Adverse Drug Reaction - SMZ

[mel_la_fee]

*Note -wasn't sure where to put this so Mods please assign/move it as you see fit.

Hey everyone,

I rarely chime in unless I really need help so, you might not recognize me even though I’ve been around for awhile. I just wanted to talk about a recent issue I had with my little neuro Cleo (2 yrs old), because it might be pertinent to others treating their squirrels with antibiotics. Also this is a loooong post. You have been advised!

Full disclosure, I am not a veterinarian or even a vet tech. I have a license to personally maintain certain Florida wildlife (raccoons and skunks) and have successfully rehabilitated many squirrels (which you do not need a license for in FL), but I am not an expert on medication, dosing, or drug interactions. One of the reasons I love this site is because so many people here have the experience I lack and I can ask questions when I encounter a new problem. So, please, take this with a grain of (anecdotal) salt, but I felt it was worth sharing.

My little Cleo is quite possibly one of the most non-releasable squirrels you will ever see (I've posted about her a couple of times). I have multiple x-rays and will at some point write a full piece about her detailing her issues. For now, just know that she has a persistent sinus infection that must be treated with antibiotics almost continuously. She has weeks where it seems to be gone, but we always end up back at the vet’s eventually. Mind you, this creature has a will to live that is enviable by any standard. She seems to not know at all what she is missing out on, and if she does have any idea, she clearly doesn’t care. It’s quite inspirational.

I know I will have to deal with the loss of her eventually, but last week I had to grapple with the reality of that much sooner than expected. She had been to the vet for new ABs and a teeth trim the weekend before and seemed fine, but started to get lethargic just a few days later. She also did this weird thing where she shivered/trembled almost rhythmically over and over when she curled up to sleep. She was still eating and drinking and going to the bathroom so I presumed her condition was due to her constant infection, and since we had put her on new antibiotics I thought it would get better soon. By Sunday she was even more lethargic and acting disoriented whenever she was awake, but bodily functions were continuing on schedule (well, not a schedule really but you know what I mean) but she was eating less and refusing formula entirely. By Monday afternoon, she didn’t want to be awake for any period of time, ate or drank very little, and could hardly get around. I naturally thought of MBD even though she eats HHBs, gets no nuts or seeds except for the occasional almond to offset seizures (low-phosphorus diet in general), and lives in a room with plenty of sunlight and a UV lamp. Anytime you have an indoor squirrel, MBD should be something you look out for, and right away I put her on a heating pad and started following the calcium protocol just to be on the safe side.
I also bought new liquid calcium, new uv bulbs (what if the old ones weren’t working well anymore?), and scheduled a vet appointment.

We went in first thing Wed morning and did new x-rays, bloodwork, the whole nine, and spent a very pretty penny. On Thurs her bloodwork came back and showed some issues related to her bacterial infection that were expected (high white cell count, etc) but that the antibiotics were working. It also showed she was dehydrated and hypoglycemic, which I related to the fact that she was not eating or drinking very much prior to the visit. The vet tech who called to relay the information said that MBD wasn’t apparent, but as I had already started supplementing, it could not be ruled out and we needed to see what the radiologist said about her x-rays. So I should continue what I was doing.

Friday afternoon she would no longer eat or drink anything. I managed to force some pasty, berry-flavored tums into her (my liquid calcium hadn’t arrived on time- damn you, Amazon) and getting plain, elemental calcium water into her proved next to impossible, as did everything else. Anything I put into her mouth she let dribble down her chin with her mouth just hanging open. She didn’t even try to swallow, despite being very dehydrated. I managed to get water into her by dropping some into her mouth and rubbing her throat, but when I later tried this with vanilla Boost for children (as she had already refused formula multiple times), she slightly aspirated on it before I’d even given her even 1cc. Like, aspirational pneumonia is EXACTLY what I wanted to add to this situation (insert some kind of frustrated weeping emoji)….I cursed myself, but tried to entice her again with all of her favorite foods, even if they weren’t the best things for her. She just shook her head and gazed around glassy-eyed before falling to her side and sleeping/trembling. She no longer even cared to curl up or get in a comfortable position. She slept where you put her or where she dropped, that’s how weak she was. I had to constantly force her to drink and then carry her to her ‘pee-rug’ to go to the bathroom.

It goes without saying I’d been crying almost continuously since Monday. I went over every possible thing I might’ve done wrong or taken for granted. If it was MBD, why, after 5 days had she only continued to decline? The bloodwork showed that calcium levels in her blood were up...no other factors had presented themselves as being very problematic... In fact, the vet tech told me that according to their tests, she should be doing better. I was a mess and scoured this forum relentlessly looking for an answer.

