Despite several claims to the contrary over the years, the consensus now is that MRSA is, in general, not more virulent or pathogenic than its susceptible counterpart, MSSA.
For a bacterium to both acquire a resistance mechanism and to become more virulent at the same time is in contradiction to evolutionary theory, and would not only be surprising but would be a bit scary as well. Most of the time, acquisition of resistance genes by a bacterium comes with a cost both in terms of fitness and virulence, although this cost is often not measurable in practical terms.
So having said all that, why is mortality from MRSA infection still consistently higher than that of MSSA infection?
There are three main reasons:
- Delay in getting the correct treatment. If the empirical treatment given to a patient (e.g. a cephalosporin), covers MSSA infection but not MRSA infection, then by the time the MRSA infection is identified, there may have been a significant delay in initiating appropriate treatment. For the frankly septic patient, every hour delay before iniating appropriate treatment can increase the mortality.
- Treatment not as good. The traditional treatments for invasive MSSA infection, flucloxacillin and cloxacillin, are more efficacious antibiotics than the traditional treatment for MRSA infection, which has been vancomycin. Thus cure rates will be higher for the MSSA group. This is why people are looking hard for, and in many cases now using better alternatives than vancomycin for treating invasive MRSA infection.
- Sicker cohort of patients. Particularly with regards to the “hospital type” MRSA strains E15,E16 etc., the cohort of patients who are colonised and infected by these bacteria tend to be older, frailer and with more co-morbidities than those with MSSA. Thus the mortality rate will naturally differ between the two cohorts.
As you can see, mortality is influenced by many factors, not just the virulence of the bacterium.
More on mortality and MRSA in the next post, when the story gets even more complicated!
Michael
Hi Michael,
Great post as always. Great blog, great website.
I want to ask about increased virulence and antibiotic resistance being counter to evolutionary theory.
It is my understanding that insertion sequences and other mobile genetic elements carrying ab resistance genes often additionally code elements related to enhanced virulence. For example CA MRSA, associated with outbreaks of skin and soft tissue infection and severe pulmonary infections. Whilst these are things that MSSA strains are capable of it is my understanding that strains containing IS sequences enhanced virulence is can be selected for by ab use?
Thanks again Michael. I learn a lot from these posts
Thanks Sam, the more questions that are asked, the more complex it gets! In truth it is probably a more dynamic interplay between three things; resistance, virulence and fitness. My post is also more attributable to the MRSA population in general, with the admission that certain strains are more pathogenic than average. I have a couple of nice papers on the relationship between resistance, fitness and virulence, but I don’t understand all of what is written. I’ll add the links to the post in the next day or two.
I guess my premise remains though, more gut instinct than anything. It would be very worrying if a bacterial population could become both hypervirulent and multi-resistant. Most bacteria that are inherently multi-resistant are fairly docile, e.g. Stenotrophomonas etc. The closest example we have to something which is both relatively resistant and virulent is N. gonorrhoeae. However this is a little bit of an exception as it operates in a closed system. See this article for more…
Hope this helps!
Cheers, Michael
Here is an article looking at the relationship between resistance, virulence, and fitness. In parts it is suggesting that a bacterial species can be both more resistant and virulent at the same time, but at the cost of fitness. Complex!