Tag Archives: antibiotic susceptibility testing

“Do we perform too much antimicrobial susceptibility testing?”

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

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?

Michael

“The dark art of antibiotic resistance surveillance”

Antimicrobial Resistance, ,

This post is best read with a glass of wine…

As a profession, I think we are really not very good at measuring antibiotic resistance/antibiotic susceptibility patterns…

We are very happy to proclaim at the start of presentations “Antibiotic resistance is increasing”, or “In the era of increasing antibiotic resistance.” without providing any data to support this claim.

We need to move away from this type of talk. We are after all, scientists, not politicians.

However antimicrobial resistance surveillance is deceptively difficult. Here are a few reasons why high quality surveillance data is hard work, and requires a lot of thought and planning…

  • It is actually the trends that are critical:- There is a big difference between providing an annual antibiogram to clinicians, and presenting graphs which show changes in antimicrobial susceptibility over time. For example a GP looks at an annual antibiogram provided by the microbiology laboratory and sees that organism X has a resistance rate to antibiotic Y of 10%. Doesn’t sound too bad and certainly a viable treatment option. But if we knew that the resistance rate was 5% last year and 2% the year before that, then we have a problem. It seems obvious, but antimicrobial resistance surveillance is all about trends, not snapshots.
  • Too many permutations:-  There are more than 50 different commercially available antibiotics, and many hundreds of microrganisms identifiable on MALDI-TOF. So the number of antibiotic:microbe combinations is well in to the thousands. So which ones should be measured? The obvious ones are those that are commonly encountered and used, e.g susceptibility of E. coli to trimethoprim, ones that are clinically very important, e.g. susceptibility of Streptoccus pneumoniae to penicillin, or those of great public health importance, e.g. susceptibility of E. coli to meropenem. The ones to be avoided is where the combination falls outside these groups, particularly those where the numbers seen are insufficent to get meaningful data. e.g. Selenomonas spp. susceptibility to ciprofloxacin.  The important thing here is to decide on the microbe:antibiotic combinations to be measured before you start your surveillance program. Otherwise the data is open to exploitation, with people picking antimicrobial resistance surveillance data to suit their particular agenda. e.g. Antibiotic resistance is increasing because Microbe A is becoming more resistant to antibiotic B, and ignore the fact that Microbe C is becoming less resistant to antimicrobial D…
  • Different Definitions:- Because there are different antimicrobial testing standards out there, e.g. CLSI, EUCAST, CDS, etc., one person’s definition of resistant may not be the same as anothers… It is very important to ensure everyone has the same “definitions” of what is resistant and what is not resistant, before you even start. Otherwise you are on a hiding to nothing…
  • Politics:- Everybody has their own wishes and desires, and it is no different when it comes to measuring antibiotic resistance surveillance. Everybody wants to look at different antibiotic:microbe combinations, use different testing methodologies, present the data differently. This can cause problems with not only the accuracy of the data, but also in getting any surveillance data at all, when multiple laboratories are required to work together. When antibiotic resistance data requires the political co-operation of different countries then the difficulties move onto a whole new level altogether. Despite there being a willingness to work together, getting multi-national agreement on surveillance is a monumental task.
  • The goalposts get moved. Every so often the breakpoints get changed, for various reasons, so that an isolate that was once susceptible can become resistant (on paper), and vice versa. This is why using MIC values for surveillance purposes is so important, as it is an objective measurement which has no interpretation applied to it. This facilitates the acquisition of accurate surveillance data over many years.
  • Memory is erased. Sometimes when the laboratory information sytem (LIS) in a microbiology laoratory gets changed, a lot of the historical susceptibility data can get lost, either because it is not compatible with the new system, or not thought to be important enough to keep. Although electronic storage of laboratory data has been around for at least 20 years, as far as I am aware many microbiology laboratories do not have 20 years of data, for exactly this reason. It is a very important point to consider when considering a change of LIS.
  • Biases:- So many things can lead to bias in the surveillance data… Participation bias, sampling bias, patient cohort bias, testing bias, etc.. The list is virtually endless. All these things need to be considered and corrected for as best as possible when performing antimicrobial resistance surveillance.

So it is not easy, by any stretch of the imagination.

Good antimicrobial stewardship programmes should be based on having sound, standardised and objective baseline antimicrobial resistance data against which any interventions can be audited.

The other big area of surveillance which is essential to antimicrobial stewardship programmes is antimicrobial usage data. This data goes hand in hand with antimicrobial resistance surveillance.

Although it’s easy to talk about increasing antibiotic resistance, it is actually very difficult to measure properly…

Michael

“Choices”

Antimicrobial Resistance, The Art of Microbiology,

2011-July-HI-2VitekCardsNEW

How many antibiotic susceptibilities do you release to the clinicians for any particular isolate?

At the extreme end of the scale, some microbiology laboratories think nothing of releasing 15-20 antibiotic susceptibilities for the one isolate. This sometimes happens in labs rich enough to have a Vitek or Phoenix where the system panels contain many different antibiotics, often customised for a particular institution.

However more is not always necessarily better…

The main reasons for not routinely releasing an antibiotic susceptibility on an isolate are as follows:

  • Unnecessarily broad spectrum for the clinical indication.
  • Low threshold to developing antibiotic resistance.
  • Relatively poor efficacy compared to other antibiotics for the clinical indication.
  • Logistically difficult to use.

The majority of mainstream diagnostic labs probably give a choice of 5-10 antibiotics per isolate. Even then that is still a lot of antibiotics for the clinicians to mull over. It also gives a lot of scope for non-standardised practice…

More laboratories, including my own, are looking more and more towards focused antibiotic reporting, in order to “guide” clinicians towards the optimal treatment regime.

For example we routinely release 2 antibiotics for a Staphylococcus aureus isolate from a general wound swab. (If MALDI-ToF succeeds in reliably differentiating between MSSA and MRSA, then one could potentially release flucloxacillin/cloxacillin alone, without doing formal susceptibility testing, and with a comment “Further susceptibilities available on request”)

We routinely release 4 antibiotics on urinary E.coli isolates. I am thinking of reducing this to 3.

For MSSA (Methicillin Susceptible Staphylococcus aureus) isolates from blood cultures and invasive sites we routinely release just the one antibiotic, flucloxacillin. The same principle applies with Streptococcus pneumoniae and penicillin from blood cultures. By doing this we make it crystal clear what the expected standard treatment is. Of course we have a few others ‘up our sleeve’ should they be required in the case of allergy, treatment failure etc.

And then of course it is always important to remember that we have the choice of releasing (or testing) zero antibiotics, where the clinical details are absent or they are not indicative of acute infection. We should probably use the zero option more, along with a comment saying “Antibiotic susceptibilities available on request”.

Occasionally we get calls from clinicians, a little bit upset or grumpy that we have not released more antibiotics. Being thick skinned, I don’t mind this at all. It gives me the opportunity to build relationships with the clinicians, and also to explain our thinking…

Michael