Polymyxin B
| Evidence Level: L4 | Predicted Indications: 2 |
Table of Contents
Polymyxin B: From Topical Antibacterial Use to Bronchitis
One-Sentence Summary
Polymyxin B is a polypeptide antibiotic active against Gram-negative bacteria. In Canada it is marketed in topical antibiotic creams, ointments, and eye/ear drops. The TxGNN model predicts it may be effective for bronchitis, with no registered clinical trials and 12 publications (mostly small or older studies, some showing a safety concern) currently touching this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not specified in the Canadian licence data (products are topical antibiotic preparations) |
| Predicted New Indication | Bronchitis |
| TxGNN Prediction Score | 0.9987 |
| Evidence Level | L4 |
| Canada Market Status | Marketed (marketed DINs on record: at least 20) |
| Number of DINs | at least 20 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, polymyxin B is a cationic polypeptide antibiotic that disrupts the outer membrane of Gram-negative bacteria, including multidrug-resistant strains. Mechanistically, it could be relevant to bacterial tracheobronchitis or ventilator-associated respiratory infections caused by resistant Gram-negative organisms such as Pseudomonas aeruginosa and Acinetobacter baumannii.
The link is weak, however. Several publications report that inhaled polymyxin B provokes bronchoconstriction and bronchial hyperreactivity in people with asthma and chronic bronchitis. It has even been used as a non-specific bronchial provocation agent and to create eosinophilic bronchitis animal models. This safety signal undermines the repurposing rationale.
The high TxGNN score is a computational prediction only and is not backed by trial data. One other prediction was also generated: laryngotracheitis (score 0.9962) has no trials or literature at all. Randomized evidence exists for conjunctivitis, but it concerns the existing trimethoprim–polymyxin B eye-drop combination, which is an established use rather than a new one.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| 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 | Inhaled polymyxin B in 19 patients with multidrug-resistant Gram-negative respiratory infections (pneumonia and tracheobronchitis) |
| 4373513 | 1974 | Not classified | J Kans Med Soc | Systemic gentamicin plus polymyxin B aerosol for Pseudomonas tracheobronchitis |
| 4322737 | 1971 | Review | Ann Intern Med | “Danger of polymyxin B inhalation” (safety warning) |
| 231152 | 1979 | Cohort | Lung | Bronchial reactivity to inhaled polymyxin B in asthma and chronic obstructive bronchitis |
| 2984629 | 1985 | Cohort | Orv Hetil | Polymyxin B sulfate used as a non-specific bronchial provocation agent in asthma and chronic bronchitis |
| 4319158 | 1970 | Cohort | Chest | Experimental observations of endobronchial polymyxin B in chronic bronchitis |
| 7402949 | 1980 | Not classified | Pneumonol Pol | Exercise, histamine and polymyxin B provocation tests in asthma and chronic obstructive bronchitis |
| 8054833 | 1994 | Animal study | Clin Auton Res | Guinea-pig eosinophilic bronchitis model induced by intranasal polymyxin B |
| 28441858 | 2017 | Animal study | Zhonghua Yi Xue Za Zhi | Mouse eosinophilic bronchitis model induced by polymyxin B |
Only one of these publications (2013) directly compares polymyxin B treatment outcomes, and the data compiled for this report classify it as a review rather than a randomized trial. Most others show polymyxin B being used to provoke airway reactions rather than to treat bronchitis.
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02236954 | Band-Aid Brand Adhesive Bandages Plus Antibiotic | Not listed | Not listed |
| 02552418 | Soothe Antibiotic Drops | Not listed | Not listed |
| 02230844 | Polysporin Antibiotic Cream | Not listed | Not listed |
| 02230251 | Antibiotic Ointment USP | Not listed | Not listed |
| 02181908 | Polyderm Ointment USP | Not listed | Not listed |
All 20 licences are valid single-ingredient authorizations; none are cancelled. They include topical creams and ointments, eye and ear drops, and ophthalmic combination products such as Maxitrol and Optimyxin. Dosage form and indication text are not available in the data compiled for this report.
Safety Considerations
- Drug Interactions: 73 interactions were identified. Examples of Major interactions:
- Amikacin
- Botulinum toxin type A
- Cisatracurium
- Cidofovir
- Deferasirox
- Intravenous human immunoglobulin G
- Iodinated contrast agents (iothalamic acid, diatrizoate)
- Live cholera vaccine
- Other immune globulins (botulinum neurotoxin A/B, cytomegalovirus)
Examples of Moderate interactions: ethinylestradiol, estradiol, mestranol, mesalazine, balsalazide, ibandronate, capreomycin, picosulfuric acid, clofarabine.
- Respiratory safety signal: The literature indicates inhaled polymyxin B can cause bronchoconstriction and airway hyperreactivity, particularly in people with asthma or chronic bronchitis.
- Hypersensitivity: A case of anaphylaxis to polymyxin B–trimethoprim eye drops has been reported (PMID 26922212).
Please refer to the package insert for formal warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The bronchitis prediction rests on a computational score alone. There are no registered trials, and the literature includes repeated reports that inhaled polymyxin B provokes bronchospasm in patients with bronchitis and asthma. The only supportive evidence is observational data on resistant Gram-negative tracheobronchitis.
To proceed, the following is needed:
- Health Canada package insert warnings and contraindications (a blocking gap for safety screening)
- Mechanism of action data
- A clear definition of the target population (e.g., bacterial tracheobronchitis from multidrug-resistant Gram-negative organisms, rather than general bronchitis)
- Controlled efficacy and inhaled-route safety data, including bronchospasm risk
- Confirmation of the available routes and formulations (the Canadian products are topical, with no inhaled product)
Note on other predictions: Conjunctivitis (L2) has randomized comparisons of polymyxin B/trimethoprim versus moxifloxacin and other antibiotics. This appears to be an existing clinical use, so it should be confirmed against labeling before being treated as repurposing. Laryngotracheitis (L5) has no supporting evidence.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.