“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

“Too much information”

The Art of Microbiology, ,

Can the microbiology lab give too much information to the clinicians?

Take the following hypothetical example regarding reporting of enteric type organisms:

Patient X presents with acute appendicitis with perforation. They are taken to theatre for appendicectomy and peritoneal washout, and started on IV cefuroxime and metronidazole. The sample of peritoneal fluid is returned from the microbiology lab as being “mixed enteric flora”. the patient recovers well, and they are discharged after 3 days on oral co-amoxiclav to complete a 1 week course of antibiotics.

Patient Y presents with acute appendicitis with perforation. They are taken to theatre for appendicectomy and peritoneal washout, and started on IV cefuroxime and metronidazole. However, in this patient, the microbiology lab decides to work up the individual organisms in the peritoneal fluid sample. The report states that the patient has grown an ESBL E.coli, an Enterococcus faecium, a Pseudomonas aeruginosa and a Candida albicans. Even though the patient is recovering well, the clinician feels obliged to cover the organisms that the micro lab has grown and reported, and changes the antibiotic therapy to meropenem, vancomycin and fluconazole. The patient unfortunately develops a bout of Clostridium difficile diarrhoea (!), extending their hospital stay by a week.

Microbiology labs can get very nervous about reporting “mixed enteric flora” from sterile site samples. They really shouldn’t be.

Here are a few pointers as to when it may be reasonable for the microbiology laboratory to report “mixed enteric flora”

  • Non-sterile site samples:- almost always
  • When several organism types are present- the number of different microorganism types present in a sample is inversely proportional to the value the lab can provide to the clinician
  • When no specific organism is dominant over the others
  • When source control has been achieved-this is important as in the hypothetical example above.
  • Drain samples- generally of low value unless the drain has just been inserted
  • When the clinical microbiologist has liaised with clinical team and clear that patient is doing well on current therapy- Treat the patient, not the result.

Such an approach saves the lab time and money, and may also be beneficial to the patient, as demonstrated above. Sometimes in our efforts to do the right thing, we end up trying just a bit too hard…

Michael

 

 

 

“Less is more in the microbiology laboratory?”

The Art of Microbiology, , ,

I am by nature quite a lazy person. Don’t get me wrong, I am not afraid of working hard at times, but I am always on the lookout for ways in which I can optimise the productivity and the quality of the laboratory, whilst creating time and resource for other opportunities.

Time and effort are terrible performance metrics…

Aside from efficiencies, can doing less work in the microbiology laboratory actually lead to better patient outcomes? We know that our ultimate aim is to improve patient management. Are there circumstances where in our enthusiasm to optimise patient care, we might actually do the opposite?

Here are some examples where doing less work in the microbiology lab might actually be beneficial to patient care:

Minimising work up on probable contaminants – If coagulase negative staphylococci isolated from blood cultures are routinely reported with susceptibility profiles without any supporting clinical information that they might actually be significant, this will lead to unnecessary antibiotic use with the potential for adverse effects, along with the potential for delayed patient discharge.

Avoiding tests with low clinical utility – Sputum cultures in the community setting are rarely useful, and the results may lead to undertreatment, overtreatment or simply the wrong treatment.

Reducing unnecessary microbiology tests– Rejecting urine cultures from patients where there is no evidence of UTI symptoms on the request form prevents unnecessary treatment of these patients with antibiotics.

Not processing duplicate specimens – Rejecting repeat samples (e.g. urine, sputum, stool) submitted on the same day from the one patient means that conflicting results are avoided.

Avoiding overuse of broad-range multiplex PCR panels – Running a full respiratory viral panel for a simple upper respiratory tract infection may end up delaying patient discharge from hospital. More targeted testing is often better.

Following proper sample collection and rejection criteria – Rejecting poorly collected specimens (e.g., saliva instead of sputum for pneumonia testing) avoids misleading results and unnecessary treatments.

Optimised result reporting – For example, reporting Group C/G beta-haemolytic streptococci from throat swabs in patients with acute pharyngitis may lead to unnecessary antibiotic prescribing. Along the same lines, testing and reporting unnecessarily broad antibiotics when performing susceptibility testing can lead to unnecessarily broad antibiotic coverage with concomitant side-effects on the patient and selection of antibiotic resistant bacteria.

As demonstrated above, there are lots of ways in which doing less work in the microbiology lab is not only cost-efficient, but it can also improve the overall management of the patient.

As the range of different assays we are able to offer in the microbiology lab continues to increase, we need to constantly review our current test repertoire and whether it is providing significant value to the clinicians, and ultimately the patient.

Less is often more when it comes to the microbiology laboratory.

Michael