RESUMO
High efficiency of a combined preparation including synergistic polymyxin B and 4-hexylresorcinol was shown for treatment of experimental sepsis caused by an antibiotic-resistant highly virulent hypermucoid Klebsiella pneumoniae strain KPM9Pmr in mice. Complex therapy with polymyxin B (1 mg/kg) and 4-hexylresorcinol (30 mg/kg) led to cure in 80%; in 20% of these mice, no bacterial cells were found. After treatment with polymyxin B alone, only 50% animals survived and all of them contained bacterial cells. Comparative analysis of the results of monotherapy and combined treatment indicates that 4-hexylresorcinol not only increases the efficiency of antibiotic, but also minimizes persistence of the infection agent and therefore, the risk of development of antibiotic resistance.
Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Hexilresorcinol/farmacologia , Klebsiella pneumoniae/efeitos dos fármacos , Sepse/tratamento farmacológico , Animais , Animais não Endogâmicos , Antibacterianos/farmacologia , Modelos Animais de Doenças , Sinergismo Farmacológico , Feminino , Infecções por Klebsiella/complicações , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/patologia , Klebsiella pneumoniae/patogenicidade , Camundongos , Testes de Sensibilidade Microbiana , Polimixina B/farmacologia , Polimixina B/uso terapêutico , Polimixinas/análogos & derivados , Polimixinas/farmacologia , Polimixinas/uso terapêutico , Sepse/microbiologiaRESUMO
The therapeutic efficacy of enterocin S760, a broad spectrum antimicrobial peptide produced by Enterococcus faecium LWP760 was tested on mice infected with Bacillus anthracis M-71 to induce anthrax (second Tsenkovsky's vaccine). Intraperitoneal four-, two- or one-fold administration of the peptide in a dose of 25 mg/kg for 10 days for prophylactic (1 hour after the contamination) and therapeutic (24 hours after the contamination) purposes prevented or cured the infection in 90-100% of the mice versus the 100-percent lethality in the control (untreated animals). The antimicrobial activity of enterocin S760 against B. anthracis M-71 in vivo correlated with activity in vitro. Enterocin S760 is considered a novel promising antimicrobial for the treatment of grampositive and gramnegative infections.
Assuntos
Antraz/tratamento farmacológico , Antibacterianos/administração & dosagem , Bacillus anthracis/efeitos dos fármacos , Bacteriocinas/administração & dosagem , Animais , Antibacterianos/isolamento & purificação , Bacteriocinas/isolamento & purificação , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Enterococcus faecium/química , CamundongosRESUMO
AIM: To demonstrate treatment efficacy of bacteriocin S760 synthesized by Enterococcus faecium 760 for septic Salmonella infection in mice. MATERIALS AND METHODS: One hundred mice, which were intraperitoneally inoculated with 100 LD50 of Salmonella enteritidis strain 92 Rif(r), received bacteriocin 1 hour (prevention) or 48 hours (treatment) after inoculation in doses 25, 50, or 100 mg/kg every 6 hours during 5 or 10 days. RESULTS: Use of peptide S760 for prophylaxis in dose 50 mg/kg during 10 days prevented lethal infection in 100% of animals, whereas its use for treatment cured 70% of animals with generalized salmonellosis. Shortening of treatment course from 10 to 5 days and reducing dose of bacteriocin led to less pronounced treatment effect but in all animals it was expressed by increase of mean length of life compared to control (not treated). CONCLUSION: Obtained results demonstrated high treatment efficacy of bacteriocin S760 during septic salmonellosis and perspectives of its use in medicine and animal health.