Analysis of antibacterial activity of ceftazidime/avibactam against carbapenem resistant <i>Klebsiella pneumoniae in vitro</i>_West China Medical Journal

Authors：

ZHOU Qin , YANG Xianggui , WANG Dan , FANG Yingzi , BAI Tingting ,  XU Ying

Department of Laboratory Medicine, the First Affliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610500, P. R. China;

Corresponding author：

XU Ying, Email: yingxu@cmc.edu.cn

Keywords：

Carbapenem resistant Klebaiella pneumoniae; Ceftazidime/avibactam; Antibacterial activity

DOI：

10.7507/1002-0179.202006368

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Objective To study the antibacterial activity of ceftazidime/avibactam against carbapenem-resistant Klebaiella pneumoniae (CRKP) in vitro and detect the resistance genes of CRKP, so as to provide reference for the treatment of patients with CRKP infection.Methods A total of 120 CRKP strains isolated from clinical specimens from May 2014 to November 2017 were collected. The activitis of 11 antimicrobial agents against those CRKP strains were detected by broth microdilution method, and the genes related to resistance to ceftazidime/avibactam were detected by polymerase chain reaction in the 120 CRKP isolates.Results The resistance rate of the 120 CRKP isolates against ceftazidime/avibactam was 16.67% (20/120), which was significantly lower than that against cefotaxime (100.00%), aztreonam (98.33%), ceftazidime (95.83%), cefoperazone/sulbactam (95.83%), meropenem (95.83%), imipenem (95.00%), levofloxacin(92.50%), amikacin (54.17%), minocycline (39.17%), and tegacycline (23.33%). Among the 20 CRKP strains resistant to ceftazidime/avibactam, there were 12 Klebsiella pneumoniae carbapenemase (KPC)-2-producing strains, 3 KPC-3-producing strains, 1 New Delhi metallo-β-lactamase-1 (NDM-1)-producing strain, and 1 oxacillin β-lactamase-48-producing strain; none of the 20 strains had KPC mutation.Conclusions Ceftazidime/avibactam is an effective agent agianst CRKP, and its resistance rate is significantly lower than that of other commonly used antimicrobial agents, especially other β-lactam antibiotics. In terms of resistance genes, except for one isolate producing NDM-1, no other known gene resistant to ceftazidime/avibactam has been found.

Citation： ZHOU Qin, YANG Xianggui, WANG Dan, FANG Yingzi, BAI Tingting, XU Ying. Analysis of antibacterial activity of ceftazidime/avibactam against carbapenem resistant Klebsiella pneumoniae in vitro. West China Medical Journal, 2020, 35(8): 918-923. doi: 10.7507/1002-0179.202006368 Copy

