Reversion of multidrug resistance in clinical isolates of Escherichia coli using non-steroidal anti-inflammatory drugs (NSAIDs)
摘要
Antibiotics have transformed the treatment of bacterial infections, but their efficacy is increasingly threatened by antimicrobial resistance (AMR). Resistance mechanisms, such as target site modification, efflux pumps, and porin loss, necessitate alternative strategies, including the use of non-antibiotic adjuvants. This study evaluated the synergistic effects of non-steroidal anti-inflammatory drugs (NSAIDs) combined with antibiotics on the antimicrobial susceptibility of multidrug-resistant Escherichia coli. Clinical E. coli strains were exposed to antibiotics (ciprofloxacin, tetracycline, ampicillin) with or without NSAIDs (acetylsalicylic acid, ibuprofen). Antibiotic susceptibility was assessed via disk diffusion, while minimum inhibitory/bactericidal concentrations (MICs/MBCs) were determined to quantify interactions. Membrane integrity was evaluated through cytoplasmic contents release assays. NSAIDs significantly enhanced antibiotic susceptibility, reducing MICs/MBCs in most strains. Membrane leakage assays demonstrated increased release of intracellular components, suggesting compromised membrane integrity. The strongest synergy was observed with ciprofloxacin-ibuprofen combinations. NSAIDs potentiate antibiotic activity against resistant E. coli, likely through membrane disruption. This adjuvant approach could help combat AMR and warrants further investigation.