Polymyxin B (Systemic, Topical)

Brand names: Poly-Rx
Drug class: Antineoplastic Agents

Usage of Polymyxin B (Systemic, Topical)

Meningitis and Other CNS Infections

Alternative for treatment of meningeal infections caused by susceptible gram-negative bacteria, including Pseudomonas aeruginosa, Escherichia coli† [off-label], Klebsiella pneumoniae† [off-label], and Haemophilus influenzae.

Used intrathecally or intraventricularly† [off-label] for treatment of meningitis or other CNS infections. May be effective when used intrathecally alone, but usually used in conjunction with a parenteral anti-infective (e.g., IV or IM polymyxin B, IV meropenem, IV penicillin, IV cephalosporin).

Penetrates poorly into CSF following IM or IV administration; do not use parenteral polymyxin B alone for treatment of meningitis or other CNS infections.

Used for infections that are resistant to or do not respond to regimens of choice.

Respiratory Tract Infections

Alternative for treatment of respiratory tract infections† [off-label], including nosocomial pneumonia, ventilator-associated pneumonia, or healthcare-associated pneumonia, caused by multidrug-resistant gram-negative bacteria (e.g., Ps. aeruginosa, Acinetobacter baumannii). Used in these infections only when other less toxic anti-infectives are ineffective or contraindicated.

IV polymyxin B has been used alone or in conjunction with IV aztreonam for treatment of nosocomial pneumonia caused by multidrug-resistant Ps. aeruginosa, including those that produce metallo-β-lactamases. Nosocomial infections caused by metallo-β-lactamase-producing Ps. aeruginosa have a high mortality rate, and fatalities may occur despite appropriate anti-infective therapy. Optimal regimens for treatment of these infections not identified to date.

Administered by oral inhalation via nebulization† [off-label] for treatment of respiratory tract infections† caused by susceptible gram-negative bacteria (e.g., Ps. aeruginosa, A. baumannii). Generally used in conjunction with a parenteral anti-infective (e.g., IV polymyxin B); has been effective when given by oral inhalation alone in some patients with infections caused by susceptible gram-negative bacteria.

Although safety and efficacy not established and additional study needed, ATS, IDSA, and other clinicians suggest that adjunctive use of aerosolized polymyxin B can be considered for treatment of serious respiratory tract infections (e.g., ventilator-associated pneumonia) caused by multidrug-resistant gram-negative bacteria that have not responded to treatment with parenteral anti-infectives alone.

Septicemia

Treatment of septicemia or bacteremia caused by susceptible Ps. aeruginosa, Enterobacter aerogenes, or K. pneumoniae. Also has been used for treatment of bloodstream infections caused by multidrug-resistant A. baumannii†.

Generally used only when other less toxic anti-infectives are ineffective or contraindicated.

May be a drug of choice for treatment of septicemia or bacteremia caused by Ps. aeruginosa. Has been used alone or in conjunction with other anti-infectives (e.g., aztreonam) for infections caused by multidrug-resistant Ps. aeruginosa, including those that produce metallo-β-lactamases. Nosocomial blood stream infections caused by metallo-β-lactamase-producing Ps. aeruginosa have a high mortality rate, and fatalities may occur despite appropriate anti-infective therapy. Optimal regimens for treatment of these infections not identified to date.

Urinary Tract Infections (UTIs)

Treatment of serious UTIs caused by susceptible Ps. aeruginosa or E. coli,

Generally used only when other less toxic anti-infectives are ineffective or contraindicated.

Bacteriuria and Bacteremia Associated with Indwelling Catheters

Fixed-combination solution for irrigation containing polymyxin B and neomycin used in abacteriuric patients for short-term (≤10 days) irrigation or rinse of the urinary bladder to help prevent bacteriuria and gram-negative rod septicemia associated with use of indwelling catheters.

Some clinicians state that irrigation or rinse of the urinary bladder with anti-infective solutions is unlikely to be of benefit while the catheter is in place and such a strategy is not recommended.

Use fixed-combination solution for irrigation only for irrigation of the bladder; do not use for irrigation of other areas.

Relate drugs

How to use Polymyxin B (Systemic, Topical)

Administration

Usually administered IV. May be given by IM injection, but IM administration not routinely recommended because severe pain occurs at injection site, especially in infants and children.

