Individualized vancomycin dosing in infants: prospective evaluation of an online dose calculator

Amanda L Wilkins; Tony Lai; Xiao Zhu; Srinivas Bolisetty; Roberto Chiletti; Noel Cranswick; Kaya Gardiner; Rodney Hunt; Atul Malhotra; Brendan McMullan; Bhavesh Mehta; Joanna Michalowski; Himanshu Popat; Meredith Ward; Stephen Duffull; Nigel Curtis; Amanda Gwee

doi:10.1016/j.ijantimicag.2023.106728

Individualized vancomycin dosing in infants: prospective evaluation of an online dose calculator

Int J Antimicrob Agents. 2023 Mar;61(3):106728. doi: 10.1016/j.ijantimicag.2023.106728. Epub 2023 Jan 16.

Authors

Amanda L Wilkins¹, Tony Lai², Xiao Zhu³, Srinivas Bolisetty⁴, Roberto Chiletti⁵, Noel Cranswick⁶, Kaya Gardiner⁷, Rodney Hunt⁸, Atul Malhotra⁹, Brendan McMullan¹⁰, Bhavesh Mehta¹¹, Joanna Michalowski⁴, Himanshu Popat¹², Meredith Ward¹³, Stephen Duffull¹⁴, Nigel Curtis¹⁵, Amanda Gwee¹⁵

Affiliations

¹ Department of General Medicine, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia. Electronic address: Amanda.wilkins@rch.org.au.
² Pharmacy Department, The Children's Hospital at Westmead, Westmead, New South Wales, Australia; School of Pharmacy, The University of Sydney, New South Wales, Australia.
³ Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai, China.
⁴ Department of Newborn Care, Royal Hospital for Women, Randwick, New South Wales, Australia.
⁵ Department of Intensive Care, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia; Paediatric Intensive Care Research Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Department of Critical Care, The University of Melbourne, Melbourne, Victoria, Australia.
⁶ Department of General Medicine, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Clinical Pharmacology Unit, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia; Melbourne Children's Trials Centre, Murdoch Children's Research Institution, Parkville, Victoria, Australia.
⁷ Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Research Operations, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.
⁸ Monash Newborn, Monash Children's Hospital, Clayton, Victoria, Australia; Department of Paediatrics, Monash University, Clayton, Victoria, Australia; Clinical Sciences Theme, Murdoch Children's Research Institution, Parkville, Victoria, Australia.
⁹ Monash Newborn, Monash Children's Hospital, Clayton, Victoria, Australia; Department of Paediatrics, Monash University, Clayton, Victoria, Australia.
¹⁰ Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia; Department of Immunology and Infectious Disease, Sydney Children's Hospital, Randwick, New South Wales, Australia.
¹¹ Grace Centre for Newborn Intensive Care, The Children's Hospital at Westmead, Westmead, New South Wales, Australia; Discipline of Paediatrics & Child Health, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
¹² Grace Centre for Newborn Intensive Care, The Children's Hospital at Westmead, Westmead, New South Wales, Australia; NHMRC Clinical Trial Centre, Camperdown, New South Wales, Australia; Sydney Children's Hospital Westmead Clinical School, The University of Sydney, New South Wales Australia.
¹³ Department of Newborn Care, Royal Hospital for Women, Randwick, New South Wales, Australia; School of Women's and Children's Health, University of New South Wales, Randwick, New South Wales, Australia.
¹⁴ School of Pharmacy, University of Otago, Dunedin, New Zealand.
¹⁵ Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia; Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Infectious Diseases, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.

PMID: 36657532
DOI: 10.1016/j.ijantimicag.2023.106728

Abstract

Background: Empiric vancomycin dosing regimens fail to achieve recommended target trough concentrations of 10-20 mg/L in the majority of infants. This study assessed the performance of a model-based dosing calculator (Vanc App) in achieving target vancomycin concentrations at first steady-state level.

Methods: This was a multicenter prospective study in four tertiary pediatric hospitals over an 18-month period. Infants aged 0-90 days with suspected Gram-positive sepsis requiring empiric vancomycin treatment were included if they did not meet any of the exclusion criteria: post-menstrual age (PMA) <25 weeks, weight <500 g, glycopeptide allergy, receiving extracorporeal membrane oxygenation, vancomycin use within the previous 72 h, and renal impairment. The Vanc App used a published population pharmacokinetic model to generate a dose based on the infant's PMA, weight, creatinine, and target vancomycin concentration.

Results: A total of 40 infants were included; 40% were female, median (range) weight was 2505 (700-4460) g and median (range) PMA was 37.4 (25.7-49.0) weeks. The median (range) vancomycin dose was 45 (24-79) mg/kg/day. All infants had trough vancomycin concentrations measured at steady-state (24-<48 hours) and 30 (75%) infants achieved target concentrations. Five infants had supratherapeutic (median 25, range 21-38 mg/L) and five had subtherapeutic (median 6, range <5-9 mg/L) concentrations. An area under the concentration-time curve (AUC_0-24) of 400-650 mg/L.h was achieved in 33 (83%) infants. There were no infusion-related reactions or nephrotoxicity.

Conclusion: Individualized intermittent vancomycin dosing using a model-based online calculator resulted in 75% and 83% of infants achieving target trough and AUC_0-24, respectively, at first steady-state level. There were no vancomycin-related nephrotoxicity or infusion-related reactions.

Keywords: individualized dosing; infants; neonates; pharmacokinetics; vancomycin.

Publication types

Multicenter Study

MeSH terms

Anti-Bacterial Agents / therapeutic use
Child
Female
Gram-Positive Bacterial Infections* / drug therapy
Humans
Infant
Male
Prospective Studies
Renal Insufficiency*
Retrospective Studies
Vancomycin / therapeutic use

Substances

Vancomycin
Anti-Bacterial Agents