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

[cowanify]

Hi Jo
In a bit of a panic here, just when we were seeing some light at the end of the tunnel.
We have just made it to alternate day dosing, after being diagnosed with SRMA late October. We're currently on 7.5mg every other day for a 30-31kg white 2yo male intact boxer.
Shiva has a UTI and anecdotally in the SRMA facebook group I'm part of, other owners have seen their dogs relapse after infections including UTIs. 
I'm aware there's the concept of a "steroid umbrella" that should be used around stressful events including surgery and illness with dogs who've been on high-dose long-term pred or are still on it.
Plumb's says: "Should the animal undergo a stressor (eg, surgery, trauma, illness) during the tapering process or until normal adrenal and pituitary function resume, additional glucocorticoids should be administered."
My question is, what dose should be used for a steroid umbrella, and particularly for one around a UTI? Do you agree a steroid umbrella would be a good idea around the UTI? Or is a UTI potentially minor and only serious illness would require upping of the steroid? He seems otherwise good.
Obviously reluctant to put him back to higher doses as it's been a long and rocky, Cushingoid road to get here and we are still dealing with calcinosis from the prednisolone, but equally - if he relapses because of the stress on his system of the UTI, we'll be right back to the start which I can't see how his body could take. So, seems like it might be wise to do a steroid umbrella until the UTI is cleared?
Can you point me to how to calculate what dose we should return him to during the UTI?

Also, incidentally, his urine culture and sensitivity came back saying it's a heavy growth of E. coli and a very light growth of Proteus Sp. The sensitivity is saying  the strains he has are resistant to Amox/Clav, Amoxycillin, Cefovecin, Cephalexin and Tri/Sulpha. The only drug they included in the panel that the strains are susceptible to is Enrofloxacin, which Plumb's says has CNS stimulation as an adverse effect and should be used with caution in dogs with seizure disorders. Since SRMA is inflammation of the CNS, it seems like Enrofloxacin is contraindicated and too risky, in terms of the possibility it could trigger relapse of the SRMA? Do you agree it's not a good choice? The lab is doing a further panel but I'm worried what we'll do if it comes back saying the strains are resistant to a whole other bunch of drugs, and we don't have any safer option that Enrofloxacin that is going to be effective against the UTI. Do you have any ideas what antibiotics we should suggest the lab test if the second panel doesn't come back with any options? Or any advice what to do? I'm worried the UTI unchecked could trigger SRMA relapse as the immune system gears up to fight infection and has as stress reaction with impaired adrenals due to the pred etc.

Please let me know what you recommend, with all your experience.

Thank you in advance, as always,
Jane & Shiva

[Jo CIMDA]

Hi Jane

Getting down to 7.5mg EOD is a big achievement, and so well done. 

Recurring UTI's are common place when a dog is on steroids, because the immune system is functioning under par and leaves the body vulnerable to picking up infections.  This has to be accepted when a dog is on high doses of steroids, and although Shiva is now on a relatively low, every other day dose, this will still have some impact - hence the UTI.    I would say a good percentage of dogs who have been on immunosuppressive therapy will get one or more UTI's during the treatment duration.

The way over this is the use of the appropriate antibiotic to kill off the bacteria.  If you increase the steroid dose then you are essentially reducing further the dog's natural ability to fight infection and this is likely to make the infection worse or even more prolonged. 

Some UTI's are very stubborn and need extended duration of antibiotic before the culture is clear of bacteria.  Increasing the preds is not a good idea.  I would only increase the dose of steroids if Shiva proved to be relapsing SRMA, then the dose has to be immunosuppressive.   

SRMA has an entirely different disease process, and genetic predisposition, to those dogs that develop epilepsy, and Shiva doesn't have seizures, so this is not a particular concern.  I can only give a personal opinion and it is better to treat the UTI with the appropriate antibiotic (or more than one antibiotic if necessary)  for that strain of bacteria than not to treat at all. 

