4 Identifying resistance mechanisms

4.1 Why knowing the mechanism is important

  • Why might it be important to know what the resistance mechanism is for an isolate, rather than just whether it is susceptible to the antimicrobial you are testing?

  • Knowing the resistance mechanism is important from both a broader public health and a local infection control perspective. Some resistance mechanisms have more public health consequences than others, for example MRSA versus beta-lactamase producing S. aureus (see section 3.2.1 above) or transmissible carbapenemases compared to efflux pump-mediated resistance, because of their ability to spread combined with high-level resistance to critically important antimicrobials.

Activity 7 What the resistance mechanism tells us

Timing: Allow 10 minutes

Imagine that a novel pathogen-antimicrobial combination has been found in your country or institution for the first time. What important questions from a public health or infection control perspective need answering? How might knowing the underlying resistance mechanism(s) of the isolate help answer these questions?

Make notes in the text box below before looking at the example answer.

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Discussion

Important questions include:

  1. Is this mechanism new in this species?
  2. For example, a completely new type of plasmid-mediated colistin resistance gene (mcr-1) found in E. coli isolated from pigs was discovered in China in 2015. There are now nine variants of this resistance gene, mcr-1 to mcr-9 (Liu et al., 2016).
  3. Where did the resistance mechanism originate from? Has it jumped from another bacterial species?
  4. For example, although the mcr-1 gene’s origins are not yet known, others are, for example the CTX-M gene in Klebsiella came from a different Gram-negative organism (Kluyvera) originally.
  5. Is resistance transmissible? Is it on a plasmid?
  6. For example, the mcr-1 gene being plasmid-borne can easily transfer between different bacteria, and has now been reported in E. coli, Salmonella enterica, K. pneumoniae, and Enterobacter species. Since the discovery of the mcr-1 gene in China, it has now been reported in over 30 countries.
  7. Is it linked to other resistance genes? Many resistance genes are found on plasmids along with a wide range of other resistance genes leading to MDR organisms. If it has been found in animals, has it also spread to human populations?
  8. For example, the mcr-1 gene has moved from pig pathogens into pathogens found in people and the mcr plasmids are now circulating within populations of human pathogens.
  9. Can it still be contained? Or has it already spread too widely by the time it is detected?
  10. What infection control measures are advisable? Have similar pathogen-resistance combinations been controlled successfully in the past?

3.3.2 Sexually transmitted pathogens

4.2 The approach used to determine the resistance mechanism