PENETRATION OF AMOXICILLIN-CLAVULANIC ACID INTO BRONCHIAL-MUCOSA WITHDIFFERENT DOSING REGIMENS

Background - The efficacy of an antibiotic is related to its concentra tion at the site of infection. Previous studies of the concentrations of amoxycillin and clavulanic acid (co-amoxiclav) in respiratory secre tions or whole lung tissue have suffered from methodological problems. The concentration of amoxycillin and clavulanic acid was determined i n bronchial mucosal biopsy samples obtained at bronchoscopy following five different dosing regimens. Methods - Bronchial biopsy and serum s amples were obtained from 50 patients undergoing diagnostic bronchosco py. Ten patients each received 375 mg, 625 mg, 750 mg, and 3.25 g oral , and 1.2 g intravenous co-amoxiclav 1-3 hours before bronchoscopy. Th e concentrations of clavulanic acid and amoxycillin were determined by high performance liquid chromatography using a microbore column, soli d phase extraction, and preconcentration to improve sensitivity tenfol d over previous methods. Results - Concentrations of both clavulanic a cid and amoxycillin in bronchial mucosa were dose related and were wel l above the MIC,, of co-amoxiclav for the common bacterial respiratory pathogens including Haemophilus influenzae, Micrococcus catarrhalis a nd Streptococcus pneumoniae for ah dosing regimens. Mean mucosal level s were 200% and 118% of the corresponding serum levels for amoxycillin and clavulanic acid respectively. Conclusions - Amoxycillin and clavu lanic acid are concentrated in bronchial mucosa and, even at the lowes t dose of 375 mg orally, are Likely to produce tissue levels in the lu ng sufficient to inhibit all the common community acquired respiratory pathogens.