Inhibition of the beta-lactamases of Branhamella catarrhalis by clavulanic acid and other inhibitors.

The beta-lactamases of Branhamella catarrhalis Ravasio and strain 1908 were readily inhibited by low concentrations of sulbactam, beta-halopenicillanic acids, MM 13902 and clavulanic acid. More detailed studies on the interaction of the Ravasio beta-lactamase with clavulanic acid demonstrated that the enzyme had high affinity for the inhibitor (Ki = 0.07 mumol/L) and was rapidly inhibited (t1/2 = 21 sec, kinhib. = 0.033/sec). Two types of enzyme-inhibitor complex were formed, a transiently stable species (t1/2 = 5.3 minutes at pH 7.3 and 37 degrees C) and a more stable species (t1/2 approximately equal to 2 hours at pH 7.3 and 37 degrees C). Irreversible inactivation of the enzyme was not achieved. Permeability studies on whole cells showed that beta-lactam antibiotics and beta-lactamase inhibitors readily penetrated the outer membrane of B. catarrhalis.