Polymyxin B (Maxitrol) is a group of basic polypeptide antibiotics that is indicated for severe infections that are resistant to commonly used medications. It is commonly used as creams, ointments, and powder for superficial skin and mucosal infections.

Polymyxin B (Maxitrol) Uses:

• Acute Infections:
  • Pseudomonal infections:
    • Used in the treatment of infections of the urinary tract, meninges, and bloodstream caused by susceptible strains of Pseudomonas aeruginosa
• Serious infections:
  • Used in the treatment of serious infections caused by susceptible strains of the following organisms, when less potentially toxic drugs are ineffective or contraindicated:
    • H. influenzae, specifically meningeal infections;
    • Escherichia coli, specifically urinary tract infections;
    • Klebsiella pneumoniae, specifically bacteremiaAerobacter aerogenes, specifically bacteremia.
  • In meningeal infections, polymyxin B sulfate should be administered only by the intrathecal route.

Polymyxin B (Maxitrol) Dose in Adults

 Note: Dosing presented as units; 10,000 units = 1 mg.

Polymyxin B (Maxitrol) Dose as an alternative agent in the treatment of CNS infections: Intrathecal:

Note: Use a preservative-free preparation.

• Intrathecal/Intraventricular: 50,000 units once in a day, in combination with systemic therapy.
• When intraventricular polymyxin B is administered via a ventricular drain, clamp drain for 15 to 60 minutes after administration (allows the solution to equilibrate in CSF).

Note: Intraventricular administration is generally reserved for use in patients who fail parenteral therapy despite the removal of CSF shunt or when CSF shunt cannot be removed.

Polymyxin B (Maxitrol) Dose in the treatment of Ocular infections:

• Ophthalmic: A concentration of 0.1 percent to 0.25 percent (10,000 to 25,000 units/mL) is administered as 1 to 3 drops every hour, then increasing the interval as response indicates.
• A subconjunctival injection of up to 100,000 units per day may be used for P. aeruginosa corneal and conjunctival infections.

Note: Avoid total systemic and ophthalmic doses of more than 25,000 units per kg per day.

Polymyxin B (Maxitrol) Dose in the Systemic infections:

Note:

• Most of the available limited data evaluating polymyxin B for multidrug-resistant pathogens cite manufacturer's labeling dosing of 15,000 to 25,000 units per kg per day IV divided every 12 hours.
• More recent publications have cited alternate dosing regimens based on pharmacokinetic/pharmacodynamic data (eg, Monte Carlo simulations), which support using a loading dose to rapidly achieve target serum concentrations and higher dosing regimens, particularly for severe infections (pathogens with a MIC ≤2 mcg per mL);
• however, actual clinical data employing these higher dosing regimens remain limited.
• Despite the paucity of data, loading doses are recommended in all patients, especially critically ill patients with sepsis or septic shock.
• Monitor closely for nephrotoxicity. Dosing based on actual body weight has been suggested for patients within a normal weight range for their height.

Infections (eg, intraabdominal infections, meningitis, pneumonia [hospital-acquired or ventilator-associated], sepsis), due to susceptible ( MIC ≤2 mcg/mL) multidrugresistant gram-negative bacilli (eg, Pseudomonas aeruginosa, Acinetobacter spp) (off-label dose):

• IV: Loading dose: 20,000 to 25,000 units per kg, followed by a maintenance dose of 12,500 to 15,000 units per kg every 12 hours.

Note:

• Safety data for doses of more than 30,000 units per kg per day or for single infusions more than 2,000,000 units are limited.
• Pharmacokinetic data do not support capping upper absolute dose although infusion-related adverse effects (eg, dyspnea, hypoxemia, sudden thoracic pain, paresthesias, dizziness,) may increase with higher doses.
• To minimize bacterial regrowth and heteroresistance, consider use in combination with other antibiotics depending on the infection site and susceptibilities.
• Inhalation (off-label route):
  • 500,000 units every 12 hours; an aerosolized beta-2 agonist should be given ~20 minutes prior to polymyxin B.

Note: In the treatment of pneumonia, concomitant IV administration may also be necessary.     

Polymyxin B (Maxitrol) Dose in Childrens

Note:

• Due to increased toxicity risks, the systemic use of polymyxin B should be limited to life-threatening, multidrug-resistant infection where less toxic alternatives are not effective or not tolerated.
• Multiple routes of administration available for use (eg,  ophthalmic IV, IM, intrathecal) and dosing is different based upon route; use extra precaution to verify dose and route of administration.
• Dosing may be presented as units or mg; 10,000 units = 1 mg, use extra caution with prescribing and/or dispensing.

