COMBINATION BETA-LACTAM AND BETA-LACTAMASE-INHIBITOR PRODUCTS - ANTIMICROBIAL ACTIVITY AND EFFICIENCY OF ENZYME-INHIBITION

Classification schemes for gram-negative beta-lactamases are presented , mechanisms by which beta-lactamases inactivate beta-lactam antibioti cs are reviewed, and methods for assessing the efficiency of beta-lact amase inhibitors are evaluated. Beta-lactamases are commonly produced by Staphylococcus species, the Enterobacteriaceae, Pseudomonas aerugin osa, Acinetobacter spe species, and some anaerobes. Currently availabl e beta-lactamase inhibitors are thought to be ''suicide inhibitors'' t hat form stable complexes between the bacterial beta-lactamase and the beta-lactamase inhibitor in a multistep chemical reaction. Each step can be quantitated; however, the overall process is difficult to measu re. Thus, a comparative evaluation of commercially available beta-lact amase inhibitors is extremely difficult and must be done under standar dized test conditions. In general, sulbactam, clavulanate, and tazobac tam are all potent inhibitors of staphylococcal penicillinase; chromos omal beta-lactamases produced by Bacteroides species, Proteus vulgaris , Haemophilus influenzae, Neisseria gonorrhoeae; and type IV enzymes o f Klebsiella species. Although sulbactam possesses activity against TE M-1 and TEM-2 beta-lactamases, it does not have reliable activity agai nst SHV-1 beta-lactamases. Clavulanate and tazobactam are potent inhib itors of both TEM and SHV-1 beta-lactamases. P. aeruginosa and some En terobacteriaceae produce an inducible, extremely potent, broad-spectru m enzyme (type I beta-lactamase). Tazobactam is the only currently ava ilable beta-lactamase inhibitor with activity against type I beta-lact amases; however, some enzymes are not inhibited by tazobactam.