Finally, it occurred to me that the only real change in our routine had been in her antibiotics. We’d moved from using Baytril to SMZ because we were afraid her bacterial infection had grown resistant. My sister used to work in a hospital and did some of her hours in the E.R. so I asked her how long it would typically take to see an adverse drug reaction. I expected her to tell me minutes or hours, but she actually said it could take a few days, though usually less than 2 weeks. That would be in humans, of course, but it sent me on a quest nonetheless. I found that plenty of symptoms Cleo had were noted in dogs or horses or people. I didn’t think that counted as evidence, so I dug a little deeper into google and found a clinical trial for SMZ using rats. It noted anorexia, hypoglycemia, disorientation, lethargy and weakness. Granted, these trials were probably using larger doses than a rat would ordinarily require, for testing purposes. They may have been using the drug more frequently than it would ever be prescribed, just to see what it did. That means the effects of the drug might be exaggerated or the results inconclusive for my purposes. It made me sad for the rats… it also made me stop the SMZ antibiotic I had been giving to Cleo.

I don’t know that it caused her issues or decline for sure. I’m not an expert. What I do know is that several hours after her first skipped dose I was finally able to interest her in a tiny piece of papaya and she willingly drank 7.5cc of hydration solution. That was after a full day of refusing everything I tried, including millennial favs like avocados and almonds, and water when she was observably dehydrated. Here it is, almost a full week after I thought I was going to lose her and she’s back to being my baby. By which I mean, she is awake before I am, wrestling with her blanket, grunting at me to keep my distance while she’s eating her blocks, and behaving like the obstinate jerk I love again.

Now, SMZ is actually considered very safe, and I don’t want anyone thinking I’m advocating we never use it. Sometimes it’s necessary and the side effects I mentioned/found are generally rare. That’s one of the reasons it hadn’t occurred to me as a possible problem in the beginning. By all accounts it should still be in your lexicon of drugs that can be used for squirrels, if that’s what your vet prescribes or what is pertinent to your specific problem, because it has saved lives.
I’m only trying to point out that even ‘safe’ drugs might not work for every animal, just as they might not work for every person. It’s important to observe your furr-kids and monitor them.That tremble/shaking that Cleo had was one of the first signs (it has since completely vanished) but it was a small thing that not everyone would notice right away. It was something you could only feel if you were holding her or supporting her with your hand and paying attention. Unfortunately, I didn’t know what it meant. Sometimes the signs aren’t completely obvious. They become obvious sooner or later, but by then you’re waging a war against time. I feel awful that I didn’t recognize the problem sooner... Right up until Friday evening, the 2 things I was sure she had gotten every day were calcium and her antibiotics.

I’ll also make clear that after stopping her ABs on Friday, I went to the vet again on Sat. because even though I chose to stop the SMZ, that’s still the kind of thing you should bring up with your practitioner. While they couldn’t confirm my report of adverse effects (she was still very lethargic and we’d only skipped 2 doses by then), they also didn’t disbelieve me. My vet put her back on Baytril to deal with her infection. The reversal of symptoms was even more noticeable after a full 24 hrs of stopping the SMZ, and my girl is basically back to normal (well, her normal!).
So, overall, trust your vet, but trust your instincts as well, and be willing to look at every aspect of a situation, even if it doesn’t make sense. Our babies can’t speak for themselves so someone who watches them must always be paying attention.

P.S. Still waiting on x-ray results, but my liquid calcium came in finally so we’re going to continue with mild calcium supplementation until I hear to do otherwise.

[redwuff]

Wow, thanks for such a well written observation on your girl. It sounds like a wake up call for us all. So glad everything was turned around!

[Diggie's Friend]

https://www.ayurtimes.com/sulfa-allergy/

Sulfa allergy is known in humans and animals.

With the bacteria that is being targeted, the use of sulfa drugs aim is to disable folic acid that the bacteria need to reproduce. As this article notes:

https://takecareof.com/articles/bene...acid-vs-folate

intake of folic acid exceeds their capacity to process it, it can overwhelm the liver and potentially end up in the bloodstream. The unmetabolized folic acid that remains in the bloodstream has been associated with serious health risks that are worth noting.

https://mpkb.org/home/food/folic

https://chronicillnessrecovery.net/i...article&id=169

The unnatural sourced synthetic toxic form of B9, Folic acid, "doesn’t exist in natural foods, but is sourced from petroleum derivatives, acids, and acetylene", is an accident looking for a place to happen. Unlike the natural sourced form of folate found in leafy greens and vegetables, this form is known to build up in the bloodstream, which provides ready fodder in support of bad bacteria.

