Coagulase negative staphylococcal sepsis in neonates: do we need to adapt vancomycin dose or target?

BACKGROUND: Despite differences in types of infection and causative organisms, pharmacokinetic-pharmacodynamic (PKPD) targets of vancomycin therapy derived from adult studies are suggested for neonates. We aimed to identify doses needed for the attainment of AUC/MIC > 400 and AUC/MIC > 300 in neonates with sepsis and correlate these targets with recommended doses and treatment outcome. METHODS: Neonates who had Vancomycin therapeutic drug monitoring (TDM) performed between January 1, 2010 and December 31, 2012 were studied. Clinical characteristics, episodes of Gram-positive sepsis with outcomes and all neonatal blood culture isolates in hospital were collected from medical records. To estimate probability of target attainment of AUC/MIC >400 and AUC/MIC >300 a 1000-subject Monte Carlo simulation was performed by calculating AUC using Anderson’s (Anderson et al. 2006) and TDM trough concentrations (C(trough)) based population PK models. RESULTS: Final dataset included 76 patients; 57 with confirmed Gram-positive sepsis. TDM was taken after the 1(st) to 44(th) dose. 84.1% of C(trough) were within the range 5–15 mg/L. Currently recommended doses achieved probability of the targets (PTA) of AUC/MIC >400 and AUC/MIC >300 in less than 25% and 40% of cases, respectively. Doses required for 80% PTA of AUC/MIC > 400 for MIC ≥2 mg/L resulted in C(trough) values ≥14 mg/L. Mean AUC/MIC values were similar in treatment failure and success groups. CONCLUSION: With currently recommended vancomycin dosing the therapeutic target of AUC/MIC > 400 is achieved only by 25% of neonates. Appropriate PKPD targets and respective dosing regimens need to be defined in prospective clinical studies in this population.