Inadequate vancomycin therapy in term and preterm neonates: a retrospective analysis of trough serum concentrations in relation to minimal inhibitory concentrations

Abstract

BackgroundVancomycin is effective against gram-positive bacteria and the first-line antibiotic for treatment of proven coagulase-negative staphylococcal infections. The aim of this study is bipartite: first, to assess the percentage of therapeutic initial trough serum concentrations and second, to evaluate the adequacy of the therapeutic range in interrelationship with the observed MIC-values in neonates.MethodsIn this study, preterm and term neonates admitted at a tertiary NICU in the Netherlands from January 2009 to December 2012 and treated with vancomycin for a proven gram-positive infection were included. Trough serum concentrations were measured prior to administration of the 5th dose. Trough concentrations in the range of 10 to 15 mg/L were considered therapeutic. Staphylococcal species minimal inhibitory concentrations (MIC’s) were determined using the E-test method. Species identification was performed by matrix-assisted laser desorption/ionisation mass spectrometry.ResultsOf the 112 neonates, 53 neonates (47%) had sub-therapeutic initial trough serum concentrations of vancomycin, whereas 22% had supra-therapeutic initial trough serum concentrations. In all patients doses were adjusted on basis of the initial trough concentration. In 40% (23/57) of the neonates the second trough concentration remained sub-therapeutic. MIC’s were determined for 30 coagulase-negative Staphylococcus isolates obtained from 19 patients. Only 4 out of 19 subjects had a trough concentration greater than tenfold the MIC.ConclusionsForty-seven percent of the neonates had sub-therapeutic initial trough serum concentrations of vancomycin. The MIC-data indicate that the percentages of underdosed patients may be greater. It may be advisable to increase the lower limit of the therapeutic range for European neonates.

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

“…These results suggest that current dosing recommendations in NeoFax [and likely also in British National Formulary (BNF)] may not be adequate for treatment of neonatal CoNS sepsis. The same conclusion was reached by authors who studied vancomycin C troughs achieved by neonates and compared these to vancomycin MICs of CoNS isolates [25]. …”

Vancomycin use, dosing and serum trough concentrations in the pediatric population: a retrospective institutional review

“…A majority of nephrotoxicity that was associated with vancomycin plus concomitant nephrotoxic agents occurred on the first day of vancomycin therapy. Most studies report vancomycin-associated nephrotoxicity generally occurring after several days of receipt of drug and the relationship between vancomycin serum concentrations, the presence of other nephrotoxic drugs and incidence of nephrotoxicity remains unclear but suggest that other drugs may be important contributors 15,16,17…”

Continuous Versus Intermittent Vancomycin Infusions in Infants: A Randomized Controlled Trial

“…Studies reveal that these current dosing recommendations result in poor attainment of target vancomycin levels. [3][4][5] Another problem with IIV dosing is the incorrect timing of trough samples, resulting in inappropriate dose adjustments. 6 Continuous infusions of vancomycin (CIV) are an attractive alternative to IIV in young infants.…”