Chapter 10 – Sulfonamides and Trimethoprim


Sulfonamides are commonly used in swine medicine. However, numerous resistances have developed against sulfonamides over the years so they can be used with other antimicrobials to potentiate the effect. Trimethoprim potentiates the action of sulfonamides by acting on the same pathway but at a second location. Sulfas are used to treat susceptible bacteria responsible for post-weaning diarrhea, mastitis-metritis-agalactia syndrome or even atrophic rhinitis when it was still an issue in swine production. However, due to the high amount of resistances against these antimicrobials, it is recommended to perform an antibiogram before treatment and to evaluate the evolution of the situation after a few days.

Useful molecules to know in swine medicine:

  • Sulfonamides can be used alone or in combination with chlortetracycline in swine.

Mechanism of Action

Sulfonamides and trimethoprim both act the folic acid pathway but at different points creating a sequential inhibition. Sulfonamides act as false substrates for some enzymes of the pathway while trimethoprim competes with another substrate and inhibits another enzyme in the pathway.
Why is folic acid important in the bacterial growth? It is necessary for the synthesis of amino-acids and nucleic acid bases.

Check your learning: Sulfonamides and trimethoprim and mechanism of action


The spectrum of these antimicrobials is moderate and even further limited by the extent of the bacterial resistances. Both Gram + and Gram – bacteria are susceptible if they do not host resistances. Mycoplasma spp. and Enterococcus are intrinsically resistant. Sulfonamides and trimethoprim are usually not effective against intracellular pathogens. Eukaryotic cells are not susceptible to these molecules because they do not create folic acid, it is provided through nutrition. (Remember the vitamins pregnant women need to take to ensure a healthy development of the fetus: folic acid is one of the most important components!).


Sulfonamides a weak acidic, water soluble molecules whereas, trimethoprim is a weak lipophilic base. The combination of the two has a good bioavailability and highly binds to plasma protein.


Sulfonamides and trimethoprim have a moderate volume distribution but have a good tissue penetration.


Sulfonamides and trimethoprim undergo phase I and phase II metabolism in the liver and are filtered at the glomerulus and excreted in the urine. Sulfonamides usually have a shorter half-life but large variation have been observed between patients.

Adverse effects

Sulfonamides with or without trimethoprim are relatively safe to use in swine. Mild diarrhea can be noted if the used dose is high. Extra attention should be paid to withdrawal time because sulfonamide residues have been found at the processing plant.

Resistances against sulfonamides are common. They can affect the antimicrobial process in different ways. Some mutations modified the structure of the enzyme in the folic acid pathway, preventing sulfonamides to bind and compete against the original substrate. Other mechanisms include increasing the number of enzymes or decreasing drug penetration into the bacterial cell.


Sulfonamides are used in combination with other bacteriostatic time dependent antimicrobials such as chlortetracycline. If the bacteria is sensitive to both sulfonamides and trimethoprim, that is another synergy that can be used.


Swine Antibiotherapy Handbook Copyright © by Perle Zhitnitskiy. All Rights Reserved.

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