Polymyxin B Sulfate topical

Class: Polymyxins
VA Class: AM900
CAS Number: 1405-20-5
Brands: Poly-Rx, Neosporin G.U. Irrigant

• 
  

  Administer IV, IM, or intrathecally only to hospitalized patients under constant supervision by a clinician.^{100 101 102}

  
  


• 
  

  Nephrotoxic.^{100 101 102} Assess renal function prior to therapy.^{100 101 102} Reduce dosage in patients with renal damage and nitrogen retention.^{100 101 102} Polymyxin B-associated nephrotoxicity usually manifests as albuminuria, cellular casts, and azotemia.^{100 101 102} Discontinue in patients with decreasing urine output and increasing BUN.^{100 101 102}

  
  


• 
  

  Neurotoxic.^{100 101 102} Neurotoxicity may be manifested by irritability, weakness, drowsiness, ataxia, perioral paresthesia, numbness of the extremities, and vision blurring.^{100 101 102} Usually associated with high polymyxin B serum concentrations found in patients with impaired renal function and/or nephrotoxicity.^{100 101 102}

  
  


• 
  

  Neurotoxicity may result in respiratory paralysis from neuromuscular blockade, especially when given soon after anesthesia and/or muscle relaxants.^{100 101 102}

  
  


• 
  

  Avoid concomitant or sequential use of neurotoxic and/or nephrotoxic drugs, particularly bacitracin, aminoglycosides (amikacin, gentamicin, kanamycin, neomycin, paromomycin, streptomycin, tobramycin), cephaloridine (not commercially available in the US), colistimethate/colistin, and viomycin (not commercially available in the US).^{100 101 102 145}

  
  


• 
  

  Safety not established in pregnant women.^{100 101 102}

  
  

Introduction

Antibacterial; polymyxin antibiotic structurally and pharmacologically related to colistin.^{14 105}

Uses for Polymyxin B Sulfate

Meningitis and Other CNS Infections

Alternative for treatment of meningeal infections caused by susceptible gram-negative bacteria, including Pseudomonas aeruginosa, Escherichia coli†, Klebsiella pneumoniae†, and Haemophilus influenzae.^{100 101 102 113 136}

Used intrathecally^{100 101 102 136} or intraventricularly† for treatment of meningitis or other CNS infections.^{113 136} 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).^{113 136}

Penetrates poorly into CSF following IM or IV administration;^{100 101 102} do not use parenteral polymyxin B alone for treatment of meningitis or other CNS infections.¹⁴⁶

Used for infections that are resistant to or do not respond to regimens of choice.^{100 101 102 105 136}

Respiratory Tract Infections

Alternative for treatment of respiratory tract infections†, including nosocomial pneumonia, ventilator-associated pneumonia, or healthcare-associated pneumonia, caused by multidrug-resistant gram-negative bacteria (e.g., Ps. aeruginosa,^{115 122 126} Acinetobacter baumannii).^{115 117 122} Used in these infections only when other less toxic anti-infectives are ineffective or contraindicated.^{100 101 102 105 117 121 122}

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.¹²⁶ Nosocomial infections caused by metallo-β-lactamase-producing Ps. aeruginosa have a high mortality rate, and fatalities may occur despite appropriate anti-infective therapy.¹²⁶ Optimal regimens for treatment of these infections not identified to date.¹²⁶

Administered by oral inhalation via nebulization† for treatment of respiratory tract infections† caused by susceptible gram-negative bacteria (e.g., Ps. aeruginosa, A. baumannii).^{105 109 112 116 117 122 127} Generally used in conjunction with a parenteral anti-infective (e.g., IV polymyxin B);^{116 117 122} has been effective when given by oral inhalation alone in some patients with infections caused by susceptible gram-negative bacteria.^{116 122}

