By Wendy C. Brooks, DVM, DipABVP
Educational Director, VeterinaryPartner.com
Brand Names: Tribrissen, Septra, Bactrim, Cotrim, Sulfatrim, Sulfadiazine
80 mg trimethoprim/400 mg sulfadiazine
80 mg trimethoprim/400 mg sulfamethoxazole
160 mg trimethoprim/800 mg sulfadiazine
(Sulfadiazine is used in veterinary formulations, sulfamethoxazole is used in human formulations)
Ever since the development of penicillin, there has been a drive to make antibiotics better: better ability to penetrate into infected tissue, better efficacy against a broader spectrum of bacterial organisms, less potential to harm host tissues. The combination of trimethoprim and sulfa antibiotics has created a unique method to combat bacteria called the sequential blockade, which will be described below.
An essential nutrient used in the synthesis of many important biochemicals is folic acid. Folic acid is made from para-amino benzoic acid through a step-by-step process involving two enzymes. The sulfa drug inhibits the first enzyme and trimethoprim inhibits the second enzyme. This double inhibition is called the sequential blockade and causes death of the bacterium whereas either antibiotic alone might not be strong enough to do so. Mammal enzymes are far less sensitive to the blockade than bacterial enzymes, but what really protects the infected host from the blockade is the simple fact that mammals do not have to manufacture their own folic acid; they can eat it in their diet.
How this Medication is Used
There are several advantages to using trimethoprim-sulfa (sometimes called trimethoprim-sulfadiazine). First, this medication has the advantage of being able to penetrate into exudates and infected tissues that usually stop other antibiotics at their surface. Similarly, trimethoprim-sulfa can penetrate sequestered sites of the body where there is a natural barrier separating certain tissues from the rest. This means trimethoprim sulfa can enter not only abscessed tissue but can penetrate the prostate gland, the blood brain barrier, and the eye, and treat infections in these locations.
Trimethoprim-sulfa is a broad spectrum antibiotic with excellent activity against most gram negative organisms and against Staphylococci in the skin. This makes trimethoprim-sulfa a good choice for skin infections or as a general antibiotic when the identity of the infecting organism is not known. Trimethoprim sulfa is, however, not generally effective against Pseudomonas aeruginosa, which is particularly resistant where ever it emerges.
Trimethoprim sulfa is generally prescribed for once or twice a day use. It may be given with or without food and should be stored at room temperature. It costs relatively less compared to other antibiotics, which makes it a popular choice. Infections for which trimethoprim sulfa are especially helpful are:
In general, drug side effects are classified as either common or serious (with rare drugs having side effects that are both common and serious). As with most drugs, trimethoprim sulfa has common side effects and rare serious side effects.
Common Side Effects
Upset stomach symptoms of vomiting/nausea, diarrhea, or appetite loss can be seen with this medication. The oral suspension is famous for its awful taste and may elicit drooling as pets try to get the taste out of their mouths. These side effects are inconvenient and may even necessitate changing to another medication but are not regarded as serious.
Inability to produce adequate tears (dry eye)
Sulfa drugs of any kind are capable of disrupting tear function. Classically, this occurs after long term therapy (i.e. weeks to months) of use but occasionally certain individuals suffer from dry eyes after only one dose of sulfa. In most cases, tear function resumes normally after the drug is discontinued but occasionally the effect is long term or permanent despite withdrawal of the drug. Watch for goopy, mucous eye discharge and/or rubbing or signs of eye discomfort.
Serious Side Effects
A broad inflammatory syndrome has been observed in some individuals sensitive to trimethoprim sulfa. This includes arthritis, fever, muscle soreness, hives, kidney inflammation/glomerulonephritis, and even inflammation in the eye (uveitis.) This syndrome has been formally studied and has been found to occur almost exclusively after a previous uneventful exposure to trimethoprim sulfa and occurs 8-20 days after therapy has started. The Doberman pinscher seems to be over-represented and complete recovery can be expected within one week of discontinuing the medication but must be recognized for what it is in order to avoid permanent effects. This reaction is immune-mediated so often steroids for immune suppression are needed for rapid resolution in addition to discontinuing the trimethoprim sulfa. Because of this reaction, many experts feel this drug should not be used in the Doberman pinscher. Watch for facial swelling, difficulty/painful movement, listlessness, cloudy eyes.
