Tag Archives: antimicrobial resistance

“Trending…”

I get the occasional anxious phone call from clinicians concerned about the “rising rates ” of trimethoprim resistance to E. coli…

Not being entirely convinced, I did a (20 year) search for E. coli resistance to trimethoprim at my lab, analysing over 2 million isolates, and came up with the following graph.

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I couldn’t work out how to insert a trendline into the graph (I am so useless…), but I think you will agree that it is going to be fairly flat.

The antibiotic apocalypse is not arriving in New Zealand anytime soon. In fact the whole concept of “antibiotic resistance” as perceived by the public is horribly generic and oversimplified…

This example above of course is just one microbe/antimicrobial combination out of many hundreds that could have been analysed, but the observation did highlight a couple of things to me:

  • If antibiotic usage is relatively constant in a population over a prolonged period of time, then antimicrobial resistance does not necessarily rise inexorably. (q.e.d.)
  • Always back your claims up with objective data wherever possible. It is the trends which are critical in the surveillance of antibiotic resistance. We are lucky that at my lab we can now search back through 20 years of electronic data. Before 1996 the data was paper based (and likely lost in a basement or incinerated by now!)

If you did a similar exercise for all the possible microbe/anti-microbial combinations (I just might if the Christmas holidays are quiet!), you will find some trends that are upwards, some that are static, and some where the resistance rate is trending downwards.

A bit like Twitter really….

So when someone says to you. “Antibiotic resistance is increasing all the time. In 10 years time, all infections will essentially be untreatable” (I really detest this type of generic, off the cuff, unsubstantiated statement…)

…you should respond with something along the lines of “Exactly which microbe and antimicrobial combination are you talking about?” and “Show me your data…”.

Some infections will be, and already are, untreatable (mostly due to extreme and focused selection pressure), but the chances of a whole bacterial species becoming pan-resistant are remote. There are two main reasons for this. i) Bacteria survive in open systems, and ii) Bacteria need to expend energy to become resistant.

But these are other stories altogether…

Michael

“Defying Nature”

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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”

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!