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In combination therapy, synergy is said to occur when the combined effect is greater than the sum of the individual effects. An additive effect is observed with the combined effect which is equal to the sum of the individual effects. Indifference is observed when there is no interaction between one another. Antagonism is defined when the combined effect is less than when the two compounds are individually applied. The reversal of resistance is said to occur when a synergistic outcome is observed. As an example, one of the strategies employed was to screen against β-lactamase producers and by mechanism-based inhibition of the active-site serine hydrolases for compounds that can antagonize the antibiotic-destroying hydrolases. Clavulanic acid (sulbactam or tazobactam) from a streptomycete in combination with amoxicillin was the outcome of this approach [34]. However, the victory against bacterial resistance did not last long; the frequent use of clavulanic acid has led to the emergence of resistant variants like any other of its antibiotic ancestors [35]. As resistant bacterial strains will eventually emerge in response to widespread use of a particular antibiotic and limit its lifetime, knowledge of the principal and specific resistance mechanisms provides scientists the insights into strategies for development of new therapeutics. In the past, when resistance to a β-lactam antibiotic occurred, pharmaceutical scientists modified the periphery of the β-lactam warhead to obtain a more effective variant and that was how the second- and third generation β-lactams of both the penicillin and cephalosporin emerged.
Combination between conventional antimicrobial agents and essential oils is a new concept; a few examples are described (Table 22). Sometimes, essential oils have been found to be synergistic enhancers in that though they may not produce any significant inhibitory effects when used alone, but when they are used in combination with the standard drugs, the combinatory effect surpasses their individual performance and produces enhanced antimicrobial activity [11]. Synergistic activity exerted using essential oils has been found to reduce the minimum effective dose of antibiotics in the treatment of infections. This reduces the adverse effects of the antibiotic. Most importantly, association of antibiotics with essential oils targeting resistant bacteria may have different mechanism of action and it may lead to new choices to overcome the onslaught of microbial resistance. Exploitation of essential oils in preventing bacterial resistance is believed to be more promising because essential oils are multi-component in nature compared to many conventional antimicrobials that only have a single target site.
In combination therapy, synergy is said to occur when the combined effect is greater than the sum of the individual effects. An additive effect is observed with the combined effect which is equal to the sum of the individual effects. Indifference is observed when there is no interaction between one another. Antagonism is defined when the combined effect is less than when the two compounds are individually applied. The reversal of resistance is said to occur when a synergistic outcome is observed. As an example, one of the strategies employed was to screen against β-lactamase producers and by mechanism-based inhibition of the active-site serine hydrolases for compounds that can antagonize the antibiotic-destroying hydrolases. Clavulanic acid (sulbactam or tazobactam) from a streptomycete in combination with amoxicillin was the outcome of this approach [34]. However, the victory against bacterial resistance did not last long; the frequent use of clavulanic acid has led to the emergence of resistant variants like any other of its antibiotic ancestors [35]. As resistant bacterial strains will eventually emerge in response to widespread use of a particular antibiotic and limit its lifetime, knowledge of the principal and specific resistance mechanisms provides scientists the insights into strategies for development of new therapeutics. In the past, when resistance to a β-lactam antibiotic occurred, pharmaceutical scientists modified the periphery of the β-lactam warhead to obtain a more effective variant and that was how the second- and third generation β-lactams of both the penicillin and cephalosporin emerged.
Combination between conventional antimicrobial agents and essential oils is a new concept; a few examples are described (Table 22). Sometimes, essential oils have been found to be synergistic enhancers in that though they may not produce any significant inhibitory effects when used alone, but when they are used in combination with the standard drugs, the combinatory effect surpasses their individual performance and produces enhanced antimicrobial activity [11]. Synergistic activity exerted using essential oils has been found to reduce the minimum effective dose of antibiotics in the treatment of infections. This reduces the adverse effects of the antibiotic. Most importantly, association of antibiotics with essential oils targeting resistant bacteria may have different mechanism of action and it may lead to new choices to overcome the onslaught of microbial resistance. Exploitation of essential oils in preventing bacterial resistance is believed to be more promising because essential oils are multi-component in nature compared to many conventional antimicrobials that only have a single target site.
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