This article provides a note on chloramphenicol.
Chloramphenicol is a highly active, broad spectrum antibiotic with excellent pharmacokinetic properties.
Source:
It is obtained from Actinomyces venezuelae. It is the first antibiotic to be synthesised commercially.
Chemistry:
It is a derivative of di-chloroacetic acid and contains nitrobenzene moiety. It is a white or grey or yellow fine crystalline powder. It is more stable than oxytetracycline and chlortetracycline.
Chloramphenicol has a bitter taste and poorly soluble in water. Hence, it is not fit for oral administration. Chloramphenicol plamitate is tasteless and hence preferred for oral administration. It is hydrolysed in the gastrointestinal tract to release the active drug.
Mechanism of Action:
It is a bacteriostatic antibiotic that interferes with protein synthesis. It binds to the 50S ribosomal subunit of the 70S ribosome, preventing peptide bond formation by interfering with the amino acid containing end of the tRNA to the 50S ribosomal subunit. It also inhibits mitochondrial protein synthesis in mammalian bone marrow cells.
Antimicrobial Activity:
Effective against a variety of pathogens which includes Staphylococci, Salmonella, Pasteurella, Bordetella, Haemophilus, Coliform organisms, Chlamydia and Rickettisa. It is the second drug of choice for anaerobic bacterial infection.
Pharmacokinetics:
In monogastric animals and pre-ruminant calves chloramphenicol is well absorbed from the gastrointestinal tract. Oral administration provides antibiotic concentrations in blood comparable with or better than the intramuscular or subcutaneous administrations.
In ruminants, the drug is inactivated in the rumen. The drug is also absorbed per rectum. About 45% of the drug in the blood is bound to plasma proteins. The drug can pass cellular barriers readily and effective concentrations are achieved in most tissues and body fluids including the cerebrospinal fluid and aqueous humor.
It is one of the antibiotics which can cross the blood brain barrier in the absence of meningitis. Chloramphenicol is of clinical importance because the drug will cross the placental barrier and will not get metabolised in the foetal liver. It also enters into the pleural, peritoneal and synovial cavities.
Although, the drug is excreted in milk, for the treatment of mastitis the drug is administered intramammarily. Chloramphenicol, when administered as chloramphenicol sodium succinate achieves a higher concentration in blood, but to be active, it should be hydrolysed to the parent compound.
Chloramphenicol is lipophilic and the apparent volume of distribution is large. Hepatic metabolism is the principal process of elimination especially glucuronidation. Hence, in cats the drug is not metabolised readily because of the failure of glucuronidation. A large proportion of the drug is excreted in urine as inactive metabolites and hence is not useful in treating urinary infections.
Resistance:
Resistance to chloramphenicol results from:
1. Plasmid mediated bacterial production of chloramphenicol acetyl transferase.
2. Reduced target sites on the ribosome.
3. Reduced permeability of the bacteria to the drug.
Chloramphenicol acetylase is a plasmid mediated enzyme responsible for the occurrence of resistance. So it is transmitted from one organism to another of the same species or different species. Since this drug is useful for typhoid in human beings, it should be used with discretion in animals so as to reduce the chances of resistance.
Drug Interaction:
Generally, chloramphenicol should not be used concurrently with bactericidal drugs in treating infections when host defences are poor. It should not be used with penicillin G, lincosamides and macrolides. If it is used with ionophores severe muscle degeneration can occur in broilers.
Chloramphenicol is a potent inhibitor of microsomal enzymes. So it prolongs the duration of action of many drugs administered along with it like phenobarbital, NSAIDs and coumarins. Since the drug suppresses the immune response it should not be used during vaccination.
Chloramphenicol also delays the response of anaemia to iron, folic acid and vitamin B12. Aqueous solution of chloramphenicol sodium succinate should not be mixed with other preparations before administration because of a high incidence of incompatibility.
Toxicity and Adverse Reactions:
Chloramphenicol causes bone marrow toxicity.
This toxicity can be of two types:
1. Dose dependent reversible suppression of bone marrow activity. This occurs when the dose is high.
2. Small doses can cause irreversible bone marrow depression leading to aplasia and fatal anaemia. A few cases of anaemia has been reported after exposure to chloramphenicol in the form of ophthalmic ointment or while handling. Hence, the use of chloramphenicol is banned in food producing animals.
Anaphylaxis, vomiting and diarrhoea have occasionally been reported in dogs and cats.
Administration:
This drug is available for oral and parenteral use. For oral use chloramphenicol is used as the free base or palmitate ester. For parenteral use chloramphenicol is available as free base or as sodium succinate. It is also available for ophthalmic use and topical application. Excessive topical application may delay wound healing.
Clinical Application:
Chloramphenicol is used in the treatment of systemic salmonellosis, deep infection of the eye and for the treatment of meningitis. Chronic respiratory infections, bacterial meningeoencephlitis, brain abscesses, ophthalmitis and intraoccular infection, podo dermatitis, dermal infections and otitis externa are the other conditions for which chloramphenicol can be used.
Effect on Laboratory Tests:
Chloramphenicol causes elevated alkaline phosphatase levels and may increase prothrombin times. Decrease in white blood cells and thrombocyte count may also be seen. A false glucosuria test is possible.
Thiamphenicol:
It is a derivative of chloramphenicol with a similar spectrum of activity without causing bone marrow depression.
Florphenicol:
It is an analogue of thiamphenicol with a greater spectrum of activity than chloramphenicol.