II. Indications
- Rare use in the United States (due to adverse effects)
- Avoid unless other Antibiotics have failed and infection has known susceptibility to Chloramphenicol
- Bacteriostatic Activity (very broad spectrum)
- Conditions: Topical Use
- Bacterial Conjunctivitis
- Otitis Externa (risk of Ototoxicity)
- Surgical Wound Infection prophylaxis
- Conditions: Life-threatening Infections
- Typhoid Fever
- Rickettsial infections (including Rocky Mountain Spotted Fever)
- Meningitis (high CSF penetration, but due to toxicity is NOT a first-line agent)
III. Contraindications
- Acute porphyria
- G6PD Deficiency
- Young Infants (esp. Preterm Infants) or lactating mothers
- Grey baby Syndrome risk (see below)
IV. Mechanism
- First identified in 1948 and was among the first synthetic Antibiotics
- Semisynthetic broad spectrum, Bacteriostatic Antibiotic derived from Streptomyces venequelae
-
Anti-Ribosomal Antibiotic that inhibits Bacterial Protein synthesis
- Diffuses across the Bacterial cell wall and reversibly binds the Bacterial 50S Ribosome
- Inhibits peptidyl transferase activity at the tRNA ribosomal attachment A site
- Blocks transfer of Amino Acids to a growing polypeptide chain
V. Dosing: Serious, Life threatening Infections
- Adult (e.g. Typhoid Fever, Rickettsial infection)
- Give 50 mg/kg/day divided every 6 hours IV
- Doses as high as 75 to 100 mg/kg/day may be needed for organisms resistant to other agents
- Decrease dose in hepatic dysfunction: 1 g IV load, then 500 mg every 6 hours
- Child (e.g. Meningitis)
- Give 50 to 100 mg/kg/day divided every 6 hours IV
- Doses as high as 75 to 100 mg/kg/day may be needed for organisms resistant to other agents (esp. Pneumococcus)
VI. Adverse Effects
- Ototoxicity (Ear Drops)
- Esophagitis
- Neurotoxicity (includes Optic Neuritis)
- Metabolic Acidosis
- Blood Dyscrasias and Marrow Suppression
- Type 1: Reversible, dose-dependent mild Anemia, Thrombocytopenia, Neutropenia
- Type 2: Idiosyncratic Pancytopenia or Aplastic Anemia (rare, 1 in 24,000)
- Deaths have occurred
- More common when taken with Cimetidine
- Other uncommon to rare effects
- Secondary Leukemia
- Grey baby Syndrome
- Results from very high, toxic Chloramphenicol blood levels due to poor Renal Clearance in infants
- Presents with grey Skin Color, poor feeding, irritability, Vomiting, Abdominal Distention, cardiovascular collapse
- High mortality (up to 40%)
VII. Safety
- Avoid in pregnancy (despite pregnancy category C)
- Avoid in Lactation
- Grey baby Syndrome risk
- Monitoring
- Complete Blood Count (CBC) every 2 days
- Serum drug levels
- Therapeutic peak: 10 to 20 mcg/ml
- Therapeutic trough: 5 to 10 mcg/ml
VIII. Pharmacokinetics
- Hepatic conjugation with glucuronide
- Renal excretion
IX. Drug Interactions
-
Aminoglycosides
- Chloramphenicol interferes with Aminoglycoside transfer into Bacterial cells
- Drugs that decrease Chloramphenicol levels
- Drug levels that are increased by Chloramphenicol
- Barbiturates
- Phenytoin
- Warfarin (INR)
X. Resources
- Chloramphenicol powder for intravenous solution (DailyMed)
XI. References
- Hamilton (2020) Tarascon Pocket Pharmacopoeia
- Oong (2023) Chloramphenicol, StatPearls, Treasure Island, Florida +PMID: 32310426 [PubMed]