Polymyxin B
| Evidence Level: L4 | Predicted Indications: 3 |
Table of Contents
Polymyxin B: From Ophthalmic Antibacterial Combination Products to Bronchitis
One-Sentence Summary
Polymyxin B is an antibiotic active against Gram-negative bacteria. In New Zealand it was licensed only in neomycin-containing eye ointment and eye drops (Maxitrol), and both licenses are now cancelled. The TxGNN model predicts it may be effective for bronchitis with a very high score, but no clinical trials and only 12 publications (mostly small, old, preclinical or safety-focused) are available. The evidence is weak, and some of it points to a safety concern with inhaled use.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the New Zealand license data (licensed as eye ointment and eye drops combined with neomycin) |
| Predicted New Indication | Bronchitis |
| TxGNN Prediction Score | 99.87% |
| Evidence Level | L4 |
| New Zealand Market Status | Cancelled only (no valid licenses) |
| Number of Authorizations | 2 (both cancelled) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Polymyxin B is a cationic lipopeptide antibiotic. It is known to disrupt the outer membrane of Gram-negative bacteria. This provides a plausible link to bacterial tracheobronchitis or lower respiratory infections caused by multidrug-resistant Gram-negative organisms such as Pseudomonas aeruginosa and Acinetobacter baumannii.
Its known use is topical and ophthalmic, so the connection to bronchitis is indirect. It rests on the antibacterial mechanism being applicable to airway infection, and on published reports of systemic or inhaled polymyxin B in respiratory infections. Several publications suggest caution. Inhaled polymyxin B can cause bronchoconstriction and has been used as a non-specific bronchial provocation agent in asthma and chronic bronchitis. Eosinophil-related findings come from animal models, where polymyxin B is used to induce eosinophilic bronchitis, so they do not support a therapeutic effect.
The high TxGNN score is therefore not backed by clinical trial data.
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 | 19 patients with multidrug-resistant Gram-negative respiratory infections treated with inhaled polymyxin B (14 pneumonia, with tracheobronchitis as initial treatment) |
| 4322737 | 1971 | Case report | Ann Intern Med | Reports a danger associated with polymyxin B inhalation |
| 231152 | 1979 | Cohort | Lung | Bronchial reactivity to inhaled polymyxin B in subjects with asthma and chronic obstructive bronchitis |
| 4319158 | 1970 | Cohort | Chest | Experimental observations of endobronchial polymyxin B in chronic bronchitis |
| 2984629 | 1985 | Cohort | Orv Hetil | Polymyxin B-induced non-specific bronchial provocation in asthma and chronic bronchitis |
| 4373513 | 1974 | Not classified | J Kans Med Soc | Pseudomonas tracheobronchitis treated with systemic gentamicin plus polymyxin B aerosol |
| 8054833 | 1994 | Preclinical | Clin Auton Res | Guinea-pig model: intranasal polymyxin B induces eosinophilic bronchitis, used to study cough |
| 11359434 | 2001 | Preclinical | Clin Exp Allergy | Guinea pigs: polymyxin B-induced airway eosinophil accumulation reduced bronchial responsiveness |
| 28441858 | 2017 | Preclinical | Zhonghua Yi Xue Za Zhi | Mouse model of eosinophilic bronchitis induced by polymyxin B; examined eosinophil activation and airway hyperresponsiveness |
New Zealand Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 207381 | Maxitrol (cancelled) | Eye ointment 0.1% with neomycin sulphate 0.35% and polymyxin B sulphate 6,000 u per g | Not stated in the record |
| 207454 | Maxitrol (cancelled) | Eye drops 0.1% with neomycin sulphate 0.35% and polymyxin B sulphate 6,000 u per ml | Not stated in the record |
Both licenses are cancelled and there are no valid single-ingredient or combination licenses. Both products are ophthalmic, so no inhaled or systemic route is currently available in New Zealand.
Safety Considerations
- Respiratory risk with inhalation: Several publications describe bronchoconstriction after inhaled polymyxin B, and the drug has been used as a bronchial provocation agent in asthma and chronic bronchitis.
- Hypersensitivity: A case report describes anaphylaxis to polymyxin B-trimethoprim eye drops.
- Drug interactions: 73 interactions were identified. Those classified as Major include:
- Botulinum toxin type A
- Amikacin
- Cisatracurium
- Cidofovir
- Deferasirox
- Iothalamic acid
- Diatrizoate
- Intravenous human immunoglobulin G
- Human botulinum neurotoxin A/B immune globulin
- Human cytomegalovirus immune globulin
- Live cholera vaccine (Vibrio cholerae CVD 103-HgR strain)
Moderate interactions include the estrogens (ethinylestradiol, estradiol, mestranol), mesalazine, balsalazide, ibandronate, capreomycin, picosulfuric acid and clofarabine.
Please refer to the package insert for label warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests on a high model score, without any registered clinical trial. The literature is small, old, and largely preclinical or safety-focused, and it raises a bronchoconstriction concern with inhaled use. No valid New Zealand license exists, and the previous products were ophthalmic only.
Among the other predictions for this drug, conjunctivitis has much stronger support. It has several randomized comparisons of polymyxin B/trimethoprim ophthalmic solution versus moxifloxacin or chloramphenicol. However, these studies test a fixed combination, so they do not isolate polymyxin B alone. This looks more like an established topical use than a true repurposing signal. It is worth evaluating separately as a research question.
To proceed, the following is needed:
- Mechanism of action data
- Package insert warnings and contraindications (not currently available)
- Controlled clinical data on inhaled or systemic polymyxin B for bronchitis, including a bronchoconstriction safety assessment
- Verification of whether a suitable product and route could be marketed in New Zealand, given that both licenses are cancelled
- For conjunctivitis, confirmation of whether this is already a label use and a review of the contribution of polymyxin B alone
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.