Tobramycin
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Tobramycin: From Bacterial Eye and Staphylococcal Infections to Exposure Keratitis
One-Sentence Summary
Tobramycin is an aminoglycoside antibiotic, originally used for bacterial infections such as conjunctivitis, uveitis-related eye disease, and Staphylococcus aureus infection. The TxGNN model predicts it may be effective for Exposure Keratitis, but no clinical trials and only 8 publications (in vitro studies, case reports, and one retrospective cohort) are available, with no controlled human evidence for this indication.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Bacterial and ocular infections (e.g., conjunctivitis, Staphylococcus aureus infection), based on the knowledge graph; no approved indication text is available in the US license records |
| Predicted New Indication | Exposure keratitis |
| TxGNN Prediction Score | 99.93% |
| Evidence Level | L4 |
| US Market Status | Cancelled only (no currently valid licenses) |
| Number of NDAs | 15 (all cancelled; includes 2 NDAs and 13 ANDAs) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, tobramycin is an aminoglycoside antibiotic with activity against Gram-negative bacteria (including Pseudomonas aeruginosa) and Staphylococcus aureus. Its efficacy in bacterial eye infections is established, and topical ophthalmic use is well known.
Exposure keratitis is mainly a non-infectious condition caused by corneal drying and epithelial injury, usually from incomplete eyelid closure. A mechanistic fit therefore exists only in a limited sense: tobramycin could prevent or treat secondary bacterial infection of a compromised cornea. One case report in the data describes bacterial keratitis in a patient who could not close his eyes, which illustrates this scenario.
There is also a notable concern. An in vitro study found that aminoglycosides, including tobramycin, are toxic to corneal epithelial cells. This is a worry in an epithelium that is already damaged. The prediction is therefore plausible only as infection prophylaxis or treatment, not as treatment of the underlying condition.
Clinical Trial Evidence
Currently no related clinical trials registered for exposure keratitis.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 42842711 | 2026 | Retrospective cohort | Cornea | Compares clinical features, susceptibility, treatment, and outcomes of MRSA vs. MSSA keratitis |
| 2707046 | 1989 | In vitro study | Current Eye Research | Compared corneal epithelial toxicity of neomycin, gentamicin, tobramycin, and amikacin in rabbit cell culture |
| 17228760 | 2006 | In vitro study | Nippon Ganka Gakkai Zasshi | MIC and postantibiotic effect of antibiotic eyedrops against isolates from infectious keratitis in Japan |
| 34987857 | 2021 | Case report | Oxford Medical Case Reports | Multidrug-resistant Shewanella algae keratitis in a patient unable to close his eyes |
| 12861116 | 2003 | Case report | Eye & Contact Lens | Bilateral MRSA keratitis after photorefractive keratectomy |
| 11581057 | 2001 | Case report | Ophthalmology | Contact lens-related Bacillus cereus keratitis |
| 14574976 | 2003 | Case report | Yan Ke Xue Bao | Paracentral corneal dellen as a rare sign of Graves ophthalmopathy |
| 42358321 | 2026 | In vitro study (veterinary) | Frontiers in Veterinary Science | Effect of fluorometholone on antibiotic susceptibility of canine ocular bacteria |
None of these studies directly tests tobramycin for exposure keratitis.
US Market Information
All 15 US licenses are cancelled. Approved indication text is not available in the data compiled for this report. The main licenses are:
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA201688 | TOBI Podhaler (Viatris Specialty LLC) | Capsule | Not available (cancelled) |
| NDA205433 | Kitabis Pak (Pari Respiratory Equipment) | Solution | Not available (cancelled) |
| ANDA207444 | Tobramycin (St. Mary’s Medical Park Pharmacy) | Solution/Drops | Not available (cancelled) |
| ANDA211189 | Tobramycin (Xiromed LLC) | Lyophilized powder for injection | Not available (cancelled) |
| ANDA217344 | Tobramycin (Micro Labs Limited) | Inhalant | Not available (cancelled) |
The other 10 licenses are also cancelled generic ANDAs (solution, injection, and eye-drop forms).
Safety Considerations
- Knowledge-graph contraindication signals (from the drug-disease network, not label text): kidney disease, myasthenia gravis and other neuromuscular junction diseases, Parkinson disease and parkinsonian disorders, and glaucoma and ocular hypertension. Several eye conditions are also listed: herpes simplex virus keratitis, fungal or viral eye infection, ocular tuberculosis, ophthalmic herpes zoster, and corneal pigmentation. Others include diabetes mellitus, diabetic ketoacidosis, hypercalcemia, nephrocalcinosis, Clostridium difficile colitis, and perinatal necrotizing enterocolitis.
- Ocular surface toxicity: in vitro data show aminoglycoside toxicity to corneal epithelial cells, which matters in exposure keratitis.
- Drug Interactions: 100 interactions were found. Major ones include magnesium sulfate and mannitol. Moderate ones include other aminoglycosides and antibiotics (neomycin, kanamycin, vancomycin), amphotericin B, proton pump inhibitors (omeprazole, lansoprazole, pantoprazole, rabeprazole, dexlansoprazole), aspirin, and aminosalicylates (mesalazine, sulfasalazine, balsalazide, olsalazine).
Please refer to the package insert for official warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is high, but exposure keratitis is mainly a non-infectious condition, and no trials or controlled studies support tobramycin for it. Supporting literature is limited to in vitro work and case reports, and in vitro data raise corneal epithelial toxicity concerns.
To proceed, the following is needed:
- Clarification of the intended role (prophylaxis or treatment of secondary bacterial infection) versus standard care, such as lubrication and eyelid protection
- Comparative clinical data on safety and efficacy of topical tobramycin in patients with compromised corneal epithelium
- Mechanism of action data and package insert warnings and contraindications
- Current US market status for ophthalmic tobramycin, since all licenses in the data are cancelled
Other predictions reviewed: Otitis externa is the most plausible, with a mechanistic link through Pseudomonas aeruginosa and Staphylococcus aureus and historical case reports of tobramycin use in malignant otitis externa. However, it is closer to confirming an existing use than novel repurposing, and no controlled human trials were provided. Other predictions (post-bacterial disorder, infective urethral stricture, epidemic keratoconjunctivitis, and several non-bacterial conditions) have weak, indirect, or no evidence and are not recommended for advancement.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.