Sinus tissue pharmacokinetics after oral administration of amoxicillin/clavulanic acid

Abstract

Objectives: The in vitro synergy of the amoxicillin/clavulanic acid combination has not always translated in vivo into clinical superiority compared with 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 inadequate target tissue pharmacokinetics. To explore this possibility in the sinuses, we undertook the present investigation. Study Design: A randomized, open, single-dose, sinus tissue pharmacokinetic study with oral amoxicillin/clavulanic acid. Methods: Twenty-three adult patients with chronic rhinosinusitis who had been selected for surgery were randomly allocated to receive a tablet of 875/125 mg amoxicillin/clavulanate 2 to 4 hours before surgery began. During the operation tissue samples were collected at specific sinonasal sites for determination of both amoxicillin and clavulanic acid concentration levels. Results: Amoxicillin displayed adequate tissue levels throughout the sinuses, high enough to cover common susceptible pathogens. However, the presence of clavulanate was detected in only half of the sinonasal tissue samples. Conclusions: The kinetics of oral clavulanic acid apparently fails to provide a widespread anti-β-lactamase activity capable of enhancing the activity of amoxicillin in all parts of the sinuses. Despite this, amoxicillin/clavulanic acid maintains a central role in the treatment of acute rhinosinusitis, because amoxicillin is still the most effective oral β-lactam against Streptococcus pneumoniae, a particularly virulent and increasingly resistant upper respiratory tract pathogen. Also, as our data show, a concomitant anti-β-lactamase activity can be expected to occur, although in an unpredictable fashion.