“Our results can directly impact patient care,” says Courtney Lawrence, a PhD student who is also a practising pharmacist. “It feels rewarding to participate in a study that’s aimed at improving the quality of life of dialysis patients.”

At the annual Research Day, held virtually on April 6, Lawrence presented findings from a current UM study funded by the Kidney Foundation of Canada. She is a co-investigator for the project led by pharmacy professor Dr. Sheryl Zelenitsky, her PhD advisor.

Their study focuses on optimizing antibiotic dosing for patients receiving hemodialysis for kidney disease. Although these patients are at high risk for serious infections, there has been very little research on appropriate antibiotic dosing for them.

“Currently, everybody gets the same dose, regardless of important factors like body weight and residual renal function,” Lawrence says.

Lawrence is analyzing the levels of two prescribed antibiotics in pre- and post-dialysis blood samples from study participants. Her presentation focused on the drug cefazolin. She and Zelenitsky found that the current recommended dose may result in below-target levels of the drug in nearly one-third of patients.

“Our goal is to develop new, evidence-based dosing recommendations,” Lawrence says.

The award winner for the best poster presentation was Donica Janzen, a PhD candidate and pharmacist whose supervisor is Dr. Silvia Alessi-Severini. Their study used linked, anonymized health data to compare patients with psychotic disorders who were prescribed different medications.

They found that drugs known as “second generation long-acting injectable antipsychotics” reduced the risk of treatment failure, incarceration and treatment discontinuation in patients by about 30 per cent compared with the other antipsychotic drugs that were studied. However, they found no significant difference in psychiatric hospitalization.

The keynote address at Pharmacy Research Day also highlighted how anonymized health databases can be mined to study “real-world” drug effects in large populations.

“It’s a very cool resource,” said the speaker, Dr. Helen Tremlett, professor of neurology at the University of British Columbia and Canada Research Chair in neuroepidemiology and multiple sclerosis (MS).

Tremlett’s team recently published studies that used anonymized health data to show that current drugs for MS were associated with a 23 per cent lower risk of hospitalization, compared with taking no drug. But the drugs did not show this benefit in patients over the age of 55.

Tremlett has also used data to look back in time and trace health-system use in the “prodromal period” – the years before a patient reports classical MS symptoms and is diagnosed with the disease.

By analyzing data for people with MS and comparing them with matched controls, Tremlett’s team found that those with MS had significantly higher health-care use in the five years leading up to the onset of MS. These patients were seeking help for a wide range of health issues, such as depression, digestive and urological problems, headaches and sleep disturbances.

Notably, in the year preceding MS onset, patients had 78 per cent more hospital visits, 88 per cent more physician service use and 49 per cent more prescriptions filled than the matched controls.

This evidence of an “MS prodrome” points to exciting potential to identify people whose symptoms and risk factors indicate that they are at high risk for the disease, Tremlett said. As “neuroprotective” drugs are developed in the future, such patients could be offered enrolment in clinical trials.

“Maybe we could recognize MS earlier,” she said. “Maybe we could intervene earlier and prevent disability.”

Drs. Heather Adam, Philippe Lagacé-Wiens, Lindsay Nicolle, Frank Schweizer, Sheryl Zelenitsky and George Zhanel join 190 other Canadian scientists on the list of more than 6,600 researchers from around the globe. Of the world’s scientists, Highly Cited Researchers are one in 1,000.

The names of the researchers on the list are drawn from the publications that rank in the one per cent by citations for field and publication year in the Web of Science, a global citation database. The list is created by Clarivate, a company that specializes in analytics and owns the Web of Science.  

“Drs. Schweizer, Adam, Lagacé-Wiens, Nicolle, Zelenitsky and Zhanel, leaders in the field of anti-microbial resistance, are seeking solutions that will advance patient care in the battle against infectious disease,” said Dr. Peter Nickerson, vice-dean (research), Rady Faculty of Health Sciences, and a distinguished professor of internal medicine at the Max Rady College of Medicine.

