A novel combination therapy for multidrug resistant pathogens using chitosan nanoparticles loaded with β-lactam antibiotics and β-lactamase inhibitors

Antimicrobial resistance is one of the greatest global threats. Particularly, multidrug resistant extended-spectrum beta-lactamase (ESBL)-producing pathogens confer resistance to many commonly used medically important antibiotics, especially beta-lactam antibiotics. Here, we developed an innovative combination approach to therapy for multidrug resistant pathogens by encapsulating cephalosporin antibiotics and beta-lactamase inhibitors with chitosan nanoparticles (CNAIs). The four combinations of CNAIs including two cephalosporin antibiotics (cefotaxime and ceftiofur) with two beta-lactamase inhibitors (tazobactam and clavulanate) were engineered as water-oil-water emulsions. Four combinations of CNAIs showed efficient antimicrobial activity against multidrug resistant ESBL-producing Enterobacteriaceae. The CNAIs showed enhanced antimicrobial activity compared to naive chitosan nanoparticles and to the combination of cephalosporin antibiotics and beta-lactamase inhibitors. Furthermore, CNAIs attached on the bacterial surface changed the permeability to the outer membrane, resulting in cell damage that leads to cell death. Taken together, CNAIs have provided promising potential for treatment of diseases caused by critically important ESBL-producing multidrug resistant pathogens.

Automated summary

Antimicrobial resistance poses a major global threat, especially multidrug resistant ESBL-producing pathogens. Researchers developed a novel therapy combining cephalosporin antibiotics and beta-lactamase inhibitors encapsulated in chitosan nanoparticles, effectively combating drug-resistant Enterobacteriaceae and showing promising potential for treating critically important infections.