Category Archives: Confessions of a Microbiologist

“Sometimes you just have to admit that you were wrong”

Confessions of a Microbiologist, The Science of Microbiology, , ,

Many microbiology laboratories, including my own, have in place a CSF leucocyte count cut-off of 5 × 10⁶/L as a criterion for performing multiplex PCR in the investigation of meningoencephalitis. This diagnostic stewardship policy has attempted to focus testing on those most likely to have CNS infection, and to reduce unnecessary testing. However, growing evidence indicates that this approach is not appropriate when there is clinical suspicion of encephalitis…

Take this hypothetical case study…

A 58-year-old man, Mr J Bloggs, presents with fever, headache, confusion and a vague history of what could be a focal seizure. MRI was unremarkable. A lumbar puncture is performed within eight hours of presentation. The CSF shows a white cell count of 4 × 10⁶/L, normal glucose, and mildly elevated protein. Under existing laboratory policy, the CSF multiplex PCR panel is not performed because the leucocyte count is below 5 × 10⁶/L. Empirical acyclovir therapy is discontinued on the basis of the normal CSF leucocyte count. However, the diagnosis remained uncertain and persistent symptoms prompted a repeat CSF several days later. HSV-1 DNA is detected by PCR on the second CSF sample.

CSF analysis is excellent for detecting meningeal inflammation, as occurs in meningitis, but it is less reliable for parenchymal infection, which characterises encephalitis. In encephalitic processes, inflammation may be largely confined to the brain parenchyma, without a corresponding CSF pleocytosis, especially early in the disease. Leucocyte thresholds designed for meningitis are therefore poorly suited to encephalitis and potentially risk giving false reassurance.

Recent evidence has demonstrated that a substantial proportion of patients with encephalitis have normal CSF leucocyte counts. The most compelling data to date come from a recent large retrospective study by Habis et al., involving 597 adult patients with encephalitis. They found that 25.3% had no CSF pleocytosis (<5 × 10⁶/L). Among those with infectious encephalitis, 19% lacked pleocytosis, and notably, 23.7% of HSV-1 encephalitis cases had normal CSF cell counts at presentation. Patients without pleocytosis were also less likely to receive empiric acyclovir, showing how laboratory thresholds influence clinical care. These findings strongly challenge the validity of using a fixed leucocyte cut-off to determine whether PCR testing should be performed, as it would exclude roughly one in four encephalitis patients, including many with HSV infection.

In addition, and as also shown by Habis et al., patients without pleocytosis are less likely to receive prompt antiviral therapy. This matters because early treatment, particularly for HSV encephalitis, improves outcomes. Diagnostic stewardship should promote timely, appropriate testing, not create barriers based on outdated assumptions…

Laboratory protocols should always be responsive to new data. When high-quality evidence emerges that challenges existing practice, policies must be reviewed and revised. While a 5 × 10⁶/L CSF leucocyte threshold may remain reasonable in the investigation of suspected meningitis, it is no longer valid in the setting of suspected encephalitis, where pleocytosis may be absent in a substantial proportion of cases. Stewardship frameworks should incorporate these distinctions, and most importantly, allow flexibility in order to optimise patient safety.

Laboratory practice must evolve with emerging data to ensure that diagnostic stewardship supports, rather than hinders, accurate and timely diagnosis. I am a diagnostic stewardship enthusiast, but I am the first to admit that we don’t get it right all the time.

Michael

p.s. Check out this great editorial on this topic!

References

“Trying to escape microbiology”

Confessions of a Microbiologist, The Science of Microbiology, The Wandering Microbiologist, , ,

“You can take the microbiologist out of the lab, but you can’t take the lab out of the microbiologist”

I was fortunate enough to attend the Olympics in Paris last month, the first time I have ever been to the Olympics. It was a fantastic experience, and we managed to see several events, including football, tennis, athletics, cycling, Rugby 7s and triathlon. Moreover, Paris is my favourite city, so I take every opportunity to visit!

I was hoping to forget all about all things microbiological for a month, and to a large extent this happened, until I was watching the triathletes swimming in the Seine!

You are probably aware of the story, but it was a big thing, and something of a propaganda stunt, allowing the Olympic athletes to swim in the River Seine, and the French Government invested heavily in cleaning up the Seine in order to facilitate this. 

In the end it was touch and go. Heavy rain before the Olympics put the E.coli counts up in the river, and at least one of the training sessions and the men’s individual event had to be postponed due to levels exceeding the acceptable limits.

A few athletes got sick after swimming in the Seine but of course it was virtually impossible to prove that the river swimming caused the illnesses.

Which got me thinking. “What are the acceptable faecal contamination limits for swimming in rivers, and is the risk any different for elite athletes in the Olympics?

There are safety standards set by World Triathlon, which indicate that colony-forming units (CFU) of E. coli per 100 milliliters of water should not exceed 1,000 and enterococci levels should be below 400 CFU/100ml. As one can see from this report, levels were acceptable on the day of the race, but not on several other days.

Of course, the cut-offs for E. coli and enterococci are completely arbitrary… The higher the counts, the higher the level of faecal contamination, and thus the higher the risk. E. coli and enterococci are of course only indicators, as most E. coli and enterococci do not cause gastrointestinal illness. There are a whole range of infections that one can acquire by swimming in faecally contaminated river water, including bacteria, viruses, & spirochaetes. Gastroenteritis is likely the highest risk but ear infections and skin infections can also occur.

There are several other factors that may affect the overall risk. The risk will depend on the range of gastrointestinal pathogens present in the water. I.e. swimming in a river in India might carry a different risk to swimming in a river in Paris even if the E. coli levels are equivalent. The amount of water ingested will also be a factor. I imagine an elite athlete going hell for leather in the Olympic triathlon will be intaking a lot more water whilst swimming than if President Macron goes for a leisurely dip in the Seine, if he ever does. The exposure time will also be a factor. The athletes competing in the 10km distance swimming event will have a lot more cumulative exposure than the triathletes swimming 1500m. Finally, the “host” needs to be taken into account. The cohort swimming in the Olympics will be overwhelmingly young, fit and immunocompetent thus potentially at less risk than the general population.

So clearly it is not as simple as just saying >1000 E. coli per 100ml of water is unsafe and less than that is safe. It is far more nuanced than that.

For elite athletes, whose livelihoods depend on competing in such events, they really have little choice in the matter. For myself however, who is definitely not an elite athlete, I like looking at the Seine, and it certainly appears cleaner than in years gone by, but I will pass on the swimming just for now.

Michael

 

 

 

“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