If a dog is going to relapse during the period of weaning down off  the preds,  then this will either occur when the dose is low - and this signifies that the immune system wasn't in remission anyway and there were still immune cells that are programmed to attack,  or the dog has encountered a new 'trigger' that has activated a new set of aberrant target cells.

I wouldn't use potentiated sulphonamide antibiotics because these are known to have the potential to 'trigger' an immune response resulting in an AI disease.

There is no way of knowing if a dog is in remission or not.  Only time will tell once the dog is off steroids altogether.

It is common place, if a dog gets an infection of any kind during steroid treatment, to address the bacteria with use of antibiotics. You may consider giving Cantharis homoeopathic remedy to see if it works or give it alongside the appropriate antibiotic recommended by the Laboratory who performed the culture.  Also, encourage Sheva to drink plenty of water to dilute the urine. This is an interesting link:

https://www.msdvetmanual.com/pharmacology/systemic-pharmacotherapeutics-of-the-urinary-system/bacterial-urinary-tract-infections

I don't think you have a any choice about this treatment.  It has to be the appropriate antibiotic for the bacteria otherwise the bacteria will grow and multiply and you will have a much bigger problem getting it under control. You may consider probiotics to replace the good gut bacteria that the antibiotics will destroy.

I do hope you can work with the vet and Lab to get the correct treatment for Shiva, and things improve very soon. It is great that you are so informed and you can work together with your vet. 

Jo

[cowanify]

Jo, oh my god I can't thank you enough. You're an angel through all of this. I honestly honestly don't know where I'd be without you. I'm halfway round the twist with this 7 month odyssey as it is, but without you we'd be so much worse off. Thank you. I hope you know how much your presence means to us and I'm sure so many others you help.

I started him on the Enrofloxacin and hope to do a high dose short duration approach where we test the urine again after 3 days, based on the recommendations in Plumb's, which I bought a subscription with once you alerted me to its value a long time ago. It's a lifesaver.

I pored over the link you sent and it was so incredibly helpful, not least because of the mention of the added risk in intact male dogs (which Shiva is) of UTIs lodging in the prostate. The fact that Enrofloxacin is recommended for intact male dogs, as well as being the one the lab found Shiva's strains are susceptible to, makes me feel a little better for putting him through the "CNS stimulation" adverse side effect. The pills definitely make him feel nauseous but I gave it at midnight and by morning he was starting to feel somewhat less unwell. And it helps to know potentially with this approach maybe only 2 more days, maybe 3 if we have to wait for urine test results to hopefully show the infection has cleared before stopping. Thank you also for mentioning the seizure risk may well not apply to Shiva. Do you think the CNS stimuation is a potential relapse trigger for SRMA?

I also have ordered some cranberry-based, d-mannose bladder support to hopefully support the urinary tract and prevent any more UTIs. Do you think this is safe for an SRMA dog? https://au.iherb.com/pr/zesty-paws-cranberry-bladder-bites-for-dogs-urinary-kidney-support-all-ages-chicken-liver-flavor-90-soft-chews/81147

I really valued your pointing out the antibiotics to avoid for SRMA dogs. HUGELY appreciate that and will know to avoid them if they ever come up.

One thing I'm not sure of — would it be okay and not diminish the effectiveness at all of the Enrofloxacin to give it with food. I gave it last night on an empty stomach because I'd read that it was ideally given on an empty stomach? But like I say he definitely felt very sick, constantly licking lips, restless, lying-where he lies when he doesn't feel well (and have certainly felt in the past giving antibiotics with quite a bit of food helped him cope with them). Plumb's says this:

The presence of food in the stomach generally delays the rate but not the extent of absorption, but foods with increased divalent or trivalent cation concentrations (eg, milk) can reduce bioavailability.

But it also says it works this way:

Enrofloxacin is a bactericidal agent. The bactericidal activity of enrofloxacin is concentration dependent, with susceptible bacteria cell death occurring within 20 to 30 minutes of exposure.

