Predictability of vancomycin pharmacokinetics in neonates

Abstract

Dear Editor, We read with great interest the paper of Cunha et al. on the cost-ineffectiveness of measuring serum vancomycin trough concentrations in adult hospitalized patients receiving parenteral vancomycin. Based on a retrospective analysis of observations collected in 351 patients, the authors illustrated that vancomycin dosed by creatinine clearance estimations, based on serum creatinine values, was acceptably accurate [1]. We would like to add to the discussion that the conclusions formulated by Cunha et al. in adults might be extrapolated to neonatal populations in whom vancomycin dosed by creatinine clearance estimations is acceptable once serum creatinine values reflect renal function. Since glycopeptides are almost exclusively eliminated according to the glomerular filtration rate (GFR), developmental changes in renal clearing capacity in the neonate have to be taken into account. We therefore would like to report here our recently published data on vancomycin clearance in the first month of life in 214 neonates and compare them with the findings of Cunha et al. [1, 2]. Size explained 49.8%, postmenstrual age 18.2%, and renal function (serum creatinine values) 14.1% of vancomycin clearance variability, resulting in over 80% of explained variability in vancomycin clearance in the first 4 weeks of postnatal life [2]. In children and adults, serum creatinine values serve as a useful and reliable marker of renal clearance. In neonates, however, serum creatinine values at birth mainly reflect the maternal renal function and only turn into a reliable marker of renal clearance after the first week of life [3]. The overall high predictability of vancomycin clearance in this cohort of neonates therefore mainly relates to the fact that this drug is only very rarely administered in the very first days of life when creatinaemia does not yet reflect neonatal GFR and is in contrast to the limited predictability of renal drug clearance at birth [4]. The bactericidal activity of glycopeptide antibiotics is based on the inhibition of bacterial cell-wall synthesis. Glycopeptide antibiotics are the drugs of choice for methicillin-resistant staphylococcal infections and are widely used as empiric treatment for infections related to the central venous line in neonates. These infections are often caused by coagulase-negative staphylococci. Taking these epidemiological factors into account, vancomycin is only rarely administered in the first days of life but is a frequently administered drug in neonates for the abovementioned pathogens [5]. We therefore suggest extrapolating the conclusions formulated by Cunha et al. in adults to all populations in whom vancomycin dosed by creatinine clearance estimations is acceptably accurate hereby excluding the first days of postnatal life in addition to other specific conditions such as extracorporeal membrane oxygenation. Eur J Clin Microbiol Infect Dis (2007) 26:847–848 DOI 10.1007/s10096-007-0367-4