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.^{107 112 116 122}

Septicemia

Treatment of septicemia or bacteremia caused by susceptible Ps. aeruginosa, Enterobacter aerogenes, or K. pneumoniae.^{100 101 102 124} Also has been used for treatment of bloodstream infections caused by multidrug-resistant A. baumannii†.¹¹⁷

Generally used only when other less toxic anti-infectives are ineffective or contraindicated.^{100 101 102 105 121 124}

May be a drug of choice for treatment of septicemia or bacteremia caused by Ps. aeruginosa.^{100 101 102} 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.¹²⁴ 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.¹²⁴ Optimal regimens for treatment of these infections not identified to date.¹²⁴

Urinary Tract Infections (UTIs)

Treatment of serious UTIs caused by susceptible Ps. aeruginosa or E. coli,^{100 101 102}

Generally used only when other less toxic anti-infectives are ineffective or contraindicated.^{100 101 102 105 121}

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.^{103 104}

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.¹⁴⁶

Use fixed-combination solution for irrigation only for irrigation of the bladder; do not use for irrigation of other areas.^{103 104}

Polymyxin B Sulfate Dosage and Administration

Administration

Usually administered IV.^{100 101 102} May be given by IM injection, but IM administration not routinely recommended because severe pain occurs at injection site, especially in infants and children.^{100 101 102}

Administer intrathecally^{100 101 102 136} or intraventricularly† for treatment of meningitis or other CNS infections.^{113 114 136} 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.^{100 101 102 136}

Although safety and efficacy not established, has been administered by oral inhalation via nebulization† for adjunctive treatment of respiratory tract infections†.^{105 107 112 116 117 127}

Fixed-combination solution for irrigation containing polymyxin B and neomycin is administered by continuous irrigation of the urinary bladder.^{103 104}

IV Administration

Reconstitution

Reconstitute polymyxin B powder for injection by dissolving 500,000 units of the drug in 300–500 mL of 5% dextrose injection^{100 101 102} to provide solutions containing approximately 1000–1667 units/mL.

Rate of Administration

IV infusions of polymyxin B usually are given over 60–90 minutes.¹⁰⁵ An infusion period <30 minutes should not be used.¹⁰⁵ Because of risk of neuromuscular blockade, avoid rapid IV injections.¹⁰⁵

IM Administration

Inject deeply into upper outer quadrant of gluteal muscle;^{146 a} alternate injection sites.¹⁴⁶ Severe injection site pain may occur, especially in infants and children.^{100 101 102}

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^{100 101 102} 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.^{100 101 102} Do not use procaine hydrochloride solutions to prepare intrathecal injections.^{146 a}

Oral Inhalation

For oral inhalation via nebulization†, 0.5% solutions have been prepared using 0.9% sodium chloride.¹¹² Polymyxin B concentrations >10 mg/mL should not be used for administration by oral inhalation since bronchial irritation may occur.¹⁰⁵

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.^{103 104}

Administer diluted solution for irrigation via a 3-way catheter at a rate of 1 L every 24 hours (approximately 40 mL/hour).^{103 104} If patient's urine output is >2 L/day, the manufacturers recommend that inflow rate be adjusted to deliver 2 L every 24 hours.^{103 104}

If not used immediately, store diluted irrigation solution at 4°C and use within 48 hours.^{103 104}

Administer continuously for up to 10 days; do not interrupt the inflow or rinse solution for more than a few minutes.^{103 104}

Dosage

Available as polymyxin B sulfate; dosage expressed in terms of polymyxin B activity (units of polymyxin B)^{100 101 102 105} or mg of polymyxin B base.^{100 101 102}

Each mg of polymyxin B is equivalent to 10,000 units of polymyxin B.^{100 101 102 105}

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.^{100 101 102} 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.^{100 101 102}

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.^{100 101 102}

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.¹³⁶

Septicemia or Urinary Tract Bacterial Infections

IV

Infants with normal renal function: Up to 40,000 units/kg daily.^{100 101 102}

Children with normal renal function: 15,000-25,000 units/kg daily (1.5–2.5 mg/kg daily).^{100 101 102}

