Over the years I have been used to teaching everyone that MRSA is resistant to all cephalosporins, or indeed, all beta-lactams.
However I have been having to revise that statement recently with the advent of the new “5th generation” cephalosporins, ceftaroline and ceftobiprole.
These broad spectrum antibiotics have activity against MRSA by having enhanced affinity for the PBP2A binding protein. As new antibiotics go, they are not overly expensive. Their main downside is that they both need to be given intra-venously.
They have actually been around for a while now, but only more recently available in New Zealand.
So will I use these “new” antibiotics in clinical practice?
Possibly, although I always think that new broad spectrum antibiotics such as these should be protected from widespread use in order to minimise resistance selection.
However if they are not used at all, they will be commercially unviable and be withdrawn from the market. A catch 22 situation.
I now have to revise my lectures. MRSA is resistant to most beta-lactams, with a couple of exceptions….”
You’ll no doubt have seen a headline like this in some paper or other…
“MRSA Superbug kills 100 people in local hospital”
So what does that mean?
Well it might mean that 100 people died who were colonised with MRSA.
….or it might mean that 100 people who died of something or other, had an MRSA infection at some point during their admission.
…..or it might mean that 100 people died from documented MRSA infection.
…but it probably doesn’t mean that 100 people died specifically because their Staph aureus infection was resistant to beta-lactams.
Staph aureus is a virulent organism. Staph aureus bacteraemias, regardless of whether they are methicillin susceptible or resistant, have a mortality rate of approximately 20% depending on the cohort studied.
However trying to attribute mortality specifically to the Staph aureus being resistant is an almost impossible task.
So a more accurate headline might be “100 people in local hospital die from Staph aureus infection. An unknown proportion of these patients, probably quite small, died because the infecting bacterium was resistant to most beta-lactam antibiotics.”
Not much of a headline, nor would it sell many papers….
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!