Streptococcus pneumoniae is the leading cause of community-acquired pneumonia. Pneumococcal disease leads to over three million hospitalizations and hundreds of thousands of deaths annually. While vaccines to protect against the bacteria are available, these vaccines are not effective against all strains. Currently, there are very limited treatment options for combating multidrug-resistant S. pneumoniae infections.
In order to test the effects of novel treatments for antibiotic-resistant S. pneumoniae, the researchers conducted a series of experiments with mice. Fomepizole is an FDA-approved drug normally used as an antidote for the ingestion of toxic alcohols, and works by inhibiting the enzyme alcohol dehydrogenase.
For the study researchers inoculated mice with a multidrug-resistant S. pneumoniae and tested the effect of fomepizole in a combinatorial treatment with antibiotics. They quantified the bacterial burden in the organs of infected mice, comparing the experimental group with the control group.
The researchers found that using Fomepizole blocked normal energy production by S. pneumoniae and enhanced the bacteria’s susceptibility to antibiotics and reduced bacterial burden in the lungs of mice with pneumonia. The combination treatment was effective in preventing the development of invasive disease.
Future research is needed however, as this novel drug treatment has not been replicated in clinical studies on humans, who may present with complicating factors such as comorbidities, advanced age, or environmental variables that may play a role in disease outcomes.
Hansol Im, Madison L. Pearson, Eriel Martinez, Kyle H. Cichos, Xiuhong Song, Katherine L. Kruckow, Rachel M. Andrews, Elie S. Ghanem, Carlos J. Orihuela. Targeting NAD+ regeneration enhances antibiotic susceptibility of Streptococcus pneumoniae during invasive disease. PLOS Biology, 2023; 21 (3): e3002020 DOI: 10.1371/journal.pbio.3002020
PLOS. “Fomepizole helps overcome antibiotic-resistant pneumonia in mice, study finds.” ScienceDaily. ScienceDaily, 16 March 2023. <www.sciencedaily.com/releases/2023/03/230316140934.htm>.
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