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Polymyxin B

Generic name: polymyxin b systemic

Boxed Warning

Appropriate use:

When this drug is given IM, IV, or intrathecally, it should be given only to hospitalized patients, so as to provide constant supervision by a physician.


Renal function should be carefully determined, and patients with renal damage and nitrogen retention should have reduced dosage. Patients with nephrotoxicity due to polymyxin B sulfate usually show albuminuria, cellular casts, and azotemia. Diminishing urine output and a rising blood urea nitrogen (BUN) are indications for discontinuing therapy with this drug.


Neurotoxic reactions may be manifested by irritability, weakness, drowsiness, ataxia, perioral paresthesia, numbness of the extremities, and blurring of vision. These are usually associated with high serum levels found in patients with impaired renal function and/or nephrotoxicity.

Concurrent therapy:

The concurrent or sequential use of other neurotoxic or nephrotoxic drugs with polymyxin B sulfate, particularly bacitracin, streptomycin, neomycin, kanamycin, gentamicin, tobramycin, amikacin, cephaloridine, paromomycin, viomycin, and colistin should be avoided.

Neuromuscular blockade:

The neurotoxicity of polymyxin B sulfate can result in respiratory paralysis from neuromuscular blockade, especially when the drug is given soon after anesthesia or muscle relaxants.

Use in pregnancy:

The safety of this drug in human pregnancy has not been established.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Injection:

Generic: 500,000 units (1 ea)

Solution Reconstituted, Injection [preservative free]:

Generic: 500,000 units (1 ea)


Mechanism of Action

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



Not absorbed from GI tract.


Tissue diffusion is poor; critically ill patients: Central Vd: ~0.09 L/kg; peripheral Vd: 0.33 L/kg (Sandri 2013a); does not cross blood brain barrier into CSF or into the eye (Hoeprich 1970)


Urine (<1% as unchanged drug within first 12 hours; as therapy continues, up to 60% as unchanged drug in the urine [Evans 1999]); Critically ill adults: Urine (median: 4% [range: 0.98% to 17.4%] as unchanged drug) (Sandri 2013a)

Time to Peak

Serum: IM: Within 2 hours (Hoeprich 1970)

Half-Life Elimination

6 hours, increased with reduced renal function (Evans 1999)

Protein Binding

~60% (Kassamali 2015); 79% to 92% (critically ill patients) (Zavascki, 2008)

Use: Labeled Indications

Infections, acute:

Pseudomonal infections: Treatment of infections of the urinary tract, meninges, and bloodstream caused by susceptible strains of Pseudomonas aeruginosa

Serious infections: 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; Aerobacter aerogenes, specifically bacteremia; Klebsiella pneumoniae, specifically bacteremia

In meningeal infections, polymyxin B sulfate should be administered only by the intrathecal route.


Hypersensitivity to polymyxin B or any component of the formulation

Dosage and Administration

Dosing: Adult

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

CNS infections (alternative agent): Intrathecal: Note: Use a preservative-free preparation.

Intrathecal/Intraventricular: 50,000 units once daily, in combination with systemic therapy (ESCMID/EUCAST [Tsuji 2019]; IDSA [Tunkel 2004]; IDSA [Tunkel 2017]; Segal-Maurer 1999). When intraventricular polymyxin B is administered via a ventricular drain, clamp drain for 15 to 60 minutes after administration (allows solution to equilibrate in CSF) (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]). Note: Intraventricular administration is generally reserved for use in patients who fail parenteral therapy despite removal of CSF shunt or when CSF shunt cannot be removed (Baddour 2018).

Ocular infections: Ophthalmic: A concentration of 0.1% to 0.25% (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/day may be used for P. aeruginosa corneal and conjunctival infections. Note: Avoid total systemic and ophthalmic doses of >25,000 units/kg/day.

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/kg/day IV divided every 12 hours (Furtado 2007; Ouderkirk 2003). More recent publications have cited alternate dosing regimens based on pharmacokinetic/pharmacodynamic data (eg, Monte Carlo simulations) (Sandri 2013a), which support using a loading dose to rapidly achieve target serum concentrations and higher dosing regimens, particularly for severe infections (pathogens with an MIC ≤2 mcg/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 (ESCMID/EUCAST [Tsuji 2019]). Monitor closely for nephrotoxicity. Dosing based on actual body weight has been suggested for patients within a normal weight range for their height (ESCMID/EUCAST [Tsuji 2019]; Kassamali 2015; Pai 2013; Sandri 2013a).

