Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
BACTRIM DS vs BACTRIM
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
BACTRIM DS is a combination of sulfamethoxazole and trimethoprim. Sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA), while trimethoprim inhibits dihydrofolate reductase, blocking reduction of dihydrofolate to tetrahydrofolate. This sequential blockade of folic acid synthesis leads to bactericidal action.
BACTRIM (sulfamethoxazole/trimethoprim) inhibits bacterial folate synthesis. Sulfamethoxazole, a sulfonamide, inhibits dihydropteroate synthase, blocking PABA incorporation into dihydrofolic acid. Trimethoprim inhibits dihydrofolate reductase, blocking conversion of dihydrofolic acid to tetrahydrofolic acid. Sequential blockade leads to bactericidal effect.
FDA-approved: Urinary tract infections, acute otitis media, acute exacerbations of chronic bronchitis, traveler's diarrhea, shigellosis, Pneumocystis jirovecii pneumonia (PCP), toxoplasmosis,Off-label: Methicillin-resistant Staphylococcus aureus (MRSA) infections, Stenotrophomonas maltophilia infections, nocardiosis, Wegener's granulomatosis (as second-line therapy), inflammatory bowel disease
Urinary tract infections,Acute otitis media,Acute exacerbations of chronic bronchitis,Traveler's diarrhea,Shigellosis,Pneumocystis jirovecii pneumonia (treatment and prophylaxis),Toxoplasmosis (prophylaxis in immunocompromised),Nocardia infections,Methicillin-resistant Staphylococcus aureus (MRSA) infections (off-label)
One double-strength tablet (trimethoprim 160 mg-sulfamethoxazole 800 mg) orally every 12 hours.
1 DS tablet (160 mg TMP/800 mg SMX) orally every 12 hours for 10-14 days.
Sulfamethoxazole: 8-10 hours; Trimethoprim: 8-12 hours; prolonged in renal impairment (creatinine clearance <30 m L/min: up to 24-48 hours).
Sulfamethoxazole: 9-12 hours (prolonged in renal impairment); Trimethoprim: 8-10 hours (prolonged in renal impairment).
Sulfamethoxazole is metabolized primarily by N-acetylation and glucuronidation; trimethoprim is metabolized by O-demethylation and N-oxidation. Both are eliminated renally via glomerular filtration and tubular secretion.
Sulfamethoxazole is metabolized primarily via N-acetylation in the liver (N-acetyltransferase-2, NAT2). Trimethoprim is metabolized via O-demethylation and alpha-hydroxylation by cytochrome P450 (CYP) enzymes, mainly CYP3A4, with minor contribution from CYP1A2 and CYP2C9.
Renal: 50-70% as sulfamethoxazole (unchanged and acetylated metabolite), 40-60% as trimethoprim (unchanged); biliary: <10% for both; fecal: <4%.
Renal: sulfamethoxazole 20-30% unchanged, trimethoprim 40-70% unchanged; biliary/fecal: minimal (<10%) for both components.
Sulfamethoxazole: 68% bound (albumin); Trimethoprim: 44% bound (albumin, alpha-1-acid glycoprotein).
Sulfamethoxazole: 70% bound to albumin; Trimethoprim: 30-40% bound to albumin.
Sulfamethoxazole: 0.21 L/kg; Trimethoprim: 1.3-1.8 L/kg (wide distribution, higher in tissues than plasma).
Sulfamethoxazole: 0.21 L/kg; Trimethoprim: 1.8 L/kg (high tissue penetration including lung, kidney, and CSF).
Oral: >90% for both components; IV: 100%.
Oral: 100% for both components (well absorbed).
Cr Cl >30 m L/min: No adjustment; Cr Cl 15-30 m L/min: 50% of usual dose every 12 hours; Cr Cl <15 m L/min: Not recommended.
Cr Cl >30 m L/min: No adjustment. Cr Cl 15-30 m L/min: 50% of standard dose. Cr Cl <15 m L/min: Contraindicated.
Child-Pugh Class A: No adjustment; Child-Pugh Class B: Use with caution, no specific dose recommendation; Child-Pugh Class C: Contraindicated.
Child-Pugh Class A: No adjustment. Child-Pugh Class B: Use with caution, monitor for toxicity; consider dose reduction. Child-Pugh Class C: Avoid use.
Based on trimethoprim component: 8 mg/kg/day of trimethoprim divided every 12 hours. For severe infections, up to 20 mg/kg/day of trimethoprim divided every 6 hours.
