Tag Archives: CLSI

“Keeping it simple or keeping it accurate…”

Let’s say you are a clinician and you are looking at two different microbiology results on two different patients (A&B). Both have an E. coli UTI. Both results state that the E. coli is susceptible to trimethoprim. However what you don’t know is that the E. coli isolate on Patient A had a trimethoprim disc diffusion zone of 18mm (right on the EUCAST breakpoint), whilst for patient B the corresponding zone was a much more comfortable 26 mm.

And who knows, if you repeated the same testing on patient A a dozen times, the chances are you would have a few “non-susceptible”results, due to the natural margin of error of the test.

If I was a clinician, and had this extra (zone diameter) information, I would be a lot happier prescribing trimethoprim to patient B, even though they both have in-vitro “susceptibility” reported on the result. (The same principle of course applies if we were talking about Minimum Inhibitory Concentration (MIC) values instead of zone diameters.)

But do clinicians really want this extra information?

They are usually very busy, …and not particularly interested in microbiology.

In my experience all clinicians generally want to know is if an isolate is susceptible or resistant. They are not particularly interested in the details, with the exception of blood culture and sterile site isolates, when there is at least a modicum of interest in the degree of susceptibility or resistance.

So which is better.. a susceptibility result full of information, but potentially difficult to understand and interpret, or a result reduced to its simplest form.

There is no right answer of course…

I am not even convinced antimicrobial susceptibility breakpoints have a long term future.

More and more, year by year, the anti-microbial susceptibility committees (EUCAST, CLSI) are trying to take into account antibiotic dose,  renal function, degree of infection, etc. when setting antimicrobial breakpoints.

But they are really only scratching the surface…

Time for some major disruption!


“The end of Clinical Breakpoints as we know them?…””


During the ASM conference in Boston, I attended a couple of talks on the process of anti-microbial susceptibility testing (AST). There are really only two main players (a duopoly of sorts) left standing with regards to setting standards for AST. These are the Clinical & Laboratory Standards Institute (CLSI) and the EUropean Committee on Anti-microbial Susceptibility Testing (EUCAST).

Representatives from each organisation spoke during the conference sessions. Reading between the lines,  I did not get the impression that a unification of the two organisations was imminent, mainly because I did not detect any warmth between the respective speakers…

There was considerable discussion on the setting of Clinical Breakpoints. Clinical Breakpoints are necessarily a “messy” compromise between Epidemiological Cut-off values (ECOFFs), pharmaco-kinetic & pharmaco-dynamic (PK-PD) data, and most importantly, clinical response. As long as this model continues, EUCAST and CLSI committees will continue to tinker with and argue about the breakpoints, but in the painful knowledge that a single value can never be agreed upon as being a definitive answer. There are just too many variables.

The problem is therefore ripe for an app-based solution…

I foresee a future in anti-microbial susceptibility testing where the main variables are taken much more into account than they currently are.

I see the time when all the microbiology laboratory will do will be to provide an organism identification and  MIC values for a restricted number of key antibiotics.

The clinician will then take his smartphone app, enter this lab information, but also add in key patient variables such as site of infection, renal function & body mass index, and degree of immunocompromise.

The app will then process all these variables together and give for each antibiotic the likelihood of clinical response of a certain antibiotic, not only for this particular organism, but for this particular patient.

And thus there will no longer be a need for concrete/single value clinical breakpoints, but rather the focus will be on personalising the lab information to each particular patient.

I can see such apps for MIC interpretation being developed in the next few years. 

And if I were a lead member of NCCLS or EUCAST I would be recruiting the services of a good IT applications specialist on to the steering committee, and sooner rather than later…



“GLOBAL Antimicrobial Susceptibility Programme badly needed”

Trying to find antimicrobial resistance data for different countries can be frustrating. With a couple of clicks on a mouse I should be able to find the ESBL or MRSA rate for a particular country, and whether this rate is going up or down.

But I can’t…

To make real impact on susceptibility rates on a global basis, we need global surveillance, to know what the baseline resistance rates are in each country. We also need antimicrobial consumption rates that are comparable across countries.


Unfortunately this is just not happening at present. “SENTRY” made a decent effort and got some good data out, but for whatever reason (probably money) it seems to have downsized recently, not expanded (correct me if I’m wrong).

Europe has a good surveillance system (EARSS), but it is only Europe.

I know anecdotally that ESBL rates in some parts of Asia are extremely high but there is very little information out there on exactly how high.

There needs to be real political will with the necessary funding to acheive this goal. Unfortunately trying to acheive global co-operation in anything is incredibly difficult.

It is one thing to make impassioned appeals regarding the potential threat of antimicrobial resistance. (Click here for such an appeal by Dame Sally Davies, the Chief Medical officer of England.) However such appeals need to be backed up by cold hard objective evidence to have real impact.

The problem is compunded further by the fact that we have different international standards for measuring antimicrobial resistance. If the two main bodies, CLSI and EUCAST could put aside their differences and combine to form a global committee (GCAST…), it would go a long way to making the dream of global antimicrobial resistance surveillance a reality.

I think a (genuinely) Global Antimicrobial Resistance Surveillance programme will get underway at some point during my working career. If it does, it will be long overdue…