Beta-lactamase inhibition by acetylmethylene penicillanic acid compared to that of clavulanate and sulbactam.

The beta-lactamase inhibitory properties of 6-acetylmethylene penicillanic acid (6-AMPA) were investigated and compared with those of other beta-lactamase inhibitors. 6-AMPA inhibited the TEM-1, TEM-2, SHV-1, PSE-1, PSE-2, PSE-3, PSE-4, OXA-2, OXA-3, and Staphylococcus aureus beta-lactamases. It also inhibited the chromosomally-mediated beta-lactamases of the Richmond-Sykes type Ia, Ic and Id type and the type IV Klebsiella enzymes. Beta-lactamases of Branhamella catarrhalis and Bacteroides fragilis were inhibited. The 6-AMPA I50 values for various enzymes were less than 0.01 microgram/ml TEM-1 and PSE-4, and 0.01 microgram/ml SHV-1, 0.02 microgram/ml S. aureus, 0.04 microgram/ml Proteus vulgaris, 0.04 microgram/ml K. oxytoca, 6.8 micrograms/ml P99, and 9.7 micrograms/ml Sabath-Abraham Pseudomonas enzyme. With isolated beta-lactamases 6-AMPA was a more potent inhibitor than clavulanate or sulbactam. 6-AMPA was an irreversible inhibitor of beta-lactamases. The penetration index for Escherichia coli JT4 was 23 compared to 3 for clavulanate. 6-AMPA at 10 micrograms/ml acted synergistically with ampicillin against beta-lactamase containing bacteria, but it was less active than clavulanate and did not act synergistically with ampicillin against Enterobacter, Citrobacter or Pseudomonas. Although 6-AMPA has excellent beta-lactamase inhibitory properties with isolated enzymes, it is less useful with intact organisms.