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It’s a basic law of medicine — the more you use antibiotics, the less effective they become.
Bacterial resistance due to antibiotic overuse is inevitable, because germs will always look for ways to survive new drugs. It’s a phenomenon that Sir Alexander Fleming, the scientist who discovered penicillin, warned of as early as the 1940s, and today it’s considered a worldwide public health threat.
Each year, the U.S. Centers for Disease Control and Prevention (CDC) and organizations around the world hold awareness-raising observances to help offset that threat, including U.S. Antibiotic Awareness Week in November. CDC offers a wide range of educational resources on using antibiotics, from guidelines and white papers for providers, to clear, easy-to-understand information for patients, including this quiz and this fun, informative video.
Most large hospitals and health systems — including Allegheny Health Network (AHN) — now have Antibiotic or Antimicrobial Stewardship Programs in place to guide decision-making and prescription protocols related to antibiotic use and common infectious diseases. At Highmark Health, antimicrobial stewardship is part of the health plan business as well. Here are just a couple examples of how teams across the enterprise are innovating to ensure good antimicrobial stewardship.
AHN’s Antimicrobial Stewardship Program is led by Thomas Walsh, MD. He and his team work to ensure that Allegheny General Hospital (AGH), West Penn Hospital, and other AHN facilities follow evidence-based decision-making algorithms and local management guidelines when it comes to antibiotic deployment, in order to maximize clinical benefits while minimizing unintended consequences associated with antibiotic use.
But sometimes, guidelines are only as good as your diagnosis.
When a patient is hospitalized with an unidentified bloodstream infection, for example, clinicians have little choice but to prescribe broad-spectrum antibiotics, giving the patient a formidable weapon against the bacteria most likely responsible for sepsis.
Broad-spectrum antibiotics can kill all sorts of bacteria — but wiping out all of the susceptible bacteria can also lead to the flourishing of resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA) and Clostridioides difficile (C. diff).
Narrow-spectrum antibiotics, meanwhile, are effective against sensitive bacteria, and they cause less downstream harm.
In other words, the sooner a patient is treated with a targeted, narrow-spectrum antibiotic, the better.
That’s where a new breed of rapid-diagnostic blood tests comes in. AHN is among the first health systems in the country to utilize a new diagnostic test called the Accelerate Pheno system, which rapidly identifies the bacteria in the bloodstream responsible for a patient’s septic reaction, and indicates the best course of treatment for the infection.
“A process that once took two to five days — from the detection of bacteria in the blood culture, to the identification of the bacteria that grows in the culture, to a determination of the best antibiotic to use based on susceptibility testing — can now be completed in under eight hours,” explains Dr. Walsh.
Until recently, the process of identifying a germ was pretty old-fashioned — you put a few drops of blood in a dish, wait a few days for the germs to grow, then spend a few more days figuring out exactly what’s in the dish. The technology hadn’t changed much over the last several decades.
But the Accelerate Pheno instrument, and others like it, rapidly determines what bacteria are in the bloodstream and provides critical information that allows clinicians to determine an optimal, antibiotic therapy within a few hours.
Time is of the essence when a bloodstream infection is suspected. Sepsis — a systemic, life-threatening reaction to a bloodstream infection — is the leading cause of death in U.S. hospitals. One study found that one-year mortality from sepsis increases by as much as 10% for every hour that optimal treatment is delayed.
“Many of those deaths could be prevented if patients received the optimal treatment more quickly,” Dr. Walsh says.
AGH has been using the Accelerate Pheno system since May 2019. In that time, among non-ICU patients at AGH with gram-negative bacteria in the bloodstream, length of stay is reduced by two days per patient, and the patient’s course of antibiotics is reduced from 14 days to 10 days. AGH is also seeing a trend toward lower readmissions.
That’s huge for the patient. And it’s also a big deal when it comes to antibiotic stewardship: Moving patients off of broad-spectrum antibiotics as soon as possible mitigates a lot of the collateral damage associated with these powerful drugs, including the escalation of further antibiotic resistance.
