Effects of Chronic Antidiabetic Drugs on Antibiotic Efficacy Against Intestinal Escherichia coli Isolates
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Background: Diabetic patients often need combined antimicrobial and antidiabetic treatment, however, the impact of chronic metabolic medications on antibiotic effectiveness is poorly understood. The objective of this study was to investigate these drug-modulatory effects on the antibacterial activity of antibiotics in vitro using commonly prescribed antidiabetic drugs (Metformin, Glimepiride, and Dapagliflozin). Methodology: The antibacterial interactions were evaluated against clinical isolates of Escherichia coli obtained from diabetic patients and healthy individuals, as well as a standard pathogenic strain O157:H7. Methods: In this study, we examined 11 different antibiotics and assessed all baseline susceptibility as well drug-drug interactions with antidiabetic drugs by the disk diffusion method. Results: Baseline testing demonstrated a significant multidrug resistance burden with absolute (100%) resistance to Trimethoprim, and Fusidic acid across diabetic clinical isolates, while fluoroquinolones (Levofloxacin, Ciprofloxacin) and Meropenem collectively retained complete (100%) susceptibility. Importantly, Metformin showed an extremely selective and microbiome-sparing inhibition only against the pathogenic E. coli O157:H7 strain. Pharmacodynamics and drug interactions assays demonstrated that potent, strain-dependent in vivo modulation of antibiotic efficacy could be achieved. Obligate antagonism was found with all combinations of Ampicillin tested (≤5 mm decrease in inhibition zones) and Levofloxacin to be a consistently reliable synergistic partner for >80% of antibiotics assessed, producing significantly larger inhibition zones. In addition, unique interaction profiles were identified between isolates from subjects with and without diabetes. Conclusion: These data undermine the assumed pharmacological neutrality of antidiabetic agents in the management of bacterial infections. The microbiome-mediated differential responses to these microbes in relation to the host microenvironment provide a clinical paradigm shift: when it comes to cohort of diabetics, in order to limit the risk of failure related to antibiotic treatment, empirical antibiotic selection has to deal not only with the pharmacokinetic and pharmacodynamics profile associated with concurrent antidiabetic treatment.
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