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Application of azithromycin in reversing antibiotic resistance of food animal-derived pathogenic bacteria

A technology of antibiotic resistance and azithromycin, applied in the direction of antibacterial drugs, pharmaceutical formulations, organic active ingredients, etc., to achieve the effect of enhancing sensitivity, enhancing antibacterial activity, and reducing the dosage used

Pending Publication Date: 2021-02-05
HENAN AGRICULTURAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Drugs used in combination with azithromycin include erythromycin, cephalosporins, and Chinese herbal medicines. No specific research has been reported on the effect of the combination of azithromycin and colistin on the resistance of animal-derived pathogens to colistin.

Method used

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  • Application of azithromycin in reversing antibiotic resistance of food animal-derived pathogenic bacteria
  • Application of azithromycin in reversing antibiotic resistance of food animal-derived pathogenic bacteria
  • Application of azithromycin in reversing antibiotic resistance of food animal-derived pathogenic bacteria

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Observation on the effect of azithromycin in reversing the colistin resistance of clinical isolate Escherichia coli E57

[0021] (1) Test drugs

[0022] Azithromycin: content 97%, purchased from Sichuan Hengrui Tongda Co., Ltd.

[0023] Colistin sulfate: potency ≥ 23000u / mg, purchased from Hebei Shengxue Dacheng Tangshan Pharmaceutical Co., Ltd.

[0024] Azithromycin was prepared with 30% absolute ethanol and deionized water to make a stock solution with an initial concentration of 1280 μg / mL; colistin sulfate was prepared with deionized water to make a stock solution with an initial concentration of 1280 μg / mL, and stored at -20 °C.

[0025] (2) Strains

[0026] The clinically isolated colistin-resistant strain E. coli E57 was positive for mcr-1, and it was verified by cloning and sequencing that the drug resistance of the strain was mediated by the mcr-1 gene, provided by the Pharmacology Laboratory of Henan Agricultural University.

[0027] (3) culture medium

[...

Embodiment 2

[0050] Effect of azithromycin on reversing colistin resistance of clinical isolate Escherichia coli ED16

[0051] Experimental drugs, culture medium, instruments, bacterial solution preparation and MIC determination and determination methods are basically the same as in Example 1, the difference is:

[0052] The strain used was Escherichia coli isolate ED16, negative for mcr-1, which was proved to be a colistin-resistant strain mediated by chromosomal mutation or increased expression by next-generation sequencing of the whole genome, provided by the Pharmacology Laboratory of Henan Agricultural University.

[0053] Embodiment 2 experimental result is as follows:

[0054] Table 2 Effect of azithromycin on drug resistance of Escherichia coli isolate ED16

[0055]

[0056] Note: COL: colistin; AZI: azithromycin; 1 / 2MIC AZI: the amount of azithromycin added is 16 μg / mL; 1 / 4MICAZI: the amount of azithromycin added is 8 μg / mL; 1 / 8MIC AZI: the amount of azithromycin added is 4 μg / m...

Embodiment 3

[0059] Colistin and Azithromycin Combined Drug Test in Vitro

[0060] Test medicine, culture medium, instrument and bacterial liquid preparation are identical with embodiment 1, difference is:

[0061] The experimental strain was Escherichia coli isolate ELX11, which was positive for mcr-1. It was verified by cloning and sequencing that the drug resistance of the strain was mediated by the mcr-1 gene, provided by the Pharmacology Laboratory of Henan Agricultural University.

[0062] MIC and FIC index determination:

[0063] The determination and interpretation of MIC were the same as in Example 1. The FIC (Fractionalinhibitory concentration, partial inhibitory concentration index) index of the combination of colistin and azithromycin against Escherichia coli was determined, and the in vitro antibacterial activity of the combination of the two drugs was determined by the 8×8 checkerboard method. FIC = MIC of colistin combination / MIC of colistin alone + MIC of azithromycin comb...

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Abstract

The invention relates to the technical field of microbial drug resistance, and particularly discloses application of azithromycin in reversing antibiotic resistance of food animal-derived pathogenic bacteria. The antibiotics are polymyxin antibiotics. The application of azithromycin in reversing the drug resistance of animal-derived pathogenic bacteria on polymyxin is found for the first time, provides a novel medication strategy, and has important values in new preparation research and development and clinical application.

Description

technical field [0001] The invention relates to the technical field of microbial drug resistance, in particular to the application of azithromycin in reversing the antibiotic resistance of pathogenic bacteria derived from food animals. Background technique [0002] Polymyxin is a group of polypeptide antibiotics produced by Paenibacillus polymyxa, including polymyxin A, B, C, D, E and other components. Polymyxin E, also known as colistin (COL for short), and polymyxin B are two cationic polypeptide antibacterial drugs commonly used in human and veterinary clinics. It mainly interacts with the lipid A on the outer membrane of the bacterial cell through the polycation ring in the molecule, displacing cations such as calcium and magnesium in the outer membrane, destroying the negatively charged outer membrane of negative bacteria and reducing the stability of the cell membrane, making the important intracellular The outflow of substances produces a bactericidal effect. In rec...

Claims

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Application Information

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IPC IPC(8): A61K38/12A61P31/04A61K31/7052
CPCA61K38/12A61K31/7052A61P31/04A61K2300/00Y02A50/30
Inventor 胡功政罗行炜刘建华翟亚军
Owner HENAN AGRICULTURAL UNIVERSITY
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