Variations in amoxicillin pharmacokinetic/pharmacodynamic parameters may explain treatment failures in acute otitis media.
Pharmacokinetic/pharmacodynamic (PK/PD) modeling and Monte Carlo simulations suggest that amoxicillin should rarely fail as therapy for Streptococcus pneumoniae and Haemophilus influenzae acute otitis media (AOM) infections except when the S. pneumoniae are highly penicillin resistant or the H. influenzae are beta-lactamase producing. However, important and not infrequent exceptions to this expectation have been described. The objective of this review was to define the biologic variations in amoxicillin PK/PD parameters for the treatment of AOM in children and assess whether these variations could explain why the commonly employed amoxicillin PK/PD model is imperfect in predicting outcome for every patient in this clinical setting. To this end, a literature search of MEDLINE (1966-2006) and EMBASE (1974-2006) was conducted to identify studies that evaluated ampicillin or amoxicillin intestinal absorption, serum concentrations, and/or middle ear fluid (MEF) concentrations. Analysis of studies identified for review showed that the intestinal bioavailability of amoxicillin depends on passive diffusion and a saturable 'pump' mechanism that produces variable serum concentrations of the antibacterial agent. Indeed, substantial differences from patient to patient in serum (5- to 30-fold) and MEF (up to 20-fold) concentrations of amoxicillin occur following oral administration, and 15-35% of children have no detectable amoxicillin in MEF. These findings suggest that variability in PK/PD parameters may impact amoxicillin concentrations in serum and MEF, possibly explaining some AOM treatment failures.
Pichichero
Michael E
ME
Rochester General Research Institute, Legacy Pediatric Group, Rochester, New York, USA. Michael.Pichichero@rochestergeneral.org
Reed
Michael D
MD
D000208:Acute Disease; D000658:Amoxicillin / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002648:Child; D006801:Humans; D010033:Otitis Media / Q000188:drug therapy*; D017211:Treatment Failure
D000890:Anti-Infective Agents; D000658:Amoxicillin