Administer intrathecally or intraventricularly† for treatment of meningitis or other CNS infections. Do not use IV or IM administration alone for treatment of meningitis or other CNS infections since distribution into CNS is expected to be low following these routes.

Although safety and efficacy not established, has been administered by oral inhalation via nebulization† for adjunctive treatment of respiratory tract infections†.

Fixed-combination solution for irrigation containing polymyxin B and neomycin is administered by continuous irrigation of the urinary bladder.

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Reconstitution

Reconstitute polymyxin B powder for injection by dissolving 500,000 units of the drug in 300–500 mL of 5% dextrose injection to provide solutions containing approximately 1000–1667 units/mL.

Rate of Administration

IV infusions of polymyxin B usually are given over 60–90 minutes. An infusion period <30 minutes should not be used. Because of risk of neuromuscular blockade, avoid rapid IV injections.

IM Administration

Inject deeply into upper outer quadrant of gluteal muscle; alternate injection sites. Severe injection site pain may occur, especially in infants and children.

Reconstitution

Reconstitute polymyxin B powder for injection by adding 2 mL of sterile water for injection, 0.9% sodium chloride injection, or 1% procaine hydrochloride injection to vial containing 500,000 units to provide a solution containing approximately 250,000 units/mL.

Intrathecal Administration

Reconstitution

Reconstitute polymyxin B powder for injection by adding 10 mL of 0.9% sodium chloride injection to a vial containing 500,000 units to provide a solution containing approximately 50,000 units/mL. Do not use procaine hydrochloride solutions to prepare intrathecal injections.

Oral Inhalation

For oral inhalation via nebulization†, 0.5% solutions have been prepared using 0.9% sodium chloride. Polymyxin B concentrations >10 mg/mL should not be used for administration by oral inhalation since bronchial irritation may occur.

Urinary Bladder Irrigation

Dilution

Add contents of a 1-mL ampul of the fixed-combination solution for irrigation containing 200,000 units of polymyxin B and 40 mg of neomycin to 1 L of 0.9% sodium chloride solution using strict aseptic technique.

Administer diluted solution for irrigation via a 3-way catheter at a rate of 1 L every 24 hours (approximately 40 mL/hour). If patient's urine output is >2 L/day, the manufacturers recommend that inflow rate be adjusted to deliver 2 L every 24 hours.

If not used immediately, store diluted irrigation solution at 4°C and use within 48 hours.

Administer continuously for up to 10 days; do not interrupt the inflow or rinse solution for more than a few minutes.

Dosage

Available as polymyxin B sulfate; dosage expressed in terms of polymyxin B activity (units of polymyxin B) or mg of polymyxin B base.

Each mg of polymyxin B is equivalent to 10,000 units of polymyxin B.

Pediatric Patients

Meningitis and Other CNS Infections Intrathecal

Infants <2 years of age: Initially, 20,000 units once daily for 3–4 days or 25,000 units once every other day. With either regimen, continue treatment with 25,000 units once every other day given for at least 2 weeks after CSF cultures are negative and CSF glucose is normal.

Children ≥2 years: 50,000 units once daily for 3 to 4 days, followed by 50,000 units once every other day given for at least 2 weeks after CSF cultures are negative and CSF glucose is normal.

Although safety and efficacy not established, a variety of other dosage regimens of intrathecal or intraventricular† polymyxin B (with or without concomitant parenteral therapy with IV or IM polymyxin B or other anti-infectives) have been used.

Septicemia or Urinary Tract Bacterial Infections IV

Infants with normal renal function: Up to 40,000 units/kg daily.

Children with normal renal function: 15,000-25,000 units/kg daily (1.5–2.5 mg/kg daily).

Daily dosage may be given in 2 divided doses every 12 hours.

IM

Infants with normal renal function: Up to 40,000 units/kg daily. Premature and full-term neonates have received up to 45,000 units/kg daily (4.5 mg/kg daily) for treatment of sepsis caused by Ps. aeruginosa in clinical studies.

Children with normal renal function: 25,000-30,000 units/kg daily (2.5–3 mg/kg daily).

Daily dosage may be divided and given at 4- or 6-hour intervals.

Adults

Meningitis and Other CNS Infections Intrathecal

50,000 units once daily for 3–4 days, followed by 50,000 units once every other day given for at least 2 weeks after CSF cultures are negative and CSF glucose is normal.