... I'm not clear whether giving with food will diminish the "concentration" that's mentioned? What do you think? I think it would definitely be easier on him with food but need it to work properly so we can weather it on empty stomach if need be. And do you know if that mention of needing to avoid "divalent or trivalent cation concentrations like milk) means I can or cannot give it with his normal home-cooked dinner or, say, a can of Hill's k/d (which he's on at the moment as a low-Phosphorous diet to hopefully deal with high phosphate in his blood. (Not sure btw whether that is related to his calcinosis circumscripta from the pred that we're still battling, big lumps and still on his tongue too, but better there than it was and I think the lumps might be getting worse before they hopefully get better. )

Again, Jo, thank you from the bottom of my heart.
Jane & Shiva

[Jo CIMDA]

Hi Jane

I am pleased you found the information useful.

There are many drugs that interact with certain foods and of course it is best to avoid giving enrofloxacin with dairy products etc., because that will inhibit absorption. That doesn't mean he can't have dairy, but not within at least 2 hours of administration of the drug.  d-mannose bladder support is worth trying too.

If, even for 3 days, Shiva is going to feel absolutely awful with nausea and sickness then is far better to give the medication with a little food, non-dairy of course.  Also, if Shiva's nausea is severe, although it is prescribed once a day the dose can be divided and given twice a day if necessary. Once you have started the drug, and it is in his system, the subsequent doses will continue to provide at the desired rate of absorption.  It is a question of weighing up the pros and cons of treatment and determining the best protocol for the individual based on their reactions.    You have all the information in the Plumb's Veterinary Drug Handbook, and what a benefit this is!  It may be that the duration of treatment has to be longer but it is worth trying the short duration/high dose first.

As for potential risks for triggering an AI response - anything within the environment or hormones, stress etc., can trigger an immune response in a genetically predisposed dog, but often it needs a set of circumstances (unknown to us - possibly external and metabolic) for the trigger to be effective.  Many potential known triggers, in isolation, may never spark a reaction in one individual, but may do so in another.  Not enough is known about this aspect of AI disease but we cannot safeguard our dogs from all the potential triggers out there.

Fingers crossed this high dose, short intensity protocol works.

Jo

[cowanify]

Jo giving with food did help last night. He still got some nausea but not as bad as the first time and we both managed to get better sleep through the night. This morning, like last time, he's through the worst of it and quite happy and even a bit playful again. Didn't need to pee on the pee pad before we left the house for our little walk this morning so maybe the Enrofloxacin is starting to work on the UTI.

BTW in case it's useful for your massive repository of knowledge... Our veterinary nutritionist (in NZ) has said this about cranberry supplements for preventing future UTIs:

I don't know of anything I'd recommend. If I were you, I would look for a product that's been given to dogs as part of a research study, preferably for a long period of time. This product was used in the study below:
https://www.crananidin.com/
https://onlinelibrary.wiley.com/doi/pdf/10.1111/jvim.14613
There are probably a few others around too. Highly concentrated supplements containing anthocyanins make me a bit nervous; we did a safety study on a blackcurrant anthocyanin supplement at Massey and the lowest dose gave several of the dogs acute kidney injury, and the study had to be discontinued. The manufacturer of the supplement wouldn't allow publication of the results, but this may be the mechanism responsible for kidney injury due to grape and raisin feeding.
Having said that, lots of people seem to use it, despite fairly scanty evidence that it's effective, so hopefully it's safe!

So Jo, do you think products like these two (which I think are quite different from each other) are a better idea, although the bites still have cranberry? Or other things I can do to support urinary tract health? 

https://au.iherb.com/pr/zesty-paws-cranberry-bladder-bites-for-dogs-urinary-kidney-support-all-ages-chicken-liver-flavor-90-soft-chews/81147

http://www.naturalwonderpets-store.com/Primalix-NUMBER-1-p/pn1.htm

*****Would love if you could share a link to the kind of d-mannose product you'd recommend?

We have the third of the three-day course of doses tonight and I feel better about our ability to manage it now.

