Combinations

Treatment with a single antimicrobial is sufficient for most infections. The indications for use of two or more antimicrobials are:

• To avoid the development of drug resistance, especially in chronic infections where many bacteria are present (hence the chance of a resistant mutant emerging is high), e.g. tuberculosis.

• To broaden the spectrum of antibacterial activity: (1) in a known mixed infection, e.g. peritonitis following gut perforation or (2) where the infecting organism cannot be predicted but treatment is essential before a diagnosis has been reached, e.g. septicaemia complicating neutropenia or severe community-acquired pneumonia; full doses of each drug are needed.

• To obtain potentiation (or 'synergy'), i.e. an effect unobtainable with either drug alone, e.g. penicillin plus gentamicin for enterococcal endocarditis.

• To enable reduction of the dose of one component and hence reduce the risks of adverse drug reactions, e.g. flucytosine plus amphotericin B for Cryptococcus neoformans meningitis.

Selection of agents. A bacteriostatic drug, by reducing multiplication, may protect the organism from a bactericidal drug (see above, Antagonism). When a combination must be used blind, it is theoretically preferable to use two bacteriostatic or two bactericidal drugs, lest there be antagonism.

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