Although safety and efficacy not established, a variety of other dosage regimens of intrathecal or intraventricular† polymyxin B (with or without concomitant parenteral therapy with IV or IM polymyxin B or other anti-infectives) have been used.

Respiratory Tract Infections† Oral Inhalation†

Adults have received 2.5 mg/kg daily in divided doses every 6 hours for adjunctive treatment of respiratory tract infections caused by susceptible Ps. aeruginosa. If a 0.5% solution of the drug is prepared using 0.9% sodium chloride and this dosage regimen is used, the average 70-kg patient would receive 6 mL of solution per dose.

Adults have received 500,000 units twice daily given approximately 20 minutes after an oral inhalation dose of a β2-adrenergic agonist.

Oral inhalation has been used in conjunction with IV polymyxin B for treatment of pneumonia; oral inhalation has been used alone for treatment of tracheobronchitis caused by Ps. aeruginosa.

Oral inhalation treatment has been continued for an average of 14 days (range: 4–25 days).

Septicemia and Urinary Tract Bacterial Infections IV

Adults with normal renal function: 15,000–25,000 units/kg daily (1.5–2.5 mg/kg daily).

Daily dosage may be given in 2 divided doses every 12 hours.

IM

Adults with normal renal function: 25,000-30,000 units/kg daily (2.5–3 mg/kg daily).

Daily dosage may be divided and given at 4- or 6-hour intervals.

Bacteriuria and Bacteremia Associated with Indwelling Urinary Catheters Urinary Bladder Irrigation

Administer via a 3-way catheter at a rate of 1 L every 24 hours (approximately 40 mL/hour). If patient’s urine output is >2 L/day, administer at a rate of 2 L every 24 hours.

Duration of irrigation therapy should not exceed 10 days.

Prescribing Limits

Pediatric Patients

Septicemia and Urinary Tract Infections IV

Infants with normal renal function: Maximum dosage 40,000 units/kg daily.

Children with normal renal function: Maximum dosage 25,000 units/kg daily.

IM

Premature and full-term neonates: Limited experience with dosages as high as 45,000 units/kg daily.

Infants with normal renal function: Maximum dosage 40,000 units/kg daily.

Adults

Septicemia and Urinary Tract Infections IV

Adults with normal renal function: Maximum dosage 25,000 units/kg daily.

IM

Adults with normal renal function: Maximum dosage 30,000 units/kg daily.

Bacteriuria and Bacteremia Associated with Indwelling Urinary Catheters Urinary Bladder Irrigation

Maximum duration 10 days.

Special Populations

Renal Impairment

Decrease dosage in patients with renal impairment. Monitor serum polymyxin B concentrations and adjust IV or IM dosage to maintain desired serum concentrations of the drug.

Various dosage regimens have been recommended; these regimens are not well established and are not based on pharmacokinetic data from patients with renal impairment.

It has been recommended that patients with Clcr 30–80 mL/minute receive an IV loading dose of 2.5 mg/kg on the first day of treatment followed by 1–1.5 mg/kg daily and that those with Clcr <25–30 mL/minute receive these doses once every 2–3 days. For anuric patients, some clinicians recommend an IV loading dose of 2.5 mg/kg followed by 1–1.5 mg/kg given once every 5–7 days.

Some clinicians suggest that patients with Clcr >20 mL/minute receive 75–100% of the usual daily dose in 2 divided doses every 12 hours, those with Clcr 5–20 mL/minute receive 50% of the usual daily dose in 2 divided doses every 12 hours, and those with Clcr <5 mL/minute receive 30% of the usual daily dose every 12–18 hours. Some have used 75% of the usual daily dose in those with Clcr 20–50 mL/minute and 33% of the usual daily dose in those with Clcr <20 mL/minute.

Warnings

Contraindications

  • Polymyxin B: History of hypersensitivity to polymyxins.
  • Fixed combination solution for irrigation containing polymyxin B and neomycin solution: Hypersensitivity to polymyxins, neomycin, or any ingredient in the formulation. History of hypersensitivity or serious toxic reaction to an aminoglycoside.

    • Warnings/Precautions

    Warnings

    Nephrotoxicity

    Can cause potentially serious nephrotoxicity.

    Polymyxin B-associated nephrotoxicity is considered to be dose-dependent, has been reported in 6–25% of patients receiving usual dosages, and generally is reversible after the drug is discontinued.

