P059 Klebicin as a novel therapy for Klebsiella infection management
Karaliute, I.(1)*;Tilinde, D.(1);Ramonaite, R.(1);Kupcinskas, J.(2);Misiunas, A.(3);Denkovskiene, E.(3);Gleba, Y.(4);Razanskiene, A.(3);Skieceviciene, J.(1);
(1)Lithuanian University of Health Sciences, Institute for Digestive Research, Kaunas, Lithuania;(2)Lithuanian University of Health Sciences, Department of Gastroenterology, Kaunas, Lithuania;(3)Nomads UAB, Nomads UAB, Vilnius, Lithuania;(4)Biozentrum Halle, Nomad Bioscience GmbH, Halle, Germany;
Background
Common infections are becoming almost untreatable, all because of the emergence and spread of drug-resistant pathogens. The highest risk is carried by rapidly spreading multi and pan-resistant bacteria that cause infections untreatable with existing antibiotics. Nowadays the biggest concern is Klebsiella bacteria which reportedly has resistance percentages of 25% or higher for third-generation antimicrobial medicine (WHO, 2022). Orally delivered recombinant bacteriocins, like klebicins, could be employed as oral antimicrobials to eradicate multidrug-resistant Klebsiella from the intestinal tract before hospitalization.
Methods
This study aimed to investigate the antimicrobial efficacy of orally delivered Eudragit - coated klebicin (KvarM) in a murine gastrointestinal tract model of K. pneumoniae infection. Biomodels were used (5 animals/group) to test the antimicrobial efficacy of orally delivered klebicin KvarM: vehicle-only control group (K. pneumoniae, Eudragit coating) and experimental group with K. pneumoniae and KvarM coated to be released in small and large intestines. Faecal samples were used for the analysis of Klebsiella haemolysin gene (khe), which is highly specific for Klebsiella species, using RT-PCR.
Results
The gastrointestinal model of K. pneumoniae infection in mice was achieved per os without any antibiotic pretreatment following the introduction of coated klebicin KvarM therapy once per day for four days. In the first experimental group, the amounts of K. pneumoniae changed from 6,15 x 106 CFU/50 mg after K. pneumoniae administration to 4,68 x 106 CFU/50 mg after the last dose of therapy (23,9 percent efficacy) in the experimental group. Nonetheless, there was a significant difference between the vehicle-control group and the first group after klebicin administration (p=0,023).
Conclusion
Our study shows that the K. pneumoniae infection in the intestinal tract of mice was reduced by 23,9 percent and can be significantly lowered in bacterial counts using orally delivered klebicin.