Ashlan Kunz Coyne on Polymicrobial Infections and Antimicrobial Stewardship

As resistant Gram-negative infections and antimicrobial stewardship challenges continue to evolve, pharmacists are increasingly tasked with balancing timely, effective therapy against the risks of overtreatment and resistance. In this interview, Ashlan Kunz Coyne, PharmD, MPH, assistant professor at the University of Kentucky College of Pharmacy, discusses emerging research on polymicrobial infections involving Pseudomonas and Stenotrophomonas, the potential clinical applications of co-culture modeling, and factors associated with outcomes in serious infections. She also addresses unanswered questions surrounding infection-related neuropsychiatric vulnerability in people living with HIV, the role of early empiric therapy, and key antimicrobial stewardship trends she is following at the first MAD-ID/SIDP joint meeting.

Pharmacy Times: Can you introduce yourself?

Ashlan Kunz Coyne, PharmD, MPH: I'm Ashlan Kunz Coyne, assistant professor at the University of Kentucky College of Pharmacy.
Pharmacy Times: Why were ceftazidime/avibactam plus aztreonam and levofloxacin selected as the agents of interest?

Kunz Coyne: So for the first study, we really wanted to evaluate if a patient was found to be sick by the clinical team, and both Pseudomonas and Stenotrophomonas were isolated in culture, what single drug regimen may result in as effective killing compared to if only one of those bacteria were isolated? So it's almost a monomicrobial versus polymicrobial evaluation. So with my somewhat stewardship hat on, we decided to evaluate aztreonam with avibactam, with or without the ceftazidime, or cefiderocol, or levofloxacin.

So, the whole idea was to pick drugs or pick dosing regimens that would be effective against each of them separately, and then to evaluate how their activity held up when they were cultured together. So that's how we decided on those 3 agents. And I mean, there's definitely other combination therapy that we could have evaluated, but we wanted to start first with if there was a single regimen that we could use, what might hold up better.

Pharmacy Times: How do you foresee this type of co-culture modeling becoming more integrated into drug development or clinical decision-making?

Kunz Coyne: Yeah, for drug development, it's a little difficult to say right now because we're really working on those mechanistic underpinnings of what might be happening. Why did one agent perform just as better with polymicrobial compared to the monomicrobial evaluation? So I think once we get a little closer to having those mechanistic understandings—or at least, beginning to understand them—then possibly that information could be used when we're talking about drug development and being able to develop drugs that are resilient to both bugs when they're together. 'Cause I mean, that is a common occurrence clinically is when both are isolated together.

For clinical practice, I mean, I certainly hope that everything we do at the bench in some way provides quality data for clinicians to use. So again, common occurrence to isolate these 2 together. There's always the question of which one might be more virulent. Are they both virulent? Do we wanna treat one? Do we wanna treat both? So hopefully, some of our data is able to provide a little bit of insight into, well, we should probably try to target both, and so maybe this regimen will give us a one-up.

Pharmacy Times: Your next analysis found substantially higher mortality among patients with cultures obtained after 48 hours of admission. What do you think explains that difference?

Kunz Coyne: Yeah, there's a number of things possibly. So if we look at the cohort that had cultures collected after 48 hours of hospital admission, they did have a higher Charlson Comorbidity Index at admission. Okay, so that's one thing.

They did have a lower 10-year survival probability, so definitely have to keep those things in consideration. Maybe they were, slightly more, I guess, at risk or had a higher mortality, coming into the hospital than the within 48-hour group. So that's possible.

Some other things that we may not know with a retrospective study is were the isolates in general different? So you have a patient that's been in the hospital for 48 hours. Is the isolate or the strain more virulent? What does their susceptibility pattern look like? All those things, you know, we try to look at retrospectively, but if it's not standard process with clinical microbiology labs, we may just never get that information. So some of the things we're gonna work hard to look at a little closer, and some of the things we just might not have that information.

Pharmacy Times: How can pharmacists—and other health care professionals—balance the need for early empiric therapy with the risks of overtreatment or unnecessary broad-spectrum antibiotic use?

Kunz Coyne: Yeah, that's like the golden question. For the last 10 to 15 years, we have this group of newer antimicrobials for our resistant Gram-negatives, and the question on every clinician's mind is: In what patients do we need to go that direction, and in what patients maybe do we have a little more confidence in sticking with standard of care like cefepime or piperacillin-tazobactam upfront? So we do not have that answer definitively. What we also don't have is we don't have much literature cluing us into specific patient characteristics, predictors that help tell us, yes, maybe go to the newer agents or, no, we could stick with standard of care.

So I think that's really an area that we know from multiple recent studies, including one study out of our lab that was published in [Open Forum Infectious Diseases] fall of 2025, that earlier initiation of active therapy, including some of the newer agents, results in lower rates of mortality, better patient outcomes. But we're still missing those predictors. So that was really the goal of this study is to try to clue in for patients with Stenotrophomonas infections, what patients to start that coverage for Stenotrophomonas early.

Pharmacy Times: One of the findings was that psychiatric comorbidity was associated with a longer interval before hospitalized infection. Did that result surprise you?

Kunz Coyne: Yeah, I'm surprised by a lot of data that we get when we first start retrospective studies and data analysis. But I would say for this specific study, yeah, because when we think of psychiatric comorbidity, it's often associated with overall, you know, poor health outcomes, potentially increased infection risk.

But I think what our study really finds is that this relationship is much more complex. So, is this a scenario where patients with documented psychiatric disorders actually have more follow-up with the health care setting, or do they have more access to mental health services, case management, are they started on HIV therapy, monitoring other interventions earlier that are helping them prevent these required hospitalizations for serious bacteria or fungal infections? So that's something that we're really focused on right now for this study. Again, EHR studies are limited when it comes to this complex relationship, but, surprising data, yes, we have a lot more to look into specific to it.

Pharmacy Times: What unanswered questions remain about the bidirectional relationship between severe infection and neuropsychiatric vulnerability in people living with HIV?

Kunz Coyne: I think it's unanswered in both cases, so causality and then also directionality. So we did demonstrate with our data, this prelim data, the substantial increase in the neuropsychiatric disorders following hospitalization with a serious bacterial or fungal infection. But it really remains unclear whether this infection directly accelerates neurocognitive or even psychiatric decline, whether underlying vulnerability may predispose these patients to poor outcomes, or whether both of these things are happening at the same time. So I always go back to mechanism, thinking about things that we can and cannot get from the patient chart, so chronic inflammation, maybe immune dysregulation, their history of substance use disorder (SUD), but not just the disorder itself, but their actual treatment of SUD. And then, of course, we have the complexity of social determinants of health. So all of these things just result in this complex interplay of characteristics that, you know, we have a wealth of information from our inpatient and outpatient HIV care here at UK Healthcare, so we're just starting the process of really looking into that deeper.

Pharmacy Times: As an attendee of MAD-ID/SIDP this year, what themes or trends in antimicrobial stewardship are you most interested in following?

Kunz Coyne: So, most of our work right now is in resistant Gram-negative infection. So I'm always interested in seeing, looking at the approach of these new antimicrobials 10 years ago or so when they came out, and then seeing how it almost progresse and, just the use of the agents, what we know about them, their resilience or lack of resilience in the health care setting, how that really unfolds over 10 years.
So I think there's multiple really, really exciting talks that'll be happening at the very first MAD-ID/SIDP meeting.

So, seeing that data all in one place and hearing from the experts on how they would approach these infections using these different agents is something that I'm always looking forward to.