Investigation of the effects of iron and iron metabolism on antimicrobial susceptibility in gram negative bacteria

Bacterial agents are the most common microorganisms in both community and hospital-acquired infections. Especially in hospital-acquired isolates, the necessity of widespread use of antibiotics is a well-known process that results in bacteria developing resistance to the antibiotics used. The result of this is that new antibiotics come into use and are used for a while. This study was carried out from another point of view, to investigate the effectiveness of the combination of iron with antibiotics, which is an essential element for many important physiological functions of gram-negative bacteria, such as energy production, oxygen transport and regulation of gene expression, on bacteria. A total of 55 clinical isolates including 11 clinical isolates of E. coli, K. pneumoniae, P. aeruginosa, A. baumannii and P. mirabilis, and the standard bacterial strains from the archives of Gaziantep University Faculty of Medicine Department of Medical Microbiology were included in the study. Disc diffusion and microdilution tests were performed in accordance with EUCAST standards for cefepime, amikacin, meropenem, tigecycline, ceftriaxone, colistin and levofloxacin in all isolates. The relationship of the efficacy of these antibiotics with iron chelators deferasirox (DFX) and deforaxamine (DFO) and ambient iron concentration was tested using disc diffusion, checkerboard synergy test, and broth microdilution methods. For tested antibiotics in E. coli, K. pneumoniae, P. aeruginosa and A. baumannii isolates no change were detected in the antibiotic susceptibility results and efficacy of antibiotics in combination with iron chelators and ambient iron concentration were not detected. Zone diameters of cefepime, amikacin, meropenem, tigecycline and levofloxacin antibiotics were found to increase statistically significantly with the addition of DFO in P. mirabilis isolates. With the checkerboard synergy test, a synergistic effect was detected between tigecycline, cefepime, amikacin and colistin antibiotics and DFO for P. mirabilis isolates. It was concluded that new strategies should be developed in the fight against pathogens, and depriving bacteria of iron may be one of these methods, as determined in this study.