Category Archives: Future of Microbiology

“A Smorgasbord of Microbiology”

Future of Microbiology, The Art of Microbiology, The Wandering Microbiologist,

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

“Metagenomic disruption of the diagnostic microbiology lab”

Future of Microbiology, ,

I am 50 now, so I only have another 25-30 years of my working career left. So much to do in so little time!

I often wonder what the microbiology lab will look like on my last day at work. (I have posted on this before). Possibly a more interesting question is how I will look on my last day at work…

I am interested in how metagenomic approaches are going to disrupt the diagnostic microbiology lab and whether this will eventually become a mainstay of microbiological diagnosis, and eventually consign the agar plate to the museum.

The strangely named “shotgun metagenomic sequencing” involves sequencing all genes present in a clinical sample thus allowing identification of pathogens, and (as a bonus) their associated resistance genes and pathogenicity factors.

It sounds relatively straightforward, but there are certain challenges that one needs to be aware of.

  • Sensitivity:- Unlike PCR, the process does not involve an amplification step, therefore it may not be as sensitive as other currently existing methodology. In addition, if the sample contains a lot of human DNA, or DNA from non-pathogens, then the pathogen can be “drowned out” in the testing process. (stoichiometric ratios). Methods to enhance pathogen and suppress non-pathogen/host nucleic acid during the sequencing process are in development to mitigate this issue, but it is a work in progress.
  • Turnaround Time:- Traditional sequencing can take 1-2 weeks when you add the time for the various steps; extraction, library preparation, sequencing and bioinformatic analysis. This is still slow compared to current culture-based and PCR methodology. Newer Real-time sequencing techniques such as Oxford Nanopore can potentially reduce this turnaround down to a couple of days.
  • Cost:- Cost is coming down, and depending on what sequencing platform you use, can be anything from a hundred dollars to a few hundred dollars per sample. The cost will almost certainly come down further but we are still some way from the cost of a couple of agar plates.
  • Bioinformatic analysis and validation thereof:- The bioinformatic analysis of genetic sequences remains somewhat foreign to most microbiologists. Slowly but surely automated bio-informatic pipelines are being developed which automates this step for an increasing number of pathogens. However, validation of these pipelines is laborious and difficult and requires the input of specialist bioinformaticians.

There are now metagenomic assays commercially available in several areas, the most promising possibly being metagenomic analysis of CSF samples for infective causes of meningo-encephalitis. But it is still only a small niche area of the market, and it has a long way to go before becoming mainstream.

If you look at MALDI-TOF, it took approximately 25 years from the technology becoming available, until being widely adopted in clinical microbiology labs. The reason it has been so successful is because it is fast, accurate, cost-efficient and scalable. I think metagenomic sequencing will take just as long. Operationalisation of exciting technology is a protracted and somewhat painful process…

So, on my last day at work, around about 2050, I think metagenomics will be commonplace in most reasonable sized diagnostic microbiology laboratories. But I have a feeling that the tried and trusted agar plate will still be around… 

Michael

“The Molecular Revolution”

Confessions of a Microbiologist, Future of Microbiology, , ,

Time to get back to some writing “post” COVID!

When I started at the laboratory I currently work at in New Zealand in 2007, we only did one molecular assay, a chlamydia PCR, and we did this with separate extraction and amplification platforms on an open bench, with all sorts of potential for contamination. And we were/are not a small lab, a sizeable regional centre, processing well over 1000 microbiology samples a day.

2007, it’s actually not that long ago…

Fast forward 15 years and everything has changed. We now have a very sizeable menu of molecular assays performed on a range of different platforms. CSF, respiratory virus and GI panels, gonorrhoea, trichomonas, HSV/VZV,  HIV, HBV &HCV viral loads, Legionella spp., Mycoplasma pneumoniae, C. pneumoniae, C. difficile to name just a few. We even have a Mpox PCR!

A lot of these assays are now on commercial platforms that perform both the extraction and amplification steps in an automated fashion in a closed environment, essentially allowing placement of the platform anywhere, and can be run by most of our staff. The results are often available within a few hours of the sample being received in the laboratory.

In summary, the clinical service we can now offer is vastly improved from 15 years ago. I suspect it is much the same in many diagnostic labs throughout the world.

The big question is what will happen in the next 15 years? Will high volume sample types such as throat swabs, vaginal swabs, sputum samples, all still culture based at my lab, succumb to the revolution and go molecular? It is entirely possible that this will be the case. It will probably come down to cost first and foremost. Personally I see throat swabs switching to molecular very soon.

And what place will there be for whole genome sequencing in the diagnostic lab? That is a whole other question in itself but there are quite a few labs now in NZ who have acquired Nanopore Minions and are now “playing” with them in the areas of Infection Control and metagenomics.

My prediction is by 2030, for most diagnostic microbiology labs, their molecular department will be bigger than their traditional culture-based bacteriology department…

What do you think?

Michael