Trimethoprim-Sulfadiazine

Trimethoprim–sulfadiazine is a potentiated sulfonamide antimicrobial used in veterinary species including dogs and horses. Sequential inhibition of microbial folate metabolism provides activity against selected bacterial and some protozoal pathogens. Oral and parenteral preparations have distinct product applications, and their clinical usefulness depends on organism susceptibility and infection site.

Group

Potentiated sulfonamide antibacterial

Mechanism of Action

Sulfadiazine inhibits microbial dihydropteroate synthase through competition with para-aminobenzoic acid. Trimethoprim then inhibits dihydrofolate reductase, reducing formation of tetrahydrofolate required for nucleic-acid synthesis. This sequential folate blockade produces synergistic activity in susceptible organisms. Resistance at either target and differences in exposure affect the combination’s antibacterial or antiprotozoal effect.

Dose Rates

Dogs

Use / stage	Dose	Route	Schedule	Instructions
Susceptible bacterial infection	15 mg/kg	PO	Every 12 h	Combined-total dose; typical initial courses in the source are 7-14 days, adjusted to infection and response.
Susceptible bacterial infection - alternative	30 mg/kg	PO	Every 12–24 h	Combined-total dose; choose the interval for the specific infection rather than treating the interval range as interchangeable.
Toxoplasmosis	30 mg/kg	PO	Every 12 h	Combined-total alternative regimen; source also lists 15 mg/kg every 12 hours for 28 days.
Toxoplasmosis - alternative	15 mg/kg	PO	Every 12 h	Up to 28 days; Combined-total dose.
Chronic pyoderma	30 mg/kg	PO	Every 12 h	Up to 42 days; Combined-total dose; courses 21-42 days.
Bacterial urinary tract infection	30 mg/kg	PO	Every 12 h	Combined-total dose.
Systemic infection or bacteraemia	30–45 mg/kg	PO	Every 12 h	Up to 5 days; Combined-total dose; course 3-5 days.
Coccidiosis	30 mg/kg	PO	Every 24 h	Up to 10 days; Combined-total dose.
Pneumocystosis	15 mg/kg	PO	Every 8 h	Up to 21 days; Combined-total dose.
Pneumocystosis	30 mg/kg	PO	Every 12 h	Up to 21 days; Combined-total dose.

Cats

Use / stage	Dose	Route	Schedule	Instructions
Susceptible bacterial infection	15 mg/kg	PO	Every 12 h	Combined-total dose; typical initial courses in the source are 7-14 days, adjusted to infection and response.
Susceptible bacterial infection - alternative	30 mg/kg	PO	Every 12–24 h	Combined-total dose; choose the interval for the specific infection rather than treating the interval range as interchangeable.
Toxoplasmosis	30 mg/kg	PO	Every 12 h	Combined-total alternative regimen; source also lists 15 mg/kg every 12 hours for 28 days.
Toxoplasmosis - alternative	15 mg/kg	PO	Every 12 h	Up to 28 days; Combined-total dose.

Ferrets

Use / stage	Dose	Route	Schedule	Instructions
Susceptible bacterial infection	30 mg/kg	PO	Every 12 h	Combined-total dose.
Coccidiosis	30 mg/kg	PO	Every 24 h	Up to 14 days; Combined-total dose.

Rabbits

Use / stage	Dose	Route	Schedule	Instructions
Susceptible bacterial infection	15–30 mg/kg	PO	Every 12–24 h	Combined-total oral regimen.

Chinchillas

Use / stage	Dose	Route	Schedule	Instructions
Susceptible bacterial infection	15–30 mg/kg	PO	Every 12 h	Combined-total dose.

Gerbils

Use / stage	Dose	Route	Schedule	Instructions
Susceptible bacterial infection	15–30 mg/kg	PO	Every 12 h	Combined-total dose.

Guinea pigs

Use / stage	Dose	Route	Schedule	Instructions
Susceptible bacterial infection	15–30 mg/kg	PO	Every 12 h	Combined-total dose.

Hamsters

Use / stage	Dose	Route	Schedule	Instructions
Susceptible bacterial infection	15–30 mg/kg	PO	Every 12 h	Combined-total dose.

