Help please: how to up pred when dog gets UTI during taper?

[cowanify]

Jo, you always manage to comfort while providing straight information too. You're a big part of keeping me halfway sane.

We are into day 5 now of diarrhea. There was a sign of blood in the most recent poop, but hasn't been previously. Overnight the poor bugger woke me up to urgently go out four times - 1230, 1:15, 5am, 7:30 before breakfast. Normally we wouldn't go out between last walk at 10pm and after breakfast at 7:30am.

I took a foecal sample to the vet along with the urine retest yesterday. The good news is the UTI is clear. Nil WBCs and nil bacteria in urine! So the 3 day high dose enrofloxacin that was so rough on him was at least able to clear the E coli. Big relief.

The poop culture is still in process but the initial results showed negative for parasites (we haven't wormed him since January because of the fear these products are perhaps triggers for SRMA and he's an apartment dog in a big city so we're thinking chances of infection low but we need some natural worm prevention methods long term once we're through this.. I've heard things like pumpkin seeds?), and negative for giardia. The fecal occult blood was a weak positive but the vet says to ignore that? I have to ask her about it, but I'm thinking perhaps blood is to be expected with diarrhea? 

I see in my facebook group that other SRMA dogs have been prescribed Metronidazole/Flagyl for diarrhea and it's seemed to work? But Plumb's says it can have neurotoxic effects and it sounds pretty scary? We obviously don't want to go for what would be his 5th antibiotic in 7 months if it's not a bacterial infection, so I'm hoping the poop culture will tell us that?

My question is: what do you think of this drug Metronidazole/Flagyl for SRMA dogs?

What would you be doing for the diarrhea that's gone on this long?

He can be encouraged to play at times and other than the distress when he needs to dash out urgently, he doesn't seem at death's door. He is still eating and drinking. In fact, is hungry. But I don't want to let a stomach infection run and cause relapse. But I also don't want an antibiotic to cause relapse (others seem to think this has happened in their dogs?).

I'm sorry for being so high maintenance at the moment. Thank you again. Somehow it feels as desperate as ever that we can't seem to manage to get out from under these problems and have a clear run.

Jane & Shiva

[Catherine]

It may be the  Enrofloxacin that has caused his diarrhoea.  I would not be wanting to give him anything else like Metronidazole at the moment unless absolutely necessary. Metronidazole can cause serious problems, usually with older dogs.

I would also stop the probiotics as I have known them to cause diarrhoea although lots of dogs will be okay with them. At the moment I think less is best and to just stick to his normal diet (preferably several smaller meals during the day whilst he has the diarrhoea).

Have you tried Canikur Pro Paste? I usually let diarrhoea run its course if it is only a day or so but if it goes on or is quite severe I will use Canikur and have had good results with that.

If you do not see any worms in his faeces and there is not much chance of him scavenging etc. I would not worry about worming him.

I have found giving 1 cranberry extract tablet (not juice) a day - https://www.naturesaid.co.uk/cranberry-5000mg.html helps to keep urine infections away. It may be best to start with half a tablet or even a quarter a day first all and perhaps when the diarrhoea stops.

Blood in the poo is to be expected when diarrhoea is severe and goes on a long time but it should cease and if he is bright and eating it should not be something to worry about - just monitor.

[Jo CIMDA]

Hi Jane

As the diarrhoea has gone on for several days I would say you need something to regulate the bowel again and personally, I would use metronidazole.  Metronidazole is an antibiotic but it also has the ability to slow down the gut and allow the excess water to be extracted, as usual,  by the intestinal system. 

Metronidazole, as Catherine suggests,  can cause neurological symptoms but usually,  it is when the treatment duration is prolonged (many weeks)  and if this happens, as soon as the drug is stopped the dog will recover and over a couple of days will return to normal again. I have personal experience of this with one of my dogs - he was on it for 2 months for demodex.    If there is no bacteria present then you may only need one or two doses of metronidazole to regulate the stools and return to normal consistency.  A whole course of treatment  is not always necessary.  They are handy to have in and to use, as an when diarrhoea is a problem.  Make sure Shiva is drinking enough water  to balance the fluid loss.

