异丙氧苯胍联合黏菌素对肺炎克雷伯菌体外协同抗菌作用

doi:10.11843/j.issn.0366-6964.2024.12.041

Abstract

Abstract:

This work aimed to study the antibacterial synergistic ability and the preliminary combined mechanism of isopropoxy benzene guanidine (IBG) combined with colistin, and to evaluate whether IBG can act as an effective colistin synergist and enhance the anti-bacterial effect of colistin. The findings of this study will provide a theoretical basis for the effective treatment of multidrug resistant bacterial infections in the clinic. This study investigated the preliminary combined mechanism and synergistic effect of IBG with colistin against Klebsiella pneumoniae using the minimal inhibitory concentration, checkerboard test, time killing curves, resistance induction and fluorescent dye test. IBG has no antimicrobial activity against K. pneumoniae alone, but has a synergistic effect against K. pneumoniae in combination with colistin and an additive effect in combination with amoxicillin. Time killing curves indicate that when the two drugs are used in combination, IBG enhances the susceptibility of K. pneumoniae to colistin, with a synergistic decrease in bacterial counts of >2 lg(CFU·mL^-1) compared to the effect of colistin alone. In the long-term induced resistance test, resistance was less likely to be induced by colistin in the combination group than in the colistin monotherapy group. The results of the synergistic mechanism test showed that colistin and IBG, when used in combination, can destroy the permeability of the cytoplasmic membrane, affect the potential of the cell membrane, and dissipate the proton kinetic potential energy, so that it is difficult for cell membranes to perform their normal functions. In this study, we found that the combination of IBG and low concentration of colistin, has good synergistic antibacterial activity against K. pneumoniae and enhances the antibacterial effect of colistin. It suggests that IBG can restore the susceptibility of multidrug resistant K. pneumoniae to colistin, and can be used as a potential therapeutic option for the treatment of K. pneumoniae infections.

Key words: Klebsiella pneumoniae, mcr, isopropoxy benzene guanidine, colistin, synergistic antimicrobial activity

CLC Number:

S859.796

WU Sujuan, LIN Changcheng, WAN Peng, LI Jie, LU Yixing, HU Jianxin, PENG Xianfeng, ZENG Zhenling. Synergistic Antimicrobial Effect of Isopropoxy Benzene Guanidine Combined with Colistin on Klebsiella pneumoniae in vitro[J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(12): 5792-5801.

Figures/Tables 9

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References 24

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菌株 Strain	MIC/(μg·mL^-1)
菌株 Strain	IBG	CL
ATCC 700603	>1 280	1
P135	>1 280	4
C14	>1 280	8
C20	>1 280	16
124C	>1 280	16

联用组合 Combination	MIC/(μg·mL^-1)		部分抑菌浓度指数 FICI	作用关系 Functional relationship
联用组合 Combination	异丙氧苯胍联合/单药 IBG(in combination)/IBG	B药联合/单药 Drug B(in combination)/Drug B	部分抑菌浓度指数 FICI	作用关系 Functional relationship
IBG+CL	64/1 000	0.25/1.00	0.31	协同
IBG+AMO	8/1 000	32/64	0.50	相加
IBG+TMP	32/1 000	32/32	1.03	无关
IBG+GEN	32/1 000	0.5/8.0	0.10	无关
IBG+AMP	4/1 000	8/4	2.00	无关
IBG+CAZ	256/1 000	16/16	1.25	无关
IBG+MEM	4/1 000	0.5/0.5	1.00	无关
IBG+FOX	256/1 000	32/32	1.25	无关
IBG+TIG	4/1 000	2/1	2.00	无关
IBG+CIP	256/1 000	64/64	1.25	无关
IBG+FFC	8/1 000	32/16	2.00	无关
IBG+NEO	8/1 000	4/2	2.00	无关

菌株 Strains	耐药基因 Resistance genes	MIC/(μg·mL^-1)		部分抑菌浓度指数 FICI	作用关系 Functional relationship
菌株 Strains	耐药基因 Resistance genes	异丙氧苯胍联合/单药 IBG(in combination)/IBG	黏菌素联合/单药 CL(in combination)/CL	部分抑菌浓度指数 FICI	作用关系 Functional relationship
ATCC 700603	-	64/1 000	0.25/1.00	0.31	协同
P135	bla_SHV、mcr-8	32/1 000	0.25/4.00	0.10	协同
124C	bla_CTX-M、bla_SHV	32/1 000	0.125/16.000	0.04	协同
C14	bla_SHV	32/1 000	0.5/8.0	0.10	协同
C20	bla_SHV	32/1 000	0.125/16.000	0.04	协同

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Synergistic Antimicrobial Effect of Isopropoxy Benzene Guanidine Combined with Colistin on Klebsiella pneumoniae in vitro

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