Co-trimoxazole is the mixture of trimethoprim with sulfamethoxazole, with sulfamethoxazole 400 mg and trimethoprim 80 mg in ratio of 5:1.
Trimethoprim has a large volume of distribution, so its dose is decreased. It is quickly absorbed. Plasma protein binding of trimethoprim is also less than sulfamethoxazole.
Advantages of Using Co-Trimoxazole
- Bactericidal (Individual drugs are bacteriostatic)
- Wide antibacterial spectrum
- Increased efficacy
- Less dose of each drug
- Less incidence of toxicity
- Have same half life (TMP 11 hrs. SMZ 10 hrs.)
- Both inhibit the same metabolic pathway, so synergize each others effect.
- Decreased chances of resistance (because if bacterium is resistant to one drug, it will be sensitive to other)
Can be given orally or I/V. After oral administration absorption is good, peak plasma levels appear within 2 hours. Given I/V for infectious conditions.
Trimethoprim is a weak base with pH of 7 .2. It is found in bile, sputum, high concentration in CSF, also concentrates in acidic media of prostate and vagina.
Plasma protein binding of trimethoprim is 40-45% while that of sulfamethoxazole is 60%.
Volume of distribution of trimethoprim is 9 times more than sulfamethoxazole.
Most products are excreted in urine; traces of drug appear within 24 hours. Dose is adjusted as required (esp. in renal insufficiency).
Mechanism of Action
Anti bacterial spectrum
Combination has wider antibacterial spectrum.
- Gram positive
- Gram negative bacteria
- Some enterobacteria
- Salmonella Typhi and Para typhi
- Klebsiella Nocardia
- Pneumocystis Jiroveci
- Escherichia coli
- Staphylococcus aureus
- Staphylococcus epidemidis
- Respiratory infections:
Highly effective in:
- Chronic bronchitis
- Community acquired Pneumonia
- Otitis media in children
- Acute maxillary sinusitis
- Pneumocystis Jiroveci Pneumonia
- Non tuberculous mycobacterial infections –esp. AIDS
- Hemophilis influenzae
- Streptococcus Pneumoniae
- Moraxella Catarrhalis
- Klebsiella Pneumoniae
Has no activity in Pharyngitis
2. GIT Infections:
- Although amoxicillin is good, trimethoprim is highly effective in Shigellosis
- Typhoid Fever (SMX 800mg: TMP 160mg BD) (cephalosporin or ceftriaxone are 1st line for typhoid fever. Use as alternative
- Systemic Salmonella infection (Typhoid Fever) for Salmonella Typhae and Paratyphae, effective when used for prophylaxis given for 3 months
- Said to be effective against uncomplicated and chronic & recurrent UTI. Given either 800 mg x 160 mg or small dose is administered for management of chronic recurrent UTI in 200 mg SMZ 40 mg TMP BD dose.
- As highly concentrated in acidic media effective in Prostatitis
- Acute Gonococcal Urethritis
Other drugs used in UTI include ampicillin, fluroquinolones, and in uncomplicated refractory cases even sulfonamides can be used.
Drug of choice is doxycycline, streptomycin and gentamicin.
Co-trimoxazole is used as alternative.
Also used in sensitive MRSA.
- I/V preparation is ideally used for Pneumocystis Pneumonia
- Gram negative bacterial sepsis
- Typhoid Fever
I/V preparations are used when drugs cannot be given orally or patient is uncooperative.
As the main component is sulfonamide, all effects are also seen and include:
Trimethoprim –megaloblastic anemia, leukopenia, thrombocytopenia, granulocytopenia
Prevented by simultaneous administrations of folic acid 6 – 8 mg/D which does not enter bacteria for 3-6 weeks
2. Hypersensitivity reactions -rashes, fever, vasculitis
3. CNS effects –headache, depression, hallucinations
4. GIT disturbance – nausea, vomiting, glossitis & stomatitis.
5. HIV patients with Pneumocystis pneumonia or immune compromised show fever, rashes, leukopenia, diarrhea, elevation of hepatic aminotransferases, hyperkalemia, hyponatremia.