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.