In terms of what happens then: do you know with UTIs whether you then stop treatment and wait before retesting urine to make sure it's clear or should you only come off once the urine tests clear? Vet is not experienced with SRMA at all, and has never done the short course high dose treatment for UTIs but is saying the lab says you stop the antibiotic and then wait a week and test urine... but doesn't that risk antibiotic resistance if you're coming off it before knowing the infection is gone? Or can't you get an accurate reading while still on the antibiotics? I'm not sure whether the concern would be you'd get a false negative because the antibiotics suppress the infection while still present even if it's not really gone? or a false positive because the infection can take some days after finishing treatment to clear? What do you recommend? *****Stop after the 3 days or only stop the drugs after doing a urine test and it coming back clear?

Thanks again, so much, for being there and for having the knowledge.

Jane & Shiva 

[Jo CIMDA]

Hi Jane

I am pleased Shiva is coping better with the antibiotics when given with a little food.

I do not have time now to answer all your points but I found this excellent paper (human) that may give you some useful information.


https://www.nice.org.uk/guidance/ng112/documents/evidence-review

Jo

[Jo CIMDA]

Hi Jane

I hope Sheva's therapy is proving to be working and he is feeling much better in himself.

I have read different reports about cranberry juice.  Many say how good it is for UTI but when you look at the research papers they say that it makes no difference.  I have used homoeopathic Cantharis and it has worked well and I have also recommended it to others and the feedback is also very positive.  Conventional vets do not consider homoeopathy as an effective treatment so I would say it is up to you if you want to use appropriate homoeopathic remedies.  With that in mind Primalix looks very promising.  http://www.naturalwonderpets-store.com/Primalix-NUMBER-1-p/pn1.htm

I can't recommend a d-mannose product but this is very informative: 
https://www.medicalnewstoday.com/articles /323938.php

As the particular bacteria has been identified and Shiva is being treated conventionally with antibiotics,  perhaps you should see if the enrofloaxin solves the problem before adding anything else.  Some UTI's can be persistent and this is why testing has to be done following antibiotic  treatment.  Go with what the Lab suggests but be prepared for the treatment to take many weeks before a conclusive  negative result is seen.
Good luck
Jo

[cowanify]

Thanks so much Jo. What do you think about this one? Would any of the ingredients be dangerous for an SRMA dog?

https://au.iherb.com/pr/Zesty-Paws-Cranberry-Bladder-Bites-for-Dogs-Urinary-Kidney-Support-All-Ages-Chicken-Liver-Flavor-90-Soft-Chews/81147?gclid=Cj0KCQjwrdjnBRDXARIsAEcE5YngodGIa-IfPCigdig8lqSlREdnwyGcSXwdY1gqTSB0KHYp4M1nrKYaAmBbEALw_wcB&gclsrc=aw.ds

The ingredients are:

Cran-Max® Cranberry (Vaccinium macrocarpon), Concentrate (standardized for 7% [14 mg] proanthocyanidins), Organic Marshmallow Root, D-Mannose (naturally derived), Organic Astragalus, Organic Licorice, Nettle Seed, Pea Flour, Palm Fruit Oil, Garbanzo Flour, Tapioca Flour, Flaxseed Meal, Chicken Liver, Sunflower Lecithin, Coconut Glycerin, Powdered Cellulose, Rosemary Extract, Mixed Tocopherols, Sorbic Acid (Natural Preservative)

I'm asking because the below pasted comment is what our veterinary nutritionist said about cranberry supplements when I asked her. I'm not sure what to make of it because the reviews of products like the above one are so glowing online for preventing and even curing UTIs.

If you don't think this Cranberry Bladder Bites product has any contraindications for an SRMA dog and can at worst be ineffective, I'm inclined to give it a try.

Love your advice.

