Co-Trimoxazole

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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

  1. Bactericidal (Individual drugs are bacteriostatic)
  2. Wide antibacterial spectrum
  3. Increased efficacy
  4. Less dose of each drug
  5. Less incidence of toxicity
  6. Have same half life (TMP 11 hrs. SMZ 10 hrs.)
  7. Both inhibit the same metabolic pathway, so synergize each others effect.
  8. Decreased chances of resistance (because if bacterium is resistant to one drug, it will be sensitive to other)

Pharmacokinetics

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.

  1. Gram positive
  2. Gram negative bacteria
  3. Some enterobacteria
  4. Shigella
  5. Salmonella Typhi and Para typhi
  6. Klebsiella Nocardia
  7. Pneumocystis Jiroveci
  8. Escherichia coli
  9. Serratia
  10. MRSA
  11. Staphylococcus aureus
  12. Staphylococcus epidemidis
  13. Proteus
  14. Brucella

Clinical Uses

  1. Respiratory infections:

Highly effective in:

  1. Chronic bronchitis
  2. Community acquired Pneumonia
  3. Otitis media in children
  4. Acute maxillary sinusitis
  5. Pneumocystis Jiroveci Pneumonia
  6. Non tuberculous mycobacterial infections –esp. AIDS
  7. Hemophilis influenzae
  8. Streptococcus Pneumoniae
  9. Moraxella Catarrhalis
  10. Klebsiella Pneumoniae

 

Has no activity in Pharyngitis

2. GIT Infections:

  1. Although amoxicillin is good, trimethoprim is highly effective in Shigellosis
  2. Typhoid Fever (SMX 800mg: TMP 160mg BD) (cephalosporin or ceftriaxone are 1st line for typhoid fever. Use as alternative
  3. Systemic Salmonella infection (Typhoid Fever) for Salmonella Typhae and Paratyphae, effective when used for prophylaxis given for 3 months

3. UTI:

  1. 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.
  2. As highly concentrated in acidic media effective in Prostatitis
  3. Acute Gonococcal Urethritis

Other drugs used in UTI include ampicillin, fluroquinolones, and in uncomplicated refractory cases even sulfonamides can be used.

  1. Brucellosis

Drug of choice is doxycycline, streptomycin and gentamicin.

Co-trimoxazole is used as alternative.

5. MRSA

Also used in sensitive MRSA.

Intravenous Uses:

  1. I/V preparation is ideally used for Pneumocystis Pneumonia
  2. Gram negative bacterial sepsis
  3. Shigellosis
  4. Typhoid Fever
  5. UTI

I/V preparations are used when drugs cannot be given orally or patient is uncooperative.

Adverse Effects

As the main component is sulfonamide, all effects are also seen and include:

  1. Hematological

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.

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The writer enjoys medical education and has special interest in community medicine.