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.