Chloramphenicol

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

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

Chloramphenicol has a wide spectrum of activity against

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

• Rickettsia, Mycoplasma, Chlamydia, and Chlamydophila species

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

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

• Plague meningitis or endophthalmitis because other plague medications penetrate these spaces poorly

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

Chloramphenicol has a high rate of serious toxicities and is contraindicated if another antibiotic can be used instead.

Use of chloramphenicol during pregnancy results in fetal medication levels almost as high as maternal levels. Use has been associated with gray baby syndrome in newborns but no teratogenic effects. It may be used in pregnancy to treat Rocky Mountain spotted fever if a second-line agent is required, but caution is warranted in the third trimester.

Chloramphenicol enters breast milk. It should not be used during breastfeeding; serious adverse reactions are possible, particularly in young or low weight infants.

Adverse effects of chloramphenicol 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 month of age > 25 mg/kg/day initially, and doses should be adjusted based on blood levels of the medication.