Review of Tobramycin Dosing in Pediatric Patients With Cystic Fibrosis
Taylor A Imburgia1, Ryan M Seagren1, Hanna Christensen1
1Department of Pharmacy (TAI, RMS, HC, MCB), American Family Children's Hospital at University of Wisconsin Health, Madison, WI.
Insights
Empiric tobramycin dosing in pediatric cystic fibrosis (CF) patients often fails to reach target levels. Older children achieve therapeutic tobramycin (an antibiotic) levels more consistently, suggesting younger CF patients may need higher doses.
Area of Science:
- Pharmacology and Therapeutics
- Pediatric Medicine
- Infectious Diseases
Background:
- Cystic Fibrosis (CF) exacerbations frequently require intravenous antibiotics like tobramycin.
- Optimizing tobramycin dosing is crucial for efficacy and minimizing toxicity in pediatric CF patients.
- Current empiric dosing strategies may not consistently achieve therapeutic pharmacokinetic targets.
Purpose of the Study:
- To evaluate the efficacy and safety of empiric tobramycin dosing and monitoring in pediatric CF patients.
- To investigate the relationship between patient age and tobramycin dosing required to achieve target Area Under the Curve (AUC).
Main Methods:
- Retrospective review of a tobramycin pharmacokinetics (PK) database from 2009-2019.
- Calculation of tobramycin doses needed to achieve a target AUC of 100 mg·hr/L.
- Collection of serum creatinine and concomitant nephrotoxin use as safety endpoints.
Main Results:
- Only 43.5% of pediatric CF patients achieved the target tobramycin AUC with empiric dosing.
- Doses of 9.5-11.9 mg/kg every 24 hours achieved goal AUC in 77% of encounters.
- Older children (10 and 15 years) had significantly higher odds of achieving goal AUC compared to younger children.
- Acute kidney injury occurred in 10.8% of encounters.
Conclusions:
- Empiric tobramycin dosing (10 mg/kg every 24 hours) is insufficient for achieving target AUC in a majority of pediatric CF patients.
- Patient age is a significant factor influencing AUC attainment, with older children requiring fewer dose adjustments.
- Consideration of higher weight-based tobramycin doses for younger pediatric CF patients may be necessary to optimize therapeutic outcomes.
Objective:
An institution's tobramycin pharmacokinetics (PK) database was reviewed to evaluate the efficacy and safety of empiric tobramycin dosing and monitoring strategies used in pediatric patients with cystic fibrosis (CF). The relationship between patient age and tobramycin dosing needed to achieve the area under the curve (AUC) goal was investigated.
Methods:
Retrospective chart review was performed for patients who received tobramycin during a CF exacerbation from 2009 to 2019 who received PK monitoring by pediatric pharmacists. Tobramycin dosing needed to achieve an AUC of 100 mg·hr/L was calculated for each patient. Serum creatinine and concomitant nephrotoxin use were collected as surrogate nephrotoxicity endpoints to evaluate safety.
Results:
Goal AUC (100 ± 15 mg·hr/L) was achieved based on initial or repeat PK calculations in 43.5% (95% CI, 37.7-49.3) of 85 unique patients across 326 encounters. Patients with calculated recommended doses of 9.5 to 11.9 mg/kg every 24 hours empirically achieved goal AUC in 77% (78/101) of encounters. The odds of achieving goal AUC were 56% higher for children aged 10 vs 5 years (OR = 1.56; 95% CI, 1.04-2.34; p = 0.033) and 32% higher for children aged 15 vs 10 years (OR = 1.32; 95% CI, 1.07-1.61; p = 0.008). Overall rates of acute kidney injury and concomitant nephrotoxin use were 10.8% (95% CI, 6.2-15.5) and 80.7% (95% CI, 74.3-87.1), respectively.
Conclusions:
Desired AUC was achieved by 43.5% of pediatric patients with CF using tobramycin 10 mg/kg every 24 hours. Older patient age was associated with higher initial AUC attainment and fewer dose modifications. Younger children may require higher weight-based dosing to meet AUC goals.
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