8 mg/kg/day TMP / 40 mg/kg/day SMX in two divided doses every 12 hours (max 320 mg TMP/1600 mg SMX per day). For PCP treatment: 15-20 mg/kg/day TMP / 75-100 mg/kg/day SMX in 3-4 divided doses.
Monitor renal function; adjust dose based on Cr Cl. Increased risk of hyperkalemia and folate deficiency; consider folate supplementation.
Initiate at lower doses; monitor renal function closely; contraindicated if Cr Cl <15 m L/min; adjust based on Cr Cl (see renal adjustment).
BACTRIM DS carries a black box warning for severe hypersensitivity reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and fulminant hepatic necrosis. Also warns about fatal reactions such as agranulocytosis, aplastic anemia, and other blood dyscrasias. Additionally, use in pregnancy at term may cause kernicterus in the newborn.
BACTRIM may cause life-threatening severe adverse reactions including: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Discontinue at first sign of skin rash or any sign of adverse reaction. Hypersensitivity reactions can occur even with re-challenge of the same or other sulfonamides.
Hypersensitivity reactions: risk of SJS/TEN, especially in patients with HIV, folate deficiency, or genetic susceptibility (e.g., HLA-B*1502, HLA-A*3101). Discontinue at first sign of rash.,Hematologic toxicity: monitor CBCs; caution in patients with folate deficiency, renal impairment, or prolonged therapy.,Hepatic toxicity: can cause cholestatic jaundice, hepatic necrosis; avoid in hepatic impairment.,Renal toxicity: maintain adequate hydration to prevent crystalluria; adjust dose in renal impairment.,Hyperkalemia: risk with high-dose trimethoprim; monitor potassium, especially in patients with renal dysfunction or on potassium-sparing diuretics.,Hypoglycemia: risk in patients with renal impairment or malnutrition; caution with sulfonylureas.,Photosensitivity: avoid excessive sun exposure.,Pregnancy: avoid at term due to risk of kernicterus; use only if benefit outweighs risk.,Lactation: caution due to potential for kernicterus in infants with G6PD deficiency.
Fatal hypersensitivity reactions including SJS/TEN,Hepatotoxicity and hepatic failure,Blood dyscrasias (leukopenia, thrombocytopenia, agranulocytosis),Clostridioides difficile-associated diarrhea,Renal impairment: risk of crystalluria; maintain adequate fluid intake,Hyperkalemia in patients with renal disease or on potassium-sparing drugs,Megaloblastic anemia in folate-deficient patients,Elderly patients at increased risk of severe adverse reactions,Pregnancy: avoid near term due to risk of kernicterus (sulfonamide displaces bilirubin),Lactation: caution; sulfonamides excreted in breast milk,Photosensitivity
Hypersensitivity to sulfamethoxazole, trimethoprim, or any component.,History of drug-induced immune thrombocytopenia with sulfonamides or trimethoprim.,Severe hepatic disease (e.g., acute hepatitis, cirrhosis with jaundice).,Severe renal impairment (Cr Cl <15 m L/min) unless dialysis is available.,Megaloblastic anemia due to folate deficiency.,Pregnancy at term and nursing mothers (due to risk of kernicterus).,Concurrent use with dofetilide (increased risk of arrhythmias).,Infants <2 months of age (sulfonamides can cause kernicterus).
Hypersensitivity to sulfonamides, trimethoprim, or any component,History of drug-induced immune thrombocytopenia with sulfonamides or trimethoprim,Megaloblastic anemia due to folate deficiency,Severe hepatic or renal impairment (Cr Cl <15 m L/min),Pregnancy at term and during breastfeeding,Infants less than 2 months of age,Combination with dofetilide (increased risk of torsades de pointes)
Avoid high-potassium foods (e.g., bananas, oranges, potatoes) as trimethoprim can increase serum potassium. Avoid alcohol, which may cause disulfiram-like reaction (flushing, nausea, tachycardia). No significant food-drug interactions beyond potassium and alcohol.
Avoid high-potassium foods (bananas, oranges, potatoes) if hyperkalemia is a concern. No specific food interactions; however, maintain adequate fluid intake to prevent crystalluria.
First trimester: Folate antagonist; associated with neural tube defects, cardiovascular malformations, and cleft palate. Second trimester: Growth restriction, preterm birth. Third trimester: Kernicterus risk due to bilirubin displacement from albumin. Avoid during entire pregnancy.
