SAN FRANCISCO -- In the 10 years since the "ESKAPE" acronym was coined to describe some of the most deadly pathogens where antibiotics were desperately needed, there has been progress in antibiotic stewardship and infection control, a researcher said here.
Antibiotic stewardship has gained wider acceptance in hospitals and rates of hospital-associated infections are declining. However, antibiotic development is more of a mixed bag, with mostly small and medium-sized companies involved in developing antibiotics.
"I am actually optimistic, more optimistic than I was 10 years ago. In another 10 years, I think we'll be in an even better position," said Louis Rice, MD, of Brown University in Providence, Rhode Island, in a talk at ASM Microbe.
Rice coined the acronym "ESKAPE" to comprise Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. It appears as a subtitle to he wrote in 2009, saying that the idea came to him "in the middle of the night."
The commentary, Rice said, was a polite rebuttal to members of the NIH who had submitted an article about how much money the NIH was spending on antibiotic research ($800 million), and research on antibiotic resistance ($200 million). As chair of the Infectious Diseases Society of America (IDSA) Research on Resistance Working Group, Rice was invited to write a response on behalf of the group.
"My first reaction [to the NIH article] was not positive at all -- I was very angry. It was really remarkable in its misrepresentation," he said. "I needed to [respond] in a polite way, saying 'Yes, you're spending all this money, but I can't tell you what the important problems are.'"
The term took off -- with Rice noting there have been more and more references to it on PubMed every year.
"If you want to be able to follow a term, misspell it," he said.
But much has changed in the 10 years since this commentary, starting with the NIH efforts into funding research in antibiotics and antibiotic resistance. Rice said that "we can quibble about how much money is being spent," but between the NIH and the Biomedical Advanced Research and Development Authority (BARDA), the NIH is paying attention to this problem.
He also said that antibiotic stewardship has improved, citing CDC data that shows in 2016, 64% of hospitals had stewardship programs. Rice also pointed to several meta-analyses showing that, most importantly, none have shown a suggestion of increased mortality associated with stewardship, even with less use of antibiotics.
"Every single study looking to shorter duration of therapy has shown us the effects are equivalent," he said. "The evidence is overwhelming."
Moreover, CDC data has indicated declines in catheter-associated urinary tract infections (UTIs), methicillin-resistant Staphylococcus aureus bacteremia, and C. difficile events, with Rice adding, "overall infection events are getting better in hospitals."
In terms of antibiotic development, Rice noted the highly publicized story of biopharmaceutical company Achaogen , but said there are "reasons to be hopeful and reasons to be cautious" about antibiotic development.
Antibiotics are now mostly the purview of small and medium-sized companies, with only GlaxoSmithKline and Merck as large pharmaceutical companies involved in antibiotic development. AstraZeneca, Novartis, and Sanofi are no longer developing antibiotics as of 2016, Rice noted.
"Large pharma decided after dipping its toe back in the water, this is not going to be an area that will be an emphasis for them," he said.
But he added that there are 13 antibiotics currently in phase III trials -- seven with activity versus ESKAPE pathogens and five with activity versus CDC urgent or World Health Organization (WHO) critical threat pathogens. In addition, three new antibiotics were approved last year, with three additional candidates submitting new drug applications.
During the Q&A, one clinician also pointed to challenges in antibiotic discovery, arguing that any new antibiotics should be brought to market in a slow, deliberate fashion.
"It's super hard to find new, important antibiotics. This is not a 5-10 year problem. In 300 years, [society] is going to want effective antibiotics, so rushing 45 antibiotics to market in the next decade is a bad idea," the commenter said.
Disclosures
Rice disclosed support from Macrolide Pharmaceuticals and Zavante Pharmaceuticals.
Primary Source
ASM Microbe
Rice L "Ten years since ESKAPE -- Are we making progress?" ASM Microbe 2019; Session S283.