头孢他啶/阿维巴坦单独和联合磷霉素碳青霉烯类耐药革兰阴性菌体外抗菌活性研究

doi:10.3969/j.issn.1673-8640.2020.10.006

摘要/Abstract

摘要：

目的分析新型β-内酰胺/β-内酰胺酶抑制剂复合制剂头孢他啶（CAZ）/阿维巴坦（AVI）单独和联合磷霉素对碳青霉烯类耐药革兰阴性菌的体外抗菌活性。方法收集2014—2017年温州医科大学附属第一医院分离的碳青霉烯类耐药大肠埃希菌（CREC）56株、碳青霉烯类耐药肺炎克雷伯菌（CRKP）43株和碳青霉烯类耐药铜绿假单胞菌（CRPA）53株,以碳青霉烯敏感大肠埃希菌（CSEC）51株、碳青霉烯敏感肺炎克雷伯菌（CSKP）43株和碳青霉烯敏感铜绿假单胞菌（CSPA）51株作为对照。采用琼脂稀释法检测菌株对CAZ/AVI的最小抑菌浓度（MIC）;采用微量棋盘稀释法测定CAZ/AVI联合磷霉素对菌株的部分抑菌浓度指数（FICI）,用于评价联合抑菌效果。结果 297株革兰阴性菌对CAZ/AVI的总耐药率为18.18%,碳青霉烯类耐药革兰阴性菌对CAZ/AVI的总耐药率高达30.26%,显著高于碳青霉烯敏感菌株（5.52%）（P<0.05）;CRKP对CAZ/AVI的耐药率为9.30%,显著低于CREC和CRPA的耐药率（39.29%和37.74%）（P<0.05）。CAZ/AVI联合磷霉素对CRKP和CRPA表现出协同作用,对CREC表现为相加作用。结论 CAZ/AVI对CRKP具有较好的体外抗菌活性,可以作为临床治疗CRKP的首选抗菌药物;CAZ/AVI联合磷霉素可能成为新的治疗3种常见碳青霉烯类耐药革兰阴性菌的治疗策略。

关键词: 碳青霉烯耐药, 革兰阴性菌, 头孢他啶, 阿维巴坦, 磷霉素, 药物联合

Abstract:

Objective To investigate in vitro antibacterial activity of a novel β-lactam/β-lactamase inhibitor ceftazidime（CAZ）/avibactam（AVI） alone and in combination with fosfomycin against carbapenem-resistant Gram-negative bacilli. Methods A total of 56 carbapenem-resistant Escherichia coli（CREC）,43 carbapenem-resistant Klebsiella pneumoniae（CRKP）,53 carbapenem-resistant Pseudomonas aeruginosa（CRPA）,51 carbapenem-susceptible Escherichia coli（CSEC）,43 carbapenem-susceptible Klebsiella pneumoniae（CSKP） and 51 carbapenem-susceptible Pseudomonas aeruginosa（CSPA） were collected from the First Affiliated Hospital of Wenzhou Medical University from 2014 to 2017. The minimum inhibitory concentration（MIC） against CAZ/AVI was determined by agar dilution method. The fractional inhibitory concentration index（FICI） of CAZ/AVI in combination with fosfomycin was determined by checkerboard method to evaluate the combined antibacterial effect. Results The total resistance rate of 297 Gram-negative bacilli to CAZ/AVI was 18.18%. The resistance rate of carbapenem-resistant Gram-negative bacilli to CAZ/AVI was 30.26%,which was higher than that of carbapenem-susceptible isolates（5.52%）（P<0.05）. The resistance rate of CRKP to CAZ/AVI was 9.3%,which was lower than those of CREC and CRPA（39.29% and 37.74%）（P<0.05）. CAZ/AVI in combination with fosfomycin showed synergistic effect on CRKP and CRPA and additive effect on CREC. Conclusions CAZ/AVI has a high in vitro antibacterial activity towards CRKP,and can be the first choice for clinical treatment of CRKP. CAZ/AVI in combination with fosfomycin may be a new treatment strategy for the treatment of 3 common carbapenem-resistant Gram-negative bacilli.

Key words: Carbapenem resistance, Gram-negative bacillus, Ceftazidime, avibactam, Fosfomycin, Drug combination

中图分类号:

R446.5

陈涛, 徐晔, 董郭枫, 周翠, 徐雯雅, 周铁丽. 头孢他啶/阿维巴坦单独和联合磷霉素碳青霉烯类耐药革兰阴性菌体外抗菌活性研究[J]. 检验医学, 2020, 35(10): 988-993.

CHEN Tao, XU Ye, DONG Guofeng, ZHOU Cui, XU Wenya, ZHOU Tieli. In vitro antibacterial activity of ceftazidime/avibactam alone and in combination with fosfomycin against carbapenem-resistant Gram-negative bacilli[J]. Laboratory Medicine, 2020, 35(10): 988-993.

图/表 4

参考文献 21

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菌株类型	菌株数/株	MIC₅₀/（μg/mL）	MIC₉₀/（μg/mL）	范围/（μg/mL）	耐药率/%
碳青霉烯耐药
CREC	56	8/4	≥128/4	≤0.12/4~>128/4	39.29^#
CRKP	43	4/4	8/4	0.5/4~128/4	9.30
CRPA	53	8/4	64/4	0.25/4~>128/4	37.74^#
碳青霉烯敏感
CSEC	51	≤0.12/4	1/4	≤0.12/4~128/4	1.96^*
CSKP	43	0.5/4	1/4	≤0.12/4~>128/4	6.98
CSPA	51	2/4	8/4	≤0.12/4~>128/4	7.84^*
合计					18.18

菌株类型	菌株数/株	MIC₅₀/（μg/mL）	MIC₉₀/（μg/mL）	范围/（μg/mL）	耐药率/%
碳青霉烯耐药
CREC	56	8/4	≥128/4	≤0.12/4~>128/4	39.29^#
CRKP	43	4/4	8/4	0.5/4~128/4	9.30
CRPA	53	8/4	64/4	0.25/4~>128/4	37.74^#
碳青霉烯敏感
CSEC	51	≤0.12/4	1/4	≤0.12/4~128/4	1.96^*
CSKP	43	0.5/4	1/4	≤0.12/4~>128/4	6.98
CSPA	51	2/4	8/4	≤0.12/4~>128/4	7.84^*
合计					18.18

菌株分类	菌株数	CAZ/AVI MIC
菌株分类	菌株数	<4/4/（μg/mL）	4/4~8/4/（μg/mL）
CREC	34	25^*	9^*
CRKP	39	16	23
CRPA	33	17	16

菌株分类	菌株数	CAZ/AVI MIC
菌株分类	菌株数	<4/4/（μg/mL）	4/4~8/4/（μg/mL）
CREC	34	25^*	9^*
CRKP	39	16	23
CRPA	33	17	16

表型/基因型	菌株数/株	MIC₅₀/（μg/mL）	MIC₉₀/（μg/mL）	范围/（μg/mL）	耐药率/%
NDM	31	>128/4	>128/4	≤0.12/4~>128/4	67.74
KPC-2	54	2/4	8/4	≤0.12/4~>128/4	7.41
IMP	1			1/4~1/4	0
KPC-2+IMP	2			1/4~4/4	0
不产酶	64	4/4	64/4	≤0.12/4~>128/4	32.81
合计	152				30.26