Category Archives: The Science of Microbiology

“Do we perform too much antimicrobial susceptibility testing?”

As lab workers, we like to be helpful. In general, we want to provide as good a service as possible. But sometimes I think we try a little too hard…

One of our key areas of work is antimicrobial susceptibility testing. This is our bread and butter of course. This is one thing that we can do but no one else can, and we like to show off our skills! But there are many circumstances where performing antimicrobial susceptibility testing adds little value for the patient and thus unnecessarily uses up valuable laboratory resources.

Polymicrobial cultures The clinical value of antimicrobial susceptibility testing is inversely proportional to the number of different organism types present in the sample. This includes sterile site samples. Many times in my career I have been asked to do susceptibilities on samples which have grown several different organisms. I almost always push back on this. It should very much be the exception as opposed to the norm.

Eye and Ear Swabs Conjunctivitis and otitis externa are primarily managed by topical preparations, which can even be antiseptics as opposed to antibiotics. In-vitro susceptibility testing correlates poorly with response to topical antibiotics. Antimicrobial susceptibility testing on ear and eye swabs should only happen in a small minority of cases.

Enterobacteriaceae, enterococci & pseudomonas in superficial wound swabs These organisms cause infection in only a very small proportion of samples that they are actually found in. Susceptibilities should only be performed when there is compelling evidence from the clinical details that they are causing problems. 

Enterococci in urines In contrast to wounds, enterococci commonly cause urinary tract infections (they can also represent contamination). However, because amoxycillin achieves concentrations in urine which exceed the MICs of most Enterococcus faecalis and Enterococcus faecium isolates (check out this reference), susceptibility testing is essentially futile, unless the clinical details suggest the patient has a penicillin allergy. A simple comment to this effect will suffice.

Beta-haemolytic streptococci Because beta-haemolytic streptococci are inherently susceptible to beta-lactams, susceptibility testing for these antibiotics is somewhat academic in the majority of simple wound/soft tissue infections.  I would do if the clinical details suggested penicillin allergy.

Anaerobes Anaerobes rarely require formal susceptibility testing. Bacteroides fragilis has predictable response to beta-lactam/beta-lactamase inhibitor combinations. and is often part of a polymicrobial infection anyway (see polymicrobial cultures). In our lab anaerobic susceptibility testing is most often performed for C. acnes causing joint infections, where we test penicillin (almost always susceptible, maybe we don’t need to test…) and clindamycin (very occasionally resistant).

Coagulase negative staphylococci from blood cultures Again these should only be performed when it is clear that the coagulase negative staph is the suspected pathogen (prosthetic material, premature neonates, etc.) which will only be the small majority of the total number of isolates.

Pseudomonas in sputa Once a patient with COPD becomes colonised with Pseudomonas aeruginosa in their sputum, it is generally there to stay. Pseudomonas susceptibility testing should only be done when it is clear from the clinical details that it is causing a problem, i.e. the patient is failing standard management. We also need to review susceptibility testing protocols on pseudomonas isolates from patients with bronchiectasis and cystic fibrosis. There is now increasing evidence that annual susceptibility testing on Pseudomonas isolates from Cystic Fibrosis patients is more than sufficient.

Candida from vaginal swabs It’s not just bacteria! Recurrent vaginal candidiasis is a common problem, and we are often asked to perform antifungal susceptibilities on such isolates. In my opinion it is hardly ever justified. Nystatin based topical therapy often works in these patients. Candida albicans isolates are usually susceptible to generous dosing of azoles. It is only Nakaseomyces glabrata (formerly known as Candida glabrata), where I occasionally acquiesce and perform susceptibility testing…

Of course, we can perform antimicrobial susceptibility testing but not report the results, having them stored just in case. But my view is that we should minimise this approach as it is generally wasteful. We should perform antimicrobial susceptibility testing when we are confident that we are going to report the results of at least some of the antibiotics from a testing panel.

At my lab we have progressed a lot in this area over the past decade and now perform minimal amounts of antimicrobial susceptibility testing in all of the areas above. What about your own lab? Is there room for improvement, and can you think of other areas where too much antimicrobial susceptibility testing is performed, that I have not thought of?


“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!


“Cohort Bias”

At my laboratory we only test nasal Staphylococcus aureus susceptibility to mupirocin in the following two circumstances:

  • Prior to joint replacement surgery as part of a Staphylococcal decolonisation bundle
  • In patients where the clinical details state recurrent skin infections

In the patients about to get their joints replaced, our nasal Staph aureus resistance rate to mupirocin is 3%. Not surprising really. This is a generally older cohort, less likely to suffer from impetigo and skin boils etc., and thus less likely to have been exposed recently to mupirocin.

In the patients who have recurrent skin infections, our nasal Staph aureus resistance rate to mupirocin is 15%. This is not surprising either. This cohort is generally young, and due to their clinical history are much more likely to have been exposed to a lot of mupirocin. As a cohort, they potentially have a lot of physical contact with each other (in kindergartens, in the school playground, on the sports field, in cinemas, backs of cars etc..,) facilitating cross-transmission.

This is a good demonstration of how much antibiotic resistance can vary, depending on what population you are looking at. 3% is markedly different from 15% and management of these different rates might be very different from an antibiotic stewardship point of view.

It also reflects the difficulties in measuring antibiotic resistance and then how to report such results in a meaningful manner.

We like to simplify things, and have just one result regardless of what biases might be at play. Measuring resistance rates is complicated enough due to the sheer number of microbe-antimicrobial combinations that can be permutated. To add another level of complexity by calculating different values for any one microbe-antimicrobial combination is too much for most of us to handle! 

But sometimes the difference in values between different population cohorts (as demonstrated above) is just too much to be ignored…