Chloromycetin (Chloramphenicol)

Chloromycetin Review

Chloramphenicol is an antibiotic that is clinically useful for, and should be reserved for, serious infections caused by organisms susceptible to its antimicrobial effects when less potentially hazardous therapeutic agents are ineffective or contraindicated.

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Chloromycetin Drug Class and Mechanism

Chloramphenicol is bacteriostatic (that is, it stops bacterial growth). It functions by inhibiting peptidyl transferase activity of the bacterial ribosome, binding to A2451 and A2452 residues in the 23S rRNA of the 50S ribosomal subunit, preventing peptide bond formation. While chloramphenicol and the macrolide class of antibiotics both interact with the 50S ribosomal subunit, chloramphenicol is not a macrolide. Furthermore, their mechanisms are slightly different. While chloramphenicol directly interferes with substrate binding, macrolides sterically block the progression of the growing peptide.

Chloromycetin Uses

Because it functions by inhibiting bacterial protein synthesis, chloramphenicol has a very broad spectrum of activity: it is active against Gram-positive bacteria (including most strains of MRSA), Gram-negative bacteria and anaerobes.It is not active against Pseudomonas aeruginosa or Enterobacter species. It has some activity against Burkholderia pseudomallei, but is no longer routinely used to treat infections caused by this organism (it has been superseded by ceftazidime and meropenem). In the West, chloramphenicol is mostly restricted to topical uses because of the worries about the risk of aplastic anaemia. The original indication of chloramphenicol was in the treatment of typhoid, but the now almost universal presence of multi-drug resistant Salmonella typhi has meant that it is seldom used for this indication except when the organism is known to be sensitive. Chloramphenicol may be used as a second-line agent in the treatment of tetracycline-resistant cholera. Because of its excellent CSF penetration (far superior to any of the cephalosporins), chloramphenicol remains the first choice treatment for staphylococcal brain abscesses. It is also useful in the treatment of brain abscesses due to mixed organisms or when the causative organism is not known. Chloramphenicol is active against the three main bacterial causes of meningitis: Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae. In the West, chloramphenicol remains the drug of choice in the treatment of meningitis in patients with severe penicillin or cephalosporin allergy and GPs are recommended to carry intravenous chloramphenicol in their bag. In low income countries, the WHO recommend that oily chloramphenicol be used first-line to treat meningitis. Chloramphenicol has been used in the U.S. in the initial empirical treatment of children with fever and a petechial rash, when the differential diagnosis includes both Neisseria meningitidis septicaemia as well as Rocky Mountain spotted fever, pending the results of diagnostic investigations. Chloramphenicol is also effective against Enterococcus faecium, which has led to it being considered for treatment of vancomycin-resistant enterococcus. Although unpublished, recent research suggests that chloramphenicol could also be applied to frogs to prevent their widespread destruction from fungal infections

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Chloromycetin Side Effects

The most serious adverse effect of chloramphenicol is bone marrow depression. Serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia and granulocytopenia) are known to occur after the administration of chloramphenicol. An irreversible type of marrow depression leading to aplastic anemia with a high rate of mortality is characterized by the appearance weeks or months after therapy of bone marrow aplastia or hypoplasia. Peripherally, pancytopenia is most often observed, but in a small number of cases only one or two of the three major cell types (erythrocytes, leukocytes, platelets) may be depressed. A reversible type of bone marrow depression, which is dose related, may occur. This type of marrow depression is characterized by vacuolization of the erythroid cells, reduction of reticulocytes and leukopenia, and responds promptly to the withdrawal of chloramphenicol. An exact determination of the risk of serious and fatal blood dyscrasias is not possible because of lack of accurate information regarding 1) the size of the population at risk, 2) the total number of drug-associated dyscrasias, 3) the total number of non-drug associated dyscrasias.

Chloromycetin Pregnancy

Chloromycetin Overdose

Chloramphenicol sodium succinate must be hydrolyzed to its microbiologically active form and there is a big lag in achieving adequate blood levels compared with the base given IV. 'The oral form of chloramphenicol is readily absorbed and adequate blood levels are achieved and maintained on the recommended dosage. Patients started on IV chloramphenicol sodium succinate should be changed to the oral form as soon as practicable.

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