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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

beta-Lactamase types amongst Staphylococcus aureus isolates in relation to susceptibility to beta-lactamase inhibitor combinations.

Relationships between beta-lactamase type and antimicrobial susceptibility were investigated for Staphylococcus aureus isolates collected recently at UK and Irish hospitals, and for reference producers of types A, B, C and D enzymes. Producers of types A and C beta-lactamases predominated amongst the isolates. Tazobactam and clavulanate combinations were studied, as previous observation showed that these inhibitors incompletely reversed the in-vitro amoxycillin and piperacillin resistance of beta-lactamase-positive staphylococci. Further penicillins and cephalosporins served as controls. Organisms with type C beta-lactamase were less susceptible than those with type A enzyme to piperacillin/tazobactam and amoxycillin/tazobactam in disc and MIC tests, and to co-amoxiclav in disc tests only. Conversely, producers of type A enzyme were less susceptible to cephazolin than those with type C enzyme. Kinetic assays showed that type A enzymes bound piperacillin and amoxycillin less tightly than did type C enzyme (higher Kmapp), and were more susceptible to inhibition by clavulanate and tazobactam (lower I50s). However, the susceptibility to beta-lactamase inhibitor combinations for the few producers of types B and D enzymes tested could not be similarly explained by Kmapp and I50 data. It therefore seems that other factors besides beta-lactamase affinity co-determine the susceptibility of the staphylococci. Possible variables include the exact chemistry of the enzyme-inhibitor interaction, and the degree of beta-lactamase induction. Both tazobactam and clavulanate induced staphylococcal types A and C penicillinases.[1]


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