Where Are They Now? Q & A with Dr. Sylwia Marianski

By: Andrew Madon, PharmD

Dr. Sylwia Marianski, PharmD

Dr. Marianski is a Clinical Pharmacist at Endeavor Health Evanston Hospital. She completed her PGY-1 residency program at Endeavor Health Glenbrook Hospital (NorthShore University HealthSystem) and her Fellowship Program at Midwestern University Downers Grove Campus. Her interests include pharmacokinetics and pharmacodynamics of anti-infective agents, individualized dosing strategies to improve patient outcomes, and clinical outcomes research in serious bacterial infections

Research title: Evaluation of Ceftriaxone Population Pharmacokinetics (PK) and Pharmacodynamics (PD) in Critically Ill Pediatric Population.

Questions:

1. What led your group to investigate vancomycin in the pediatric population? 

Our group was particularly interested in ceftriaxone because, despite its widespread use in pediatrics, there is limited pharmacokinetic data in critically ill children with multiple organ dysfunction syndrome (MODS). MODS is characterized by the impairment of several organ systems due to severe acute events, such as sepsis, major trauma, or other life-threatening illnesses. These patients often have significant physiologic changes, including variations in renal function, volume status, and protein binding, that can substantially affect drug exposure. Given that ceftriaxone is frequently used as empiric therapy in severe pediatric infections, we wanted to better understand whether standard dosing achieves pharmacodynamic targets in this vulnerable population.

2. What were the challenges around doing a study in this population?

Conducting PK studies in critically ill children presents several challenges:

• Logistical concerns around blood sampling in pediatric patients (e.g. limited volumes) which led us to use volumetric absorptive microsampling (VAMS) to minimize blood volume collection; however, this required precise handling and validation.

• Rapidly changing physiology in MODS, making PK variability significant

• Heterogeneity in renal function (eGFR ranging widely in our cohort)

3. Did any of the findings surprise you?

While we were not surprised by the findings, I think they will surprise the general community. Despite applying allometric scaling and adjusting for renal function, there was still substantial between-subject variability in both clearance and volume of distribution.

Additionally, we observed that while target attainment was adequate for MIC ≤1 mg/L, it became highly variable at MICs of 2–4 mg/L and dropped below 50% at 8 mg/L. Given how commonly ceftriaxone is used, this variability highlights a potential risk of underexposure in critically ill children, particularly against less susceptible organisms.

4. How have the results of your study impacted your practice? 

These findings reinforced the importance of being cautious when using standard dosing in critically ill pediatric patients. In practice, it increases awareness that:

• Renal function estimates alone may not fully explain variability

• Higher MIC organisms may not be adequately covered

• There may be a role for therapeutic drug monitoring (TDM), particularly for MIC ≥2 mg/L

  
  

It has also strengthened interdisciplinary discussions around dosing strategies and antimicrobial stewardship in critically ill children.

5. Based on this research, what areas do you believe should be further investigated? 

Future research should focus on:

• Qualification of pharmacokinetic models for ceftriaxone

• Evaluation of alternative dosing strategies (e.g., extended or continuous infusions)

• Inclusion of patients on extracorporeal support

• Investigation of protein binding variability in critically ill pediatric populations

• Correlating PK/PD target attainment with clinical outcomes

Ultimately, linking pharmacometric findings to patient-centered outcomes will be essential to guide precision dosing in this population.

The MAD-ID ‘Where Are They Now?’ series highlights research presented at the MAD-ID Annual Meeting now published in the infectious diseases literature.