Antagonism antimicrobial combinations

Most infections should be treated with a single antimicrobial agent. Although indications for combination therapy exist, antimicrobial combinations are often overused in clinical practice. The unnecessary use of antimicrobial combinations increases toxicity and costs and may occasionally result in reduced efficacy due to antagonism of one drug by another. Antimicrobial combinations should be selected for one or more of the following reasons ... 

The use of an antagonistic antimicrobial combination does not preclude other potential beneficial interactions. For example, rifampin may antagonize the action of anti-staphylococcal penicillins or vancomycin against staphylococci. However, the aforementioned antimicrobials may prevent the emergence of resistance to rifampin. 

Some combinations of antimicrobials are potentially antagonistic. For example, agents that are capable of inducing /1-lactamase production in bacteria (such as cefoxitin) may antagonize the effects of enzyme-labile drugs such as penicillins or imipenem. 

Drugs are considered to act additively when the activity of drugs in combination are equal to the sum of their independent activity. The overall effect of two antimicrobial drugs can be less (antagonism) or more (synergism) than the sum effect. 

There are few clinically relevant examples of antimicrobial antagonism. The most striking example was reported in a study of patients with pneumococcal meningitis. Patients who were treated with the combination of penicillin and chlortetracycline had a mortality rate of 79% compared with a mortality rate of 21% in patients who received penicillin monotherapy (illustrating the first mechanism set forth below). 

In terms of bactericidal actions, the outcome of the combined use of two antimicrobials may be indifference, synergism, potentiation, or antagonism (see Chapter 61). Such actions are more readily demonstrated in vitro than at the clinical level. Some mechanisms that may account for synergism follow. 

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