Usage
Chloramphenicol is a bacteriostatic, broad-spectrum antibiotic indicated for serious infections where less toxic alternatives are ineffective or contraindicated. These infections typically include:
- Typhoid fever
- Meningitis (caused by H. influenzae)
- Rickettsial infections (e.g., Rocky Mountain spotted fever)
- Serious Gram-negative infections resistant to other antibiotics
Its pharmacological classification is antibiotic.
Chloramphenicol inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit, preventing peptide bond formation and blocking chain elongation.
Alternate Names
Chloromycetin is a common alternate name and major brand name.
How It Works
Pharmacodynamics: Chloramphenicol inhibits bacterial protein synthesis by binding reversibly to the peptidyl transferase component of the 50S ribosomal subunit. This action prevents peptide bond formation, halting protein synthesis and resulting in bacteriostatic activity.
Pharmacokinetics:
- Absorption: Well-absorbed orally; rapid IV administration achieves high serum levels. IM absorption is unpredictable.
- Distribution: Widely distributed, including cerebrospinal fluid.
- Metabolism: Primarily hepatic, via glucuronidation. Chloramphenicol palmitate (oral) is hydrolyzed to chloramphenicol in the GI tract, while chloramphenicol succinate (IV) is hydrolyzed to its active form in the liver, kidneys, and lungs.
- Elimination: Mainly renal excretion, with some biliary excretion.
Mode of Action: Inhibits protein synthesis by binding to the 50S ribosomal subunit, blocking the action of peptidyl transferase. This prevents peptide chain elongation.
Elimination Pathways: Primarily renal excretion, with a smaller fraction excreted in bile.
Dosage
Standard Dosage
Adults:
50 mg/kg/day IV or orally, divided every 6 hours. For severe infections (e.g., meningitis, septicemia), initial doses may be doubled to 100 mg/kg/day, but should be reduced to 50 mg/kg/day as soon as clinically feasible. The maximum daily dose is 4 g.
Children:
Generally, the same as adult dosing (50 mg/kg/day divided every 6 hours). However, for neonates and premature infants, a lower dose of 25 mg/kg/day, divided every 6 hours, is recommended due to immature hepatic and renal function. For serious infections, higher doses (up to 100 mg/kg/day) may be necessary, but should be reduced as soon as possible.
Special Cases:
- Elderly Patients: Standard adult dose, adjusted based on renal and hepatic function. Close monitoring is required.
- Patients with Renal Impairment: Dose reduction may be required. Monitor drug levels.
- Patients with Hepatic Dysfunction: Dose reduction may be required. Monitor drug levels.
- Patients with Comorbid Conditions: Careful monitoring and dose adjustments are necessary depending on the specific comorbidity.
Clinical Use Cases
Dosing in specialized clinical situations such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations is generally consistent with the standard adult or pediatric recommendations provided above, with careful attention given to the severity of infection, patient-specific factors, and the need for therapeutic drug monitoring.
Dosage Adjustments
Dose adjustments are necessary for patients with renal or hepatic impairment, based on their individual clearance rates and metabolic capacity. Therapeutic drug monitoring is recommended in these situations.
Side Effects
Common Side Effects:
- Nausea, vomiting, diarrhea
- Glossitis, stomatitis
- Headache
- Transient stinging or burning sensation (with topical ophthalmic use)
- Transient blurred vision (with topical ophthalmic use)
Rare but Serious Side Effects:
- Bone marrow suppression (dose-related and idiosyncratic aplastic anemia)
- Gray baby syndrome (in neonates)
- Optic neuritis
- Ototoxicity
Long-Term Effects:
Aplastic anemia can be a delayed, irreversible consequence of chloramphenicol use.
Adverse Drug Reactions (ADR):
- Aplastic anemia
- Gray baby syndrome
- Severe hypersensitivity reactions
Contraindications
- Hypersensitivity to chloramphenicol
- Treatment of trivial infections or prophylactic use
- Active immunization
- Porphyria
- Pre-existing blood dyscrasias (including aplastic anemia), or family history thereof
- Pregnancy (especially near term) and breastfeeding
Drug Interactions
Chloramphenicol interacts with numerous medications. Clinically significant interactions include:
- CYP450 interactions: Chloramphenicol inhibits CYP3A4, potentially increasing levels of drugs metabolized by this enzyme (e.g., warfarin, phenytoin).
- Bone marrow suppressants: Additive effects with other myelosuppressive drugs.
- Live vaccines: Reduced efficacy of live vaccines.
Pregnancy and Breastfeeding
Chloramphenicol is contraindicated in pregnancy, especially near term, due to the risk of gray baby syndrome in newborns. It is also contraindicated during breastfeeding. The drug crosses the placenta and enters breast milk, posing risks to the fetus and neonate.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit.
- Side Effects: Nausea, vomiting, diarrhea, bone marrow suppression, gray baby syndrome.
- Contraindications: Hypersensitivity, trivial infections, pregnancy, breastfeeding, blood dyscrasias.
- Drug Interactions: CYP3A4 inhibitors, bone marrow suppressants, live vaccines.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adults: 50 mg/kg/day q6h; Children: similar to adult dose, with lower doses for neonates.
- Monitoring Parameters: CBC, drug levels, liver and renal function tests.
Popular Combinations
Chloramphenicol is generally not used in combination therapy due to its toxicity and potential for interactions. Its use is reserved for situations where other antibiotics are ineffective.
Precautions
- Monitor for blood dyscrasias during treatment.
- Closely observe neonates for gray baby syndrome.
- Avoid in patients with hepatic or renal impairment unless absolutely necessary, and adjust dosage accordingly.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Chloramphenicol?
A: Adults: 50 mg/kg/day IV or orally, divided every 6 hours. Children: similar to adult dosing, with lower doses for neonates (25 mg/kg/day divided every 6 hours). Dose adjustments are necessary for patients with renal or hepatic impairment.
Q2: What is Gray Baby Syndrome?
A: A serious adverse reaction in newborns (especially premature infants) characterized by circulatory collapse, cyanosis, abdominal distension, and potentially death. It’s associated with high chloramphenicol levels due to immature metabolic function.
Q3: What are the most serious side effects of Chloramphenicol?
A: Bone marrow suppression (dose-related and aplastic anemia) and gray baby syndrome.
Q4: Can Chloramphenicol be used during pregnancy or breastfeeding?
A: No, Chloramphenicol is contraindicated in pregnancy, especially near term, and during breastfeeding due to the risk of fetal and neonatal toxicity.
Q5: What are the main indications for Chloramphenicol?
A: Typhoid fever, meningitis (caused by H. influenzae), rickettsial infections, and serious Gram-negative infections resistant to other antibiotics.
Q6: How does Chloramphenicol work?
A: It inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit.
Q7: What are the common side effects of Chloramphenicol?
A: Nausea, vomiting, diarrhea, glossitis, stomatitis.
Q8: What drugs interact with Chloramphenicol?
A: Chloramphenicol interacts with many drugs, notably those metabolized by CYP3A4, bone marrow suppressants, and live vaccines.
Q9: What precautions should be taken when prescribing Chloramphenicol?
A: Close monitoring for blood dyscrasias, careful observation of neonates for gray baby syndrome, and dose adjustments for patients with hepatic or renal impairment.
Q10: Why is Chloramphenicol considered a “drug of last resort”?
A: Due to the risk of serious, potentially fatal side effects such as aplastic anemia and gray baby syndrome, it’s reserved for life-threatening infections resistant to other antibiotics.