Thanks again,
Jane

Here's what she said:

I don't know of anything I'd recommend. If I were you, I would look for a product that's been given to dogs as part of a research study, preferably for a long period of time.

This product was used in the study below:

https://www.crananidin.com/
https://onlinelibrary.wiley.com/doi/pdf/10.1111/jvim.14613

There are probably a few others around too. Highly concentrated supplements containing anthocyanins make me a bit nervous; we did a safety study on a blackcurrant anthocyanin supplement at Massey and the lowest dose gave several of the dogs acute kidney injury, and the study had to be discontinued. The manufacturer of the supplement wouldn't allow publication of the results, but this may be the mechanism responsible for kidney injury due to grape and raisin feeding.

Having said that, lots of people seem to use it, despite fairly scanty evidence that it's effective, so hopefully it's safe!

[Jo CIMDA]

Hi Jane

I think the best mantra is: When in doubt, don't!

Shiva is being treated conventionally with the correct antibiotic for the strain of bacteria present, and as Shiva is probably considered to be a complicated UTI case, I think the best thing to do is to keep the treatment simple.  Test after a week to see if the bacteria is still present.  If it isn't then carry on as normal, and to be confident,  I would test again in another week,  if it is still present then you know that a further course of antibiotics is needed, and this is not unusual, in fact most UTI's have to have prolonged treatment for many weeks with the appropriate antibiotic.

It worries me that things like Xylitol, which is fine for humans but can be lethal to dogs, may be present in over the counter remedies.   Here are a couple of websites that you should read, if you haven't done so already.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3134992/

https://www.preventivevet.com/cats/cranberry-and-your-pets-urinary-health

I would keep it simple for now Jane. Fingers crossed Shiva will be clear of UTI soon.

Jo

[cowanify]

Thanks Jo. In the end I went to use the Zesty Paws product but then changed my mind when I found on WebMD that one of the ingredients, the Organic Astragalus, is not advisable for those with autoimmune disease, I think because it's thought to stimulate the immune system, when what we're trying to do is damp down an overreactive immune system?

On that note, do you think probiotics are advisable or inadvisable for dogs recovering from SRMA? I can't tell with ether they're a good idea because they're immunomodulatory, or a bad idea because they're immunostimulatory? I know others have seen them make their dogs feel better, but I do worry about whether there could be also a relapse risk? But then you can find articles like this https://www.intechopen.com/books/probiotics-current-knowledge-and-future-prospects/probiotic-applications-in-autoimmune-diseases that seem to suggest mostly an immunomodulatory effect and a role in treating autoimmune conditions? What does your experience suggest about probiotics and SRMA?

J

[Jo CIMDA]

Hi Jane

The Jury is out on so many of these supplements, but I personally believe that the gut pays a significant role in our well-being, our vulnerability to developing diseases and homoeostasis.  The gut links so many body systems together, it is even said to have its own brain.  therefore I am a great believer in good gut health and pre and probiotics, in my opinion, are beneficial and lead to a balance in the gut especially if the patient has been on a course of antibiotics - which kill off good bacteria as well as bad.   The link you gave is fascinating.

On a personal note, many years ago I had an intensive course of several different antibiotics.  They worked wonders, but for the year following I had diarrhoea. When it was investigated I was told that the antibiotics had killed off all the good bacteria that is necessary to have good digestion and I was prescribed probiotics.   It solved the problem and returned my gut back to working order.

So I am in favour of probiotics, especially following a course of antibiotics.  This is interesting:

https://www.frontiersin.org/articles/10.3389/fmicb.2014.00146/full

Jo

[cowanify]

I absolutely think the same about the role of gut health in overall health. And I definitely think Shiva could benefit because he's been on 4 different types of antibiotics now in the past 7 months. The thing that has me worried though in the case of SRMA dogs is that it's said you shouldn't take probiotics if you have a compromised immune system?

