Antibiotic resistance: the best offense is a good defense


Ken Stover, Ph.D

The rapid increase in antimicrobial resistance (AMR)—including antibiotic resistance (ABR)—is one of the most pressing public health issues of our time, threatening the return to a pre-antibiotic era. In fact, a World Health Organization (WHO) report in April of this year said that the threat is “no longer a prediction for the future, it is happening right now in every region of the world and has the potential to affect anyone.”

There are as many reasons for why we’ve come to this dire situation—including inappropriate overuse of broad-spectrum antibiotics—as there are for why it’s so potentially devastating to the practice of modern medicine and human health. The Centers for Disease Control (CDC) says that in the U.S. alone, as many as 99,000 people die in our hospitals every year from bacterial infections; about 70,000 of these deaths are from drug-resistant bacteria. What’s worse is that these infections have begun coursing into the community at large.

As David Shlaes explains in his book Antibiotics: The Perfect Storm, effective antibiotics are an essential cornerstone to modern medicine as we know it—They are key to preventing or treating infections associated with immunosuppression in transplant operations, the treatment of chronic inflammatory diseases as well as implementing many cancer therapies and complex surgical procedures.

The problem is that antibiotics, a major triumph for modern medicine, have been taken for granted, and the development of new antibiotics hasn’t been a priority for industry or society. But now, there has been growing attention to the challenge of AMR, including a World Health Assembly (WHA) resolution on AMR that urges member states to strengthen drug management systems, support research to extend the lifespan of existing drugs, and to encourage the development of new diagnostics and treatment options.

For our part, we’re guided by the principle that the optimal offense against drug resistance is a strong defensive strategy to prevent serious bacterial infections. This would largely reduce the need for antibiotics in the first place and reserve them for active infections. This has stimulated interest in alternative pathogen-specific strategies, including monoclonal antibody (mAb) technology, for targeting the most problematic microorganisms.

At this week’s Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), we’ll discuss how we’ve been looking at such novel antibody clinical candidates, including a symposium presentation on these alternative treatment approaches for bacterial infections.

What’s unique about the field of modern antibody discovery and development technology as it relates to bacterial infection and AMR is the strong potential to create molecules that are narrow-spectrum, pathogen-specific and longer-lived than traditional antibiotics. We believe that mAbs, which disarm the bacteria’s damaging pathogenic mechanisms or help to clear the bacteria from the host, will complement traditional antibiotics. These molecules may reduce the use of antibiotics and augment the patient’s defense against infection in adjunctive treatment with antibiotics, without stimulating antibiotic cross-resistance between different bacterial species.

And, our research with two of these molecules— MEDI4893 and MEDI3902 —has been encouraging. Recent preclinical studies with Staphylococcus aureus and Pseudomonas aeruginosa have demonstrated that engineered multi-mechanistic mAbs may not only protect against infection and work synergistically with marginally active antibiotics against drug-resistant strains, they may also have potential to prevent co-infections with multiple bacteria.

These studies exemplify pathogen-specific strategies to preserve and augment antibiotics by harnessing modern antibody technology. And, we’re developing these investigational clinical candidates—currently aimed at S. aureus and P. aeruginosa,two of the most problematic, drug-resistant bacterial pathogens that we see today,—in collaboration with the European Commission’s Innovative Medicines Initiative program, under the New Drugs for Bad Bugs (ND4BB) project.

Our goal is to face off the AMR and ABR dilemma and to ameliorate what we—and others—believe is a dangerous threat to the practice of modern medicine.