Chapter 9: Combinatorial Drug Therapy for Salmonella Biofilm Disruption

Salmonella, a Gram-negative bacterium, presents significant public health challenges due to its ability to form biofilms, which are complex, surface-adhering structures that confer resistance to conventional antibiotics. This resistance leads to chronic infections with high morbidity and mortality, necessitating the development of effective therapeutic strategies, including combinatorial drug therapy. Biofilms protect bacteria from physical and chemical barriers and utilize adaptive mechanisms like efflux pumps and metabolic changes, complicating treatment. Understanding these resistance mechanisms is essential for devising strategies to prevent or slow resistance development. Efflux pump inhibitors, for example, can be combined with antibiotics to enhance drug efficacy, while targeting matrix and quorum sensing pathways can inhibit biofilm formation and persistence. Non-antibiotic strategies such as phage therapy and immunomodulatory agents reduce selective pressure for resistance. Novel drug classes with different molecular targets and mechanisms, along with nanoparticle technology, offer promising approaches to improve drug delivery within biofilms. Enzymatic degradation of biofilm components can also enhance antibiotic penetration. Effective dosing strategies, including time-dependent dosing and achieving high peak concentrations, are crucial for successful combinatorial drug therapy. Personalized medicine, tailored to the specific characteristics of the infecting Salmonella strain and individual patient conditions, utilizes whole-genome sequencing and biofilm assays to guide drug selection and treatment decisions. Despite its potential, personalized medicine faces challenges such as the complexity and cost of genetic testing and advanced biofilm assays, necessitating standardized protocols for clinical integration.