“A Question of Significance”

Confessions of a Microbiologist, , ,

We may not always realise it, but reading and reporting bacterial cultures often involves several decisions, which are often performed sub-consciously. What do we work up on the agar plates? What do we report? How do we report it?  Do we perform and report susceptibilities? Should we add a comment to the report? All these decisions influence how the result is perceived and acted upon by clinicians. Don’t underestimate the influence that the microbiology report can have on how the patient is subsequently managed.

For example, let’s say we receive 5 theatre samples from a patient undergoing a routine prosthetic joint revision, and 1 of the 5 samples has a light growth of Staphylococcus epidermidis. If we report this out with antibiotic susceptibilities, and without a qualifying comment, there is a decent chance that the orthopaedic surgeon will act on this result and the patient may well end up on several weeks of antibiotics. On the other hand, if we suppress the susceptibilities, and add a comment stating. “This result is of doubtful significance. Clinical correlation is required. Antibiotic susceptibilities are available on request.”, then it is very likely that the surgeon will simply note the result and observe the patient.

On the other hand, if we isolated a Cutibacterium acnes from a shoulder aspirate in a patient with a history of rotator cuff repair, then it is likely that this isolate is significant and we should convey the result as such, along with antimicrobial susceptibilities.

Best of all in these cases of course is to liaise directly with the requestor/clinician/surgeon, so that further clinical details can be obtained, the likely significance can be better ascertained, and a subsequent management plan developed. However, this is not always possible, nor practical for every single patient.

Whilst I always encourage pragmatic reporting, one needs to be aware of the potential consequences of reporting something as a likely contaminant. I.e. What if this organism is genuinely causing infection? What are the likely consequences for the patient if it has not been reported as such? Can we obtain further samples for culture to confirm or negate the initial result? With sterile site samples & blood cultures, obviously the stakes are higher than with a simple wound swab, but the same principles apply for both scenarios.

Over-reporting of organisms on agar plates is often driven by inexperience or fear. I have seen it many times in my career. Scientists and clinical microbiologists alike are responsible for ensuring that over-reporting of results is minimised. This is very much a team game. In particular, colonies thought to represent plate contamination should hardly ever make it on to the laboratory report. Along the same lines, when an obvious pathogen, e.g. Staphylococcus aureus is found on a mixed plate, to what extent should the other organisms be worked up and reported. If a plate is clearly growing a mixture of enteric organisms, you need a very good reason not to report it as mixed enteric flora, and leave it at that.

The “easy way out” for the microbiology scientist and the clinical microbiologist is to report everything that is found on the plate along with antimicrobial susceptibilities, and then let the clinician make head or tail of it. However, this is dumbed down microbiology and often leads to sub-optimal management of the patient.

Michael

“When the bugs take their time…”

The Science of Microbiology, ,

You are probably familiar with the scenario… A blood culture takes a couple of days to become positive. A Gram stain shows Gram negative rods. The plates are subbed but after another couple of days there is still no growth on the plates. The clinicians are getting impatient and are phoning the lab looking for an identification…

It is certainly a frustrating situation but one that occurs not infrequently.

Is there anything that can be done to help the clinician, and more importantly the patient, whilst we are waiting for the organism to grow?

There are several organisms to consider in this sort of scenario. We should be thinking about HACEK organisms, anaerobes, Pasteurella spp., oxidative non-fermentors like Burkholderia spp., Capnocytophaga spp. Consider micro-aerophilic bacteria such as Campylobacter spp. and Helicobacter spp.  And don’t forget about exotic organisms such as Brucella spp.  Even then, this list is by no means exhaustive, and I am sure there are others that you have come across that I have forgotten about!

What can the lab/clinical microbiologist do to narrow the differential down and manage accordingly pending plate growth?

A few things come to mind:

Aerobic or anaerobic bottle positive?: If the aerobic bottle only is positive it can point to non-fermentors like Burkholderia spp. If the anaerobic bottle only is positive, then one must think about anaerobes (e.g. Bacteroides spp. Fusobacterium spp. )

Gram stain appearance: A cocco-bacillary appearance should make one think of Haemophilus and Brucella. Longish, pleomorphic spindle-shaped organism on Gram point towards Capnocytophaga. “Seagulls” or “squiggles” should send you in the direction of Campylobacter/Helicobacter

Patient History: A history of dog bites/exposure should make one think of Capnocytophaga. A prosthetic valve or other valve disease, or clinical stigmata of endocarditis can indicate a HACEK organism. A history of injecting drug use makes one suspicious of Burkholderia cepacia. A travel history to an endemic area could make one think of Brucella spp. or Burkholderia pseudomallei. In a patient with neck pain and swelling, you don’t want to miss a Fusobacterium necrophorum. If the patient is frankly septic, you want to make sure they are getting covered for Capnocytophaga and Pasteurella.

Of course, all this is speculation, and our educated guesses may be completely wrong in the end. It is however important speculation… We want to make sure that the patient is being covered for the most likely and the most serious possibilities.

Taking another, but no less important angle, from a lab point of view it is essential that any slow growing Gram-negative organisms are worked up in a biohazard cabinet. Laboratory exposure incidents for organisms such as Brucella spp.  and Burkholderia pseudomallei are resource-intensive, stressful for the staff, and for the most part avoidable.

And sometimes the bugs just like to mock us, even make fools of us. Just recently, I was convinced a wavy Gram negative rod in (multiple) positive blood cultures from a patient was going to turn out to be a Campylobacter, only for it to finally be identified as a Helicobacter cinaedi… Wrong again!

Michael

“Perfect is the enemy of good (microbiology)”

The Art of 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