Efficacy
The results of this study indicate that both AUC24 and
Cmax serve as relatively accurate predictors of clinical
efficacy, defined as a return to baseline or improvement in
FEV1, with 75.8% and 80.3% of patients with
therapeutic parameters achieving clinical efficacy, respectively. The
lack of correlation between increasing AUC24 or
Cmax and subsequent development of AKI, in combination
with the correlation of clinical efficacy and AUC24 ≥80
mg*hr/L, suggest benefit in targeting an AUC24 ≥80
mg*hr/L with minimal risk of additive toxicity.
Our institution guidelines recommend minimizing the calculated time
undetectable, defined as time for which tobramycin serum concentration
is <0.5 mg/L, to less than eight hours in an attempt to
improve therapeutic efficacy. The lack of correlation between efficacy
and time undetectable seen within this study may indicate that time
undetectable does not play a significant role in influencing the
efficacy of IV tobramycin in patients with CF being treated for a
pulmonary exacerbation. Given the significantly increased incidence of
AKI associated with multi-daily dosing of IV tobramycin found within
this study, particularly in pediatric patients, multi-daily dosing to
prevent the prolongation of time undetectable alone should be
discouraged.