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Comparison of adherence between twice- and thrice-daily regimens of oral amoxicillin/clavulanic acid


  • Conflict of interest statement: The MEMS containers were provided through a grant from GlaxoSmithKline. The authors declare that they did not receive any direct economical support for undertaking this study.

Carl Llor, Primary Healthcare Centre Jaume I, c. Felip Pedrell, 45-47, 43005 Tarragona, Spain. Email:


Background and objective:  Few studies have analysed adherence with antibiotic treatment in patients with respiratory tract infections. The aim of this study was to compare the compliance of patients taking a pharmacokinetically enhanced formulation of amoxicillin/clavulanic acid twice daily with that of patients taking the standard formulation thrice daily.

Methods:  Patients with suspected bacterial lower respiratory tract infections, pharyngitis and dental infections were included. Adherence was assessed by electronic monitoring, which recorded every opening of the patient's bottle of pills. The outcome variables were compliance with taking the medication, taking the correct dose and with timing of the dose.

Results:  A total of 240 patients were enrolled (167 in the thrice-daily group and 73 in the twice-daily group). The percentage of doses taken was greater with the twice-daily regimen (84.5 ± 22.8%) than with the thrice-daily regimen (72.7 ± 20.1%; P < 0.001). Forty patients in the twice-daily group opened the container every 12 ± 6 h during at least 80% of the course (54.8%), while only 19.6% of the patients assigned to the thrice-daily formulation did so every 8 ± 4 h (P < 0.001). The percentage of patients who opened the container a satisfactory number of times per day was significantly higher among those taking the twice-daily regimen on days three, four, five, six and seven. Moreover, the thrice-daily group more frequently forgot to take the afternoon dose.

Conclusions:  The rate of compliance with amoxicillin/clavulanic acid therapy was very low. However, compliance with the new formulation that is taken twice-daily was significantly better.

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