Polymyxin B
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Polymyxin B: From Topical and Local Antibacterial Use to Bronchitis
One-Sentence Summary
Polymyxin B is a polypeptide antibiotic active against Gram-negative bacteria. In Singapore it is registered only in single-ingredient licences for ear, eye, skin and vaginal products. The TxGNN model predicts it may be useful for bronchitis, but this prediction rests on no registered clinical trials and a small, dated body of literature, much of it experimental or about safety concerns. The more credible related directions are respiratory tract infection (5 clinical trials, one completed Phase 2) and conjunctivitis (several randomized comparisons of polymyxin B/trimethoprim), although conjunctivitis is already a marketed use.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the registration data compiled for this report |
| Predicted New Indication | Bronchitis |
| TxGNN Prediction Score | 99.87% |
| Evidence Level | L4 (bronchitis); L2 for respiratory tract infection and conjunctivitis |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 4 |
| Recommended Decision | Hold (bronchitis) |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. From general knowledge, polymyxin B binds lipopolysaccharide on the outer membrane of Gram-negative bacteria and disrupts it, which is bactericidal. It is often a last-line option for multidrug-resistant organisms such as Pseudomonas aeruginosa, Acinetobacter baumannii and carbapenem-resistant Klebsiella pneumoniae.
This makes bacterial infections of the airways a plausible target. One cohort study reported inhaled polymyxin B for salvage treatment of pneumonia and initial treatment of tracheobronchitis caused by multidrug-resistant Gram-negative bacilli, and a comparison study looked at ventilator-associated pneumonia and tracheobronchitis.
There is an important caution. Much of the bronchitis-related literature is not about treatment. It describes polymyxin B as a bronchial provocation agent that triggers bronchoconstriction and basophil degranulation in asthma and chronic bronchitis, and as a tool for creating eosinophilic bronchitis in animal models. One 1971 report warns about the danger of inhalation. So the high model score reflects a biological association, but the real-world evidence does not clearly support use for bronchitis in general.
Clinical Trial Evidence
No clinical trials are registered for bronchitis itself. The table below shows trials for the related prediction respiratory tract infectious disease (rank 4), which is the closest clinically studied area.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT07086391 | N/A | Recruiting | 144 | Jet versus vibrating-mesh nebulization of polymyxin B in mechanically ventilated patients with carbapenem-resistant Gram-negative pneumonia; no results yet |
| NCT06076603 | N/A | Unknown | 30 | Lung fluid versus blood levels of IV versus IV plus nebulized polymyxin B in ventilator-associated pneumonia |
| NCT04839653 | N/A | Unknown | 60 | Selective digestive decontamination in ICU; polymyxin is part of a prevention strategy, not treatment |
| NCT05685615 | Phase 2 | Completed | 39 | IV BV100 plus polymyxin B versus best available therapy in carbapenem-resistant A. baumannii ventilator-associated pneumonia; PK-focused |
| NCT02134106 | Phase 2/3 | Withdrawn | 0 | Combination antibiotics for extensively drug-resistant Gram-negative infections; no participants enrolled, so no evidence |
Literature Evidence
Publications most relevant to the top prediction (bronchitis), plus the key conjunctivitis randomized trials.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 23124906 | 2013 | Review | Infection | Compared polymyxin B with other antimicrobials for ventilator-associated pneumonia and tracheobronchitis caused by P. aeruginosa or A. baumannii |
| 17350201 | 2007 | Cohort | Diagn Microbiol Infect Dis | 19 patients given inhaled polymyxin B for multidrug-resistant Gram-negative respiratory infections (pneumonia and tracheobronchitis) |
| 4373513 | 1974 | Clinical study | J Kans Med Soc | Pseudomonas tracheobronchitis treated with systemic gentamicin and polymyxin B aerosol |
| 4322737 | 1971 | Case report | Ann Intern Med | Warns of the danger of polymyxin B inhalation |
| 231152 | 1979 | Experimental | Lung | Inhaled polymyxin B provokes bronchial reactivity in asthma and chronic obstructive bronchitis |
| 4319158 | 1970 | Experimental | Chest | Experimental endobronchial polymyxin B in chronic bronchitis |
| 11359434 | 2001 | Preclinical (guinea pig) | Clin Exp Allergy | Polymyxin B-induced airway eosinophil accumulation reduced bronchial responsiveness |
| 23092529 | 2013 | RCT | J Pediatr | Single-blinded trial of polymyxin B-trimethoprim versus moxifloxacin in children with acute conjunctivitis |
| 19043945 | 2008 | RCT | J Pediatr Ophthalmol Strabismus | Multicentre comparison of polymyxin B/trimethoprim and moxifloxacin on speed of clinical efficacy in bacterial conjunctivitis |
| 19043943 | 2008 | RCT | J Pediatr Ophthalmol Strabismus | Moxifloxacin versus polymyxin B/trimethoprim in paediatric bacterial conjunctivitis |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN04945P | POLYDEXA EAR DROPS | Solution | Not stated |
| SIN04358P | MAXITROL STERILE OPHTHALMIC SUSPENSION | Solution | Not stated |
| SIN04413P | POLYBAMYCIN OINT. | Ointment | Not stated |
| SIN07745P | POLYGYNAX VAGINAL CAPSULE | Capsule | Not stated |
All four licences are valid, single-ingredient registrations. The registered products are for ear, eye, skin and vaginal use, and none is an inhaled or injectable respiratory product.
Safety Considerations
- Inhalation risk: The literature repeatedly reports bronchoconstriction and histamine release after inhaled polymyxin B, particularly in atopic asthma and chronic obstructive bronchitis. This is directly relevant to a bronchitis indication.
- Nephrotoxicity: A multicentre cohort study identifies renal failure as the main adverse effect of polymyxins when given systemically.
- Hypersensitivity: A case of anaphylaxis to polymyxin B-trimethoprim eye drops has been reported.
- Drug Interactions: 73 interactions were identified. Major-level interactions include:
- Amikacin
- Cidofovir
- Cisatracurium
- Deferasirox
- Botulinum toxin type A
- Iodinated contrast agents (iothalamic acid, diatrizoate)
- Intravenous immunoglobulin and related immune globulins
- Live cholera vaccine
Moderate-level interactions include capreomycin, estrogens (estradiol, ethinylestradiol, mestranol), mesalazine, balsalazide and ibandronate.
Please refer to the package insert for the full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold (for bronchitis)
Rationale: The bronchitis prediction has a very high model score but no registered trials. The literature is mostly dated, experimental, or about polymyxin B as an airway irritant, and it carries a real inhalation safety signal. Respiratory tract infection (aerosolized or combination therapy in resistant Gram-negative pneumonia) and conjunctivitis are better supported, rated "Research Question". The conjunctivitis use, however, is already marketed as a fixed combination with trimethoprim, so it is not true repurposing.
To proceed, the following is needed:
- Package insert warnings and contraindications for the registered products
- Mechanism of action data from DrugBank
- A defined target population, such as bacterial tracheobronchitis from multidrug-resistant Gram-negative organisms rather than bronchitis in general
- Phase 2/3 efficacy and safety data for aerosolized polymyxin B, including bronchospasm monitoring and a plan for patients with asthma or COPD
- An assessment of route compatibility, since no inhaled or injectable product is currently registered in Singapore
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.