Effect of artesunate combined with levofloxacin on antibacterial activity of carbapenem-resistant Escherichia coli
Objective To investigate the effect of artesunate combined with levofloxacin on the antibacterial activity of carbapenem-resistant Escherichia coli (CRECO). Methods 20 strains of CRECO isolated from the laboratory were collected and the minimum inhibitory concentrations (MIC) of artesunate, levofloxacin, ceftazidime and imipenem were determined by broth microdilution methods. The synergistic antibacterial activity of artesunate with levofloxacin, ceftazidime and imipenem was determined by broth microdilution checkerboard methods. The effects of different treatment groups on the growth of clinical strain (E5)of CRECO were observed by bacterial growth curve method. The expression of efflux pump gene and regulatory gene was detected by RT-PCR. Results The MIC50 of artesunate, levofloxacin, ceftazidimeandimipenem were >8192,64,2048 and 32 µg/mL, respectively. Synergistic antibacterial test showed that when artesunate was combined with levofloxacin at 1024 µg/ mL, the MIC50 decreased from 64 µg/mL to 16 µg/mL (i.e. ,1/4 MIC50), and the combined effect was mainly synergistic. When combined with ceftazidime, its MIC50 decreased from 2048 µg/mL to 1024 µg/mL (i. e. ,1/2 MIC50), and the combined effect was mainly additive. The results of the growth curve showed that artesunate combined with levofloxacin could effectively inhibit the growth of CRECO, and the curve tended to be flat. All 20 strains carried the efflux pump genes, AcrA and AcrB genes. RT-PCR results showed that artesunate combined with levofloxacin could reduce the expression of efflux pump gene AcrB. The decrease of its expression level was associated with the decreased expression of the regulatory gene AcrB. Conclusion Artesunate has no antibacterial activity against CRECO, but artesunate combined with levofloxacin could effectively enhance the antibacterial action of antibiotics, and its synergistic inhibitory mechanism may be related to the reduction of the expression of efflux pump gene AcrB.
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