The Cost of Antibiotic Resistance

Drug Topics Journal, Drug Topics November 2021, Volume 165, Issue 11

Continued vigilance is needed in the health care field to only prescribe antibiotics when they are truly needed.

Despite technological advances, new antibiotics, and pharmacists’ involvement, antibiotic resistance is still a major health care challenge in the United States.

The Scope of the Problem

Although data on antibiotic resistance are hard to pin down and underreported, experts estimate the problem has increased in recent years.

“The number of [antibiotic] prescriptions that are going out and the number of prescriptions that are inappropriate in the ambulatory setting are increasing,” said Lucas T. Schulz, PharmD, BCIDP, clinical coordinator for infectious diseases at University of Wisconsin Health and clinical associate professor at University of Wisconsin-Madison School of Pharmacy.

“Antibiotic resistance is the next COVID-19 if we ignore it or [if we] choose not to focus on it. We know it’s here. If we don’t make more people and more legislators aware—and we don’t do something about it now—there are going to be bad outcomes,” Schulz added.

The prevalence of some resistant organisms, like extended-spectrum β-lactamases (ESBLs), is increasing, according to Athena Hobbs, PharmD, BCIDP, infectious diseases clinical pharmacy coordinator at Methodist University Hospital in Memphis, Tennessee.

The spike in ESBLs is “a huge concern because this means that patients may not receive the correct antibiotic initially before we know what organism is causing the infection,” Hobbs explained. “This will also force clinicians to use more broad-spectrum antibiotics up front, which will lead to worse antimicrobial resistance down the road.

“We need to continue to be vigilant in the health care field as well as in the community to only prescribe or take antibiotics when they are needed.”

In a large study published in JAMA Network Open, investigators found that antimicrobial use deviated from recommended practices for 55.9% of patients who received antimicrobials for community-acquired pneumonia or urinary tract infection present at admission or who received fluoroquinolone or intravenous vancomycin treatment.1

In addition, infections caused by bacteria resistant to multiple antibiotics led to $1.9 billion in health care costs and more than 10,000 deaths among older adults across the US in 2017, according to a recent study published in Clinical Infectious Diseases.2

These findings are a “stark reminder of the incredible and costly burden of antibiotic-resistant infections on our patients and our nation’s health care system,” said Daniel McQuillen, MD, president of the Infectious Diseases Society of America (IDSA), in a news release.3 “We must respond to this growing public health threat with strong federal investments in key areas to ensure that safe and effective antibiotics, upon which modern medicine relies, are available when patients need them.”

IDSA is calling for government investment in antibiotic stewardship, antibiotic innovation, surveillance, research, diagnostics, infection prevention, the infectious diseases workforce, and global coordination. In particular, the bipartisan Pioneering Antimicrobial Subscriptions to End Upsurging Resistance Act,4“which would change the way the federal government pays for novel antibiotics to revitalize the pipeline and promote stewardship,” is a critical piece of the solution, the organization said.3

The CDC’s 2019 antibiotic resistance threats report5 found that nearly 3 million people in the United States each year experience an infection due to an antimicrobial-resistant pathogen, said Monique Bidell, PharmD, BCPS, a former clinical pharmacy specialist at Massachusetts General Hospital in Boston.

“However, this number is likely even higher due to underreporting,” she said.

At the same time, antibiotic prescribing practices have improved during the past two years due to COVID-19. Between April 2020 and February 2021, there was a marked decrease in respiratory virus detection, which resulted in a 79% decline in ambulatory antibiotic prescribing rates for respiratory infections.6

“This is probably because physicians and patients knew that their respiratory symptoms were due to COVID-19, and we could do rapid diagnostics [to determine if patients were positive for it],” Schulz said, adding that patients also understand that COVID-19 is a virus and that antibiotics are not typically prescribed to treat a virus.

Advances and Best Practices

Pharmacists have been making great headway in the antibiotic resistance conundrum for several years by serving as valuable leaders and members of antibiotic stewardship teams and through educating patients and other health care providers on appropriate prescribing.

“We have certainly increased awareness of antimicrobial resistance and [it being] a driver of negative patient outcomes,” said Ronak G. Gandhi, PharmD, BCPS, senior attending clinical pharmacist of infectious diseases at Massachusetts General Hospital in Boston.

The advances made by the infectious disease community during the past 10 to 15 years in terms of diagnostics, software, and other resistance mechanisms are invaluable, Gandhi said.

Schulz noted: “Pharmacists should be encouraging the use of rapid diagnostic testing, which [helps] us identify the right patient [for antibiotics], and you will see improved patient outcomes.”

Several newer tests detect genes that code for specific antibiotic-resistant determinants, Bidell explained. “While great in theory, there are challenges with many of these platforms in that most methodologies do not provide actual antibiotic susceptibility data at the time of identification, so there is not always an opportunity to guide therapeutic decisions at that time,” she said.

One best practice for implementation is to have dedicated personnel, such as antibiotic stewardship team members, respond to the results “so that if therapeutic changes need to be made, they can be done so in a timely manner,” Bidell advised. “Stewardship programs need to decide at the program level if they have both the patient volume and personnel to support effective implementation of these technologies.”

Rapid tests identifying whether the infection is viral or bacterial are increasing in clinics, emergency departments, and other point-of-care sites, Schulz said. “We know that viral infections are not going to respond to antibiotics, and we don’t need to use antibiotics. That is a very simple way to slow or stop [antibiotic resistance].”

