In neonates, vancomycin, a narrow-spectrum antibiotic, is the first choice of treatment of late-onset sepsis predominantly caused by Gram-positive bacteria (coagulase-negative staphylococci and enterococci). Although it has been used for >50 years, prescribing the right dose and dosing regimen remains a challenge in neonatal intensive care units for many reasons including high pharmacokinetic variability, increase in the minimal inhibition concentration against staphylococci, lack of consensus on dosing regimen and way of administration (continuous or intermittent), duration of treatment, use of therapeutic drug monitoring, limited data on short- and long-term toxicity, risk of mutant selection and errors of administration linked to concentrated formulations. This article highlights and discusses future research directions, with specific attention given to dosing optimization of vancomycin, including the advantages of modeling and simulation approaches.
Keywords: continuous infusion; dosing optimization; formulation; modeling and simulation; neonates; nephrotoxicity; ototoxicity; pharmacokinetics; therapeutic drug monitoring; vancomycin.