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.	李維特, 張捷. 耐碳青霉烯腸桿菌科細菌耐藥機制的研究進展. 中華醫院感染學雜志, 2017, 27(3): 714-716.
2.	姚科, 許琳. 多種抗生素聯合應用對耐碳青霉烯酶類肺炎克雷伯菌的體外抗菌活性研究. 臨床合理用藥雜志, 2018, 11(5): 80-81.
3.	國家衛生計生委合理用藥專家委員會, 全國細菌耐藥監測網. 2016 年全國細菌耐藥監測報告. (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, 劉曄華, 穆紅. 腹腔感染病原菌分布及耐藥分析. 中華醫院感染學雜志, 2013, 23(21): 5341-5343.
8.	馬正安. 新型 β 內酰胺酶抑制劑-阿維巴坦及其復方制劑研究進展. 甘肅科技, 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.	張浩元. 新型雙環 β-內酰胺酶抑制劑及二十八烷醇的合成. 廈門: 廈門大學, 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. 質粒介導喹諾酮類藥物耐藥機制的研究現狀及進展. 西部醫學, 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, 徐曉剛. 美國 2010-2015 年產 OXA-48 樣碳青霉烯酶的碳青霉烯類耐藥腸桿菌科細菌. 中國感染與化療雜志, 2017, 17(1): 101.
17.	姚志宏, 劉真真. 耐碳青霉烯類肺炎克雷伯菌的流行病學、耐藥與傳播機制研究進展. 中國抗生素雜志, 2017, 42(12): 1107-1112.
18.	代強, 鄭波. 2012 美國疾病預防控制中心耐碳青霉烯類腸桿菌控制指南簡介. 中國醫學前沿雜志 (電子版), 2013, 5(8): 30-31.
19.	趙慧錚, 師志云, 李剛, 等. 耐碳青霉烯類腸桿菌科細菌耐藥性分析與分子流行病學研究. 中華醫院感染學雜志, 2016, 26(3): 494-497.
20.	黃秋艷, 邵世和, 周海健, 等. 耐碳青霉烯肺炎克雷伯菌基因檢測及其同源性分析. 中國抗生素雜志, 2017, 42(1): 56-61.
21.	楊春. 耐碳青霉烯類抗菌藥物腸桿菌科細菌耐藥機制研究. 長春: 吉林大學, 2016.
22.	陳麗, 員靜, 楊潔, 等. 耐碳青霉烯類腸桿菌科細菌 KPC 與 NDM 的研究. 中華醫院感染學雜志, 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.	豆清婭, 鄒明祥, 李春輝, 等. 耐亞胺培南肺炎克雷伯菌的耐藥機制研究. 中華醫院感染學雜志, 2016, 26(13): 2906-2909.
26.	龐峰, 李艷華, 賈秀芹, 等. VITEK-2 Compact 高級專家系統檢測腸桿菌科碳青霉烯酶的性能評價. 中華醫院感染學雜志, 2013, 23(20): 5104-5106.
27.	賀曉珊. 肺炎克雷伯菌耐藥機制的研究進展. 西部醫學, 2014, 26(1): 124-126.
28.	王琴, 鄒自英, 譚積善, 等. 頭孢他啶-阿維巴坦在耐碳青霉烯類肺炎克雷伯菌中的藥物敏感性分析. 檢驗醫學與臨床, 2019, 16(6): 88-90.

1. 李維特, 張捷. 耐碳青霉烯腸桿菌科細菌耐藥機制的研究進展. 中華醫院感染學雜志, 2017, 27(3): 714-716.
2. 姚科, 許琳. 多種抗生素聯合應用對耐碳青霉烯酶類肺炎克雷伯菌的體外抗菌活性研究. 臨床合理用藥雜志, 2018, 11(5): 80-81.
3. 國家衛生計生委合理用藥專家委員會, 全國細菌耐藥監測網. 2016 年全國細菌耐藥監測報告. (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, 劉曄華, 穆紅. 腹腔感染病原菌分布及耐藥分析. 中華醫院感染學雜志, 2013, 23(21): 5341-5343.
8. 馬正安. 新型 β 內酰胺酶抑制劑-阿維巴坦及其復方制劑研究進展. 甘肅科技, 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. 張浩元. 新型雙環 β-內酰胺酶抑制劑及二十八烷醇的合成. 廈門: 廈門大學, 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. 質粒介導喹諾酮類藥物耐藥機制的研究現狀及進展. 西部醫學, 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, 徐曉剛. 美國 2010-2015 年產 OXA-48 樣碳青霉烯酶的碳青霉烯類耐藥腸桿菌科細菌. 中國感染與化療雜志, 2017, 17(1): 101.
17. 姚志宏, 劉真真. 耐碳青霉烯類肺炎克雷伯菌的流行病學、耐藥與傳播機制研究進展. 中國抗生素雜志, 2017, 42(12): 1107-1112.
18. 代強, 鄭波. 2012 美國疾病預防控制中心耐碳青霉烯類腸桿菌控制指南簡介. 中國醫學前沿雜志 (電子版), 2013, 5(8): 30-31.
19. 趙慧錚, 師志云, 李剛, 等. 耐碳青霉烯類腸桿菌科細菌耐藥性分析與分子流行病學研究. 中華醫院感染學雜志, 2016, 26(3): 494-497.
20. 黃秋艷, 邵世和, 周海健, 等. 耐碳青霉烯肺炎克雷伯菌基因檢測及其同源性分析. 中國抗生素雜志, 2017, 42(1): 56-61.
21. 楊春. 耐碳青霉烯類抗菌藥物腸桿菌科細菌耐藥機制研究. 長春: 吉林大學, 2016.
22. 陳麗, 員靜, 楊潔, 等. 耐碳青霉烯類腸桿菌科細菌 KPC 與 NDM 的研究. 中華醫院感染學雜志, 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. 豆清婭, 鄒明祥, 李春輝, 等. 耐亞胺培南肺炎克雷伯菌的耐藥機制研究. 中華醫院感染學雜志, 2016, 26(13): 2906-2909.
26. 龐峰, 李艷華, 賈秀芹, 等. VITEK-2 Compact 高級專家系統檢測腸桿菌科碳青霉烯酶的性能評價. 中華醫院感染學雜志, 2013, 23(20): 5104-5106.
27. 賀曉珊. 肺炎克雷伯菌耐藥機制的研究進展. 西部醫學, 2014, 26(1): 124-126.
28. 王琴, 鄒自英, 譚積善, 等. 頭孢他啶-阿維巴坦在耐碳青霉烯類肺炎克雷伯菌中的藥物敏感性分析. 檢驗醫學與臨床, 2019, 16(6): 88-90.

West China Medical Journal

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

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