Chloramphenicol

# Chloramphenicol ## Overview - **Classification**: Broad-spectrum antibiotic, protein synthesis inhibitor. - **Mechanism**: Reversibly binds to 50S ribosomal subunit, inhibiting peptide bond formation and protein synthesis in bacteria. ## Primary Indications 1. **Severe Bacterial Infections** - Meningitis, rickettsial infections (e.g., Rocky Mountain spotted fever), typhoid fever, bacteremia. 2. **Anaerobic Infections** - Brain abscesses, intra-abdominal infections, especially when safer alternatives are contraindicated. 3. **Conjunctivitis** - Ophthalmic formulations for bacterial conjunctivitis. ## Adult Dosing ### Standard Dosing **Severe Infections (e.g., Meningitis, Typhoid, Rickettsial)** - **Dose**: **50 mg/kg/day** - **Frequency**: Divided every 6 hours (**q6h**) - **Route**: Intravenous (IV) or Oral (PO) - **Duration**: Typically 7-14 days depending on infection type and response. - **Maximum**: **4 g/day** **Less Severe/Other Infections** - **Dose**: **25-50 mg/kg/day** - **Frequency**: Divided every 6 hours (**q6h**) - **Route**: IV or PO ### Dose Adjustments - **Renal Impairment**: No routine dose adjustment for renal failure, but accumulation of inactive metabolites may occur. Monitor serum levels closely. - **Hepatic Impairment**: Reduce dose by 50% or more. Monitor serum levels closely due to impaired metabolism. - **Elderly Patients**: Start at lower end of dosing range. Increased risk of adverse effects due to reduced hepatic/renal function. ## Pediatric Dosing ### Neonates (0-28 days) - **Indication**: Life-threatening infections only, with no suitable alternatives. - **Postnatal Age < 7 days**: **25 mg/kg/day** IV/PO. - **Frequency**: Divided every 12-24 hours (**q12-24h**). - **Postnatal Age > 7 days** (Term): **50 mg/kg/day** IV/PO. - **Frequency**: Divided every 6-12 hours (**q6-12h**). - **Preterm Neonates**: **25 mg/kg/day** IV/PO. - **Frequency**: Divided every 12-24 hours (**q12-24h**). - **Maximum**: Avoid exceeding prescribed daily dose due to toxicity risk. - **Special Notes**: HIGH risk of **Grey Baby Syndrome** due to immature hepatic glucuronidation. **Therapeutic Drug Monitoring (TDM) is essential**. ### Infants (1-12 months) - **Dose**: **50-75 mg/kg/day** IV/PO. - **Frequency**: Divided every 6 hours (**q6h**). - **For severe infections** (e.g., meningitis): Up to **100 mg/kg/day**. - **Maximum**: **4 g/day**. ### Children (1-12 years) - **Dose**: **50-75 mg/kg/day** IV/PO. - **Frequency**: Divided every 6 hours (**q6h**). - **For severe infections** (e.g., meningitis): Up to **100 mg/kg/day**. - **Maximum**: **4 g/day**. ### Adolescents (13-18 years) - **Dose**: Generally follows adult dosing: **50 mg/kg/day** IV/PO. - **Frequency**: Divided every 6 hours (**q6h**). - **Maximum**: **4 g/day**. ## Safety Information ### Contraindications - **Absolute**: Prior hypersensitivity to chloramphenicol. - **Absolute**: Minor infections (due to severe toxicity risk). - **Absolute**: Concurrent use with myelosuppressive drugs. - **Absolute**: Pregnancy (near term), lactation. - **Absolute**: Routine prophylaxis. - **Relative**: Pre-existing bone marrow depression, active immunization. ### Common Adverse Effects - **Very Common (>10%)**: Dose-related anemia, nausea, vomiting, diarrhea. - **Common (1-10%)**: Headache, rash, fever, stomatitis, glossitis. - **Serious but Rare**: **Aplastic anemia** (irreversible, fatal), **Grey Baby Syndrome** (neonates), peripheral/optic neuritis, bone marrow depression (reversible, dose-related), Stevens-Johnson syndrome. ### Key Drug Interactions - **Warfarin**: Chloramphenicol inhibits CYP2C9; enhances anticoagulant effect. Monitor INR closely, adjust warfarin dose. - **Phenytoin, Phenobarbital**: Chloramphenicol inhibits their metabolism. Monitor drug levels, adjust anticonvulsant dose. - **Oral Contraceptives**: May reduce efficacy (less common). Advise backup contraception. - **Iron Salts, Vitamin B12, Folic Acid**: May interfere with hematopoietic response to these agents. ## Monitoring & Follow-up - **Before Treatment**: Complete Blood Count (CBC) with differential & reticulocyte count, renal/hepatic function tests. - **During Treatment**: - **CBC**: Every 2-3 days, especially for reticulocyte count. Discontinue if significant drop. - **Serum Chloramphenicol Levels**: **Essential for neonates, liver/renal impairment, severe infection**. Trough: 5-10 mcg/mL; Peak: 10-25 mcg/mL. - **Clinical Signs**: Monitor for fever, rash, bleeding, neurological symptoms. - **Clinical Signs**: Watch for signs of Grey Baby Syndrome in neonates: poor feeding, vomiting, abdominal distention, progressive pallid cyanosis, hypotonia, circulatory collapse. ## Clinical Pearls - 💡 **Use Judiciously**: Reserve for severe, life-threatening infections where benefits outweigh high risk of toxicity. - 💡 **TDM is Key**: Therapeutic drug monitoring significantly reduces risk of toxicity, especially in neonates and patients with impaired metabolism. - 💡 **Bone Marrow Suppression**: Be vigilant for signs of dose-related anemia, thrombocytopenia, leukopenia; often reversible upon discontinuation. - 💡 **Ophthalmic Use**: Systemic absorption is minimal, so systemic toxicity is rare with eye drops/ointments. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.