NSTK · 01.2026Independent supplement reference
NutriStack
Edition 1.0Updated July 13, 2026

Trimethoprim-Sulfamethoxazole

Prescription ·Exploratory record · not publication-reviewed ·Updated July 13, 2026

A synergistic combination antibiotic containing trimethoprim and sulfamethoxazole in a 1:5 ratio. Effective against many gram-positive and gram-negative organisms. A first-line agent for uncomplicated urinary tract infections, the drug of choice for Pneumocystis jirovecii pneumonia (PCP) treatment and prophylaxis, and used for MRSA skin infections, Stenotrophomonas, nocardiosis, and toxoplasmosis.

Evidence tier
Strong
Indexed sources
10 2014–2024
Interactions
0
Depletes
1 nutrient
Read the sources → Compare profiles
Publication status

Exploratory record, not a reviewed medical publication.

See the editorial and medical-review policies for the publication gate.

This generated database record has not completed a claim-level review by a qualified human medical reviewer. Bibliography links and evidence labels are not approval. The page remains available for reference and is excluded from search indexing.

In short

What the research says.

A quick, data-only summary. The full evidence, dosing, and sources are below.

A synergistic combination antibiotic containing trimethoprim and sulfamethoxazole in a 1:5 ratio. NutriStack rates the supporting evidence as strong. Common adult dosing is 1 DS tablet (160/800 mg) every 12 hours; PCP prophylaxis: 1 DS tablet daily or 1 SS tablet daily; PCP treatment: 15-20 mg TMP/kg/day IV divided every 6-8 hours (as prescribed by your physician), though a prescriber sets the actual dose. With long-term use it can deplete folate. This profile indexes 10 sources.

What it's good for
  • First-line for uncomplicated urinary tract infections7
  • Treatment and prophylaxis of PCP (Pneumocystis jirovecii)10,3
  • Treats community-acquired MRSA skin and soft tissue infections6,9
  • Treats Stenotrophomonas maltophilia infections8,9
  • Treats toxoplasmosis
What to watch for
  • Nausea and vomiting
  • Skin rash (including Stevens-Johnson syndrome, rare)
  • Hyperkalemia (trimethoprim blocks ENaC in collecting duct)
  • Known sulfonamide allergy
  • Megaloblastic anemia due to folate deficiency6

The bottom line

Evidence rating strong. Most-documented uses: first-line for uncomplicated urinary tract infections, treatment and prophylaxis of pcp (pneumocystis jirovecii), treats community-acquired mrsa skin and soft tissue infections. 10 sources indexed (2014–2024), with 0 interaction records on file.

The science

How it works, mechanistically.

Core mechanism

Sequentially inhibits two enzymes in the bacterial folate synthesis pathway. Sulfamethoxazole is a structural analog of para-aminobenzoic acid (PABA) that competitively inhibits dihydropteroate synthase, blocking the incorporation of PABA into dihydrofolic acid. Trimethoprim then inhibits dihydrofolate reductase (DHFR), preventing the reduction of dihydrofolic acid to tetrahydrofolic acid. The sequential blockade at two steps produces synergistic bactericidal activity.

Class
Sulfonamide/Diaminopyrimidine Combination
Dosing

Dosing & protocol.

Common range
1 DS tablet (160/800 mg) every 12 hours; PCP prophylaxis: 1 DS tablet daily or 1 SS tablet daily; PCP treatment: 15-20 mg TMP/kg/day IV divided every 6-8 hours (as prescribed by your physician)
Recommended form
Oral tablets (single-strength, double-strength) or suspension; IV for severe infections

Well absorbed orally (85-100% bioavailability for both components). Can be taken with or without food. Ensure adequate hydration to prevent crystalluria (especially in high-dose therapy).10

Depletions

What it depletes.

Nutrients this medication can lower over time, and what to replace.

Folate

Moderate

Trimethoprim inhibits dihydrofolate reductase and sulfamethoxazole adds antifolate pressure, which can lower functional folate status in susceptible patients.

Replace Folic AcidMonitor CBC + serum folate or RBC folateOnset Usually after prolonged or high-dose therapy, especially with low folate stores

Full Trimethoprim-Sulfamethoxazole depletion and interaction guide →

Safety

Full safety detail.

Side effects

  • Nausea and vomiting
  • Skin rash (including Stevens-Johnson syndrome, rare)
  • Hyperkalemia (trimethoprim blocks ENaC in collecting duct)
  • Bone marrow suppression (especially in folate-deficient patients)
  • Photosensitivity
  • Crystalluria (with inadequate hydration)
  • Elevated creatinine (trimethoprim competitively inhibits creatinine secretion without affecting GFR)
  • Hepatotoxicity (rare)

Contraindications

  • Known sulfonamide allergy
  • Megaloblastic anemia due to folate deficiency6
  • Severe hepatic impairment1
  • Severe renal impairment (CrCl <15 mL/min)1
  • Pregnancy at term (risk of neonatal kernicterus)6
  • Infants under 2 months (except for congenital toxoplasmosis)
Sources

Sources, by evidence tier.

Numbered references. Citations throughout the page link here.

Meta-analyses & systematic reviews

6

Reference material

4
FAQ

Common questions.

Quick answers about Trimethoprim-Sulfamethoxazole, drawn from the data on this page.

What is Trimethoprim-Sulfamethoxazole?

A synergistic combination antibiotic containing trimethoprim and sulfamethoxazole in a 1:5 ratio. Effective against many gram-positive and gram-negative organisms. A first-line agent for uncomplicated urinary tract infections, the drug of choice for Pneumocystis jirovecii pneumonia (PCP) treatment and prophylaxis, and used for MRSA skin infections, Stenotrophomonas, nocardiosis, and toxoplasmosis.

What is Trimethoprim-Sulfamethoxazole used for?

Commonly cited benefits of Trimethoprim-Sulfamethoxazole include: First-line for uncomplicated urinary tract infections; Treatment and prophylaxis of PCP (Pneumocystis jirovecii); Treats community-acquired MRSA skin and soft tissue infections; Treats Stenotrophomonas maltophilia infections; Treats toxoplasmosis. NutriStack rates the overall evidence as strong.

What is a typical dose of Trimethoprim-Sulfamethoxazole?

A typical adult dose of Trimethoprim-Sulfamethoxazole is 1 DS tablet (160/800 mg) every 12 hours; PCP prophylaxis: 1 DS tablet daily or 1 SS tablet daily; PCP treatment: 15-20 mg TMP/kg/day IV divided every 6-8 hours (as prescribed by your physician). The commonly recommended form is Oral tablets (single-strength, double-strength) or suspension; IV for severe infections. These are general ranges, not personalized advice; confirm the right dose with a clinician.

What are the side effects of Trimethoprim-Sulfamethoxazole?

Reported side effects include nausea and vomiting, skin rash (including stevens-johnson syndrome, rare), hyperkalemia (trimethoprim blocks enac in collecting duct), bone marrow suppression (especially in folate-deficient patients), photosensitivity, crystalluria (with inadequate hydration). This is educational information; check with a healthcare professional before use.

How strong is the evidence for Trimethoprim-Sulfamethoxazole?

NutriStack rates this as Strong, meaning multiple high-quality meta-analyses or systematic reviews converge on the same finding. Full tier criteria are at https://nutristackapp.com/methodology/evidence-tiers.

Use this with your stack

Trimethoprim-Sulfamethoxazole in NutriStack.

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