Chloramphenicol, a broad-spectrum antibiotic, was first isolated from Streptomyces venezuelae in 1947. In 1949, it became the first antibiotic to be produced synthetically on an industrial scale, thanks to the efforts of chemists like Mildred Rebstock at Parke-Davis Initially, it was widely used to treat serious infections such as typhoid fever and meningitis. However, its use became highly restricted due to the discovery of serious and potentially fatal side effects, including aplastic anemia.
Chloramphenicol is a broad-spectrum antibiotic employed in treating various serious bacterial infections. It is commonly used topically as an eye ointment to manage conjunctivitis. Systemic administration, either orally or via intravenous injection, is reserved for severe conditions such as meningitis, plague, cholera, and typhoid fever.
BRAND NAMES
Chloromycetin: A well-known brand, also available as Chloromycetin Ophthalmic for eye infections.
Chloroptic: A brand of chloramphenicol used for ophthalmic (eye) conditions.
Paraxin: A brand offered in various forms, including capsules, suspensions, and ear drops.
Ak-Chlor: An ophthalmic brand used for bacterial conjunctivitis.
Ocu-Chlor: Another brand for eye infections, which is an ophthalmic solution.
Isopto Fenicol: A Canadian brand of ophthalmic chloramphenicol.
MECHANISM OF ACTION
Target: Chloramphenicol works by inhibiting bacterial protein synthesis.
Ribosomal binding: It binds reversibly to the 50S ribosomal subunit of bacteria, which prevents the formation of peptide bonds and stops the growing peptide chain.
Effect: The drug is primarily bacteriostatic, meaning it stops bacteria from multiplying, but it can be bactericidal (kill bacteria) at high concentrations.
PHARMACOKINETICS:
Absorption
Chloramphenicol is readily absorbed from the gastrointestinal tract when administered orally, with an approximate bioavailability of 80%. It may also be absorbed systemically after ophthalmic and otic administration. The peak serum concentration after an oral dose typically occurs within 1 to 3 hours.
Distribution
The drug is widely distributed throughout the body, including the cerebrospinal fluid (CSF), liver, kidneys, and ocular tissues. In patients with uninflamed meninges, CSF concentrations range from 21% to 50% of plasma levels, and in those with inflamed meninges, concentrations can reach 45% to 89%. Chloramphenicol crosses the placenta and is excreted into breast milk. Approximately 60% of the drug binds to plasma proteins.
Metabolism
Chloramphenicol is primarily metabolized in the liver through conjugation with glucuronic acid, forming inactive metabolites.
Excretion
Approximately 30% of an intravenous dose is excreted unchanged in the urine, with the remainder eliminated as inactive metabolites. Small amounts are excreted in the bile and feces. The elimination half-life in adults with normal renal and hepatic function ranges from 1.5 to 4 hours. In neonates and infants, the half-life is significantly prolonged due to immature metabolic pathways.
PHARMACODYNAMICS
Chloramphenicol is a broad-spectrum antibiotic that primarily functions as a bacteriostatic agent by inhibiting bacterial protein synthesis. Its pharmacodynamics encompass its mechanism of action, antimicrobial spectrum, and effects on bacterial and host cells.
ADMINISTRATION
Chloramphenicol is a potent antibiotic available in various formulations, including intravenous (IV) injection, eye and ear drops, and ointment. While oral capsules were once used, they have been withdrawn from the U.S. market due to the significant risk of fatal aplastic anemia associated with this route of administration. Consequently, systemic use—whether IV or oral—is now reserved for severe infections where other, safer antibiotics are ineffective or contraindicated. In countries like the United States, oral chloramphenicol is not approved for use in humans
DOSAGE AND STRENGTH
Oral Administration (Capsules and Suspension): Oral chloramphenicol is commonly prescribed for severe systemic infections such as typhoid fever and meningitis. The typical dosage is 12.5 mg per kg of body weight every 6 hours, with capsules available in strengths of 250 mg and 500 mg. It's crucial to adhere to the prescribed dosage and complete the full course of treatment to ensure effectiveness.