In 1997 the old standard of synthetic Folic acid was found to have toxicity issues; yet today it is still included in many processed foods, including rodent block diets. The good news is that there is a new form on the market that is bio identical to that the body metabolizes folate from leafy greens and vegetables, that is highly bioavailable.

https://www.amazon.com/Thorne-Resear.../dp/B00506WNCC


Without supplementation of pre/probiotic, the long term ABs will otherwise wipe out the good gut flora that comprise over 70 % of the whole body immune system of animals, devastating the immune system which results in the weakening the animal, making it susceptible to bacterial infections. To support the use of ABs, it is vital to continually supply a source like unto which these animals have access to in the wild.

Pet Flora by Vitality Science is a Soil Based Pre/Probiotic source. Include 1/64 Tsp. daily with meals for maintenance. For this situation I would double this to the same measure twice a day. Store the left over powder in the capsule in a small sealed plastic container for future use.

https://www.amazon.com/Pet-Flora-cap...4C6K82V36PBN2N

[HRT4SQRLS]

Mel, I’ve been pondering your post. Yes, any antibiotic or actually any drug can cause adverse drug reactions. I also agree that they aren’t common. I remember speaking with an infectious disease doc about SMZ-TMP. It is an older antibiotic. Actually, sulfa drugs are some of the first antibiotics. The interesting thing about them is that they haven’t developed the resistance that the newer antibiotics have.
The ID doc told me that they weren’t used as often due to side effects. The more devastating side effects are autoimmune disorders and one particularly bad side effect is Stevens Johnson syndrome. It’s a condition where the entire skin is affected and results in a burn like injury on the entire body. It is often fatal. Fast forward a few years and now these older antibiotics are rapidly resurfacing due to bacterial resistance. SMX-TMP is now the drug of choice for uncomplicated MRSA infections. While other antibiotics have failed, the sulfa drugs are once again being used more often.

My concern is now regarding Cleo. I’m concerned when an infection is persistent. By the way, I don’t think Baytril is a good antibiotic for sinus issues. Actually a neuro shouldn’t take Baytril as it can lower the seizure threshold and cause seizures. Central Nervous System issues with the fluoroquinolone antibiotics is a recognized risk factor.

Tell us more about this sinus infection. Have the teeth been X-rayed? Is there a head X-Ray? Often sinus issues in squirrels are tooth related. Has odontoma been ruled out? When I hear sinus issues, I think about two things. (1) tooth infection (?odontoma) in which case I would use Clavamox or Clindamycin for infection and address the cause. There might be a bone infection seeding this persistent infection. (2) An atypical infection like Mycoplasma or Bordetella . If something like that I would use doxycycline.

Maybe we can help. Thank you for documenting this so nicely. It’s always good to have cases like this on file for reference. You just never know when it will help someone else.

[mel_la_fee]

My concern is now regarding Cleo. I’m concerned when an infection is persistent. By the way, I don’t think Baytril is a good antibiotic for sinus issues. Actually a neuro shouldn’t take Baytril as it can lower the seizure threshold and cause seizures. Central Nervous System issues with the fluoroquinolone antibiotics is a recognized risk factor.

Tell us more about this sinus infection. Have the teeth been X-rayed? Is there a head X-Ray? Often sinus issues in squirrels are tooth related. Has odontoma been ruled out? When I hear sinus issues, I think about two things. (1) tooth infection (?odontoma) in which case I would use Clavamox or Clindamycin for infection and address the cause. There might be a bone infection seeding this persistent infection. (2) An atypical infection like Mycoplasma or Bordetella . If something like that I would use doxycycline.

Maybe we can help. Thank you for documenting this so nicely. It’s always good to have cases like this on file for reference. You just never know when it will help someone else.

Thank you for the considerate response. You are of course correct about the possibilities. In her short 2 years of life Cleo has been x-rayed 4 times (the most recent time being last week). This includes full body scans and also just views of her skull and teeth. It's one of the reasons I wanted to eventually make a more comprehensive post about her issues. I have a lot of images and documents that I hope might be instructive, or at least informative, to others.
Cleo was brought to me as a 4 ½-5 week old girl that fell over 20 ft straight down onto an asphalt road, was totally comatose, leaking bloody fluids from her nose and mouth, and who had to have tooth particles vacuumed out of her mouth because everything she’d just started to grow in had been shattered. She didn’t get an x-ray that first day but it was assumed she had swelling on the brain and a possible skull fracture. After a kitchen sink’s worth of subq and medication had been thrown at her she remained unresponsive, and I was on the verge of taking her in to be euthanized when she finally woke up, promptly peed on me, and then made it clear she was hungry and thirsty and that I should do something about this. I’ve been her willing human servant ever since.

