Evaluation of the Synergistic Activity of Melatonin with Ampicillin, Streptomycin, and Colistin Against <i>Escherichia coli</i>

Abstract

Background: Antimicrobial resistance represents a major global health challenge that reduces the effectiveness of conventional antibiotic therapies and underscores the need for alternative adjunctive strategies. Melatonin, an endogenous neurohormone with antioxidant and immunomodulatory properties, has recently emerged as a potential antibiotic adjuvant. Objectives: To evaluate the synergistic effects of melatonin in combination with colistin, streptomycin, and ampicillin against Escherichia coli ATCC 25922. Methods: Antibacterial activity was assessed using broth microdilution and checkerboard assays. Bacterial growth was quantified by measuring the optical density (OD600), and the fractional inhibitory concentration index (FICI) was calculated to determine drug interactions. Results: Melatonin exhibited synergistic activity in combination with streptomycin (FICI = 0.245; 8-fold potency) and ampicillin (FICI = 0.37; 4-fold potency), whereas an additive effect was observed with colistin (FICI = 0.75; 2-fold potency). The melatonin–streptomycin combination showed the strongest synergistic interaction. Conclusions: Melatonin enhanced the in vitro antibacterial activity of the tested antibiotics in a class-dependent manner. These preliminary findings provide a basis for further investigating melatonin as a potential antibiotic adjuvant in clinically relevant models.