Vancomycin Toxicity in Neonates: A Review of the Evidence

Jodi M. Lestner; Louise F. Hill; Paul T. Heath; Mike Sharland

Disclosures

Curr Opin Infect Dis. 2016;29(3):237-247. 

In This Article

Conclusion

Despite historical concerns, a large body of evidence now exists to support the favourable safety profile of vancomycin in humans. In adults, nephrotoxicity is exposure-dependent, and more aggressive dosing may result in a significantly increased risk of toxicity. By comparison, current dosing regimens in neonates are conservative, and result in subtherapeutic concentrations in a large proportion of patients. At present, insufficient evidence exists to inform conclusions about the safety of higher doses of vancomycin in neonates. Furthermore, the clinical difficulty in ascertaining a diagnosis of sepsis with certainty in neonates makes risk–benefit analyses challenging. The development and use of novel diagnostic biomarkers are likely to improve clinical decision-making and trial design in the years to come.[94] Dose modification based on trough vancomycin concentrations, which are, in turn, largely determined by renal function, adds complexity in determining exposure–toxicity relationships. These issues are probably best addressed with detailed prospective, observational data that define renal impairment according to standardized criteria and allow for a more clinically valid estimation of risk.

Ototoxicity appears rare in patients of all ages treated with vancomycin. Diagnostic OAE and ABR may detect subtle high-frequency hearing loss following vancomycin exposure. These tests can only reliably be carried out in babies above 34 weeks, before which many preterm neonates will already have receive courses of vancomycin. UNHS at term is unlikely to detect subtle hearing impairment and identify exposure–toxicity relationships. Prospective studies that use robust and standardized definitions of hearing impairment based on diagnostic testing, such as with visual reinforcement audiometry at 8–12 months, are needed to further clarify the risk of clinically significant ototoxicity.

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