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

IV: Loading dose: 20,000 to 25,000 units/kg, followed by a maintenance dose of 12,500 to 15,000 units/kg every 12 hours (ESCMID/EUCAST [Tsuji 2019]; Kassamali 2015; Sandri 2013a).

Note: Safety data for doses >30,000 units/kg/day or for single infusions >2,000,000 units are limited (ESCMID/EUCAST [Tsuji 2019]; John 2017; Sandri 2013b). Pharmacokinetic data do not support capping upper absolute dose although infusion-related adverse effects (eg, sudden thoracic pain, paresthesias, dizziness, dyspnea, hypoxemia) may increase with higher doses (ESCMID/EUCAST [Tsuji 2019]; John 2017). To minimize bacterial regrowth and heteroresistance, consider use in combination with other antibiotics depending on infection site and susceptibilities (Bergen 2015; ESCMID/EUCAST [Tsuji 2019]; Kassamali 2015; Rigatto 2015).

Inhalation (off-label route): 500,000 units every 12 hours; an aerosolized beta-2 agonist should be given ~20 minutes prior to polymyxin B (Pereira 2007). Note: In the treatment of pneumonia, concomitant IV administration may also be necessary (Pereira 2007).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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, IV, IM, intrathecal, ophthalmic) 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.

Severe, life-threatening, multidrug resistant infection (excluding meningitis): Note: From experience in adult patients, safety data for single doses >30,000 units/kg/dose or total daily doses >2,000,000 units/day are extremely limited (Kassamali 2015).


IM: 25,000 to 40,000 units/kg/day divided every 4 to 6 hours; Note: Routine IM administration not recommended due to severe pain at injection site.

IV: 15,000 to 40,000 units/kg/day divided every 12 hours

Children and Adolescents:

IM: 25,000 to 30,000 units/kg/day divided every 4 to 6 hours; Note: Routine IM administration not recommended due to severe pain at injection site.


Manufacturer's labeling: 15,000 to 25,000 units/kg/day divided every 12 hours

Alternate dosing: Children ≥2 years and Adolescents: Very limited data available: Dosing based on previous recommendations (Hoeprich 1970) and extrapolations from adult pharmacokinetic modeling (Sandri 2013) which assumes that dosing for pediatric patients ≥2 years and adults is the same (per current manufacturer's labeling); some centers have used the following:

Loading dose: 25,000 units/kg

Maintenance dose: 25,000 to 30,000 units/kg/day divided every 12 hours; consider higher doses for organisms with higher MIC

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 daily for 3 to 4 days, then every other day for at least 2 weeks after cultures of CSF are negative

CNS infection (VP-shunt infection, ventriculitis): Limited data available: Children and Adolescents: Intraventricular/intrathecal: 20,000 to 50,000 units/day; lower doses should be used in smaller patients (Hoeprich 1970; Tunkel 2004)

Ocular infection; Pseudomonas aeruginosa: Infants, Children, and Adolescents: Ophthalmic:

Topical: 0.1% to 0.25% 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/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

Dosing: Obesity

Pharmacokinetic data do not support capping upper absolute doses in patients with high total body weight, however, data on the safety of infusions >2,000,000 units remain limited (ESCMID/EUCAST [Tsuji 2019]; John 2017; Sandri 2013a). Infusion-related adverse effects may increase with higher doses (ESCMID/EUCAST [Tsuji 2019]; John 2017). Due to minimal data in morbidly obese patients, consider dosing based on adjusted body weight in these patients (Kassamali 2015; Pai 2013; Sandri 2013a).


IV infusion: Dissolve 500,000 units in 300 to 500 mL D5W

IM injection: Dissolve 500,000 units in 2 mL NS, or 1% procaine HCl

Intrathecal: Dissolve 500,000 units in 10 mL NS (preservative free) (concentration: 50,000 units/mL)

Ophthalmic: Dissolve 500,000 units in 20 to 50 mL SWFI or NS (concentration: 10,000 to 25,000 units/mL [0.1 to 0.25%])


IV: Infuse over 1 hour (ESCMID/EUCAST [Tsuji 2019]).

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 (Pereira 2007).

Intrathecal/intraventricular: 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.


