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Bacterial resistance to antibiotic treatment is a huge concern: introductionof any new antibiotic is shortly followed by the emergence of resistantbacterial isolates in the clinic. This issue is compounded by a severe lack ofnew antibiotics reaching the market. The significant rise in clinicalresistance to antibiotics is especially problematic in nosocomial infections,where already vulnerable patients may fail to respond to treatment, causingeven greater health concern. A recent focus has been on the development ofanti-virulence drugs as a second line of defence in the treatment ofantibiotic-resistant infections. This treatment, which weakens bacteria byreducing their virulence rather than killing them, should allow infections tobe cleared through the body's natural defence mechanisms. In this way thereshould be little to no selective pressure exerted on the organism and, as such,a predominantly resistant population would be unlikely to emerge. However, muchcontroversy surrounds this approach with many believing it would not bepowerful enough to clear existing infections, restricting its potentialapplication to prophylaxis. We have developed a mathematical model thatprovides a theoretical framework to reveal the circumstances under whichanti-virulence drugs may or may not be successful. We demonstrate that byharnessing and combining the advantages of antibiotics with those provided byanti-virulence drugs, given infection-specific parameters, it is possible toidentify treatment strategies that would efficiently clear bacterialinfections, while preventing the emergence of resistant subpopulations. Ourfindings strongly support the continuation of research into anti-virulencedrugs and demonstrate that their applicability may reach beyond infectionprevention.

Bacterial fitness shapes the population dynamics of antibiotic-resistant  and -susceptible bacteria in a model of combined antibiotic and  anti-virulence treatment