Safety
Within both pediatric and adult cohorts, an increasing AUC24 or Cmax was not associated with subsequent development of AKI (Table 4 ). The mean AUC24 in encounters where patients developed AKI was 104.3 mg*hr/L versus a mean AUC24 of 119.6 mg*hr/L in encounters in which the patient did not develop AKI (p=0.031). In patient encounters where the AUC24 was considered subtherapeutic (<80 mg*hr/L), the rate of AKI development was 45.2% versus a rate of 28.3% in patient encounters where the AUC24 was considered therapeutic (AUC24≥80 mg*hr/L) (p=0.073). In patient encounters in which the Cmax was considered to be therapeutic (Cmax ≥8 to 10-fold the MIC), there was an associated incidence of AKI of 27% versus 36.4% in patient encounters with a Cmax considered subtherapeutic (Cmax <8 to 10-fold the MIC) (p=0.218). A statistically significant increase in incidence of AKI was noted in pediatric and adult patients receiving IV tobramycin dosed multiple times daily versus extended-interval dosing (at least every 24 hours) with 50% versus 28.7% of patient encounters developing AKI, respectively (p=0.047) (Table 5 ).