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Antimicrobial Resistance Threat Continues During COVID

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July 1, 2021 -- The stark realities of antimicrobial resistance – including rising rates of difficult-to-treat infections, a lack of robust pipeline of future antimicrobials, and COVID-19 treatments that leave people more vulnerable to infections -- remain urgent priorities, experts say.

For some patients, the pandemic and antimicrobial resistance (AMR) are intertwined.

"One patient I'm seeing now in service really underscores how the two interact," Vance Fowler, MD, said during a June 30 media briefing sponsored by the Infectious Diseases Society of America (IDSA). A man in his mid-40s, married with a small child, developed COVID-19 in early January 2021. He was intubated, spent about one month in the ICU, and managed to survive.

"But since then he has been struck with a series of progressively more drug resistant bacteria," said Fowler, professor of medicine at Duke University School of Medicine in Durham, North Carolina and Chair of the IDSA Antimicrobial Resistance Committee.

The patient acquired Pseudomonas ventilator-associated pneumonia while on the ventilator. Although the infection initially responded to standard antibiotics, he has experienced relapses over the past few months. Through these multiple infections the Pseudomonas grew increasingly pan-resistant to treatment.

The only remaining antimicrobial agent for this patient, Fowler said, is "a case study in what we are describing … a drug that is used relatively infrequently, that is fairly expensive, but for that particular patient is absolutely vital."

A 'Terrifying' Personal Experience

Tori Kinamon, a Duke University medical student and FDA Antibacterial Drug Resistance Fellow, joined Fowler at the IDSA briefing. She shared her personal journey of surviving a methicillin-resistant Staphylococcus aureus (MRSA) infection, one that sparked her interest in becoming a physician.

"I had a very frightening and unexpected confrontation with antimicrobial resistance when I was a freshman in college," Kinamon said.

A few days after competing in a Division One gymnastics championship, she felt a gradual onset of pain in her left hamstring. The pain grew acutely worse and, within days, her leg become red, swollen and painful to the touch.

Kinamon was admitted to the hospital for suspected cellulitis and put on I.V. antibiotics.

"However, my clinical condition continued to decline,” she recalled. “Imaging studies revealed a 15 cm abscess deep in my hamstring.”

The limb- and life-threatening infection left her wondering if she would come out of surgery with both legs.

"Ultimately, I had eight surgeries in two weeks," she said.

"As a 19-year-old collegiate athlete, that's terrifying. And I never imagined that something like that would happen to me – until it did," said Kinamon, who is also an NCAA Infection Prevention Advocate.

When Kinamon's kidneys could no longer tolerate vancomycin, she was switched to daptomycin.

"I reflect quite frequently on how having that one extra drug in the stockpile had a significant impact on my outcome," she said.

Incentivizing New Antimicrobial Agents

A lack of new antimicrobials in development is not a new story.

"There's been a chill that's been sustained on the antibiotic development field. Most large pharmaceutical companies have left the area of anti-infectants and the bulk of research and development is now in small pharmaceutical companies," Fowler said. "And they're struggling."

One potential solution is the Pasteur Act, a bipartisan bill reintroduced in Congress and supported by IDSA. The bill encourages pharmaceutical companies to develop new antimicrobial agents with funding not linked to sales or use of the drugs.

Furthermore, the bill emphasizes appropriate use of these agents through effective stewardship programs.

Although some institutions shifted resources away from AMR out of necessity when COVID-19 struck, "I can say certainly from our experience at Duke at least stewardship was alive and well. It was not relegated to the to the side," Fowler said.

"In fact,” he added, “if anything, COVID really emphasized the importance of stewardship" by helping clinicians with guidance on the use of remdesivir and other antivirals during the pandemic.

Also, in some instances, treatments used to keep people with COVID-19 alive can paradoxically place them at higher risk for other infections, Fowler said, citing corticosteroids as an example.

Everyone's Concern

AMR isn’t just an issue in hospital settings, either. Kinamon reiterated that she picked up the infection in an athletic environment.

"Antimicrobial resistance is not just a problem for ICU patients in the hospital. I was the healthiest I had ever been and just very nearly escaped death due to one of these infections,” she said. "As rates of resistance rise as these pathogens become more virulent, AMR is becoming more and more of a community threat," she added.

Furthermore, consumers are partially to blame as well, Fowler noted.

"It's interesting when you look at the surveys of the numbers of patients that have used someone else's antibiotics" or leftover antimicrobial agents from a prior infection.

"It's really startling … that's the sort of antibiotic overuse that directly contributes to antibacterial resistance,” he said.

Reasons for Optimism

Promising advances in diagnostics, treatment and prevention of AMRs are underway, Fowler said.

"It always gets me really excited to talk about it. It's amazing what technology and scientific discovery can bring to this discussion and to this threat," he said.

For example, there is a "silent revolution" in diagnostics with the aim to rapidly provide life-saving actionable data on a real patient in nearly real time.

Traditionally, "you start off by treating what should be there" while awaiting results of tests to narrow down therapy, Fowler said. However, a whole host of new platforms are in development to reduce the time to susceptibility results. This kind of technology has "the potential to transform our ability to take care of patients, giving them the right drug at the right time and no more,” he said.

Another promising avenue of research involves bacteriophages. Fowler is principal investigator on a clinical trial underway to evaluate bacteriophages as adjunct therapy for MRSA bacteremia.

When it comes to prevention on AMR infections in the future, "I continue to be optimistic about the possibility of vaccines to prevent many of these infections,” Fowler said, adding companies are working on vaccines against these kinds of infections caused by MRSA or E. coli, for example.

Patient Outcomes

The man in his 40s with the multidrug resistant Pseudomonas infections "is now to the point where he's walking in the halls and I think he'll get out of the hospital eventually," Fowler said.

"But his life is forever changed,” he added.

Kinamon's recovery from MRSA included time in the ICU, one month in a regular hospital setting, and five months at home.

"It sparked my interest in antibiotic research and development because I see myself as a direct beneficiary of the stockpile of antibiotics that were available to treat my infection," Kinamon said. "Now as a medical student working with patients who have similar infections, I feel a deep empathy and connectedness to them because they ask the same questions that I did."

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