“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.


“A Question of Significance”

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.


“When the bugs take their time…”

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!