Policy for high CFU/Endo count

[Ian Wilde]

Does anyone have a departmental policy of what to do in the case of a high TVC/Endo count?

The standard reply is to continue but without HDF, but why?

As we know when you get your high result you have already done a week on water that wasn't up to spec.
Usual response is to retest in case of handling/lab error so that's another week on HD rather than HDF

I'm thinking of doing an experiment; running a machine on tap water (to enable a consistently high TVC/Endo count) in the workshop and sampling both the raw water and the HDF sub fluid on a daily basis for a week to see what happens.

I personally think the endotoxin filters can handle it...

Anyone else done similar or have any thoughts?

Will technology prevail over what people MAY think happen??

[Mark W]

Hi Ian,

There is a very good flow chart on page 226 (Figure 8.5) in the book "Water and Dialysis Fluids A QUALITY MANAGEMENT GUIDE" by Carlo Boccato, David Evans, Rui Lucena and Jörg Vienken, which explains the various actions depending upon how high the count is.  The response is different as you would expect if the Maximum Level is exceeded versus the Action Level being exceeded.  Unfortunately I can't share it due to copyright which I appreciate isn't particularly helpful.  It advocates that if the maximum level is being exceeded an extraordinary disinfection should be carried out and both water and dialysis fluid samples be monitored.

I'm interested to understand where the "standard reply" comes from?

As for running a machine on tap water I think you may struggle as it should prevent it from operating because of the conductivity being too high.

I still think you may be right with the endotoxin filters, especially as you should have redundancy as substitution fluid is required to be produced under single fault condition.  However I don't think this is really the point as you want to be avoiding the proliferation of bacteria in your dialysis machine in the first place.

I hope that helps.
Mark

[Chris Bates]

Might be an idea to put the tap water through carbon filtration to get rid of the chlorine; like you would get in a main plant or home setup.
I have seen a lot of biofilm gel in the pipes after the carbon but not so much before.

[Ian Wilde]

Thanks both for quick replies to my question.

The "standard reply" I mention comes from my limited exposure to the question when I have been at the odd conference or promotional/training day.  The standard reply (even from the mighty "F" company) appears to be to continue in normal HD mode only until a suitable quality is achieved.

I would just like to point out that I am in no way supporting a blasé attitude to monitoring our water quality and that every effort needs to be made to ensure our plants produce water with readings well below any action levels. I just have concerns that up and down the country there may be techs who when faced with a result that is questionable won't know what the correct course of action is to do?


I have said book in front of me and am studying the flowchart.  The actions feel as though they are written for you if you can get an instant result of your "Rw" (results water analysis).  The flowchart makes perfect sense on paper.  In the real world I don't find it quite so straight forward.

When an extraordinary disinfection is called into action that is only part of the solution/action - we still have to wait a week to get the result and my thoughts with the experiment where to see what the suggestion may be in regards to type of treatment available/allowable?

[Mark W]

Good morning Ian,

The mighty "F" company's response seems very belt and braces with regards to HDF.

Ian Wilde wrote

I would just like to point out that I am in no way supporting a blasé attitude to monitoring our water quality and that every effort needs to be made to ensure our plants produce water with readings well below any action levels.

I understand and I hadn't interpreted it in any other way.

Ian Wilde wrote

I just have concerns that up and down the country there may be techs who when faced with a result that is questionable won't know what the correct course of action is to do?

I agree.

Ian Wilde wrote

I have said book in front of me and am studying the flowchart.  The actions feel as though they are written for you if you can get an instant result of your "Rw" (results water analysis).  The flowchart makes perfect sense on paper.  In the real world I don't find it quite so straight forward.

The "white" book's flow chart is the best I've found.  I believe this diagram is referenced within the newly revised 23500-1:2019 standard.

Ian Wilde wrote

When an extraordinary disinfection is called into action that is only part of the solution/action - we still have to wait a week to get the result and my thoughts with the experiment where to see what the suggestion may be in regards to type of treatment available/allowable?

I think that performing the tests is a worthwhile exercise.  I've done them myself unintentionally with 2 separate poorly performing RO machines measuring before and after the ETRF and the after results were all of ultrapure quality.  Also remember that you can't test for sterile substitution fluid.

Overall it's a question of risk management.  I'd be expecting the clinicians to be correlating any patient symptoms.

[Garry]

Hi Ian,

We had a similar experience a few years ago when one of our aging plants was consistently failing microbiology.  We did stop HDF treatments.  The view I took was that the quality of fluid required for infusing was based on the equipment being supplied with water meeting the BS13959 limits.  Fortunately we had introduced clean dialysate filters on all of our non HDF equipment.  During this time we introduced weekly sampling at the equipment sample points and all samples  returned <0.050eu/ml and 0 CFU/ml thus confirming water quality still met the standard for dialysis.

