Polymyxin B

Polymyxin B is a potent polypeptide antibiotic used primarily to treat severe systemic and local infections caused by susceptible Gram-negative bacteria. It is often reserved for multi-drug resistant cases under strict medical supervision.

For systemic infections, the standard intravenous (IV) dosage for adults with normal renal function is typically 15,000 to 25,000 units per kilogram of body weight per day. This total daily dose is usually divided into two doses administered every 12 hours. For intramuscular (IM) administration, the dose may range from 25,000 to 30,000 units/kg/day.

In infants and children with normal renal function, the intravenous dose can be up to 40,000 units/kg/day if necessary for life-threatening infections. Dosage is strictly calculated based on weight and the severity of the infection. Use in pediatric patients must be closely monitored by a specialist.

Renal Impairment

Because Polymyxin B is cleared by the kidneys, patients with impaired renal function (reduced GFR) require significant dose reductions. Healthcare providers will monitor serum creatinine and urea levels to adjust the frequency and amount of the drug to prevent toxicity.

Hepatic Impairment

Standard dosing is generally used as the drug is not primarily metabolized by the liver, though overall clinical status must be monitored.

Elderly Patients

Older adults often have age-related declines in kidney function. Dosing should be conservative, usually starting at the lower end of the range.

Polymyxin B is almost exclusively administered in a hospital or clinical setting when given systemically. For topical or ophthalmic use, patients should follow the specific application instructions provided on the label, ensuring they do not touch the dropper or tube tip to any surface to prevent contamination. Storage should be at room temperature (20°C to 25°C), protected from light and moisture.

In a hospital setting, nursing staff will manage the schedule. If you are using a topical or eye drop form at home and miss a dose, apply it as soon as you remember. However, if it is almost time for the next dose, skip the missed dose and return to the regular schedule. Do not double the dose.

Signs of systemic overdose include acute kidney failure (decreased urination), muscle weakness, and respiratory paralysis. In the event of a suspected overdose, emergency medical intervention is required, which may include respiratory support and management of fluid/electrolyte balance.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose without medical guidance.

When applied topically or ophthalmically, common side effects include:

• Local Irritation: Redness, stinging, or burning at the application site.
• Blurred Vision: Temporary blurring after applying eye ointments.

For systemic (IV/IM) use:

• Pain at Injection Site: Significant discomfort or thrombophlebitis (vein inflammation).
• Dizziness: A feeling of lightheadedness or vertigo.

• Paresthesia: Numbness or tingling in the extremities or around the mouth.
• Fever: Drug-induced fever or chills shortly after administration.
• Urticaria: Skin rash or hives.

• Anaphylaxis: A severe, life-threatening allergic reaction.
• Electrolyte Imbalance: Specifically low magnesium or potassium levels due to renal effects.

> Warning: Stop taking Polymyxin B and call your doctor immediately if you experience any of these:

• Nephrotoxicity: Signs include significantly decreased urination, swelling in the legs/ankles, or blood in the urine (indicating kidney damage).
• Neurotoxicity: Signs include extreme muscle weakness, confusion, or difficulty breathing (potential respiratory paralysis).
• Ototoxicity: Ringing in the ears (tinnitus) or sudden hearing loss.
• Superinfection: Development of a new infection (like oral thrush or vaginal yeast infection) caused by resistant organisms or fungi.

Prolonged systemic use is rare but can lead to permanent kidney damage or chronic vestibular (balance) issues. Topical use over long periods may lead to sensitization, where the patient develops an allergy to the drug.

Polymyxin B carries a significant FDA Black Box Warning regarding:

1. 1Nephrotoxicity: It can cause damage to the kidney tubules. Close monitoring of renal function is mandatory.
2. 2Neurotoxicity: It may cause sensory disturbances and neuromuscular blockade, which can lead to respiratory arrest, especially when used with other neurotoxic drugs or in patients with pre-existing neuromuscular disorders.

Report any unusual symptoms to your healthcare provider.

Polymyxin B is a potent antibiotic that must be used with extreme caution. It is not effective against viral infections like the flu or the common cold. Misuse or overuse of this antibiotic can lead to the development of resistant bacteria.

According to the FDA-approved labeling, Polymyxin B Sulfate for injection is associated with a high risk of nephrotoxicity (kidney damage) and neurotoxicity (nerve damage). Physicians must monitor kidney function daily through blood tests (creatinine and BUN). Patients must be observed for signs of respiratory distress, as the drug can interfere with the signals between nerves and muscles.

• Allergic Reactions: Patients with a history of hypersensitivity to any polymyxin class drug should not use Polymyxin B.
• Nephrotoxicity Risk: The risk of kidney damage is dose-dependent and increases in patients with pre-existing renal disease or dehydration.
• Neuromuscular Blockade: Polymyxin B can act like a muscle relaxant, potentially causing breathing failure. This is a critical concern for patients with Myasthenia Gravis.
• Monitoring Requirements: Baseline and frequent follow-up tests for renal function (Serum Creatinine, Creatinine Clearance) and neurological assessments are mandatory during systemic therapy.

