Nomogram based on actual body weight for estimation of vancomycin maintenance dose in infants

Abstract

Background: Vancomycin is the first-choice antibiotic for infants with β-lactam-resistant gram-positive bacterial infection. Despite long experience of prescribing of this drug optimal dosing is still challenging. This study aimed at investigating variables predicting vancomycin clearance in order to propose optimal maintenance dosing in infants treated for suspected or culture-proven sepsis.

Methods: Vancomycin pharmacokinetics was calculated in a one-compartmental model based on serum concentrations. A linear regression model was used to explore relationships between vancomycin clearance and expected covariates.

Results: Twenty-two patients were enrolled into the study. Median (IQR) postnatal age was 157 (112–238) days. The median (IQR) volume of distribution and clearance for vancomycin were 0.50 (0.39–0.94) L/kg and 0.112 (0.095–0.133) L/h/kg, respectively. Vancomycin clearance was associated with actual body weight, height, body surface area, gestational age, postnatal age, postmenstrual age and estimate glomerular filtration rate. Actual body weight was the best predictive variable for vancomycin clearance. Daily maintenance dose (mg) calculated as 76.28 × actual body weight (kg) – 41.57 most closely approximated optimal dosing based on individual pharmacokinetics. This relationship was used to construct a dosing nomogram.

Conclusions: We developed an easy-to-use dosing nomogram for maintaining a vancomycin average steady-state concentration of 22.5 mg/L based on actual body weight.

Keywords:

• Vancomycin
• pharmacokinetics
• infants
• therapeutic drug monitoring
• actual body weight

Acknowledgements

We are grateful to prof. Dick Tibboel and prof. Karel Allegaert for conceptual advice.

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This study was supported by the Charles University under grant Progress Q25 and SVV 260373, the Ministry of Health of the Czech Republic under grant MH CZ-DRO–VFN64165, and an unrestricted research grant from the Intensive Care of the ErasmusMC-Sophia Children’s Hospital.