Chloramphenicol, Discovery, Action, Uses, Side effects, Contraindications and Brands

Introduction

Chloramphenicol is an antibiotic medication known as phenicols. It is effective against a wide range of bacteria commonly used to treat various bacterial infections, including respiratory tract infections, skin infections, eye infections, and certain types of meningitis.

Its broad-spectrum activity against a wide range of bacteria made it invaluable in combating life-threatening infections, especially before the development of many other antibiotics.

Chloramphenicol’s ability to penetrate tissues and cross the blood-brain barrier made it particularly useful in treating infections of the central nervous system, including meningitis. It has also been widely used in the treatment of typhoid fever, rickettsial infections, and various other bacterial diseases.

Despite its effectiveness, the use of chloramphenicol has declined over the years due to concerns about its potential side effects, particularly the risk of bone marrow suppression. However, it remains an important antibiotic in certain situations where other treatment options are limited, and it continues to be included in the World Health Organization’s List of Essential Medicines.

Discovery

The discovery of chloramphenicol dates back to 1947 when researchers at Parke-Davis, a pharmaceutical company (now part of Pfizer), isolated the compound from a soil bacterium called Streptomyces venezuelae. This bacterium was found in soil samples obtained from Venezuela.

The discovery of it was a significant breakthrough in the field of medicine as it marked the identification of one of the first broad-spectrum antibiotics. Its ability to effectively inhibit the growth of a wide range of bacteria made it a valuable tool in the treatment of various infectious diseases, including life-threatening ones.

Following its discovery, chloramphenicol underwent extensive testing to assess its safety and efficacy in treating bacterial infections. It was found to be highly effective against many bacterial species and became widely used in clinical practice.

Mechanism of Action

Chloramphenicol works by inhibiting the synthesis of bacterial proteins, which are essential for bacterial growth and survival. It does this by binding to the 50S subunit of the bacterial ribosome, which is responsible for protein synthesis. This binding prevents the assembly of amino acids into proteins, effectively stopping the growth and reproduction of the bacteria.

Chloramphenicol enters the bacterial cell and binds to the 50S subunit of the ribosome. This binding causes a conformational change in the ribosome, preventing the attachment of transfer RNA (tRNA) to the ribosome. Without tRNA, amino acids cannot be assembled into proteins.

Protein synthesis is halted, and the bacterial cell cannot grow or reproduce. The bacterial cell eventually dies due to its inability to produce essential proteins. its mechanism of action is selective for bacterial cells, as it binds specifically to the bacterial ribosome and not to the ribosomes of mammalian cells. This makes it an effective antibiotic against a wide range of bacterial infections.

Various Forms

Chloramphenicol is available in various forms, including:

Capsules: Oral capsules containing chloramphenicol palmitate or chloramphenicol succinate.
Tablets: Oral tablets containing chloramphenicol palmitate or chloramphenicol succinate.
Injectable solutions: Chloramphenicol sodium succinate for intravenous or intramuscular injection.
Eye drops: Chloramphenicol solution for topical application in the eye.
Eye ointment: Chloramphenicol ointment for topical application in the eye.
Ear drops Chloramphenicol solution for topical application in the ear.
Topical cream: Chloramphenicol cream for topical application on the skin.
Topical powder: Chloramphenicol powder for topical application on the skin.

Chloramphenicol Uses

Chloramphenicol is used to treat various bacterial infections due to its broad-spectrum antibiotic activity. Some common uses of chloramphenicol include:

Respiratory Tract Infections

Chloramphenicol is used to treat respiratory tract infections caused by susceptible bacteria. This includes infections such as pneumonia, bronchitis, and sinusitis.

Skin and Soft Tissue Infections

Chloramphenicol is effective against bacterial skin infections, including cellulitis, abscesses, and infected wounds. It is used topically as well as systemically, depending on the severity of the infection.

Eye Infections

Chloramphenicol is available in eye drop or ointment form and is commonly used to treat bacterial conjunctivitis (pink eye) and other eye infections caused by susceptible bacteria.

Central Nervous System Infections

Chloramphenicol penetrates the blood-brain barrier, making it effective in treating central nervous system infections such as bacterial meningitis. It is used when other antibiotics are not suitable or available for the treatment of these serious infections.

Typhoid Fever

Historically, chloramphenicol is used to treat typhoid fever caused by Salmonella typhi. However, due to concerns about antibiotic resistance, it is not commonly used as a first-line treatment and is reserved for cases where other antibiotics are not effective.

Rickettsial Infections

Chloramphenicol is effective against infections caused by Rickettsia bacteria, including Rocky Mountain spotted fever and typhus fever. It is used to treat these potentially severe infections when appropriate.

Other Infections

It is also used to treat other bacterial infections, including those caused by anaerobic bacteria and certain Gram-negative and Gram-positive organisms. It is particularly useful in cases where the infecting bacteria are susceptible to chloramphenicol and other treatment options are limited.

