“If antibiotics lose their effectiveness it will spell “the end of modern medicine.”
Professor Dame Sally Davies
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 2010, the Infectious Diseases Society of America proposed the 10×20 Initiative, which calls for the development of ten new, safe, and efficacious systemic antibiotics by 2020. Infectious Diseases Society of America. The 10 x ’20 Initiative: pursuing a global commitment to develop 10 new antibacterial drugs by 2020. Clin Infect Dis. 2010;50:1081-83.
In 2013, a status report regarding the antibiotic pipeline identified some, yet insufficient, progress.
In 2019, a new Infectious Diseases Society of America review of the number of antibiotic drugs in development identified tangible progress in the development and approval of several clinically relevant, new antibiotics. Driven by new financial incentives and increased regulatory flexibility, this positive trend has raised the possibility of reaching twenty new antibiotics by 2020, instead of the initial target of ten. However, most of the newly approved / in-pipeline antibiotics are only modifications of existing classes of antibiotics, rather than new drug classes using new targets and modes of action that could stop resistance to those drugs developing too quickly.
So although the 20×20 target may indeed be met, it may well be the high point of antibiotic drug development for future decades. As pharmaceutical companies and investors continue to pull out of the field, more economic incentives and new reimbursement models will be essential to ensure the development of new antibiotics.
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To prioritize research and development of new antibiotics, World Health Organization published a Priority Pathogens List. Aditionnally, through a joint initiative with Drugs for Neglected Diseases initiative called the Global Antibiotic Research and Development Partnership (GARDP), it seeks to catalyse public-private partnerships. By 2023, this partnership aims to develop and deliver up to four new treatments, through improvement of existing antibiotics and acceleration of the entry of new antibiotic drugs. The Priority Pathogens List was published by World Health Organization in a bid to promote.
Commercialization and first detection of resistant bacteria for some classes of antibiotics
Adapted from “Antibiotic Resistance Threats in the United States. Centers for Disease Control and Prevention, 2013”.
Alternatives to 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.
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 to use 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.
Clustered Regularly Interspaced Short Palindromic Repeat DNA sequences 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.