Unexplained head tilt? "Vestibular" problem? Has your cat ever taken metro?

Putative Metronidazole Neurotoxicosis in a Cat - Veterinary Pathology September 2005 vol. 42 no. 5 665-669

Metronidazole (Flagyl, G. D. Searle & Co., Chicago, IL) is a nitroimidazole antibiotic that is commonly used in veterinary medicine to treat a wide variety of conditions, including anaerobic bacterial infections,10,17 protozoal infections (e.g., giardiasis),10,17 Helicobacter-associated gastritis,15,22 and hepatoencephalopathy.17,23,24 In addition to its anti-protozoal and bactericidal properties, metronidazole is thought to have some immunomodulatory effects and is commonly used to treat inflammatory bowel disease (IBD) in both dogs and cats.10,17 The drug is lipophilic and has a wide tissue distribution with oral bioavailability ranges from 50 to 100%.8,17 Metronidazole is primarily metabolized in the liver and has been shown to rapidly cross the blood-brain barrier.7,10 Another study using 14C-labeled metronidazole detected accumulation of the unchanged drug in the cerebellum and hippocampal areas of mice after intravenous (IV) administration.16 Central nervous system (CNS) side effects associated with metronidazole toxicosis have been reported in humans2,9,11–14 and in veterinary species, including rats,19 dogs,5,6,8,21,25 and cats.4,20 Peripheral neuropathies are frequently reported in human cases of metronidazole toxicosis; however, nausea, dizziness, tremors, ataxia, and seizures have also been reported. In dogs and cats, central vestibular and cerebellar dysfunctions resulting in ataxia, nystagmus, head tilt, tremors, and seizures are commonly reported in cases of metronidazole toxicosis.10 To our knowledge, this is the first report to document histologic lesions in the CNS associated with metronidazole administration in a cat.

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Bold, my emphasis


http://onlinelibrary.wiley.com/doi/...ionid=10A9E24AF413556339009C8B7849E5AC.f03t03

For more information:

Metronidazole: beware of neurotoxic side effects http://www.vetcontact.com/en/art.php?a=572

Metronidazole: Uses, toxicity and management of neurologic sequllae http://veterinarynews.dvm360.com/dvm/article/articleDetail.jsp?id=113198

Treatment of Metronidazole toxicity http://www.vetlearn.com/standards-of-care/treatment-of-metronidazole-toxicity (You have to sign up to sign in, but it's free)

Metronidazole Toxicity: Prevention and Treatment: http://www.vetneuro.com/Resources/Reference/NeuroNews/eNewsletterApril2010/tabid/9024/Default.aspx

Metronidazole has long been used in veterinary medicine as an antibiotic to treat many infectious diseases in dogs and cats. Neurotoxicity can occur from acute overdoses or even from "recommended" doses in animals on chronic therapy. Cats and small dogs may be more susceptible to acute overdoses. Common strengths for metronidazole are 500 mg and 250 mg tablets. Even a quarter of a 250 mg tablet given twice daily to a 10 pound dog has the potential to cause neurological signs.

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Again, bold my emphasis. This article has links to video clips of dogs with metro toxicosis.

Interesting links, thank you for posting both those about the Metronidazole and the Diazepam.  Anyone reading, do make sure you read the link with the potential side effects for cats with the Diazepam treatment for the neurotoxisis as well as the others.

Yes - what surprised me is that while most discussion of metro mention the potential for neurotoxicity with metro, it is almost always mentioned as being a side-effect with long term use. But these indicate that even at regular doses and short-course treatments it can happen. SO many animals are on metro, obviously it's rare. But combined with its potential as a carcinogen, at this point, I won't be using metro again. Not even in the ferals with giardia. I'll figure out how to get panacur into them.

Here's the metro / flagyl discussion as re: cancer http://www.thecatsite.com/t/270801/...tro-is-genotoxic-and-potentially-carcinogenic

Patches has been on metro several times for IBD flares but it has always been what is a normal lenghth of time for an antibiotic.  I was really surprised to hear of kitties here that had been on metro long term for IBD.  I don't think any antibiotic should be taken long term.  I don't know if there are vets that think this is preferable to a steroid or if they are just thinking about it's anti-inflammatory effects and forgetting that it is an antibiotic.

Since Patches has been on the steroid he has only had two mild flares both in the spring, he was given metro both times.  He is prone to constipation with the IBD and I think it is caused by the extra hair he is swallowing in the spring.  I am going to try giving him Miralax daily through shedding season this year and see if he can get through without getting sick.

The whole thing is concerning given the regularity the drug is used both in long and short term.  The added thing for me was that while some symptoms can be treated the treatment itself (Diazepam) can then have severe and long term or fatal consequences.  You have to go for the treatments though otherwise the cat is going to be sick anyway, but it is so scary to think what a thin tightrope veterinarian (and human)  medicine still is.

Well, actually, in most instances there is an alternative. Metro is most frequently used for giardia and IBD - and yet most strains of giardia are now resistant to it. Panacur is the preferred drug of choice for giardia now.

That's part of the problem: there are, in most cases, options. And vets aren't telling people about the risks.

And with IBD, Tylosan can be an option. It also exhibits the anti-inflammatory effects that metro does in the GI system. http://www.vetinfo.com/treating-diarrhea-tylosin.html

And for IBD kitties, given that it is becoming increasingly clear that it is, in fact, a gut flora imbalance that triggers it (though of course genetics and environment are factors), while an antibiotic *may* be needed if there is a particularly pathogenic overgrowth - in many instances, PCR tests and fecal exams come up negative. In those instances, there isn't any reason the IBD can't be treated with Diagel and much larger doses of human grade probiotics to repopulate the gut with healthy bacteria. A few years back there was a metro shortage, and many vets were "prescribing" Diagel instead (Diagel is herbal and does not "require" a prescription).