    Nephrotoxicity usually is manifested by albuminuria or proteinuria, cylindruria, azotemia, increasing blood concentrations of the drug (not related to an increase in dosage), and an increase in serum creatinine concentration and decrease in Clcr. Acute tubular necrosis, oliguria, hematuria, leukocyturia, and excessive excretion of electrolytes may occur.

    Determine baseline renal function prior to initiation of polymyxin B therapy; monitor renal function frequently during therapy using blood tests and urinalysis. The manufacturers also recommend that serum concentrations of the drug be monitored frequently during therapy. Use reduced dosage in patients with impaired renal function or renal damage and nitrogen retention. (See Renal Impairment under Dosage and Administration.)

    Discontinue polymyxin B if urine output diminishes or BUN concentration increases.

    Avoid concurrent or sequential use of other nephrotoxic drugs. (See Interactions.)

    Neurotoxicity

    Can cause potentially serious neurotoxicity.

    Polymyxin B-associated neurotoxicity is considered to be dose-dependent and generally subsides after the drug is discontinued.

    Neurotoxicity may manifest as facial flushing, dizziness that may progress to ataxia, altered mental status or mental confusion, irritability, nystagmus, muscle weakness, drowsiness, giddiness, and peripheral paresthesia (circumoral and stocking glove).

    Numbness, blurring of vision or vision disturbances, slurred speech, coma, and seizures also can occur.

    Avoid concurrent or sequential use of other neurotoxic drugs. (See Interactions.)

    Neuromuscular Blockade

    Respiratory paralysis resulting in respiratory failure or apnea may occur as a result of neuromuscular blockade, especially in patients with neuromuscular disease such as myasthenia gravis or in patients who are receiving neuromuscular blocking agents or general anesthetics. (See Interactions.)

    Polymyxin B-induced neuromuscular blockade is not easily reversed and is resistant to neostigmine and edrophonium; calcium chloride has been used successfully in some cases.

    If signs of respiratory paralysis occur, assist respiration and discontinue polymyxin B. Neuromuscular blockade usually improves within 24 hours after polymyxin B is discontinued.

    Sensitivity Reactions

    Hypersensitivity

    Fever, rash, pruritus, urticaria, skin exanthemata, eosinophilia, and anaphylactoid reactions with dyspnea and tachycardia reported rarely during parenteral polymyxin B therapy.

    General Precautions

    Selection and Use of Anti-infectives

    To reduce development of drug-resistant bacteria and maintain effectiveness of polymyxin B and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.

    When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing. In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.

    Superinfection

    As with other anti-infectives, use of polymyxin B may result in overgrowth of nonsusceptible organisms, including fungi. Institute appropriate therapy if superinfection occurs.

    Precautions Related to Fixed-combination Solution for Bladder Irrigation

    Consider the precautions and contraindications related to both polymyxin B and neomycin.

    Should be used only for irrigation of the bladder; do not use for irrigation of other areas.

    Do not use for prophylactic bladder care if there is a possibility of systemic absorption. The likelihood of toxicity following topical irrigation of the intact urinary bladder is low since appreciable amounts of polymyxin B or neomycin do not enter systemic circulation if the duration of irrigation is ≤10 days. However, absorption of neomycin from the denuded bladder surface has been reported. Systemic absorption after topical application of neomycin to open wounds, burns, and granulating surfaces is clinically significant, and serum concentrations comparable to or higher than those attained following oral and parenteral therapy have been reported.

    Use only for continuous prophylactic irrigation (maximum of 10 days) of the lumen of the intact urinary bladder of patients with indwelling catheters who are under constant supervision by a clinician. Because of the risk of toxicity due to systemic absorption following diffusion into absorptive tissues and spaces, avoid use if there are defects in bladder mucosa or bladder wall, such as vesical rupture, or in association with operative procedures on the bladder wall.

    If absorption occurs, consider that both polymyxin B and neomycin are nephrotoxic and neurotoxic and that the effects of the drugs may be additive.

    Collect urine specimens for urinalysis, culture, and susceptibility testing during prophylactic bladder care; positive cultures suggest the presence of organisms resistant to polymyxin B and neomycin.

    Take appropriate measures if overgrowth of nonsusceptible organisms, including fungi, occurs.

    Specific Populations

    Pregnancy

    Polymyxin B: Safety not established in pregnant women.

