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Faculty Findings on Antibiotic Resistance in Critically Ill Patients Published in Pharmacotherapy

Published on 09 July 2019

Research conducted by two St. Louis College of Pharmacy faculty members has offered evidence that each additional day of antibiotic exposure in critically ill patients can lead to higher rates of antibiotic resistance.

The findings, which were recently published in Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, are the result of years of work by Scott Micek, Pharm.D., FCCP, BCPS, professor of pharmacy practice at the College and director of the College’s Center for Health Outcomes Research and Education, and Besu Teshome, Pharm.D., BCPS, assistant professor of pharmacy practice at the College.

In 2017, Micek and Teshome teamed up with Scott Vouri, Pharm. D., Ph.D., BCGP, clinical assistant professor of pharmaceutical outcomes and policy at the University of Florida, to examine the effects of keeping patients, specifically those dealing with severe sepsis or septic shock, on antibiotics longer than necessary.

Data was collected on a total of 7,118 patients at Barnes-Jewish Hospital in St. Louis from 2010-2015. Any adult with the discharge diagnosis of severe sepsis or septic shock who received at least one dose of the broad-spectrum antibiotics cefepime, meropenem or piperacillin-tazobactam, was followed for 60 days, starting with the day of their first dose. In some cases, this timeframe was impacted based on time of death, a separate resistance event or the official conclusion date of the study.

Depending on the needs of the patients being studied, some received just one day of antibiotics, while others received up to 60 days of antibiotics. The research team used an analysis that factored the differences between those patients. Through that analysis, they were able to evaluate how each additional day of exposure impacted the development of new resistance.

The study found that the prolonged use of antibiotics could make bacteria in the body become immune to the medications and begin to fight them off, causing antibiotic resistance in patients.

“Bacteria are living, breathing organisms,” Teshome explained. “Almost like a pitcher in baseball, if you have a really good pitch that you continually use, batters start to wise up and get hits off you. The more we use antibiotics, the more these bacteria start to get wiser and are able to fight them off.”

Health care practitioners in most hospital settings prescribe broad-spectrum antibiotics for either 7, 10, 14 or 21 days based on certain guidelines and patient needs. In most cases, health care teams maintain the originally prescribed antibiotic regimen, even if patients are feeling better in a shorter amount of time. According to Teshome, this can be dangerous because resistance can begin building in the days after the patient is showing improvement.

“Since there is usually no adverse effect with these antibiotics and patients are able to tolerate them well, health care teams often feel comfortable with keeping a patient on an antibiotic for an extra day or two,” said Teshome. “Our study shows that there are resistance risks associated with extending antibiotic treatment for just one additional day. With antibiotic resistance having the potential to lead to increased risk of mortality and immobility, this is important information that health care providers need to be aware of.”

Micek explains that once a patient becomes resistant to certain antibiotics, the course of treatment becomes more difficult, especially amongst sepsis patients.

“If patients become infected with a resistant bacteria, there is a 50% or less chance that we will find an antibiotic that’s both available and will work for them,” Micek said. “If the antibiotics we prescribe don’t work, the patient faces more time in the hospital as we work to find a replacement. This wait time could result in death in a lot of these patients.”

Teshome relates the possibility of widespread antibiotic resistance to the mass-resistance to penicillin that developed just a few years after its introduction in the mid-20th century. As penicillin was being used extensively to fight-off diseases and bacteria, many infections began to fight it off. Today, penicillin can only be used to treat a handful of infections.

“Penicillin was like the magic bullet in the 1940s, but it now only treats a select number of infections, ” Teshome said. “Within our lifetime we might actually see the rise and fall of antibiotics if we’re not careful. Hopefully, we can start practicing better stewardship so we can prevent that fall.”

As more and more hospitals work to take patients off of antibiotics more quickly, Micek and Teshome are providing evidence that this is, in fact, the proper course of action to prevent resistance, and one that can potentially save lives. 

“The practice in all hospitals is one of stewardship, so you ideally try to treat patients with the shortest duration possible and the narrowest spectrum as possible,” Micek said. “We use the word ‘de-escalation’ to describe that philosophy of practice we’re currently studying. It’s never been shown, ever, to be linked to prevention of resistance even though that’s why we practice it. We’re trying to show that association and that what we practice actually makes a difference.”

This study marks the first round of Micek and Teshome’s research on antibiotic resistance. With this study focused on duration of use, the second portion of the study will focus on the spectrum of activity.

The full study, published in March 2019, can be found in volume 39, number 3 of Pharmacotherapy. To learn more about research at the College, visit stlcop.edu/research.

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