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Study on the Mechanism of Levofloxacin Combined with Imipenem Against Pseudomonas aeruginosa

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Abstract

Pseudomonas aeruginosa can develop resistance. Therefore, it is necessary to design proper treatment for it. Pseudomonas aeruginosa can develop resistance against levofloxacin due to the development of efflux pumps. However, the development of these efflux pumps cannot develop resistance against imipenem. Additionally, the MexCDOprJ efflux system which is responsible for the resistance of Pseudomonas aeruginosa to levofloxacin is highly susceptible to imipenem. The objective of the study was to evaluate the emergence of resistance of Pseudomonas aeruginosa against 750 mg levofloxacin, 250 mg imipenem, and a combination of 750 mg levofloxacin and 250 mg imipenem. An in vitro pharmacodynamic model was selected for the evaluation of the emergence of resistance. Pseudomonas aeruginosa strain 236, Pseudomonas aeruginosa strain GB2, and Pseudomonas aeruginosa strain GB65 were selected. Susceptibility testing of both antibiotics was done by agar dilution methodology. A disk diffusion bioassay was performed for antibiotics. RT-PCR measurement was done for the evaluation of expressions of Pseudomonas aeruginosa genes. Samples were tested at 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, and 30 h. Levofloxacin and imipenem both individually reported a decrease in colony-forming unit per milliliter of strength in the initial stage but in the later stage both develop resistance individually. Levofloxacin with imipenem had no resistance to Pseudomonas aeruginosa during 30 h. Time after the start of development of resistance or decrease in clinical efficacy was higher for levofloxacin and imipenem combination in all strains. The concentration of Pseudomonas aeruginosa at the time after the start of development of resistance or decrease in clinical efficacy was fewer for levofloxacin and imipenem combination. Levofloxacin with imipenem is recommended for the treatment of infection due to Pseudomonas aeruginosa.

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Correspondence to Qiang Lu.

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Lu, Q., Yang, Q. Study on the Mechanism of Levofloxacin Combined with Imipenem Against Pseudomonas aeruginosa. Appl Biochem Biotechnol 196, 690–700 (2024). https://doi.org/10.1007/s12010-023-04516-8

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