Dr. Heather Adam

Adam, an assistant professor of medical microbiology/infectious diseases at the Max Rady College of Medicine, focuses her research on documenting the common bacteria causing infections in primarily hospitalized patients, assessing the frequency these bacteria are resistant to commonly prescribed antimicrobial treatments and evaluating how the bacteria become resistant. The Canadian Antimicrobial Resistance Alliance (CARA) team, of which she is a member, also studies newly developed antimicrobials to find out which bacteria they will be most helpful in treating. 

“The recognition of being on the highly cited researchers list is a direct reflection of the remarkable opportunity I have had to work with our incredible research team, the Canadian Antimicrobial Resistance Alliance, for the past 20 years,” Adam said. “I believe the frequent citations of our work highlight the importance, and the increasing focus on antimicrobial resistance at both the national and international levels.”

Dr. Philippe Legace-Wiens

Lagacé-Wiens, an assistant professor of medical microbiology/infectious diseases at the Max Rady College of Medicine, works to better understand the resistance to antibiotics in bacteria and evaluate new antibiotics against resistant bacteria to confirm that they might work to treat patients with similar infections in the future. He also conducts research to evaluate new diagnostic tools in the laboratory to help diagnose infectious disease and antibiotic resistance.

“I’m both surprised and elated to be on the list,” Lagacé-Wiens said. “Being recognized for the work one does is a sure way to breathe new energy into the sometimes challenging aspects of research.”

Dr. Lindsay Nicolle

Nicolle, a professor emeritus of internal medicine at the Max Rady College of Medicine, is no longer active in research, but throughout her career, a major topic she addressed was clinical studies relevant to urinary tract infection. One question studied was the management of asymptomatic bacteriuria, which has become a topic of major interest in the last decade as antimicrobial stewardship initiatives have become essential in the management of infectious diseases.

“My research, and other activities relevant to it, such as guideline development, remains relevant and it is gratifying to know that work which was performed even decades ago is still contributing,” Nicolle said.  

Dr. Frank Schweizer

Schweizer, a professor of medical microbiology/infectious diseases at the Max Rady College of Medicine, and a professor of chemistry at the Faculty of Science, focuses his research on therapeutic approaches to overcome bacterial resistance. He studies the development of helper molecules, which, when combined with antibiotics, rescue antibiotics from resistance.

“It’s a great feeling that our research can inspire other investigators,” Schweizer said. “It is great to see that some of our papers generate wide interest all over the world. It provides motivation and confirms that we are on the right track and have an impact on the research community.”

Dr. Sheryl Zelenitsky

Zelenitsky, a professor at the College of Pharmacy, studies how best to use antibiotics while limiting the risk of harmful effects and antibiotic resistance. She focuses on vulnerable patients, such as people who are undergoing surgery, on dialysis or critically ill.

“I’m pleased that our work is being read,” Zelenitsky said. “I have always been interested in research that can improve patient care. My publications often stem from questions I have as to why something is or isn’t being done with the goal of advancing clinical practice.” 

Dr. George Zhanel

Zhanel is a professor of medical microbiology/infectious diseases at the Max Rady College of Medicine. As director of CARA, he works with researchers and clinicians from across the country to study which patients get infected with resistant infections, how organisms develop resistance and how best to treat these patients with existing and new antibiotics.

“Our group has worked incredibly hard to produce high-quality, practice changing research with local, national and international relevance,” Zhanel said. “This recognition is a testament to the dedication and hard work of all of our research trainees, staff and collaborators.”

Dr. Sheryl Zelenitsky [B.Sc.Pharm/89], a faculty member of the College of Pharmacy for the past 28 years, studies the optimal use of antimicrobials (antibiotics), particularly in hospitals. Her research was interprofessional long before it became a buzzword.

“I think I was onto something!” says the professor, who has worked closely with experts in anesthesiology, surgery, critical care, kidney disease, infectious diseases and more.

“This field is not limited to one organ,” she says. “You can have bloodstream infections, lung infections, kidney infections. It allows you to work with a lot of different disciplines. And with antimicrobial resistance, things change constantly, so it’s a very dynamic area.”

