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[Experimental study on chemotherapy of acute glanders]
Abstract:
Glanders is a zoonotic infection inducing acute forms of the disease (pneumonia, sepsis) in humans and animals under certain conditions, which even with the use of modern chemotherapy have unfavourable prognosis. Insufficient of efficacy of antibiotics with in vitro low MIC for planktonic bacterial suspension of Burkholderia mallei in chemotherapy of acute forms of glanders was due to the capacity of the pathogen for intracellular survival and formation of biofilms. Under such conditions the susceptibility of B. mallei to antibiotics lowered by several orders of magnitude. Chemotherapy of the glanders acute forms in animals usually provided only an increase of the lifespan, while among the survivors there was recorded a high relapse rate. More favourable outcomes were observed with the use of in vitro effective antibiotics in the form of clathrate compounds or especially liposomal forms. In the experiments with golden hamsters the survival rate reached 100% in 1000 Dlm infection even with the treatment onset by meropenem liposomal form 48 hours after the infection. Chemotherapeutics in the liposomal form significantly lowered resistance of B. mallei in both the experiments with a suspension of planktonic organisms and the use of bacteria interned in eukaryotic cells (Tetrahymena pyriformis).
Insights
Glanders treatment efficacy improved using liposomal antibiotics against Burkholderia mallei. Liposomal formulations overcome bacterial resistance, offering better outcomes for this zoonotic disease.
Area of Science:
- Veterinary Medicine
- Infectious Diseases
- Microbiology
Background:
- Glanders, a zoonotic infection caused by Burkholderia mallei, presents acute forms like pneumonia and sepsis with poor prognoses.
- Conventional antibiotic efficacy is limited by B. mallei's intracellular survival and biofilm formation, significantly reducing susceptibility.
- Current chemotherapy often prolongs lifespan but results in high relapse rates in glanders cases.
Purpose of the Study:
- To evaluate the efficacy of liposomal formulations of antibiotics against Burkholderia mallei.
- To investigate if liposomal delivery can overcome antibiotic resistance in B. mallei infections.
- To improve treatment outcomes for acute glanders in animal models.
Main Methods:
- Testing in vitro antibiotic susceptibility of planktonic and intracellular Burkholderia mallei.
- Comparing efficacy of conventional antibiotics versus liposomal formulations in a golden hamster model (1000 Dlm infection).
- Assessing survival rates and relapse rates post-treatment with meropenem liposomal form.
Main Results:
- Liposomal antibiotic formulations demonstrated significantly enhanced efficacy compared to conventional treatments.
- Meropenem liposomal form achieved 100% survival in golden hamsters when treatment was initiated 48 hours post-infection.
- Liposomal delivery reduced B. mallei resistance in both planktonic and intracellular settings, including within Tetrahymena pyriformis.
Conclusions:
- Liposomal antibiotic formulations represent a promising strategy to overcome Burkholderia mallei resistance in glanders.
- This approach offers a more favorable prognosis for acute glanders, potentially leading to higher survival and lower relapse rates.
- Further research into liposomal drug delivery systems is warranted for treating intracellular bacterial infections.
