Tag Archives: antimicrobial resistance surveillance

“Cohort Bias”

At my laboratory we only test nasal Staphylococcus aureus susceptibility to mupirocin in the following two circumstances:

  • Prior to joint replacement surgery as part of a Staphylococcal decolonisation bundle
  • In patients where the clinical details state recurrent skin infections

In the patients about to get their joints replaced, our nasal Staph aureus resistance rate to mupirocin is 3%. Not surprising really. This is a generally older cohort, less likely to suffer from impetigo and skin boils etc., and thus less likely to have been exposed recently to mupirocin.

In the patients who have recurrent skin infections, our nasal Staph aureus resistance rate to mupirocin is 15%. This is not surprising either. This cohort is generally young, and due to their clinical history are much more likely to have been exposed to a lot of mupirocin. As a cohort, they potentially have a lot of physical contact with each other (in kindergartens, in the school playground, on the sports field, in cinemas, backs of cars etc..,) facilitating cross-transmission.

This is a good demonstration of how much antibiotic resistance can vary, depending on what population you are looking at. 3% is markedly different from 15% and management of these different rates might be very different from an antibiotic stewardship point of view.

It also reflects the difficulties in measuring antibiotic resistance and then how to report such results in a meaningful manner.

We like to simplify things, and have just one result regardless of what biases might be at play. Measuring resistance rates is complicated enough due to the sheer number of microbe-antimicrobial combinations that can be permutated. To add another level of complexity by calculating different values for any one microbe-antimicrobial combination is too much for most of us to handle! 

But sometimes the difference in values between different population cohorts (as demonstrated above) is just too much to be ignored…



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.



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…


“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.


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!