Oral amoxicillin/clavulanic acid in newborns: do we reach target levels?
Author(s): ,
René Kornelisse
Affiliations:
Erasmus MC- Sophia Children's Hospital
,
Nico Hartwig
Affiliations:
Franciscus Gasthuis & Vlietland
,
Jacqueline van der Sluijs
Affiliations:
Maxima Medical Center
,
Arianne van Driel
Affiliations:
IJsselland Hospital
,
Sandra Kenter
Affiliations:
Franciscus Gasthuis & Vlietland
,
Jojanneke Heidema
Affiliations:
Antonius Hospital
,
Paul den Butter
Affiliations:
Ikazia Hospital
,
Birgit Koch
Affiliations:
Erasmus Medical Center
,
Irwin Reiss
Affiliations:
Erasmus MC-Sophia Children's Hospital
,
Karel Allegaert
Affiliations:
Erasmus MC-Sophia Children's Hospital
Gerdien Tramper-Stranders
Affiliations:
Franciscus Gasthuis & Vlietland
ESPID Education. Keij F. May 8, 2019; 263088 Disclosure(s): -
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Abstract
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Background
Oral antibiotic use is scarce in neonates due to pharmacokinetic uncertainties in the first weeks of life. Amoxicillin/clavulanic acid covers most causative pathogens of early-onset neonatal sepsis, eg. group B streptococci (GBS) and E. coli. Efficacy of amoxicillin depends on time above MIC; for clavulanic acid the area under the curve (AUC) and peak concentration are used. It has a good bio-availability in children and adults, but evidence in neonates is lacking. We evaluated the pharmacokinetics of oral amoxicillin/clavulanic acid in term newborns (0-28 days of age).

Methods
This study is part of a multicenter RCT evaluating the non-inferiority of neonatal intravenous-to-oral switch therapy in probable bacterial infection. Pharmacokinetic analysis was performed in patients allocated to the switch group. After 48 hours of intravenous penicillin/gentamicin, they switched to amoxicillin/clavulanic acid suspension (25/6.25 mg/kg tid). Two bloodsamples from different dosing intervals were obtained and directly stored at -80°C. Analysis was performed batchwise using Liquid Chromatography and Mass Spectrometry. For amoxicillin, an MIC of 8 mg/L for ≥50% of time was considered appropriate. Unfortunately, for clavulanic acid, a target is currently lacking.

Results
Samples of the first 15 patients have been analysed. Patients switched to oral therapy on average after 2.5 days. Amoxicillin levels were all above MIC of GBS (0.25 mg/L) and E. coli (8 mg/L); range: 9.10-30.6 mg/L. Clavulanic acid was absorbed in all patients but a great variance in serum level was observed (range: 0.26-4.82 mg/L), as showed in figure 1.

Conclusions
Oral amoxicillin is well absorbed in newborns leading to adequate serum levels. Clavulanic acid is absorbed as well, but great variance is seen in through levels. Data on peak levels and AUC will follow soon.


Trial Registration
This trial has been registered in Clinicaltrials.gov Trial number NCT03247920
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