Chloramphenicol Side effects

Chloramphenicol, while effective in treating bacterial infections, can also cause side effects. Some of the potential side effects  include:

Bone Marrow Suppression

One of the most serious side effects of chloramphenicol is bone marrow suppression, which can lead to a decrease in the production of red blood cells, white blood cells, and platelets. This results in anemia, leukopenia (low white blood cell count), and thrombocytopenia (low platelet count). Bone marrow suppression is dose-dependent and reversible upon discontinuation of the drug, but it can be life-threatening in severe cases.

Gray Syndrome

In newborns and premature infants, chloramphenicol causes a condition called “gray syndrome,” characterized by abdominal distension, vomiting, pallor, cyanosis, and cardiovascular collapse. This is due to the immature liver’s inability to metabolize chloramphenicol properly, leading to toxic levels of the drug in the bloodstream.

Allergic Reactions

Some individuals experience allergic reactions to chloramphenicol, which can range from mild skin rashes to severe allergic reactions such as anaphylaxis. Symptoms of an allergic reaction may include rash, itching, hives, swelling of the face, lips, or tongue, difficulty breathing, and dizziness.

Gastrointestinal Disturbances

Common gastrointestinal side effects of chloramphenicol include nausea, vomiting, diarrhea, and abdominal pain. These symptoms are usually mild and resolve upon discontinuation of the drug.

Hematologic Effects

In addition to bone marrow suppression, chloramphenicol can also cause other hematologic effects, such as aplastic anemia, agranulocytosis, and hemolytic anemia. These are rare but serious side effects that require immediate medical attention if they occur.

Neurological Effects

Rarely, chloramphenicol may cause neurological side effects such as headache, confusion, delirium, and optic neuritis. These effects are more common with prolonged use or high doses of the drug.

Liver Toxicity

Chloramphenicol has been associated with liver toxicity, including hepatotoxicity and cholestatic jaundice. Patients with pre-existing liver disease or liver dysfunction may be at increased risk of developing liver-related side effects.

Dosage

The typical dosages for different formulations and indications:

Oral Chloramphenicol

• For adults: The usual dose is 500 mg to 1 gram every 6 hours. In severe infections, higher doses may be given, up to 4 grams daily.
• For children: The dose is based on body weight and is typically 25 to 50 mg/kg/day divided into 4 doses.

Intravenous (IV) Chloramphenicol

• For adults: The usual dose is 1 to 3 grams daily, divided into 3 to 4 doses.
• For children: The dose is based on body weight and is typically 25 to 50 mg/kg/day divided into 4 doses.

Eye Drops or Ointment

• For bacterial conjunctivitis: Apply 1 to 2 drops of 0.5% chloramphenicol eye drops into the affected eye(s) every 2 to 6 hours, depending on the severity of the infection.
• For other eye infections: Follow the dosage instructions provided by a healthcare professional.

Contraindications

Chloramphenicol is not used in certain situations due to the risk of serious adverse effects. Contraindications to the use of chloramphenicol include:

Hypersensitivity

Individuals who have a known hypersensitivity or allergic reaction to chloramphenicol or any of its components should not use the medication.

Gray Syndrome

Chloramphenicol is contraindicated in newborns, particularly premature infants, due to the risk of developing “gray syndrome.” This condition is characterized by symptoms such as abdominal distension, vomiting, pallor, cyanosis, and cardiovascular collapse. Newborns have immature liver function, which leads to toxic levels of chloramphenicol in the bloodstream and increases the risk of adverse effects.

Bone Marrow Suppression

Patients with a history of bone marrow suppression or blood dyscrasias (abnormalities in blood cell production) should avoid chloramphenicol due to the risk of exacerbating these conditions. Chloramphenicol can suppress bone marrow function, leading to aplastic anemia, leukopenia, and thrombocytopenia.

Liver Dysfunction

Chloramphenicol is used with caution or avoided in patients with pre-existing liver disease or impaired liver function. Hepatic dysfunction impairs the metabolism and elimination of chloramphenicol, leading to increased plasma concentrations and potential toxicity.

Renal Dysfunction

Patients with severe renal impairment require dosage adjustments or avoidance of chloramphenicol due to its renal excretion. Accumulation of it occurs in patients with impaired renal function, increasing the risk of adverse effects.

Pregnancy and Lactation

Chloramphenicol crosses the placenta and is excreted in breast milk. While there is limited data on the safety of chloramphenicol use during pregnancy and lactation, it should generally be avoided unless the potential benefits outweigh the risks and no safer alternatives are available.

Use with Caution in Elderly

Chloramphenicol is used with caution in elderly patients, who may be more susceptible to adverse effects such as bone marrow suppression and hepatic dysfunction.

Chloramphenicol Brands

Here are some brands of chloramphenicol available in Pakistan:

Dexachlor

Manufacturer: Dexa Laboratories of Biomolecular Sciences (Pvt) Ltd.

Optachlor

Manufacturer: The ACME Laboratories Ltd.

Methachlor

Manufacturer: Medinex Laboratories (Pvt) Ltd.

Chloromycetin

Manufactured by Pfizer Pakistan Limited.

Clogen

Manufactured by PharmEvo (Pvt) Ltd.

Hlorafen

Manufactured by Novamed Pharmaceuticals (Pvt) Ltd.