Polymyxin B
| Evidence Level: L4 | Predicted Indications: 3 |
Table of Contents
Polymyxin B: From Gram-Negative Bacterial Infections to Bronchitis
One-Sentence Summary
Polymyxin B is a polypeptide antibiotic that acts against Gram-negative bacteria. The data compiled for this report do not include its approved indication text. The TxGNN model predicts it may be effective for bronchitis (score 99.87%), but there are 0 registered clinical trials and only 12 publications retrieved, mostly small, old, or indirect studies. Two other predictions were also generated: laryngotracheitis (no supporting evidence) and conjunctivitis (19 publications, including several randomized trials of polymyxin B/trimethoprim combination products).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available in the data compiled for this report (approved indication text is blank in all licenses) |
| Predicted New Indication | Bronchitis |
| TxGNN Prediction Score | 99.87% |
| Evidence Level | L4 |
| US Market Status | Cancelled only (no currently valid licenses) |
| Number of NDAs | 5 (all ANDAs, all cancelled) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available. Based on general knowledge, polymyxin B is a cationic polypeptide antibiotic that disrupts the outer membrane of Gram-negative bacteria. This makes a link plausible to bacterial tracheobronchitis or pneumonia caused by multidrug-resistant organisms such as Pseudomonas aeruginosa and Acinetobacter baumannii.
However, the supporting evidence is weak and the signals are mixed. Some studies examine inhaled polymyxin B in respiratory infections (a ventilator-associated pneumonia/tracheobronchitis comparison, and a small case series of 19 patients). Others show that inhaled or endobronchial polymyxin B can provoke bronchoconstriction, is used as a non-specific bronchial provocation agent in asthma and chronic bronchitis, and induces airway eosinophil accumulation in animal models. This raises a respiratory safety concern for airway delivery. The very high TxGNN score is not backed by trial data, and ventilator-associated pneumonia is not equivalent to bronchitis.
The other two predictions fare differently. Laryngotracheitis (croup) is mostly viral, and the prediction rests on the model score alone, with no trials or literature. Conjunctivitis is mechanistically coherent, but polymyxin B/trimethoprim ophthalmic solution is already used for bacterial conjunctivitis, so this is closer to an established use than a novel repurposing.
Clinical Trial Evidence
Currently no related clinical trials registered for bronchitis (and none for the other two predicted indications).
Literature Evidence
Selected publications for the top prediction (bronchitis):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 23124906 | 2013 | Comparative study/review | Infection | Compared polymyxin B with other antimicrobials for VAP and tracheobronchitis caused by P. aeruginosa or A. baumannii |
| 17350201 | 2007 | Case series | Diagn Microbiol Infect Dis | 19 patients given inhaled polymyxin B for MDR Gram-negative respiratory infections (14 pneumonia, remainder tracheobronchitis) |
| 4373513 | 1974 | Clinical report | J Kans Med Soc | Systemic gentamicin plus polymyxin B aerosol for Pseudomonas tracheobronchitis |
| 4322737 | 1971 | Safety report | Ann Intern Med | Danger of polymyxin B inhalation |
| 231152 | 1979 | Physiology study | Lung | Bronchial reactivity to inhaled polymyxin B in asthma and chronic obstructive bronchitis |
| 4319158 | 1970 | Experimental observation | Chest | Endobronchial polymyxin B in chronic bronchitis |
| 2984629 | 1985 | Provocation study | Orv Hetil | Polymyxin B-induced non-specific bronchial provocation in asthma and chronic bronchitis |
| 11359434 | 2001 | Animal study | Clin Exp Allergy | Polymyxin B-induced airway eosinophil accumulation reduced bronchial responsiveness in guinea pigs |
| 8054833 | 1994 | Animal model | Clin Auton Res | Polymyxin B used to create a guinea-pig eosinophilic bronchitis model for cough studies |
For the conjunctivitis prediction, the stronger studies are randomized trials of polymyxin B/trimethoprim (combination product, not polymyxin B alone):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 23092529 | 2013 | RCT | J Pediatr | Single-blinded trial of polymyxin B-trimethoprim vs moxifloxacin in children with acute conjunctivitis |
| 19043945 | 2008 | RCT | J Pediatr Ophthalmol Strabismus | Multicenter comparison of polymyxin B/trimethoprim vs moxifloxacin for speed of clinical efficacy |
| 19043943 | 2008 | RCT | J Pediatr Ophthalmol Strabismus | Moxifloxacin vs polymyxin B/trimethoprim in pediatric bacterial conjunctivitis |
| 6188739 | 1983 | Multicentre trial | J Antimicrob Chemother | 230 patients; trimethoprim-polymyxin B vs neomycin-polymyxin B-gramicidin and chloramphenicol; all effective |
| 2850891 | 1988 | Double-blind RCT | Curr Med Res Opin | Trimethoprim-polymyxin B vs chloramphenicol ointment (42 patients); no significant differences |
| 11270936 | 2001 | Review | Drugs | Comparative review of 16 topical ophthalmic antibacterials; polymyxin B targets Gram-negative species |
No literature is available for laryngotracheitis.
US Market Information
All five US authorizations are generic (ANDA) injectable products and are listed as cancelled. Approved indication text is not available in the data compiled for this report.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ANDA202766 | Polymyxin B (Xellia) | Injection, powder, for solution | Not available |
| ANDA207322 | Polymyxin B (Gland Pharma) | Injection, powder, lyophilized, for solution | Not available |
| ANDA065372 | Polymyxin B (Fresenius Kabi) | Injection, powder, lyophilized, for solution | Not available |
| ANDA206589 | Polymyxin B (Eugia) | Injection, powder, lyophilized, for solution | Not available |
| ANDA060716 | Polymyxin B (Hikma) | Injection, powder, for solution | Not available |
Safety Considerations
- Drug Interactions: 73 interactions were recorded. Examples of Major-level interactions include:
- Amikacin
- Cisatracurium
- Cidofovir
- Deferasirox
- Botulinum toxin type A
- Intravenous human immunoglobulin G
- Iodinated contrast agents (iothalamic acid, diatrizoate)
- Live cholera vaccine
- Moderate-level examples: capreomycin, mesalazine, balsalazide, ibandronate, clofarabine, estradiol, ethinylestradiol.
- Respiratory concern from the literature: inhaled or endobronchial polymyxin B can cause bronchoconstriction and airway eosinophilic inflammation, which is directly relevant to the bronchitis prediction.
- Ocular concern from the literature: a case report describes anaphylaxis to polymyxin B-trimethoprim eye drops.
Please refer to the package insert for the full warnings and contraindications, which were not available in the data compiled for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: For bronchitis, the evidence is limited to indirect, small, or old studies and animal models, with no registered trials, and the literature raises airway safety concerns. The high TxGNN score alone is not enough. Laryngotracheitis has no supporting evidence at all. Conjunctivitis is supported by randomized comparisons, but these involve the polymyxin B/trimethoprim combination, which is already an established use, so it is not a new repurposing finding.
To proceed, the following is needed:
- Package insert warnings and contraindications (a blocking gap for safety screening)
- Mechanism of action data and the original approved indication text
- For bronchitis: controlled clinical data on inhaled polymyxin B with a respiratory safety assessment (bronchospasm risk), and a clear distinction between bronchitis and ventilator-associated pneumonia or tracheobronchitis
- For conjunctivitis: confirmation of the current US status of polymyxin B ophthalmic products, since the injectable licenses listed are all cancelled, and evaluation of polymyxin B alone versus the combination
- Route and formulation compatibility assessment (currently only injectable forms are listed)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.