Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
Scopus CiteScore – 3.4 (CiteScore Tracker 3.4)
Index Copernicus  – 161.11; MEiN – 140 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2020, vol. 29, nr 8, August, p. 993–1000

doi: 10.17219/acem/121934

Publication type: review article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Clinical outcomes of continuous vs intermittent meropenem infusion for the treatment of sepsis: A systematic review and meta-analysis

Peng Chen1,A,B,C,D,E,F, Fuchao Chen2,F, Jiexin Lei3,F, Benhong Zhou1,F

1 Department of Pharmacy, Renmin Hospital of Wuhan University, China

2 Department of Pharmacy, Dongfeng Hospital, Hubei University of Medicine, Shiyan, China

3 Department of Endocrinology, Renmin Hospital of Wuhan University, China

Abstract

The antibiotic meropenem is commonly administered to patients with sepsis and septic shock. The aim of this study was to conduct a meta-analysis to evaluate the clinical efficacy and safety of continuous compared to intermittent meropenem infusion for the treatment of sepsis. Electronic databases such as PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure (CNKI) were researched to collect clinical trials comparing continuous and intermittent infusion of meropenem in patients with sepsis. After data extraction and quality assessment of the included studies, Stata v. 12.0 software (Stata Corporation LLC, College Station, USA) was used for a meta-analysis of mortality, clinical cure, microbiological eradication, and safety. Seven studies with a total of 1,191 participants met the inclusion criteria and were included in the meta-analysis. The meta-analysis showed that continuous meropenem infusion was superior to intermittent infusion in terms of mortality (combined risk ratio (RR) = 0.66, 95% confidence interval (95% CI) = 0.46–0.98, p = 0.03), clinical cure rate (combined RR = 1.15, 95% CI = 1.02–1.30, p = 0.026) and microbiological eradication (combined RR = 1.20, 95% CI = 1.01–1.42, p = 0.04), although it may increase the incidence of some adverse events (AEs). Compared with intermittent dosing, administration of meropenem antibiotics through continuous infusion in patients with sepsis is associated with decreased hospital mortality, increased clinical cure rates and greater microbiological eradication. Further high-quality studies should be conducted to confirm our findings.

Key words

sepsis, meropenem, continuous infusion

References (38)