Enrofloxacin is a good, but hard antibiotic and I am not surprised Shiva has been left with this.

As Catherine says, if Shiva has worms then you will see them in his faeces, so I wouldn't bother giving anything unless you have proof.

I hope things calm down for you soon.  It is tough.

Jo

[cowanify]

Thank you so much for this Jo, and Catherine.

I got some Metronidazole from the vet but am holding off on using it at the moment as we're now at last seeing some improvement just on the bland diet and the probiotics. I agree with you it's a good thing to have on hand and will resort to it if we need to.

The poop test came back showing clear of everything except for "moderate growth" of an anaerobe, most likely Clostridium. The pathology report said:

Isolated anaerobic organism is likely Clostridium sp. Generally, Clostridium sp. is part of normal faecal flora. Gastrointestinal upset, stress
and protracted antimicrobial therapy can create an imbalance amongst the microbial populations.
Certain genera are normal gastrointestinal inhabitants capable of opportunistic infection (C. perfringens) and others are pathogens (C. difficle).
Amoxy/clav, Clindamycin and / or Metronidazole are recommended if antimicrobial therapy is necessary.

So for the moment we're holding off on antibiotic but will resort to it if things go backwards.

We also did a blood test yesterday and though the liver enzymes are hugely better, the WBCs are concerning me because they are worse than the previous test a month prior, even though we are a month further along in terms of the pred taper (now on 0.25mg/kg ie 7.5mg every other day and a week away from transitioning to every third day dosing) and presumably we're a month further away from SRMA.

In the previous test all WBCs were normal except for a slight monocytosis and there was no toxic change at all.

However now, we have:

* mild toxic change
* slightly elevated Band neutrophils (0.4 compared to reference range of 0-0.2)
* slightly low lymphocytes (0.7 compared to reference range 0.9-4.1))

The monocytosis is slightly improved on last time (1.3 now down from 1.7 with a reference range of 0.2-1.0)

My question is:

Could the recent UTI (which we completed treatment for 11 days prior to blood test and tested clear of 4 days before the blood test) or the current diarrhea or a suspected current active infection of the pred-caused calcinosis on his tongue cause elevated band neutrophils and mild toxic change? And what about the low lymphocytes? (Because of course the worry is this bloodwork could indicate movement towards SRMA.)

Does your experience give you any insight into interpreting these results?

NOTE We're yet to attack the infected tongue calcinosis with antibiotics this time (though we have on several previous occasions) because we're waiting on a swab of the tongue to see if it can tell us anything about the strain of bacteria at play, and because we want to let his diarrhea subside before hitting him with any more antibiotics.

Warmest thanks
Jane

[Jo CIMDA]

Hi Jane

The WBC count that you are seeing, I believe, can all be attributed to prednsiolone administration, and this is normal for a dog on glucocorticoid therapy.  This is an excellent paper and I believe will answer your questions and put your mind at ease.

https://endocrinevet.blogspot.com/2012/04/how-glucocorticoids-affect-complete.html

If Shiva isn't already on essential fatty acids (EFA's) then you might consider supplementing with,  for example, evening primrose oil and fish oil.  Prednisolone breaks down the skin barrier and this can be repaired by supplementing with EFA's.   EFA's are also know to be 'steroid sparing' meaning that over a period of time the effect means that less steroids are needed.   The use of EFA's may prevent calcinosis appearing on Shiva's body.  EFA's do take a couple of months to reach full benefit though.

https://www.ncbi.nlm.nih.gov/pubmed/15214949

https://veterinary-practice.com/article/essential-fatty-acids-in-veterinary-dermatology-do-they-have-a-place

Jo

[cowanify]

Thank you so much for this Jo. I will have a good read and no doubt come back to you with more questions! The thing that worried me was that his WBCs were normal on all these fronts - normal band neutrophils, normal lymphocytes and no toxic change a month ago and now we're on lower pred so expected it should be normal still?

Reckon the band neutrophils and the toxic change could be caused by mouth infection?

