Impact of Patient-Specific Aminoglycoside Monitoring for Treatment of Pediatric Cystic Fibrosis Pulmonary Exacerbations

Brianna Hemmann; Elizabeth Woods; Tanya Makhlouf; Chris Gillette; Courtney Perry; Mary Subramanian; Holly Hanes

doi:10.5863/1551-6776-27.7.655

Impact of Patient-Specific Aminoglycoside Monitoring for Treatment of Pediatric Cystic Fibrosis Pulmonary Exacerbations

J Pediatr Pharmacol Ther. 2022;27(7):655-662. doi: 10.5863/1551-6776-27.7.655. Epub 2022 Sep 26.

Authors

Brianna Hemmann¹, Elizabeth Woods², Tanya Makhlouf², Chris Gillette³, Courtney Perry^{2

3}, Mary Subramanian², Holly Hanes⁴

Affiliations

¹ Department of Pharmacy (BH), Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
² Departments of Pharmacy (EW, TM, CP, MS), Wake Forest Baptist Health Brenner Children's Hospital, Winston-Salem, NC.
³ Department of Physician Assistant Studies (CG, CP), Wake Forest School of Medicine, Winston-Salem, NC.
⁴ Department of Pediatrics (HH), Wake Forest Baptist Health Brenner Children's Hospital, Winston-Salem, NC.

Abstract

Objective: Aminoglycosides are frequently used for empiric and definitive treatment of cystic fibrosis (CF) pulmonary exacerbations. Various methods have been described for aminoglycoside therapeutic drug monitoring. The objective of this study is to evaluate the effect of patient-specific pharmacokinetic calculations for aminoglycosides used to treat CF pulmonary exacerbations.

Methods: Ambidirectional cohort study of patients admitted to a children's hospital from June 1, 2018, through February 28, 2019, and June 1, 2019, through February 8, 2021. The primary outcome was the occurrence of dosing changes after analysis of initial serum concentrations in either group. Secondary outcomes included occurrence of nephrotoxicity, duration of antibiotics, and length of stay.

Results: Twenty-four patients (75%) in the intervention group versus zero in the control group required dosing adjustments after initial analysis of serum concentrations were completed (p < 0.001). There was not a statistically significant between-group difference for duration of antibiotics in days (median, 14 vs 13.5; Z, 1.07; p = 0.29) or length of stay (median, 11 vs 11; Z, -0.31; p = 0.76). There was also not a statistically significant between-group difference in forced expiratory volume in one second (FEV₁) change from admission to discharge (11.4% vs 13.9%; t, 0.61; Degrees of Freedom, 39; p = 0.55). Two patients (6.25%) in the intervention group experienced nephrotoxicity compared with zero patients in the control group (risk difference, 6.25%; 95% CI, -2.14 to 14.64; number needed to harm, 16).

Conclusions: Patient-specific pharmacokinetic monitoring led to significantly more dosing changes and was associated with similar patient outcomes as trough-only monitoring. Further studies are needed to identify methods to optimize aminoglycoside dosing and monitoring for these patients with the goal of reducing toxicities while maximizing efficacy.

Keywords: aminoglycoside; cystic fibrosis; exacerbation; monitoring; pulmonary.