Drug-Resistant Pathogens Surging in Hospitals

Already classified as a high priority, “urgent” threat in 2019, Candida auris infections increased 60% in 2020 as the chaos of the pandemic derailed infection prevention and antimicrobial stewardship efforts, the Centers for Disease Control and Prevention (CDC) reports.

Kept somewhat at bay in 2019, drug-resistant pathogens overall caused a 15% surge in healthcare-associated infections (HAIs) and a similar increase in patient deaths in 2020.

In the 2022 report, the CDC analyzed the state of antimicrobial resistance in the United States immediately following the 2020 peaks of the COVID-19 pandemic. Increased resistant infections after hospitalization — amid the overall 15% jump — included carbapenem-resistant Acinetobacter, which spiked up 78% from 2019 to 2020. A 32% increase was seen in multidrug-resistant Pseudomonas for the same period.

“During the first year of the pandemic, more than 29,400 people died from antimicrobial-resistant infections commonly associated with healthcare,” the CDC reports.¹ “Of these, nearly 40% of the people got the infection while they were in the hospital.”

Those estimates are based on a considerable undercount, since the CDC is missing data on many key pathogens as a result of pandemic disruptions. Traditional estimates are that “antimicrobial-resistant infections and Clostridioides difficile — a bacterium that is not typically resistant but can cause deadly diarrhea and is associated with antibiotic use — cause more than 3 million infections and 48,000 deaths in the United States each year,” the CDC notes.

Relentless and prolific when given the opportunity, drug-resistant bacteria and fungi are like the metaphorical “rust” that never sleeps. “It is inevitable that antimicrobial resistance will continue to emerge and spread, but the pandemic has negatively impacted core actions to limit the spread and its impact,” the CDC states in the new report.¹ “Infection prevention and control practices were especially impacted — the most foundational and successful tool to protect people in healthcare settings and communities from getting an infection and the spread of antimicrobial-resistant germs.”

In addition, the agency lamented that “historic gains made on antibiotic stewardship were reversed as antibiotics were often the first option given to treat those who presented with a febrile pulmonary process even though this presentation often represented the viral illness of COVID-19.”

As infection preventionists are well aware, needless administration of antibiotics for viral illnesses only selects out the drug-resistant pathogens in the patient’s microbiome. Still, clinicians were trying to save lives while dealing with a new pathogen and a starkly different patient population than they saw pre-pandemic.

COVID-19 patients admitted in the first year of the pandemic needed prolonged hospital stays, creating more opportunities for antibiotic-resistant pathogens to arise and spread in hospitals.

It is a vexing challenge, but infection preventionists have primary responsibilities in both preventing infections and in antibiotic stewardship, says Linda Dickey, RN, president of the Association for Professionals in Infection Control and Epidemiology.

Supporting education and working with antibiotic stewardship teams is a natural synergy for infection preventionists.

“The two work very closely hand to hand,” Dickey says. “One example is C. diff. There is a direct impact of antimicrobial use and the development of C. diff infection. Anything we can do to help promote appropriate use of antibiotics — preoperatively for surgical patients, as another example. I think there is a very critical role for infection preventionists to support antimicrobial stewardship.”

As antimicrobial resistance pathogens emerge in hospitalized patients, infection preventionists must stop the threat to other patients by implementing transmission-based contact precautions.

“With these types of pathogens — either with infection or colonization — we’re either going to see their emergence due to the use of antimicrobials or cross-transmission from the environment or healthcare workers passing it on. Either way, it is very problematic.”

As reported previously, the chaos of 2020 resulted in an increase in bloodstream infections and other significant HAIs, as infection preventionists were overwhelmed or assigned to other pandemic duties.² (See Hospital Infection Control & Prevention, October 2021.) A good portion of these infections were undoubtedly resistant to antibiotics, so the data sets from the two CDC reports probably overlap to some degree.

The Fungal Threat

First discovered in 2009, C. auris had been on a steady rise since 2015, then exploded during the pandemic. The fungus poses a serious risk to the individual patient and can spread through environmental contamination to cause outbreaks.

“It has high rates of antimicrobial resistance,” said Joe Sexton, PhD, team lead for CDC’s Mycotic Diseases Branch Laboratory. “For a little bit of context, I think it’s important to appreciate that because fungi are eukaryotic organisms, like ourselves, it’s challenging to find unique drug targets that can hurt the fungal pathogen without having side effects on us.”

Given that, there are limited antifungal drugs overall, and less so when trying to treat C. auris. Speaking at a workshop meeting with Food and Drug Administration (FDA) officials, Sexton said that more than 80% of isolates are resistant to one class of antifungals.

“Over 25% of isolates in the United States are resistant to two classes,” he said. “And we’re really concerned to now see isolates popping up that are resistant to all three classes of antifungals that are currently available.”

Pan-resistant C. auris is the stuff of nightmares because the pathogen already can cause significant mortality.

“We’re learning that 5% to 10% of colonized patients go on to develop invasive infections, and of those, we’re seeing over 45% mortality within the first 30 days,” he said. “C. auris also causes large outbreaks in healthcare settings that are hard to control, and we see colonization prevalence go very high. In some units, it can be equal to or even greater than 70% of the patients are colonized by C. auris.”

Risk factors for colonization include mechanical ventilation, recent acute care, antibiotic treatment, and exposure to systemic fluconazole, a commonly used antifungal drug that typically spurs C. auris resistance.

“Caring for colonized patients requires increased resources to adhere to transmission-based precautions, and enhanced communication across units and between other facilities,” said Sexton. “One example includes special attention to disinfectants. We learned early on that many hospital disinfectants with general fungicidal claims are often not effective against C. auris.”