Oh and yes I'm a big believer in the fish oil. He's been on that for some time now and I do believe it helps. The calcinosis as we've gotten to lower doses of pred is no longer appearing in new sites. I will be using activated charcoal on the lumps too, others have had great success with it drawing out the calcium/phosphate. He's been on a nutritionist-designed low-P diet recently too, to try to get down inexplicably elevated P in the bloods. It seems to now be coming down. Ever seen elevated phosphate in SRMA/prednisolone dog bloodwork before?

Oh and some good news: his CRP came back 0.7!!! It had been about 1 or 2 all during treatment but last month was 4 so I was worried it might be moving upwards... but I gather immunosuppressive doses of pred suppress CRP readings so you get an artificially low result while on those doses? So I was trying to tell myself it might have come up to the 4 just because it was no longer suppressed by the high doses of pred.. so DELIGHTED to see it be 0.7 now that we're on alternate day dosing of 0.25mg/kg and a week out from going to every third day dosing of 0.25mg/kg ie 7.5mg for Shiva at 31kg.

J

[Jo CIMDA]

Hi Jane

I hope Shiva is doing better.   Elevated phosphate levels are seen in dogs who are on steroids or who have naturally induced Cushing's -  it is not unique to SRMA.

Personally, I don't take much notice of CRP levels when a dog is on steroids because the accuracy of results can't be relied on.

I think you will start to see a huge improvement now Shiva is on an EOD dose of steroids and reducing.  Until the steroids have been withdrawn, for at least a few weeks (or more), you will not be able to assess accurately any of the blood results that are known to be affected.

Jo

[cowanify]

Belated thanks for this Jo. You are the first person to tell us that elevated P is known to be associated with steroids. None of the vets could make sense of it. I don't suppose you can point me to a source on this so I can pass it on?

BTW we are now in week 6 of every third day dosing of 0.25mg/kg which for Shiva is 7.5mg every third day. Calcinosis lumps still a problem but we are treating with activated charcoal and hope it might help over time. Also now we have a new problem: elbow hygromas caused by the calcinosis on the elbows (love any advice you have on that) but otherwise doing well and now full of personality and better energy.

I think I'm deciding to add an extra 6 week taper after this one, of 5mg every third day. My logic for this is that as I understand it pred meets physiologic requirements not at one specific dosage for all dogs but within a range of 0.05-0.25mg/kg/per day. Our current every third day dose when divided by 3 comes out at 0.08mg/kg/per day. I figure since we've been on pred now for 9 months, Shiva's adrenals have been severely affected and need good support in coming back into function. So it seems like, given the range goes down to 0.05mg/kg/per day, it might be smart to stay on the pred until we get as close as possible to that lower end of the range? Going to 5mg every third day will equate to 0.05mg/kg/per day for us. What do you think? Do you think we ought do yet another taper after that too, ie go to 2.5mg every third day which would be 0.03mg/kg/per day so that it takes us BELOW the 0.05mg/kg/per day ie so that we know the adrenals are definitely having to kick back in, but we are keeping some prednisolone in the system during that period for support?

We don't want to stay on the pred any longer than necessary because we can't resolve the calcinosis until we're off the drug, but equally, no point getting off it only to have the adrenals not cope, and get a poor coping response to stress/excitement and then relapse and have to go back to the start.

Would dearly love to know whether you think this is sound logic based on your knowledge of how things work with the adrenals and what's happened for other dogs in your decades of paying attention to SRMA.. and how far down you'd take the taper before going off the pred.

Thanks as always,
Jane

[cowanify]

Catherine I wanted to thank you for the warning about Metronidazole/Flagyl and to alert you, Jo, to the fact that several owners in the SRMA group on facebook I'm part of either gave Metronidazole before onset of SRMA or before onset of relapse. There is a warning about Metronidazole on the dailymed.nlm.nih.gov site under the listing for the drug that under the heading Central and Peripheral Nervous System Effects mentions aseptic meningitis alongside seizures and other possibly side effects.

What do you both think of tylan powder/tylosin as an alternative? (Other SRMA dogs have used this instead of Flagyl/Metronidazole.)

