Chloramphenicol

Chloramphenicol is a broad-spectrum antibiotic with excellent tissue and CSF penetration, used for typhoid, bacterial meningitis, rickettsial disease, plague and conjunctivitis where alternatives are unavailable or unsuitable. Dose-related and idiosyncratic marrow toxicity limits its use, but it remains in practice in resource-limited settings.

Classification. Phenicol.

Mechanism. Binds the 50S ribosomal subunit and blocks peptidyl transferase; bacteriostatic, bactericidal against Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae.

Spectrum. Salmonella Typhi (resistance in multidrug-resistant strains), Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae, anaerobes including Bacteroides fragilis, Rickettsia, Chlamydia, Brucella, Yersinia pestis, Vibrio cholerae. Resistance is common in Enterobacterales and staphylococci.

Pharmacokinetics. Oral bioavailability about 80%; IV chloramphenicol succinate is a prodrug (about 70% converted). Half-life 3 to 4 hours (longer in neonates and liver disease). Excellent CSF penetration (about 50% of serum). Hepatic glucuronidation and renal excretion.

Maximum 4 g daily.

Adults, oral or IV, every 6 hours.

• Usual dose: 50 mg/kg/day in 4 divided doses (12.5 mg/kg every 6 hours), usually 500 mg to 1 g every 6 hours.
• Bacterial meningitis (where cephalosporins are unavailable): 100 mg/kg/day (maximum 4 g) in 4 divided doses for 7 to 10 days.
• Typhoid fever (where susceptible): 50 mg/kg/day in 4 divided doses for 14 days.
• Rickettsial disease (pregnancy and tetracycline contraindication): 500 mg every 6 hours until afebrile for 3 days.
• Plague, brucellosis (alternative), anaerobic brain abscess: 12.5 mg/kg every 6 hours.
• Epidemic meningococcal meningitis (field use): oily chloramphenicol 100 mg/kg (maximum 3 g) IM as a single dose, with a second dose after 48 hours if no improvement.
• Topical: 0.5% eye drops every 2 to 6 hours or 1% ointment at night, for 5 days; ear drops.

Children. 50 to 75 mg/kg/day divided every 6 hours (maximum 4 g daily); meningitis 100 mg/kg/day (maximum 4 g) for 7 to 10 days. Use levels for children under 4 years.

Neonates (specialist only, with levels). 25 mg/kg once daily in the first week of life, then 25 mg/kg every 12 hours in term infants; avoid in premature infants.

Alternatives. Ceftriaxone, doxycycline, azithromycin, ciprofloxacin, meropenem.

Boxed-warning level risks. Serious and fatal blood dyscrasias (aplastic anaemia, pancytopenia, leukaemia after recovery); gray baby syndrome in neonates.

Contraindications. Hypersensitivity; neonates and premature infants (except with levels); porphyria; minor infections; concurrent marrow-suppressing drugs; prophylactic use.

Adverse effects. Dose-related reversible marrow suppression (anaemia, leucopenia, thrombocytopenia), nausea, vomiting, diarrhoea, glossitis, optic neuritis, peripheral neuropathy. Serious: irreversible aplastic anaemia (about 1 in 25 000 to 40 000, unrelated to dose, can appear weeks after therapy), gray baby syndrome (abdominal distension, vomiting, hypothermia, grey colour, collapse), haemolysis in G6PD deficiency, Clostridioides difficile infection, hypersensitivity.

Interactions. Inhibits CYP2C9, CYP2C19 and CYP3A4: raises levels of phenytoin, warfarin, sulphonylureas and tacrolimus. Rifampicin, phenobarbital and phenytoin lower chloramphenicol levels. Additive marrow suppression with other cytotoxic drugs. Reduced response to iron, vitamin B12 and folate.

Common prescribing errors. Use in newborns without levels, missing blood counts, treating minor infection, and no dose reduction in liver disease.

Special groups.

• Pregnancy: avoid near term (gray baby syndrome); use earlier only when no alternative.
• Breastfeeding: avoid (marrow toxicity risk in the infant).
• Older adults: monitor counts closely.
• Kidney impairment: no adjustment for chloramphenicol; succinate prodrug conversion is reduced, so oral use is preferred.
• Liver impairment: reduce the dose by about 50% and monitor levels.
• Region: low cost and widely available in East Africa, used for typhoid and meningitis outbreaks when ceftriaxone is unavailable; use ceftriaxone when it can be given.

Preparation. Oral on an empty stomach (1 hour before or 2 hours after food), capsules or suspension. IV: reconstitute 1 g vial with 10 mL sterile water and infuse over 30 to 60 minutes (or give as a slow push over at least 1 minute); do not give IM except as oily depot in field use.

Baseline and monitoring. - Baseline: full blood count, reticulocyte count, liver tests, G6PD status where available, pregnancy test, medication review. - During treatment: full blood count every 2 to 3 days (twice weekly) and weekly for courses beyond 14 days; levels where possible (peak 15 to 25 mg/L, trough 5 to 15 mg/L; in meningitis peak 15 to 25 mg/L).

Stop rules. Stop for neutropenia, thrombocytopenia, anaemia not explained by infection, new bruising, bleeding or sore throat, optic neuritis, neuropathy or gray baby syndrome.

Referral and escalation. Refer for pancytopenia or aplastic anaemia (haematology), treatment failure and meningitis not responding at 48 to 72 hours.