Daily dosage may be given in 2 divided doses every 12 hours.^{100 101 102}

IM

Infants with normal renal function: Up to 40,000 units/kg daily.^{100 101 102} 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.^{100 101 102}

Children with normal renal function: 25,000-30,000 units/kg daily (2.5–3 mg/kg daily).^{100 101 102}

Daily dosage may be divided and given at 4- or 6-hour intervals.^{100 101 102}

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.^{100 101 102}

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.¹³⁶

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.^{122 127} 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.¹¹²

Adults have received 500,000 units twice daily given approximately 20 minutes after an oral inhalation dose of a β₂-adrenergic agonist.¹¹⁶

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.¹¹⁶

Oral inhalation treatment has been continued for an average of 14 days (range: 4–25 days).¹¹⁶

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).^{100 101 102}

Daily dosage may be given in 2 divided doses every 12 hours.^{100 101 102}

IM

Adults with normal renal function: 25,000-30,000 units/kg daily (2.5–3 mg/kg daily).^{100 101 102}

Daily dosage may be divided and given at 4- or 6-hour intervals.^{100 101 102}

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).^{103 104} If patient’s urine output is >2 L/day, administer at a rate of 2 L every 24 hours.^{103 104}

Duration of irrigation therapy should not exceed 10 days.^{103 104}

Prescribing Limits

Pediatric Patients

Septicemia and Urinary Tract Infections

IV

Infants with normal renal function: Maximum dosage 40,000 units/kg daily.^{100 101 102}

Children with normal renal function: Maximum dosage 25,000 units/kg daily.^{100 101 102}

IM

Premature and full-term neonates: Limited experience with dosages as high as 45,000 units/kg daily.^{100 101 102}

Infants with normal renal function: Maximum dosage 40,000 units/kg daily.^{100 101 102}

Adults

Septicemia and Urinary Tract Infections

IV

Adults with normal renal function: Maximum dosage 25,000 units/kg daily.^{100 101 102}

IM

Adults with normal renal function: Maximum dosage 30,000 units/kg daily.^{100 101 102}

Bacteriuria and Bacteremia Associated with Indwelling Urinary Catheters

Urinary Bladder Irrigation

Maximum duration 10 days.^{103 104}

Special Populations

Renal Impairment

Decrease dosage in patients with renal impairment.^{14 100 101 102 105 112 125} Monitor serum polymyxin B concentrations and adjust IV or IM dosage to maintain desired serum concentrations of the drug.^{105 146}

Various dosage regimens have been recommended; these regimens are not well established and are not based on pharmacokinetic data from patients with renal impairment.^{105 109 115 125 134}

It has been recommended that patients with Cl_cr 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 Cl_cr <25–30 mL/minute receive these doses once every 2–3 days.¹³⁴ 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.^{112 134}

Some clinicians suggest that patients with Cl_cr >20 mL/minute receive 75–100% of the usual daily dose in 2 divided doses every 12 hours, those with Cl_cr 5–20 mL/minute receive 50% of the usual daily dose in 2 divided doses every 12 hours, and those with Cl_cr <5 mL/minute receive 30% of the usual daily dose every 12–18 hours.¹⁰⁵ Some have used 75% of the usual daily dose in those with Cl_cr 20–50 mL/minute and 33% of the usual daily dose in those with Cl_cr <20 mL/minute.¹¹⁵

Cautions for Polymyxin B Sulfate

Contraindications

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  Polymyxin B: History of hypersensitivity to polymyxins.^{100 101 102}

  
  


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  Fixed combination solution for irrigation containing polymyxin B and neomycin solution: Hypersensitivity to polymyxins, neomycin, or any ingredient in the formulation.^{103 104} History of hypersensitivity or serious toxic reaction to an aminoglycoside.^{103 104}

  
  

Warnings/Precautions

Warnings

Nephrotoxicity

Can cause potentially serious nephrotoxicity.^{100 101 102 105 111 112 115 117 122}

