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Comparison of the predictive value of area under the curve versus maximum serum concentration of intravenous tobramycin in cystic fibrosis patients treated for an acute pulmonary exacerbation
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  • Katherine Landmesser,
  • Elizabeth Autry,
  • Brian Gardner,
  • Katherine Bosko,
  • Aric Schadler,
  • Robert Kuhn
Katherine Landmesser
University of Kentucky
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Elizabeth Autry
University of Kentucky Medical Center
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Brian Gardner
University of Kentucky Medical Center
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Katherine Bosko
University of Kentucky Medical Center
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Aric Schadler
University of Kentucky College of Pharmacy
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Robert Kuhn
University of Kentucky College of Pharmacy
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Abstract

OBJECTIVES: The primary objective of this study was to compare the therapeutic predictive value of area under the curve (AUC24) versus maximum concentration (Cmax) in cystic fibrosis (CF) patients receiving intravenous (IV) tobramycin for a Pseudomonas aeruginosa (PsA) acute pulmonary exacerbation (APE). Acute kidney injury (AKI) incidence and the relationship between time undetectable and efficacy were also assessed. METHODS: A retrospective review was conducted in patients aged at least one month with a diagnosis of CF receiving IV tobramycin for treatment of a PsA APE and admitted to the University of Kentucky between August 2015 and August 2019 . Patients were excluded if they had no growth of PsA on sputum culture or if two post-dose tobramycin levels were not obtained following a dose adjustment of ≥20%. RESULTS: A total of 44 pediatric and 107 adult patient encounters met inclusion criteria. In patients with therapeutic success (n=91), 75.8% had an AUC24 ≥80 and 80.3% had a Cmax ≥8 times the highest PsA minimal inhibitory concentration (MIC). There was a significant correlation between AUC24 and Cmax (r2 = 0.727; p<0.001). AKI incidence was significantly higher in patients receiving IV tobramycin dosed multiple times daily versus at least every 24 hours (50% versus 28.7%; p=0.047). CONCLUSIONS: The results of this study indicate that both AUC24 and Cmax serve as relatively accurate predictors of tobramycin efficacy. Additionally, given the significant increase in incidence of AKI, multi-daily dosing of IV tobramycin should be used only in select pediatric and adult patients with CF.

Peer review status:UNDER REVIEW

03 Jan 2021Submitted to Pediatric Pulmonology
04 Jan 2021Submission Checks Completed
04 Jan 2021Assigned to Editor
05 Jan 2021Reviewer(s) Assigned
11 Feb 2021Review(s) Completed, Editorial Evaluation Pending
22 Feb 2021Editorial Decision: Revise Minor
19 Apr 20211st Revision Received
20 Apr 2021Submission Checks Completed
20 Apr 2021Assigned to Editor
20 Apr 2021Reviewer(s) Assigned
14 Jun 2021Review(s) Completed, Editorial Evaluation Pending