Polymyxin B (Maxitrol) Dose in the Severe, life-threatening, multidrug-resistant infection (excluding meningitis):

Note: From experience in adult patients, safety data for single doses more than 30,000 units/kg/dose or total daily doses more than 2,000,000 units per day are extremely limited (Kassamali 2015).

• Infants:
  • IM:
    • 25,000 to 40,000 units per kg per day divided every 4 to 6 hours;
    • Note: Routine IM administration not recommended due to severe pain at the injection site.
  • IV:
    • 15,000 to 40,000 units per kg per day divided every 12 hours
• Children and Adolescents:
  • IM: 25,000 to 30,000 units per kg per day divided every 4 to 6 hours;
  • Note: Routine IM administration not recommended due to severe pain at the injection site.
  • IV:
    • Manufacturer's labeling: 15,000 to 25,000 units per kg per day divided every 12 hours
    • Alternate dosing:
      • Children ≥2 years and Adolescents:
        • Very limited data available:
          • Dosing based on previous recommendations and extrapolations from adult pharmacokinetic modeling which assumes that dosing for pediatric patients 2 or more than years and adults is the same (per current manufacturer's labeling); some centers have used the following:
      • Loading dose: 25,000 units per kg
      • Maintenance dose: 25,000 to 30,000 units per kg per day divided every 12 hours; consider higher doses for organisms with higher MIC

Polymyxin B (Maxitrol) Dose in the treatment of Meningitis; Pseudomonas aeruginosa or Haemophilus influenzae:

• Infants and Children <2 years:
  • Intrathecal:
    • 20,000 units once daily for 3 to 4 days or 25,000 units once every other day;
    • continue 25,000 units once every other day for at least 2 weeks after cultures of the CSF are negative
• Children ≥2 years and Adolescents:
  • Intrathecal: 50,000 units in a day for 3 to 4 days, then every other day for at least 2 weeks after cultures of CSF are negative

Polymyxin B (Maxitrol) Dose in the treatment of CNS infection (VP-shunt infection, ventriculitis): Limited data available:

• Children and Adolescents:
  • Intraventricular/intrathecal:
    • 20,000 to 50,000 units per day;
    • lower doses should be used in smaller patients.

Polymyxin B (Maxitrol) Dose in the treatment of Ocular infection; Pseudomonas aeruginosa:

• Infants, Children, and Adolescents: Ophthalmic:
  • Topical: 0.1 percent  to 0.25 percent  solution (prepared from parenteral injection):
    • 1 to 3 drops every hour, then increasing the interval as response indicates
  • Subconjunctival injection:
    • Up to 100,000 units per day not to exceed 25,000 units/kg/day

Note: Combined total therapy (systemic and ophthalmic instillation) should not exceed 25,000 units/kg/day   

Polymyxin B (Maxitrol) Pregnancy Risk Category: 

• [US Boxed Warning]: Safety in pregnancy has not been established.
  • Systemic use of antibiotics in pregnancy is not recommended due to the relative toxicities.
  • Because of poor tissue diffusion, it is possible for topical use to pose minimal risk to either the mother or the fetus.
  • We have limited data on systemic pregnancy use.

Use of polymyxin B during breastfeeding

• It is unknown if polymyxinB is found in breast milk.
• Polymyxin B, if present in breastmilk, is not well absorbed from a normal intestinal tract.

Polymyxin B (Maxitrol) Dose in Kidney Disease:

Note:

• Manufacturer labeling recommends a dosage reduction in renal impairment however, some clinical data suggest that total body clearance of polymyxin B is not altered in renal impairment and that dose adjustment is not necessary.
• Decreasing daily doses in renal impairment may lead to suboptimal plasma exposure, adverse clinical outcomes, clinical failures, and resistance development.
• This is supported by data suggesting ≤13,000 units per kg per day is associated with increased mortality.
• Some data suggest that non-renal pathways are primarily responsible for elimination.
• However, use is associated with nephrotoxicity.
• Recent data suggest polymyxin B undergoes a selective uptake process into renal cells, which plays a primary role in nephrotoxicity potential.
• One small study in patients receiving polymyxin B with a normal baseline renal function observed an overall prevalence rate of nephrotoxicity of 46 percent with a median onset of 9 days.
• Guideline recommendations advise against dose adjustment in renal insufficiency and further suggest the need for larger pharmacokinetic studies to validate dosing in this patient population.
• Intermittent hemodialysis, peritoneal dialysis:
  • The manufacturer's labeling doesn't provide any dosage adjustments.
• CVVHD:
  • No dosage adjustment Required.

Polymyxin B (Maxitrol) Dose in Liver disease:

• The manufacturer's labeling doesn't provide any dosage adjustments.

