The COVID-19 pandemic has hindered progress in antibiotic stewardship and hospital infections, and antibiotic resistance in the human population is a growing threat.
A decade-old estimate (PDF) from the Centers for Disease Control and Prevention (CDC) pegs annual healthcare costs related to antimicrobial resistance (AMR) at $20 billion, plus $35 billion in costs to society for lost productivity. Some estimates calculate AMR could cost from $300 billion to more than $1 trillion annually by 2050 worldwide.
The Pew Charitable Trusts conducted a study earlier this year on antibiotic use in hospitalized COVID-19 patients early in the pandemic and found that most admissions led to one or more antibiotics being prescribed, often without confirmation of a bacterial infection. Potential contributing factors include challenges in distinguishing between COVID-19 pneumonia and bacterial pneumonia and limited understanding of how to manage these types of patients early in the pandemic.
To spur the development of new antibiotics, which are necessary to fighting new drug-resistant viral variants, Congress has introduced the PASTEUR Act. But, experts say, solving the problem of antibiotic resistance requires more than creating new drugs. Ahead of World Antimicrobial Awareness Week, Fierce Healthcare spoke to experts about what it will take to turn this worrying trend around and how providers can avoid further contributing to the problem.
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Working with what we've got
Surgical site infections (SSIs) are the most common (and costly) type of hospital infection. About 90% of surgeries are at risk of an infection, according to Anthony J. Senagore, M.D., a colorectal surgeon.
That’s why usually, 24 hours before surgery, patients receive antibiotics—commonly via an IV or as an oral dose, he told Fierce Healthcare. But there are several inevitable risk factors associated with that approach. Between steps like ordering and preparing the medication, there is room for clinical errors. It’s difficult to be certain that the right antibiotic is being given, Senagore said.
Antibiotics that go throughout the whole body leave the patient at risk for adverse effects, like Clostridium difficile infections, along with the potential for harm to their microbiome, which is responsible for maintaining vital functions and overall health. And, since the drug is not anchored to the surgical site itself, it will diminish over time, still leaving the wound exposed to potential bacteria.
With all these potential complications, it’s prudent to reconsider the way existing antibiotics are administered, explained Senagore, who is also the senior medical director of PolyPid, a biopharmaceutical company. PolyPid, with products currently undergoing clinical trials, uses a polymer-lipid combination to anchor a drug to one location on the body. Its product candidate for SSIs releases doxycycline over a period of four weeks, in theory minimizing the patient’s systemic exposure to the drug. “You’re able to carpet-bomb one area rather than drop just one bomb,” Senagore said, thereby helping ensure the bacteria are successfully conquered. Prolonged or inappropriate exposure of bacteria to medication runs the risk of creating multidrug-resistant bacteria.
In Senagore’s view, new antibiotics should be reserved for fighting bugs that are already known to be resistant to existing treatments. If new medications are used on bacteria not already resistant, however, that leads to further resistance.
PolyPid hopes an initial study will be completed in the first quarter of the new year.
Populations most at risk
Antibiotic-resistant bacteria caused 30,000 deaths in the U.S. in 2017. The Medicare-aged population accounted for more than a third of those figures.
The number of antibiotics in development is insufficient. So believes David Hyun, M.D., director of Pew’s antibiotic resistance project. No new classes of antibiotics have been invented for decades. The elderly—who are more likely to touch the healthcare system and have weaker immune systems—are particularly at risk for infections and “desperately need these new antibiotics,” he told Fierce Healthcare. “But also it’s for all Americans.”
Hyun emphasized the importance of federal government intervention in addressing this issue. Because most healthcare provided to this age group comes from Medicare, the Centers for Medicare & Medicaid Services should focus on improving antibiotic use, he told Fierce Healthcare.
Patients on a ventilator are also at greater risk of developing bacterial infections that are more likely to be antibiotic-resistant, said Kerry LaPlante, an infectious diseases pharmacist at a hospital in Rhode Island. (Infectious disease pharmacists make sure that prescriptions are being given to patients at the right dose and the right time.) COVID patients, who need to be kept on a ventilator longer than normal, are particularly at risk. So clinicians are acutely aware of the threat of bacterial infection.
“We’re always in this very fine dance of when to start antibiotics in a patient with COVID,” LaPlante said. “If they’re necessary, we need to get it right: which antibiotic to start, how to dose it and how long. Because if we get it wrong, we can have worse outcomes.”
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There have been growing concerns about how the ongoing labor shortages will affect patient care, LaPlante noted. Maintaining patient safety, infection control, fielding questions from worried families—“it all seems to kind of fall to our nurses,” she said. Pharmacists like LaPlante are constantly thinking about ways to collaborate with clinicians at the hospital to uphold best practices and alleviate their burdens.
But one of the most important approaches to minimizing the risk of emerging resistance, experts agree, is antibiotic stewardship. With certain key principles, this approach is used as a way to ensure judicious antibiotic prescribing practices. Various stewardship programs exist across hospitals, for instance for opioid use. But, during the pandemic, infectious disease pharmacists at hospitals around the country were pulled away from their usual roles in these programs to focus on COVID patients and therapies, Hyun said. Several recent studies have confirmed as much. One infectious diseases pharmacist told Pew that some programs were shuttered entirely.
LaPlante believes in the power of innovation and the promise of localized therapy, like PolyPid's drug candidate.
“These bacteria are always a step ahead of us. We really need to be judicious with our antibiotic use,” LaPlante said. “We can’t rest.”
Other components of safety include maintaining a SSI reduction goal and prevention bundle, Senagore said. But even when everything is done right, the risk of complications, infections and multidrug-resistant bacteria still exists. “It just is a gap in the treatment protocol,” he said.