At this moment in time, all attention has been turned to the novel coronavirus that is circling the globe and upending life as we know it. Not only is the virus highly contagious, but it is particularly dangerous because there are no effective treatments. For those who contract it and whose immune systems are vulnerable due to age, underlying conditions or other reasons, the infection is life-threatening.
In the US, we are at the beginning of seeing how this ultimately will play out. During one of the most recent pandemics in modern history, the influenza pandemic of 1918-1919, the greatest cause of mortality during was secondary bacterial infections according to the National Institutes of Health. The first antibiotic wasn’t approved until 1942, so we are better positioned today than we were then, and we are hopeful that we won’t see many lethal secondary infections as was the case in 1918.
Yet, as national and global attention is turned to the impact of infection without treatment, it’s important to remind ourselves of another threat: the current crisis of multidrug resistance for bacterial infections. Just last year, in 2019, the Centers for Disease Control and Prevention compiled a report on Antibiotic Resistance Threats in the United States, highlighting that more than 2.8 million antibiotic-resistant infections occur in the US each year, ending in death for more than 35,000 Americans annually.
Resistance to antibiotic treatment has been a threat since their discovery. Bacteria naturally evolve to protect themselves against the threat of being eradicated. However, for many years, labs were able to keep pace with the evolution of bacteria through strong investment in research and development, which yielded new classes of antibiotics.
However, after a “golden era” of antibiotic discovery, which resulted in multiple new classes of antibiotics, discovery slowed. No new classes of antibiotics have been discovered since the 1970s, and the few new antibiotics that have been introduced to market since that time are modified versions of older drugs.
The results are telling. The World Health Organization estimates that superbugs will kill up to 10 million people globally each year by 2050. Thirty-five percent of common human infections already are resistant to currently available medicines in some high-income countries. The impact goes beyond infection: antibiotics often are used as critical prophylaxis enabling surgery and cancer chemotherapy. If they are not available, these other medical interventions are threatened.
Fortunately, the scientific and medical communities are working toward solutions. From developing new antibiotics to using diagnostics to ensure the right antibiotics are prescribed for the right infections, to exercising stewardship in prescribing, a variety of strategies are being exercised with a goal toward mitigating the current trajectory.
Another option, which has its scientific roots in the pre-antibiotic era, is bacteriophage therapy, commonly referred to as phage therapy. Phage therapy was first explored as a potential treatment for bacterial infections in the 1920s and for over 100 years, has been used as a therapy in Eastern Europe at centers like the Eliava Institute, Tbilisi, Georgia.
In Europe and North America development of phage therapy was almost forgotten due to the overwhelmingly positive results the medical community was witnessing with antibiotics. Infections were no longer certain death as had been the case in years before. However, we are now at the point in time, with the growing bacterial resistance to antibiotics, that there has been renewed interest in phage therapy. So what can we learn from this Old World therapy as the entire world faces the growing challenge of multidrug resistant bacterial infections?
Phages are bacterial viruses that exclusively destroy targeted bacteria – including bacteria that have become resistant to all known antibiotic drugs. Phages have existed and co-evolved with bacteria over the past 3.8 billion years. There is a practically unlimited number of phages on earth; estimates put the number of unique phages in the 1031 range. What’s special about phage is that they continue to co-evolve with bacteria and, when they are screened for potential deleterious genes and purified, their safety profile is well established.
While antibiotics are a static therapy that work for a period of time until the bacteria evolve to resist them, phage are able to co-evolve with the bacteria in their quest for their own existence. What we’ve learned from our experience with antibiotics is that applying a static solution to an evolving problem will be effective only for a period of time.
When the right phage meet the right bacteria in humans, the results can be dramatic as witnessed in patients who have received phage therapy under FDA Compassionate Use Guidelines, with dramatic, life and limb-saving results. Several companies are pursuing these therapies now, with different approaches. Phage therapy has the promise of saving patients’ lives and limbs, by destroying life-threatening bacteria and getting very sick patients out of the ICU and back to living the lives they once knew.
Sadly and devastatingly, the impact of an infection that cannot be treated is playing out around the world. As we look toward a return to our daily lives, let’s pursue infectious disease solutions so that we can continue to deliver the hopeful prognoses we’ve come to expect from antibiotics. By learning from the past, we may have a much better arsenal against antimicrobial-resistant bacteria in the near future.
Photo: spawns, Getty Images