Co trimoxazole syp
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Now I have comprehensive information. Here is a complete overview of Co-trimoxazole Syrup (TMP-SMX):
Co-trimoxazole Syrup (Trimethoprim + Sulfamethoxazole)
Other names: TMP-SMX, TMP-SMZ, Cotrimoxazole, Bactrim, Septran
Composition
Co-trimoxazole is a fixed-ratio combination of:
- Trimethoprim (TMP) + Sulfamethoxazole (SMX) in a 1:5 ratio
Syrup formulation: 40 mg TMP + 200 mg SMX per 5 mL (standard pediatric suspension)
The ratio is designed so that peak plasma concentrations are approximately 1:20 (TMP:SMX), which is optimal for synergistic antibacterial activity.
Mechanism of Action
Acts on two sequential steps of the bacterial folate synthesis pathway:
- SMX — inhibits dihydropteroate synthase → blocks conversion of PABA to dihydrofolic acid
- TMP — inhibits dihydrofolate reductase (DHFR) → blocks conversion of dihydrofolate to tetrahydrofolate, which is essential for purine/thymidylate synthesis and ultimately DNA synthesis
- Individually: bacteriostatic
- In combination: bactericidal (for sensitive organisms)
- TMP is ~100,000× more selective for bacterial DHFR than human DHFR
— Goodman & Gilman's The Pharmacological Basis of Therapeutics
Antimicrobial Spectrum
| Category | Organisms |
|---|---|
| Gram-positive | S. aureus (incl. MRSA in community), S. pneumoniae, S. pyogenes, viridans streptococci |
| Gram-negative | E. coli, Klebsiella, Proteus mirabilis, Enterobacter, Serratia, Shigella, Salmonella, H. influenzae |
| Other | Nocardia asteroides, Stenotrophomonas maltophilia, Pneumocystis jirovecii (PCP), Cyclospora, Isospora, Brucella |
| Resistant | Pseudomonas aeruginosa, Bacteroides fragilis, Enterococcus |
Pharmacokinetics
| Parameter | TMP | SMX |
|---|---|---|
| Absorption | Well absorbed orally | Well absorbed orally |
| Time to peak | ~2 hours | ~4 hours |
| Half-life | ~11 hours | ~10 hours |
| Protein binding | ~40% | ~65% |
| Volume of distribution | Large (lipid-soluble) | Smaller |
| Excretion | 60% in urine (24 h) | 25–50% in urine (24 h) |
- TMP penetrates well into CSF, sputum, bile, prostatic fluid, and vaginal fluid
- Dose reduction required when creatinine clearance is 15–30 mL/min
Clinical Uses (Syrup / Pediatric Focus)
| Indication | Notes |
|---|---|
| Urinary tract infections (UTIs) | First-line for sensitive E. coli; avoid if local resistance >20%; 3 days for uncomplicated cystitis, 10–14 days for complicated/pyelonephritis |
| Acute otitis media | Effective for H. influenzae and S. pneumoniae |
| Shigellosis / Traveller's diarrhea | Alternative when susceptibility confirmed; increasing resistance |
| Respiratory infections | Acute exacerbations of chronic bronchitis; NOT for streptococcal pharyngitis |
| PCP prophylaxis/treatment | High-dose TMP 15–20 mg/kg/day + SMX 75–100 mg/kg/day in 3–4 divided doses |
| MRSA skin/soft tissue infections | Adjunct to drainage of community-acquired MRSA abscesses |
| Nocardiosis, Brucellosis | Alternative regimens |
| Toxoplasma prophylaxis | In HIV-infected patients |
Pediatric Dosing (Syrup: 40/200 mg per 5 mL)
| Indication | Dose (TMP component) | Frequency | Duration |
|---|---|---|---|
| UTI / Respiratory / Otitis | 4–6 mg/kg/day TMP (= 20–30 mg/kg/day SMX) | Divided every 12 h | 5–10 days |
| PCP treatment | 15–20 mg/kg/day TMP | Divided every 6–8 h | 14–21 days |
| PCP prophylaxis | 150 mg/m²/day TMP | Once daily or 3 days/week | Ongoing |
⚠️ Not recommended in infants < 2 months — risk of kernicterus (sulfonamides displace bilirubin from albumin)
Adverse Effects
- Hematological: Megaloblastic anemia, agranulocytosis, thrombocytopenia, granulocytopenia, Henoch-Schönlein purpura, sulfhemoglobinemia
- Dermatological: Rashes (5.9%); Stevens-Johnson syndrome (especially in HIV)
- Renal: Crystalluria (SMX); increased serum creatinine (TMP inhibits tubular creatinine secretion)
- Electrolytes: Hyperkalemia — TMP has a triamterene-like potassium-sparing effect
- Hepatic: Cholestatic jaundice (rare)
- HIV patients: High frequency of hypersensitivity reactions (rash, neutropenia, SJS, pulmonary infiltrates)
Drug Interactions
| Drug | Interaction |
|---|---|
| Warfarin | TMP-SMX inhibits warfarin metabolism → increased anticoagulation, bleeding risk |
| Methotrexate | TMP-SMX increases methotrexate levels → serious toxicity; avoid |
| Potassium-elevating agents | Additive hyperkalemia risk |
| Bone marrow suppressants | Additive myelosuppression with high-dose TMP-SMX |
Resistance Mechanisms
- Reduced cell permeability to TMP
- Overproduction of DHFR
- Plasmid-encoded altered DHFR with reduced TMP binding (most common; encoded on conjugative transposons — spreads rapidly among species)
- Resistance to combination is lower than resistance to either drug alone
Contraindications
- Age < 2 months
- Severe renal or hepatic impairment
- Megaloblastic anemia due to folate deficiency
- Known sulfonamide hypersensitivity
- Pregnancy near term (kernicterus risk)
— Goodman & Gilman's The Pharmacological Basis of Therapeutics; Katzung's Basic and Clinical Pharmacology, 16th Ed.; Smith & Tanagho's General Urology, 19th Ed.
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