Definitions
For the purposes of data analysis, a therapeutic AUC24was defined as 80-120 mg*hr/L, which is consistent with previously cited
targets for therapeutic drug monitoring of IV tobramycin in pediatric
and adult CF patients 7, 10-11. Cmaxwas considered to be therapeutic if the concentration was equal to or
exceeded eight-fold the highest documented PsA MIC. All sputum cultures
growing PsA obtained prior to and during admission were collected and
analyzed to determine the highest MIC.
The surrogate marker of clinical efficacy utilized in this study was the
categorization of end-of-treatment FEV1, from baseline.
FEV1 was obtained on admission, immediately prior to
discharge, and at the clinic appointment immediately following
discharge. Due to variance in methods utilized to calculate the percent
predicted FEV1 (ppFEV1)
between outpatient and inpatient settings, FEV1 in
liters was used to compare the patient’s baseline, discharge and
follow-up FEV1. The baseline FEV1 was
defined as the best FEV1obtained within the 6 months
preceding admission. If the patient did not have pulmonary function
tests (PFTs) obtained within 6 months of admission, the PFTs obtained at
their previous annual clinic appointment were utilized to define
baseline FEV1. A patient was considered to have returned
to baseline if the FEV1 obtained at discharge was within
10% of baseline FEV1. Of note, if a patient was
permitted to complete IV tobramycin therapy as outpatient, the
FEV1 obtained at their follow-up appointment immediately
following cessation of therapy was utilized for comparison to baseline.
The baseline serum creatinine was defined as the patient’s lowest serum
creatinine obtained within six months preceding admission. If the
patient did not have a serum creatinine obtained within the six months
preceding admission, the serum creatinine obtained at the patient’s
annual clinic appointment was considered baseline. The Kidney Disease
Improving Global Outcomes (KDIGO) definition of an increase in serum
creatinine by ≥0.3 mg/dL within 48 hours or an increase to ≥1.5 times
baseline within 7 days was utilized to define patients with AKI12.