Category Archives: The Art of Microbiology

“Bias in the diagnostic microbiology laboratory”

We are all fundamentally flawed as humans. We just have to do the best we can given our limitations.

I attended an interesting clinical Grand Round at my local hospital last week. Whilst the case presented was intriguing, it was the presenters’ focus on the different types of cognitive bias which are seen in clinical medicine which really caught my attention. 

It got me thinking… Do the same types of bias apply when reading and interpreting microbial cultures on agar plates?

The answer is of course yes.

Below are examples of the main types of cognitive bias one might be subject to when reading agar plates:

  • Confirmation Bias – Scientists may interpret bacterial growth in a way that confirms their expectations or prior hypotheses. For example, if they expect a certain antibiotic to inhibit growth, they might unconsciously downplay colonies that appear resistant.

  • Anchoring Bias – The first observation or previous experience can heavily influence interpretation. If a scientist has seen a particular growth pattern before, such as satellitism of Haemophilus influenzae around Staphylococcus aureus they might assume it’s the same species or reaction without fully considering other possibilities. 

  • Availability Heuristic – The tendency to rely on readily available examples in memory. If a scientist recently encountered an unusual bacterial isolate, they might overestimate its likelihood when analysing new plates, leading to misidentification.

  • Observer-Expectancy Effect – The scientist’s expectations may subtly influence how they interpret ambiguous results. For instance, if they believe a sample contains Streptococcus pneumoniae, they might unconsciously interpret the MALDI-TOF result as such, and ignore the possibility of Streptococcus mitis.

  • Hindsight Bias – After identifying bacterial species via additional testing, e.g. MALDI-TOF, scientists might believe the identification was more obvious than it actually was when first observing the plate, leading to overconfidence in future interpretations.

…and then of course there is the classical clinical judgement bias, that of “Premature Closure” where an “easy” or quick diagnosis is made, and further investigations into a more challenging/important secondary diagnosis are withheld because of this. It happens not infrequently in clinical medicine. An example of this in the microbiology laboratory might be a patient with crystals in a synovial fluid sample leading to a diagnosis of gout, where sufficient duration of culture was not performed to pick up the secondary diagnosis of septic arthritis!

Now that we can simply google the key biochemical reactions of E. coli, maybe cognitive bias is the sort of thing we should be teaching microbiology students, so that they are aware of the sub-conscious ways we can slip up when reading agar plates, no matter how good our intentions… A nice exam question perhaps!

Michael

 

 

“A Smorgasbord of Microbiology”

I was fortunate enough to have attended the ECCMID conference in Barcelona a couple of weeks ago, the so-called “Glastonbury” of microbiology conferences. (it is just the drugs that are different…). In general, the conference venue wasn’t great, but the industry exhibition was very impressive, a massive well-lit hall with a true smorgasbord of microbiology tests & platforms available. There were literally hundreds of stands offering a vast array of products. Some of the stands were very flashy affairs, demonstrating fully functioning microbiology platforms. Most importantly, some were even offering free coffee!, although we all know there is no such thing as a “free lunch”. Microbiology is big business now. It can’t have been cheap to hire the floor space at ECCMID, so it must be worth their while.

Healthcare in general is becoming ever more expensive to fund. There are good reasons for this. There is so much more that we can do now than even a generation ago. Stem cell transplants, CAR-T therapy, new anti-cancer drugs, minimally invasive cardiac procedures (e.g. TAVI) to name but a few. In addition, we have a lot more elderly people. Good healthcare and its associated cost will keep a patient alive, who will then inevitably present later in life with further health issues to manage. Spending on healthcare undoubtedly improves life expectancy, but there is a ceiling on life expectancy and there is a law of diminishing returns which eventually kicks in…

