Intermittent Vancomycin Infusion Subtherapeutic Compared With Continuous Dosing

Continuous infusion of vancomycin as opposed to intermittent infusions of vancomycin was associated with earlier and improved attainment of target concentrations in infants, according to data from a randomized control trial published in Pediatrics.

This multicenter trial was conducted in 2 tertiary neonatal units over a 40-month period.  A total of 111 infants aged 0 to 90 days who required vancomycin treatment were randomly assigned to either continuous or intermittent infusion of vancomycin. A total of 104 were included in the intention-to-treat analysis.

Compared with infants who received intermittent infusions, the percentage of infants who achieved target concentrations at the first steady-state level was higher in recipients of continuous infusion (85% vs 41%; P <.001). The infants in the continuous-infusion group also required fewer dose adjustments, with the median being 0 (range 0 -1) compared with a median of 1 (range 0-3; P <.001) in participants in the intermittent-infusion group. The mean time to target concentration in the continuous-infusion group was 27.1 hours, but was 33.6 hours in participants in the intermittent-infusion group (P =.003). In addition, after the initial trough level, 12% of infants in the intermittent-infusion group had subtherapeutic troughs, whereas this occurred in 9% of infants in the continuous-infusion group. No drug-related adverse events were reported in either group, but the mean daily dose required to achieve target concentrations was lower using continuous infusion of vancomycin compared with intermittent infusions (40.6 mg/kg per day [standard deviation 10.7 mg/kg per day] vs 60.6 mg/kg per day [standard deviation 53.0 mg/kg per day]; P =.01).

Investigators noted that as this was the first randomized controlled trial of vancomycin dosing in infants, they were unable to recruit sufficient sample sizes to assess a difference in vancomycin-related nephrotoxicity or infection-related mortality. The trial also did not analyze the costs of continuous vs intermittent infusion of vancomycin, but evidence from trials in adults suggest a significant reduction in costs with continuous infusion. Investigators also noted that audiology assessments were not done because “the ototoxicity of vancomycin is controversial, particularly in a population of premature infants receiving concomitant aminoglycosides.” However, area under the curve to minimum inhibitory concentration ratios were calculated and will be reported separately.

The results of this randomized controlled trial demonstrated that in young infants continuous infusion of vancomycin was associated with earlier and improved attainment of target concentrations, compared with intermittent infusions of the antibiotic. In addition, continuous infusion was associated with lower daily doses and fewer required adjustments. Investigators suggested that future work is needed with focus on the effect of continuous infusion vs intermittent infusions of vancomycin on the clinical outcomes of gram positive infections in infants.

Reference

Gwee A, Cranswick N, McMullan B, et al. Continuous versus intermittent vancomycin infusions in infants: A randomized controlled trial [published online January 30 2019]. Pediatrics. doi:10.1542/peds.2018-2179