2 Antimicrobial resistance

2.1 Resistance mechanisms

The resistance mechanisms that bacteria have evolved to counter the action of antimicrobials are sophisticated. In the Introducing antimicrobial resistance module you learned about the main mechanisms of antimicrobial resistance. See if you can remember them in Activity 5.

Activity 5 Antimicrobial resistance mechanisms

Timing: Allow 10 minutes

Part 1

Figure 2 shows an overview of the main mechanisms of antimicrobial resistance. Use the drop-down list to match the mechanism to the appropriate part of the diagram.

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Discussion

Figure 2 Main mechanisms of bacterial resistance

1. Preventing antimicrobial entry
2. Increasing efflux
3. Modifying the antimicrobial
4. Destroying the antimicrobial
5. Modifying the target
6. Protecting the target
7. Amplifying the target.

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Unlike hydrolysing enzymes which in general provide high levels of resistance, some mechanisms only produce low-level resistance on their own. However, different mechanisms can combine to increase the level of resistance provided. For example, porin loss combined with an over-expression of efflux pumps can lead to carbapenem resistance which is hard to distinguish on AST from the hydrolysing activity of a carbapenemase, and which has the same effect clinically in reducing the efficacy of treatment.

The β-lactam-hydrolysing enzymes are interesting in that they can sometimes be blocked by using a second substance along with the antimicrobial. This enzyme blocker is called an inhibitor, for example clavulanic acid, which can be administered alongside an antimicrobial, and acts to neutralise the hydrolysing enzyme and protect the antimicrobial during treatment (Drawz and Bonomo, 2010). An example of a commonly used antimicrobial inhibitor combination is co-amoxiclav, which contains amoxicillin and clavulanic acid.