Amoxicillin-Clavulanate Dosing in Newborns
For newborns (neonates less than 3 months of age), amoxicillin-clavulanate is dosed at 30 mg/kg/day of the amoxicillin component divided every 12 hours, based on incompletely developed renal function affecting drug elimination in this age group. 1
Age-Specific Dosing Algorithm
Neonates and Infants ≤3 Months (≤12 weeks)
The maximum recommended dose is 30 mg/kg/day of amoxicillin divided every 12 hours (15 mg/kg/dose every 12 hours) due to immature renal function in this age group 1
For oral suspension dosing in neonates, use the 125 mg/5 mL concentration and calculate the volume based on 15 mg/kg per dose given every 12 hours 1
Treatment duration should be a minimum of 48-72 hours beyond clinical improvement or evidence of bacterial eradication 1
Gestational Age and Postnatal Age Considerations
While the FDA label provides general guidance for infants under 3 months 1, more nuanced dosing exists based on gestational age:
For preterm neonates with gestational age <30 weeks and postnatal age <14 days: amoxicillin alone (not the combination) at 50 mg/kg/dose IV every 12 hours 2
For preterm neonates with gestational age >34 weeks and postnatal age ≤7 days: amoxicillin alone at 50 mg/kg/dose IV every 12 hours 2
For term neonates with gestational age >34 weeks and postnatal age >7 days: amoxicillin alone at 75 mg/kg/dose IV every 12 hours 2
Critical Clinical Context
Important Limitation for Neonatal Use
Amoxicillin-clavulanate combination is NOT routinely recommended as first-line therapy for neonatal sepsis or serious bacterial infections in the first weeks of life. The standard neonatal sepsis regimen is ampicillin plus gentamicin 2, and the pediatric dosing guidelines primarily address amoxicillin alone rather than the combination product for neonates 2
When Amoxicillin-Clavulanate May Be Considered
For specific indications requiring beta-lactamase coverage (e.g., urinary tract infections with known beta-lactamase producing organisms) in infants approaching 3 months of age 2
The oral formulation at 20-40 mg/kg/day in 3 doses can be used for urinary tract infections in febrile infants 2-24 months 2
Pharmacokinetic Evidence
Research demonstrates that oral amoxicillin achieves adequate serum levels in neonates at 50 mg/kg/day divided every 12 hours, with peak levels of 38-59 mcg/mL and trough levels maintaining therapeutic concentrations 3
A pooled pharmacokinetic study confirmed that 50 mg/kg/day divided twice daily achieves adequate exposure (50% time above MIC of 8 mg/L) for gram-negative coverage in neonates, with 87% oral bioavailability 4
In preterm infants <32 weeks gestational age, 25 mg/kg every 12 hours IV resulted in peak levels of 53.6 mg/L and trough levels of 16.0 mg/L, well above MIC for major neonatal pathogens 5
Common Pitfalls to Avoid
Never use the higher pediatric doses (45-90 mg/kg/day) in neonates under 3 months - this violates FDA labeling and risks toxicity due to immature renal clearance 1
Do not use amoxicillin-clavulanate as empiric therapy for neonatal sepsis - ampicillin plus an aminoglycoside remains the standard of care 2
Verify the suspension concentration before dispensing - the 125 mg/5 mL formulation is appropriate for neonatal dosing calculations 1
Ensure adequate hydration and monitor renal function - clavulanate clearance is dependent on glomerular filtration rate, which is reduced in neonates 5