Bactrim®

Trimethoprim / Sulfamethoxazole · oral tablet

Antibiotic

Approved uses

Urinary tract infection, acute otitis media, acute exacerbation of chronic bronchitis, shigellosis, Pneumocystis pneumonia, travelers' diarrhea

Adults: 1 DS tablet (800 mg/160 mg) PO q12h. Children 2 months and older: 40 mg/kg/day sulfamethoxazole with 8 mg/kg/day trimethoprim divided q12h. Pneumocystis treatment: 75 to 100 mg/kg/day sulfamethoxazole with 15 to 20 mg/kg/day trimethoprim divided q6h for 14 to 21 days.

OFF-LABELNot in the FDA label for this product

Preseptal cellulitis or eyelid abscess, MRSA suspected or culture-proven

1600 mg/320 mg (2 DS tablets) PO BID x 7 days, the regimen used in the drained-abscess trial

RCT · n=1247 · indirect

No trial has studied preseptal cellulitis specifically. In 1247 patients with a drained uncomplicated skin abscess (45.3% MRSA-positive), clinical cure was 80.5% versus 73.6% with placebo (difference 6.9 percentage points, 95% CI 2.1 to 11.7); ocular and periocular MRSA isolates remain largely susceptible, with 8.7% resistance among 399 culture-positive ocular and periocular MRSA cases in a northern California pediatric series.

Talan DA, Mower WR, Krishnadasan A, et al. Trimethoprim-Sulfamethoxazole versus Placebo for Uncomplicated Skin Abscess. N Engl J Med. 2016;374(9):823-32 (randomized controlled trial). Amato M, Pershing S, Walvick M, Tanaka S. Trends in ophthalmic manifestations of methicillin-resistant Staphylococcus aureus (MRSA) in a northern California pediatric population. J AAPOS. 2013;17(3):243-7 (retrospective cross-sectional review).

Nonpurulent cellulitis, MRSA coverage added to a cephalosporin

320 mg/1600 mg PO BID x 7 days added to cephalexin 500 mg PO QID x 7 days

RCT · no added benefit

Adding it to cephalexin for uncomplicated nonpurulent cellulitis did not raise cure rates: 83.5% versus 85.5% per protocol (difference -2.0 percentage points, 95% CI -9.7 to 5.7, P = .50). Enrollment excluded abscess, wound, and purulent drainage, and the authors noted the modified intention-to-treat estimate was imprecise and did not exclude a clinically important benefit.

Moran GJ, Krishnadasan A, Mower WR, et al. Effect of Cephalexin Plus Trimethoprim-Sulfamethoxazole vs Cephalexin Alone on Clinical Cure of Uncomplicated Cellulitis: A Randomized Clinical Trial. JAMA. 2017;317(20):2088-2096.

Prophylaxis of recurrent toxoplasmic retinochoroiditis

One tablet, trimethoprim 160 mg with sulfamethoxazole 800 mg, PO every 3 days for up to 20 months

RCT · n=124 · open-label

In 124 patients with a history of recurrent toxoplasmic retinochoroiditis randomized to this regimen or to observation, recurrence occurred in 4 of 61 treated (6.6%) versus 15 of 63 untreated (23.8%), P = .01, over up to 20 months. The trial was open-label with no placebo arm, and a Cochrane review graded the recurrence reduction as moderate-quality evidence but found no good evidence of a visual acuity benefit (low-quality, 93 participants, mean difference -1.00 letters, 95% CI -7.93 to 5.93), noting that absence of evidence of effect is not the same as evidence of no effect.

Silveira C, Belfort R, Muccioli C, et al. The effect of long-term intermittent trimethoprim/sulfamethoxazole treatment on recurrences of toxoplasmic retinochoroiditis. Am J Ophthalmol. 2002;134(1):41-6 (randomized controlled trial). Pradhan E, Bhandari S, Gilbert RE, Stanford M. Antibiotics versus no treatment for toxoplasma retinochoroiditis. Cochrane Database Syst Rev. 2016;2016(5):CD002218.

Contraindications

Known hypersensitivity to trimethoprim or sulfonamides.
Documented megaloblastic anemia due to folate deficiency.
Pregnancy and nursing; sulfonamides cross the placenta and enter milk, with kernicterus risk.
Infants under 2 months of age.
Marked hepatic damage, or severe renal insufficiency when renal function cannot be monitored.

Available Forms

800 mg/160 mg double-strength tablets

Mechanism of Action

Sulfamethoxazole blocks bacterial dihydrofolic acid synthesis by competing with para-aminobenzoic acid, and trimethoprim reversibly inhibits dihydrofolate reductase, the next enzyme in the pathway. Blocking two consecutive folate steps shuts down nucleic acid and protein synthesis in many bacteria, and in vitro resistance develops more slowly than with either component alone.

Warnings & Precautions

Fatal sulfonamide reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, and aplastic anemia are rare but have been fatal; rash, sore throat, fever, arthralgia, pallor, purpura or jaundice may be early indications, and the drug should be stopped at the first skin rash or any sign of adverse reaction.
Respiratory hypersensitivity: Cough, shortness of breath, and pulmonary infiltrates have been reported as hypersensitivity reactions of the respiratory tract in association with sulfonamide treatment.
Sulfonamide cross-sensitivity: Chemical similarity to acetazolamide, thiazides, oral hypoglycemics, and goitrogens means cross-sensitivity may exist with those agents.
G6PD deficiency: Hemolysis may occur and is frequently dose-related.
Blood dyscrasias: Complete blood counts are warranted frequently during therapy, with discontinuation for any significant fall in a formed blood element.
Hyperkalemia: Trimethoprim raises serum potassium in renal insufficiency, disordered potassium metabolism, or concurrent ACE inhibitor use; high-dose therapy causes a progressive, reversible rise.
Group A streptococcal infection: Sulfonamides will not eradicate the organism in established infection and will not prevent sequelae such as rheumatic fever.
Clostridioides difficile diarrhea: Ranges from mild diarrhea to fatal colitis and has been reported over two months after the last antibacterial dose.
Crystalluria: Adequate fluid intake and urine output are needed throughout therapy.
Higher-risk patients: Impaired renal or hepatic function, possible folate deficiency (elderly, chronic alcoholism, anticonvulsant therapy, malabsorption, malnutrition), severe allergies, bronchial asthma, porphyria, and thyroid dysfunction.

Common Side Effects

Ocular: Conjunctival and scleral injection, listed among allergic reactions.
Systemic: Nausea, vomiting, anorexia, rash, and urticaria are the most common.
Severe cutaneous: Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, erythema multiforme, angioedema, photosensitivity; rare, occasionally fatal.
Hematologic: Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, neutropenia, hemolytic and megaloblastic anemia, methemoglobinemia, eosinophilia.
Renal: Renal failure, interstitial nephritis, crystalluria, rising BUN and creatinine.
Metabolic: Hyperkalemia; hypoglycemia in non-diabetics is rare and usually appears after a few days of therapy.
Neurologic: Aseptic meningitis, convulsions, peripheral neuritis, ataxia, vertigo, tinnitus, headache.

Pregnancy & Lactation

Pregnancy: Contraindicated; sulfonamides cross the placenta and may cause kernicterus. Category C, with cleft palate in rats at high doses and increased fetal loss in rabbits at 6 times the human trimethoprim dose.

Lactation: Contraindicated; excreted in human milk, with the same kernicterus risk.

Pediatric Use

Interactions: Prothrombin time may be prolonged with warfarin; phenytoin half-life rose 39% and digoxin levels rise, especially in the elderly; free methotrexate increases.

Contraindicated in infants under 2 months of age.