    Some clinicians state that polymyxin B should not be used during pregnancy, except in rare situations when other appropriate anti-infectives cannot be used.

    Fixed-combination solution for irrigation containing polymyxin B and neomycin: If use is being considered for a pregnant woman, inform the woman of the potential hazard to the fetus. Aminoglycosides cross the placenta and there have been reports of complete, irreversible, bilateral congenital deafness in children whose mothers received an aminoglycoside (i.e., streptomycin) during pregnancy.

    Pediatric Use

    Polymyxin B: Used IV in infants and children. IM route not routinely used in infants and children because severe pain occurs at the injection site, especially in this age group.

    Fixed-combination solution for irrigation containing polymyxin B and neomycin: Safety and efficacy not established in children.

    Renal Impairment

    Risk of nephrotoxicity and neurotoxicity may be increased in patients with renal impairment; use reduced dosage. (See Renal Impairment under Dosage and Administration.)

    Common Adverse Effects

    IV or IM: Nephrotoxicity, neurotoxicity, fever, rash, pruritus, urticaria. Severe pain at IM injection site; thrombophlebitis at IV site.

    Intrathecal: Meningeal irritation, headache, fever, stiff neck, increased leukocytes and protein in the CSF.

    Oral inhalation via nebulization†: Bronchial irritation, cough, bronchospasm, acute airway obstruction.

    Bladder irrigation with fixed-combination solution containing polymyxin B and neomycin: Irritation of bladder mucosa.

    What other drugs will affect Polymyxin B (Systemic, Topical)

    Nephrotoxic and Neurotoxic Drugs

    Since nephrotoxic and neurotoxic effects may be additive, concurrent or sequential use of polymyxin B and other nephrotoxic and/or neurotoxic drugs, particularly bacitracin, aminoglycosides (amikacin, gentamicin, kanamycin, neomycin, paromomycin, streptomycin, tobramycin), colistimethate/colistin, and viomycin (not commercially available in the US) should be avoided.

    Specific Drugs

    Drug

    Interaction

    Comments

    Aminoglycosides (amikacin, gentamicin, kanamycin, neomycin, paromomycin, streptomycin, tobramycin)

    Possible potentiation of nephrotoxic and/or neurotoxic effects

    Avoid concomitant or sequential use

    Azithromycin

    In vitro evidence of synergistic antibacterial effects between polymyxin B and azithromycin against some strains of multidrug-resistant Ps. aeruginosa; the combination has been bactericidal against some strains, but bacteriostatic against other strains

    Clinical importance of in vitro studies evaluating combination of polymyxin B and azithromycin against gram-negative bacteria is unclear

    Carbapenems (imipenem, meropenem)

    In vitro evidence of synergistic antibacterial effects between polymyxin B and imipenem against Ps. aeruginosa; indifferent antibacterial effects in vitro when combined with meropenem

    Conflicting in vitro results reported with imipenem or meropenem against A. baumannii; in vitro antibacterial effects have been synergistic, partially synergistic, additive, or indifferent

    Clinical importance of in vitro studies evaluating combinations of polymyxin B and carbapenems against gram-negative bacteria is unclear

    Colistimethate/colistin

    Possible potentiation of nephrotoxic effects

    Possible potentiation of neuromuscular blockade

    Avoid concomitant use; use caution

    Neuromuscular blocking agents and general anesthetics (ether, succinylcholine, tubocurarine, gallamine, decamethonium)

    Possible potentiation of neuromuscular blockade which may precipitate respiratory depression, especially if polymyxin B is given soon after anesthesia and/or muscle relaxants

    Avoid concomitant use

    If signs of respiratory paralysis occur, assist respiration and discontinue polymyxin B

    Rifampin

    In vitro evidence of synergistic antibacterial effects between polymyxin B and rifampin against multidrug-resistant Ps. aeruginosa; a 3-drug combination of polymyxin B, rifampin, and imipenem was more consistently bactericidal against these strains

    In some in vitro studies, combination of polymyxin B and rifampin (with or without imipenem) was synergistic or additive against A. baumannii

    Combination of polymyxin B and rifampin was synergistic in vitro against K. pneumoniae

    Clinical importance of in vitro studies evaluating combinations of polymyxin B and rifampin against gram-negative bacteria is unclear

    Sodium citrate

    May precipitate respiratory depression

    Avoid concomitant use

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