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
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.