Pharmacokinetic/pharmacodynamic evaluation of amoxicillin, amoxicillin/clavulanate and ceftriaxone in the treatment of paediatric acute otitis media in Spain.

Abstract

INTRODUCTION:

Acute otitis media is the most common respiratory tract infection in infancy and early childhood that is managed with antimicrobial agents. Ninety-three per cent of the cases diagnosed in Spain are treated with antibiotics, and Streptococcus pneumoniae and untypeable Haemophilus influenzae are the most frequently isolated pathogens. The aim of this work was to evaluate the usefulness of amoxicillin, amoxicillin/clavulanate and ceftriaxone for the empirical treatment of acute otitis media, looking at the pharmacokinetic variability and the antimicrobial susceptibility of paediatric strains of the two main pathogens responsible for AOM in Spain, Streptococcus pneumoniae and Haemophilus influenzae.

METHODS:

Free-drug plasma concentrations were simulated and the probability of target attainment at each minimum inhibitory concentration and the cumulative fraction of response (CFR) were determined. Microbiological susceptibility information was extracted from SAUCE 3 surveillance.

RESULTS:

CFR with amoxicillin varied from 83% to 96% against S. pneumoniae and from 78% to 86% against H. influenzae. CFR was always >85% with amoxicillin/clavulanate. With the 3-day ceftriaxone regimen, the probability of achieving free concentrations above MIC at 72 hours significantly increased compared to the single dose, with which CFR ranged from 70% to 84%.

CONCLUSIONS:

High-dose amoxicillin (at least 80 mg/kg/day) should be the first-line therapy in uncomplicated infections, whereas amoxicillin/clavulanate (40 mg/kg/day) should be the choice when additional coverage for H. influenzae is desired. Administration of 3 daily doses of ceftriaxone increases bacteriological eradication probability when compared with one-day regimen, although additional clinical evaluations are necessary to establish the best target attainment with ceftriaxone.

• Authors: Arantxazu Isla, Iñaki F Trocóniz, Andrés Canut, Alicia Labora, José Emilio Martín-Herrero, José Luis Pedraz, Alicia R Gascón
• Journal: Enfermedades infecciosas y microbiologia clinica (Enferm Infecc Microbiol Clin) Vol. 29 Issue 3 Pg. 167-73 (Mar 2011) ISSN: 1578-1852 [Electronic] Spain
• PMID: 21334779 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright © 2009 Elsevier España, S.L. All rights reserved.

Chemical References

• Amoxicillin-Potassium Clavulanate Combination
• Ceftriaxone
• Amoxicillin

Topics

• Amoxicillin (blood, pharmacokinetics, pharmacology, therapeutic use)
• Amoxicillin-Potassium Clavulanate Combination (blood, pharmacokinetics, pharmacology, therapeutic use)
• Ceftriaxone (blood, pharmacokinetics, pharmacology, therapeutic use)
• Child
• Computer Simulation
• Dose-Response Relationship, Drug
• Haemophilus Infections (drug therapy, microbiology)
• Haemophilus influenzae (drug effects, enzymology, isolation & purification)
• Humans
• Microbial Sensitivity Tests
• Monte Carlo Method
• Otitis Media (drug therapy)
• Pneumococcal Infections (drug therapy, microbiology)
• Streptococcus pneumoniae (drug effects, enzymology, isolation & purification)
• beta-Lactam Resistance