Chloramphenicol is a broad-spectrum antibiotic known for its effectiveness against a wide range of bacteria. Despite its potent antibacterial action, its use has become highly restricted due to the potential for serious side effects.
How Chloramphenicol Fights Infections
Chloramphenicol works by inhibiting bacterial protein synthesis, a process fundamental for bacterial growth and multiplication. It achieves this by binding specifically to the 50S ribosomal subunit of bacterial ribosomes, preventing the formation of peptide bonds between amino acids. This disruption halts the elongation of the bacterial polypeptide chains, thereby stopping protein production.
The drug is generally considered bacteriostatic, meaning it stops bacterial growth rather than directly killing bacteria. However, against certain susceptible organisms like Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae, it can be bactericidal at higher concentrations. Chloramphenicol is lipid-soluble, allowing it to easily diffuse through bacterial cell membranes to reach its target within the cell.
When Chloramphenicol is Prescribed
Chloramphenicol is reserved for specific, often severe and life-threatening bacterial infections where other, safer antibiotics are ineffective, not tolerated, or contraindicated.
It is used for:
- Serious bacterial meningitis, especially when caused by Haemophilus influenzae, Neisseria meningitidis, or Streptococcus pneumoniae, or in patients with penicillin allergies. Its ability to penetrate the cerebrospinal fluid effectively makes it suitable for these brain and spinal cord infections.
- Certain rickettsial infections, such as Rocky Mountain spotted fever, particularly if doxycycline is unavailable or ineffective.
- Severe eye infections like bacterial conjunctivitis, often used topically as eye drops or ointment.
- Typhoid fever and other Salmonella infections, especially when resistance to other drugs is present.
- Conditions like plague and cholera.
Understanding Potential Side Effects
The most serious and potentially fatal side effect associated with chloramphenicol is aplastic anemia, a rare condition where the bone marrow fails to produce enough new blood cells. This irreversible condition can occur even after short-term or topical use and may manifest weeks or months after treatment has stopped. Symptoms can include unusual tiredness or weakness, easy bruising, increased risk of infections, and pale skin.
A more common, dose-related, and reversible type of bone marrow suppression can also occur. This suppression typically resolves after the drug is discontinued. Regular blood tests, including complete blood counts, are recommended during treatment to monitor for these changes.
In infants, especially premature babies, chloramphenicol can cause a serious condition known as “Gray Baby Syndrome”. This occurs because young infants have underdeveloped liver enzymes that struggle to metabolize the drug efficiently, leading to its accumulation in the body. Symptoms, which typically appear 2 to 9 days after starting the medication, include vomiting, poor feeding, abdominal distension, hypothermia, irregular respiration, and a distinct ashen-gray skin discoloration. If not promptly addressed by discontinuing the antibiotic, this syndrome can lead to low blood pressure, cardiovascular collapse, and can be fatal.
Less severe, but more common, side effects include gastrointestinal disturbances such as nausea, vomiting, and diarrhea. Patients may also experience oral or vaginal thrush due to the disruption of normal bacterial balance. Other reported side effects include headaches, confusion, and peripheral neuropathy, characterized by tingling or numbness in the extremities.
Important Considerations and Administration
Chloramphenicol can be administered orally, intravenously, or topically as eye drops or ointment. Oral administration is well-absorbed, while intravenous injection is often reserved for more serious systemic infections.
Dosage considerations require careful adjustment, particularly in patients with impaired liver or kidney function, as these organs are involved in the drug’s metabolism and excretion. Neonates and children under four years old also require close monitoring and dosage adjustments due to differences in metabolic maturity. Therapeutic plasma levels are generally aimed at 10-20 µg/mL, with levels above 40 µg/mL considered potentially toxic.
Chloramphenicol is contraindicated in newborns, pregnant women, and breastfeeding mothers. It should also be avoided in individuals with pre-existing bone marrow depression or those with a history of hypersensitivity to the drug. Its use for minor infections, colds, or influenza is not recommended.
Several drug interactions can alter chloramphenicol’s effectiveness or increase its toxicity. It can inhibit the metabolism of drugs like warfarin, phenytoin, and sulfonylureas, potentially leading to increased levels of these medications in the blood. Conversely, drugs such as phenobarbital and rifampicin can decrease chloramphenicol levels. Chloramphenicol can also show antagonistic effects with certain beta-lactam antibiotics, like cephalosporins.