Betamethasone + Chloramphenicol + Polymyxin B

Usage

This combination medication is prescribed for superficial bacterial infections of the eye and ear, especially those with an inflammatory component. It is effective against a range of gram-negative bacteria. Examples of conditions it treats include:

• Conjunctivitis (pink eye)
• Otitis externa (swimmer’s ear)
• Blepharitis

Pharmacological Classification: Antibiotic and corticosteroid combination.

Mechanism of Action: Chloramphenicol and polymyxin B are antibiotics. Chloramphenicol inhibits bacterial protein synthesis by binding to the bacterial 50S ribosomal subunit and inhibiting peptidyl transferase activity, while polymyxin B disrupts the bacterial cell membrane permeability by interacting with membrane phospholipids like lipid A component of lipopolysaccharide (LPS) of Gram-negative bacteria, leading to leakage of intracellular contents and cell death. Betamethasone is a corticosteroid that reduces inflammation, redness, and itching by binding to glucocorticoid receptors in the cytoplasm, translocating to the nucleus, and modulating gene expression to suppress inflammatory mediators.

Alternate Names

Often referred to by brand names, which vary depending on the region and manufacturer. Common examples include:

• Olycin B
• Polycure D
• Polymed-B

There might be slight variations in formulations and combinations depending on the region and manufacturer.

How It Works

Pharmacodynamics: Chloramphenicol and polymyxin B work synergistically to kill bacteria. Betamethasone provides anti-inflammatory and antipruritic effects locally.

Pharmacokinetics:

• Absorption: Minimal systemic absorption from topical ocular or otic administration.
• Metabolism: Chloramphenicol undergoes hepatic metabolism. Polymyxin B is not extensively metabolized. Betamethasone is metabolized primarily in the liver by CYP450 enzymes.
• Elimination: Chloramphenicol metabolites are primarily excreted in urine. Polymyxin B is excreted mainly through non-renal routes. Betamethasone is eliminated primarily via renal excretion of metabolites.

Mode of Action: Chloramphenicol inhibits bacterial protein synthesis, polymyxin B disrupts the bacterial cell membrane, and betamethasone exerts anti-inflammatory action via glucocorticoid receptor binding and modulation of gene transcription, inhibiting the synthesis of inflammatory mediators such as prostaglandins, leukotrienes, and cytokines.

Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Betamethasone binds to glucocorticoid receptors. Chloramphenicol inhibits bacterial peptidyl transferase. Polymyxin B interacts with bacterial cell membrane phospholipids.

Dosage

Standard Dosage

Adults:

• Ophthalmic (Eye): Instill 1–2 drops into the affected eye(s) every 4–6 hours. The frequency can be increased for severe infections as directed by the physician.
• Otic (Ear): Instill 2–3 drops into the affected ear(s) 3-4 times a day.

Children:

Use in children should be under strict medical supervision. Dosage and frequency should be determined by the child’s weight and the severity of the infection. Consult specialized pediatric dosing guidelines before prescribing.

Special Cases:

• Elderly Patients: Close monitoring for potential side effects is recommended. Dose adjustment is usually not required unless renal impairment is present.
• Patients with Renal Impairment: Systemic absorption from topical use is minimal, so dose adjustment is not routinely necessary. Systemic polymyxin B dosing requires careful adjustment in renal impairment; consult specific guidelines.
• Patients with Hepatic Dysfunction: Caution advised; monitor for adverse effects. Dose adjustment may be necessary.
• Patients with Comorbid Conditions: Consider individual patient factors and adjust the dosage as needed.

Clinical Use Cases

The primary clinical use cases are the treatment of bacterial eye and ear infections. Dosing adjustments for specific clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations are generally not relevant to this topical formulation.

Dosage Adjustments

Refer to special cases under standard dosage for specific dose modifications based on patient-specific factors like renal/hepatic dysfunction.

Side Effects

Common Side Effects:

• Ophthalmic: Eye discomfort, irritation, burning sensation, transient blurred vision.
• Otic: Mild irritation, temporary ear discomfort.

