A New Strategy to Tackle Antibiotic Resistance

We all know that the discovery of penicillin by Alexander Fleming was a turning point in medical history, which led to the development of lifesaving antibiotics. But who would have thought that decades down the road, we would be battling antibiotic resistance on a global scale. Data from the European Centre for Disease Prevention and Control (ECDC), released at the end of last year, showed a marked increase in carbapenem-resistant infections across Europe. Mortality rates have increased as well due to the limited options of antibiotics available to treat these infections. According to the European Commission, the widespread prevalence of antibiotic resistance has been estimated to cause approximately 25,000 deaths annually and more than €1.5 billion in healthcare expenses and productivity losses in Europe alone. A June 2013 report by IMS Health, “Avoidable Costs in US Healthcare,” noted that in 2012, there were 900,000 hospital admissions for drug-resistant conditions. According to IMS Health, the avoidable cost from antibiotic misuse ranges between $27 billion to $42 billion.

We are at war! It’s bugs versus drugs and we desperately need new antibiotics. However, the clinical lifespan of new antibiotics could be relatively short if not used responsibly. Drug resistance will develop as long as we use antibiotics and this course of evolution is inevitable.

Interestingly, scientists from the University of Edinburgh have proposed a new strategy that could potentially solve the problem of antibiotic resistance. Instead of killing the target organism or inhibiting pathogen growth (which is how current treatments work), this strategy disarms the bacteria by targeting the virulence factors (i.e., specific proteins and toxins that cause infections) in the bacteria. Allen et al. provided arguments for the use of anti-virulence drugs, backed up with findings from their research that bacterial growth and the expression of virulence factors are often disconnected considerably. Based on the understanding that drug resistance follows the recovery of bacterial growth after antibiotic exposure, agents (such as anti-virulence drugs) that do not affect the growth rate of the bacteria would therefore not impose selection for resistance.

The opinion paper, published in Nature Reviews Microbiology, suggests that the correct use of anti-virulence drugs could in fact reduce the natural selection for resistant strains and even reverse drug resistance given the considerable disconnect between bacterial growth and the expression of virulence factors. While this discovery could potentially revolutionize drug development for bacterial infections and provide a solution to the growing threat of antibiotic resistance, the research is still at its infancy and the authors have cautioned that more work needs to be done to further understand the applications of anti-virulence drugs before their full benefits can be utilized.

R.C. Allen et al., Nature Reviews Microbiology, 4 (12) 300–308 (2014).