Serum amoxicillin levels in young infants (0-59 days) with sepsis treated with oral amoxicillin

Arch Dis Child. 2020 Dec;105(12):1208-1214. doi: 10.1136/archdischild-2019-317342. Epub 2020 May 13.


Background: WHO recommends simplified antibiotics for young infants with sepsis in countries where hospitalisation is not feasible. Amoxicillin provides safe, Gram-positive coverage. This study was done to determine pharmacokinetics, drug disposition and interpopulation variability of oral amoxicillin in this demographic.

Methods: Young infants with signs of sepsis enrolled in an oral amoxicillin/intramuscular gentamicin treatment arm of a sepsis trial in Karachi, Pakistan, were studied. Limited pharmacokinetic (PK) sampling was performed at 0, 2-3 and 6-8 hours following an index dose of oral amoxicillin. Plasma concentrations were determined by high-performance liquid chromatography/mass spectrometry. Values of ≥2 mg/L were considered as the effect threshold, given the regional minimal inhibitory concentration (MIC) of resistant Streptococcus pneumoniae. RESULTS: Amoxicillin concentrations were determined in 129 samples from 60 young infants. Six of 44 infants had positive blood cultures with predominant Gram-positive organisms. Forty-four infants contributing blood at ≥2 of 3 specified timepoints were included in the analysis. Mean amoxicillin levels at 2-3 hours (11.6±9.5 mg/L, n=44) and 6-8 hours (16.4±9.3 mg/L, n=20) following the index dose exceeded the MIC for amoxicillin (2.0 mg/L) against resistant S. pneumoniae strains. Of 20 infants with three serum levels, 7 showed a classic dose-exposure profile and 13 showed increasing concentrations with time, implying delayed absorption or excretion.

Conclusion: Amoxicillin concentrations in sera of young infants following oral administration at 75-100 mg/kg/day daily divided doses exceeds the susceptibility breakpoint for >50% of a 12-hour dosing interval.Oral amoxicillin may hold potential as a safe replacement of parenteral ampicillin in newborn sepsis regimens, including aminoglycosides, where hospitalisation is not feasible.

Trial registration number: NCT01027429.

Keywords: SATT Pakistan; oral amoxicillin; population pharmacokinetics; young infants.

MeSH terms

  • Administration, Oral
  • Amoxicillin / administration & dosage
  • Amoxicillin / blood*
  • Amoxicillin / pharmacokinetics*
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / blood*
  • Anti-Bacterial Agents / pharmacokinetics*
  • Drug Therapy, Combination
  • Female
  • Gentamicins / administration & dosage
  • Humans
  • Infant
  • Infant, Newborn
  • Injections, Intramuscular
  • Male
  • Microbial Sensitivity Tests
  • Sepsis / drug therapy*
  • Streptococcus pneumoniae / drug effects
  • Time Factors


  • Anti-Bacterial Agents
  • Gentamicins
  • Amoxicillin

Associated data