“The faster we can get patients off of the broad-spectrum antibiotics and onto a more targeted, optimal therapy, the better it is for the patient, and the better it is for public health,” Dr. Walsh says. “No matter the setting, physicians need to be judicious with antibiotics. We should be prescribing them only when needed.”
Derek Bremmer, PharmD, a clinical pharmacy specialist at Allegheny Health Network and program director for its Infectious Diseases Pharmacy Specialty Residency.
Pharmacists in a health system play a critical role in antibiotic stewardship. At AHN, one way pharmacists carry out stewardship’s “three Ds” — right drug, right dose, right duration — is to challenge whether patients are allergic to penicillin.
Derek Bremmer, PharmD, developed an algorithm that guides when challenges are made and how to proceed. He explains that only about 10% of people who believe they are allergic to penicillin are truly allergic.
That’s a problem, because penicillin and other beta-lactam class antibiotics are the safest, most effective first line of treatment for most infections. When a patient lists an allergy, providers may use alternatives that have a higher risk of adverse events, increased resistance, and complications like C. diff infection. People getting surgery have higher rates of surgical infections, and certain disease states have higher mortality rates, when alternatives are used. A mislabeled allergy can also delay administering an antibiotic.
Bremmer says mislabeled allergies are most often due to mistaking a sensitivity, like a mild rash or upset stomach, with a true anaphylactic allergic reaction.
“Throughout AHN, pharmacists at each site review inpatients,” he says. “If we see that someone has an infection or is scheduled for surgery that would benefit from a beta-lactam, but they’re listed as allergic, we want to proactively determine whether it’s a true allergy.”
The first step is often talking directly to the patient, using a template of eight questions. Bremmer says the top three questions are especially important: What happened when you took penicillin? Did the reaction happen immediately after taking it? How long ago did you have a reaction?
“The answer to ‘what happened?’ helps us identify whether someone had an intolerance versus an anaphylactic reaction,” he explains. “We ask whether a reaction happened immediately — typically within one hour of taking the drug — because a reaction outside that period is unlikely to be related to an anaphylactic reaction. We ask when it happened, because even with an anaphylactic-type reaction, about 80 percent of people lose that allergy after 10 years.”
Based on this information, Bremmer says patients are categorized as no risk, low risk, or high risk. No risk means it is certain that the patient did not have an allergic reaction previously, and then penicillin or another beta-lactam antibiotic would be prescribed as normal.
For a low-risk patient who reports having had a delayed reaction, like a rash, the protocol involves what is called an oral challenge.
“Typically, we administer 10% of a normal dose, a very low oral dosage, and have close monitoring for the first hour. If there are no rashes, vitals are stable, and they don’t have any itching, then we do the remaining 90% of that challenge dose and continue monitoring closely,” Bremmer explains. “If there hasn’t been a reaction within the first two hours, it is very unlikely that you’ll have any anaphylactic-type reaction, so at that point we feel confident to prescribe normally.”
He adds that about 5% of patients develop a rash or itchiness during a challenge, but that can be addressed with very little risk and then alternative medication would be discussed.
Only about 10% of patients listed as allergic to penicillin have a true allergy. Instead of going straight to an alternate treatment that may be less effective and have more risks, an algorithm used at AHN helps clinicians and pharmacists assess whether penicillin can be used safely.
A high-risk patient — one confirmed to have had a previous anaphylactic reaction — would be referred to an allergist for testing.
Bremmer says that about 90% of patients are no risk or low risk — which means the challenge algorithm can help many patients get penicillin sooner, and without the delays and costs of unnecessary testing.
Given that such a high percentage of people mistakenly believe they are allergic to penicillin, should more people try to confirm an allergy before they are in a hospital?
“I don’t know that it’s a must-do-it-now thing, but you could bring it up at your next PCP visit, and then they could determine whether to refer you to an allergist,” Bremmer says. “However, people with an immunocompromising disorder, transplant recipients, a cancer patient — anyone likely to have infections — should confirm or correct the allergy as soon as possible, because a beta-lactam is likely to be beneficial if they become infected.”
