SULBACTAM AND CLAVULANIC ACID - ENZYME-KINETICS AND SYNERGY WITH AMPICILLIN AND MEZLOCILLIN (REPRINTED FROM IMMUN INFEKT, VOL 15, PG 103, 1987)

The two beta-lactamase inhibitors, sulbactam and clavulanic acid, exhi bit high affinity (K-1 < 10(-6) mol/l) for the beta-lactamases of Gram -negative organisms with predominantly penicillinase activity and much less affinity (especially clavulanic acid) for organisms with predomi nantly cephalosporinase activity. In tests to compare the synergy of t hese beta-lactamase inhibitors with other antibiotics, clavulanic acid and ampicillin or mezlocillin demonstrated greater synergy than sulba ctam and ampicillin or mezlocillin, with isolates forming either a pla smid-coded beta-lactamase or a chromosomal enzyme with predominantly p enicillinase activity. However, neither sulbactam nor clavulanic acid were able to protect ampicillin or mezlocillin adequately against inac tivation by beta-lactamase overproducing variants of Klebsiella pneumo niae or Klebsiella oxytoca, irrespective of the extent of synergy seen with the corresponding wild strains. It was interesting to note the s ynergy between mezlocillin and sulbactam with respect to beta-lactamas e overproducing variants of clinical isolates of Enterobacter cloacae. A statistically significant correlation between the quantities of bet a-lactamase formed and synergy between the beta-lactamase inhibitor an d the antibiotic with which it was combined was not retained in studie s of clinical isolates in any case. These observations correlate well with the results obtained in routine testing of the combinations of am oxycillin/ clavulanic acid and ampicillin/sulbactam.