Q&A: How to respond to the WHO's top 12 superbugs list

Editor’s note: In February, The World Health Organization (WHO) published its first list of a dozen families of antibiotic-resistant “priority pathogens” that pose the greatest threat to humanity. 

"This list is a new tool to ensure R&D responds to urgent public health needs," said Marie-Paule Kieny, WHO's assistant director-general for health systems and innovation, in a press release. "Antibiotic resistance is growing, and we are fast running out of treatment options. If we leave it to market forces alone, the new antibiotics we most urgently need are not going to be developed in time." 

The pathogens on the list were chosen based on: 
•    How long a hospital stay they require
•    How frequently they’re resistant to existing antibiotics 
•    How contagious they are
•    Whether they can be prevented through things like good hygiene and vaccination
•    The number of treatment options available
•    Whether there are new antibiotics to treat them in the research and development (R&D) pipeline 

The following is an edited Q&A about the WHO’s list with Jennifer Pisano, MD, medical director of the antimicrobial stewardship program (ASP) at the University of Chicago Medicine and Biological Sciences, and Trevor Van Schooneveld, MD, FACP, medical director of the University of Nebraska Medical Center’s ASP, program director of its infectious disease fellowship, and associate professor in its Division of Infectious Disease. The interviews were conducted separately.

PSMJ: Why is it so hard to develop new antibiotics? Are there any reports or signs of new antibiotic(s) coming out in the next five years? 

Pisano: It is very expensive to develop any drug, and antibiotics are particularly difficult. A lot of times it’s likely not worth a pharmaceutical company investing the money into creating a drug that will only be used for a short period of time (around seven to 14 days) when drugs that people take for lifestyle diseases like HTN [hypertension] and DM [dermatomyositis] are taken for much longer periods—often a lifetime. 

Additionally, since there’s a bigger emphasis on stewardship programs and saving drugs for when you really need them, any new antibiotic likely will be restricted to “save” it and hinder the development of resistance. It has been frustrating that even with the new antibiotics that have come out to treat resistant Gram-negative infections, they’ve offered new beta-lactamase inhibitors but not necessarily new mechanisms of action.

Van Schooneveld: The process of developing and obtaining regulatory approval for a new antibiotic takes roughly 10 years and many hundreds of millions of dollars. There are new antibiotics in the pipeline, but there are not very many, and there are very few truly new antibiotics. Additionally, there are very few new antibiotics which will have activity against some of these highly resistant pathogens.

PSMJ: The WHO’s priority pathogens list is non-binding, and it doesn’t provide financial incentives. What effect, if any, do you think it will have on antibiotic R&D?

Pisano: It provides a road map to need, but without incentives, it is hard to gauge how much new drug development it will stimulate. One of the questions a company asks itself during the development stages is how likely a drug is to be approved by the FDA, and if it addresses a need on this list, the answer would be very likely.

Van Schooneveld: It may have some effect, but the few companies still involved in antimicrobial drug development are already aware of these pathogens.

PSMJ: How long have the resistant strains of the infections on the list been around? Are the listed pathogens relatively new?

Van Schooneveld: The pathogens identified are not new, nor are problems with resistance in these pathogens. Many of the pathogens listed have been problems for many years. For example, drug resistance and Acinetobacter has been reported for many years. But the WHO is trying to prioritize what we should focus on.

Pisano: New drugs and the development of resistance go hand in hand. It’s been like this since the discovery of penicillin—even before penicillin was used in clinical practice, the first strains of [resistant] bacteria were identified. Carbapenem-resistant Enterobacteriaceae (CRE) have been increasing over the past 15 years. First described in 2009, New Delhi metallo-B-lactamase—containing Pseudomonas aeruginosa and Enterobacteriaceae—has emerged as a threat. Methicillin-resistant Staphylococcus aureus (MRSA) was first reported in 1962, two years after methicillin was introduced, and it was only inevitable that vancomycin-intermediate and -resistant strains of Staphylococcus aureuswould be reported increasingly over the past 10 years, as our use of vancomycin has been steadily increasing to combat MRSA.

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