[Jo CIMDA]

HI Jane

Anecdotally, I have known many dogs on steroids to have probiotics following a course of antibiotics.  I think the other consideration is how much pred is the dog on?  Shiva is only on 7.5mg/kg EOD and for a dog of his size, this is a very low dose and certainly not immunosuppressive or even anti-inflammatory.

You are so well informed, I think you should have a thorough discussion with your vet about the use of probiotics and arrive at an agreed,  informed decision.  The info' you have about not giving dogs with SRMA probiotics - does this apply to dogs with other autoimmune diseases, or is it just SRMA?   

Jo

[cowanify]

The vets I've not found useful actually in helping to arrive at a decision about probiotics in the case of SRMA dogs. They seem to just say, Sure - go for it. But I'm not confident it's because they've thought it through for the specific case of SRMA dogs, but more because they just see probiotics as harmless in general.

I don't have advice that probiotics are to be avoided in SRMA dogs, or in cases of autoimmune disease generally. It's more just by extrapolating from what we do know, and in trying to think it through, that I arrive at the worry about whether they're a good idea or not, despite wanting to give them and knowing they will bestow benefits. I'm just worried about the possibility of other unintended other effects. Thinking it through: the treatment for SRMA has been to suppress an overactive immune system. So if anything we give an SRMA dog has an immunostimulatory effect, you would think there must be some risk of retriggering that process that caused the SRMA in the first place? Like, I've encountered advice in places like webmd that, for instance, some ingredient that is immunostimulatory should be avoided if you have an autoimmune disease. That's where I'm coming from with it. And from references to the fact that some probiotics are immunstimulatory, and some down regulate the immune system, but we don't seem to know which strain does which?

I think it does also explicitly say on webmd or somewhere similar that probiotics should be avoided in immunosuppressed individuals. That's where I'm getting that notion from. I think I've read reference to that being because they can cause infection in those people/animals? Which maybe isn't a worry for us when, as you say, we're no longer at immunosuppressive levels of pred. That's a good point. But there must be a hangover effect of immunosuppression after being on the high dose for so long? Ordinarily I wouldn't expect him to be getting UTIs but he has, and it's happened on our current low dose, so I'm thinking it's going to take some time for his system to get back to full strength?

Having said all that Shiva, 5 days after finishing the most recent antibiotic, came down with diarrhea that has lasted so far 4 days. Starting to see perhaps some improvement now. So I've bitten the bullet and decided that perhaps the benefits of probiotics outweigh the risks, and outweighs the risks of allowing his gut flora to stay out of whack, especially given the possibility autoimmune diseases could have some genesis in the gut. I've begun giving him a multi strain probiotic, hoping that by giving multistrains, any with immunostimulatory effects might be balanced by others with immunomodulatory effects.

What do you make of all that?

This process sure is exhausting.

Thank you again for being there, and for caring.

[Jo CIMDA]

Hi Jane

I think, following diarrhoea,  I would have done the same as you and start with the probiotics.  I believe there is more good to be had than bad especially as Shiva is not on a daily immunosuppressive dose of prednsiolone. 

The hangover effect of historic administration of pred is there in every cell of Shiva's body,  but it is not biologically active - that activity only lasts 12-36 hours following administration so I don't think that is cause for concern.

In a genetically predisposed dog, a relapse can occur at any time if the 'appropriate' trigger is met, or if the immune system was not suppressed significantly enough, or the duration of immunosuppression wasn't long enough then the immune system may not have entirely returned to normal function and the aberrant immune cells can become active again and a relapse occurs.  There is no way of monitoring this or knowing if this will happen.  SRMA has an excellent prognosis as long as the treatment protocol is correct.  Relapses can and do happen especially when the dog is young but for most SRMA dogs they eventually reach a state of homoeostasis and very often another relapse never happens.     

I do hope the diarrhoea stops as quickly as it starts.

It is a steep learning curve for sure but you have managed it well, and Shiva is on the road to remission.

Fingers crossed.

Jo