  1. Hidalgo F, Mas D, Rubio M, Garcia-Hierro P. Infections in critically ill burn patients. Med Intensiva. 2016;40(3):179–185.
  2. McKinney CW, 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.
  3. Liu YF, Yan JJ, Lei HY, et al. Loss of outer membrane protein C in Escherichia coli contributes to both antibiotic resistance and escaping antibody-dependent bactericidal activity. Infect Immun. 2012;80(5):1815–1822.
  4. Wiklund S, Fagerberg I, Örtqvist Å, et al. Knowledge and understanding of antibiotic resistance and the risk of becoming a carrier when travelling abroad: A qualitative study of Swedish travelers. Scand J Public Health. 2015;43(3):302–308.
  5. Tiberi S, Payen MC, Sotgiu G, et al. Effectiveness and safety of meropenem/clavulanate-containing regimens in the treatment of MDR-and XDR-TB. Eur Respir J. 2016;47(4):1235–1243.
  6. Afshartous D, Bauer SR, Connor MJ, et al. Pharmacokinetics and pharmacodynamics of imipenem and meropenem in critically ill patients treated with continuous venovenous hemodialysis. Am J Kidney Dis. 2014;63(1):170–171.
  7. Chalhoub H, Sáenz Y, Rodriguezvillalobos H, et al. High-level resistance to meropenem in clinical isolates of Pseudomonas aeruginosa in the absence of carbapenemases: Role of active efflux and porin alterations. Int J Antimicrob Agents. 2016;48(6):740–743.
  8. Laishram S, Anandan S, Devi BY, et al. Determination of synergy between sulbactam, meropenem and colistin in carbapenem-resistant Klebsiella pneumoniae and Acinetobacte rbaumannii isolates and correlation with the molecular mechanism of resistance. J Chemother. 2016;28(4):297–303.
  9. Payen MC, Muylle I, Vandenberg O, et al. Meropenem-clavulanate for drug-resistant tuberculosis: A follow-up of relapse-free cases. Int J Tuberc Lung Dis. 2018;22(1):34–39.
  10. Cheatham SC, Fleming MR, Healy DP, et al. Steady-state pharmacokinetics and pharmacodynamics of meropenem in morbidly obese patients hospitalized in an intensive care unit. J Clin Pharmacol. 2014;54(3):324–330.
  11. Lenhard JR, Bulitta JB, Connell TD, et al. High-intensity meropenem combinations with polymyxin B: New strategies to overcome carbapenems resistance in Acinetobacter baumannii. J Antimicrob Chemother. 2017;72(1):153–165.
  12. McCarthy MW, Walsh TJ. Meropenem/vaborbactam fixed combination for the treatment of patients with complicated urinary tract infections. Drugs Today (Barc). 2017;53(10):521–530.
  13. Shabaan AE, Nour I, Eldegla HE, Nasef H, Shouman B, Abdel-Hady H. Conventional versus prolonged infusion of meropenem in neonates with Gram-negative late onset sepsis: A randomized controlled trial. Pediatr Infect Dis J. 2017;36(4):358–363.
  14. Zhao HY, Gu J, Jie L, 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. Chin Med J (Eng). 2017;130(10):1139–1145.
  15. Dulhunty JM, Roberts JA, Davis JS, et al; BLING II Investigators for the ANZICS Clinical Trials Group. A multicenter randomized trial of continuous versus intermittent β-lactam infusion in severe sepsis. Am J Respir Crit Care Med. 2015;192(11):1298–1305.
  16. Abdul-Aziz MH, Sulaiman H, Mat-Nor MB, et al. Beta-Lactam Infusion in Severe Sepsis (BLISS): A prospective, two-centre, open-labelledrandomised controlled trial of continuous versus intermittent beta-lactam infusion in critically ill patients with severe sepsis. Intensive Care Med. 2016;42(10):1535–1545.
  17. 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;16(3):R113–R116.
  18. Helmy TA, Abdelghaffar AA, Fathy EM, et al. Continuous versus intermittent intravenous meropenem in severe sepsis. IJPBS. 2015;5:4457.
  19. Fahmi H, Noorizan AA, Yahaya H, Hazlinda AH. Clinical outcomes of critically Ill patients with sepsis receiving extended and standardmeropenem infusion in Malaysian hospitals. Int J Pharm Pharm Sci. 2016;10:S12S12.
  20. Yusuf E, Spapen H, Pierard D. Prolonged vs intermittent infusion of piperacillin/tazobactam in critically ill patients: A narrative and systematic review. J Crit Care. 2014;29(6):1089–1095.
  21. Chu DC, Mehta AB, Walkey AJ. Practice patterns and outcomes associated with procalcitonin use in critically ill patients with sepsis. Clin Infect Dis. 2017;64(11):1509–1515.
  22. Zielske J, Bohne S, Brunkhorst FM, Axer H, Guntinas-Lichius O. Acute and long-term dysphagia in critically ill patients with severe sepsis: Results of a prospective controlled observational study. Eur Arch Otorhinolaryngol. 2014;271(11):3085–3093.
  23. Del BV, Giacobbe DR, Marchese A, et al. Meropenem for treating KPC-producing Klebsiella pneumoniae bloodstream infections: Should we get to the PK/PD root of the paradox? Virulence. 2016;8(1):66–73.
  24. Kristoffersson AN, David-Pierson P, Parrott NJ. Simulation-based evaluation of PK/PD indices for meropenem across patient groups and experimental designs. Pharm Res. 2016;33(5):1115–1125.
  25. Vardakas KZ, Voulgaris GL, Maliaros A, Samonis G, Falagas ME. Prolonged versus short-term intravenous infusion of antipseudomonal β-lactams for patients with sepsis: A systematic review and meta-analysis of randomised trials. Lancet Infect Dis. 2018;18(1):108–120.
  26. Dong H, Zhong Y. Response to: Continuous versus intermittent infusion of vancomycin in adult patients: A systematic review and meta-analysis. Int J Antimicrob Agents. 2016;48(1):114–115.
  27. Yang H, Zhang C, Zhou Q, Wang Y, Chen L. Clinical outcomes with alternative dosing strategies for piperacillin/tazobactam: A systematic review and meta-analysis. PLoS One. 2016;10(1):274–289.
  28. Sato Y, Sandoh M, Hanaki H, et al. Evaluation of usefulness and PK-PD analysis of meropenem in children with various infections. Gan To Kagaku Ryoho. 2012;60(3):335–341.
  29. Delfino E, Fucile C, Del VB, et al. Pharmacokinetics of high-dose extended-infusion meropenem during pulmonary exacerbation in adult cystic fibrosis patients: A case series. New Microbiol. 2018;41(1):47–51.
  30. Sjövall F, Alobaid AS, Wallis SC, Perner A, Lipman J, Roberts JA. Maximally effective dosing regimens of meropenem in patients with septic shock. J Antimicrob Chemother. 2018;73(1):191–198.
  31. Shotwell MS, Nesbitt R, Madonia PN, et al. Pharmacokinetics and pharmacodynamics of extended infusion versus short infusion piperacillin-tazobactam in critically ill patients undergoing CRRT. Clin J Am Soc Nephrol. 2016;11(8):1377–1383.
  32. Cojutti PG, Barbarino C, De AM, Hope W, Pea F. Higher than standard meropenem and linezolid dosages needed for appropriate treatment of an intracerebral hemorrhage patient with augmented renal clearance. Eur J Clin Pharmacol. 2018;74(8):1091–1092.
  33. Martínková J, Malbrain ML, Havel E, Šafránek P, Bezouška J, Kaška M. A pilot study on pharmacokinetic/pharmacodynamic target attainment in critically ill patients receiving piperacillin/tazobactam. Anaesthesiol Intensive Ther. 2015;48(1):23–30.
  34. Patel PR, Cook SE. Stability of meropenem in intravenous solutions. Am J Health Syst Pharm. 1997;54(4):412–421.
  35. Tomasello C, Leggieri A, Cavalli R, Di Perri G, D’Avolio A. In vitro stabilifighty evaluation of different pharmaceutical products containing meropenem. Hosp Pharm. 2015;50(4):296–303.
  36. Katip W, Wientong P, Sornsuvit C. The stability of generic meropenem in tropical countries. Int J Pharm Pharm Sci. 2015;7(1):236–238.
  37. Franceschi L, Cojutti P, Baraldo M, Pea F. Stability of generic meropenem solutions for administration by continuous infusion at normal and elevated temperatures. Ther Drug Monit. 2014;36(5):674–669.
  38. Roberts DM, Roberts JA, Roberts MS, et al; RENAL Replacement Therapy Study Investigators. Variability of antibiotic concentrations in critically ill patients receiving continuous renal replacement therapy: A multicentre pharmacokinetic study. Crit Care Med. 2012;40(5):1523–1528.
© Wroclaw Medical University