Systemic Polymyxin B may cause dizziness or blurred vision. Patients should not drive or operate heavy machinery until they know how the medication affects them.

While there is no direct chemical interaction with alcohol, alcohol can dehydrate the body, potentially increasing the risk of kidney toxicity. It is generally advised to avoid alcohol during treatment for serious infections.

For systemic infections, the full course must be completed to ensure the infection is eradicated. Stopping early can lead to the return of a more resistant infection.

> Important: Discuss all your medical conditions with your healthcare provider before starting Polymyxin B.

• Neuromuscular Blocking Agents: Drugs like succinylcholine or tubocurarine must not be used with Polymyxin B, as the combination can lead to prolonged respiratory paralysis.
• Other Polymyxins: Concurrent use with Colistin increases the risk of severe toxicity exponentially.

• Nephrotoxic Drugs: Avoid or use with extreme caution alongside aminoglycosides (e.g., Gentamicin, Amikacin), Amphotericin B, Vancomycin, or certain NSAIDs (e.g., high-dose Ibuprofen). These combinations significantly increase the risk of kidney failure.
• Loop Diuretics: Medications like Furosemide (Lasix) may enhance the toxicity of Polymyxin B by altering its concentration in the kidneys.

• Cisplatin: This chemotherapy agent can worsen the kidney and ear toxicity associated with Polymyxin B.

There are no known significant food interactions with systemic Polymyxin B, as it is not administered orally. However, maintaining adequate hydration (water intake) is vital to protect the kidneys unless otherwise directed by a doctor.

• Nephrotoxic Herbs: Avoid supplements that may stress the kidneys, such as high doses of Vitamin C or certain traditional herbal remedies, without consulting a pharmacist.

Polymyxin B does not typically interfere with standard laboratory chemical tests, but it will affect the results of bacterial cultures by inhibiting the growth of susceptible organisms.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking.

• Hypersensitivity: Polymyxin B is strictly contraindicated in individuals who have had a severe allergic reaction (anaphylaxis, severe rash) to Polymyxin B or Polymyxin E (Colistin).
• Concurrent Neurotoxic/Nephrotoxic Drugs: It should not be used simultaneously with other drugs known to cause nerve or kidney damage unless the benefit clearly outweighs the extreme risk.

• Myasthenia Gravis: Due to the risk of neuromuscular blockade, this drug should be used with extreme caution in patients with this condition, as it may trigger a myasthenic crisis (severe muscle weakness affecting breathing).
• Pre-existing Renal Impairment: While not an absolute contraindication, it requires expert-level dose adjustment and intensive monitoring.

Patients allergic to Colistin (Polymyxin E) are highly likely to be allergic to Polymyxin B due to their similar chemical structures.

> Important: Your healthcare provider will evaluate your complete medical history before prescribing Polymyxin B.

Polymyxin B is classified as FDA Pregnancy Category B (or C depending on the specific manufacturer's label). Animal studies have not always shown a risk, but there are no adequate, well-controlled studies in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, particularly in life-threatening situations.

It is unknown whether Polymyxin B is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Polymyxin B is approved for use in children, including infants, for specific severe infections. However, the risk of kidney damage is significant, and dosing must be meticulously calculated based on body weight. It is not recommended for minor infections in children where safer alternatives exist.

Clinical studies have shown that patients over 65 are at a higher risk for nephrotoxicity. This is often due to diminished renal reserve. Frequent monitoring of renal function is essential for this population.

In patients with a GFR below 50 mL/min, the dose must be reduced. For patients on hemodialysis, the drug is not efficiently removed, so supplemental doses are generally not required after a dialysis session, but serum levels should be monitored if possible.

> Important: Special populations require individualized medical assessment.

Polymyxin B is a cyclic lipopeptide. The molecule contains a fatty acid tail that integrates into the bacterial cell membrane. Specifically, it interacts with the lipid A portion of lipopolysaccharides (LPS) in the outer membrane of Gram-negative bacteria. This interaction displaces calcium and magnesium ions that normally stabilize the membrane, leading to increased permeability and cell lysis (bursting).

Polymyxin B exhibits concentration-dependent killing. This means that higher concentrations of the drug at the site of infection lead to faster and more complete bacterial eradication. The duration of its effect is linked to its ability to remain bound to bacterial surfaces.

| Parameter | Value |

|---|---|

| Bioavailability | Negligible (Oral); 100% (IV) |

| Protein Binding | 70% to 90% |

| Half-life | 4.3 to 6 hours (Adults) |

| Tmax | ~2 hours (IM) |

| Metabolism | Non-CYP mediated; minimal hepatic |

| Excretion | Renal 60% (unchanged) |

• Molecular Formula: C55H96N16O13 (for Polymyxin B1)
• Molecular Weight: ~1301.5 g/mol (Sulfate salt)
• Solubility: Highly soluble in water and isotonic saline.

Polymyxin B is the prototypical member of the Polymyxin-class Antibacterials. It is chemically distinct from aminoglycosides and beta-lactams.