Photo by Kikko Kåhre
Trimethoprim-sulfa Antibiotics and Deerhounds Do. Not. Mix.
by John Dillberger, DVM, PhD
Also printed in the March/April 2026 issue of The Claymore.
Trimethoprim-sulfa (T-S) antibiotics kill Deerhounds – not every time, but often enough to avoid using them unless absolutely necessary.
I don’t make this statement lightly. Antibiotics can be lifesaving. And T-S antibiotics have the advantages of convenience (once-a-day dosing) and being able to penetrate tissues like the prostate gland that are hard for other antibiotics to reach. But in Deerhounds, these potential benefits are just not worth the risk.
I first warned about the dangers of using T‑S antibiotics 29 years ago in a 1997 Claymore article entitled Lethal Weapons: Trimethoprim-sulfa Antibiotics. At that time, I had been an SDCA member for only 7 years, and yet I already knew of a half dozen Deerhounds that became sick or died from taking a T-S antibiotic.
Since my article appeared, Deerhounds have continued to sicken and die from taking a T-S antibiotic. Two people whose hounds have had bad reactions to a T-S antibiotic encouraged me to share their experiences to warn other Deerhounders how dangerous these drugs are.
Lynne Lozano and Ben
In April 2020, Lynne’s Deerhound, Ben, was given the antibiotic BACTRIM™ for a mild urinary tract infection. Within days, Ben was lethargic and running a fever. Lynne immediately took Ben to an emergency clinic, where they discovered he had almost no neutrophils (a type of white blood cell) in his blood. Without neutrophils, Ben had little ability to defend himself against bacteria. Dogs and people with few neutrophils can develop fatal infections.
Lynne suspected Ben’s condition might be a reaction to BACTRIM™ because Lynne herself reacts badly to T-S antibiotics. Ben was immediately switched to a different antibiotic given intravenously. After a couple of days, Ben’s white blood cell count was rising back to normal, and his fever abated. Luckily, Ben recovered completely, but it was a close call, took two days in hospital, and cost Lynne thousands of dollars.
Madelaine Dale and Arrow
In October 2025, Madelaine Dale took her bitch, Arrow, for a routine wellness visit. The veterinarian noticed a small abscess on Arrow’s tail and sent her home with 10 days’ worth of SmzTmp tablets. During the days that followed, Madelaine’s husband was out of the country, another of her dogs suffered a coyote attack that required surgery and at-home nursing, and Madelaine herself ended up at the Emergency Room and then on crutches from a knee injury. Madelaine takes up the story from there.
By the time Arrow finished her course of Smz Tmp pills on a Friday, she was clearly not herself. She actually turned around halfway through the evening walk and headed home. I put the sluggishness down to Indian Summer heat, but on Saturday she refused her dinner (Arrow always cleaned her dish). Sunday, I bought her a roast chicken which she gobbled and later threw up. Monday morning, I took her to the vet where we discovered that her platelets were dangerously low. The diagnosis was immune-mediated thrombocytopenia, possibly due to a tick-born disease.
It is a small practice and, at the outset, they offered two options: I could take Arrow to the University Vet center in Raleigh, NC for a platelet transfusion, or they could administer a type of chemo therapy treatment. They couldn’t predict the outcome of either course of action, so I decided to keep Arrow where I could visit and hoped for the best. I spent a few hours with her daily and hand fed her canned food. By Friday, her platelets had returned to normal, and she seemed to have turned a corner, though she had lost ten pounds.
The vet sent her home with a ton of medications (that I assume include antibiotics since they believed they were treating her for a tick-borne disease). She was weak but able to eat and appeared to be on the mend. The revival was deceptive; perhaps she was just relieved to be home. On Sunday morning, she began throwing up, first food, then bile. I called the vet and was told they could dispense anti-nausea pills, but no one was on call to receive her. Monday morning, I raced back to the vet with a dog that could barely walk. They discovered that her platelets had crashed and administered IVs and I don’t know what all. Early Tuesday morning, the vet called to advise euthanasia because Arrow’s kidneys or liver (I was too upset to remember) had failed and her skin bruised at the touch. When I arrived, the life had gone from her eyes, and it was clear that it was best to end Arrow’s suffering.
What Happened to Ben and Arrow?
Ben and Arrow each experienced a sudden dangerous drop in circulating blood cells caused by a T-S antibiotic. In Ben, it was neutrophils; in Arrow, platelets. The medical term for a low number of circulating blood cells is “cytopenia.” Ben’s cytopenia would be called neutropenia, while Arrow’s would be called thrombocytopenia.
Cytopenia is a well-known potential side effect of T-S antibiotics. A 1960 study in Beagles first identified that T-S antibiotics can cause cytopenia. Burroughs Wellcome conducted the study to support the approval of the first T-S antibiotic for human use, called TRIBRISSEN®. When the company later developed the drug for veterinary use, it changed the sulfa component from sulfamethoxazole to sulfadiazine and did another study in Beagles in 1982. The second study confirmed that T-S antibiotics can cause cytopenia in dogs, even at the recommended dose level. Cytopenia tended to develop after at least three weeks of administration; therefore, the TRIBRISSEN® label recommended using the drug for no longer than two weeks.
