Assessment of initial vancomycin trough levels and risk factors of vancomycin-induced nephrotoxicity in neonates.

Objectives: Vancomycin is a glycopeptide antibiotic commonly used in neonatal intensive care units (NICUs) to treat late onset sepsis. It is recommended that vancomycin trough levels at steady state following intermittent dosing regimen be maintained at 10-20 mg/L, which is largely dependent on the type of infection. Our objective is to assess the ability of initial vancomycin dosing regimens to obtain target trough levels and to assess the percentage and risk factors associated with the development of acute kidney injury (AKI) while on vancomycin.

Methods: This is a retrospective review of all NICU patients admitted between January 2016 and December 2017 who received vancomycin according to the NeoFax at either 10 mg/kg/dose (low-dose group, LDG) or 15 mg/kg/dose (high-dose group, HDG), with a frequency based on the postmenstrual age (PMA) and postnatal age (PNA). Both regimens were compared by their ability to attain target trough levels and the episodes of vancomycin-induced AKI. Other outcomes included identification of risk factors associated with the development of vancomycin-induced nephrotoxicity.

Results: Of 182 patients evaluated, 44 (24%) were in the LDG and 138 patients (76%) were in the HDG. Ninety-one patients (50%) attained target trough levels of 10-20 mg/L. Among these and according to patients' PMA, 48% in the HDG versus 7% in the LDG in PMA ≤29 weeks and 69% in the HDG versus 18% in the LDG in PMA 30-36 weeks attained target trough levels (p=0.006 and p<0.001, respectively). According to PNA, 47% in the HDG versus none in the LDG in patients <7 days old and 61% in the HDG versus 10% in the LDG in patients aged 8-14 days attained target trough levels (p=0.025 and p=0.016, respectively). A total of 14% developed AKI in the LDG vs 7% in the HDG (p=0.225). Only PMA ≤29 weeks (OR, 4.5, 95% CI 1.5 to 13), vancomycin trough levels >20 mg/L (OR 5.1, 95% CI 1.5 to 17), hypotension (OR 11.02, 95% CI 3.5 to 34) and furosemide (OR 4.4, 95% CI 1.4 to 13.5) were significantly associated with vancomycin-induced AKI in our NICU.

Conclusion: Vancomycin dosing in neonates according to the NeoFax did not provide sufficient attainment of target trough levels (10-20 mg/L). However, using the higher dosing range at 15 mg/kg/dose was more likely to reach target levels, with no measured increased risk of nephrotoxicity. Extreme premature neonates, supratherapeutic vancomycin trough levels, hypotension and furosemide use are associated with an increased incidence of vancomycin-induced nephrotoxicity.