Polymyxin B

Summary

Polymyxin B is a cyclic lipopeptide antibiotic used primarily as a salvage therapy for multidrug‑resistant gram‑negative bacterial infections such as Pseudomonas aeruginosa and Acinetobacter spp. It is administered intravenously, intramuscularly, intrathecally, ophthalmically, or as a topical preparation for ear canal infections. In addition to its antimicrobial role, limited case series report its use in hemoperfusion for refractory anti‑MDA5 dermatomyositis.

Mechanism of Action

Polymyxin B binds to the lipid A component of lipopolysaccharide in the outer membrane of gram‑negative bacteria. This interaction displaces stabilising cations, disrupts membrane integrity, increases permeability, and leads to rapid bacterial cell lysis. The bactericidal effect is concentration‑dependent and is the basis for its activity against resistant gram‑negative organisms.

What the Research Shows

International consensus guidelines (2019) provide the first comprehensive recommendations for polymyxin B dosing, pharmacokinetic/pharmacodynamic targets, combination therapy, and toxicity monitoring in adults. A 2020 review highlighted the need to adjust polymyxin B dosing during continuous renal replacement therapy, noting that earlier dosing tables may no longer be appropriate. A 2023 evidence review for acute otitis externa listed polymyxin B among topical agents, stating no single preparation has proven superiority. A 2024 rheumatology review reported case‑series evidence that polymyxin B hemoperfusion may benefit patients with refractory anti‑MDA5 dermatomyositis, but data remain limited to small, uncontrolled studies. Overall, robust data support intravenous use for multidrug‑resistant gram‑negative infections, while evidence for other routes and indications is preliminary.

Reported Benefits

When used intravenously, polymyxin B offers potent activity against carbapenem‑resistant gram‑negative pathogens, providing a critical option when other antibiotics fail. Topical formulations effectively treat ear canal infections caused by Pseudomonas or Staphylococcus species. Preliminary reports suggest hemoperfusion with polymyxin B may improve survival in severe anti‑MDA5 dermatomyositis, though this remains investigational.

Limitations of the Evidence

Optimal dosing is complex, especially in patients undergoing continuous renal replacement therapy, where empirical regimens may be outdated. Nephrotoxicity and neurotoxicity limit its safety profile, requiring careful monitoring. Evidence for hemoperfusion and ophthalmic use derives mainly from case series and lacks randomized trial confirmation. Comparative data for topical preparations are insufficient to declare superiority over other agents.

Safety Considerations

Polymyxin B can cause acute kidney injury and neurotoxic effects such as paresthesia, dizziness, or respiratory muscle weakness, particularly at high plasma concentrations. Renal function should be monitored, and dose adjustments are advised in renal impairment and during continuous renal replacement therapy. Intrathecal administration carries a risk of neurotoxicity and must follow strict dosing guidelines. Vigilance for hypersensitivity reactions is also recommended.

How It Is Administered

Polymyxin B is supplied for intravenous, intramuscular, intrathecal, ophthalmic, and topical use. Intravenous or intramuscular injection is employed for systemic infections; intrathecal injection is reserved for central nervous system infections; ophthalmic drops treat eye infections; topical ear preparations are used for otitis externa. Formulations and concentrations differ by route, and dosing must be individualized to the infection site and patient characteristics.

Routes of Administration

Goals & Uses

• Topical skin/eye infection treatmentAntibacterialHigh
• Treatment of MDR Gram-negative infectionsAntimicrobialModerate
• Treatment of Gram‑negative bacterial infectionsAntibacterialHigh
• Treatment of Pseudomonas aeruginosa infectionsAntibacterial TherapyModerate
• Endotoxin neutralizationImmunomodulatoryLow
• Treatment of Acinetobacter baumannii infectionsAntibacterialModerate

Contraindications

• Concurrent use of other nephrotoxic agents (systemic)Drug InteractionHigh
• Hypersensitivity to polymyxinsAllergyHigh
• Severe renal impairmentOrganModerateKidney function concerns
• Known hypersensitivity to polymyxinsAllergyHigh
• Severe renal impairment (systemic use)Organ ImpairmentHigh
• Concurrent use of neuromuscular blocking agentsDrug InteractionHigh

Adverse Effects

• Hypersensitivity reactionsImmunologicRare
• NeurotoxicityNeurologicalUncommon
• Injection site pain/phlebitisLocalCommon
• Electrolyte disturbancesMetabolicUncommon
• SuperinfectionInfectiousUncommon
• NephrotoxicityRenalCommon

Drug Interactions

• AminoglycosidesHigh
• Other nephrotoxic agents (e.g., aminoglycosides, vancomycin)Moderate
• Neuromuscular blocking agentsModerate
• VancomycinModerate
• NSAIDsModerateMay increase renal risk in susceptible patients
• Neuromuscular blocking agents (e.g., vecuronium, succinylcholine)High
• Loop diuretics (e.g., furosemide)Moderate

Population Constraints

• PregnancyReproductive SafetyRelative
• Renal impairmentOrgan ImpairmentRelative
• Pediatric patientsAgeRelative
• Myasthenia gravisNeuromuscular DiseaseRelative
• Elderly patientsAgeRelative
• Pregnant womenReproductiveRelative

Regulatory Status

• European UnionApprovedApproved: Severe Gram‑negative infections, Topical ophthalmic and dermatologic formulationsSame safety considerations as US
• United StatesApprovedApproved: Complicated skin and skin‑structure infections, Urinary tract infections, Inhalation therapy for cystic fibrosisAvailable as injectable solution and topical ointment; restricted use due to toxicity
• United KingdomApprovedApproved: Serious Gram-negative infections caused by susceptible organisms, Topical combination antibiotic productsAvailable in the UK; systemic use primarily as last-resort therapy for MDR infections; MHRA-regulated

Restricted to severe infections due to nephro‑ and neurotoxicity; monitored dosing and renal function required.

Evidence & Sources

• Recommendation of Antimicrobial Dosing Optimization During Continuous Renal Replacement Therapy
  Journal ArticleModerateLi L, et al.2020-01-01T00:00:00.000000Z
• Subtypes and Mimics of Sepsis
  Journal ArticleModerateKellum JA, et al.2022-01-01T00:00:00.000000Z
• New therapies in anti-MDA5 antibody-positive dermatomyositis
  Journal ArticleModerateYasui M, Iwamoto T, Furuta S2024-01-01T00:00:00.000000Z
• Acute Otitis Externa: Rapid Evidence Review
  Journal ArticleModerateJackson EA, Geer K2023-01-01T00:00:00.000000Z
• International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP)
  Journal ArticleLowTsuji BT, et al.2019-01-01T00:00:00.000000Z

Frequently Asked Questions