1. Clinical Overview
Chloramphenicol is a broad-spectrum bacteriostatic antibiotic originally derived from *Streptomyces venezuelae*. It is a potent inhibitor of bacterial protein synthesis. Due to its association with serious and potentially fatal adverse effects like aplastic anemia and gray baby syndrome, its systemic use is now highly restricted in clinical practice. In India, it is primarily reserved for the treatment of severe, life-threatening infections caused by susceptible organisms where safer alternatives are contraindicated or ineffective, such as typhoid fever, bacterial meningitis, and rickettsial infections.
| Onset | Duration | Bioavailability |
|---|---|---|
| Oral: 1-2 hours for peak plasma concentrations. IV: Immediate onset of systemic availability. | Approximately 4-6 hours, necessitating multiple daily doses. | Oral: 75-90% (well absorbed). IV: 100%. |
2. Mechanism of Action
Chloramphenicol binds reversibly to the 50S subunit of the bacterial 70S ribosome. It inhibits the peptidyl transferase activity, thereby preventing the transfer of the growing peptide chain to the newly attached aminoacyl-tRNA at the A-site. This action blocks peptide bond formation, a crucial step in protein synthesis.
3. Indications & Uses
- Severe Typhoid Fever (Salmonella Typhi) resistant to fluoroquinolones and cephalosporins
- Bacterial Meningitis (especially due to *H. influenzae*, *N. meningitidis*, *S. pneumoniae*) when penicillin/cephalosporins are contraindicated
- Rickettsial Infections (e.g., Scrub typhus, Rocky Mountain spotted fever) where tetracyclines are contraindicated
4. Dosage & Administration
Adult Dosage: Oral/IV: 50 mg/kg/day in 4 divided doses (approx. 1gm every 6 hours for a 50kg adult). Maximum daily dose: 4 gm. For severe infections (e.g., meningitis): 75-100 mg/kg/day in divided doses.
Administration: **IV Route (Primary for systemic use):** Reconstitute 1gm vial with 10ml Water for Injection. Further dilute in 100ml of compatible IV fluid (e.g., 5% Dextrose, 0.9% Sodium Chloride). Infuse over 30-60 minutes. **Oral:** Take on an empty stomach (1 hour before or 2 hours after meals) for optimal absorption, but can be taken with food to reduce GI upset. Complete the full prescribed course.
5. Side Effects
Common side effects may include:
- Nausea, vomiting, diarrhea
- Bitter or metallic taste
- Headache
- Mild skin rashes
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Warfarin, Acenocoumarol | Chloramphenicol inhibits hepatic metabolism of coumarins, potentiating anticoagulant effect, increasing INR and bleeding risk. | Major |
| Phenytoin, Phenobarbital | Complex interaction. Chloramphenicol can inhibit metabolism of these drugs, increasing their levels and toxicity. Conversely, these drugs may induce chloramphenicol metabolism, reducing its efficacy. | Major |
| Sulfonylureas (e.g., Glibenclamide) | Increased risk of hypoglycemia due to inhibited metabolism. | Moderate |
| Rifampicin | Rifampicin induces chloramphenicol metabolism, significantly reducing its serum levels and therapeutic effect. | Major |
| Paracetamol (Acetaminophen) | Potential increased risk of bone marrow suppression and hepatotoxicity. | Moderate |
| Other Myelosuppressive Drugs (e.g., Chemotherapy, Zidovudine, Clozapine) | Additive risk of bone marrow toxicity. | Major |
7. Patient Counselling
- DO complete the full course of therapy as directed by your doctor.
- DO inform all your doctors and your dentist that you are taking chloramphenicol.
- DO get regular blood tests (CBC) as advised by your doctor during and after therapy.
- DONT use this medicine for colds, flu, or other viral infections.
- DONT give this medicine to anyone else; it is prescribed based on a specific serious infection.
- DONT consume alcohol while on this medication.
8. Toxicology & Storage
Overdose: Symptoms of dose-related reversible bone marrow suppression (anemia, leukopenia). In neonates/infants: 'Gray Baby Syndrome' (vomiting, refusal to feed, rapid respiration, abdominal distension, cyanosis (ashen-gray color), hypothermia, vasomotor collapse, death).
Storage: Store in a cool, dry place, protected from light. For reconstituted IV solution: Use immediately. Stability varies with diluent; consult product literature. Do not freeze. Keep out of reach of children.