Antibiotic and AI Drug

"Most physicians have the vague feeling that if one anti-microbial drug is good, two should be better, and three should cure almost everybody of almost every ailment"

This "vague feeling" has proved to be valid in a number of instances, but there is also good evidence that sometimes the very opposite is true. This situation has fuelled a keen debate about the desirability or otherwise of combining antimicrobial agents which has gone on for many years, and various schemes have been published which try to provide a logical framework for predicting the likely outcome. One of the serious difficulties is the often poor correlation between in vitro and in vivo studies so that it is difficult to get a thoroughly reliable indication of how antimicrobial agents will behave together in clinical practice. Some of the synopses in this chapter illustrate these difficulties very clearly.

Some of the arguments in favour of combining antimicrobial agents are as follows. Where the infections are acute and undiagnosed the presence of more than one drug increases the chance that at least one effective antimicrobial is present. This may be especially important if the patient is infected by more than one organism. The possibility of the emergence of resistant organisms is decreased by the use of more than one drug, and in some cases two drugs acting at different sites may be more effective than one drug alone. It may also be that two drugs administered below their toxic thresholds may be as effective and less toxic than one drug at a higher concentration.

In contrast there are other arguments against using antimicrobials together. One serious objection is that two drugs may actually be less effective than one on its own In theory this could arise if a bactericidal drug, which requires actively dividing cells for it to be effective, were used with a bactenostatic drug. However in practice this seems to be less important than might be supposed and there are relatively few well-authenticated clinical examples. Another objection is that some broad-spectrum drugs may be suboptimal for particular organisms and may inadequately control the infection. Toxic side-effects may possibly also be increased by the use of more than one drug.

An indiscriminate and "blunderbuss" approach to the treatment of infections is no longer in favour, the general consensus of informed opinion being that the advantages of combined antimicrobial treatment are balanced by a number of clear disadvantages, and that usually one drug alone, properly chosen, is likely to be equally effective.

Some of the synopses in this chapter are concerned with the adverse effects of combining antimicrobials together but most of them deal with the interactions caused by non-infective agents Interactions where the antimicrobials are the affecting or interacting agent are dealt with in other chapters.