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Chloramphenicol

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Chloramphenicol, Grey baby Syndrome

  • Indications
  1. Rare use in the United States (due to adverse effects)
  2. Avoid unless other Antibiotics have failed and infection has known susceptibility to Chloramphenicol
  3. Bacteriostatic Activity
    1. Gram Positive Bacteria
    2. Gram Negative Bacteria
    3. Anaerobic Bacteria
  4. Conditions: Topical Use
    1. Bacterial Conjunctivitis
    2. Otitis Externa (risk of Ototoxicity)
    3. Surgical Wound Infection prophylaxis
  5. Conditions: Life-threatening Infections
    1. Typhoid Fever
    2. Rickettsial infections
    3. Meningitis
      1. HaemophilusInfluenzae
      2. Neisseria Meningitidis
      3. Streptococcus Pneumoniae
  • Contraindications
  1. Acute porphyria
  2. G6PD Deficiency
  3. Young Infants (esp. Preterm Infants) or lactating mothers
    1. Grey baby Syndrome risk (see below)
  • Mechanism
  1. First identified in 1948 and was among the first synthetic Antibiotics
  2. Semisynthetic broad spectrum, Bacteriostatic Antibiotic derived from Streptomyces venequelae
  3. Inhibits Bacterial Protein synthesis
    1. Diffuses across the Bacterial cell wall and reversibly binds the Bacterial 50S Ribosome
    2. Inhibits peptidyl transferase activity at the tRNA ribosomal attachment A site
    3. Blocks transfer to Amino Acids to a growing polypeptide chain
  • Dosing
  • Serious, Life threatening Infections
  1. Adult (e.g. Typhoid Fever, Rickettsial infection)
    1. Give 50 mg/kg/day divided every 6 hours IV
    2. Doses as high as 75 to 100 mg/kg/day may be needed for organisms resistant to other agents
    3. Decrease dose in hepatic dysfunction: 1 g IV load, then 500 mg every 6 hours
  2. Child (e.g. Meningitis)
    1. Give 50 to 100 mg/kg/day divided every 6 hours IV
    2. Doses as high as 75 to 100 mg/kg/day may be needed for organisms resistant to other agents (esp. pneumococcus)
  • Adverse Effects
  1. Ototoxicity (Ear Drops)
  2. Esophagitis
  3. Neurotoxicity (includes Optic Neuritis)
  4. Metabolic Acidosis
  5. Blood Dyscrasias and Marrow Suppression
    1. Type 1: Reversible, dose-dependent mild Anemia, Thrombocytopenia, Neutropenia
    2. Type 2: Idiosyncratic Pancytopenia or Aplastic Anemia
      1. Deaths have occurred
      2. More common when taken with Cimetidine
    3. Other uncommon to rare effects
      1. Secondary Leukemia
  6. Grey baby Syndrome
    1. Presents with grey Skin Color, poor feeding, irritability, Vomiting, Abdominal Distention, cardiovascular collapse
    2. High mortality (up to 40%)
  • Safety
  1. Avoid in pregnancy (despite pregnancy category C)
  2. Avoid in Lactation
    1. Grey baby Syndrome risk
  3. Monitoring
    1. Complete Blood Count (CBC) every 2 days
    2. Serum drug levels
      1. Therapeutic peak: 10 to 20 mcg/ml
      2. Therapeutic trough: 5 to 10 mcg/ml
  • Pharmacokinetics
  1. Hepatic conjugation with glucuronide
  2. Renal excretion
  • Drug Interactions
  1. Aminoglycosides
    1. Chloramphenicol interferes with Aminoglycoside transfer into Bacterial cells
  2. Drugs that decrease Chloramphenicol levels
    1. Barbiturates
    2. Rifampin
  3. Drug levels that are increased by Chloramphenicol
    1. Barbiturates
    2. Phenytoin
    3. Warfarin (INR)
  • Resources
  1. Chloramphenicol powder for intravenous solution (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aed29594-211d-49ef-813f-131975a8d0e3
  • References
  1. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  2. Oong (2023) Chloramphenicol, StatPearls, Treasure Island, Florida +PMID: 32310426 [PubMed]