  Bacterial resistance to antibiotic treatment is a huge concern: introduction
of any new antibiotic is shortly followed by the emergence of resistant
bacterial isolates in the clinic. This issue is compounded by a severe lack of
new antibiotics reaching the market. The significant rise in clinical
resistance to antibiotics is especially problematic in nosocomial infections,
where already vulnerable patients may fail to respond to treatment, causing
even greater health concern. A recent focus has been on the development of
anti-virulence drugs as a second line of defence in the treatment of
antibiotic-resistant infections. This treatment, which weakens bacteria by
reducing their virulence rather than killing them, should allow infections to
be cleared through the body's natural defence mechanisms. In this way there
should be little to no selective pressure exerted on the organism and, as such,
a predominantly resistant population would be unlikely to emerge. However, much
controversy surrounds this approach with many believing it would not be
powerful enough to clear existing infections, restricting its potential
application to prophylaxis. We have developed a mathematical model that
provides a theoretical framework to reveal the circumstances under which
anti-virulence drugs may or may not be successful. We demonstrate that by
harnessing and combining the advantages of antibiotics with those provided by
anti-virulence drugs, given infection-specific parameters, it is possible to
identify treatment strategies that would efficiently clear bacterial
infections, while preventing the emergence of resistant subpopulations. Our
findings strongly support the continuation of research into anti-virulence
drugs and demonstrate that their applicability may reach beyond infection
prevention.