With regards to microbiology, there is no difference really. There are so many more things we can offer in a microbiology lab which we could not offer even 20 years ago. Multi-plex & rapid turnaround PCRs, 16s RNA sequencing, metagenomics are a few examples. There are more antibiotics to perform susceptibilities on, and we can now perform both phenotypic and genotypic susceptibility testing. There are a lot more infectious conditions we can now effectively diagnose, usually with PCR based methods. We are also required to spend a lot more money on good quality assurance frameworks, and rightly so, it’s critically important! The landscape has changed out of all recognition in the microbiology lab. A generation ago, it was mainly culture-based bacteriology. Times have changed

All of this means that diagnostic stewardship plays an increasingly important role in the microbiology laboratory, if we are to have any hope of limiting costs whilst providing good value to the clinicians and patients. What tests and platforms should we have in the laboratory, and which patients should we perform these tests on? Personally, I think diagnostic stewardship should be a key component and focus of the jobs of both clinical microbiologists and laboratory managers alike.

“Diagnostic Stewardship is a never-ending process…”

When wandering around the industry exhibition hall, it is easy to get caught up in the euphoria and hype; “I’ll have one of those, and I’ll take that as well”, but there is now an almost infinite array of things that a microbiology lab can have… The key is to listen to what the industry reps have to offer, and then work out what is going to give most value to your particular patient cohort. Will that 24-plex respiratory PCR improve patient management over and above the incumbent 16-plex? Will this assay which gives me susceptibility results from positive blood cultures in 2 hours instead of 6 hours decrease patient mortality? 

Diagnostic stewardship is a fascinating area. Industry presents us with all these options. It takes an effective team working together in the lab to make the right decisions.

Michael

“Perfect is the enemy of good (microbiology)”

This quote attributed to Voltaire (“Le mieux est l’ennemi du bien”), rings true to me. I have never been a perfectionist, and the idealistic pursuit of perfectionism can hinder real-life achievement and progress. 

The quote came back into my conciousness during the early days of the COVID pandemic when I listened to a great speech by Dr Mike Ryan from the WHO when urging countries to act quickly in the face of the rapidly developing COVID situation.

Of course, such a concept can also apply to the microbiology laboratory.. Here are a few examples:

Protracted work-up of samples: When a sample arrives into the microbiology laboratory, the clock is ticking. In relentless pursuit of isolating that fastidious bacterium, time passes by and before you know it a week has passed… The clinical usefulness of a microbiological result is inversely proportional to the time spent to produce it. In the hospital setting, the average length of stay is 3-4 days… Excessive time spent on certain samples is not only a waste of resources, it also generally does nothing for the patient. Get a result out, even if it is not the perfect one that you are striving for.

Excessive work-up of samples: The classic example of this is identifying every bacterial isolate in a mixture of enteric flora. For the most part, such an exercise is futile, even when isolated from a sterile site. Enteric flora isolated from sterile sites usually represent a source control issue, and who knows what the pathogen might be in the mixture, if any. Such practice is generally a waste of resources, and reporting individual isolates along with individual susceptibilities is time-consuming and often leads to poor antimicrobial stewardship. Working up bacteria within a mixture of enteric flora might be “technically perfect” but does little to help the patient.

Excessive testing protocols: A good example of this is stool samples arriving into the microbiology laboratory. There are many microbiological tests that one can do with a stool sample, culture, PCR for bacterial & viral pathogens, microscopy for parasites, C. difficile testing, the list goes on. However, to perform all the available tests on every stool sample in the hope of maximising the odds of isolating a pathogen would be incredibly expensive, but in most cases would do little to change patient management. Enteric testing should very much be tailored depending on what is on the microbiology request form.

I am sure there are many other examples that one could think of. Perfection in the microbiology laboratory is very much a pipe dream, and can actually be detrimental to good patient care. We cannot possibly hope to identify all potential pathogens in every sample and do it in a timeframe that is beneficial to the patient. We need to move past our fear of missing something…

When developing testing methodologies or reviewing individual patient samples, we should always be asking ourselves “By doing what we are doing, are we providing overall value to the patient?” 

Michael