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[Detoxifying effect of antibiotics and their effectiveness in experimental plague at the stage of explicit
Abstract:
The effect of antibiotics such as amikacin, rifampicin, doxycycline, polymyxin B and cefotaxime on the toxins of the plague microbe (lipopolysaccharide + fraction II according to Beiker) was studied in vitro and in vivo. The study on the antibiotic neutralization of plague toxins revealed that only polymyxin had toxin neutralizing capacity which depended on the dose. Investigation of the polymyxin effect at various stages of plague infection showed that when polymyxin in a dose of 1250 units and a mixture of plague toxins in lethal doses were administered simultaneously to albino mice, the positive effect amounted to 100 per cent. When the antibiotic was administered 30 or 60 minutes later, the antibiotic efficacy proved to be lower by 90 or 76.6 per cent, respectively. The intoxication in later periods (in 90-120 minutes) resulted in a decrease in animal survival up to 40-15 per cent. It was demonstrated on the model of the plague infection in albino mice that the use of amikacin, cefotaxime, rifampicin or doxycycline during polymyxin therapy at the stage of marked generalization of the infection provided a significant increase in the animal survival (60 to 80 per cent) as compared to that after the use of the same drugs alone (0 to 20 per cent).
Insights
Polymyxin B is the only antibiotic that neutralizes plague toxins. Early administration of Polymyxin B significantly improves survival rates in plague infections, especially when combined with other antibiotics.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Context:
- Plague, caused by Yersinia pestis, remains a significant public health concern.
- Antibiotic resistance and treatment efficacy are critical challenges in managing plague.
- Plague toxins, including lipopolysaccharide, contribute to disease severity.
Purpose:
- To evaluate the in vitro and in vivo efficacy of various antibiotics against plague toxins.
- To determine the toxin-neutralizing capacity of specific antibiotics.
- To assess the impact of antibiotic administration timing and combination therapy on plague infection outcomes.
Summary:
- Only Polymyxin B demonstrated dose-dependent toxin-neutralizing capacity against plague toxins (lipopolysaccharide + fraction II).
- Simultaneous administration of Polymyxin B (1250 units) with lethal doses of plague toxins resulted in 100% survival in mice.
- Delayed administration of Polymyxin B significantly reduced efficacy, while combination therapy with amikacin, cefotaxime, rifampicin, or doxycycline improved survival in generalized infections.
Impact:
- Highlights Polymyxin B's crucial role in neutralizing plague toxins.
- Emphasizes the importance of early Polymyxin B administration for effective plague treatment.
- Suggests combination therapy strategies to enhance survival rates in severe plague cases.