Chloramphenicol (Phenicol)

Chloramphenicol is an antibiotic useful for the treatment of a number of bacterial infections. This includes as an eye ointment to treat conjunctivitis. By mouth or by injection into a vein, it is used to treat meningitis, plague, cholera, and typhoid fever. Its use by mouth or by injection is only recommended when safer antibiotics cannot be used. Monitoring both blood levels of the medication and blood cell levels every two days is recommended during treatment.

Common side effects include bone marrow suppression, nausea, and diarrhea. The bone marrow suppression may result in death. To reduce the risk of side effects treatment duration should be as short as possible.  People with liver or kidney problems may need lower doses. In young children a condition known as gray baby syndrome may occur which results in a swollen stomach and low blood pressure.  Its use near the end of pregnancy and during breastfeeding is typically not recommended. Chloramphenicol is a broad-spectrum antibiotic that typically stops bacterial growth by stopping the production of proteins.

Chloramphenicol was discovered after being isolated from Streptomyces venezuelae in 1947. Its chemical structure was identified and it was first artificially made in 1949, making it the first antibiotic to be made instead of extracted from a micro-organism. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. It is available as a generic medication. The wholesale cost in the developing world of an intravenous dose is about US$0.40–1.90. In the United States an intravenous dose costs about $41.47

Therapeutic Indication

Typhoid fever and life threatening infections, particularly those caused by haemophilus influenza, where other antibiotics will not suffice. It is effective against tetracycline-resistant vibrios. It is also used in eye drops or ointment to treat bacterial conjunctivitis.

Eye drops or ointment

Before using chloramphenicol, tell you doctor if you're using other eye drops or ointment, or if you normally wear contact lenses. It's also important to speak to your doctor if you have:
  • any problems with your eyesight, or severe eye pain
  • swollen eyes, and a rash on your face or head
  • a cloudy eye
  • unusual looking pupils - irregular size, dilated (bigger than normal), or not reacting to light
  • had a recent eye injury, or something in your eye
  • recently had conjunctivitis
  • dry eye syndrome (when your eyes don't produce enough tears)
  • glaucoma
  • had eye surgery or laser treatment in the last 6 months

Ear drops

Before using chloramphenicol ear drops, tell your doctor if you:

  • have a perforated (burst) eardrum
  • are allergic to polyethylene glycol (an ingredient used in some medicines and cosmetics, and found in some foods)
How and when to use it

Chloramphenicol comes in different strengths. How you apply the medicine depends on what you're taking it for and whether you're using the eye drops, eye ointment or ear drops.

If you're using 0.5% chloramphenicol eye drops, put one drop into the affected eye every 2 hours (during waking hours) for the first 2 days. Then every 4 hours for the next 3 days, or as your doctor advises.

If you're using 1% chloramphenicol eye ointment, apply it to the affected eye every 3 hours (during waking hours). Do this 3 to 4 times a day, or as your doctor advises.

With more severe infections, your doctor may recommend using eye ointment at bedtime and eye drops during the day. This is because the ointment sticks to the surface of the eye and eyelid and works while you sleep. The eye drops allow you to get on with your day as normal, as they don't affect your eyesight.

If you're using 5% or 10% chloramphenicol ear drops, put 3 drops into the affected ear 2 to 3 times a day, or as your doctor advises.

To use the medicine:

  • always wash your hands before (and after) using chloramphenicol - this prevents you from passing the infection to the other eye or ear
  • remove the cap just before using your medicine and replace it as soon as you've finished
  • do not touch the nozzle of the bottle or tube with your fingers
  • make sure the nozzle doesn't touch your eye or ear, or your skin
  • use a mirror to help you see what you are doing
  • tilt your head back or to the side to put drops in your eyes or ears

How to apply the eye drops

Gently pull down your lower eyelid with a clean finger and tilt your head back. Hold the bottle over your eye and allow a single drop to fall into the space between your lower lid and your eye. Close your eye for a few minutes. Wipe away any extra liquid with a clean tissue.

How to apply the eye ointment

Gently pull down your lower eyelid with a clean finger and tilt your head back. Hold the tube with the nozzle close to your eye and gently squeeze about 1 centimetre of ointment into the space between your lower lid and your eye. Close your eye for a few minutes.

How to apply the ear drops

Tilt your head and bring the tube up to the affected ear, with the nozzle close to your ear hole. Squeeze the drops into your ear. If you can, lie down for at least 10 minutes afterwards. Turn your head to one side, so your affected ear is towards the ceiling. After this, put some cotton wool in your ear.

