Vancomycin therapeutic drug monitoring in the NICU - methods, targets, thoughts?

Hi all,

This is an open request to the community to share your policy about vancomycin therapeutic drug monitoring in your units. I anticipate a lot of variability 🙂

You may follow my structure or write your take freeform.

Indications:

Suspected or proven infection with gram-positive bacteria, usually MRSA. Also as prophylaxis around surgery (often as a single dose).

Dosage:

We currently strive to administer a loading dose of 20 mg/kg (this is a relatively new practice for us, for years our neonatologists refrained from vancomycin loading doses, possibly due to habit/tradition) regardless of infant age and renal function to reach steady state as quickly as possible. According to Jacqz-Aigrain et al., J Antimicrob Chemother, 2019, a loading dose of 25 mg/kg significantly increased the percentage of neonates reaching the target AUC_ss–24 of 400 mg·h/L. We prefer the slightly lower dose of 20 mg/kg.

Following the loading dose we would administer doses of 15 mg/kg if no renal impairment is apparent, and we use NeoVanco to select the most appropriate dosing interval. NeoVanco is a freely available prediction tool developed by Adam Frymoyer, MD (Stanford University - Stanford Children's Health) according to a population pharmacokinetic model developed by Frymoyer A et al. (2014). It is not a 'full' Bayesian calculator, but rather a prediction tool for starting treatment (it is not possible to enter vancomycin serum levels to tailor dosage to the individual infant). It provides the estimated AUC and Ctrough for several dosage regimens, as well as the probability to reach AUC > 400 mg·h/L and Ctrough > 20 mg/L at steady state.

Monitoring:

In infants with no apparent renal impairment, we draw serum levels before the 4th dose. In extremely preterm infants (< 28 GA) or infants with renal impairment, we would draw serum levels before the 2nd dose. The most recent guidelines on vancomycin dosing and monitoring are the Rybak et al. guidelines (2020), which provide recommendations for adults, pediatric and neonatal patients, although most of the neonatal recommendations are based on the pediatric recommendations and it is stated that data are limited in that population.

Dosing adjustment:

Based on serum levels we may adjust the treatment regimen, preferably by adjusting dosing interval and not the dose (to avoid high peaks and troughs), although that may not always be possible/desired (sometimes we would prefer longer intervals to minimize tampering with the IV line to reduce risk of infections). We find the dosing adjustment recommendations of the Australasian Neonatal Medicines Formulary (ANMF) convenient and sensible.

Limitations:

• We do not use a dedicated Bayesian vancomycin calculator (many Bayesian calculators we are aware of require a paid subscription and most do not offer a dedicated PK model for neonates. Additionally, our volume of vancomycin treatments may not justify such an expense), so in essence we still rely on Ctrough, which is not recommended anymore. We hope that the combination with the NeoVanco predictions helps us to avoid toxicity.

• We tried to utilize 1st order PK equations as an alternative to Bayesian calculations, but these require timed measurements and both peak and trough measurements, which complicate monitoring too much.

• We do not implement continuous infusions of vancomycin, even though in certain clinical scenarios it may seem suitable. This is still under debate in the literature.

• Speaking of literature, there are so many papers and texts of vancomycin monitoring in general and in neonates, that it is so easy to get lost and confused about the optimal course of action.

Please share your thoughts and methods for the benefit of the community, thanks!