Sulfonamide antibiotics, or sulfa drugs, are synthetic drugs made from a chemical containing sulfur. Most are antibiotics, but some are used in the treatment of ulcerative colitis. Sulfa antibiotics have been around since 1936. They have a wide range of uses and are available in many forms including oral solutions, injection, and tablets.

WHAT ARE SULFONAMIDE ANTIBIOTICS?

Sulfonamide antibiotics are a group of synthetic medications containing sulfonamide chemicals. These antimicrobials include sulfonylureas, furosemide, thiazide diuretics, furosemide, some COX-2 inhibitors, and acetazolamide.

Sulfonamide antibiotics are available under the following brands, but many are only available in generic form:

  • Sulfisoxazole (Truxazole)
  • Sulfamethoxazole/trimethoprim (Bactrim, Bactrim DS, Septra, Septra DS)
  • Sulfasalazine (Azulfidine, Sulfazine)

HOW ARE SULFONAMIDE ANTIBIOTICS PRESCRIBED?

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Co-trimoxazole  (sulfamethoxazole and trimethoprim in a fixed ratio 1:5) is available as:

  • Tablets - 80/400 mg (80 mg trimethoprim  with  400 mg sulfamethoxazole)
  • Oral liquid - 40/200 mg/5 mL (40 mg trimethoprim with  200 mg in 5 mL sulfamethoxazole)
  • Injection - 80/400 mg/5 mL (80 mg trimethoprim with 400 mg in 5 mL sulfamethoxazole)

Infection Treatment Dosage:

  • Children six weeks to five months - 20/100 mg (2.5 mL), twice a dy
  • Children six months to five years - 40/200 mg (5 mL), twice a day
  • Children six to twelve years - 80/400 mg (10 mL or one tablet), twice a day
  • Children over twelve years old and adults -160/800 mg (two tablets), twice a day

Co-trimoxazole dosage can be calculated by a child's weight:

  • Children six weeks to twelve years - 0.5 mL/kg oral liquid, twice a day

There is a risk of jaundice in infants under six weeks of age.

USES

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Sulfonamide antibiotics are used in cases where antibiotics are ineffective or contraindicated. Co-trimoxazole is used in the treatment of nocardiosis, a rare bacterial infection of the brain, lungs, or skin, and in those who are immunocompromised.  Co-trimoxazole is also used in the treatment of mild cases of lower urinary tract infections in children.

Co-trimoxazole is used as a second-line antibiotic to treat the following infections:

  • Acute exacerbations of chronic bronchitis
  • Adult pneumonia
  • Childhood otitis media
  • Sinusitis
  • Cellulitis
  • Diabetic foot complications
  • Salmonellosis
  • Acute pyelonephritis

Patients who do not respond well to antibiotics as their first-line treatment should be tested for the presence of MRSA if they have an infected surgical or non-healing wound. Sulfonamide antibiotics can be used as a second-line treatment.

SIDE EFFECTS

Sulfonamide antibiotics have been known to cause sun sensitivity leading to severe sunburn. Patients should avoid prolonged sun exposure and should apply sunscreen.

Although rare, anemia, low platelet count (thrombocytopenia), low white blood cell count (leucopenia) and liver damage can occur. It is important to drink a lot of water to avoid urinary crystals.

CONTRAINDICATIONS

Sulfonamide antibiotics should be avoided in those with severe hepatic damage or prior hypersensitivity reactions. Agranulocytosis, bone marrow depression and severe renal impairment are also contraindications of co-trimoxazole. Exceptions to this would be if the clinical need outweighs the risk with the patient being closely monitored.

Long-term use requires a monthly full blood count, especially in those who are folate-deficient or malnourished.

DRUG INTERACTIONS

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These are some of the known drug interactions. They are more prevalent in elderly patients and those taking other medications:

  • Warfarin
  • Sulfonylureas (gliclazide, glipizide)
  • Methotrexate
  • ACE inhibitors, ARBs, Spironolactone
  • Phenytoin
  • Clozapine

Sulfonamide antibiotics can lead to abnormal bleeding in patients who are taking blood-thinning drugs such as warfarin (Coumadin). Increased cyclosporine metabolic activity in the liver reduces cyclosporine effectiveness and can increase kidney damage. When urine is acidic, sulfonamide antibiotics may cause crystallization in the urine.

