Trimethoprim/sulfamethoxazole

Trimethoprim/sulfamethoxazole
INN
Drug class
Routes of administration	Oral, Intravenous infusion
Pregnancy category	AU: C, US: C
Bioavailability
Metabolism
Elimination half-life
Excretion
Legal status	AU: S4 (Prescription only), US: ℞-only, CA: ℞-only, UK: POM
CAS Number	8064-90-2
PubChem	358641
DrugBank
ChemSpider
KEGG	D00285

Trimethoprim and sulfamethoxazole

THF synthesis pathway

Trimethoprim/sulfamethoxazole (brand names: Bactrim, Cotrim, Septra) is a fixed-dose combination antibiotic that combines two active ingredients, trimethoprim and sulfamethoxazole. It is used to treat a variety of bacterial infections, including urinary tract infections (UTIs), methicillin-resistant Staphylococcus aureus (MRSA) skin infections, traveler's diarrhea, respiratory tract infections, and cholera. This medication is also utilized for the treatment and prevention of Pneumocystis jirovecii pneumonia (PCP) and toxoplasmosis in individuals with HIV/AIDS and other forms of immunosuppression.

Pharmacology

Trimethoprim and sulfamethoxazole work synergistically to inhibit the microbial synthesis of folate, a vital nutrient for bacterial DNA synthesis and replication. Trimethoprim is a dihydrofolate reductase inhibitor, which inhibits the conversion of dihydrofolic acid to tetrahydrofolic acid. Sulfamethoxazole is a sulfonamide antibiotic, which prevents the conversion of para-aminobenzoic acid (PABA) to dihydrofolic acid. Together, these actions disrupt the bacterial folate pathway, ultimately leading to bacterial death.

Medical Uses

Trimethoprim/sulfamethoxazole is a versatile antibiotic that is used to treat a broad range of bacterial infections.

Urinary Tract Infections (UTIs)

Trimethoprim/sulfamethoxazole is commonly prescribed to treat UTIs caused by susceptible bacteria. It is effective against many common pathogens, including Escherichia coli, the most frequent cause of UTIs. It works by inhibiting bacterial folate synthesis, preventing the bacteria from growing and reproducing.

Respiratory Tract Infections

This combination is used to treat respiratory tract infections such as acute bronchitis, pneumonia, and sinusitis. The drug is particularly useful against certain bacterial pathogens like Haemophilus influenzae and Moraxella catarrhalis, both of which are common causes of respiratory infections.

Methicillin-Resistant Staphylococcus aureus (MRSA)

Trimethoprim/sulfamethoxazole is effective against MRSA skin infections. It is often prescribed when other antibiotics, such as methicillin or oxacillin, fail due to bacterial resistance.

Traveler’s Diarrhea

The drug can be used to treat traveler's diarrhea caused by bacterial infections, especially those caused by Enterotoxigenic Escherichia coli (ETEC) and other enteric pathogens.

Cholera

Trimethoprim/sulfamethoxazole is used as part of the treatment regimen for cholera, an acute diarrheal infection caused by the bacterium Vibrio cholerae. It helps reduce the severity and duration of the disease.

Pneumocystis jirovecii Pneumonia (PCP)

Pneumocystis jirovecii pneumonia (PCP) is a significant concern for individuals with weakened immune systems, such as those with HIV/AIDS. Trimethoprim/sulfamethoxazole is the first-line treatment for both the prevention and treatment of PCP in these populations. In individuals with HIV/AIDS, the risk of PCP is elevated, especially in those who have a CD4+ T cell count below 200 cells/μL.

Toxoplasmosis

The drug is also used in the treatment and prevention of toxoplasmosis, a parasitic infection caused by Toxoplasma gondii, in immunocompromised individuals, particularly those with HIV/AIDS.

Dosage and Administration

Trimethoprim/sulfamethoxazole is available in oral tablet, suspension, and intravenous formulations. The oral tablets typically come in strengths of 80 mg of trimethoprim and 400 mg of sulfamethoxazole (commonly prescribed as one tablet twice daily for adults, depending on the severity of the infection). For intravenous administration, the dosage is adjusted based on the patient's weight and the severity of the infection.

The typical dosage regimens for common infections are as follows:

• For uncomplicated UTIs: 160 mg trimethoprim/800 mg sulfamethoxazole every 12 hours.
• For PCP treatment: 15 mg/kg/day of trimethoprim and 75 mg/kg/day of sulfamethoxazole in divided doses.

Side Effects

Common side effects of trimethoprim/sulfamethoxazole include:

• Rash
• Nausea and vomiting
• Anorexia
• Headache
• Photosensitivity

Serious side effects may include:

• Hepatotoxicity (liver toxicity)
• Renal impairment
• Blood dyscrasias (e.g., leukopenia, thrombocytopenia)
• Severe allergic reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis)

Contraindications

Trimethoprim/sulfamethoxazole is contraindicated in individuals with a history of severe allergic reactions to sulfonamides or trimethoprim. It should be used with caution in individuals with renal insufficiency or liver disease.

Pregnancy and Lactation

Trimethoprim/sulfamethoxazole falls under pregnancy category C in both the United States and Australia, indicating that its safety during pregnancy has not been well established. It is typically recommended only when the benefits outweigh the risks. The drug is excreted into breast milk, so caution is advised when administered to breastfeeding mothers.

Resistance

Resistance to trimethoprim/sulfamethoxazole has been reported in certain bacterial species, such as Escherichia coli, Streptococcus pneumoniae, and Staphylococcus aureus. Mechanisms of resistance include mutations in the target enzymes (dihydrofolate reductase and dihydropteroate synthase) and the increased expression of efflux pumps.

History

Trimethoprim/sulfamethoxazole was first introduced in the 1960s. It was marketed under various trade names, including Bactrim and Septra. It has since become a widely used antibiotic, particularly in the treatment of infections in immunocompromised individuals.

Society and Culture

Legal Status

Trimethoprim/sulfamethoxazole is classified as a prescription-only medication in most countries, including the United States, the United Kingdom, Australia, and Canada. It is available both as a generic medication and under brand names such as Bactrim and Septra.

Market Trends

In 2022, trimethoprim/sulfamethoxazole was the 143rd most commonly prescribed medication in the United States, with over 3 million prescriptions.

See Also

• Sulfonamide antibiotics
• Trimethoprim
• Pneumocystis jirovecii pneumonia
• HIV/AIDS
• Traveler's diarrhea
• Methicillin-resistant Staphylococcus aureus (MRSA)
• Cholera

External Links

• Trimethoprim/Sulfamethoxazole: Pharmacology and Clinical Applications - NCBI
• WHO's Essential Medicines List

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