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Topics: Clinical & Translational Research, Education & Training, Five Questions

Preventing Antimicrobial Resistance: What Works and What Doesn’t?

Five Questions with C/T Research Academy physician-scientist Christina Manice.

Christina Manice, MD, has taken on one of the most pressing public health threats of our time: anti-microbial resistance, and specifically, the development of antibiotic-resistant “superbugs.” The World Health Organization, the U.S. Centers for Disease Control and Prevention (CDC), and the United Nations have each recognized this as a global health priority. By CDC estimates, nearly three million antibiotic-resistant infections occur in the U.S. annually, resulting in about 35,000 deaths caused by resistant organisms.

Manice, a clinical fellow in infectious diseases at Boston Children’s Hospital and trainee (2021-2023) with our Clinical and Translational (C/T) Research Academy, is taking aim at the problem with a three-tiered, mixed-methods approach. Her research project combines qualitative focus groups with a national survey to determine how pediatric specialty centers track and manage antimicrobial use. Lastly, she’s employing big-data mining to compare patterns of antimicrobial use and health outcomes at those centers. The ultimate aim of her research is to inform best practices in preventing antimicrobial resistance in pediatric populations.

What gap does your research program seek to fill?

As an infectious disease physician, I consider antimicrobial resistance to be one of the biggest public health threats. I believe incentivizing health systems to promote effective antimicrobial stewardship is an important part of the solution.

“As an infectious disease physician, I consider antimicrobial resistance to be one of the biggest public health threats.”

My focus is in pediatrics. Essentially, pediatric stewardship programs function to improve appropriate antimicrobial use. By doing so, they improve patient outcomes and reduce healthcare expenditures, at both the hospital level and across the global healthcare system.

In the U.S., hospitals have devised various strategies to achieve their goals for the use of antimicrobials. In a pre-authorization or restricted model, a clinician can’t prescribe certain antimicrobials unless an infectious diseases expert verifies in advance that it’s appropriate. Other hospitals do something called audit and feedback, where they look at all the antibiotic orders after the fact and give providers feedback on the drug choice and its appropriate use. Hybrids of these two approaches also exist.

For me, the gap is that there’s never been a rigorous analysis of which of these approaches is better in achieving the outcomes desired. My aim for the C/T Research Academy project is to characterize the differences in implementation strategies across U.S. pediatric centers and elucidate the drivers of these differences. Ultimately, I hope to understand the association between different stewardship strategies and antimicrobial outcomes.

With antimicrobial resistance being such a recognized problem, why haven’t researchers examined what’s working to address it and what’s not?

We have looked at what’s working and what’s not, and we know that stewardship programs do effectively improve appropriate antibiotic use. They improve mortality rates and they reduce hospital expenditures. But we haven’t looked at a more detailed view of how different hospitals are actually enacting stewardship and whether that has an impact on outcomes.

My project is three-tiered. The first part, which I’ve focused on during C/T Research Academy for the past two years, is qualitative research. We conducted five different focus groups with medical practitioners (pharmacy experts and medical directors) at pediatric antimicrobial stewardship programs. We wanted to understand the facilitators and barriers to enacting stewardship, which parts of their jobs were satisfying or not, and how those are all interconnected. It has been really fascinating and fun.

The results from my qualitative project informed a survey design which is currently being fielded to stewardship programs across the country. It encompasses nuts-and-bolts questions, such as whether they meet the core tenets the CDC has laid out, as well as more targeted questions borne out of the focus group research.

After the results of the survey are tallied, the third step is to examine hospital-level outcomes on antibiotic use from a large pediatric data set. By comparing our survey findings to those outcomes, we hope to determine whether certain stewardship strategies or setups are more successful than others.

Our research might uncover, for example, that hospitals with more dedicated pharmacy specialists in their stewardship programs may also have lower antibiotic use. We can also zero in on usage patterns of broad-spectrum antimicrobials like carbapenems, which are most concerning.

How might this work potentially change clinical practice?

If we’re able to better align the incentives of hospitals with the public health goal of reducing inappropriate antimicrobial use, not only will it be better for patient care, but also from a hospital system and public health level globally.

We’ve already started to see this happen. In its Best Hospitals ratings, US News and World Report now includes as one criterion the number of full-time equivalent (FTE) pharmacy specialists who should be dedicated to antimicrobial stewardship. This could serve to motivate hospitals to increase staffing for antimicrobial stewardship.

What’s tricky is that zero antimicrobial use is not the goal, right? There are times when you need antibiotics or antimicrobials to fight infection. What we are trying to do is optimize antibiotic use: using it appropriately when it’s needed, reducing it when it’s not needed, and ensuring that we’re using as targeted an antibiotic as possible, whenever possible.

You want the correct dose, the correct duration, and the correct antimicrobial when it’s needed. And when it’s not needed, we hope to get folks off therapy.

How does the C/T Research Academy fit into your career path and what has been the value for you?

[C/T Research Academy] has really made the larger ecosystem here at Harvard very approachable, both professionally and interpersonally.

It’s been a really wonderful experience. The Harvard affiliates and academic healthcare centers form a system that can be very daunting. It’s huge. It’s made up of multiple institutions. It can be very challenging to know how to approach that system.

Part of the appeal of the C/T Research Academy for me is that it’s so small; only a handful of us are meeting weekly. It has allowed the space and time to really get to know my co-trainees. Each of us feels comfortable speaking our mind, and we can reach out to one another outside of sessions to share advice. It’s really made the larger ecosystem here at Harvard very approachable, both professionally and interpersonally.

It’s also provided me with structure for the last two research years of my clinical fellowship. I know that every single Tuesday afternoon is my “Harvard Catalyst” time. I’m either going to be getting more nuts-and-bolts skills I need to accomplish my research, like grant writing or statistics, or career-development skills that are going to help me long-term, such as physician wellness or negotiation.

How do you find work/life balance at this stage of your career?

I love the outdoors. The best times in my life are when I can be outside, especially hiking with my husband and our two little boys. Anytime we can do that, we love it.

I grew up in northern New Mexico on a cattle ranch about 45 minutes outside of Santa Fe. My nearest neighbor was 11 miles away. It was really in the middle of nowhere with no cell phone service. I never dreamt that I would be living on the East Coast for so long.

We moved here from New York in 2020, and one of the best things about moving to Boston is how accessible it is to get out in nature. I am passionate about my work, but also recognize the need to reset, and living in such a beautiful place makes that easy.

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