Dosing of amoxicillin/clavulanate for treatment of lower respiratory tract infection.

Abstract

SIR-Calver et al. [1] reported that a dosing interval of 12 hours is as effective as an interval of 8 hours for patients receiving amoxicillin/clavulanate. We have several concerns about the appropriateness of this study. The inclusion criteria for patients with acute exacerbations of chronic bronchitis were based only on an increase in the quantity and/or purulence of sputum, and no attempt was made to determine the severity of the exacerbation. To make it possible to detect differences in efficacy between treatments, it is mandatory that patients satisfy entry criteria including disease of sufficient severity, e.g., increased dyspnea, fever, leukocytosis, or bronchiectasis; a history of frequent exacerbation; or coexistent cardiopulmonary diseases [2, 3]. Nowadays, the nonspecific inflammatory response in exacerbations of chronic bronchitis is considered most prominent in the pathogenesis, and the role of infection seems to be limited in many cases. The question regarding the use of antibiotics for acute exacerbations of chronic bronchitis has still not been fully answered, but more than half of the placebo treatments may be successful [3]. Therefore, it would have been useful if Calver et al. [1] had included a placebo group in the study design. The fact that only 22% of the patients were evaluable for bacteriologic efficacy underscores the need for more detailed information on the reasons for acute exacerbations of bronchitis [4]. Calver et al. [1] made no attempt to detect viral or atypical pathogens as causes of infection. Furthermore, data on concomitant treatments and measures to improve patients' conditions are lacking in their study. As mentioned by the authors, bacterial killing by /-lactam antimicrobials is related to the duration of time that the plasma concentration of the /-lactam antimicrobial remains above the MIC for the organism. In light of this fact, we doubt whether it makes sense to increase the dose, and hence the peak plasma concentration, and to reduce the dosing frequency. The question as to why the amount of clavulanic acid per dose is not increased remains unanswered. As recently stated by Wilson et al. [2], the continued performance of studies of chronic bronchitis, largely for the purpose of new product registration and licensing, is unlikely to be valuable in assessing the role of antibiotics in the management of acute exacerbation of chronic bronchitis.