Digoxin (Lanoxin) can elevate blood levels and cause serious toxic results. Divalproex, methotrexate (Rheumatrex, Trexall), valproic acid (Depacon, Depakote ER, Depakote, Stavzor, Depakene), trimetrexate, triamterene, or pyrimethamine taken in conjuction with sulfonamide antibiotics can cause folic acid levels to drop resulting in anemia.

The combination of sulfamethoxazole/trimethoprim and angiotensin causes a conversion of enzyme (ACE) inhibitors which increase potassium blood levels.

ADVERSE EFFECTS OF SULFONAMIDE ANTIBIOTICS

Approximately 3% of those who take sulfonamide antibiotics experience adverse effects. Symptoms include:

  • Hyperkalemia
  • Serious skin rashes
  • Diarrhea
  • Lethargy
  • Headache
  • Dizziness
  • Anorexia
  • Vomiting
  • Nausea

At the first sign of a skin rash medication should be stopped before it becomes serious. The following are two examples:

Stevens-Johnson syndrome, symptoms include:

  • Peeling of the skin
  • Aching muscles
  • Blistering
  • Redness
  • Aching joints

Toxic epidermal necrolysis, symptoms include:

  • Loosening
  • Redness
  • Peeling
  • Blistering of the skin
  • Difficulty in swallowing

HYPERSENSITIVITY

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About 0.09% of patients experience a sulfonamide antibiotic reaction. It is more common in those who test positive for AIDS and HIV. Reactions include:

  • Pancytopenia
  • Systemic vasculitis
  • Interstitial nephritis
  • Hepatitis
  • Pneumonitis
  • Multi-organ hypersensitivity syndrome
  • Lupus-like syndrome
  • Serum sickness-like syndrome
  • Toxic epidermal necrolysis
  • Stevens-Johnson syndrome
  • Anaphylaxis

Hypersensitivity usually appears within one to three weeks after beginning treatment and stops one to two weeks after stopping treatment. Hypersensitivity syndrome symptoms include pulmonary infiltrates, rash, fever and hypotension. A hypersensitivity reaction can include a sore throat, difficulty breathing, cough, mucous membrane lesions, painful macro papular rash, or fever.

Anaphylaxis will usually occur with thirty minutes of taking the medication.

PREGNANCY RISKS

Co-trimoxazole is associated with an increase in the risk of methaemoglobinaemia and neonatal hemolysis and should be avoided after thirty-two weeks of gestation. As it is a folate antagonist, women in their first trimester should not take it.

Bilirubin protein displacement can occur in infant's blood when taking sulfonamide antibiotics. This can result in jaundice and kernicterus, a serious infant condition. Sulfonamide antibiotics should not be taken by women who are nursing as it can pass through breast milk causing kernicterus.

CONCLUSION

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Sulfonamide antibiotics are derived from a sulfur chemical and are in a synthetic class of drugs as opposed to antibiotics which are derived from mold and are organic. Some examples of this drug brand include sulfisoxazole (Truxazole, Gantrisin), sulfasalazine (Azulfidine, Sulfazine), and sulfamethoxazole/trimethoprim (Bactrim, Bactrim DS, Co-trimoxazole, Septra, Septra DS, Cotrim, SMZ-TMP, SMZ-TMP DS, Sulfatrim). Some of these medications are only available in generic form.

The side effects include:

  • Lethargy
  • Nausea
  • Headache
  • Anorexia
  • Dizziness
  • Diarrhea
  • Vomiting
  • Serious skin rash

Many practitioners avoid prescribing sulfur medications to patients with a history of a reaction to sulfonamide antibiotics.  Older patients are more likely to have adverse reactions with more serious results. This is due in part to the fact that many of them are taking more than one medication and they may have impaired hepatic or renal function.

This medication is not advised for pregnant women, those who plan on becoming pregnant, or breastfeeding women.

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