“Workflow trumps Fancy Tests”

I happened to be visiting a microbiology lab in a large teaching hospital last year. We were shown all the assays they used to rapidly identify a pathogen from positive blood cultures: PCR assays, FIuorescent In-Situ Hybridisation (FISH). They had the works!

The range of tests available was very impressive, and would be the envy of most diagnostic microbiology laboratories.

But there was a catch… At 8pm in the evening, the microbiology department shut up shop and everybody went home. The blood culture analyser stood there completely untouched until 8am the next morning, including any bottles that flagged positive during this time.

So a blood culture that went positive at 9pm would be sitting in the analyser for at least 11 hours before any attempt was made to identify the pathogen.

This got me thinking!

It actually doesn’t matter that much how many fancy assays you have, or how much money your laboratory has. If you can’t get your workflow right then it all becomes a bit academic.

I am a big proponent of 24/7 staffing of microbiology laboratories, or at the very least the processing of positive blood cultures being done 24/7. It is after all one of the most important samples in the microbiology department. We have plenty of lesser importance!

Turnaround times generally don’t just include the actual analysis of the sample. More often than not, it includes storage time, transport/courier time, registration time, verification time, etc.

And then the final result has to be both received and acted on by a clinician. This communication step is also vitally important. There are so many steps, pre-analytical, analytical and post-analytical that contribute to the total turnaround time.

It is useful to do intermittent vertical timeline audits of your critical samples, to see where the delays are occurring, and then sort these out first before you consider fancy assays. And often such delays can be sorted without having to spend a lot of money. It might just be a case of relocating a blood culture analyser, or adding an extra courier run…

I am not against fancy assays, they have their place, but only as part of the whole process…

Michael

“A taste of my own medicine”

I hadn’t been feeling quite right since Christmas… Upset stomach, loose bowel motions, no appetite, and worst of all I didn’t even feel like a glass of wine in the evenings! The symptoms weren’t that severe, unfortunately not even bad enough to keep me off work, but they just grumbled on and on…

After a few weeks of this, it was time to call in the help of my microbiology laboratory. And sure enough, the enzyme immunoassay for Giardia was positive on my stool sample. I was quite glad it was positive, because at least I had an answer for my symptoms, but also because I hate unnecessary laboratory testing!

I self-prescribed myself some oral metronidazole (“tut, tut…”),  at the high dose that is recommended for Giardiasis. At the higher dosage, it  is not a particularly pleasant medicine to take. It turned my urine so brown, I found myself checking my eyes for jaundice! It also made my morning coffee taste like dishwater.

I now feel much better, back to my normal incorrigible self. Looking back in retrospect, it was a classic textbook case of giardiasis. I have no idea where I got it from, and will probably never know! I don’t envy those who work in the murky waters of Public Health.

There is no better way of learning than experiencing the disease yourself. I would not recommend this however for lots of other infections. Giardiasis is probably one of the “better” ones to catch.


Giardia lamblia trophozoite

Another good way of learning about a particular infection is to get to find out its history. Giardiasis is fascinating in this respect. Giardia trophozoites were first observed in 1681 by Anthony Leeuwenhoek in his very own stool samples, on his funny looking microscopes. Thus it has to be regarded as one of the first infections to be diagnosed by a “laboratory”.

The name Giardia lamblia was in recognition of a French zoologist, Alfred Giard, and a Czech physician, Vilem Lambl,  who each contributed to the description of giardia trophozoites. Initially called Cercomonas intestinalis, it only became known as Giardia lamblia in 1915. It is also still known as Giardia intestinalis.

“Alfred Giard”

However none of these people mentioned actually made the connection between Giardia lamblia and infectious diarrhoea! In fact it wasn’t actually confirmed as a pathogen until the 1970s.

So my awareness of Giardiasis has now increased considerably, and we should all have a low threshold for testing for it in patients with chronic gastrointestinal upset, unexplained weight loss, failure to thrive, etc.

Apparently 200 million people worldwide are infected with Giardia lamblia, so I am not the only one!

Michael

Challenging the Dogma of Empirical Antibiotics

A lot of antibiotic treatment of infectious diseases is still “empirical” in nature. “Empirical” generally means “based on experience”, so to administer an empirical antibiotic means to give the antibiotic that is most likely to work based on previous experience with that infection.

Antibiotic treatment has traditionally been empirical because waiting for culture and susceptibility results was simply far too slow. Only a generation ago the average turnaround time for a microbiology culture test was 3 days and counting….

A lot of antibiotic treatment is still empirical in nature. If you go to your GP with a sore throat or a urinary tract infection, chances are high you will receive an empirical antibiotic. If you attend your local Sexual Health clinic with symptoms of gonorrhoea, you will likely be getting some empirical ceftriaxone long before the diagnosis is established. If you go to your local hospital with pneumonia, you will likely get a macrolide antibiotic (to cover atypical pathogens) as well as a beta-lactam.

However microbiology labs are improving all the time. We now have the potential in many areas to make empirical treatment redundant for certain infections. Check out the following examples:

  • Rapid antigen and PCR tests are now available for the laboratory diagnosis of sore throat, with a turnaround time of minutes to a few hours.
  • Bacteriology automation, such as Kiestra TLA, can reduce turnaround times for urine cultures to less than a day, and a day and a half for wound swabs. I suspect a lot of patients with straightforward UTIs and wound infections can wait that long for a result without outcomes being adversely affected.
  • Rapid PCR tests for atypical respiratory pathogens (Legionella spp., Mycoplasma pneumoniae, Chlamydia pneumoniae) can mean that macrolide coverage for community acquired pneumonia can be stopped early, or not even started.
  • Ultra-fast PCR tests for influenza can prevent any antibiotics being prescribed in patients who present with Upper Respiratory Tract Infection (URTI).
  • PCR tests with genotypic antimicrobial susceptibility information (e.g. Neisseria gonorrhoeae, Mycoplasma genitalium) can avoid the use of empirical antibiotics and selection pressure for antibiotic resistance.

Costing silos, resistance to change, and a lack of vision are amongst the main reasons that it takes so long for treatment protocols to move to “directed therapy” wherever possible.

There are still areas where empirical antibiotics will continue to be necessary. The acutely septic patient presenting to hospital is one such example. However large swathes of infections, particularly in the community setting are still managed by empirical antibiotic therapy. This is the way it always has been. However that doesn’t mean it is the way it always should be…

The next big revolution in clinical microbiology labs should be to challenge the dogma of empirical antibiotic treatment. This would be a huge step forward towards counteracting the development of antibiotic resistance.

Michael