Comparative Antibacterial Efficacy of Povidone-Iodine, Citric Acid, and Starch: A Study of Combined Activity and Interference Effects Against Clinically Relevant Bacteria

Povidone-iodine and citric acid are widely used antimicrobial agents. However, data on their comparative efficacy and the functional outcomes of their combination, particularly regarding the influence of common excipients like starch, is limited. Understanding these interactions is crucial for optimizing antiseptic formulations. This study aimed to evaluate and compare the antibacterial activity of povidone-iodine, citric acid (5% and 20%), and starch (5% and 20%), both individually and in combination, against clinical isolates of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The antibacterial activity of the agents was assessed using an agar well diffusion assay. Mean inhibition zone diameters were measured and compared. The study design specifically controlled for dilution effects by dissolving solid citric acid and starch directly into the povidone-iodine solution for combination testing. Citric acid demonstrated potent, concentration-dependent antibacterial activity, yielding the largest inhibition zones (27.40 ± 1.54 mm for S. aureus with 20% CA). Povidone-iodine alone showed moderate activity. In combination, the antibacterial effect of the citric acid-iodine mixture was dictated by citric acid, with its efficacy fully preserved. In contrast, starch was inactive alone and its presence significantly reduced the antibacterial effect of povidone-iodine. S. aureus consistently showed the largest inhibition zones, while E. coli showed the smallest. Citric acid is a highly effective antibacterial agent whose activity is maintained in combination with povidone-iodine. Starch demonstrates a significant interference effect that reduces the efficacy of povidone-iodine, a finding not attributable to dilution. These results highlight the potential of citric acid as a primary antimicrobial and underscore the critical importance of ensuring physicochemical compatibility in antiseptic formulations.