Why is the problem of antibiotic resistance increasing and is the problem reversible?

JT: Overuse and misuse of antibiotic therapy is causing increases in resistant bacterial strains. The development of new antibiotics is the only way to counteract this problem.

MMF: Antibiotic resistance is a surprisingly ancient phenomenon — one intriguing study identified resistance genes in 30,000-year-old bacterial samples. Nevertheless, it has been rising in the decades since the introduction and widespread use of modern antibiotics. At a basic level, it represents the natural consequence of selective evolutionary pressure. Bacteria with resistance to a certain drug survive in the presence of that drug, whereas those lacking resistance (“susceptible bacteria”) do not. Consequently, there is enrichment of the drug-resistant bacterial population. Considering the rapid rates at which bacteria replicate, their large numbers and their intrinsic diversity, resistance can escalate rapidly.

On a deeper level, a number of other factors contribute to antibiotic resistance. Unlike humans who can only transfer genes to their offspring, bacteria can transfer genes horizontally to other members of the same species or even to completely different types of bacteria. Consequently, the spread of genes encoding different resistance mechanisms can spread much more quickly. Inadequate antibacterial therapy, for example, through suboptimal drug concentrations at a site of infection can also select for antibiotic resistance. Moreover, many bacteria are multidrug-resistant, with a diversity of mechanisms that confer reduced susceptibility to antibiotics across multiple therapeutic classes. These explanations are unfortunately just the tip of the iceberg. Other factors also play a role including hospital hygiene, the use of antibiotics in agriculture and the unintended effects of antibiotics on the human microbiome. Researchers at Ohio State and worldwide are working to understand the causes, mechanisms and consequences of antibiotic resistance more completely.

How is antibiotic resistance going to affect medicine?

JT: Physicians have already become more careful about prescribing antibiotic therapy only when needed. However, the emergence of resistant strains is already causing many cases that are dangerous and difficult to treat with the drugs we have.

MMF: Consider an individual who has a life-threatening infection from an antibiotic-resistant bacterium. If the infection cannot be treated with an effective antibiotic, the likelihood of mortality increases dramatically. Such deaths were commonplace before the advent of effective antibiotics in the 20th century and are once again highly relevant. One widely quoted estimate from the UK’s Report on Antimicrobial Resistance places the annual number of deaths from antimicrobial-resistant infections (including those from bacteria as well as HIV, a virus, and malaria, a parasite) at 700,000 globally.

What areas of medicine are going to be affected the soonest?

JT: Antibiotic resistant strains have been thriving in hospital settings. The greatest risk is for patients with abnormal immune systems (transplant patients, for example) who are exposed to these strains while admitted to the hospital.

MMF: Naturally, one thinks first about the treatment of infections. Antibiotic resistance already plays an important role here. Indeed, physicians have turned increasingly in recent years to older, more toxic antibiotics like colistin/polymyxin due to resistance to other, safer, therapies. Unfortunately, there are also bacteria with resistance to the more toxic options as well. Some researchers and physicians have expressed concern that we might enter a “post-antibiotic era,” in which doctors will no longer have ready access to life-saving antibiotics due to resistance. The UK Report on Antimicrobial Resistance estimates that global deaths from resistant infections will rise to 10 million per year by 2050.

One must also consider other areas of medicine where the effective treatment of infections plays an important role. For example, many aspects of modern medicine involve immune suppression, thus limiting the natural ability of our bodies to fight infections. Examples include organ transplant, the treatment of autoimmune diseases like rheumatoid arthritis, and some forms of cancer chemotherapy. Consequently, the effects of drug-resistant infections can ripple through the rest of the healthcare system as well.

When do you think we're going to be "out of options" for many—or even most—infections?

JT: I am confident that scientific researchers like my colleagues at Chapman University will be able to develop new antibiotic strategies to address the emergence of resistant strains. This innovation, combined with the careful use of these new antibiotics, will help keep us one step ahead in this microscopic arms race.

MMF: That is a difficult question and I hope the answer is “never.” In analogy to horizontal gene transfer among bacteria, humans possess the amazing ability for horizontal knowledge transfer across scientific disciplines, institutions and nations. Coupled with our capacity for innovation and our rapidly developing understanding of fundamental biology, we may still have the upper hand. Nevertheless, it is obviously critical that we continue to invest in addressing this key threat to human health. I am proud to be at Ohio State University, whose substantial investments in infectious disease research through the Discovery Themes Initiative and the recently launched Infectious Diseases Institute, epitomize our commitment to this area. My own medicinal chemistry lab is working diligently to develop new inhibitors of bacterial topoisomerases, in the hopes of advancing new therapies for a variety of bacterial pathogens. Ohio State has a superb culture of collaboration and I have been grateful for the many enthusiastic co-investigators with diverse expertise who have joined our efforts. We are one small piece of a much larger enterprise, but we hope to have an impact on the critical issue of antibiotic resistance.