Therapeutic Drug Monitoring (TDM) refers to the practice of tailoring individualized drug dosing regimens for patients by quantitatively assessing drug exposure, pharmacokinetic markers, or pharmacodynamic endpoints based on therapeutic drug ranges. The core of TDM is personalized drug therapy. At the recent 2023 Infectious Diseases Week (IDWeek 2023), Dr. Kevin J. Downes from the Children’s Hospital of Philadelphia presented a talk titled “ Practical and Novel Approaches to Therapeutic Drug Monitoring and Antibiotic Dose Optimization ” and shared his insights with “ Infectious Disease Frontline”(IDF).
Kevin J. Downes, MD
Assistant Professor of Pediatrics
Children’s Hospital of Philadelphia, Pennsylvania, USA
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IDF: Good morning Dr. Dao, first of all I just want to say it’s a great presentation and thank you for having this interview with us. Thank you. And for the first question, could you elaborate on the current challenges in the theoretical drugs monitoring in pediatric patients? How do your practical approaches address those issues to ensure effective and safe antibiotic dosage?
Dr. Downes: Well there are a number of challenges currently to therapeutic drug monitoring in children. I think first off the monitoring step itself, the measurement, we need newer tools to be able to obtain informative drug levels. And there are some newer technologies that are available to us to use smaller samples that allow us to collect samples at a more precise time that will be informative for dosing. Additionally we need more people available to interpret the results.Measuring a single level and interpreting it within a therapeutic range only provides so much information when it comes to dosing.We need some more actionable data that can allow us to use that individual drug level and then provide drug dosing guidance back to the clinicians. And now there are software programs available to us clinically that allow us to do that and provide more precise dosing for patients.
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IDF: And you’ve worked extensively on antibiotic stewardship in children focusing on individualizing dose optimization. Could you provide specific examples or case studies where your novel approaches to antibiotic dose optimization have proven to be successful?
Dr. Downes: Yeah, so in terms of case studies I think there’s a lot of, most of therapeutic drug monitoring has focused on minimizing toxicity and there’s a lot of examples. of successes in this area when it comes to bankamycin and kidney toxicity, aminoglycosides and kidney toxicity, etc. Where I find that the most successes come is when we use that information to provide more effective targets. So when we deal with children who have altered pharmacokinetics such as those who are on ECMO or CRRT, children who may be significantly over or under weight where standard weight -based dosing is really not the optimal approach. I think that’s where we can utilize TDM to really improve the exposures that those children are receiving.
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IDF: And considering your recent articles on UTIs and acute kidney injuries in children, how does your research translate into actionable insights for theoretical drug monitoring and antibiotic dose optimization? Are there any key takeaways that clinicians can immediately implement in their practice?
Dr. Downes: Well, from a clinical side in terms of implementation, I think that the main take home is that we need to be able to set a target and that target needs to be individualized for the patient that’s in front of us. And when we do that, we can leverage some of the tools available to us to provide more effective and safe therapy. I don’t think that there is a therapeutic range for an individual patient, meaning the therapeutic range that we apply like from the lab needs to be tailored to that individual. So each patient has their own sort of range of targets and some being more likely to be successful and others being more likely to be toxic. And we just need to really make those clinical decisions to say what is the best target for this patient in front of me. And it takes time and effort to do that, which I think is another barrier to doing this regularly.
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IDF: And for the last question, looking forward, what advancements and innovations do you anticipate in the field of periodic infectious disease, particularly in therapeutic drug monitoring and antibiotic, those organizations, how can professions prepare to adapt those changes?
Dr. Downes: Yeah, I think we’re in a really exciting time for this with advancements in technology, so that advancements in the device field where we can have improvements in how we collect samples with the volume and the timing and the patient experience when it comes to collection of samples for therapeutic drug monitoring. I also think we’re in a really exciting time when it comes to advancements from a mathematical standpoint with advancements in AI. We have, I think the future is such that we’re going to be able to really provide tailored personalized dosing much more effectively with advancements in the technologies that are coming and something like continuous drug monitoring, which is an additional advancement in the field and not too far off, will really help us tailor therapy at the individual level. And I think that’s an area I’m particularly excited for is continuous drug monitoring.
