Synergistic antimicrobial effect of the combination of beta-lactam antibiotics and chitosan derivative on multidrug-resistant bacteria

Dissemination of multidrug-resistant (MDR) bacteria with CTX-M-type extended-spectrum β-lactamases (bla CTX-M ) has become the greatest challenge in public health care. This study aimed to investigate the synergistic antibacterial potential of N-alkylaminated chitosan nanoparticles (CNPs) combined with conventional β-lactam antibiotics (BLAs) against multidrug-resistant pathogen with bla CTX-M gene. The results of this study showed that the developed nano-formulation resensitized the studied E. coli MDR strain (E001) to ampicillin (AMP) and piperacillin (PIP) by causing a 1000–10,000-fold decrease in their MIC values (5000–50,000 mg/L to 5 mg/L). The conjugation of CNPs with cefoxitin (FOX) and ceftazidime (CAZ) showed a comparatively lower synergistic inhibitory effect owing to the higher susceptibility (MIC value = 0.5 mg/L–5 mg/L) of E001 to these antibiotics. The results indicate that CNPs could be effectively employed as an additive to augment the antibacterial effect of the BLAs for which MDR strains exhibit higher MIC values. • β-Lactams added with chitosan derivative (CNP) inhibited drug-resistant bacteria. • Combinatorial treatment reduced the MIC of tested β-lactams by 100–10,000 fold. • Ampicillin/piperacillin combined with CNP exhibited a stronger synergetic effect. • Combined therapy is less effective for β-lactams to which bacteria is susceptible.