Chloramphenicol is an antibiotic used for serious infections caused by bacteria that are sensitive to this medicine. It should be reserved for cases where safer antibiotics are ineffective or cannot be used. In some situations, treatment with chloramphenicol may be started based on clinical suspicion that one of these serious infections is present. At the same time, laboratory sensitivity tests should be performed so the drug can be stopped as soon as a safer effective alternative is identified. If laboratory results show that both chloramphenicol and another antibiotic are effective against the same organism, the decision to continue chloramphenicol should depend on the severity of the infection, the susceptibility of the organism, and the expected effectiveness of each drug.

In laboratory studies, chloramphenicol mainly acts as a bacteriostatic antibiotic, meaning it stops the growth of many Gram-negative and Gram-positive bacteria. It is also active against rickettsiae, the lymphogranuloma-psittacosis group, and Vibrio cholerae. It is especially effective against Salmonella typhi and Haemophilus influenzae. Chloramphenicol works by interfering with or inhibiting protein synthesis in bacterial cells. In vitro antagonism has been observed between chloramphenicol and erythromycin, clindamycin, and lincomycin. Chloramphenicol is rapidly absorbed from the gastrointestinal tract. Chloramphenicol palmitate is broken down in the GI tract and absorbed as free chloramphenicol.

After a single oral dose of 1 gram in healthy adults, peak plasma concentrations averaging about 11 mcg/mL are reached within 1 to 3 hours. With repeated dosing of 1 gram every 6 hours, the peak concentration rises to about 18 mcg/mL after the fifth dose. Mean serum concentrations remain around 8 to 14 mcg/mL over 48 hours.

Most of the drug is excreted in the urine. Although only a small amount is excreted unchanged, the concentration of free chloramphenicol in urine remains relatively high. About 8% to 12% of the antibiotic is excreted as free chloramphenicol, while the rest is eliminated as inactive metabolites, mainly glucuronide conjugates. Small amounts of active drug are also found in bile and feces. Chloramphenicol diffuses rapidly throughout the body, although its distribution is uneven. The highest concentrations are found in the liver and kidneys, while the lowest are found in the brain and cerebrospinal fluid (CSF). Even without meningeal inflammation, chloramphenicol enters the CSF, where its concentration reaches about half of that in the blood.

Chloramphenicol, like other potent drugs, should be prescribed at recommended doses known to have therapeutic activity. Inhibition of the majority of sensitive organisms may be expected at concentrations of 5 to 20 mcg/ml. The desired concentration of active drug in serum should fall within this range over most of the treatment period. Dosage of 50 mg/kg/day divided into 4 doses at intervals of 6 hours will usually achieve and sustain levels of this order. Except in certain circumstances (e.g. premature infants and neonates and individuals with hepatic or renal impairment) lower doses may not achieve these concentrations. Close observation of the patient should be maintained and in the event of any adverse reactions, dosage should be reduced or the drug discontinued, if other factors in the clinical situation permit.

Adults: should receive 50 mg/kg/day in divided doses [approximately one 250 mg capsule per each 4.5 kg (10 lbs) of body weight or one 500 mg capsule per each 9 kg (20 lbs) of body weight] in divided doses at 6 hour intervals. In exceptional cases, patients with infections due to moderately resistant organisms may require increased dosage up to 100 mg/kg/day to achieve serum levels inhibiting the pathogen, but these high doses should be decreased as soon as possible.

Adults with impairment of hepatic or renal function, or both, may have reduced ability to metabolize and excrete the drug. In instances of impaired metabolic processes, dosages should be adjusted accordingly.

Pediatric patients: Dosage of 50 mg/kg/day divided at 6 hour intervals is effective against most susceptible organisms. Severe infections (eg., bacteremia or meningitis), especially when adequate cerebrospinal fluid concentrations are desired, may require dosage up to 100 mg/kg/day; however, it is recommended that dosage be reduced to 50 mg/kg/day as soon as possible. Children with impaired hepatic or renal function may retain excessive amounts of the drug.

Newborn infants: A total of 25 mg/kg/day in 4 equal doses at 6-hour intervals usually produces and maintains concentrations in serum and tissues adequate to control most infections for which the drug is indicated.

Chloramphenicol has been shown to slow the biotransformation of tolbutamide, phenytoin, and dicoumarol in humans. It should be used cautiously when given together with lincomycin, clindamycin, or erythromycin. In vitro studies have shown that the binding sites of erythromycin, lincomycin, clindamycin, and chloramphenicol overlap, which may result in competitive inhibition. Rifampin therapy may reduce chloramphenicol concentrations.

Chloramphenicol is contraindicated in patients with a history of hypersensitivity or toxic reactions to this drug or any of its components. It should not be used to treat minor infections or conditions for which it is not indicated, such as the common cold, viral influenza, throat infections, or as a prophylactic agent to prevent bacterial infections.

During treatment with chloramphenicol, it is essential to monitor hematologic function closely. Although blood tests may detect early peripheral hematologic changes such as leukopenia, reticulocytopenia, or granulocytopenia before these changes become irreversible, they cannot be relied upon to detect bone marrow depression before aplastic anemia develops.

Serum levels above 25 mcg/ml are often considered toxic. Chloramphenicol toxicity may cause serious hematopoietic effects, including aplastic anemia, thrombocytopenia, and leukopenia. Other signs of toxicity may include increased serum iron levels, nausea, vomiting, and diarrhea. In cases of severe overdose, charcoal hemoperfusion may help remove chloramphenicol from the plasma. Exchange transfusion is of uncertain benefit after massive overdose, especially in neonates and infants.

Macrolides

Store in a cool, dry place. Keep the bottle tightly closed. Protect from light.