Pregnancy Category D. First trimester: Folate antagonist; associated with neural tube defects, cardiovascular malformations, and cleft palate. Second and third trimesters: Risk of kernicterus in neonates due to displacement of bilirubin from albumin; may cause hemolytic anemia in G6PD-deficient fetuses. Avoid use, especially near term.
Breastfeeding safety: Both trimethoprim and sulfamethoxazole are excreted into breast milk; M/P ratio for trimethoprim ~1.25, sulfamethoxazole ~0.15. Caution in infants under 2 months or with G6PD deficiency; theoretical risk of kernicterus.
Both trimethoprim and sulfamethoxazole are excreted into breast milk. M/P ratio not well defined. Potential for kernicterus in jaundiced or G6PD-deficient infants; may interfere with folate metabolism. Caution advised; consider alternative therapy.
No standard dose adjustment recommended; avoid use if possible. If necessary, ensure adequate folic acid intake; may need to increase dose due to increased clearance in pregnancy, but specific data lacking.
Trimethoprim-sulfamethoxazole dose generally unchanged but avoid in first trimester and near term. If unavoidable, consider increased folate supplementation. No specific pharmacokinetic-driven dose adjustment established; monitor clinical response and adjust based on renal function.
Bactrim DS (sulfamethoxazole/trimethoprim) is contraindicated in G6PD deficiency due to risk of hemolytic anemia. Monitor for hyperkalemia, especially in elderly or those with renal impairment. Caution with warfarin (potentiates anticoagulation). Avoid in pregnancy (teratogenic) and lactation. Use with caution in folate deficiency; supplement folate if needed.
Bactrim is contraindicated in G6PD deficiency due to risk of hemolytic anemia. Monitor renal function and potassium levels, especially in elderly patients, as sulfamethoxazole can cause hyperkalemia. Use with caution in patients with folic acid deficiency or megaloblastic anemia. Avoid in pregnancy at term and in lactating women due to risk of kernicterus. For PCP treatment, high doses may require leucovorin rescue to prevent bone marrow suppression.
Take with a full glass of water and stay well-hydrated to prevent crystalluria.,Avoid prolonged sun exposure; use sunscreen as this drug may cause photosensitivity.,Complete the full course even if you feel better to prevent antibiotic resistance.,Report any skin rash, sore throat, fever, or unusual bleeding immediately.,Do not take if you are pregnant, planning to become pregnant, or breastfeeding.,Inform your doctor if you have kidney disease, G6PD deficiency, or are on blood thinners.
Take with a full glass of water and stay well-hydrated to prevent crystalluria.,Complete the full course even if symptoms improve.,Report any signs of allergic reaction (rash, fever, sore throat) or severe skin reactions (blistering, peeling).,Avoid prolonged sun exposure; use sunscreen as photosensitivity may occur.,Do not take if you have a history of sulfa allergy or are pregnant/nursing without consulting doctor.
No interactions on record
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about BACTRIM DS vs BACTRIM, answered by our medical review team.
BACTRIM DS is a Sulfonamide Antibiotic Combination that works by BACTRIM DS is a combination of sulfamethoxazole and trimethoprim. Sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA), while trimethoprim inhibits dihydrofolate reductase, blocking reduction of dihydrofolate to tetrahydrofolate. This sequential blockade of folic acid synthesis leads to bactericidal action.. BACTRIM is a Sulfonamide Antibiotic Combination that works by BACTRIM (sulfamethoxazole/trimethoprim) inhibits bacterial folate synthesis. Sulfamethoxazole, a sulfonamide, inhibits dihydropteroate synthase, blocking PABA incorporation into dihydrofolic acid. Trimethoprim inhibits dihydrofolate reductase, blocking conversion of dihydrofolic acid to tetrahydrofolic acid. Sequential blockade leads to bactericidal effect.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between BACTRIM DS and BACTRIM depend on the specific clinical indication. These are both Sulfonamide Antibiotic Combination agents and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of BACTRIM DS is: One double-strength tablet (trimethoprim 160 mg-sulfamethoxazole 800 mg) orally every 12 hours.. The standard adult dose of BACTRIM is: 1 DS tablet (160 mg TMP/800 mg SMX) orally every 12 hours for 10-14 days.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between BACTRIM DS and BACTRIM in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. BACTRIM DS is classified as Category C. First trimester: Folate antagonist; associated with neural tube defects, cardiovascular malformations, and cleft palate. Second trimester: Growth restriction, preterm birth. Third . BACTRIM is classified as Category C. Pregnancy Category D. First trimester: Folate antagonist; associated with neural tube defects, cardiovascular malformations, and cleft palate. Second and third trimesters: Risk of . Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.