TMP-SMZ (Trimethoprim/Sulfamethoxazole)
Trimethoprim and sulfamethoxazole
Brand names:Bactrim, Bactrim DS, Septra, Septra DS, Sulfatrim
A fixed-combination antibiotic of trimethoprim and sulfamethoxazole with broad activity against many gram-positive and gram-negative organisms, including community-acquired MRSA. In tactical and deployment medicine, TMP-SMZ is used for skin and soft tissue infections (particularly suspected MRSA), urinary tract infections, and prophylaxis against certain opportunistic infections.
Pharmacology and Actions
TMP-SMZ inhibits sequential steps in bacterial folate synthesis. Sulfamethoxazole blocks para-aminobenzoic acid (PABA) incorporation into dihydrofolic acid; trimethoprim inhibits dihydrofolate reductase, blocking conversion to tetrahydrofolic acid. The two-drug combination produces synergistic bactericidal activity. Spectrum includes Staphylococcus aureus (most community-acquired MRSA), Streptococcus species (variable), most Enterobacteriaceae, Pneumocystis jirovecii, and some Stenotrophomonas. Lacks reliable activity against Pseudomonas, enterococci, and most anaerobes.
Indications
- Skin and soft tissue infections with suspected community-acquired MRSA
- Uncomplicated urinary tract infections
- Pneumocystis jirovecii pneumonia (PJP) treatment and prophylaxis
- Traveler's diarrhea in regions with susceptible pathogens
- Alternative oral antibiotic in penicillin-allergic casualties for select indications
- Acute otitis media when first-line agents are contraindicated
Absolute Contraindications
- Known sulfonamide allergy
- History of TMP-SMZ-induced Stevens-Johnson syndrome or toxic epidermal necrolysis
- Megaloblastic anemia due to folate deficiency
- Severe hepatic impairment
- Severe renal impairment (creatinine clearance below 15 mL/min)
- Pregnancy at term and breastfeeding neonates under 2 months
- Concurrent methotrexate use
Precautions and Side Effects
Rash is common and ranges from benign maculopapular eruption to life-threatening Stevens-Johnson syndrome or toxic epidermal necrolysis. Hyperkalemia, hyponatremia, and renal dysfunction can occur, particularly in elderly patients or with concurrent ACE inhibitors, ARBs, or potassium-sparing diuretics. Hematologic effects include leukopenia, thrombocytopenia, and megaloblastic anemia from folate antagonism. Photosensitivity is common. Hypoglycemia has been reported. Crystalluria can occur with inadequate hydration.
Adult Dosing
Pediatric Dosing
Pediatric dosing: 8 to 12 mg/kg/day (trimethoprim component) PO divided every 12 hours for most indications. For PJP treatment: 15 to 20 mg/kg/day trimethoprim component divided every 6 to 8 hours. Avoid in neonates under 2 months due to kernicterus risk.
Pharmacokinetics
Peak Effect: PO: 1 to 4 hours after dose
Duration: 12 hours (supports BID dosing)
Storage and Handling
Store tablets at controlled room temperature (15 to 30 degrees Celsius). Protect from moisture and light. IV preparation has specific storage requirements per manufacturer; do not refrigerate the IV solution (precipitation can occur).
Reconstitution:
Tablets require no reconstitution. IV preparation must be diluted (typically 5 mL TMP-SMZ in 75 to 125 mL D5W) before infusion over 60 to 90 minutes. Do not mix with other medications in the same IV line.
TCCC and TECC Role
TMP-SMZ is not a primary TCCC wound prophylaxis agent (the cephalosporins fill that role) but is positioned for MRSA-suspected skin and soft tissue infections, deployment-related infections where MRSA carriage is common, and as an alternative oral antibiotic for select infections in penicillin/cephalosporin-allergic casualties. The drug is also used in deployment medicine for traveler's diarrhea prophylaxis and treatment in regions with susceptible pathogens, though resistance has reduced its reliability for this indication.
TMP-SMZ is the drug carried for community-acquired MRSA suspicion in tactical and deployment settings. The double-strength tablet (DS, 160/800 mg) is the standard formulation for skin and soft tissue infection. Watch for rash development; the sulfonamide hypersensitivity reactions can be severe and require immediate discontinuation. Hyperkalemia is an underappreciated risk in casualties on ACE inhibitors or ARBs. The dosing is operationally convenient (every 12 hours), but the contraindication list is long and worth reviewing before administration.
Continuing TMP-SMZ after a rash develops, on the assumption it is a minor reaction. Sulfonamide hypersensitivity can progress rapidly from benign-appearing rash to Stevens-Johnson syndrome or TEN. Any rash during TMP-SMZ therapy warrants immediate discontinuation. The other common error is using TMP-SMZ as a default wound antibiotic in casualties without MRSA risk factors, where cefadroxil or cephalexin are the indicated agents.
This drug profile is provided as educational reference material for trained medical providers. It is not medical advice, not a substitute for formal training, and not a substitute for current published guidelines or medical direction.
Drug administration is governed by your scope of practice, agency standing orders, medical director protocols, and applicable state and federal regulations. Controlled substances are subject to additional handling, accountability, and documentation requirements per DEA and state law. Always verify dosing, indications, contraindications, and route of administration against current published guidelines and your local protocols before administration.
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Drug information evolves. Last reviewed dates and source citations are provided for each entry. Confirm currency against the cited source before clinical use.
Penn Tactical Solutions publishes this reference for educational purposes. PTS does not provide medical direction and does not assume responsibility for clinical decisions made in the field. Clinical responsibility rests with the administering provider, their medical director, and their agency.
Educational reference for trained medical providers. Not medical advice. Not a substitute for formal training, current published guidelines, or medical direction. Drug administration is governed by your scope of practice, agency standing orders, medical director protocols, and applicable state and federal regulations. Controlled substances require additional storage, accountability, and documentation per DEA and state law.
In a medical emergency, call 911. This reference is not a substitute for emergency medical services.
Verify dosing, indications, and contraindications against current published guidelines and your local protocols before administration. Confirm content currency against the source citation. Penn Tactical Solutions does not provide medical direction. Clinical responsibility rests with the administering provider, their medical director, and their agency.
TMP-SMZ (Trimethoprim/Sulfamethoxazole)
| IV/IO | Severe infection: 8 to 12 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours. (Immediate after infusion) |
| PO | Skin and soft tissue MRSA: 1 to 2 double-strength tablets (160 mg/800 mg) PO every 12 hours for 7 to 14 days. Uncomplicated UTI: 1 double-strength tablet PO every 12 hours for 3 days. PJP treatment: 15 to 20 mg/kg/day (trimethoprim component) divided every 6 to 8 hours. (1 to 2 hours (well-absorbed orally)) |