Rare but Serious Side Effects:

• Ocular: Increased intraocular pressure (IOP), cataracts, optic nerve damage, secondary ocular infections.
• Otic: Ototoxicity (hearing loss), vestibular dysfunction.
• Systemic effects (rare with topical use): Bone marrow suppression (chloramphenicol), nephrotoxicity & neurotoxicity (polymyxin B), hypothalamic-pituitary-adrenal (HPA) axis suppression, hyperglycemia (betamethasone).

Long-Term Effects:

Prolonged use, especially in children, can lead to growth retardation (betamethasone) and increased risk of ocular or otic complications.

Adverse Drug Reactions (ADR):

Any signs of hypersensitivity or severe local reactions should prompt discontinuation of the medication and immediate medical evaluation.

Contraindications

• Hypersensitivity to any component of the formulation.
• Viral, fungal, or mycobacterial infections of the eye or ear.
• Perforated eardrum (for otic use).

Drug Interactions

• Other ototoxic or nephrotoxic drugs may increase the risk of respective adverse events with systemic polymyxin B.
• Interactions with other topically administered ophthalmic or otic medications are generally not significant.

Pregnancy and Breastfeeding

• Pregnancy: Use with caution. Although systemic absorption is minimal, potential risks to the fetus should be weighed against the benefits of treatment.
• Breastfeeding: Excretion in breast milk is minimal after topical use, but caution is advised. Discuss risks and benefits with the patient.

Drug Profile Summary

• Mechanism of Action: Chloramphenicol inhibits protein synthesis, polymyxin B disrupts cell membranes, and betamethasone suppresses inflammation.
• Side Effects: Eye/ear irritation, burning, blurred vision (ophthalmic), temporary discomfort (otic). Rarely, ototoxicity, nephrotoxicity, bone marrow suppression.
• Contraindications: Hypersensitivity, viral/fungal/mycobacterial infections, perforated eardrum (otic).
• Drug Interactions: Minimal with topical use; systemic polymyxin B can interact with other ototoxic or nephrotoxic drugs.
• Pregnancy & Breastfeeding: Use with caution; weigh risks against benefits.
• Dosage: See detailed dosage guidelines above.
• Monitoring Parameters: Monitor for local reactions, IOP (ophthalmic), hearing (otic). With prolonged use, monitor growth in children, and consider periodic evaluations for signs of systemic effects.

Popular Combinations

This combination itself is a common formulation. It is not typically combined with other drugs for topical otic or ophthalmic use.

Precautions

• General Precautions: Evaluate for hypersensitivity and rule out contraindications before prescribing. Monitor for local and systemic side effects.
• Specific Populations: Use cautiously in pregnancy, breastfeeding, and children. Elderly patients should be monitored for adverse effects.
• Lifestyle Considerations: Temporary blurred vision may affect driving ability after ophthalmic use.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Betamethasone + Chloramphenicol + Polymyxin B?

A: See detailed dosage section above for adult, pediatric, and special population dosing.

Q2: Can this combination be used in patients with a perforated eardrum?

A: No, it is contraindicated in patients with a perforated eardrum.

Q3: What are the common side effects of ophthalmic use?

A: Common side effects include eye discomfort, irritation, burning sensation, and transient blurred vision.

Q4: Are there any serious side effects associated with this combination?

A: While rare with topical use, serious side effects can include ototoxicity, nephrotoxicity, bone marrow suppression, increased IOP, and cataracts.

Q5: Can this medication be used during pregnancy or breastfeeding?

A: It should be used cautiously during pregnancy and breastfeeding. Weigh the potential benefits against the risks.

Q6: How does chloramphenicol contribute to the efficacy of this combination?

A: Chloramphenicol inhibits bacterial protein synthesis, contributing to its bactericidal action.

Q7: What is the role of betamethasone in this formulation?

A: Betamethasone reduces inflammation, redness, and itching associated with infection.

Q8: How should I adjust the dose in patients with renal impairment?

A: For topical application, dosage adjustment for renal impairment is usually not necessary due to minimal systemic absorption. However, systemic polymyxin B requires dosage adjustment in renal impairment. Consult specific guidelines for systemic polymyxin B dosing.

Q9: Can this combination be used for viral eye infections?

A: No, this medication is only effective against bacterial infections. It is not effective against viral, fungal, or mycobacterial eye infections.