Polymyxin B
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
Polymyxin B: From an Established Topical Antibacterial to Bronchitis
One-Sentence Summary
Polymyxin B is an antibiotic that acts mainly against Gram-negative bacteria. In South Africa it is registered in three topical products (ointments and an eye ointment). The TxGNN model predicts it may be useful for bronchitis, but there are no registered clinical trials and only 14 publications for this indication. The publications are mostly case series, bronchial challenge experiments and animal studies, and several show inhaled polymyxin B causing bronchospasm rather than treating disease.
Quick Overview
| Item | Content |
|---|---|
| Predicted New Indication | Bronchitis |
| TxGNN Prediction Score | 99.87% (rank 1051) |
| Evidence Level | L3 |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 3 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the Evidence Pack. From what is known, polymyxin B binds lipid A in the outer membrane of Gram-negative bacteria and disrupts it. It retains activity against multidrug-resistant organisms such as Pseudomonas aeruginosa and Acinetobacter baumannii.
This gives a plausible rationale only for bacterial tracheobronchitis, particularly ventilator-associated cases caused by resistant Gram-negative bacilli. It does not support use in viral or chronic non-infectious bronchitis, which account for most cases.
The high TxGNN score is not backed by trial data. The clinical support is limited to a retrospective cohort and case series in multidrug-resistant Gram-negative tracheobronchitis. The other literature shows inhaled polymyxin B triggering histamine release and bronchoconstriction in people with asthma or chronic bronchitis. That is a safety signal, not a therapeutic one.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 23124906 | 2013 | Cohort | Infection | Compared polymyxin B with other antimicrobials for ventilator-associated pneumonia and tracheobronchitis due to P. aeruginosa or A. baumannii |
| 17350201 | 2007 | Case series | Diagn Microbiol Infect Dis | 19 patients given inhaled polymyxin B for multidrug-resistant Gram-negative respiratory infections (14 pneumonia, remainder tracheobronchitis); used as salvage or initial therapy |
| 4373513 | 1974 | Case series | J Kans Med Soc | Pseudomonas tracheobronchitis treated with systemic gentamicin plus polymyxin B aerosol |
| 4319158 | 1970 | Experimental | Chest | Endobronchial polymyxin B in chronic bronchitis; experimental observations only |
| 231152 | 1979 | Experimental (bronchial challenge) | Lung | Bronchial reactivity to inhaled polymyxin B in asthma and chronic obstructive bronchitis |
| 2984629 | 1985 | Experimental (bronchial challenge) | Orv Hetil | Polymyxin B used as a non-specific bronchial provocation agent in asthma and chronic bronchitis |
| 4322737 | 1971 | Case report/Letter | Ann Intern Med | Warning about the dangers of polymyxin B inhalation |
| 8054833 | 1994 | Preclinical | Clin Auton Res | Intranasal polymyxin B used to induce eosinophilic bronchitis in guinea pigs (a disease model, not a treatment) |
| 28441858 | 2017 | Preclinical (mouse) | Zhonghua Yi Xue Za Zhi | Polymyxin B used to induce an eosinophilic bronchitis mouse model |
South Africa Market Information
| Registration Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| G2401 (ACT 101/1965) | Terramycin Topical Ointment | Ointment | Not stated in the registration data |
| H.1158 | Maxitrol 3.5g | Eye ointment | Not stated in the registration data |
| G1625 (OLD MEDICNE) | Terracortril | Ointment | Not stated in the registration data |
All three registered products are topical (ointment or eye ointment). None is an inhaled or systemic formulation, so no registered product currently supports respiratory use. Essential Medicines List (EML) status is not available in the Evidence Pack.
Safety Considerations
Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.
Safety signals from the retrieved literature that matter for this indication:
- Inhalation bronchospasm: Inhaled polymyxin B caused bronchoconstriction in about 85% of atopic asthmatics in one challenge study (PMID 6264764), through basophil and mast-cell histamine release.
- Nephrotoxicity: A prospective cohort (PMID 26856846) identifies renal failure as the main adverse effect of polymyxins.
- No drug interaction data were found.
Conclusion and Next Steps
Decision: Hold
Rationale: There are no registered trials for bronchitis, and the supporting literature is limited to old case series and retrospective reports in multidrug-resistant Gram-negative tracheobronchitis. The high TxGNN score is not corroborated, and inhaled use carries a documented bronchospasm risk. At best this is a research question for bacterial tracheobronchitis, not for bronchitis in general.
To proceed, the following is needed:
- A safety review of the SAHPRA Professional Information, including warnings and contraindications, which is currently missing
- Mechanism of action data from DrugBank
- Confirmation of the registered original indications, which are not stated in the registration data
- Restriction of the question to culture-proven bacterial tracheobronchitis caused by multidrug-resistant Gram-negative organisms
- A plan to manage inhalation bronchospasm and nephrotoxicity before any prospective study
- Registered trials with a polymyxin B arm; the ongoing respiratory-infection trials listed under the “respiratory tract infectious disease” prediction (for example NCT07086391) could inform this
Related predictions in this Evidence Pack: Conjunctivitis has much stronger support (L1). It has several RCTs of topical polymyxin B/trimethoprim, but these are combination products and may reflect an existing labelled use. Respiratory tract infectious disease is at L2. Both are worth a separate evaluation.
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before application.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.