In most cases, the single best antimicrobial agent should be selected for use because this minimizes side effects. However, there are several instances in which two or more drugs are commonly given:
(1) To treat serious infections before the identity of the organism is known.
(2) To achieve a synergistic inhibitory effect against certain organisms.
(3) To prevent the emergence of resistant organisms. (If bacteria become resistant to one drug, the second drug will kill them, thereby preventing the emergence of resistant strains.)
Two drugs can interact in one of several ways (Figure 1). Typically their effects are additive. Sometimes there is a synergistic interaction, where the effect of the two drugs together is significantly greater than the sum of the effects of the two drugs acting separately.
Fig1. Drug interaction. The solid lines represent the response of bacteria to drug A alone, drug B alone, or no drug. The dotted lines represent the response to drug A and drug B together.
A synergistic effect can result from a variety of mechanisms. For example, the combination of a penicillin and an amino glycoside such as gentamicin has a synergistic action against enterococci (E. faecalis) because penicillin damages the cell wall sufficiently to enhance the entry of aminoglycoside, which inhibits protein synthesis. When given alone, neither drug is effective. A second example is the combination of a sulfonamide with trimethoprim. The two drugs act on the same metabolic pathway but at different steps. If one drug does not inhibit folic acid synthesis sufficiently, the second drug provides effective inhibition by blocking a subsequent step in the pathway.