This resulted in the release of a list of disinfectants effective against C. auris, as measured by a five-log reduction in the environment as defined by the Environmental Protection Agency. Expect high environmental contamination around colonized and infected patients. One reason is that the pathogen produces a high viral load in the anterior nares, which would be the obvious target for decolonization.

However, there are few decolonization strategies for C. auris and several other pathogens of concern, which was one of the reasons the CDC was meeting with the FDA and appealing to drug manufacturers for new products.

“We’re hearing from healthcare facilities that they’re struggling to transfer colonized patients out of their unit to the appropriate level of care, because some facilities and units will not accept patients known to be colonized by C. auris,” he said. “This means some patients are getting stuck at the incorrect level of care, in some cases for prolonged periods of time.”

Decolonization Needs

In addition to antibiotic stewardship — which includes both making sure the patient needs an antibiotic and, if so, is taking the right drug — the CDC is especially interested in new approaches to decolonization of carriers. In the meeting with the FDA, the CDC outlined several approaches to using decolonization to prevent infections, both in the index patient and subsequent transmission downstream to others.

“Antimicrobial resistance is really accelerating. We have more difficult-to-treat pathogens every day and fewer effective treatments,” said Michael Craig, MPP, the CDC’s director of Antimicrobial Resistance Coordination and Strategy. “We’re very supportive of new antibiotics to treat some of these infections, but we also want the conversation to be about what we can do to prevent them as well.”

Antibiotics already are used in many preventive functions, such as prophylaxis before surgery. Indeed, the healthcare system is highly dependent on drug therapies, meaning it would be devastating if they become less effective because of antibiotic-resistant pathogens.

“Modern medicine and our healthcare system is really predicated on the efficacy of antibiotic therapy,” Craig said. “We need to have treatment options, but we also need to have prevention therapies or prevention modalities that can really stop the spread of infectious diseases and deadly pathogens.”

Prevention and decolonization strategies targeted at particular body sites would be optimal; for example, the lungs of cystic fibrosis patients, he said.

“Decontaminating the lungs and reducing the burden on that community from these resistant pathogens would be a major game-changer,” Craig said. “It would be a major benefit in terms of giving them more quality of life and longer life.”

Decolonization protocols already widely in use include nasal mupirocin to prevent staph infections in surgical patients and chlorhexidine baths to routinely decolonize intensive care unit patients.

“We know that HAIs are usually caused by pathogens that colonize the patient prior to the infection onset,” said John Jernigan, MD, chief epidemiologist in the CDC’s Division of Healthcare Quality Promotion. “Greater than 80% of Staphylococcus aureus bacteremia and surgical site infections are caused by pre-infection colonizing strains. And similar observations are described for a wide variety of pathogens in a variety of healthcare settings.”

Although these studies demonstrate an “association” between colonization and infection, there is increasing evidence that colonization increases the risk of infection in the carrier of the microbe, he said.

Burden Reduction

“We want you to think about decolonization in a slightly broader context, to include pathogen burden reduction, or reduction in microbial load of the colonization pathogen,” Jernigan told the FDA workshop attendees. “Even transient reduction in microbial load might be beneficial, especially if it is strategically designed to correspond to a relatively short period of increased infection risk, such as during a period of high-risk healthcare.”

These high-risk periods include surgery and placement of in-dwelling catheters, which can seed an infection if not monitored and removed promptly when no longer medically indicated. Antibiotics can disrupt the normal flora of the gut, allowing drug-resistant pathogens to establish reservoirs and potentially spread to sterile body sites.

“Importantly, there’s also evidence that the risk of infection varies with the microbial load of colonization,” Jernigan said. “In other words, transmission between individuals, either directly or indirectly, increases the number of people who become colonized and infected with resistant organisms.”

Eventually, evolutionary fit clonal groups emerge, such as methicillin-resistant Staphylococcus aureus USA100 and USA300, Group ST258 carbapenemases-producing Klebsiella pneumoniae, and ribotype 027 Clostridioides difficile.

“Transmission of highly fit strains may be a particularly important driver of antimicrobial resistance in healthcare settings, where there exist a confluence of factors that favor transmission of resistant organisms, such as high-risk patient populations, intense antibiotic use, and dense contact networks involving close interactions among patients, healthcare workers, and the environment,” Jernigan said.

In this light, it is clear that the development of novel decolonizing agents could prevent more adverse effects of antibiotic resistance than new drugs to treat infections, he said.

There have been concerns about whether there is a sufficient market to support new antibiotic development. In a message to both the FDA and drug manufacturers, Craig said there could be a huge patient population for products that target colonization.

“If we start looking at [the] number of people who are colonized, it’s potentially a much greater engagement with the private sector to bring something to market,” he said.

The number of people colonized with a resistant pathogen may be as much as 10 times higher than the number infected, he added.

REFERENCES

1. Centers for Disease Control and Prevention. COVID-19: U.S. Impact on Antimicrobial Resistance, Special Report 2022. U.S. Department of Health and Human Services, CDC; 2022. https://www.cdc.gov/drugresistance/pdf/covid19-impact-report-508.pdf
2. Weiner-Lastinger LM, Pattabiraman V, Konnor RY, et al. The impact of coronavirus disease 2019 (COVID-19) on healthcare-associated infections in 2020: A summary of data reported to the National Healthcare Safety Network. Infect Control Hosp Epidemiol 2022;43:12-25. (Erratum in Infect Control Hosp Epidemiol 2022;43:137.)
3. United States Environmental Protection Agency. List P: Antimicrobial products registered with EPA for claims against Candida auris. https://www.epa.gov/pesticide-registration/list-p-antimicrobial-products-registered-epa-claims-against-candida-auris#products