Chloramphenicol

DEFINITION: Broad-spectrum antibiotic used to combat harmful bacteria and organisms in humans and animals

Because of chloramphenicol’s potential to cause very serious side effects, the US Food and Drug Administration has restricted the drug’s use for humans and does not approve its use at all for animal feed or food-producing animals.

Chloramphenicol (CHPC) is known by many other names, including the trade name Chloromycetin. CHPC is an effective antibiotic, particularly in those cases that require penetration through purulent material (which either contains or discharges pus) to reach the infecting bacteria, as occurs in infections of pneumonia. It is also a good choice for otherwise intractable infections involving the eye, the nervous system, and the prostate gland. The more efficient penetration of CHPC into cells compared to other antibiotics increases its advantage in killing intracellular parasites, such as chlamydia, mycoplasma, and rickettsia.

The high acidity of CHPC is believed to contribute to its ability to penetrate necrotic material and cellular membranes. It kills bacteria by interfering with the protein-manufacturing systems occurring in the ribosomes of organisms. The mode of attack is unique in that reptilian, mammalian, and avian ribosomes are unaffected. In addition, the antibiotic does not destroy all the bacteria in infected tissue. Only highly susceptible bacteria are destroyed, with the remainder merely being inhibited from reproducing. This is an advantage because the inactive residual bacteria allow B cells in the immune system to develop an immune response to the bacteria. The result is akin to the use of inactive bacterial vaccinations in fighting disease.

Discovered in 1947, CHPC was released for public use in 1949. In 1959 researchers reported cardiovascular collapse and death in three infants after they were treated with CHPC. All exhibited a gray pallor (called gray syndrome) prior to death. A more complete study found that of thirty-one premature infants treated with the drug, 45 percent died exhibiting gray syndrome, while only 2.5 percent of a group of untreated infants died. The common feature among the fatal cases was the high level of the drug used in their treatment: 230 to 280 milligrams of CHPC per kilogram of body weight per day, five to ten times what later became the recommended dose.

CHPC was subsequently found to interfere with the energy-producing capacity of mitochondria in those organs with a high rate of oxygen consumption; the heart, liver, and kidneys are at particular risk. People who are unable to detoxify the drug efficiently—such as infants—are particularly susceptible to the accumulation of toxic levels in the blood.

CHPC is known to have other negative side effects, including nausea, diarrhea, and loss of appetite. In more severe cases, blood dyscrasias may result. This is a condition in which abnormal blood cells are produced while normal blood cell production is blocked because of interaction of CHPC with the patient’s bone marrow. Patients who take CHPC orally may develop fatal anemia. Those who recover from such blood abnormalities resulting from the antibiotic have a high incidence of leukemia. Unfavorable interactions with other drugs—including phenytoin (used to treat heart disease), primidone (used for seizures), and cyclophosphamide (used in chemotherapy)—have also been noted. In addition, the antibiotic can interfere with vaccinations and is a potential carcinogen.

These side effects occur not only in humans but also in other animals. CHPC may build up to toxic levels in young animals because their liver detoxification mechanisms are not as well developed or efficient as those of adults. The antibiotic therefore is not approved for administration to food animals in the United States, as these animals may be ingested by the young. Ingestion of CHPC by pregnant or lactating creatures must be avoided for similar reasons. Loss of appetite in dolphins, whales, and California sea lions has also been a noted side effect. Environmentalists and others have raised concerns that the antibiotic may be used in some agricultural settings outside the United States, putting humans at risk. In 2010, for example, the US Food and Drug Administration seized a shipment of honey from China that was found to be contaminated by CHPC; the bees that produced the honey had been fed the antibiotic as a measure to control certain diseases in the bee population.

Although the serious side effects of CHPC are rare, a study by the California Medical Association in 1967 found the occurrence of cases in humans to be as high as one per twenty-four thousand applications, depending on dose. The accumulation of such data was sufficient for the use of CHPC to be restricted, in the 1960s, to life-threatening cases for which there is little alternative treatment.

Bibliography

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"Chloramphenicol." Merck Manuals. Merck, Aug. 2013. Web. 22 Jan. 2015.

"Chloramphenicol (Ophthalmic Route)." Mayo Clinic, 1 June 2024, www.mayoclinic.org/drugs-supplements/chloramphenicol-ophthalmic-route/side-effects/drg-20062728?p=1. Accessed 15 July 2024.

Forrest, Graeme N., and David W. Oldach. “Chloramphenicol.” Infectious Diseases. Ed. Sherwood L. Gorbach, John G. Bartlett, and Neil R. Blacklow. 3rd ed. Philadelphia: Lippincott, 2004. Print.

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