Personalized tobramycin dosing in children with cystic fibrosis: a comparative clinical evaluation of log-linear and Bayesian methods

Author:

Imani Sahand12,Fitzgerald Dominic A34,Robinson Paul D34,Selvadurai Hiran34,Sandaradura Indy567ORCID,Lai Tony8ORCID

Affiliation:

1. School of Medicine, University of Notre Dame Australia , Sydney, NSW 2010 , Australia

2. The Children’s Hospital at Westmead , Sydney, NSW 2145 , Australia

3. Department of Respiratory Medicine, The Children’s Hospital at Westmead , Sydney, NSW 2145 , Australia

4. Discipline of Child and Adolescent Health, Sydney Medical School, University of Sydney , Sydney, NSW 2145 , Australia

5. Faculty of Medicine, Westmead Clinical School, University of Sydney , Sydney, NSW 2145 , Australia

6. Centre for Infectious Diseases and Microbiology, Westmead Hospital , Sydney, NSW 2145 , Australia

7. Department of Infectious Diseases and Microbiology, The Children’s Hospital at Westmead , Sydney, NSW 2145 , Australia

8. Department of Pharmacy, The Children’s Hospital at Westmead , Sydney, NSW 2145 , Australia

Abstract

Abstract Background Children with cystic fibrosis (CF) pulmonary exacerbations receive IV tobramycin therapy, with dosing guided by either log-linear regression (LLR) or Bayesian forecasting (BF). Objectives To compare clinical and performance outcomes for LLR and BF. Patients and methods A quasi-experimental intervention study was conducted at a tertiary children’s hospital. Electronic medical records were extracted (from January 2015 to September 2021) to establish a database consisting of pre-intervention (LLR) and post-intervention (BF) patient admissions and relevant outcomes. All consecutive patients treated with IV tobramycin for CF pulmonary exacerbations guided by either LLR or BF were eligible. Results A total of 376 hospital admissions (LLR = 248, BF = 128) for CF pulmonary exacerbations were included. Patient demographics were similar between cohorts. There were no significant differences found in overall hospital length of stay, rates of re-admission within 1 month of discharge or change in forced expiratory volume in the first second (Δ FEV1) at the end of tobramycin treatment. Patients treated with LLR on average had twice the number of therapeutic drug monitoring (TDM) blood samples collected during a single hospital admission. The timeframe for blood sampling was more flexible with BF, with TDM samples collected up to 16 h post-tobramycin dose compared with 10 h for LLR. The tobramycin AUC0–24 target of ≥100 mg/L·h was more frequently attained using BF (72%; 92/128) compared with LLR (50%; 124/248) (P < 0.001). Incidence of acute kidney injury was rare in both groups. Conclusions LLR and BF result in comparable clinical outcomes. However, BF can significantly reduce the number of blood collections required during each admission, improve dosing accuracy, and provide more reliable target concentration attainment in CF children.

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology,Microbiology (medical)

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