Polymyxin B-associated nephrotoxicity is considered to be dose-dependent,^{111 112} has been reported in 6–25% of patients receiving usual dosages,^{111 112 115 117 122} and generally is reversible after the drug is discontinued.¹¹²

Nephrotoxicity usually is manifested by albuminuria or proteinuria,^{100 101 102 105 111} cylindruria,^{100 101 102 111} azotemia,^{100 101 102} increasing blood concentrations of the drug (not related to an increase in dosage),^{100 101 102} and an increase in serum creatinine concentration and decrease in Cl_cr.¹¹¹ Acute tubular necrosis,¹¹¹ oliguria,¹¹¹ hematuria,^{105 111} leukocyturia,^a and excessive excretion of electrolytes may occur.^a

Determine baseline renal function prior to initiation of polymyxin B therapy; monitor renal function frequently during therapy using blood tests and urinalysis.^{100 101 102 146} The manufacturers also recommend that serum concentrations of the drug be monitored frequently during therapy.^{100 101 102} Use reduced dosage in patients with impaired renal function or renal damage and nitrogen retention.^{100 101 102} (See Renal Impairment under Dosage and Administration.)

Discontinue polymyxin B if urine output diminishes or BUN concentration increases.^{100 101 102}

Avoid concurrent or sequential use of other nephrotoxic drugs.^{100 101 102 111 112} (See Interactions.)

Neurotoxicity

Can cause potentially serious neurotoxicity.^{100 101 102 105 111 112 117 135}

Polymyxin B-associated neurotoxicity is considered to be dose-dependent^{111 112} and generally subsides after the drug is discontinued.^{105 111 135}

Neurotoxicity may manifest as facial flushing,^{100 101 102} dizziness^{100 101 102 111} that may progress to ataxia,^{100 101 102 105} altered mental status or mental confusion,^{105 117} irritability,^{100 101 102} nystagmus,^a muscle weakness,^{105 111 122} drowsiness,^{100 101 102} giddiness,¹⁰⁵ and peripheral paresthesia (circumoral and stocking glove).^{100 101 102 105 111 117 135}

Numbness,^{105 a} blurring of vision^{100 101 102} or vision disturbances,^{111 112} slurred speech,^a coma,¹⁰⁵ and seizures^{105 111 122} also can occur.

Avoid concurrent or sequential use of other neurotoxic drugs.^{100 101 102 111 112} (See Interactions.)

Neuromuscular Blockade

Respiratory paralysis resulting in respiratory failure or apnea may occur as a result of neuromuscular blockade,^{100 101 102 105 111 112} especially in patients with neuromuscular disease such as myasthenia gravis or in patients who are receiving neuromuscular blocking agents or general anesthetics.^{100 101 102 111 112} (See Interactions.)

Polymyxin B-induced neuromuscular blockade is not easily reversed and is resistant to neostigmine¹⁰⁵ and edrophonium;^a calcium chloride has been used successfully in some cases.¹⁰⁵

If signs of respiratory paralysis occur, assist respiration and discontinue polymyxin B.^{100 101 102 111} Neuromuscular blockade usually improves within 24 hours after polymyxin B is discontinued.¹⁰⁵

Sensitivity Reactions

Hypersensitivity

Fever,^{100 101 102 105 111} rash,^{105 111} pruritus,^{105 111} urticaria,^{100 101 102 111} skin exanthemata,^a eosinophilia,^a and anaphylactoid reactions with dyspnea and tachycardia^a 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.^{100 101 102}

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.^{100 101 102} In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.^{100 101 102}

Superinfection

As with other anti-infectives, use of polymyxin B may result in overgrowth of nonsusceptible organisms, including fungi.^{100 101 102} Institute appropriate therapy if superinfection occurs.^{100 101 102}

