Category Archives: Future of Microbiology

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

“The Annual Ritual”

A lot of diagnostic clinical microbiology laboratories create an annual antibiogram at the start of each year in order to inform laboratory users of local susceptibility rates for common microbe/antibiotic combinations. Here is a link to the one for my own laboratory.

It is a time honoured tradition, a ritual of sorts… There would be uproar from the clinicians if we didn’t produce it.

And yet such antibiograms are fundamentally flawed…

They are overly simplistic because resistance rates can vary markedly in different patient cohorts and different sample types.

Take the following examples (based on my local data searches):

  • Antibiotic resistance rates for urinary isolates differ markedly according to age and sex. Urinary isolates from young women have much lower resistance rates to uropathogens than old men, with the difference being up to 25% depending on what microbe/antibiotic is being tested. This has very obvious implications for empirical antibiotic choices for UTI in different population cohorts.
  • Staphylococcus aureus resistance rates to mupirocin are much higher in young people with recurrent skin infections than in the (elderly) cohort about to go elective  joint replacement.
  • MRSA rate as a percentage of total Staphylococcus aureus isolates is significantly higher in superficial wound swabs than it is in blood cultures.

These are just a few examples of many, but the common theme here is that different exposure rates to particular antibiotics in different population cohorts lead to different resistance rates.

So I suspect the days are numbered of static antibiograms shown in table form on an A4 sheet of paper.

So last year!

I see the future being an electronic interactive antibiogram, possibly in the form of a smartphone “app”. The clinician enters a few important variables, such as patient age, sex, sampling site, and community/hospital patient, along with the microbe isolated. The app then calculates a more accurate antibiogram based on the particular cohort that this patient falls into.

This is the future, I am sure of it.

The only downside to such an approach is by splitting the total susceptibility data available into different cohorts, the sample size for analysis goes down, which can then lead to bigger margins of error in the results for less common microbe/antimicrobial combinations. This however could be addressed in the app by adding a disclaimer to resistance rates calculated from small sample numbers.

And maybe an interactive electronic antibiogram is in existence already, in an ultra-progressive laboratory somewhere… If so, please let me know!

I had better get started on creating that app!

Michael

“The Requesting Pyramid”

In many laboratories, clinical details on request forms can be structured into a pyramid shape as below.

Let’s take the example of otitis externa.

A good proportion of request forms will be at the bottom of the pyramid, where there are no clinical details present to suggest that otitis externa is the clinical suspicion (as opposed to otitis media, cellulitis of the pinna, or some other condition). Also included in this category are cases where clinical details have been included but are unrelated to sample type, e.g. an ear swab sent with clinical details of “sore throat”. This scenario happens in all sample types with disturbing frequency… (e.g. mid-stream urine sent for a patient with clinical details of chest pain!)

The next level up in the pyramid is where clinical details are present but are insufficient to justify the sample being sent to the laboratory. For example the clinical details might state “Otitis externa“. However most patients with straightforward otitis externa do not need an ear swab sent to the laboratory. Laboratory culture of an ear swab in clinically suspected otitis externa should be the exception as opposed to the rule…

The top level of the pyramid is where clinical details are not only present, but they also give a sound rationale as to why the laboratory is receiving a sample. e.g. “Recalcitrant otitis externa not responding to topical treatment.” or “Diabetic with painful inner ear and fever, clinical suspicion of malignant otitis externa“.

This requesting pyramid applies to most different sample types and clinical scenarios.

At my laboratory, we are doing our utmost to turn this pyramid on it’s head. We have made significant progress to date. In fact our pyramid is starting to look more like a rectangle.

By the end of the year we hope to have removed the base of the pyramid altogether by adopting a policy of having accompanying clinical details pre-requisite for all microbiology tests. I.e. No clinical details, no test.

And that is the way it should be…

Michael