Penetration of β-lactamase inhibitors into the periplasm of Gram-negative bacteria

Abstract

The effectiveness of a β-lactamase inhibitor/β-lactam combination against Gram-neg. pathogens depends on many interplaying factors, one of which is the penetration of the inhibitor across the outer membrane. In this work we have measured the relative penetrations of clavulanic acid, sulbactam, tazobactam and BRL 42715 into two strains of Escherichia coli producing TEM-1 β-lactamase, two strains of Klebsiella pneumoniae producing either TEM-1 or K-1, and two strains of Enterobacter cloacae each producing a Class C β-lactamase. It was shown that clavulanic acid penetrated the outer membranes of all these strains more readily than the other β-lactamase inhibitors. For the strains of E. coli and K. pneumoniae clavulanic acid penetrated approx. 6 to 19 times more effectively than tazobactam, 2 to 9 times more effectively than sulbactam and 4 to 25 times more effectively than BRL 42715. The superior penetration of clavulanic acid obsd. in this study is likely to contribute to the efficacy of clavulanic acid/β-lactam combinations in combating β-lactam resistant bacterial pathogens. [on SciFinder(R)]