Drug related skin reactions do not have characteristic appearances; in fact, they can have any appearance. They do, however, begin around the start of treatment with the offending drug and vanish with cessation of administration of the offending drug. Any drug of any kind can produce a drug reaction in the skin; trimethoprim sulfa is somewhat over-represented in cases of skin related drug eruptions. Hives and facial swelling have been described. Watch for extremely itchy skin, sores.
Liver failure can result when a sensitive individual receives this medication. Nausea, jaundice, and all the other complications that occur with liver failure of any origin may result. Discontinuing the medication should lead to recovery. If the liver is biopsied during its state of failure, changes associated with trimethoprim sulfa reaction are characteristic (i.e., it should be possible via biopsy to determine if a failing liver was caused by an idiosyncratic trimethoprim sulfa reaction. Watch for yellow pigmentations of the skin and eyes.
Blood dyscrasias are abnormal blood cells or proportions of different blood cells. Blood dyscrasias might lead to immune dysfunction, bleeding tendency, or other problems depending on which blood cells are affected. With trimethoprim sulfa, loss of red blood cells, platelets, and white blood cells have been reported. This syndrome is typically part of the joint inflammation syndrome. Watch for bruising, bleeding, weakness, paleness of the gums.
Immune mediated destruction of red blood cells can be initiated by drug reactions and this has been one of the more commonly implicated drugs. A patient with a history of immune mediated hemolytic anemia should probably avoid this medication. Watch for yellowing of the eyes and skin, weakness.
Sulfa bladder stones
Bladder stones made of the sulfa antibiotic can actually form. This has been reported in patients taking routine doses of sulfas for routine (as opposed to extended) periods of time but is very rare. Watch for bloody urine, straining to urinate.
Interactions with other Drugs
The following drugs may be enhanced by trimethoprim-sulfa use: phenylbutazone (an NSAID), thiazide diuretics, aspirin, and methotrexate (a cancer medication).
Antacids may interfere with the effectiveness of trimethoprim-sulfa.
Trimethoprim-sulfa should not be used with cyclosporine (used for airborne allergies, perianal fistulas, and immune suppression after organ transplant). This combination increases toxicity of the cyclosporine and reduces its beneficial effects.
Concurrent use of thiazide diuretics with trimethoprim-sulfa can lead to a significant drop in platelets.
Tricyclic antidepressants may not be as effective if used in conjunction with trimethoprim-sulfa.
Concerns and Cautions
- Trimethoprim-sulfa should not be used by patients with a history of liver disease, kidney disease, dry eye, blood dyscrasias, immune mediated red blood cell destruction, or known sulfa drug sensitivity.
- This medication is best not used in pregnancy. Birth defects have been reported after this medication was given to pregnant rats.
- Use of trimethoprim-sulfa should be avoided in Doberman pinschers as this breed appears predisposed to reactions against sulfa drugs.
Become familiar with the above described idiosyncratic reactions. These reactions are uncommon but it is important to be prepared. If you think your pet may be having a drug reaction, notify your veterinarian immediately.
- Signs of overdose include nausea and diarrhea, confusion and depression, bone marrow disease, and facial swelling.
- Trimethoprim-sulfa oral suspension is famous for its objectionable taste and is particularly difficult to use in cats. Sometimes liquid formulations obtained through a compounding pharmacy are more palatable.
- Trimethoprim-sulfa will interfere with thyroid function testing. It is not known precisely how long trimethoprim-sulfa should be discontinued in order to get a valid thyroid reading.
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