We have recurrent diarrhea. Originally opted not to give Metronidazole and instead resolved with probiotics.

But faecal culture at the time of the original diarrhea said:

Isolated anaerobic organism is likely Clostridium sp. Generally, Clostridium sp. is part of normal faecal flora. Gastrointestinal upset, stress
and protracted antimicrobial therapy can create an imbalance amongst the microbial populations.
Certain genera are normal gastrointestinal inhabitants capable of opportunistic infection (C. perfringens) and others are pathogens (C. difficle).
Amoxy/clav, Clindamycin and / or Metronidazole are recommended if antimicrobial therapy is necessary.

Now his bloodwork shows elevated WBCs and band neutrophils trending up. All was clear in blood test in May but then in June the bands were slightly up and now on August 1 the bands are much more elevated and the WBCs are also up. Since no other signs of infection, and tested clear for UTI, thinking it's probably the gut and if it's infected, need to treat. We've also had yellow specks and a HEAP of mucous in diarrhea for the past few weeks which I am thinking is pus/the white blood cells ie infection.

What do you think?

Since Metronidazole is off the table and every other infection we've had has been resistant to the other two drugs suggested, after we used them a lot in the early stages of the SRMA treatment... I'm thinking the tylosin. Love your advice and experience as to whether it's safe for SRMA dogs or if you've ever known it to cause problems?

[Catherine]

I am afraid I can not help you and I have not even heard of Tylan powder. Hopefully Jo will be along soon and may be able to answer you.

Did you try the Canikur Pro Paste?

[Jo CIMDA]

Hi Jane

I am sorry for the late reply.  We have been away.

I have known people to use Tylan powder, and you have nothing to lose by trying it,  but I am not sure how effective it is with certain bacteria.  It is often better to give the appropriate antibiotic when the bacteria has been identified.   Often the gut needs to reprogramme itself after a prolonged bout of diarrhoea. Slowing down the gut's function enables the water in the gut to be taken out in the usual way and this produces a normal consistency of stool. A kaolin and pro biotic paste, as Catherine suggests, might be worth a try.   It can certainly settle down the gut if a major bacteria is not the cause of diarrhoea.

Neutrophils and WBC increase when steroids have been used and are still in use. Until Shiva has been of prednsiolone for some weeks you will not know if the elevated white blood cells are due to steroid use or infection or stress leucogram. Steroid administration clouds issues because it is difficult/impossible to differentiate between a rise in white blood cells because of an infection or glucocorticoid use. 

I think I have already given you this link, but if I haven't then it is worth looking at:

https://endocrinevet.blogspot.com/2012/04/how-glucocorticoids-affect-complete.html

A vet I know gives this advice,  'believe your eyes'!  If Shiva is well in other ways, and the diarrhoea is settled at this time, then don't give anything unless you see diarrhoea again.  I wouldn't worry about the WBC at this stage because I would expect them to return to normal once Shiva has been off preds to a while.

Jo

[cowanify]

Just an update, Jo.

We're on week 4 of 6 weeks at 5mg every third day for 31kg Shiva, an extra tapering step I've added on to the Lowrie protocol for the sake of the adrenals, given we've been on pred now for 10 months. Will do 2.5mg every third day next and then off completely.

Repeating blood tests next week which will be a month since the previous ones. The monocytosis is certainly explained by the pred so I'm not worried about that reading, but the elevated band neutrophils and the slightly elevated WBCs, and the C-reactive protein that's gone up but still within normal, are actually NOT explained by the pred, according to the link you shared, so really want to see those values normalise and not be part of a slide back towards any SRMA. All those values have been normal in some of our earlier blood test results, when pred dose was much higher. At the moment my best theory is that it's something to do with either the diarrhea he had (now resolved with first slippery elm and now psyllium husk which avoids the oxalates in slippery elm that are a kidney/bladder stone risk) or the pred-caused calcinosis, though I haven't seen any reference in any literature to calcinosis showing up in bloodwork, except for sometimes in elevated Calcium, which we don't have. We do however have elevated phosphates, which are the other component of the plaques formed in calcinosis.

