Sinus tissue pharmacokinetics after oral administration of amoxicillin/clavulanic acid

Objectives: The in vitro synergy of the amoxicillin/clavulanic acid combina tion has not always translated in vivo into clinical superiority compared w ith amoxicillin alone. Specifically, conflicting reports have disputed the superiority of the combination in the treatment of both acute otitis media and acute sinusitis. One possible reason for this may have to do with inade quate target tissue pharmacokinetics. To explore this possibility in the si nuses, we undertook the present investigation, Study Design: A randomized, open, single-dose, sinus tissue pharmacokinetic study with oral amoxcillin/ clavulanic acid. Methods: Twenty-three adult patients with chronic rhinosin usitis who had been selected for surgery were randomly allocated to receive a tablet of 875/125 mg amoxicillin/ clavulanate 2 to 4 hours before surger y began. During the operation tissue samples were collected at specific sin onasal sites for determination of both amoxicillin and clavulanic acid conc entration levels. Results: Amoxicillin displayed adequate tissue levels thr oughout the sinuses, high enough to cover common susceptible pathogens. How ever, the presence of clavulanate was detected in only half of the sinonasa l tissue samples, Conclusions: The kinetics of oral clavulanic acid apparen tly fails to provide a widespread anti-beta-lactamase activity capable of e nhancing the activity of amoxicillin in all parts of the sinuses. Despite t his, amoxicillin/clavulanic acid maintains a central role in the treatment of acute rhinosinusitis, because amoxicillin is still the most effective or al beta-lactam against Streptococcus pneumoniae, a particularly virulent an d increasingly resistant upper respiratory tract pathogen, Also, as our dat a show, a concomitant anti-beta-lactamase activity can be expected to occur , although in an unpredictable fashion.