Intravenous (IV) Administration: IV chloramphenicol is utilized for serious infections requiring rapid therapeutic levels. The standard dose is 12.5 mg per kg of body weight every 6 hours, with a maximum of 1 gram per dose. For severe infections, the dose may be increased to 50–100 mg/kg/day, divided every 6 hours, not exceeding 4 grams per day. Reconstitute the vial with 10 mL of sterile water or 5% dextrose to achieve a concentration of 100 mg/mL.
Ophthalmic (Eye) Preparations: Chloramphenicol eye drops and ointments are used to treat superficial bacterial eye infections like conjunctivitis. The eye drop solution is typically a 0.5% concentration, while the ointment is commonly a 1% formulation. Dosage involves applying one drop every 1 to 4 hours for the first 48 hours, then adjusting as directed by a healthcare professional.
DRUG INTERACTIONS
Chloramphenicol is a potent antibiotic with a broad spectrum of activity, but its use is associated with several significant drug interactions that can affect its efficacy and safety profile.
Anticoagulants: Chloramphenicol may depress plasma prothrombin activity, increasing the risk of bleeding in patients on anticoagulant therapy. Dose adjustments of anticoagulants may be necessary when coadministered with chloramphenicol.
Penicillin: Chloramphenicol may interfere with the bactericidal action of penicillin. Avoid coadministration of chloramphenicol with penicillin to ensure optimal therapeutic effects.
Antacids and Iron Preparations: Taking chloramphenicol with antacids containing aluminum, calcium, or magnesium, bismuth subsalicylate, or iron-containing preparations may impair its absorption and decrease its efficacy. To avoid this, separate dosing of chloramphenicol from antacids and iron preparations.
FOOD INTERACTIONS
Iron Supplements and Multivitamins: Taking chloramphenicol with iron supplements or multivitamins containing iron can decrease its absorption, reducing its effectiveness. It's recommended to take these on an empty stomach, at least one hour before or two hours after meals.
Dairy Products: While specific interactions between chloramphenicol and dairy products are not well-documented, it's advisable to avoid consuming large amounts of dairy close to the time of taking the medication to prevent any potential interference with absorption.
CONTRAINDICATIONS
Chloramphenicol is an antibiotic that is typically reserved for serious infections when other, safer medications are ineffective or contraindicated. Due to the risk of severe side effects, there are several contraindications for its use.
Key contraindications
Hypersensitivity or allergic reactions: Do not use chloramphenicol in patients with a history of a previous hypersensitivity, toxicity, or allergic reaction to the drug or any component of the formulation.
Pre-existing blood dyscrasias: This includes conditions like aplastic anemia, hypoplastic anemia, thrombocytopenia, and granulocytopenia. This is because chloramphenicol is known to cause serious and potentially fatal blood problem
SIDE EFFECTS
Common Side Effects
Gastrointestinal Issues: Nausea, vomiting, and diarrhea are frequently reported.
Neurological Symptoms: Headache and confusion may occur.
Skin Reactions: Rashes and mouth sores are possible.
Serious Side Effects
Aplastic Anemia: A rare but serious condition where the bone marrow fails to produce enough blood cells, leading to fatigue, increased risk of infections, and unusual bleeding or bruising.
Gray Baby Syndrome: A potentially fatal condition in newborns characterized by vomiting, abdominal distension, grayish skin, and respiratory distress.
Optic Neuritis: Inflammation of the optic nerve, which can lead to vision problems.
Peripheral Neuropathy: Symptoms include weakness, numbness, or tingling sensations in the hands and feet.
Bone Marrow Suppression: Can result in decreased red blood cells, white blood cells, and platelets, increasing the risk of infections and bleeding.
Severe Allergic Reactions: Signs include swelling of the face, lips, or throat, difficulty breathing, and skin rashes.
OVER DOSE
An overdose of the antibiotic chloramphenicol can cause severe and potentially fatal toxicity, affecting the bone marrow and cardiovascular system. The specific symptoms and severity depend on age, dosage, and underlying health conditions.
TOXICITY
Chloramphenicol toxicity includes severe side effects like fatal aplastic anemia and "gray baby syndrome" in infants. Due to these risks, its use is restricted to serious infections where other antibiotics are ineffective.