1.	李维特, 张捷. 耐碳青霉烯肠杆菌科细菌耐药机制的研究进展. 中华医院感染学杂志, 2017, 27(3): 714-716.
2.	姚科, 许琳. 多种抗生素联合应用对耐碳青霉烯酶类肺炎克雷伯菌的体外抗菌活性研究. 临床合理用药杂志, 2018, 11(5): 80-81.
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4.	Shirley M. Ceftazidime-avibactam: a review in the treatment of serious Gram-negative bacterial infections. Drugs, 2018, 78(6): 675-692.
5.	Lucasti C, Popescu I, Ramesh MK, <italic>et al</italic>. Comparative study of the efficacy and safety of ceftazidime/avibactam plus metronidazole <italic>versus</italic> meropenem in the treatment of complicated intra-abdominal infections in hospitalized adults: results of a randomized, double-blind, Phase II trial. J Antimicrob Chemother, 2013, 68(5): 1183-1192.
6.	Vazquez JA, González PL, Stricklin D, <italic>et al</italic>. Efficacy and safety of ceftazidime-avibactam <italic>versus</italic> imipenem-cilastatin in the treatment of complicated urinary tract infections, including acute pyelonephritis, in hospitalized adults: results of a prospective, investigator-blinded, randomized study. Curr Med Res Opin, 2012, 28(12): 1921-1931.
7.	王世瑜, 刘晔华, 穆红. 腹腔感染病原菌分布及耐药分析. 中华医院感染学杂志, 2013, 23(21): 5341-5343.
8.	马正安. 新型 β 内酰胺酶抑制剂-阿维巴坦及其复方制剂研究进展. 甘肃科技, 2018, 34(16): 140-142.
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11.	Mazuski JE, Gasink LB, Armstrong J, <italic>et al</italic>. Efficacy and safety of ceftazidime-avibactam plus metronidazole <italic>versus</italic> meropenem in the treatment of complicated intra-abdominal infection: results from a randomized, controlled, double-blind, phase 3 program. Clin Infect Dis, 2016, 62(11): 1380-1389.
12.	张浩元. 新型双环 β-内酰胺酶抑制剂及二十八烷醇的合成. 厦门: 厦门大学, 2007.
13.	Sharma R, Park TE, Moy S. Ceftazidime-avibactam: a novel cephalosporin/β-lactamase inhibitor combination for the treatment of resistant gram-negative organisms. Clin Ther, 2016, 38(3): 431-444.
14.	王垚. 质粒介导喹诺酮类药物耐药机制的研究现状及进展. 西部医学, 2015, 27(7): 1108-1112.
15.	Li J, Learoyd M, Qiu F, <italic>et al</italic>. A randomized, phase I study to assess the safety, tolerability and pharmacokinetics of ceftazidime-avibactam in healthy Chinese subjects. Clin Drug Investig, 2016, 36(2): 119-126.
16.	盛滋科, 徐晓刚. 美国 2010-2015 年产 OXA-48 样碳青霉烯酶的碳青霉烯类耐药肠杆菌科细菌. 中国感染与化疗杂志, 2017, 17(1): 101.
17.	姚志宏, 刘真真. 耐碳青霉烯类肺炎克雷伯菌的流行病学、耐药与传播机制研究进展. 中国抗生素杂志, 2017, 42(12): 1107-1112.
18.	代强, 郑波. 2012 美国疾病预防控制中心耐碳青霉烯类肠杆菌控制指南简介. 中国医学前沿杂志 (电子版), 2013, 5(8): 30-31.
19.	赵慧铮, 师志云, 李刚, 等. 耐碳青霉烯类肠杆菌科细菌耐药性分析与分子流行病学研究. 中华医院感染学杂志, 2016, 26(3): 494-497.
20.	黄秋艳, 邵世和, 周海健, 等. 耐碳青霉烯肺炎克雷伯菌基因检测及其同源性分析. 中国抗生素杂志, 2017, 42(1): 56-61.
21.	杨春. 耐碳青霉烯类抗菌药物肠杆菌科细菌耐药机制研究. 长春: 吉林大学, 2016.
22.	陈丽, 员静, 杨洁, 等. 耐碳青霉烯类肠杆菌科细菌 KPC 与 NDM 的研究. 中华医院感染学杂志, 2016, 26(20): 4569-4571, 4575.
23.	Bathoorn E, Tsioutis C, Da Silva Voorham JM, <italic>et al</italic>. Emergence of pan-resistance in KPC-2 carbapenemase-producing <italic>Klebsiella pneumoniae</italic> in Crete, Greece: a close call. J Antimicrob Chemother, 2016, 71(5): 1207-1212.
24.	Zenati K, Touati A, Bakour S, <italic>et al</italic>. Characterization of NDM-1- and OXA-23-producing <italic>Acinetobacter baumannii</italic> isolates from inanimate surfaces in a hospital environment in Algeria. J Hosp Infect, 2016, 92(1): 19-26.
25.	豆清娅, 邹明祥, 李春辉, 等. 耐亚胺培南肺炎克雷伯菌的耐药机制研究. 中华医院感染学杂志, 2016, 26(13): 2906-2909.
26.	庞峰, 李艳华, 贾秀芹, 等. VITEK-2 Compact 高级专家系统检测肠杆菌科碳青霉烯酶的性能评价. 中华医院感染学杂志, 2013, 23(20): 5104-5106.
27.	贺晓珊. 肺炎克雷伯菌耐药机制的研究进展. 西部医学, 2014, 26(1): 124-126.
28.	王琴, 邹自英, 谭积善, 等. 头孢他啶-阿维巴坦在耐碳青霉烯类肺炎克雷伯菌中的药物敏感性分析. 检验医学与临床, 2019, 16(6): 88-90.