Zelenitsky, who grew up in Winnipeg Beach, Man., knew she wanted to pursue research that had strong clinical applications even before she earned her bachelor’s in pharmacy at UM. After completing her doctorate at the State University of New York at Buffalo, she spent two years as a clinical pharmacist at St. Boniface Hospital before joining UM in 1993. 

She has a particular interest in preventing and treating infections in high-risk patients, such as those who are immunocompromised or critically ill.

The problem of bacteria being overexposed to certain drugs and becoming resistant to them has worsened over the course of her career. “When I was in Buffalo in the early 1990s, new antibiotics were being marketed and there was a feeling that we were on top of it,” she says. “Since then, there’s been a steep increase in resistance.”

Zelenitsky recently received a prestigious appointment. She is one of about 15 experts worldwide who have been named to the Antimicrobial Resistance Commission, a new group established by the International Pharmaceutical Federation to guide global action against this threat.

Although new antimicrobials are needed to stay ahead of resistance, there is often reluctance to invest in developing them, Zelenitsky says, in part because new drugs may fall victim to resistance themselves.

The professor is an expert in pharmacokinetics (how a patient’s body handles a drug) and pharmacodynamics (how a drug works in the body), often abbreviated PK-PD.

Her more than 80 peer-reviewed publications include lab experiments on drugs’ effects, clinical studies of patients at St. Boniface Hospital, and studies that use computer simulations to predict the PK-PD effects of different antibiotic regimens in various patient populations.

Zelenitsky has a strong drive to see her findings adopted into practice. “The most important thing to me is ‘How does that translate to patient care?’”

Some of her most impactful studies have tested dosing regimens to prevent post-operative infections in surgical patients.

“I did a clinical study in colorectal surgery,” she says. “It was one of the first to show that the amount of antibiotic in the blood at the time that the surgeon closed the incision was highly correlated with the patient getting an infection or not, post-surgery. That work was broadly referenced in clinical practice guidelines and had a really positive impact.”

A recent study by one of her graduate students evaluated the standard regimen for cardiac surgery. “Based on our findings, we recommended that the standard antibiotic dose be given more frequently. There has been good uptake from that study, and the first to change its protocol was the Winnipeg Regional Health Authority cardiac program.”

Zelenitsky has also led many studies of infections in patients on kidney dialysis – an under-studied population that she says is prone to receive taken-for-granted doses that are not sufficiently grounded in evidence. “Some of our work has been internationally adopted,” she says.

Across all disciplines, she occasionally meets with pushback when her findings contradict the status quo.

“Sometimes people have been using a certain antibiotic in a certain way for their whole careers, and they’re bound and determined that it’s right. I have been challenged, like every researcher has. You need to really know your topic, know your research, and be clear and confident in presenting the evidence.”

Dr. Sheryl Zelenitsky, professor and researcher in the College of Pharmacy at the Rady Faculty of Health Sciences, recently received an Allied Health Research Grant from the Kidney Foundation of Canada for $100,000 to develop dosing recommendations for antibiotics in hemodialysis patients.

Zelenitsky’s study aims to optimize the dosing of the antibiotics cefazolin, ceftazidime, and ciprofloxacin that are commonly used in the treatment of serious, often life-threatening infections in hemodialysis patients. The multi-disciplinary study will see her working collaboratively with nephrologists, renal nurses, and pharmacists at St. Boniface Hospital, where she has a cross appointment.

Zelenitsky’s area of research is in antibiotics and infectious diseases and her specialty is on optimizing therapies for high-risk patients. She teaches antibiotics and infectious disease in the College of Pharmacy undergraduate and graduate programs.

“My idea for this project goes back a couple years when I looked into the data for dialysis patients and realized how little there was on how we should be using these drugs,” she says, “It surprised me at how little there was supporting clinicians in choosing the right doses of these important antibiotics.”

Zelenitsky completed a one-year audit at the St-Boniface Hospital’s hemodialysis unit and looked at the type of antibiotics that were prescribed.

“I reviewed the literature and these antibiotics were essentially being dosed without any data, so they’re really best guesses. And in dialysis patients, antibiotics are often dosed by protocol, so everyone gets the same dose,” she says.

