Vancomycin Dosage and Its Association with Clinical Outcomes in Pediatric Patients with Gram-Positive Bacterial Infections

Abstract

AIM: The aim of this study was to evaluate whether vancomycin trough concentrations at initial steady state are associated with clinical and microbiological outcomes along with vancomycin-related nephrotoxicity in pediatric patients with Gram-positive bacterial (GPB) infections. <br>METHODS: A retrospective cohort study of pediatric patients who received vancomycin for &gt;/=72 hours during 2008-2016 was conducted. Study patients were divided into three cohorts in accordance with their first trough levels at steady state: &lt;5 mg/L (lower-trough), 5-10 mg/L (low-trough), and &gt;10 mg/L (high-trough; reference) cohorts. <br>RESULTS: Of the 201 patients eligible for study inclusion, 60 patients in the lower- and low-trough cohorts, respectively, were idect 3ntified via propensity score matching and analyzed against 30 high-trough patients in each comparison pair (neonates were excluded due to small sample size). Lower-trough patients were at a greater risk for prolonged therapy, retreatment, and dose adjustment than high-trough patients. Final steady-state troughs remained substantially lower in both the lower- and low-trough cohorts (p&lt;0.001 and p=0.005, respectively), despite greater dose up-titration in the lower-trough cohort and percent change in daily dose in both the lower- and low-trough cohorts than in the high-trough cohort (p&lt;0.001 for all). Clinical cure and death risk, along with the risks of isolation of resistant strains and renal events, were not significantly different between cohorts in both comparison pairs. <br>CONCLUSION: Vancomycin troughs of &lt;5 mg/L at initial steady state were associated with significantly compromised clinical outcomes in terms of risk of therapy prolongation, retreatment, and aggressive dose up-titration, compared to &gt;10 mg/L troughs in pediatric patients with GPB infections.