When physicians hear the words “antibiotic stewardship”, they think of inpatient programs to control antibiotic use. However, more than 80% of antibiotics are prescribed in the outpatient setting. The Joint Commission mandates that hospitals have an inpatient antibiotic stewardship program but there is no national requirement in the outpatient setting and consequently, better stewardship of outpatient antibiotic use is essential to control multi-drug resistant bacteria.
Emergence of drug-resistant bacteria
The story of drug-resistant bacteria is the story of evolutionary biology and that story dates back more than 2 centuries ago.
It was the fall of 1827 and Charles Darwin was bored. He was in his second year of medical school at the University of Edinburgh but was neglecting his medical studies as he was more interested in studying the biology of oysters than of humans. So, his father sent him to Cambridge to study to become a county parson instead. There, he was more interested in studying entomology than religion. However, he did manage to graduate in 1831. But with no employment opportunities that interested him, he decided to sign on as a naturalist on a 5-year expedition to chart the coast of South America on the HMS Beagle. His observations of during the voyage served as the foundation for his theory of natural selection that later became the central tenet of evolutionary biology.
Perhaps nowhere has natural selection been more easily observed than in the emergence of antibiotic resistant bacteria over the past 80 years. In 1928, Alexander Fleming discovered penicillin, purely by accident. In 1941, police constable Albert Alexander became the first person treated with penicillin when he scratched his face with a rose thorn and developed a flesh-consuming infection caused by Staph aureus. After 5 days of treatment with the new drug, his infection was under control but he then relapsed when his doctors exhausted their supply of penicillin. When penicillin was initially rolled out, it killed essentially all Staph aureus bacteria. But by 1942, penicillin-resistant Staph were identified and by 1946, 12.5% of all Staph aureus isolates were resistant to penicillin. One year later, the incidence of penicillin resistant staph had tripled even further.
To fight the rapidly emerging resistance of Staph aureus to penicillin, a new semi-synthetic penicillin derivative was created in 1959 called methicillin. It was first marketed in September 1960 but only one month later, a public health lab in London identified isolates of Staph that were resistant to the new antibiotic and these were called methicillin resistant Staph aureus, or MRSA. Thirty years ago, 2% of all Staph infections were due to MRSA. Today, in the United States, most staph infections are caused by MRSA and one-third of all healthy Americans are colonized with MRSA in their noses. To treat MRSA infections, the medical community turned to vancomycin. But in 2002, the first case of vancomycin-resistant Staph aureus was identified in a diabetic patient in Michigan. Today, vancomycin-resistant Staph aureus has replaced MRSA as the bacterial bogyman in our nation’s hospitals.
Currently in the United States, there are 2.8 million infections caused by drug-resistant infections and 35,000 deaths due to antibiotic resistance every year. There are additionally 12,800 deaths each year due to Clostridium difficile that arises as a complication of antibiotic use. Antibiotic overuse and misuse is fertilizer for antimicrobial resistance. To slow the emergence of drug-resistant pathogens, it is necessary to more judiciously prescribe antibiotics, especially in the outpatient setting.
The problem of outpatient antibiotic use
In the U.S., three are 211 million outpatient antibiotic prescriptions written every year. The CDC estimates that 72% of these are necessary but 28% are unnecessary. Even when antibiotic prescriptions are necessary, we have opportunities to improve drug selection, improve drug dosing, and shorten the duration of administration. Taking all of this into consideration, about half of all outpatient antibiotics are either unnecessary or prescribed incorrectly.
All of us who practice outpatient medicine have been guilty of antibiotic misuse at one time or another. A patient comes to the office with a viral upper respiratory infection and the doctor prescribes an antibiotic that was never needed in the first place. Maybe the doctor was not aware of clinical practice guidelines for managing upper respiratory infections. Maybe the doctor wanted to make the patient happy by prescribing an antibiotic. Maybe the doctor was afraid of complications of the URI. Maybe the doctor figured he or she could bill a higher level of service for the office visit by prescribing an antibiotic. Maybe the doctor thought that it would be faster to prescribe an antibiotic than to explain why an antibiotic was not necessary. Regardless of the reason, the next time that the patient has a cold, that patient will believe that an antibiotic is necessary and expect the physician to prescribe one. This results in a vicious cycle of antibiotic misuse.