Side effects of Polymyxin B (Maxitrol):

• Cardiovascular:
  • Facial Flushing
• Central Nervous System:
  • Neurotoxicity (Includes Ataxia
  • Blurred Vision
  • Drowsiness
  • Irritability
  • Numbness Of Extremities Oral Paresthesia)
  • Dizziness
  • Drug Fever
  • Meningitis (Intrathecal Administration)
• Dermatologic:
  • Urticaria
• Endocrine & Metabolic:
  • Hypocalcemia
  • Hypochloremia
  • Hypokalemia
  • Hyponatremia
• Genitourinary:
  • Nephrotoxicity
• Hypersensitivity:
  • Anaphylactoid Reaction
• Local:
  • Pain At Injection Site
• Neuromuscular & Skeletal:
  • Neuromuscular Blockade
  • Weakness

Contraindications to Polymyxin B (Maxitrol):

Hypersensitivity to polymyxin B and any component of the formulation

Warnings and precautions

• Reactions from the local community:
  • This may cause severe pain at an IM injection site, or thrombophlebitis (IV infusion site)
• Nephrotoxicity: [US Boxed Warning]
  • Nephrotoxicity may occur; avoid simultaneous or sequential use.
  • Polymyxin B-induced kidney damage may manifest as albuminuria and cellular casts.
  • Monitor BUN, serum creatinine and urine analysis at baseline, and as indicated by the physician.
  • Stop taking any medication that causes a decrease in urinary output or an increase in BUN.
  • Research suggests that polymyxin B is selectively absorbed into the kidney cells. This plays an important role in nephrotoxicity.
  • Preexisting renal impairment, advanced aging, and dehydration are all common risk factors.
  • A small study of patients who received polymyxin B and had normal renal function found that there was an overall prevalence of nephrotoxicity at 46%.
  • The median onset was 9 days.
• Neurotoxicity: [US Boxed Warn]
  • Neurotoxicity can occur, especially if the drug is administered soon after muscle relaxants or anesthesia.
  • Avoid simultaneous or sequential use with other neurotoxic drugs.
  • Avoid concurrent use of curariform muscle relaxants and other neurotoxic drugs (eg, tubocurarine, succinylcholine, gallamine, decamethonium, ether, sodium citrate), which may cause respiratory depression.
• Superinfection
  • Extended use can lead to fungal or bacterial overinfections, such as C. difficile-associated diarrhea(CDAD), and pseudomembranous collitis. CDAD has been documented >2 months after antibiotic treatment.
• Renal impairment
  • Patients with impaired renal function should be cautious.
  • Although the manufacturer's prescribing information suggests a reduction in dosage, clinical and pharmacokinetic studies have shown that daily dose requirements are not affected by renal impairment.

Polymyxin B: Drug Interaction

Monitoring parameters:

• Neurologic symptoms and signs of superinfection;
• renal function (decreasing urine output and increasing BUN may require discontinuance of therapy);
• polymyxin serum concentrations (to ensure adequate drug exposure particularly early in therapy).

How to administer Polymyxin B (Maxitrol)?

IV: Infuse over 1 hour. Inhalation for nebulization (off-label use/route):

• Use with standard jet nebulizer connected to an air compressor; an aerosolized beta-2 agonist should be given ~20 minutes prior to polymyxin.

Intrathecal/intraventricular:

• It may be administered intrathecally;
• Intrathecal injections should only be administered in a hospital.
• Use a preservative-free preparation.

Ophthalmic:

• May be administered as a subconjunctival injection or as topical ophthalmic drops.

Mechanism of action of Polymyxin B (Maxitrol):

Binds to phospholipids, alters the permeability, and damages bacterial cytoplasmic membrane, allowing leakage of intracellular constituents

Absorption:

• It is not absorbed from the GI tract.

Distribution:

• Tissue diffusion is not good; it does not cross the blood brain barrier into CSF and into the eye.

Protein binding:

• ~60 percent;
• 79 percent to 92 percent in critically ill patients.

Half-life elimination:

• 6 hours, increased with reduced renal function.

Time to peak, serum:

• IM: Within 2 hours.

Excretion:

• Urine (less than 1 percent  as unchanged drug within first 12 hours; as therapy continues, up to 60 percent  as unchanged drug in the urine;
• Critically ill adults: Urine (median: 4 percent  [range: 0.98 percent to 17.4 percent ] as unchanged drug).

International Brand Names of Polymyxin B:

• Aerosporin
• Isopto-Biotic
• Maxitrol
• Neobacigrin
• Neosporin
• Polixin
• Alosol
• Biodexan Ofteno
• Cortisporin Otico
• Dexsul
• Glubacida
• Poly-MXB
• Polymyxin B Pfizer
• Polymyxine B FNA
• Septilisin
• Synalar
• Syntex
• Tribiot
• Trioftín

Polymyxin Brand Names in Pakistan: