Category Archives: The Art of Microbiology

“A simple approach to uncomplicated UTI”

Confessions of a Microbiologist, The Art of Microbiology, , ,

We have a “no clinical details-no test” policy at my lab, so in general, we get accompanying clinical details with the vast majority of samples received for microbiology testing. After all, at the end of the day, clinicians just want their requests processed…

This is great, but it always irritates me slightly when we get a urine sample into the laboratory from a young adult female with symptoms of a straightforward cystitis with no supporting clinical information to suggest that a “complicated UTI” is being queried.

My first reaction when seeing this is “Why are you sending this urine sample to the lab? Do you think this is going to help your patient?”

In New Zealand, and I suspect most of the rest of the world, uncomplicated UTIs are treated empirically according to local antibiograms, usually with a short course of nitrofurantoin or trimethoprim. In most cases, this settles things down, and no further medical input is required.

We receive approximately 400 urine samples for microbiology processing into our lab each day. My rough estimate is that 5-10% of these urines have clinical details that suggest an uncomplicated UTI. It doesn’t sound much, but it certainly adds up over the course of a year, and the total cost of processing all these would likely cover a scientist’s salary.

...And if we received urine cultures into the lab on every uncomplicated UTI diagnosis, then we would be completely overwhelmed!

During the early stages of the COVID pandemic, when we were getting hammered by SARS-CoV-2 PCR requests, we urged clinicians to send us critical samples only. This certainly reduced the number of requests where the clinical details suggested uncomplicated UTI. But old habits die hard, and now we are more or less back to baseline.

I have often wondered whether we should only accept urines where the clinical details are suggestive of a complicated UTI, but we have not gone there yet. Some might wonder if such an approach is too “hardline”, but it remains an option and I think a very reasonable one at that.

People sometimes think diagnostic stewardship is all about optimising the use of very expensive laboratory tests, e.g multiplex PCR assays, but in actual fact, looking after less costly but higher volume tests such as urine culture is every bit as important…

Michael

“Between the devil and the deep blue pool…”

The Art of Microbiology, ,

Pooling of COVID-19/SARS-CoV-2 samples has been an important and integral part of the NZ laboratory response to COVID-19.

Two weeks ago, following the appearance of COVID-19 cases in the community following a 100 day hiatus, test volumes surged  nationally from 4000 samples to 27000 samples a day, literally overnight…

It goes without saying that without widespread pooling of samples, we would have had testing backlogs of several days if not weeks, completely devaluing the usefulness of the results in terms of contact tracing and significantly increasing the risk of exponential growth in the outbreak.

Microbiologists, by nature, are purists. They understandably want their laboratory to produce the “perfect” result. Accreditation agencies may have similar views, with a narrow focus on the quality of the results produced. That’s their job after all…

But the world, and in particular the COVID world that we now live in, is far from perfect, and we need to keep looking at the big picture.

Pooling of clinical samples for a PCR assay has a small effect on sensitivity. Because we measure virus counts on a logarithmic scale this effect is almost, but not quite negligible, if a small number of samples are pooled. We have the potential to miss “positive” samples with very low viral loads, likely coming from patients who are almost certainly non-infectious. In my anecdotal experience, most of the results produced at the limit of detection are in patients who are recovering from infection, in the recent or not so recent past. Our experience shows that the loss of sensitivity by pooling samples is probably less than using a throat swab instead of a nasopharyngeal swab.

The other potential drawback of pooling is that if you get a positive pool, you then need to test all the samples in the pool individually. If positivity rates are high then pooling becomes self-defeating, creating even more work! However positivity rates in NZ have up until now been very low, so this has not been an issue for us.

As far as I am aware, NZ diagnostic laboratories that have utilised pooling (most of them) have validated the methodology over different platforms to the best of their ability, within the considerable time and resource constraints they have had to work within. In addition they have implemented IT solutions to facilitate the pooling of samples from a pre-analytical point of view.

Registration and molecular staff all over the world have been under the pump recently due to COVID-19 testing. Long, long hours, validation of new assays and platforms, pressure to get results out quickly… It is tough and I am in utmost admiration of our molecular team. Pooling is one of several ways to reduce this pressure on staff and try and prevent burnout. COVID-19 and the associated high testing volumes are not going to go away. This was always going to be a marathon effort, not a sprint, so testing processes need to be sustainable in the long term.

COVID-19 is a new disease but pooling of laboratory samples is not. The thing that has become very clear with regards to this infection, is that effective control depends to a large degree on testing large numbers of people and getting the results out quickly so that appropriate isolation and contact tracing can be performed. We should be embracing policies that allow us to achieve this goal.

Up until now at my own lab, our largest volume molecular test was Neisseria gonorrhoeae/Chlamydia trachomatis PCR, approximately 60,000 tests per annum. SARS-CoV-2 test numbers are going to completely and utterly dwarf this!

We need to adapt, in a pragmatic and realistic fashion, to the situation that we are currently faced with.

Michael

There are plenty of examples of SARS-CoV-2 pooling studies out there. Here is one for starters!

“Taking the crap out of enteric microbiology”

The Art of Microbiology, ,

Just because a stool sample turns up at your microbiology laboratory, it doesn’t mean you have to test it… This is old style microbiology reasoning, testing for everything in the hope that you will find something!

There are many different microbiology tests that one can do on a stool sample. Here is a sample list of what is offered at the lab I work at:

  • PCR for common bacterial pathogens, e.g. salmonella, campylobacter, shigella, VTEC, yersinia.
  • Culture for more opportunistic bacterial pathogens such as Aeromonas
  • EIA for cryptosporidium and giardia
  • GDH/PCR for C. difficile toxin
  • Faecal concentration and trichrome stain for ova, cysts and parasites
  • Immunochromatographic assay for rotavirus
  • Multiplex PCR for other enteric viruses (e.g. noro, astro, sapo)
  • Faecal antigen test for H. pylori.

With appropriate clinical details present, we can then choose objectively from the list above which tests are appropriate to perform for a specific sample.

However, without clinical details, it would be utterly unreasonable for the lab to do all of these tests, and without clinical details there is no way of deciding which tests we should be doing.

Yet so many microbiology labs still take this approach. Receive a stool sample and test it for something! This is blindfold microbiology.

Extending this philosophy further, clinical details of “diarrhoea” doesn’t really cut the mustard either. That is to some extent stating the obvious!

Fit healthy adults who present with a short history of diarrhoea in general do not require laboratory testing. Personally I get 2 or 3 episodes of loose stools every year. I am sure the rest of the world has a similar experience! I do not need laboratory testing. So clinical details simply of “diarrhoea” or “loose stools” is insufficient to justify testing. There needs to be more than that…

The lab I work at will only test stool samples if one of the following applies, even when clinical details of “diarrhoea” or something similar is on the form:

  • Something to indicate an illness on the more severe end of the spectrum, such as prolonged diarrhoea, bloody diarrhoea, hospitalised, systemic symptoms, etc.
  • Or something that suggests there might be a public health issue, e.g. food handler, group meal, overseas travel, farm worker, etc.

“Carte blanche” approaches to enteric microbiology are hideously costly, and also give rise to quality issues such as overdiagnosis and overtreatment.

If you test every stool sample you receive for putative pathogens such as Blastocystis hominis or Dientamoeba fragilis, you are going to end up overdiagnosing and overtreating a whole heap of people. Don’t go there!

By taking a considered and objective approach to microbiology testing of stool samples you can dramatically reduce the amount of testing that you perform, and increase the quality of results at the same time.

Michael