1. 李维特, 张捷. 耐碳青霉烯肠杆菌科细菌耐药机制的研究进展. 中华医院感染学杂志, 2017, 27(3): 714-716.
2. 姚科, 许琳. 多种抗生素联合应用对耐碳青霉烯酶类肺炎克雷伯菌的体外抗菌活性研究. 临床合理用药杂志, 2018, 11(5): 80-81.
3. 国家卫生计生委合理用药专家委员会, 全国细菌耐药监测网. 2016 年全国细菌耐药监测报告. (2017-12-20)[2020-06-01]. http://www.carss.cn/Report/Details/403.
4. Shirley M. Ceftazidime-avibactam: a review in the treatment of serious Gram-negative bacterial infections. Drugs, 2018, 78(6): 675-692.
5. Lucasti C, Popescu I, Ramesh MK, <italic>et al</italic>. Comparative study of the efficacy and safety of ceftazidime/avibactam plus metronidazole <italic>versus</italic> meropenem in the treatment of complicated intra-abdominal infections in hospitalized adults: results of a randomized, double-blind, Phase II trial. J Antimicrob Chemother, 2013, 68(5): 1183-1192.
6. Vazquez JA, González PL, Stricklin D, <italic>et al</italic>. Efficacy and safety of ceftazidime-avibactam <italic>versus</italic> imipenem-cilastatin in the treatment of complicated urinary tract infections, including acute pyelonephritis, in hospitalized adults: results of a prospective, investigator-blinded, randomized study. Curr Med Res Opin, 2012, 28(12): 1921-1931.
7. 王世瑜, 刘晔华, 穆红. 腹腔感染病原菌分布及耐药分析. 中华医院感染学杂志, 2013, 23(21): 5341-5343.
8. 马正安. 新型 β 内酰胺酶抑制剂-阿维巴坦及其复方制剂研究进展. 甘肃科技, 2018, 34(16): 140-142.
9. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. CLSI supplement M100. 30th ed. Wayne, PA: Clinical and Laboratory Standards Institute, 2020.
10. European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters, Version 8.1, Valid from 2018-05-15. (2018-05-15)[2020-06-01]. http://www.eucast.org/clinical_points.
11. Mazuski JE, Gasink LB, Armstrong J, <italic>et al</italic>. Efficacy and safety of ceftazidime-avibactam plus metronidazole <italic>versus</italic> meropenem in the treatment of complicated intra-abdominal infection: results from a randomized, controlled, double-blind, phase 3 program. Clin Infect Dis, 2016, 62(11): 1380-1389.
12. 张浩元. 新型双环 β-内酰胺酶抑制剂及二十八烷醇的合成. 厦门: 厦门大学, 2007.
13. Sharma R, Park TE, Moy S. Ceftazidime-avibactam: a novel cephalosporin/β-lactamase inhibitor combination for the treatment of resistant gram-negative organisms. Clin Ther, 2016, 38(3): 431-444.
14. 王垚. 质粒介导喹诺酮类药物耐药机制的研究现状及进展. 西部医学, 2015, 27(7): 1108-1112.
15. Li J, Learoyd M, Qiu F, <italic>et al</italic>. A randomized, phase I study to assess the safety, tolerability and pharmacokinetics of ceftazidime-avibactam in healthy Chinese subjects. Clin Drug Investig, 2016, 36(2): 119-126.
16. 盛滋科, 徐晓刚. 美国 2010-2015 年产 OXA-48 样碳青霉烯酶的碳青霉烯类耐药肠杆菌科细菌. 中国感染与化疗杂志, 2017, 17(1): 101.
17. 姚志宏, 刘真真. 耐碳青霉烯类肺炎克雷伯菌的流行病学、耐药与传播机制研究进展. 中国抗生素杂志, 2017, 42(12): 1107-1112.
18. 代强, 郑波. 2012 美国疾病预防控制中心耐碳青霉烯类肠杆菌控制指南简介. 中国医学前沿杂志 (电子版), 2013, 5(8): 30-31.
19. 赵慧铮, 师志云, 李刚, 等. 耐碳青霉烯类肠杆菌科细菌耐药性分析与分子流行病学研究. 中华医院感染学杂志, 2016, 26(3): 494-497.
20. 黄秋艳, 邵世和, 周海健, 等. 耐碳青霉烯肺炎克雷伯菌基因检测及其同源性分析. 中国抗生素杂志, 2017, 42(1): 56-61.
21. 杨春. 耐碳青霉烯类抗菌药物肠杆菌科细菌耐药机制研究. 长春: 吉林大学, 2016.
22. 陈丽, 员静, 杨洁, 等. 耐碳青霉烯类肠杆菌科细菌 KPC 与 NDM 的研究. 中华医院感染学杂志, 2016, 26(20): 4569-4571, 4575.
23. Bathoorn E, Tsioutis C, Da Silva Voorham JM, <italic>et al</italic>. Emergence of pan-resistance in KPC-2 carbapenemase-producing <italic>Klebsiella pneumoniae</italic> in Crete, Greece: a close call. J Antimicrob Chemother, 2016, 71(5): 1207-1212.
24. Zenati K, Touati A, Bakour S, <italic>et al</italic>. Characterization of NDM-1- and OXA-23-producing <italic>Acinetobacter baumannii</italic> isolates from inanimate surfaces in a hospital environment in Algeria. J Hosp Infect, 2016, 92(1): 19-26.
25. 豆清娅, 邹明祥, 李春辉, 等. 耐亚胺培南肺炎克雷伯菌的耐药机制研究. 中华医院感染学杂志, 2016, 26(13): 2906-2909.
26. 庞峰, 李艳华, 贾秀芹, 等. VITEK-2 Compact 高级专家系统检测肠杆菌科碳青霉烯酶的性能评价. 中华医院感染学杂志, 2013, 23(20): 5104-5106.
27. 贺晓珊. 肺炎克雷伯菌耐药机制的研究进展. 西部医学, 2014, 26(1): 124-126.
28. 王琴, 邹自英, 谭积善, 等. 头孢他啶-阿维巴坦在耐碳青霉烯类肺炎克雷伯菌中的药物敏感性分析. 检验医学与临床, 2019, 16(6): 88-90.

West China Medical Journal

Analysis of antibacterial activity of ceftazidime/avibactam against carbapenem resistant Klebsiella pneumoniae in vitro

Abstract Full text Figures/Tables Video References Cited by

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