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 ).