We (the vet and myself) know she has a tooth bone behind her sinus cavities that fractured into a rather noticeable elbow shape and then died (so, yes, it’s a tooth issue). The exposed part of the tooth fell out, so she only has one upper tooth, but there's still that dead tooth root that harbors the infection. I specifically brought this up with my vet because IMO we aren’t getting to the base cause of the issue (the bacteria are thriving in that dead tooth bone still in there), and I’ve even taken Cleo for a second opinion elsewhere because the problem is so pernicious.
Everyone we see tells me that the dead tooth needs to be extracted, but also that Cleo is not a good candidate for that kind of surgery. She does not respond well to anesthesia and the ensuing inflammation could cause her to suffocate besides.
Based on her most recent x-rays and bloodwork, she clearly has malocclusion and infection, but not an odontoma or other obvious abnormalities. I think that’s likely why they stick to Baytril for treatment. Or, you know, default back to that when she has a reaction to something else. My girl is very sensitive. Thankfully, while she has had seizures in the past and her medication might lower the threshold, we’ve managed to keep them at bay (maybe it’s the almonds?), and honestly, one of the things that made her adverse reaction so hard to understand was that it resulted in that shivering tremble I described but no actual seizures. It sounds weird but if she had seized early on, I feel like I would’ve changed what we were doing right away. In this case there was not something as obvious as that to indicate what was happening. Her decline was happening quickly, but by degrees that were difficult to pinpoint or describe. Know what I mean?

Are there links or documents you could send me about the other drugs that you mentioned, so that I can read more about them and discuss them with my vet? My vet does deal with wildlife and overall, I think she knows what she’s doing, as do the people that work with or for her. I am super grateful to have found that clinic in general. But they don’t live with Cleo and therefore cannot appreciate what I see on a day-to-day basis (and Cleo is extra special), hence why no one caught the adverse reaction sooner. It’s possible my vet knows about those medications and has not recommended them for good reason. But I wouldn’t/can't know that until I have a better understanding of how they work and can ask.

I often wish there was an easy way to make my little girl better, but at the moment I feel like the best I can do is make sure she’s comfortable and well enough to be her most squirrelly self. She can’t jump or climb trees or chatter, but who cares when there’s a perfectly good drawstring to chew on, blankets to nest in, and a stuffed animal that definitely doesn’t need all of it’s toes? As I said before, she has a will to live that is enviable. I just want to be the best fur-mom I can be and any help in that regard is appreciated.

[HRT4SQRLS]

Thanks for explaining the situation. The problem is crystal clear. Forget what I said about the atypical respiratory issues like Mycoplasma or Bordetella. That is clearly NOT the problem.

I doubt the infection will ever be cleared as long as the dead bone aka ‘foreign body’ is present. It’s just like a human with a medical device. If a person has a line infection in an indwelling port, it can’t be cleared with antibiotics. The device has to be removed for the infection to be cleared. It’s sorta like putting your finger on a flea. As long as you hold it, you suppress it. When you lift your finger the flea jumps away. Same with an infected ‘foreign body’. As long as antibiotics are present, the infection is controlled. When they stop, the infection flairs back up. Bacteria tend to produce a biofilm on medical devices or foreign bodies which is a thin layer of bacteria. Biofilms re-seed infections.

Baytril (Enrofloxacin) is very similar to the human antibiotic Ciprofloxacin. It has similar activity. Baytril (enrofloxacin) didn’t make the cut as a human antibiotic due to its association with seizures. When you treat an issue in the mouth you have to consider the organisms that are part of the usual oral flora. Those are the organisms that would be involved in an infection of the head, neck, face or mouth. The most common organisms in the mouth are Streptococcus (Viridans group) and anaerobic bacteria. Anaerobes are the organisms that grow without oxygen. Ciprofloxacin and others fluoroquinolone antibiotics in the same generation (Baytril) are inactive against anaerobes. In one study I found, 55% of the Viridans Strep were resistant to Ciprofloxacin. Likely Baytril would be the same. Lack of coverage for anaerobes and poor coverage for Viridans Strep makes Ciprofloxacin a poor choice to treat infections in the mouth.
Due to resistance, Ciprofloxacin is almost exclusively a Gram negative antibiotic. Gram negatives are predominant in the GI tract. In the mouth, Gram positive organisms are more common.

When treating an infection in the mouth, usually a penicillin class (beta lactam) antibiotic is chosen. The one we commonly use is Clavamox. We have had excellent results with it. Another antibiotic commonly used for a mouth/tooth/bone infection is Clindamycin. Clindamycin has excellent penetration in bones. You ‘might’ have a chance to clear the infection with either Clavamox or Clindamycin. I doubt that you have any chance to clear it with Baytril.

Of course, surgical intervention and removal of the dead bone would be the ultimate cure. Have you thought about taking her to Dr.Emerson? That is her specialty. She has a LOT of experience anesthetizing squirrels. She uses minimal sedation.... enough to do the job but not too deep. I realize the risks are real so I understand your reservations. I will say this though... the risks of long term Baytril on a neuro squirrel are also real.

You asked for documentation. I’ll see if I can get some links for you. All of what I posted was based on 40 years experience as a clinical microbiologist.