I also thought you might be interested in this article. It was you who first warned me of Tri/Sulpha and you're the (godsent!) reason we managed to avoid using that antibiotic when the vet (who knows we're recovering from SRMA!) suggested it. The other antibiotic I'm aware of as being associated with causing meningitis in dogs is Metronidazole/Flagyl. But this article from human medicine also mentions others like Amoxicillin and NSAIDs. https://www.mdmag.com/journals/resident-and-staff/2005/2005-12/2005-12_02

Hope things are good your end.

Thanks again for everything.

[cowanify]

Catherine, I meant to say: we didn't get to the Canikur Pro paste but used slippery elm and now psyllium as well as Protexin probiotics. Stopped the probiotics for a week at the height of the diarrhea but have reintroduced to help rebuild gut biome. Do you use the Canikur pro paste regularly in a healthy dog or just when there's a problem? It does look like good stuff from the ingredients. Thank you so much for having been there for us. What do you think of this product, compared to Canikur? Have you used it? Is Canikur Pro preferable? : https://www.protexinvet.com/pro-kolin/p6230

[Catherine]

No, I only use when there is a problem, I would not use it all the time. I will give the diarrhoea a chance to get better on its own but if not and the dog seems fairly okay otherwise I will give some paste for a few days. I keep some in stock although the best before date is not always that long. I do forget what side the "measure" has to be so I have made a note of that for future use!

To administer the correct amount of the product use the handy wheel on the syringe plunger.  Rotate the wheel until it is to the right of the number representing the desired quantity to be administered.

I have not tried the Pro-Kolin + as I found the Canikur Pro worked without any side effects so decided to stick with that.

[Jo CIMDA]

Hi Jane

Sorry for the late reply.  I have been away from the computer for a few days.  I think your tapering plan  for Shiva is perfect.  There will be very little effect on this dose and even less on the planned reduced dose but it is always better to take things steady and slowly if possible.  How is the calcinosis.  I hope it is improving now he is on such a low dose of pred.

I have read with interest the article link you gave and it brought to mind the genetic difference in individuals (even in siblings) can have a huge bearing on whether they have the genetic predisposition to AI disease or not, and also whether they have the necessary genetic make-up to block potentially harmful drug toxins.  Why are some of us allergic - or do not  have the genetic make-up to tolerate some of these modern drugs?

In some breeds of dog there is a described genetic mutation called MDR1 gene mutation.  If the dog is positive for this mutation  (meaning that the gene is not complete) it can have a dreadful reaction to many, commonly used, modern drugs.  In humans, I am aware of a similar genetic mutation called, dihydropyrimidine dehydrogenase  (DPD) and if an individual has this mutation then it can be catastrophic if given a certain chemotherapy drug.  Unless this dpd genetic mutation is tested for,  just one dose of the drug can cause serious brain problems and even death.  So I believe there is so much more to learn about the genes of the individual (whether it be dog, human or other) and the body's response to certain modern drugs. This is a relatively new area in medicine and genetics.

I had a bearded collie with demodex mange because his immune system was compromised by the steroid treatment given for an AI disease.  I was aware of the MDR1 gene mutation, especially in collies, so I was reluctant to use Ivermectin but after trying everything else I reluctantly used a  1/4 of the pipette.   He was fine.  Three days later on the Vet's advice I used another 1/4  of the pipette and within one hour his neurological symptoms started and they were alarming.  Luckily I was aware of this potential so I stopped the drug and within 3-5 days he was back to normal.

Returning to Shiva, I would believe your eyes and not read too much into blood results at this time, and certainly not until the effects of all the steroids Shiva has had has well and truly left his body.  There are  so many incidental things, such as food -  and the even stress of going to the vets,  that can alter blood results and if you took blood the following day they could be entirely different.    If the CRP is within normal limits then I think that is something to be relieved about.

You have done really well managing Shiva's AI disease and he has done so well to have responded to the treatment and is almost at the end, and ready to enjoy being drug free. Hooray!

Jo