There are a few providers of the rapid viral versus bacterial tests, but more research is needed to confirm the tests are “correct enough times,” Schulz noted.

In addition to diagnostics, the integration of stewardship platforms into the electronic medical records that allow easier reporting to the CDC’s National Healthcare Safety Network Antimicrobial Use and Resistance Module7 can help track antibiotic utilization and compare a health system to similar institutions in terms of antibiotic use, said Gandhi. "This can potentially lead to collaborations between institutions to share best practices to reduce antibiotic use.”

It is “critically important” that pharmacists are participating in those platforms, Schulz added.

Pharmacists’ Crucial Role in Antibiotic Stewardship Programs

One of the biggest things that pharmacists can do to improve antibiotic resistance is to participate in and promote antimicrobial stewardship within health care teams, Bidell noted.

Schulz agreed, adding that to combat antibiotic resistance, everyone must first think of themselves as a steward. “A steward is just being a good pharmacist: right patient, right dose, right time, and right duration,” he said. “It is something we should be doing for every patient.”

Bidell echoed that pharmacists can play a key role in facilitating use of the “right” antibiotic (ie, one that is active against the pathogen without introducing unnecessary collateral damage) at the right dose at the right time for the right duration. “And in some cases, the best stewardship approach is antibiotic cessation or taking a watch-and-wait approach...to minimize unnecessary antibiotic exposure that can place patients at risk for adverse effects and/or Clostridioides difficile infection,” she said.

An untapped area that is still contributing significantly to antimicrobial resistance is outpatient stewardship, Gandhi noted. “Antibiotics can be prescribed by so many health care professionals. Controlling what we do [in inpatient settings] is important, but [it’s] a small slice of the cake compared to managing outpatient antibiotic use,” he said. “I believe advancements in outpatient stewardship can dramatically improve antimicrobial resistance locally and globally.”

Although governmental pushes have promoted outpatient stewardship, the execution is still in its infancy, Gandhi added.

Another avenue to combat antibiotic resistance, he said, would be granting more pharmacists provider status and allowing pharmacists trained in infectious diseases to be more involved at the community level as midlevel practitioners.

Pharmacists can also encourage the use of newer antibiotics such as meropenem/vaborbactam (Vabomere) and cefiderocol (Fetroja) that target highly resistant pathogens, Schulz advised.

However, due to the higher cost of some newer medications—on average, $1000 per day vs $10 to $15 for older medications—there is a “friction point between pharmacy and providers,” Schulz said. “Too often, pharmacists are viewed as a hurdle to clear.”

The typical hospital billing system and the Centers for Medicare & Medicaid Services reimbursement guidelines are preventing newer drugs from being utilized more often, Schulz added. “We need to look beyond their initial price tag,” he said. “If you identify the handful of patients who need that drug, they are going to have better patient outcomes.”

At this year’s upcoming American Society of Health-System Pharmacists’ Midyear Clinical Meeting—being held virtually from December 5 through December 9—Bidell, Gandhi, and Thomas Lodise, PharmD, PhD, professor of infectious disease at Albany College of Pharmacy and Health Sciences in New York, will discuss roles for newer broad-spectrum therapies against resistant gram-negative pathogens.

They will also outline more nuanced clinical scenarios in which clinicians can appropriately take a “novel agent-sparing” approach, Bidell said. “The reason why the latter stance is important is because not all institutions have the same resources with respect to access to these broad-spectrum agents—for example, due to formulary restrictions—or with respect to susceptibility testing capabilities.

"We also know that use of any antibiotic brings the risk of subsequent development of resistance,” she added. “So if there is an opportunity to use a more conventional agent in place of a broader and newer agent, there are certain specific clinical scenarios where that may be a perfectly reasonable approach.”

References

  1. Magill SS, O’Leary E, Ray SM, et al; Emerging Infections Program Hospital Prevalence Survey Team. Assessment of the appropriateness of antimicrobial use in US hospitals. JAMA Netw Open. 2021;4(3):e212007. doi:10.1001/jamanetworkopen.2021.2007
  2. Nelson RE, Hyun D, Jezek A, Samore MH. Mortality, length of stay, and healthcare costs associated with multidrug-resistant bacterial infections among elderly hospitalized patients in the United States. Clin Infect Dis. Published online October 7, 2021. doi:10.1093/cid/ciab696
  3. Drug-resistant infections led to $1.9 billion in health care costs, more than 10,000 deaths among older adults in one year. News release. Infectious Diseases Society of America. October 7, 2021. Accessed October 25, 2021. https://www.idsociety.org/news--publications-new/articles/2021/drug-resistant-infections-led-to-$1.9-billion-in-health-care-costs-more-than-10000-deaths-among-older-adults-in-one-year/ 
  4. The PASTEUR Act, S.4760, 116th Cong (2019-2020). Accessed October 25, 2021. https://www.congress.gov/bill/116th-congress/senate-bill/4760
  5. CDC. Antibiotic resistance threats in the United States 2019. Accessed October 25, 2021. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf
  6. Lepak AJ, Taylor LN, Stone CA, et al. Association of changes in seasonal respiratory virus activity and ambulatory antibiotic prescriptions with the COVID-19 pandemic. JAMA Intern Med. 2021;181(10):1399-1402. doi:10.1001/jamainternmed.2021.2621
  7. National Healthcare Safety Network. Antimicrobial use and resistance (AUR) module. Accessed October 2015, 2021. https://www.cdc.gov/nhsn/pdfs/pscmanual/11pscaurcurrent.pdf