Among the injectable medications administered via a peripheral venous catheter, vancomycin has been reported to irritate the vascular wall, due to its acid (2.8–4.5) pH. The vancomycin concentration of 5 mg/mL that was peripherally administered in our case is widely used in infants or neonates and had not yet been reported to be harmful. However, an in vitro study has demonstrated that 5mg/mL vancomycin induces a loss of viability of 50% of the initial pool of endothelial cells within 24 hours. Vancomycin may therefore damage endothelial cell significantly from a 2.5 mg/mL concentration.[4] A similar delay between administration of vancomycin and apparition of a skin lesion has been reported previously in an adult patient.[3]
It is of current knowledge that vancomycin is preferentially given continuously using a central catheter. In NICU, the central venous catheter is often dedicated to the administration of continuous low-rate medications and the peripheral venous catheter to the administration of intermittent injections. Concerning the injection of vancomycin, the loading dose is preferentially given on central catheter. However, it may be given via peripheral venous catheter when the use of numerous continuous medications and their potential incompatibilities with vancomycin require the use of independent peripheral lines. Otherwise, a peripheral administration of the loading dose of vancomycin will also be preferred if the only available central venous line is used to administer continuous injectable medications with narrow therapeutic ranges to the patient (i.e. insulin, norepinephrine, heparin injection) because of the high risk of increasing harmfully the administration rate of these latter drugs.
The frailty of critically ill newborns increases their risk of exposition to adverse events. Their inflammatory and hypercatabolic state influence the high susceptibility of this population to vancomycin endothelial toxicity. Endothelial toxicity of vancomycin must be considered as skin necrosis can be an entry point to a bacteremia and thus worsen the outcome of the vulnerable preterm newborn infants.
The combination of irritant intravenous drugs administered on a peripheral venous catheter, i.e. furosemide and caffeine in our case, may have enhanced the cumulative endothelial toxicity. If this co-toxicity has not been studied yet, a recent article tested the toxicity on endothelial cells viability when vancomycin was combined with piperacillin-tazobactam, revealing no excess cell death compared with the cell death rate from vancomycin alone.[5]
Finally, evidence suggests that presence of particles in infusion fluid was a major cause of chemical phlebitis,[6] supporting that use of in-line intravenous filters could reduce infusion particles.[7]
To prevent any damaging effect, the administration of vancomycin at a concentration lower than 2.5 mg/mL should be recommended when a central venous catheter is not available for the administration of injectable vancomycin. The combination of irritant injectable drugs administered on a peripheral venous catheter should be avoided even when rinsing is performed after each infusion, to limit the cumulative endothelial toxicity at the venous access point. The use of in-line intravenous filter must be considered for each antibiotic infusion in critically ill infants.