Soon after veterinary TRIBRISSEN® hit the market, reports appeared in veterinary journals about cytopenias in dogs given the drug. The first report I can find (Giger et al., 1985) describes “serious, but reversible, allergic drug reactions” in 6 Doberman Pinschers that began 10 to 21 days after the dog started to receive a T-S antibiotic. The reactions included neutropenia in one dog and thrombocytopenia in another dog, as well as liver damage and joint inflammation. The authors pointed out that “drug allergies” caused by a T-S antibiotics could mimic autoimmune disorders. They reproduced the clinical signs by giving the dogs only the sulfa component of the antibiotic. The authors raised the possibility that Dobes as a breed might have a genetic susceptibility that made them more likely than other breeds to have an allergic reaction to a T-S antibiotic.
Later studies expanded our understanding. A 2003 report (Trepanier et al.) described 40 dogs that developed what the authors called “sulfonamide-associated hypersensitivity,” meaning that they reacted to T-S antibiotics by developing cytopenias and/or a wide range of other symptoms. Clinical signs began as early as 5 days after the first dose. The most common ones were fever and thrombocytopenia, which occurred in more than half the dogs. Liver damage and neutropenia were the next most common effects, occurring in one quarter of the dogs. The authors noted that the true incidence of neutropenia might be greater because “neutropenia tended to occur early… and to resolve without specific therapy (data not shown). Therefore, it may have been missed in some of these dogs for which blood counts were not immediately performed.” Thrombocytopenia was a bad sign in terms of prognosis: 90% of dogs without thrombocytopenia recovered, but only 63% of dogs with thrombocytopenia did so. The authors concluded by saying that veterinarians who dispense a T-S antibiotic must “consider, anticipate, and recognize these hypersensitivity reactions and adequately educate owners to watch carefully for signs of illness during treatment.”
The serious side effects caused by T-S antibiotics are due to an immune reaction triggered by the drug against specific cells, such as platelets, neutrophils, or liver cells. It is unclear why some dogs develop such antibodies and others do not, nor is it clear why the antibodies attack blood cells in some dogs and liver cells in other dogs. Researchers have sought a genetic basis for T-S hypersensitivity in Doberman Pinschers (Reinhart et al., 2018), but without success.
While antibodies triggered by a T-S antibiotic are clearly responsible for most of the symptoms that occur in a hypersensitivity reaction (Weiss 2012), a second factor may contribute to the development of cytopenia. That factor involves the B vitamin folic acid.
T-S antibiotics kill bacteria because both components block a bacterial cell’s ability to make folic acid. Without folic acid, the bacterial cell cannot reproduce. The sulfa component of the antibiotic affects only bacteria. But the trimethoprim component also can affect the developing blood cells in a dog’s bone marrow, by competing with folic acid for an enzyme the blood cell needs to reproduce. If a dog’s developing blood cells contain more trimethoprim than folic acid, then they will be unable to reproduce, and the result will be cytopenia.
This theoretically should not occur. Dogs get their folic acid from two sources: folic acid in their food, and folic acid made by their own intestinal bacteria. Of course, as soon as a dog begins taking a T-S antibiotic, its only source of folic acid is its food, because the antibiotic prevents intestinal bacteria from making folic acid.
Still, a dog theoretically should get enough folic acid from its food. Folic acid is added to most commercial dog foods to ensure that they contain enough when you buy them. However, folic acid is readily destroyed by exposure to light and oxygen, so foods that contain adequate folic acid when sealed in the bag may not have much folic acid left once the bag has been open for a while or near their expiration date.
Any dog taking a T-S antibiotic should be getting a diet that contains plenty of folic acid, and you shouldn’t assume that dog food alone will provide enough. Good sources of folic acid are liver (most animals store the bulk of their folic acid in the liver), other organ meats, soybeans, wheat germ or bran, yeast, and (of course) multiple vitamin supplements, provided they’re kept in a closed, opaque container.
Conclusions
The easiest way to avoid a hypersensitivity reaction is not to give your Deerhound a T-S antibiotic. They are sold under names like BACTRIM®, TRIBRISSEN®, SEPTRA®, SULFATRIM®, COTRIM®, PRIMOR®, CO-TRIMOXAZOLE®, PRIMSOL®, NOVO-TRIMEL®, and TMP-SMX.
If you do choose to give your hound a T-S antibiotic, then make sure it gets plenty of folic acid in its food or takes a multiple vitamin supplement during antibiotic treatment. Be alert for signs of trouble: pale gums, bleeding of any sort, a sudden turn for the worse, or the sudden appearance of a new symptom. If you plan to use these antibiotics for longer than 10 days, then have your veterinarian do a complete blood count after a week to check for cytopenia.
A Word about ALBON®
ALBON® is a sulfa antibiotic (sulfadimethoxine) with no trimethoprim component, which is often used to treat coccidiosis. It carries the same risk of causing a hypersensitivity reaction as does a T‑S antibiotic (Trepanier 2004).
A Word about Sulfasalazine
Sulfasalazine is a human drug sometimes used in dogs to treat colitis. Brand names include AZULFIDINE®, SULFAZINE, or SALAZOPYRIN®. It contains the sulfa antibiotic sulfapyridine and salicylic acid (aspirin). It carries the same risk of causing a hypersensitivity reaction as does a T-S antibiotic (Brooks 2023).
A Word about Non-antibiotic Sulfa Drugs
Only antibiotic sulfonamides have the potential to cause a hypersensitivity reaction (Trepanier 2004). There is no evidence for cross-reactivity with drugs that have a different underlying structure but share a sulfonamide moiety, such as acetazolamide, furosemide, glipizide, or hydrochlorthiazide.