Chloramphenicol Overview

Study Notes

Originally isolated from Streptomyces venezuelae
First broad-spectrum antibacterial developed (1947)
Now produced synthetically due to simple structure
Effective broad-spectrum antibiotic
Limited clinical use due to serious toxicity
Primarily bacteriostatic
Due to resistance and safety concerns, it's no longer a first-line treatment for infections in developed nations, except for topical use in bacterial conjunctivitis.

Active against a broad range of organisms, including gram-positive and gram-negative bacteria
Effective against Streptococcus, Staphylococcus, Enterococcus, Bacillus anthracis, Listeria monocytogenes (gram-positive)
Effective against Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitidis, Escherichia coli, Proteus, Salmonella, Shigella, Stenotrophomonas maltophilia, Bacteroides spp(gram-negative)
Excellent activity against anaerobes
Bactericidal against H. influenzae, N. meningitidis, and *S. pneumoniae

Well absorbed from the gut and achieves high concentrations in the central nervous system (CNS) even without inflammation
Useful in treating meningitis
30% protein bound
Metabolized by the liver to glucuronide
Excreted in the urine

Grey baby syndrome: A rare but potentially fatal toxic effect in neonates due to the liver's impaired ability to glucuronidation of the drug during the first few weeks of life, causing cyanosis, weakness, respiratory depression, hypotension, and shock.
Reversible dose-dependent anemia: Due to high drug concentration in the plasma, inhibiting ferrochelatase, which is critical for iron incorporation into heme, leading to anemia.
Aplastic anemia: A serious and generally fatal side effect appearing weeks or months after treatment, caused by bone marrow suppression as a direct toxic effect on human mitochondria. It manifests as a fall in hemoglobin levels and is fully reversible after the drug is stopped.
Increased risk of childhood leukemia

Inhibits microsomal enzymes that metabolize other drugs, such as warfarin and phenytoin.

Typhus, Rocky Mountain spotted fever
Restricted to serious systemic infections due to potential toxicity (e.g., bone marrow aplasia)
Meningitis (when other treatments are unsuitable)
Pyogenic meningitis
Anaerobic infections
Intraocular infections
Enteric fever
Whooping cough
Urinary tract infections
External ear infections
Topical use in eye infections—penetrates ocular tissues and aqueous humor due to solubility.

50-100 mg/kg/day in divided doses.
Adjustments needed for neonates and cirrhotic patients due to lower levels of glucuronosyl-transferase and impaired metabolism.

Contains a nitrobenzene moiety and a dichloroacetic acid derivative
Is non-ionized and highly lipophilic, enabling passive diffusion into bacterial cells.
Oxygen and nitrogen-containing functional groups enhance water solubility while non-ionizable hydrocarbon chains and ring systems enhance lipid solubility.