The “one-dose-fits-all” approach means patients get the same dose regardless of age, gender, body weight, or dialysis factors. Zelenitsky also found a lack of consistency in dosing guidelines from location to location.

In Zelenitsky’s study, blood samples will be collected from 60 hemodialysis patients in St. Boniface Hospital who are receiving therapy for suspected or confirmed infections. The samples will be taken to the Apotex Centre’s pharmaceutical analysis laboratory (PAL) where Zelenitsky’s co-investigator associate professor and PAL director Dr. Ted Lakowski will measure the antibiotic concentrations. Pharmacokinetic and population modeling will be used to analyze the data and translate it into practical dosing guidelines for patients.

According to the WHO, antibiotic resistance is one of the most serious threats to global human health, and dialysis patients are among the most vulnerable. They tend to be more prone to infections because of their underlying renal dysfunction and accompanying health issues such as diabetes. They are also at higher risk of resistant infections and more likely to fail therapy. A further complication is that dialysis patients handle drugs differently because of their renal disease.

Zelenitsky hopes that the study will help to establish protocols that will effectively treat dialysis patients in a way that doesn’t promote more antimicrobial resistance.

“The goal is to develop evidence-based dosing guidelines for these very important antibiotics, so we know that we’re achieving effective levels in dialysis patients. If what we’re using now is not optimal, we’ll recommend what should be done based on our study.”

As part of summer research program, these students took the opportunity to load up on even more information and data, partnering with the College of Pharmacy faculty members on a wide area of studies.

Linnea Shackel describes it as challenging—but in the best possible way.

“They threw me right into it!” she said. “They said, ‘we need an ethics proposal done’ and I’d never done one before; I didn’t even know where to start.” But that’s the whole point, she said. “I had all these people supporting me and showing me the ropes.” Ultimately, she was not only able to write that proposal, but she also got into collecting data and then writing a paper. “I didn’t know I’d be able to accomplish so much,” she enthused.

Shackel worked alongside two of her favourite professors, Dr. Grace Frankel (Pharmacy Practice Instructor and Director of Pharmacy Performance Based Assessments) and Dr. Christopher Louizos (Director of Practice Innovation and Simulation and Manager of Steele’s Apothecary) on a study of polypharmacy rates in long-term care facilities in rural Manitoba. In this case, polypharmacy meant patients taking nine or more medications. It’s research that can really make a difference to patients, and it’s also the kind of work that gets her away from the bench and into the field. “I don’t really love lab work,” she admits with a laugh. When she heard she’d be working on site at a care facility with nurses and physicians, that sealed it for her. “I thought it would be a good place to collaborate with different healthcare practitioners.”

Classmate Michelle Boyce, who also participated in the summer research program, says the highlight was the opportunity to be mentored by a top-notch professor. “I worked with Dr. Sheryl Zelenitsky—she’s basically an idol in the pharmacy world,” said Boyce. Zelnitsky is a professor and researcher in the College of Pharmacy, Rady Faculty of Health Sciences. That kind of relationship not only helped her sharpen her research skills, but also pushed her to examine her academic career and consider taking her education even further. “I don’t think I would have even gone there if I hadn’t had this experience,” says Boyce.

Her research, microbial therapy, involved examining different pathogens and resistance rates in both hemodialysis patients and post-op patients. Ultimately, the information will be used to prevent infections. She says the experience was invaluable to her future work as a pharmacist, adding that it was also refreshing to take a wider view on her studies. “I appreciated being able to learn in a different setting than always having to study in a classroom,” said Boyce. “And being able to do something a little different that not everybody gets a chance to do.”

While they were under the supervision of their professors, both students remarked on the amount of freedom they had to pursue research on their own terms. “We set our own deadlines and got our work done,” said Boyce. “It was very independent and we were shown a lot of trust.”

Shackel agrees. She says the professor she worked with had clinic work once a week and was allowed to sit in. “By the end of the summer she said, ‘It’s on you. I’ll be in the other room – go for it!’ It was such a great experience.”