The 4 components of outpatient antibiotic stewardship
The Centers for Disease Control has an excellent on-line resource for outpatient antibiotic stewardship. This resource identifies four key components that can be incorporated into any outpatient practice: commitment, action, tracking, and education.
Not only must the physician be committed to appropriate antibiotic use but the entire office staff must be committed. This implies that a consistent message will be given to patients, from the nurses, from the schedulers, from the medical assistants, and from the physicians. For example, when a patient calls in with a sore throat, the nurses can set the stage for antibiotic stewardship by saying “The doctor needs to evaluate you in person to determine if an antibiotic is necessary” rather than simply calling in an antibiotic prescription. The schedulers can help by telling the patient that the office has the ability to do on-site rapid strep screens during the patient’s office visit. The medical assistants can reinforce the message by telling the patient that a negative rapid strep test means that the sore throat is not caused by a bacteria.
Ideally, each medical practice should have a leader for the practice’s antibiotic stewardship program. This could be a pharmacist, nurse or medical assistant. This individual would be responsible for ensuring that all of the office staff know their roles in antibiotic stewardship and that the office’s commitment to antibiotic stewardship is communicated to patients. A simple way of doing this is with posters in the waiting room or in the examination rooms stating the practice’s commitment. The CDC has a down-loadable poster that can be used by any medical office. A 2014 study found that inappropriate antibiotic prescriptions were reduced by 19.7% simply by hanging commitment posters in exam rooms.
Incorporation of evidence-based guidelines for management of common outpatient infections can help ensure that the right antibiotic is prescribed for the right duration of time for any given bacterial infection. Guidelines can also help ensure that antibacterial antibiotics are not prescribed for viral infections. One of the challenges with use of evidence-based guidelines is that many national organizations publish their own guidelines for any given infection and these guidelines can differ depending on the decisions of different guideline writing committees and how long in the past the guidelines were written. Large medical centers can develop their own practice guidelines based on distillation of available literature. In smaller outpatient practices, it is best for all of the providers to agree on the use of one guideline or another – it can be confusing to staff and patients if different providers in the practice utilize different clinical guidelines. When possible, the power of the electronic medical record should be harnessed to prompt clinicians regarding test ordering or antibiotic prescriptions for any given infection based on the ICD-10 diagnoses.
A useful action plan is the use of the “over-the-counter prescription pad” to use for common viral infections – essentially a printed checklist of non-antibiotic recommendations by the provider for such items as acetaminophen, NSAIDs, decongestant nose sprays, guaifenesin, dextromethorphan, etc. Often, a printed paper to given to the patient that is customized to include the patient’s name, date, and diagnosis can be a powerful way to reinforce that antibiotics are not necessary and that the physician is invested in treating the patient (just not with an antibiotic).
For hospital-employed physicians, most compensation plans incorporate some kind of quality metric into each physician’s annual bonus. In our medical center, over the years these have included metrics such as percent of patients getting mammograms or colonoscopies, percent of patients getting influenza vaccinations, and patient satisfaction scores. Antibiotic stewardship is in many ways an ideal quality metric for outpatient and ER practices. This is because appropriate antibiotic prescription is a physician behavior whereas when a patient refuses a flu shot, is a no-show for their scheduled colonoscopy, or writes a bad patient satisfaction survey, it is a patient behavior. As a result, using these latter types of metrics for physician bonuses tends to financially reward physicians who have a “desirable” patient panel as opposed to those physicians who care for a lot of uninsured, lower income, or lower education level patients. By using a physician behavior in the bonus equation, the practice can avoid penalizing physicians for patient behaviors that are beyond the physicians’ control.
The electronic medical record can be utilized to track and report antibiotic stewardship quality metrics such as use of order sets derived from the organization’s clinical practice guidelines, use of rapid strep testing in patients given antibiotics for pharyngitis, and appropriate duration of antibiotics for uncomplicated urinary tract infections.
This requires both education of physicians and education of patients. Physician education can take the form of grand rounds and other CME events about antibiotic stewardship. But on a smaller scale, can include distribution of the organization’s clinical practice guidelines for common infections. Successful distribution can be a challenge, however – many hospitals that maintain a “clinical practice guideline” website on the hospital’s intranet find that physicians rarely access the website. Successful adoption of guidelines usually is most effectively done on a local basis, such as at medical staff meetings, at department meetings, or by incorporation of the guideline into the electronic medical record.
