Emerging Synergistic Antimicrobial Combinations against Cholera

Cholera, caused by Vibrio cholerae, remains a significant public health challenge, particularly in low- and middle-income countries. Major control strategies for cholera typically involves the use of antibiotics along with rehydration therapies. However, the increasing emergence of antibiotic-resistant strains globally has severely limited the efficacy of conventional monotherapies, complicating cholera disease management. In response, recent research has focused on synergistic drug combinations as promising alternatives to combat resistant V. cholerae infections. This review highlights the potential of combining antibiotics with quorum-sensing inhibitors, plant-derived phytochemicals, and other antimicrobial agents to enhance bactericidal activity and reduce the development of resistance. In addition, we propose a novel Phage Antibiotic Synergy (PAS) based combination therapy that has not yet been explored in the context of cholera treatment. This emerging strategy aims to maximize bacterial eradication by combining phage specificity with the broad-spectrum activity of antibiotics, potentially overcoming the limitations of monotherapy. Moreover, the review provides an overview of antibiotic synergy and its classification, and discusses general mechanisms of synergistic action in the context of other pathogens. The review also addresses the mechanistic insights behind these synergistic effects, therapeutic implications and future research directions. Additionally, it examines the practical challenges and limitations associated with implementing such combination therapies within the clinical setting. Given the global rise in antimicrobial resistance, exploring such multifaceted therapeutic avenues offers a promising future direction for more effective and sustainable cholera control.