Dr. Chingping Wan, medical director for the Highmark Inc. value-based reimbursement program.
When it comes to antibiotic stewardship, Highmark’s health plan business also plays an active role.
“This is first of all about the health plan members’ health,” says Dr. Chingping Wan, medical director for Highmark’s value-based reimbursement program. “Overutilization of antibiotics also means more cost for members and our employer customers. And this is also about the value we provide to the community, since this issue directly impacts public health.”
Dr. Wan points out that a health plan has unique leverage in addressing antibiotics with both members and providers.
“As a health plan, we can do education and member consultations so that people understand antibiotics, helping to reduce situations where members pressure providers to give them medication,” she says.
On the provider side, Dr. Wan explains that Highmark is having success influencing behavior by taking a highly collaborative approach based around sharing comprehensive claims data to give providers a more accurate picture of their practice.
For example, some physicians assume overutilization is not an issue at their practice, and comes mostly from urgent care centers, telemedicine and other sources. Breaking down antibiotic prescription claims by different prescribers and locations, Highmark was able to show physicians at AHN that only 9% of antibiotics, and less than 30% of antibiotics for respiratory infections, came from urgent care.
“By addressing their concern and showing them data, they see how much volume is from their own physicians,” she says. “That creates the ‘aha!’ moment to think about opportunities for improvement.”
Dr. Wan says the next step might be to meet with individual practices to help determine more specific problems. She said that when the health plan reviewed ICD-10 diagnosis codes for one site, for example, they found “hypertension” coded as the primary diagnosis for antibiotics.
“That didn’t make sense. So when we present such an anomaly, the provider can say, ok, let’s pull those charts and see what’s going on,” she says. “It might be coding mistakes, but if it’s something else, let’s figure out why antibiotics were prescribed.”
Dr. Wan says she often hears that what distinguishes Highmark’s approach is that they provide more resources to support providers in improving, including in-person consultation from nurses and pharmacists as well as a robust analytics team.
“I’ve had providers tell me that other health plans started using Choosing Wisely guidelines — as Right Care does — but that they went directly to medical policy changes, which can be disruptive for providers,” she says. “They’re happy that Highmark takes a more collaborative approach and helps them understand problems, rather than just saying we no longer pay for this.”
Similarly, she says that you can see the collaborative mindset at work in how antibiotic measures have evolved in recent years.
“Our True Performance value-based reimbursement program uses HEDIS guidelines, which include a couple antibiotic measures,” she says. “But we felt that had a limited scope, so when we started Right Care in 2018, we expanded what we measured.” The changes helped reduce antibiotic use by 30% in the first six months. However, some providers felt Highmark was going too far in analyzing specific diagnostic codes, including a few where prescribing antibiotics is warranted in some cases.
“So for 2019, instead of putting physicians on hold over specific diagnosis codes, we changed our measures to look at antibiotic use per thousand members, using that to rate someone on a spectrum of network providers,” she explains. “We really see the power of adding quality metrics into the value-based reimbursement program and at the same time data-sharing with physicians and discussing on a case by case basis. Leadership at the AHN Clinically Integrated Network told us this was really eye-opening, and more helpful than limiting certain conditions, because now they can look at the whole picture.”
Dr. Wan adds that better antibiotic stewardship is tied to a larger mindset shift that runs throughout the Highmark Health enterprise.
“In the past we tended to treat many things with one drug or another, but as we do more clinical research, we are learning that sometimes less is more,” she says. “Medicine is not just about giving out medication or tests or therapy, it’s also about holistic counseling and whatever we can do to help someone be healthier and feel better.”
Ryan Grisnik, Pharm D, helped start the clinical case management pharmacist team for the Highmark health plan, then worked with enterprise strategy and innovation, and recently moved into his current position as manager of clinical design and innovation. Through it all, he has voluntarily taken the initiative to promote the CDC’s U.S. Antibiotic Awareness Week for the past three years. In addition to coordinating this article and other efforts, he provided his top five tips for consumers below, based on CDC recommendations:
For more information, visit CDC’s U.S. Antibiotic Awareness Week site.
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