In fact, L. acidophilus is associated with improved B-12 uptake, and despite the info in this study about its association with weight loss in humans, because of the improved B-12 uptake, a number of people with IBD kitties are trying it. It takes three weeks to a month to see results (in terms of weight gain), but it helps. (reference: http://news.stanford.edu/news/2009/july8/probiotics-071309.html ). S. boulardii is another (yeast-based probiotic - it doesn't repopulate the gut, it has to be given on an ongoing basis) is another probiotic with promise for IBD.

My understanding is that Metro is the only antibiotic that crosses the blood-brain barrier, so any other antibiotic is a better choice if there are any options. And for the pathogenic bacteria associated with IBD, I believe there are options.

Diagel: http://www.revivalanimal.com/DiaGel.html

For the rest of the info re: gut health, IBD and probiotics:

Review arti cle: anti-inflammatory mechanisms of action of Saccharomyces boulardii. In the results, "Recent results indicate that S. boulardii may interfere with IBD pathogenesis by trapping T cells in mesenteric lymph nodes." http://www.ncbi.nlm.nih.gov/pubmed/19706150

Efficacy and safety of the probiotic Saccharomyces boulardii for the prevention and therapy of gastrointestinal disorders http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296087/

Gut flora and IBD, walking up the timeline:

2004 Probiotics in inflammatory bowel disease: is it all gut flora modulation? http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1774052/

2010, California Institute of Technology (article about the research) Biologists link gut microbial equilibrium to inflammatory bowel disease http://www.sciencedaily.com/releases/2010/04/100426092803.htm
The study: http://www.ncbi.nlm.nih.gov/pubmed/20413095

2011 Probiotics for the Control of Parasites: An Overview http://www.hindawi.com/journals/jpr/2011/610769/

2011 Yale (article about the research) Immune system malfunction may trigger inflammatory bowel disease http://medicalxpress.com/news/2011-05-immune-malfunction-trigger-inflammatory-bowel.html
The study: http://www.ncbi.nlm.nih.gov/pubmed/21565393

2013 UC Davis (press release) Scientists find key to growth of "bad" bacteria in inflammatory bowel disease http://www.ucdmc.ucdavis.edu/publish/news/newsroom/7462
The study: http://www.sciencemag.org/content/339/6120/708

No - I think there are usually better options than using metro, especially if it's for IBD.

I somehow missed this thread.

So you think non-prescription alternatives to antibiotics would be probiotics (including s. boulardii) and DiaGel? I have to admit; I don't like all the stuff I see in DiaGel, but I guess you're saying that it's better than metro. Perhaps two others would be organic extra virgin coconut oil and liquid clay (as in Luxolite by Vitality Science) to help grab toxins and bacteria as it passes through the GI tract.    I don't know much about Tylosan as an alternative. Does this have serious side effects, as well?

The vet and I think Sebastian is particularly susceptible to bacterial overgrowth in the GI tract, but I need to get him off the metro. I think I'm going to cut his dose in half starting ASAP. He has recently been attacking Caesar so violently that I can't help but wonder if it is neurological. This is unlike him and I'm very concerned. I started a thread about in in the Behavior forum: http://www.thecatsite.com/forum/newestpost/272373

ETA: Do you think metro has the potential to cause aggression related to neurological toxicity?

I don't know enough about neurotoxicity to know. Your vet should be able to look it up on VIN though.

Which ingredients in Diagel are a problem for you?

The FIV health-science group has a lot of cats on metro, so a lot of work is being done to find alternatives. This information was provided as re: the cranberry powder (the problem being the benzoic acid in them):

I thought I'd post this brief note on the basis of the recent post on the "toxicity" of cranberries for cats because they contain benzoic acid. It is true that benzoic and phenolic acids are toxic to cats. It is not, in fact, that they can't process these acids at all but that they don't process them well because only one of the two pathways by which they are metabolized by people does the same for cats. 200mg/kg of benzoic acid was fixed in a long-ago study as the maximum tolerable dose in cats. 300 mg/kg produced a mild hyperaesthesia. The benzoic and phenolic acid content of a fresh cranberry is about one half of 1%. So while I agree with those who have pointed out that adding blueberries, cranberries and the like to pet foods is probably silly and that no research has actually established that cats benefit from these things as people do, I have also yet to come across an instance of document harm. The issue strikes me as roughly equivalent to the traditional "green potatoes are toxic" warnings despite the fact that there are no documented cases of poisoning by green potato in the past 50 years.

I'm honestly not sure of the benzoic acid content of the cranberry extract products that many people have given their cats and that many vets have even recommended to cats, but elementary math skills (which well describe mine) suggest to me that cranberries don't pose much of an actual threat. There may well be better ways to treat UTI's, so I'm not making a therapeutic argument, but rather a point about how "toxic" needs to be understood as a term. Aspirin is "toxic" to cats, but that doesn't mean a cat never can or should be given aspirin.

I came to the whole subject of cranberries by way of fairly recent research indicating that cranberries inhibit calici virus. Whether this makes them useful in an actual clinical situation is unclear since the research was "in vitro," not "in cat-o."

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Honestly, I'd rely on S. boulardii and rotate various rather large doses of human probiotics. There is so much research out there now about the ability of various probiotics to crowd out different unhealthy bacterial strains - the primary overgrowth candidates being harmful strains of E. coli and clostridium - well, here's a study from 2008: http://www.vet.cornell.edu/labs/simpson/docs/Janeczko.pdf

...and we already know that S. boulardii can resolve clostridium without the use of antibiotics: http://www.thecatsite.com/t/259985/trouble-in-raw-paradise-clostridium-perfringens-and-my-cats