Mice

Use / stage	Dose	Route	Schedule	Instructions
Susceptible bacterial infection	15–30 mg/kg	PO	Every 12 h	Combined-total dose.

Rats

Use / stage	Dose	Route	Schedule	Instructions
Susceptible bacterial infection	15–30 mg/kg	PO	Every 12 h	Combined-total dose.

Horses

Use / stage	Dose	Route	Schedule	Instructions
Susceptible bacterial infection	25–30 mg/kg	PO	Every 12 h	Combined-total dose. Oral sulfadiazine products have the stronger equine evidence; administer before hay where feasible.
Foal susceptible bacterial infection	15 mg/kg	PO	Every 12 h	Foal alternative from the supplied formulary; combined-total dose.
Susceptible respiratory infection	24 mg/kg	PO	Every 12 h	Up to 10 days; Combined-total Equisul-SDT regimen: 4 mg/kg trimethoprim plus 20 mg/kg sulfadiazine.

Cattle

Use / stage	Dose	Route	Schedule	Instructions
Susceptible bacterial infection	25 mg/kg	IV, IM	Every 24 h	Combined-total historical regimen; injectable formulation must support this route.
Calf susceptible bacterial infection	48 mg/kg	IV, IM	Every 24 h	Calves only; combined-total historical regimen.

Pigs

Use / stage	Dose	Route	Schedule	Instructions
Susceptible bacterial infection	48 mg/kg	IM	Every 24 h	Combined-total regimen; use only a preparation appropriate for IM administration.

Indications

Treatment of susceptible respiratory, urinary, skin or soft-tissue bacterial infections in dogs, horses and other supported veterinary species.
Treatment of selected susceptible bacterial prostatitis in dogs.
Treatment of selected susceptible foal bacterial infections within an organism-directed plan.
Selected multiagent treatment of canine neosporosis or American canine hepatozoonosis, with limited organism- and regimen-specific evidence.

Contraindications

Sulfonamide hypersensitivity; marked hepatic damage or blood dyscrasias.
Use cautiously in renal disease, dehydration and pregnancy; Dobermans are particularly susceptible to immune-mediated reactions.

Interactions

Methotrexate or pyrimethamine increases antifolate toxicity risk.
Methenamine can promote urinary precipitation; warfarin effects may increase.
IV potentiated sulfonamides with detomidine in horses can cause cardiac arrhythmias.

Adverse effects

Keratoconjunctivitis sicca, hepatopathy, cytopenias, immune-mediated polyarthritis and skin reactions in dogs.
Vomiting, diarrhoea and reversible suppression of thyroid function; diarrhoea or colitis in horses.

Toxicity

Overdose can cause CNS signs, marrow suppression and urinary crystallisation. Provide hydration and supportive care; folinic acid may be needed for severe marrow toxicity.

Preparations

Preparation	Form	Strength	Route
Equine trimethoprim/sulfadiazine powder 67/333 mg per g Combined-total dose basis; not a trimethoprim-only dose.	Powder	trimethoprim 67 mg / g + sulfadiazine 333 mg / g	PO

Monitoring and Administration

Monitor clinical response, hydration, CBC, hepatic/renal indices and tear production with prolonged treatment; thyroid tests can be reversibly depressed.

For a 1:5 trimethoprim:sulfonamide product, 30 mg/kg combined total equals 5 mg/kg trimethoprim plus 25 mg/kg sulfonamide. Never calculate the whole dose from trimethoprim concentration alone.

Oral trimethoprim absorption is poor in adult ruminants; calf data must not be generalized to adult cattle.

Multidrug protozoal regimens: canine Neospora protocols use combined TMP/sulfa 15 mg/kg PO every 12 hours for 4 weeks with clindamycin 10 mg/kg every 12 hours or pyrimethamine 1 mg/kg daily. Hepatozoon protocols use TMP/sulfa 15 mg/kg every 12 hours, pyrimethamine 0.25 mg/kg daily and clindamycin 10 mg/kg every 8 hours; courses differ by species and disease. These combinations require the complete protocol, not isolated single-drug arithmetic.