Patients need to be educated about the difference between viral and bacterial infections and why viral infections do not require an antibacterial antibiotic. They also need to be educated about the risks of antibiotics, including costs, side effects, development of drug-resistant bacteria, and C. difficile. Patient education materials can again include posters for the examination rooms but can also include text pasted into the patient’s after visit summary. Whenever possible, after visit summaries should be printed and handed to the patient at the end of their office visit rather than simply loaded onto the patient portal in the electronic medical record – few patient actually open up their patient portal after they leave the office but a piece of paper will tend to stick around until the patient actually reads it.
The Centers for Disease control has several excellent patient education handouts that can be printed as posters for the office’s exam rooms or as paper handouts to be given to patients. These are available in both English and Spanish language versions. These can be downloaded from the CDC’s website or you can click on the images below for the English language handouts.
Penicillin allergy deserves a special mention. Fully 10% of patients report having an allergy to penicillin but only 1% of the population actually has penicillin allergy when tested for IgE-mediated reactions. In other words, 9 out of 10 patients who think they have a penicillin allergy do not actually have an allergy. One of the reasons for this is that 80% of patients who truly have a penicillin allergy lose their IgE responsiveness after 10 years. But presumption of penicillin allergy drives the use of more broad-spectrum antibiotics and the development of drug-resistant bacteria. Patients reporting penicillin allergy should be asked about the specific symptoms they had when taking penicillin in the past. When uncertainty exists, patients should undergo penicillin skin testing. In the past, this required consulting an allergist but now there are easy-to-perform penicillin allergy skin tests that can be done in the primary care office. Importantly, if the test is negative, then not only does the patient need to be informed that they are not allergic, but penicillin allergy should be removed from their electronic medical record.
The special case of dentistry
Dentists account for 10% of all outpatient antibiotic prescriptions. But dental practices generally fall outside of the purview of our nation’s hospitals. As a consequence, dental practices are largely on their own when it comes to antibiotic stewardship support. Physicians can help by participating in dental continuing education programs and by sharing effective programs and practices with local dentistry colleagues. One of the important changes over the past 20 years has been a move away from indiscriminate use of prophylactic antibiotics prior to dental procedures in patients with heart murmurs and limiting prophylactic antibiotics to only those cardiac patients that truly benefit from them. There are also CDC guidelines for when to prescribe antibiotics for common oral infections such as pulpitis, periodontitis, and pulp necrosis.
An ounce of prevention
The most effective way to reduce antibiotic misuse and development of drug-resistant pathogens is to never get infected in the first place. Keeping patients up to date with vaccinations is essential. Chief among these for bacterial infections is pneumococcal pneumonia – the new PCV20 vaccine should be given to all adults over age 65. Similarly, viral infection can mimic bacterial infections or lead to secondary bacterial infections that can result in antibiotic prescriptions. Preventing these common viral infections can thus reduce antibiotic use. All Americans should receive an annual influenza vaccine and COVID update vaccine. All people over age 60 and all pregnant women should be vaccinated against RSV.
We are fortunate to be living in an era when we have more effective vaccines for deadly diseases than ever before. Vaccine recommendations change frequently as new vaccines are developed. The CDC lists the current vaccination recommendations on their website. You can also click on the images below for the 2024 child and adult vaccine schedules.
We don’t have to lose the war…
I have watched patients die of bacterial infections that were untreatable with any known antibiotic. I have taken care of patients with such extensive drug allergies that there was only one or two antibiotics that I could use for any infection they came down with. I have taken care of patients who were admitted to our ICU with overwhelming Clostridium difficile due to taking an unnecessary antibiotic or due to taking a necessary antibiotic for longer than indicated. In all of these cases, antibiotic misuse and drug-resistant bacteria were the root causes.
The good news is that initiatives to reduce antibiotic misuse are effective. Since 2013, the CDC reports that there has been a decrease in hospital-acquired infections caused by vancomycin-resistant enterococcal, multi-drug-resistant Pseudomonas, methicillin-resistant Staph aureus, carbapenem-resistant acinetobacter, and drug-resistant Candida. However, other outpatient-acquired drug-resistant pathogens are now on the rise including erythromycin-resistant group A Strep, drug-resistant Neisseria gonorrhoeae, and ESBL-producing Enterobacteriaceae. Outpatient stewardship efforts in our physician offices, urgent care centers, and emergency departments can and will make a difference. To view an OSU MedNet-21 webcast for more information on outpatient antibiotic stewardship, click on this link.
November 22, 2023