The potential of methylethylpiridinol in treatment of bacterial infections caused by Klebsiella pneumoniae (experimental study)

Aim. Investigated the activity of methylethylpiridinol (6-methyl-2-ethyl-pyridin-3-ol hydrochloride) in the comprehensive treatment of the experimental bacterial infection caused by Klebsiella pneumoniae.

Materials and methods. The study was conducted on clinical isolates of Klebsiella pneumoniae. At the first stage of the study (in vitro) studied the effect of methylethylpiridinol in concentrations 0,25–4 mM on the growth of the strain and the activity of the sublethal concentrations of antibiotics – gentamicin, ciprofloxacin, tetracycline, ceftazidime. In the second stage of the study (in vivo) in rats Wistar simulated bacterial peritonitis by intraperitoneal injection of a suspension of Klebsiella pneumoniae and investigated the effect of methylethylpiridinol (80 mg/kg) on the effectiveness of antibiotic therapy with gentamicin (30 mg/kg), ciprofloxacin (50 mg/kg), ceftazidime (120 mg/kg) or tetracycline (80 mg/kg). The animal blood plasma was determined ceruloplasmin concentration (marker of the intensity of infectious-inflammatory process) and thiobarbiturate-jet products, erythrocytes – the concentration of reduced glutathione, catalase and glutathione peroxidase.

Results. It is found that a methylethylpiridinol inhibits the development of periodic bacterial cultures, but exhibits a pronounced antagonism with respect to gentamicin. Antioxidant slightly increases the activity of ciprofloxacin and tetracycline. The bacteriostatic effect of antioxidant reduces the action of ceftazidime in vitro. In conditions of chemotherapy by using of gentamicin and ciprofloxacin additional injection of methylethylpiridinol leads to the preservation of ceruloplasmin level to the level of non-treated animals without showing the antioxidant effect. Ceftazidime exhibits antioxidant effect, reduces the introduction of methylethylpiridinol. The antioxidant properties of methylethylpiridinol did not appear in the application of tetracycline.

Conclusion. Comparison of results in vitro and in vivo confirmed irrationality of using of methylethylpiridinol in chemotherapy with gentamicin, ciprofloxacin, ceftazidime or tetracycline for correction of peroxidation in experimental infection caused by Klebsiella pneumoniae. Methylethylpiridinol in experimental chemotherapy has no law-governed effect on free radical oxidation, and when applied gentamicin may cause reduction the effectiveness of chemotherapy, confirmed in vitro.

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