Tag Archives: antimicrobial susceptibility testing

“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…

Michael

“Too soft, too generous, too nice, and too slow…”

Guidelines for antimicrobial stewardship often include only a cursory mention of the role of the clinical microbiology laboratory, which is a shame, because in my opinion it is one of the key areas where real change to anti-microbial stewardship can be effected. (The other key area is in the writing of sensible narrow spectrum empiric antibiotic policies.)

But we don’t help ourselves…. Speaking generally, I think clinical microbiology laboratories are notoriously bad at antimicrobial stewardship.

Why?

Several reasons actually.

Because we are too soft: We often release antimicrobial susceptibilities from the laboratory even when we have no idea what is going on with the patient. I.e. no clinical details have been provided. Therefore we think nothing of releasing a range of antibiotics to the clinician when we don’t actually know what is wrong with the patient, whether they have an infection, and how severe it is.

Antibiotic susceptibilities should not be released unless the laboratory has reasonable evidence that they are required.

Because we are too generous: We are happy to test a whole range of antibiotics (often up to 20 for the one isolate!), “just in case” one of them might need to be used. This range often includes both narrow spectrum and broad spectrum agents. Probably over 95% of all the susceptibilities that we test and report are never utilised.

We need to dramatically reduce the range of antibiotics that we test for and we need to focus our reporting to the narrowest spectrum antibiotics that we can get away with.

Because we are too nice: We have a low threshold for releasing antibiotic susceptibilities on putative pathogens“. By doing this, we have just given the green light for the clinician to classify a putative pathogen as an actual pathogen, and therefore start/continue antibiotics.

If we have isolated a putative pathogen, let’s keep it putative. Report the organism, and ask the clinician to make a clinical assessment, and then to get back to the laboratory if susceptibilities are required.

Because we are too slow: We are certainly quicker than we used to be, thanks to MALDI-TOF, smart incubators, and increasingly rapid PCR platforms, but we need to be quicker still… We need to get rid of self-congratulatory, retrospective infectious serology testing and channel our test budgets into real-time diagnosis with PCR or similar, and on patients who fulfil well defined clinical criteria for testing. We need to get rapid molecular platforms for STDs into Sexual Health clinics so they are not required to prescribe an antibiotic for everybody who walks through the door. We need to increase Influenza and RSV testing during the winter season to try and reduce unnecessary antibiotic prescribing for viral infections.

Not only do we need to be quicker, we also need to be smarter…

The clinical microbiology laboratory doesn’t score very well in the antimicrobial stewardship report card. We need to be bold and innovative to change things for the better.

But it is entirely up to us…

Michael

“Keeping it simple or keeping it accurate…”

Let’s say you are a clinician and you are looking at two different microbiology results on two different patients (A&B). Both have an E. coli UTI. Both results state that the E. coli is susceptible to trimethoprim. However what you don’t know is that the E. coli isolate on Patient A had a trimethoprim disc diffusion zone of 18mm (right on the EUCAST breakpoint), whilst for patient B the corresponding zone was a much more comfortable 26 mm.

And who knows, if you repeated the same testing on patient A a dozen times, the chances are you would have a few “non-susceptible”results, due to the natural margin of error of the test.

If I was a clinician, and had this extra (zone diameter) information, I would be a lot happier prescribing trimethoprim to patient B, even though they both have in-vitro “susceptibility” reported on the result. (The same principle of course applies if we were talking about Minimum Inhibitory Concentration (MIC) values instead of zone diameters.)

But do clinicians really want this extra information?

They are usually very busy, …and not particularly interested in microbiology.

In my experience all clinicians generally want to know is if an isolate is susceptible or resistant. They are not particularly interested in the details, with the exception of blood culture and sterile site isolates, when there is at least a modicum of interest in the degree of susceptibility or resistance.

So which is better.. a susceptibility result full of information, but potentially difficult to understand and interpret, or a result reduced to its simplest form.

There is no right answer of course…

I am not even convinced antimicrobial susceptibility breakpoints have a long term future.

More and more, year by year, the anti-microbial susceptibility committees (EUCAST, CLSI) are trying to take into account antibiotic dose,  renal function, degree of infection, etc. when setting antimicrobial breakpoints.

But they are really only scratching the surface…

Time for some major disruption!

Michael