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.