中国新药杂志

磷霉素和亚胺培南对肺炎克雷伯菌体内协同作用的评价

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胡仁静 ¹ , 戴越 ² , 沈兰凤 ¹ , 刘君 ³

中国新药杂志 | 临床研究 2021,30(23): 2203-2209

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中国新药杂志 |临床研究 2021 , 30 (23) : 2203 -2209

磷霉素和亚胺培南对肺炎克雷伯菌体内协同作用的评价

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胡仁静¹, 戴越², 沈兰凤¹, 刘君³

作者信息

¹南京医科大学附属无锡市第二人民医院，无锡　214002

²无锡市精神卫生中心，无锡　214056

³无锡市第五人民医院，无锡　214005

通讯作者:

刘君，男，副主任技师，主要从事微生物实验诊断工作和肺克毒力机制的研究。联系电话：（0510）68561246，E-mail：liujun_4451@126.com。

作者简介:

胡仁静，女，副主任技师，从事肺炎克雷伯菌耐药及毒力机制的研究。联系电话：（0510）68562429，E-mail：weiweihuhu112@163.com。

Evaluation of the in vivo synergistic effect between fosfomycin and imipenem on Klebsiella pneumoniae

Ren-jing HU¹, Yue DAI², Lan-feng SHEN¹, Jun LIU³

Affiliations

¹The Affiliated Wuxi Second People's Hospital of Nanjing Medical University, Wuxi 214002, China

²The Mental Health Center of Wuxi, Wuxi 214056, China

³The Fifth People's Hospital of Wuxi, Wuxi 214005, China

出版时间: 2021-12-15

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摘要

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目的：

采用肺炎克雷伯菌的大蜡螟幼虫体内感染模型，探讨磷霉素与亚胺培南联合用药的体内抗菌活性。

方法：

收集南京医科大学附属无锡市第二人民医院2020年1月—12月分离自血液感染患者的碳青霉烯类耐药的肺炎克雷伯菌4株（CRKP），碳青霉烯类敏感的肺炎克雷伯菌4株（CSKP）。采用wzi基因测序对肺炎克雷伯荚膜血清型进行分型。采用大蜡螟毒力模型计算不同菌株96 h 80%致死量，进一步进行大蜡螟体内抗菌药物敏感实验，分析磷霉素与亚胺培南联合用药的体内抗菌活性，通过大蜡螟虫体血淋巴试验进行细菌负荷检测。

结果：

wzi基因测序显示4株CRKP的血清型均为K64型，4株CSKP血清型为K1，K2，K50，K26。联合用药的体内抗菌活性显示：当CRKP组亚胺培南的MIC值为≤8 mg·L^-1，磷霉素≤32 mg·L^-1的2株菌联合用药的抗菌效果显著优于单药，血淋巴细菌负荷清除率高；CSKP组高毒力的K1-KP531和K2-KP532两药联用优于亚胺培南单用或磷霉素单用，血淋巴细菌负荷清除率低于CSKP组低毒力菌株。

结论：

当亚胺培南MIC≤8 mg·L^-1及磷霉素敏感时，磷霉素与亚胺培南在大蜡螟幼虫肺炎克雷伯菌感染模型中显示有协同作用。

关键词

大蜡螟 / 肺炎克雷伯菌 / 毒力 / 亚胺培南 / 磷霉素

Abstract

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Objective:

To investigate the in vivo antibacterial activity of fosfomycin combined with imipenem by using the infection model of Galleria mellonella with Klebsiella pneumonia.

Methods:

Four strains of carbapenem resistant Klebsiella pneumonia (CRKP) and four strains of carbapenem sensitive Klebsiella pneumonia (CSKP) isolated from patients with bloodstream infection were collected from Wuxi Second People's Hospital Affiliated Nanjing Medical University on January to December 2020. The serotypes of Klebsiella pneumoniae capsule were typed by wzi gene sequencing. The virulence model of wax moth was used to calculate the 80% lethal dose of different strains in 96 h, then the antimicrobial susceptibility test of wax borer was carried out to analyze the antibacterial activity of fosfomycin combined with imipenem in vivo. Finally, the bacterial load was detected by the hemolymph test of wax borer.

Results:

Wzi gene sequencing showed that the serotypes of all the four CRKP strains were k64. The serotypes of four CSKP strains were K1, K2, K50 and k26, respectively. The in vivo antibacterial activity result of combined drugs showed that when the MIC value of imipenem was ≤8 mg·L^-1 and fosfomycin ≤32 mg·L^-1 in CRKP group, the antibacterial effect of the combination on two strains was significantly better than that of single drug, and the load clearance rate of hemolymph bacteria was higher. The antibacterial effect of the combination on K1-KP531 and K2-KP532 from high virulence in CSKP group was better than imipenem or fosfomycin alone, with the load clearance rate of hemolymph bacteria lower than that of low virulence strains in CSKP group.

Conclusion:

When imipenem MIC≤8 mg·L^-1 and fosfomycin was sensitive, fosfomycin and imipenem showed synergistic effect in the Klebsiella pneumoniae infection model of Galleria mellonella.

Key words

Galleria mellonella / Klebsiella pneumoniae / virulence / imipenem / fosfomycin

引用本文

胡仁静, 戴越, 沈兰凤, 刘君. 磷霉素和亚胺培南对肺炎克雷伯菌体内协同作用的评价. 中国新药杂志, 2021 , 30 (23) : 2203 -2209 .

Ren-jing HU, Yue DAI, Lan-feng SHEN, Jun LIU. Evaluation of the in vivo synergistic effect between fosfomycin and imipenem on Klebsiella pneumoniae[J]. Chinese Journal of New Drugs, 2021 , 30 (23) : 2203 -2209 .

基金

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江苏省医学青年人才培养(QNRC2016163)
无锡市卫健委青年项目(Q201901)

参考文献

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文献

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参考文献引证文献

排序方式：

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2021年第30卷第23期

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首发时间：2026-10-28
出版时间：2021-12-15

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录用日期：2021-08-10

基金

江苏省医学青年人才培养(QNRC2016163)

无锡市卫健委青年项目(Q201901)

作者信息

¹南京医科大学附属无锡市第二人民医院，无锡　214002

²无锡市精神卫生中心，无锡　214056

³无锡市第五人民医院，无锡　214005

通讯作者:

刘君，男，副主任技师，主要从事微生物实验诊断工作和肺克毒力机制的研究。联系电话：（0510）68561246，E-mail：liujun_4451@126.com。

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https://castjournals.cast.org.cn/joweb/zgxyzz/CN/1322127313123266664

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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