Bacterial resistance to penicillins and cephalosporins

The subject of bacterial resistance to penicillins and cephalosporins could be discussed from a number of points of view and clearly it is not possible in the time available to review adequately every aspect. Some selection is necessary and bearing in mind that the Symposium commemorates the thirtieth anniversary of the introduction of penicillin into medicine it seemed to me that it would be appropriate to consider primarily the changes which have taken place over this period in the incidence of resistance and the knowledge which has been gained concerning the nature of resistance to this family of antibiotics. Before we look at what the changes in resistance have been, however, it may be useful to consider what one means by the word resistant, and in fact one uses the word in two rather different ways. Used in one sense the term applies to those species of bacteria which are characteristically insensitive to penicillin, for example one may say that Pseudomonas aeruginosa is resistant to benzylpenicillin, because this is a characteristic of the species. On the other hand, the term resistant is also applied to particular strains of species of bacteria which are typically penicillin sensitive, or at least were typically sensitive at the time penicillin was first introduced into medicine, for example penicillin-resistant strains of staphylococci and penicillinresistant gonococci. As a result of these two uses of the word resistant some anomalies appear to arise. For example, strains of Escherichia coli inhibited by ampicillin at a concentration of 2 μg/ml would certainly be considered sensitive, whereas strains of gonococci inhibited by one-tenth of this concentration would be regarded as resistant and this is because typical sensitive strains are inhibited by even lower levels. Again, strains of Ps. aeruginosa requiring for inhibition a concentration of gentamicin of 10 μg/ml would be said to be resistant, but strains inhibited by carbenicillin at a level as high as 50 μg/ml are considered sensitive. Here the reason is toxicity: a level of 10 μg/ml of gentamicin could not safely be maintained in the body, whereas a level of 50 μg/ml carbenicillin can. Clearly there are two criteria for judging organisms to be resistant, one is that the concentration of drug required to inhibit growth is a level which cannot readily be achieved at the site of infection and the other is simply that the minimum inhibitory concentration is significantly higher than that of the majority of strains of that particular species. Resistance to penicillins and cephalosporins, as with other antibiotics, may arise in bacteria in one of two ways. Resistance may occur as a result of chromosomal mutation or it may arise as a result of the transfer of genetic information from a resistant bacterial cell to a sensitive cell and this transfer may take place by transformation or by conjugation or by the phage mediated process of transduction. Resistant strains, once they arise, may be at a selectional advantage when the drug is used and as a result they may become more prevalent. The frequency at which antibiotic resistant strains arise, and the rate at which they subsequently increase in numbers, varies greatly with different antibiotics and different pathogens and some of the changes in bacterial resistance to penicillins which have occurred over the past 30 years are shown in diagrammatic form in figure 1.