Tag Archives: antimicrobial resistance

“Defying Nature”

Antimicrobial Resistance, ,

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I occasionally hear people/experts saying that antibiotic resistance can be acquired by bacteria without any cost to the ‘fitness’ of the organism (i.e. it’s ability to replicate and survive in a competitive environment)

I could not disagree more…

If antibiotic resistance could be acquired without any cost to fitness, I think all the human bacteria (as well as all the environmental ones) would be pan-resistant already. It just doesn’t make sense to me.

Bacteria are masters of survival. They are also hyper-efficient, and need to carefully budget their energy quota not only on defence, but also on attack and redeployment, not to mention communication. If the bacterial population does not need to be resistant in a particular environment, it will not waste its precious energy on resistance genes for a “Just in case” scenario.

Most in-vitro studies show that acquisition of antibiotic resistance does indeed have a fitness cost. A few don’t. For those exceptions I would offer the following explanations:

  • Just like anti-microbial susceptibility testing, I suspect that in-vitro bacterial fitness correlates only roughly with in-vivo fitness.
  • The fitness cost may be so miniscule, that it is impossible to demonstrate in the laboratory setting.

So in an antibiotic free environment, the susceptible strain will eventually win out over the resistant one. This might take days, or it might take decades, depending on the relative fitness difference. The fitness gap between susceptible and resistant strains might also be narrowed by compensatory mutations, but it will never be zero. It is all just a matter of time, evolutionary time…

If a bacterium doesn’t need to be resistant, then it won’t be, and it will eventually dispose of the means to be resistant.

Bacteria are lean, mean, replicating machines. They are also highly obedient to the Laws of Evolution…

Michael

For a nice article on the above concept, with a few references attached, click here. About a 5 minute read.

“All is not quite as it seems”

Antimicrobial Resistance, ,

Look at any local antimicrobial susceptibility profile worldwide and you are likely to find that E.coli susceptibility to trimethoprim is sitting at somewhere around 75-80%.

So why therefore does trimethoprim remain such a popular choice on empirical antibiotic protocols?

There may be a few reasons for this:

  • The urine specimens that come into the lab are essentially a biased cohort. i.e. they do not represent everyone who will be diagnosed (and treated) with a UTI as many patients will get the diagnosis on the basis of symptoms or dipstick urinalysis alone.
  • Institutes that set antimicrobial susceptibility breakpoints may well err on the side of caution when setting the breakpoints. i.e. they will not want to call an antibiotic susceptible to a bacterium when it is actually resistant.
  • Trimethoprim usually acheives higher concentrations in the urine than elsewhere in the body. 

So the reason that trimethoprim remains on the empirical antibiotic protocols for UTI in so many institutions is because it generally works, and it works in almost certainly a higher percentage than we suggest it does (in the lab).

I am sure there are many stakeholders who have been disconcerted by the in-vitro trimethoprim susceptibility rates to E.coli in their local institution, and may have changed prescribing habits because of it.

In my area, E.coli susceptibility rates to trimethoprim have remained stubbornly stable at around 78-80% for the past 20 years. Trimethoprim has been an empirical choice for uncomplicated UTI in local guidelines for the whole of that time period.

Sometimes you just need to look at the data, then work out how it translates into reality.

Michael

I published a similar post several months ago but it was lost from the website due to technical problems. Apologies if this post looks familiar!

 

Old Wives Tales: Antibiotic Duration and its Effect on Antibiotic Resistance

Antimicrobial Resistance,

As a child you may remember being told by your doctor to finish your course of antibiotics so that the bug does not become resistant…. I think such a myth still exists today, possibly to a somewhat lesser extent. In reality, a longer than necessary course of antibiotics just prolongs the selection pressure for resistant organisms to thrive and thus leads to antibiotic resistance. 


In fit healthy people, antibiotic courses for straightforward UTIs, URTIs, simple soft tissue infections etc., can often be remarkably short (if antibiotics are needed at all), and people may notice a significant improvement in their symptoms after just one or two doses.

It is also important to note that the patient’s immune system usually works in tandem with antibiotic therapy so when the pathogenic bacterial load has been reduced by the first few doses of antibiotics it makes it easier for a patient’s immune system to complete the job of controlling the infection.

The real message to get across here is that antibiotic courses should be of sufficient duration to deal with the infection but not so prolonged that it unnecessarily promotes selection of resistant bacterial strains.

For most antibiotic courses, the maximal effect usually occurs after the first couple of doses and then any further effect tails off very quickly after this. I occasionally come across patients both in the hospital and community setting where the patient has been on the same antibiotic for weeks if not months to treat a particular infection. Only very rarely is this indicated, and in my opinion should never be done without consultation with a specialist.

Michael