Investigation of the Combinatorial Effects of Metformin and Selected Antibiotics on Klebsiella pneumoniae

Authors : İbrahim Serkan Avşar, Derya Doğanay, Esra Mertoğlu

Pages : 85-93

Doi:10.58854/jicm.1833035

View : 52 | Download : 186

Publication Date : 2025-12-31

Article Type : Research Paper

Abstract :Background: The escalation of multidrug-resistant (MDR) Klebsiella pneumoniae infections poses a severe global health threat, necessitating the exploration of alternative therapeutic strategies such as drug repurposing. This study aims to investigate the intrinsic antibacterial activity of the antidiabetic drug metformin and its adjuvant potential when combined with conventional antibiotics against K. pneumoniae. Materials and Methods: The antimicrobial effects of metformin were evaluated against the reference strain K. pneumoniae ATCC 700603 and an MDR clinical isolate obtained from an intensive care unit. Minimum Inhibitory Concentration (MIC) values were determined using the microdilution method. Interaction studies between metformin and three antibiotics (Levofloxacin, Amikacin, and Ceftazidime) were conducted using the checkerboard assay. The results were interpreted based on the Fractional Inhibitory Concentration Index (FICI). Results: Metformin monotherapy exhibited weak intrinsic antibacterial activity (MIC ≥ 500 µg/mL) against both the reference strain and the clinical isolate. In combination assays, metformin demonstrated an antagonistic effect with Levofloxacin, while its interactions with Amikacin and Ceftazidime were classified as indifferent. The observed antagonism with Levofloxacin is attributed to metformin’s antioxidant properties, which likely mitigate the oxidative stress required for the bactericidal action of fluoroquinolones. Furthermore, the lack of synergy with Amikacin suggests that metformin-induced disruption of the Proton Motive Force (PMF) may hinder the intracellular uptake of aminoglycosides. Conclusion: The findings indicate that metformin is ineffective as a standalone antibacterial agent against K. pneumoniae. Moreover, its adjuvant potential is highly dependent on the antibiotic class and strain-specific resistance mechanisms. Contrary to some reports of synergy, this study highlights the risk of antagonism, particularly with fluoroquinolones. Further standardized mechanistic studies are required to define the specific therapeutic windows for metformin as an antimicrobial adjuvant.
Keywords : Metformin, K.pneumoniae, çoklu ilaç direnci (MDR), sinerjizma, antagonizm

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