Store intact vials at room temperature of 20°C to 25°C (68°F to 77°F) and protect from light. After reconstitution, store at 2°C to 8°C (36°F to 46°F). Discard any unused solution after 72 hours.

Drug Interactions

Bacitracin (Systemic): Polymyxin B may enhance the nephrotoxic effect of Bacitracin (Systemic). Avoid combination

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Capreomycin: May enhance the neuromuscular-blocking effect of Polymyxin B. Monitor therapy

Cefazedone: May enhance the nephrotoxic effect of Polymyxin B. Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Avoid combination

Colistimethate: Polymyxin B may enhance the neuromuscular-blocking effect of Colistimethate. Monitor therapy

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Mecamylamine: Polymyxin B may enhance the neuromuscular-blocking effect of Mecamylamine. Avoid combination

Methoxyflurane: May enhance the nephrotoxic effect of Polymyxin B. Avoid combination

Neuromuscular-Blocking Agents: Polymyxin B may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Consider therapy modification

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Adverse Reactions

Frequency not defined.

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


Concerns related to adverse effects:

  • Local reactions: May cause severe pain at IM injection site or thrombophlebitis at IV infusion site.
  • Nephrotoxicity: [US Boxed Warning]: May cause nephrotoxicity; avoid concurrent or sequential use of other nephrotoxic drugs. Usual risk factors include preexisting renal impairment, advanced age and dehydration. Polymyxin B-induced nephrotoxicity may be manifested by albuminuria, cellular casts, and azotemia; monitor BUN, serum creatinine, and urinary analysis at baseline and as clinically indicated. Discontinue therapy with decreasing urinary output and increasing BUN. Data suggest polymyxin B undergoes a selective uptake process into renal cells, which plays a primary role in nephrotoxicity potential (Abdelraouf 2014). One small study in patients receiving polymyxin B with a normal baseline renal function observed an overall prevalence rate of nephrotoxicity of 46% with a median onset of 9 days (Dubrovaskaya 2015).
  • Neurotoxicity: [US Boxed Warning]: May cause neurotoxicity, which can also result in respiratory paralysis from neuromuscular blockade especially when the drug is given soon after anesthesia or muscle relaxants. Avoid concurrent or sequential use of other neurotoxic drugs. Avoid concurrent use of curariform muscle relaxants and other neurotoxic drugs (eg, ether, tubocurarine, succinylcholine, gallamine, decamethonium, sodium citrate), which may cause respiratory depression.
  • Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

  • Renal impairment: Use with caution in patients with impaired renal function; manufacturer’s prescribing information states dosage reduction required, however, recent pharmacokinetic/pharmacodynamic and clinical studies suggest daily dose requirement is not affected by renal function (Sandri 2013a; Nelson 2015; Thamlikitkul 2016).

Concurrent drug therapy issues:

  • Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information

Special populations:

  • Pregnancy: [US Boxed Warning]: Safety in pregnant women not established.

Other warnings/precautions:

  • IM/Intrathecal/IV administration: [US Boxed Warning]: Intramuscular/intrathecal/intravenous administration only to hospitalized patients.
  • Parenteral administration: Polymyxin B sulfate is most toxic when given parenterally; avoid parenteral use whenever possible.

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) (ESCMID/EUCAST [Tsuji 2019]).


Pregnancy Considerations

[US Boxed Warning]: Safety in pregnancy has not been established.

Limited data related to systemic use in pregnancy are available (Heinonen 1977; Kazy 2005). Based on the relative toxicity compared to other antibiotics, systemic use in pregnancy is not recommended (Knothe 1985). Due to poor tissue diffusion, topical use would be expected to have only minimal risk to the mother or fetus (Leachman 2006).

Patient Education

What is this drug used for?

  • It is used to treat bacterial infections.

Frequently reported side effects of this drug

  • Diarrhea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

  • Kidney problems like unable to pass urine, blood in urine, change in amount of urine passed, weight gain.
  • Nerve problems like sensitivity to heat or cold; decreased sense of touch; burning, numbness, or tingling; pain; or weakness in the arms, hands, legs, or feet.
  • Trouble breathing
  • Change in balance
  • Severe fatigue
  • Vision changes
  • Flushing
  • Dizziness
  • Headache
  • Stiff neck
  • Clostridium difficile (C. diff)-associated diarrhea like stomach pain or cramps, very loose or watery stools, or bloody stools.
  • Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Source: Wolters Kluwer Health. Last updated January 24, 2020.