Improving the efficacy for meropenem therapy requires a high probability of target attainment in critically ill infants and children

Zeming Wang, Jing Bi, Dianping You, Yu Tang, Gang Liu, Jinqian Yu, Zhipeng Jin, Tingting Jiang, Xue Tian, Hui Qi, Lei Dong, Lili Dong, Qunqun Zhang, Wei Zhao, Adong Shen, Zeming Wang, Jing Bi, Dianping You, Yu Tang, Gang Liu, Jinqian Yu, Zhipeng Jin, Tingting Jiang, Xue Tian, Hui Qi, Lei Dong, Lili Dong, Qunqun Zhang, Wei Zhao, Adong Shen

Abstract

Probability of target attainment is the key factor influencing the outcome of meropenem therapy. The objective of the present study was to evaluate the relationship between the time in which the plasma free concentration of meropenem exceeds the minimum inhibitory concentration of pathogens (fT >MIC) during therapy and the clinical outcome of treatment to optimize meropenem therapy. Critically ill children with infections who had received intravenous meropenem monotherapy were included. The relationship between fT >MIC of meropenem and effectiveness and safety were explored. Data from 53 children (mean age ± standard deviation, 26 months ± 38) were available for final analysis. Children with fT >MIC ≥ 5.6 h (n = 14) had a more significant improvement in antibacterial efficacy in terms of decrease in fever (p = 0.02), white blood cell count (p = 0.014), and C-reactive protein (p = 0.02) compared with children with fT >MIC < 5.6 h (n = 39) after meropenem therapy completed. No drug-related adverse events were shown to have a causal association with meropenem therapy. Our study shows the clinical benefits of sufficient target attainment of meropenem therapy. Meeting a suitable pharmacodynamic target attainment of meropenem is required to ensure better antibacterial efficacy in critically ill infants and children. Clinical Trial Registration: clinicaltrials.gov, Identifier NCT03643497.

Keywords: children; critically ill; fT>MIC; meropenem; pharmacodynamic target attainment.

Conflict of interest statement

The reviewer HH declared a shared parent affiliation with the authors ZW, GL, XT, HQ, and AS to the handling editor at the time of review. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Wang, Bi, You, Tang, Liu, Yu, Jin, Jiang, Tian, Qi, Dong, Dong, Zhang, Zhao and Shen.

References

    1. Alsultan Abdullah, Dasuqi Shereen A., Aljamaan Fadi, Omran Rasha A., Ali Syed Saeed, AlJaloud Turki, et al. (2021). Pharmacokinetics of meropenem in critically ill patients in Saudi Arabia. Saudi Pharm. J. 29, 1272–1277. 10.1016/j.jsps.2021.09.017
    1. Ariano Robert E., Anna Nyhlén, Donnelly J. Peter, Sitar Daniel S., Harding Godfrey K. M., Zelenitsky Sheryl A. (2005). Pharmacokinetics and pharmacodynamics of meropenem in febrile neutropenic patients with bacteremia. Ann. Pharmacother. 39, 32–38. 10.1345/aph.1E271
    1. Author Anonymous (2018). 2018 surveillance of meningitis (bacterial) and meningococcal septicaemia in under 16s: Recognition, diagnosis and management. London: NICE guideline CG102.
    1. Bradley John S., Sauberan Jason B., Ambrose Paul G., Bhavnani Sujata M., Rasmussen Maynard R., Capparelli Edmund V. (2008). Meropenem pharmacokinetics, pharmacodynamics, and Monte Carlo simulation in the neonate. Pediatr. Infect. Dis. J. 27, 794–799. 10.1097/INF.0b013e318170f8d2
    1. Cies J. J., Moore W. S., Enache A., Chopra A. (2017). Population pharmacokinetics and pharmacodynamic target attainment of meropenem in critically ill young children. J. Pediatr. Pharmacol. Ther. 22, 276–285. 10.5863/1551-6776-22.4.276
    1. Cies Jeffrey J., Moore Wayne S., J Dickerman Mindy, Small Christine, Carella Dominick, Chopra Arun, et al. (2014). Pharmacokinetics of continuous-infusion meropenem in a pediatric patient receiving extracorporeal life support. Pharmacotherapy 34, e175–e179. 10.1002/phar.1476
    1. Cohen-Wolkowiez Michael, Poindexter Brenda, Bidegain Margarita, Schelonka Robert L., Randolph David A., Ward Robert M., et al. (2012). Safety and effectiveness of meropenem in infants with suspected or complicated intra-abdominal infections. Clin. Infect. Dis. 55, 1495–1502. 10.1093/cid/cis758
    1. Dellinger R. Phillip, Levy Mitchell M., Rhodes Andrew, Annane Djillali, Gerlach Herwig, Opal Steven M., et al. (2013). Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock: 2012. Crit. Care Med. 41, 580–637. 10.1097/CCM.0b013e31827e83af
    1. Dudley M. N., Ambrose P. G. (2000). Pharmacodynamics in the study of drug resistance and establishing in vitro susceptibility breakpoints: Ready for prime time. Curr. Opin. Microbiol. 3, 515–521. 10.1016/s1369-5274(00)00132-6
    1. Franciscus van der Meer A., Marcus Marco A. E., DaniëlTouw J., JohannesProost H., Neef Cees. (2011). Optimal sampling strategy development methodology using maximum a posteriori Bayesian estimation. Ther. Drug Monit. 33, 133–146. 10.1097/FTD.0b013e31820f40f8
    1. Hassan Hazem E., Ivaturi Vijay, Gobburu Jogarao, Green Thomas P. (2019). Dosage regimens for meropenem in children with Pseudomonas infections do not meet serum concentration targets. Clin. Transl. Sci. 13, 301–308. 10.1111/cts.12710
    1. Kongthavonsakul Kritsana, Lucksiri Aroonrut, Eakanunkul Suntara, Roongjang Somjing, Oberdorfer Peninnah. (2016). Pharmacokinetics and pharmacodynamics of meropenem in children with severe infection. Int. J. Antimicrob. Agents 48, 151–157. 10.1016/j.ijantimicag.2016.04.025
    1. Liu Shuping, Zheng Yi, Wu Xirong, Xu Baoping, Liu Xiuyun, Feng Guoshuang, et al. (2018). Early target attainment of azithromycin therapy in children with lower respiratory tract infections. J. Antimicrob. Chemother. 73, 2846–2850. 10.1093/jac/dky273
    1. Mathew S. K., Mathew B. S., Neely M. N., Naik G. S., Prabha Ratna, Jacob G. G., et al. (2016). 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. 38, 593–599. 10.1097/FTD.0000000000000323
    1. Punpanich Warunee, Srisarang Suchada, Prachantasen Uraiwan. (2012). Therapeutic effectiveness of the generic preparation of meropenem (Mapenem) in the treatment of moderate to severe infection in children. J. Med. Assoc. Thai 95, 895–902.
    1. Rapp Mélanie, Urien Saïk, Foissac Frantz, Béranger Agathe, Bouazza Naïm, Benaboud Sihem, et al. (2019). Population pharmacokinetics of meropenem in critically ill children with different renal functions. Eur. J. Clin. Pharmacol. 76, 61–71. 10.1007/s00228-019-02761-7
    1. Scaglione F., Esposito S., Leone S., Lucini V., Pannacci M., Ma L., et al. (2009). Feedback dose alteration significantly affects probability of pathogen eradication in nosocomial pneumonia. Eur. Respir. J. 34, 394–400. 10.1183/09031936.00149508
    1. Schuler D. (1995). Safety and efficacy of meropenem in hospitalised children: Randomised comparison with cefotaxime, alone and combined with metronidazole or amikacin. Meropenem paediatric study group. J. Antimicrob. Chemother. 36, 99–108. 10.1093/jac/36.suppl_a.99
    1. Subspecialty Group of Respiratory Diseases (2013). The society of pediatrics, Chinese medical association, editorial board, Chinese journal of pediatrics[guidelines for management of community acquired pneumonia in children (the revised edition of 2013) (I)]. Zhonghua Er Ke Za Zhi 51, 745–752.
    1. Thalhammer F., Hörl W. H. (2000). Pharmacokinetics of meropenem in patients with renal failure and patients receiving renal replacement therapy. Clin. Pharmacokinet. 39, 271–279. 10.2165/00003088-200039040-00003
    1. Wang Ze-Ming, Chen Xiao-Yu, Jing Bi, Wang Mei-Ying, Xu Bao-Ping, Tang Bo-Hao, et al. (2020). Reappraisal of the optimal dose of meropenem in critically ill infants and children: A developmental pharmacokinetic-pharmacodynamic analysis. Antimicrob. Agents Chemother. 64, e00760. 10.1128/AAC.00760-20
    1. Wayne P. A. (2019). Performance standards for antimicrobial susceptibility testing. 29th ed. Wayne, PA: Clinical and Laboratory Standards InstituteCLSI supplement M100.
    1. Yun Zhuo, Nian Hua, Shang Hong, GuoSun Quan, Shang H., Sun G. Q. (2010). Pharmacokinetic-pharmacodynamic profiling of four antimicrobials against gram-negative bacteria collected from Shenyang, China. BMC Infect. Dis. 10, 171. 10.1186/1471-2334-10-171

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