Mupirocin use drives mupirocin resistance…or does it?

mupirocin

I’ve blogged before that mupirocin resistance is an inevitable consequence of mupirocin use. Whilst I still think that this is true, my old colleagues from GSTT / KCL have just published an article suggesting that mupirocin resistance in MRSA has more to do with clonal variation than with mupirocin use.

The study is part of an ambitious project to sequence the genome of around 1000 MRSA isolates from across Central and South-East London (Guy’s and St. Thomas’, King’s, and Lewisham). Each isolate was then tested for phenotypic high (HMR) and low (LMR) mupirocin resistance, the genome was scoured for the genetic determinants known to be associated with mupirocin resistance, and clone was derived from the genome sequence. Risk factors for both HMR and LMR were then explored.

Around 10% of the 795 isolates were either LMR or HMR; 6% exhibited LMR and 3% HMR, and mupirocin resistance was more common in hospital clones. Previous hospitalisation was a risk factor for LMR but not HMR. This suggests that mupirocin use, which is more common is hospitals, is a key driver for LMR but perhaps not HMR. Both LMR and HMR varied by clone, which suggests that clonal variation rather than mupirocin use is a key variable – and perhaps the key variable – in determining the prevalence of HMR and to a lesser degree LMR.

Now you could argue that mupirocin use simply selects for the clone that is more able to develop mupirocin resistance. However, this does not match the epidemiology, since ST22 (EMRSA-15) has replaced ST36 (EMRSA-16) as the dominant MRSA clone locally and nationally – and ST22 is a less resistant to mupirocin than ST36.

A fair number of the isolates that had genetic determinants associated with mupirocin resistance were mupirocin susceptible in vitro. In the case of HMR, an important finding was that mutations around the mupA gene (the HMR gene) were found in all 8 of the isolates that carried mupA but were not HMR. Even more interestingly, the mutations around a number of these genes were reversible, suggesting that MRSA could ‘activate’ the mupA gene when exposed to mupirocin.

The study did not use the WGS data to its fullest extent – and actually used the WGS data to derive MLST, which was used to delineate clone. It would have been interesting to see whether there were any clusters of related isolates within the same clone

So does this mean that we can go ahead and use mupirocin indiscriminately safe in the knowledge that mupirocin resistance is only driven by clonal variation and not mupirocin use? Certainly not – if we do this, than an increase in LMR at the very least is to be expected, and it’s difficult to see how this would not select for HMR in the long-term. A continued rational ‘screen and treat’ application of mupirocin has to be the way forward!

Image: Web MD.

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