Lipoxin B

Approved Indications:

• Serious Gram-negative Infections (Systemic use):
• Septicemia
• Meningitis
• Urinary tract infections (UTIs)
• Bacteremia
• Hospital-acquired respiratory infections (e.g., hospital-acquired pneumonia)
• Infections in burn patients caused by susceptible Gram-negative organisms
• Ophthalmic Infections (Topical use):
• Bacterial conjunctivitis
• Blepharitis
• Keratitis
• Corneal ulcers
  (Often in combination with neomycin and gramicidin)
• Dermatological or Otic Infections (Topical use):
• Superficial skin infections
• External otitis
  (Usually combined with other antibiotics or corticosteroids)

Clinically Accepted Off-label Uses:

• Multidrug-Resistant (MDR) Gram-negative Infections:
• Used for infections caused by MDR Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae when no safer alternatives are available
• Intrathecal/Intraventricular Use (Severe CNS infections):
• Meningitis or ventriculitis caused by Gram-negative organisms in patients unresponsive to systemic therapy

Systemic (Intravenous) Administration:

• Adults:
  15,000 to 25,000 units/kg/day IV, divided every 12 hours
  (Equivalent to 1.5 to 2.5 mg/kg/day based on base weight)
• Maximum daily dose typically does not exceed 1.5 million units
• Duration: 7–14 days or as clinically indicated
• Pediatrics:
• Neonates/Infants: 15,000–40,000 units/kg/day IV in 2 divided doses
• Children: 15,000–25,000 units/kg/day IV in 2 divided doses

Topical (Ophthalmic) Use:

• Eye Drops: 1–2 drops into affected eye(s) every 1–4 hours, depending on severity
• Commonly available in combination formulations

Topical (Dermatologic/Otic) Use:

• Skin: Apply 2–4 times daily to affected area
• Ear: Instill 3–4 drops into affected ear canal 3–4 times daily

Intrathecal/Intraventricular Use (Off-label):

• Adults: 5,000 units once daily
• Must be administered under specialist supervision

Special Populations:

• Renal Impairment:
  Reduce dose and/or extend dosing interval; monitor renal function closely
• Hepatic Impairment:
  No dosage adjustment typically needed

Route: IV, topical (eye/skin/ear), intrathecal/intraventricular (specialist use only)

Polymyxin B binds to the lipopolysaccharide (LPS) component of the outer membrane of Gram-negative bacteria. This interaction disrupts membrane integrity by displacing divalent cations (Ca²⁺ and Mg²⁺) that stabilize the LPS, leading to increased permeability, leakage of intracellular contents, and cell lysis. It is bactericidal and acts in a concentration-dependent manner. Because it targets bacterial membranes, it is largely ineffective against Gram-positive bacteria. Its unique mechanism makes it a valuable option for resistant Gram-negative organisms, though at the cost of potential nephrotoxicity and neurotoxicity.

• Absorption:
  Not absorbed orally. Systemically absorbed only via IV or parenteral routes
• Distribution:
• Volume of distribution: ~0.3 L/kg
• Poor penetration into CSF unless administered intrathecally
• Protein Binding: ~60–80%
• Metabolism:
  Not significantly metabolized
• Elimination:
  Primarily renal excretion via glomerular filtration
• Half-life: ~6 to 10 hours
• Prolonged in renal impairment
• Bioavailability (oral): Negligible

• Pregnancy:
  Not assigned a formal FDA category under current labeling.
  Limited human data; use only if potential benefits justify the potential risk to the fetus. Animal studies have suggested risk of fetal toxicity (nephrotoxicity).
• Lactation:
  Unknown whether excreted in human milk.
  Topical or ophthalmic use is considered safe, but caution is advised for systemic use.
• Recommendation:
  Avoid systemic use during pregnancy/lactation unless no alternatives exist. Prefer topical forms when appropriate.

• Primary Class: Antibacterial
• Subclass: Polymyxin-class antibiotic (Cyclic cationic polypeptides)
• Specifically active against aerobic Gram-negative bacilli

• Known hypersensitivity to Polymyxin B or formulation components
• Myasthenia gravis (risk of neuromuscular blockade and respiratory paralysis)
• Pre-existing renal dysfunction, unless benefits outweigh risks
• Concurrent use with other nephrotoxic or neurotoxic drugs, unless clinically justified

• Nephrotoxicity:
  Can cause acute tubular necrosis. Risk increases with high doses, prolonged use, or concurrent nephrotoxic agents (e.g., aminoglycosides, vancomycin)
• Neurotoxicity:
  Manifesting as paresthesia, dizziness, ataxia, blurred vision, or respiratory depression
• Neuromuscular Blockade:
  May result in respiratory paralysis, especially in patients with neuromuscular diseases or those receiving neuromuscular blockers
• Monitoring Requirements:
• Serum creatinine and BUN
• Neurological status
• Electrolytes during prolonged therapy
• Caution:
  In elderly, critically ill, and renally impaired populations

Common (≥1%):

• Renal:
• Elevated serum creatinine
• Reduced urine output
• Proteinuria
• Neurological:
• Dizziness
• Headache
• Numbness or tingling
• Muscle weakness
• Topical/Ophthalmic:
• Mild local irritation
• Redness or itching
• Tearing or blurred vision

Serious (Rare):

• Acute renal failure
• Seizures or coma (with high doses)
• Anaphylaxis or severe allergic reactions
• Respiratory failure from neuromuscular blockade

• Nephrotoxic Agents (e.g., aminoglycosides, amphotericin B, vancomycin):
  Additive nephrotoxicity
• Neuromuscular Blocking Agents (e.g., succinylcholine):
  Risk of prolonged neuromuscular blockade and respiratory arrest
• Anesthetic Agents (e.g., opioids, sedatives):
  Increased risk of respiratory depression
• CYP450 Involvement:
  Not metabolized by or involved with CYP450 enzymes
• Alcohol:
  No direct interaction, but should be avoided in acutely ill patients

• IDSA (Infectious Diseases Society of America) Guidelines 2023–2024:
• Recommends Polymyxin B over colistin due to lower nephrotoxicity
• Use as part of combination therapy in MDR Gram-negative infections
• WHO Recommendations:
  Lists Polymyxin B as an essential reserve antibiotic for treatment of critical infections due to carbapenem-resistant organisms
• Updated Dosing Guidance (2023):
  Weight-based dosing emphasized; avoid fixed high doses in patients with renal compromise

• Powder for Injection:
• Store at 20°C to 25°C (68°F to 77°F)
• Protect from moisture and light
• Reconstituted solutions should be used within 24 hours if refrigerated (2°C–8°C)
• Topical/Ophthalmic Preparations:
• Store at 15°C to 25°C
• Keep containers tightly closed
• Avoid freezing
• Handling Precautions:
• Use aseptic technique for reconstitution and IV preparation
• Discard unused reconstituted solution after recommended timeframe