacteriaceae with multiple carbapenem resistance mechanisms[J]. J Infect Chemother, 2018, 24 (12):1016-1019.
[23]
DOW R J, ROSE W E, FOX B C, et al. Retrospective study of prolonged versus intermittent infusion piperacillin-tazobactam and meropenem in intensive care unit patients at an academic medical center[J]. Infect Dis Clin Pract, 2011, 19 (6):413-417.
[24]
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[J]. Crit Care, 2012, 16 (3):R113.
[25]
ARNOLD H M, HOLLANDS J M, SKRUPKY L P, et al. Prolonged infusion antibiotics for suspected gram-negative infections in the ICU: a before-after study[J]. Ann Pharmacother, 2013, 47 (2):170-180.
[26]
DULHUNTY J M, ROBERTS J A, DAVIS J S, et al. Continuous infusion of beta-lactam antibiotics in severe sepsis: a multicenter double-blind, randomized controlled trial[J]. Clin Infect Dis, 2013, 56 (2):236-244.
[27]
DE WAELE J, CARLIER M, HOSTE E, et al. Extended versus bolus infusion of meropenem and piperacillin: a pharmacokinetic analysis[J]. Minerva Anestesiol, 2014, 80 (12):1302-1309.
[28]
DE WAELE J J, CARRETTE S, CARLIER M, et al. Therapeutic drug monitoring-based dose optimisation of piperacillin and meropenem: a randomised controlled trial[J]. Intens Care Med, 2014, 40 (3):380-387.
[29]
FURSTENBERG H, VOLLMER M, SCHEER C, et al. Correlation between meropenem application rate, dosing, time and outcome of patients with severe sepsis and septic shock[J]. Infection, 2013, 41 (1):S64.
[30]
HSAIKY L, MURRAY K P, KOKOSKA L, et al. Standard versus prolonged doripenem infusion for treatment of gram-negative infections[J]. Ann Pharmacother, 2013, 47 (7-8):999-1006.
[31]
LIPS M, SILLER M, STROJIL J, et al. Pharmacokinetics of imipenem in critically ill patients during empirical treatment of nosocomial pneumonia: a comparison of 0.5-h and 3-h infusions[J]. Int J Antimicrob Agents, 2014, 44 (4):358-362.
[32]
WANG Z, SHAN T, LIU Y, et al. Comparison of 3-hour and 30-minute infusion regimens for meropenem in patients with hospital acquired pneumonia in intensive care unit: a randomized controlled clinical trial[J]. Chin Crit Care Med(中华危重急救医学), 2014, 26 (9):644-649.
[33]
YU B, LIU L, XING D, et al. Effect of continuous renal replacement therapy on the plasma concentration of imipenem in severe infection patients with acute renal injury[J]. Chin Crit Care Med(中华危重急救医学), 2015, 27 (5):359-365.
[34]
ABDUL-AZIZ M H, LIPMAN J, AKOVA M, et al. Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the defining antibiotic levels in intensive care unit patients (DALI) cohort[J]. J Antimicrob Chemother, 2016, 71 (1):196-207.
[35]
ABDUL-AZIZ M H, SULAIMAN H, MAT-NOR M B, et al. Beta-lactam infusion in severe sepsis (BLISS):a prospective, two-centre, open-labelled randomised controlled trial of continuous versus intermittent beta-lactam infusion in critically ill patients with severe sepsis[J]. Intens Care Med, 2016, 42 (10):1535-1545.
[36]
PETERSSON J, GISKE C G, ELIASSON E. Standard dosing of piperacillin and meropenem fail to achieve adequate plasma concentrations in ICU patients[J]. Acta Anaesthesiol Scand, 2016, 60 (10):1425-1436.
[37]
RAHBAR A J, LODISE T P, ABRAHAM P, et al. Pharmacokinetic and pharmacodynamic evaluation of doripenem in critically ill trauma patients with sepsis[J]. Surg Infect, 2016, 17 (6):675-682.
[38]
ZHAO H Y, GU J, LYU J, et al. Pharmacokinetic and pharmacodynamic efficacies of continuous versus intermittent administration of meropenem in patients with severe sepsis and septic shock: a prospective randomized pilot study[J]. Chin Med J(中华医学杂志), 2017, 130 (10):1139-1145.
[39]
AHMED N, JEN S P, ALTSHULER D, et al. Evaluation of meropenem extended versus intermittent infusion dosing protocol in critically ill patients[J]. J Intensive Care Med, 2020, 35(8):763-771.
[40]
HANG Y, CHEN Y, XUE L, et al. Evaluating biapenem dosage regimens in intensive care unit patients with Pseudomonas aeruginosa infections: a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation[J]. Int J Antimicrob Agents, 2018, 51 (3):484-487.
[41]
HEIL E L, NICOLAU D P, FARKAS A, et al. Pharmacodynamic target attainment for cefepime, meropenem, and piperacillin-tazobactam using a pharmacokinetic/pharmacodynamic-based dosing calculator in critically ill patients[J]. Antimicrob Agents Chemother, 2018, 62 (9):e01008-1018.
[42]
ISLA A, CANUT A, ARRIBAS J, et al. Meropenem dosing requirements against enterobacteriaceae in critically ill patients: influence of renal function, geographical area and presence of extended-spectrum beta-lactamases[J]. Eur J Clin Microbiol Infect Dis, 2016, 35 (3):511-519.
[43]
GERMOVSEK E, LUTSAR I, KIPPER K, et al. Plasma and CSF pharmacokinetics of meropenem in neonates and young infants: results from the NeoMero studies[J]. J Antimicrob Chemother, 2018, 73 (7):1908-1916.
[44]
YANG D Q, NI W T, JIANG X W, et al. Progress in combination therapy to infection of carbapenem-resistant Pseudomonas aeruginosa[J]. Chin Pharm J (中国药学杂志), 2017, 52 (14):1208-1211.
[45]
LIMA D A F D S, NASCIMENTO M M P D, VITALI L H, et al. In vitro activity of antimicrobial combinations against multidrug-resistant Pseudomonas aeruginosa[J]. Rev Soc Bras Med Trop, 2013, 46(3):299-303.
[46]
ZHANG Y L. To observe the effect of meropenem combined with tigecycline for treatment of severe neonatal infection of multi drug resistant bacteria[J]. J North Pharm(北方药学), 2017, 14 (12):108-109.
2020, Vol. 55 
