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Chloramphenicol

by Hans P. Schlecht, MD, MSc, Christopher Bruno, MD

Chloramphenicol is primarily bacteriostatic. It binds to the 50S subunit of the ribosome, thereby inhibiting bacterial protein synthesis.

Pharmacology

Chloramphenicol is well absorbed orally. Parenteral therapy should be IV.

Chloramphenicol is distributed widely in body fluids, including CSF, and is excreted in urine. Because of hepatic metabolism, active chloramphenicol does not accumulate when renal insufficiency is present.

Indications

Chloramphenicol has a wide spectrum of activity against

  • Gram-positive and gram-negative cocci and bacilli (including anaerobes)

  • Rickettsia, Mycoplasma, Chlamydia, and Chlamydophila spp

Because of bone marrow toxicity, the availability of alternative antibiotics, and the emergence of resistance, chloramphenicol is no longer a drug of choice for any infection, except for

  • Serious infections due to a few multidrug-resistant bacteria that remain susceptible to this antibiotic

However, when chloramphenicol has been used to treat meningitis caused by relatively penicillin-resistant pneumococci, outcomes have been discouraging, probably because chloramphenicol has poor bactericidal activity against these strains.

Contraindications

Chloramphenicol is contraindicated if another drug can be used instead.

Use During Pregnancy and Breastfeeding

Use of chloramphenicol during pregnancy results in fetal drug levels almost as high as maternal levels. Gray baby syndrome is a theoretical concern, particularly near term, but there is no clear evidence of fetal risk.

Chloramphenicol enters breast milk. Safety during breastfeeding has not been determined.

Adverse Effects

Adverse effects include

  • Bone marrow depression (most serious)

  • Nausea, vomiting, and diarrhea

  • Gray baby syndrome (in neonates)

There are 2 types of bone marrow depression:

  • Reversible dose-related interference with iron metabolism: This effect is most likely with high doses or prolonged treatment or in patients with a severe liver disorder.

  • Irreversible idiosyncratic aplastic anemia: This anemia occurs in < 1/25,000 treated patients. It may not develop until after therapy is stopped. Chloramphenicol should not be used topically because small amounts may be absorbed and, rarely, cause aplastic anemia.

Hypersensitivity reactions are uncommon. Optic and peripheral neuritis may occur with prolonged use.

The neonatal gray baby syndrome, which involves hypothermia, cyanosis, flaccidity, and circulatory collapse, is often fatal. The cause is high blood levels, which occur because the immature liver cannot metabolize and excrete chloramphenicol. To avoid the syndrome, clinicians should not give infants 1 mo > 25 mg/kg/day initially, and doses should be adjusted based on blood levels of the drug.

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