Precautions Related to Fixed-combination Solution for Bladder Irrigation

Consider the precautions and contraindications related to both polymyxin B and neomycin.^{103 104}

Should be used only for irrigation of the bladder; do not use for irrigation of other areas.^{103 104}

Do not use for prophylactic bladder care if there is a possibility of systemic absorption.^{103 104} 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.^{103 104} However, absorption of neomycin from the denuded bladder surface has been reported.^{103 104} 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.^{103 104}

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.^{103 104} 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.^{103 104}

If absorption occurs, consider that both polymyxin B and neomycin are nephrotoxic and neurotoxic and that the effects of the drugs may be additive.^{103 104}

Collect urine specimens for urinalysis, culture, and susceptibility testing during prophylactic bladder care;^{103 104} positive cultures suggest the presence of organisms resistant to polymyxin B and neomycin.^{103 104}

Take appropriate measures if overgrowth of nonsusceptible organisms, including fungi, occurs.^{103 104}

Specific Populations

Pregnancy

Polymyxin B: Safety not established in pregnant women.^{100 101 102}

Some clinicians state that polymyxin B should not be used during pregnancy, except in rare situations when other appropriate anti-infectives cannot be used.¹⁴⁶

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.^{103 104} 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.^{103 104}

Pediatric Use

Polymyxin B: Used IV in infants and children.^{100 101 102} IM route not routinely used in infants and children because severe pain occurs at the injection site, especially in this age group.^{100 101 102}

Fixed-combination solution for irrigation containing polymyxin B and neomycin: Safety and efficacy not established in children.^{103 104}

Renal Impairment

Risk of nephrotoxicity and neurotoxicity may be increased in patients with renal impairment;^{105 112} use reduced dosage.^{14 100 101 102 105 112 125} (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

IV or IM: Nephrotoxicity,^{100 101 102 105 111 112 115 117 122} neurotoxicity,^{100 101 102 105 111 117 112 135} fever,^{100 101 102 105 111} rash,^{105 111} pruritus,^{105 111} urticaria.^{100 101 102 111} Severe pain at IM injection site;^{100 101 102 105} thrombophlebitis at IV site.^{100 101 102}

Intrathecal: Meningeal irritation,^{100 101 102 136} headache,^{100 101 102} fever,^{100 101 102} stiff neck,^{100 101 102} increased leukocytes and protein in the CSF.^{100 101 102}

Oral inhalation via nebulization†: Bronchial irritation,¹⁰⁵ cough,¹¹⁶ bronchospasm,^{105 116} acute airway obstruction.¹¹²

Bladder irrigation with fixed-combination solution containing polymyxin B and neomycin: Irritation of bladder mucosa.^{103 104}

Interactions for Polymyxin B Sulfate

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.^{100 101 102 111 112 145}

Specific Drugs

Drug	Interaction	Comments
Aminoglycosides (amikacin, gentamicin, kanamycin, neomycin, paromomycin, streptomycin, tobramycin)	Possible potentiation of nephrotoxic and/or neurotoxic effects100 101 102 111 112	Avoid concomitant or sequential use100 101 102 111 112
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 strains143	Clinical importance of in vitro studies evaluating combination of polymyxin B and azithromycin against gram-negative bacteria is unclear143
Carbapenems (imipenem, meropenem)	In vitro evidence of synergistic antibacterial effects between polymyxin B and imipenem against Ps. aeruginosa;143 indifferent antibacterial effects in vitro when combined with meropenem142 Conflicting in vitro results reported with imipenem or meropenem against A. baumannii;118 119 125 133 142 143 in vitro antibacterial effects have been synergistic, partially synergistic, additive, or indifferent118 125 133 142	Clinical importance of in vitro studies evaluating combinations of polymyxin B and carbapenems against gram-negative bacteria is unclear119 143
Colistimethate/colistin	Possible potentiation of nephrotoxic effects100 101 102 111 112 145 Possible potentiation of neuromuscular blockade145	Avoid concomitant use; use caution