How long to use it for

Eye drops - use the drops until the eye appears normal and for 2 days afterwards. Do not use them for more than 5 days, unless your doctor tells you to. This is because your eyes can become more sensitive or you could get another eye infection.

Eye ointment - use the ointment until the eye appears normal and for 2 days afterwards. Do not use it for more than a week, unless your doctor tells you to.

Ear drops - use the drops for up to a week. Avoid using the medicine for longer than this unless your doctor tells you to. This is because your ears can become more sensitive or you could get another ear infection.

When you've finished your treatment, throw away any leftover eye drops, eye ointment or ear drops.

Mechanism of action

Chloramphenicol is a bacteriostatic by inhibiting protein synthesis. It prevents protein chain elongation by inhibiting the peptidyl transferase activity of the bacterial ribosome. It specifically binds 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 ribosomes, chloramphenicol is not a macrolide. It directly interferes with substrate binding, whereas macrolides sterically block the progression of the growing peptide.

Posology and method of administration

Normal dose for adults and elderly: 50 mg/kg body weight daily in 4 divided doses. For severe infections (meningitis, septicemia) this dose may be doubled initially, but it must be reduced as soon as clinically practical. Not recommended for children
Typhoid fever and life threatening infections
Image from Wikipedia


Contraindications

Known hypersensitivity or toxic reaction to chloramphenicol or to any of the excipients. Chloramphenicol is contraindicated in prophylaxis or treatment of minor infections; during active immunization and in porphyria patients. Chloramphenicol is contraindicated in patients taking drugs liable to depress bone marrow function. Chloramphenicol must not be used in breast-feeding mothers and during pregnancy or labour, due to a risk of foetal infant damage (Grey baby syndrome)

Drug antagonistic

Chloramphenicol is antagonistic with most cephalosporins and using both together should be avoided in the treatment of infections. 

Special warning and precautions for use

Chloramphenicol should only be used if other treatments are ineffective and its use should always be carefully monitored. Dose reduction and plasma level monitoring may be required. Dose reduction and plasma level monitoring may be required in patients with hepatic or renal impairment; in the elderly and in patients concurrently treated with interacting drugs. Periodic blood testing should be conducted during prolonged or repeated treatment. Chloramphenicol should be discontinued if s significant detrimental effect is seen.

Pregnancy and lactation

The use of chloramphenicol is contraindicated as the drug crosses the placenta and is excreted in breast milk.

Effects on ability to drive and use machine
No significant effect on driving ability

Undesirable effects

The most serious undesirable effects that may arise are:
  • A reversible dose related bone marrow depression
  • An irreversible aplastic anemia with an estimated frequency between 1/4000 and 1/100000. Other undesirable effects are
  • Increasing in bleeding time
  • Immune system disorders
  • Hypersensitivity reactions including allergic skin reactions
  • Optic neuritis leading to blindness
  • Ototoxicity
  • Acidotic cardiovascular collapse
  • Nausea, vomiting, glossitis, stomatitis, diarrhea, enterocolitis
  • Pregnancy, puerperium and perinatal conditions



“Gray” syndrome, particulary in the newborn, which appears to be related to excessively high plasma levels. The Gray baby syndrome consists of abdominal distension, pallid cyanosis, vomiting, pregressing to vasomotor collapse, irregular respiration and death within a few hours of onset of symptoms. (These symptoms are thought to be dose related and rapid clearance of chloramphenicol has been associated with recovery)

Overdose

Where adverse effects show signs of developing administration must be stopped immediately and treatment is mainly supportive. If an allergy develops, oral antihistamines may be used. In severe overdose e.g. Gray baby syndrome, there is a need for a rapid reduction in plasma levels and it has been reported that resins haemoperfusion (XAD-4) substantially increases chloramphenicol clearance

Pharmacodynamics properties

Chloramphenicol is a broad spectrum antibiotic acting by interfering with bacterial protein synthesis. The most important action on the body tissue is the adverse one of bone marrow depression. There is significant plasma protein binding and the drug is largely inactivated in the liver

Pharmacokinetic properties

Chloramphenicol is readily absorbed from the G.I. tract. Particle size may affect rate of absorption, but will not affect total absorption.  Significant serum levels observable 30 minutes after ingestion and half-life may be 2-5 hours. Chloramphenicol is widely distributed in body tissues and fluids. It is found in cerebro-spinal fluid. It crosses the placental barrier and diffuses into breast milk. There is significant plasma protein binding (up to 60%). Excretion is mainly in the urine and largely inactivated in the liver


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