ring being responsible for most of these effects by stearic hindrance of access of the drug to the enzymes' active sites. Drugs that resist the action of staphylococcal P-lactamase do so by possession of an acyl side-chain. The drugs do have activity against other bacteria for which penicillin is indicated, but benzylpenicillin is substantially more active against these organisms — up to 20 times more so in the cases of pneumococci, P-haemolytic streptococci and Neisseria. Hence, when infection is mixed, it may be preferable to give benzylpenicillin as well as a p-lactamase-resistant drug in severe cases.

Examples of these agents include:

Flucloxacillin (t|/2 1 h) is better absorbed and so gives higher blood concentrations than does cloxa-cillin. It may cause cholestatic jaundice, particularly when used for more than 2 weeks or to patients > 55 years.

Cloxacillin (1% 0.5 h) resists degradation by gastric acid and is absorbed from the gut, but food markedly interferes with absorption. Recently it has been withdrawn from the market in some countries, including the UK.

Methicillin and oxacillin: their use is now confined to laboratory sensitivity tests. Identification of methicillin-resistant Staphylococcus aureus (MRSA) in patients indicates the organisms are resistant to flucloxacillin and cloxacillin, all other P-lactam antibiotics and often to other antibacterial drugs, and demands special infection-control measures.

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