Combating Multidrug Resistance in Escherichia coli and Klebsiella pneumoniae: A Synergistic Approach with Repurposed Drugs

Introduction Antimicrobial resistance (AMR) is a pressing global crisis endangering public health and the economy worldwide. The rise of multidrug-resistant (MDR) pathogens, such as Escherichia coli and Klebsiella pneumoniae , has led to a critical situation where treating infections caused by bacteria resistant to antibiotics like carbapenems and colistin, has become increasingly challenging and costly. In response, combination antibiotic therapy has emerged as a crucial strategy when single-drug treatments prove ineffective, offering a potential solution to combat the highly resistant pathogens effectively. Objectives The objective of this study was to investigate AMR in E. coli and K. pneumoniae , as well as the potential synergistic effects of combining Auranofin and MMV675968 with other FDA approved antimicrobial agents. Methods The antimicrobial susceptibility test used the broth micro-dilution method, and polymerase chain reactions were employed to detect resistance genes associated with AMR in clinical isolates. Combination studies were performed using the checkerboard assay against E. coli and K. pneumoniae isolates resistant to meropenem and colistin. Results The study revealed high rate of ESBLs and carbapenemase-producing MDR clinical isolates of E. coli and K. pneumoniae . It demonstrated that Auranofin exhibited synergistic activity with colistin (80%), meropenem (60%) levofloxacin (60%), and nitrofurantoin (90%). Additionally, a combination of MMV675968 with colistin (50%), meropenem (40%) with levofloxacin (80%), and nitrofurantoin (60%) also showed synergy against these MDR isolates. Conclusion Repurposing existing drugs and combining them in novel ways offers a rapid and resource-efficient strategy to combat MDR Gram-negative bacterial infections and address the growing threat of AMR.