Polymyxin B
| Evidence Level: L4 | Predicted Indications: 2 |
Table of Contents
Polymyxin B: Bronchitis
One-Sentence Summary
Polymyxin B is a polypeptide antibiotic that acts against Gram-negative bacteria. In India it is marketed as injectable and ophthalmic products. The TxGNN model predicts it may be effective for bronchitis, but no clinical trials are registered for this use. The 12 publications found are mostly small cohort studies, older provocation studies and animal models, so direct support is weak.
Quick Overview
| Item | Content |
|---|---|
| Predicted New Indication | Bronchitis |
| TxGNN Prediction Score | 0.9987 |
| Evidence Level | L4 |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| Recommended Decision | Hold |
The license records compiled for this report do not state an approved indication, so the original indication is not listed in this table.
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on general knowledge, polymyxin B is a bactericidal polypeptide antibiotic that disrupts the outer membrane of Gram-negative bacteria. This includes multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. It is therefore mechanistically plausible for bacterial infections of the airways caused by resistant Gram-negative organisms.
The link between the original use (Gram-negative infection) and bronchitis is indirect. The relevant literature covers two areas:
- Respiratory infection: ventilator-associated pneumonia and tracheobronchitis comparisons (2013) and an inhaled salvage-treatment report (2007).
- Provocation studies: older work from 1970 to 1985 that used inhaled polymyxin B as a bronchial provocation agent in asthma and chronic bronchitis. Several records show it can trigger bronchial reactivity and bronchoconstriction. Animal models even use it to induce eosinophilic bronchitis.
The very high TxGNN score is a model prediction only. No bronchitis-specific efficacy trial supports it. The existing evidence also raises a safety concern about inhaled use.
Conjunctivitis has randomized trials, but they test the polymyxin B/trimethoprim combination, and it is an existing marketed ophthalmic use rather than true repurposing. Laryngotracheitis has no supporting trials or literature.
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 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 pneumonia or tracheobronchitis, used as salvage or initial therapy |
| 4373513 | 1974 | Not classified | J Kans Med Soc | Pseudomonas tracheobronchitis treated with systemic gentamicin plus polymyxin B aerosol |
| 4319158 | 1970 | Cohort | Chest | Experimental observations of endobronchial polymyxin B in chronic bronchitis |
| 4322737 | 1971 | Review | Ann Intern Med | Warns of the danger of polymyxin B inhalation |
| 231152 | 1979 | Cohort | Lung | Bronchial reactivity to inhaled polymyxin B in asthma and chronic obstructive bronchitis |
| 2984629 | 1985 | Cohort | Orv Hetil | Polymyxin B-induced non-specific bronchial provocation in asthma and chronic bronchitis |
| 7402949 | 1980 | Not classified | Pneumonol Pol | Exercise-induced bronchospasm compared with histamine and polymyxin B provocation tests |
| 8054833 | 1994 | Cohort (animal) | Clin Auton Res | Intranasal polymyxin B produced a guinea-pig eosinophilic bronchitis model for cough studies |
| 11359434 | 2001 | Preclinical | Clin Exp Allergy | Polymyxin B-induced airway eosinophil accumulation reduced bronchial responsiveness in guinea pigs |
None of these is a randomized trial of polymyxin B for bronchitis. The two most relevant infection studies are cohort studies of ventilator-associated respiratory infection. Most other records use polymyxin B as an experimental provoking agent rather than a treatment.
India Market Information
Polymyxin B has 20 valid single-ingredient registrations. Most are injectables, and a few are ophthalmic (eye ointment, eye drops, eye/ear drops). No inhaled or nebulized product appears among the registrations, so a bronchitis use would not match an existing route. The license records do not state approved indications. Five main registrations are shown below.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 189646 | Reinvexin 5MIU Injection (Wockhardt) | Injection, vial of 1 ml | Not stated in license record |
| 115011 | Jetmixin 5MIU Injection (Scutonix Lifesciences) | Injection, vial | Not stated in license record |
| 175417 | Paxyb Injection (Glenmark) | Injection, vial of 5 ml | Not stated in license record |
| 174942 | Paximid 500000IU Injection (Cipla) | Injection, vial | Not stated in license record |
| 177905 | Poly C Eye Ointment (Kaizen Pharmaceuticals) | Eye ointment, tube of 5 gm | Not stated in license record |
Safety Considerations
- Respiratory risk with inhalation: the retrieved literature shows inhaled polymyxin B can provoke bronchial reactivity and bronchoconstriction, particularly in people with asthma or chronic bronchitis.
- Systemic toxicity: systemic use carries a risk of nephrotoxicity and neurotoxicity.
- Drug Interactions: 73 interactions were identified. Major-level interactions include:
- Aminoglycosides (amikacin)
- Neuromuscular agents (cisatracurium, botulinum toxin type A, botulinum neurotoxin A/B immune globulin)
- Nephrotoxic agents (cidofovir, deferasirox, iodinated contrast agents such as iothalamic acid and diatrizoate)
- Human immunoglobulin G (intravenous) and human cytomegalovirus immune globulin
- Live cholera vaccine (Vibrio cholerae CVD 103-HgR)
Moderate-level interactions include ethinylestradiol, estradiol, mestranol, mesalazine, balsalazide, ibandronate, capreomycin, clofarabine and picosulfuric acid.
Please refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The 0.9987 score is a prediction only. There are no registered trials, and the literature is limited to small cohort studies of resistant Gram-negative respiratory infection, older provocation studies, and animal models. The inhalation-related bronchospasm signal and systemic toxicity must be resolved before further investment.
To proceed, the following is needed:
- Package insert warnings and contraindications from the India regulator’s website, which are not yet available and block safety screening
- Detailed mechanism of action data
- Direct clinical evidence in bacterial bronchitis, ideally a controlled trial
- A safety assessment of any inhaled or nebulized route, including bronchospasm risk, as no such formulation is registered
- A defined target population, since most bronchitis is viral or non-bacterial and a stewardship plan would be needed
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.