A lack of new antibiotics
After decades of new antibiotic development and a view that infectious diseases had almost been eliminated, antibiotic research was neglected due to changes in drug development priorities. With the emergence and rapid spread of resistant bacteria, the world is now left with a decreasing stock of effective antibiotics, and policy makers are trying to increase research activities in this field again. In 2011, the European Commission published an action plan to address the rising threats from antimicrobial resistance,(29) and in 2013 the Pharmaceutical Research and Manufacturers of America asked the FDA for a more flexible approach to the regulation of new antibiotics.(30) In the meantime, the European Medicines Agency has relaxed its guidelines for clinical antibiotic trials and the Infectious Diseases Society of America has proposed the 10 x 20 Initiative, which calls for the development of ten new, safe, and efficacious systemic antibiotics by 2020.(31)
Commercialization and first detection of resistant bacteria for some classes of antibiotics
Until now, new antibiotics have been developed to replace older, increasingly ineffective ones. However, human innovation may no longer outpace bacterial mutation. There is a current shortage of new antibiotics, with fewer pharmaceutical companies engaged in the process of drug development since the 1990s.
Even if we were able to find new drugs which are effective against antibiotic resistant bacteria, history is likely to repeat itself. Bacteria have a big advantage over us; they are far older from the evolutionary point of view, and far more numerous and prolific. Hence, as Pasteur — a pioneer of microbiology — once predicted, bacteria will always be ahead of us. For now, our best chances rely on making better use of current antibiotics and also revisiting the use of older molecules (which have sometimes been under-used because of drawbacks and side effects).
Therefore, in order to bypass the problems of antibiotic resistance and a lack of new drugs, radical new ways of treating infection are being researched. Instead of killing bacteria, these drugs stop bacteria from mounting an attack, or prevent them from forming “biofilms”, or impair their chemical “communication” with each other.
Alternatively, “phage therapy” is being explored which uses phage viruses (that may or may not be genetically engineered) or phage enzymes in order to destroy bacteria. Strategies relying on “probiotics” — recruiting, enhancing or replacing our normal flora with beneficial bacteria to keep disease-causing bacteria in check — are also a possible alternative.
CRISPR technology offers the possibility of using a bacteriophage hidden in a probiotic to cause bacteria to make lethal cuts to their own DNA. The benefit of using a bacteriophage capable of targeting and killing a single species of germ would be to leave the “good” bacteria intact, in contrast to the way broad-spectrum antibiotic therapies work by killing both good and bad bacteria. This technology could eventually be developed into highly precise antimicrobial treatments.
Additionally, innovative solutions such as faecal transplantation have been used to successfully cure recurrent C. difficile infections, and immunotherapeutic treatments (use of antibodies to block bacterial infection) are in development. However, most of these strategies are still at an early stage and not routinely used.
Another interesting approach to curb the spread of resistance is the early and improved identification of immunocompromized patients in order to enhance infection prevention in a “personalized medicine” approach. For example, patients who have experienced serious trauma or burns, major surgery, serious medical problems or sepsis may become immunocompromised for weeks. In addition, an increasing number of patients receive medical therapies which weaken their immune systems (for example, chemotherapy and radiotherapy, corticosteroids, and other immune-suppressing agents). These patients are more susceptible to acquire a healthcare-associated infection (HAI), thereby requiring antibiotic therapy with the risk of triggering antibiotic resistance . HAIs may also lengthen the duration and costs of hospitalization, and increase morbidity and mortality. The development of host immune response biomarkers allowing the diagnosis and measurement of the degree of immune failure would therefore be useful to identify patients at increased risk of HAI in order to implement infection prevention measures.