Fomepizole helps defeat antibiotic-resistant pneumonia in mice, study finds

Pneumococcal disease causes more than three million hospitalizations and hundreds of thousands of deaths each year. A study published on March 16 in the open access journal PLOS Biology by Carlos J. Orihuela of the University of Alabama in Birmingham, Alabama, USA, and colleagues suggest that the FDA-approved drug Fomepizole may reduce disease severity in the lungs of mice with certain forms of bacterial pneumonia and improve the effectiveness of the antibiotic also erythromycin.

Streptococcus pneumoniae is the main cause of community-acquired pneumonia. Although vaccines to protect against the bacteria are available, these vaccines are not effective against all strains, with some versions being particularly problematic as they are multi-drug resistant. Currently, there are very few treatment options to combat multidrug resistance S. pneumoniae infections.

To test the effects of new treatments against antibiotic resistance S. pneumoniae, the researchers conducted a series of experiments with mice. Fomepizole is an FDA-approved drug normally used as an antidote for ingesting toxic alcohols (such as methanol or ethylene glycol) and works by inhibiting the alcohol dehydrogenase enzyme. Researchers inoculated mice with a multidrug-resistant drug S. pneumoniae and tested the effect of fomepizole in a combinatorial treatment with antibiotics. They quantified the bacterial load in the organs of infected mice, comparing the experimental group to the control group.

Researchers found that using Fomepizole blocked normal energy production by S. pneumoniae and improved the sensitivity of bacteria to antibiotics and reduced the bacterial load 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 new drug treatment has not been replicated in clinical studies on humans, who may have complicating factors such as comorbidities, advanced age, or environmental variables that may play a role. in disease outcomes.

Orihuela adds: “Pharmacological targeting of fermentation pathways is a new way to improve the susceptibility of certain bacteria to antimicrobials. A combination treatment of erythromycin and fomepizole, an alcohol dehydrogenase inhibitor, prevented the live spread of antibiotics Streptococcus pneumoniae.”