Another reason to stop is that the extremely low sensitivity levels required to confirm fluid is suitable for infusion makes it very difficult to provide assurance on the water quality in-house (or with a standard outside lab).  For this reason we stop HDF treatments once water quality is confirmed as exceeding limits.

[Chris Pearson]

I find it quite interesting that nobody ever used to worry about the huge amounts of backfiltration we used to get with high flux hollow fibre dialysers and low uf rates on standard machines with no endotoxin filters,can't remember anyone seeing and reporting febrile reactions then ?

[Ian Wilde]

I saw a presentation once from a well known professor where he mentioned that the human gut is a ticking time bomb of endotoxin levels that are off the chart compared to what we are looking for in our water and dialysate.

[Chris Pearson]

Won't a normal high flux polysulphone hollow fibre dialyser membrane just act as it's own endotoxin filter with no clinical issues short term until you get the water problem sorted ?

[Ian Wilde]

I think the issue is Chris that with hdf the fluid is infused directly into the bloodstream although it will come through a filter first anyway.  I think the main question is simply how good are these filters? What levels can you put I to them and still get pure water out?

[Chris Pearson]

Sorry Ian my reply wasn't very clear,I meant why it's OK to go back to normal HF PS dialysis even if the counts are too high for HDF.

[mike.jones]

Not much of a policy but having been through some high levels on portable RO's this is what I learnt.

Please correct me if I am wrong as I am no expert.

CFU's can be on the higher side 100+ and not give much in the way of adverse?

1000+ would suggests highly contaminated bio film membrane which then leads, depending on disinfection/pasteurisation, high Endo.

Endotoxin above the normal 0.25 to a point can be caught by Diasafe/Cutfilter/ultrafilter etc but when Endo approaches 1eu/ml level then it would be suggested that there is also another contaminant present which I know as a EXO toxin.

EXO toxin are not analysed in renal samples and can pass the filter leading to epo resistance and immflamation etc etc.

So in short I believe a very high TVC or an elevated Endo is when I start to panic.

Mike

[Chris Bates]

As I understand it Endotoxin is lipopolysaccharide from cell walls of dead or damaged bacteria and are pyrogenic.

Exotoxins are proteins secreted by living cells and are non-pyrogenic but cause a strong immune reaction. I have no idea if they can penetrate an ultrafilter.

So if you are interested in exotoxins its probably the CFU count that would be relevant.

Botox is an exotoxin and the most deadly substance in existence !

[Ian Wilde]

I'd not heard of Exotoxin before...

[Ian Wilde]

So high CFU sounds like it would mean more EXOTOXIN being released which means more chance of a patient reaction?

I was going to say why are we not testing for it however we must be via the CFU measurement indirectly?

[fraser gilmour]

I agree with Chris P, setting your policy to say it's OK to switch from HDF to HD in the event of a one off sample coming back outside of the microbiology limits doesn't seem logical to me. You will still get infusion of dialysis fluid through the dialyser in high flux HD, rather than infusion of the blood circuit after at least two ultrafilter stages in HDF mode.
The filters in HDF machines are capable of producing infusion quality fluid from two stages of ultrafiltration when fed with water that is well outside of the limits.
It would make more sense to move to a period of more frequent testing to assess if there actually is a problem, starting with an immediate retest, followed by some remedial action, i.e. run an extra thermal or chemical disinfection.
What we see with our systems is most of the time we return results that meet ultrapure standard post RO from the loop, occasionally we register a low CFU count or a slightly elevated EU. If we suddenly had a TVC or EU outside of the limits I wouldn't automatically suspect we have uncontrolled growth in the loop. I'd suspect external contamination of the sample. I'd be looking for a number of consecutive samples with elevated results before I was convinced of a problem.
Exotoxin is only one of a number of harmful metabolites that could be present in the water if you have unchecked growth in your RO system. We can't test for these, that's why it's important to have proactive disinfection regimes to prevent bacteria from getting a foothold.
As for patient reactions, I'd be surprised if these are immediately apparent. The symptoms will only be seen after years of over stimulation of the patients immune system.        

[Ian Wilde]

Great posts from all.  It's good to hear people's views on it.

I am currently on day 5 of my experiment so will have results to share in around a week.

[Ian Wilde]

Experiment results.  I don't have a theory on why the TVC from the tap water continued to rise?
Never the less, it is safe to say that the filters are more than capable of providing a safety net while action is taken on any raised levels from your RO samples.

[Roger Moore]

Diasafes performing admirably and cleaning up the good old 'council pop'.

It will be interesting to hear the views of others and discussions around how this could influence action to be or indeed not to be taken.

[Chris Bates]

Good stuff.
Shows the filters do what they claim.
One consultant I talked to a while ago said you could use pond water and be OK - at least against TVC and EU ?