Tobramycin
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Tobramycin: From Topical Ophthalmic Antibacterial to Exposure Keratitis
One-Sentence Summary
Tobramycin is an aminoglycoside antibiotic. Its two South African registrations are for eye drops and eye ointment, so its original use is topical ocular anti-infective therapy. The TxGNN model predicts it may be useful for exposure keratitis. The current support is weak: 2 registered trials (neither actually tests tobramycin) and 7 publications (case reports, in vitro and laboratory studies, no randomised trials).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the registration data. Ophthalmic dosage forms suggest topical ocular anti-infective use. |
| Predicted New Indication | Exposure keratitis |
| TxGNN Prediction Score | 99.93% (model rank 671) |
| Evidence Level | L4 |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 2 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in the Evidence Pack. Tobramycin is known to be a bactericidal aminoglycoside that binds the 30S ribosomal subunit. It is already used on the eye surface in the form of the registered drops and ointment.
Exposure keratitis occurs when the cornea is not adequately protected by the eyelids. Examples are patients who cannot close their eyes, such as those who are sedated or in a vegetative state. The dried, damaged corneal surface is prone to secondary bacterial infection, and a topical antibacterial could plausibly help treat or prevent that infection. Note that the benefit would come from treating the infection, not from any effect on the underlying exposure.
A safety concern runs against this. An in vitro study (PMID 2707046) found that aminoglycosides, including tobramycin, are toxic to corneal epithelial cells. On an already compromised ocular surface, this could work against healing.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT05313828 | N/A | Unknown | 40 | Treatment options for dendritic (viral) corneal ulcer. Tobramycin is not a confirmed intervention and has no antiviral activity. |
| NCT06200727 | N/A | Unknown | 170 | Platelet-rich fibrin membrane in ophthalmic disease, including corneal ulcer. Not a tobramycin study. |
No SANCTR or PACTR registrations were identified in the Evidence Pack. Both trials were graded low relevance (C), so they provide no direct support for this prediction.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 34987857 | 2021 | Case report | Oxford Med Case Rep | Multidrug-resistant Shewanella algae keratitis in a patient who could not close his eyes, which is the exposure setting. |
| 11581057 | 2001 | Case report | Ophthalmology | Bacillus cereus keratitis linked to contact lens wear. |
| 12861116 | 2003 | Case report | Eye & Contact Lens | Bilateral MRSA keratitis after photorefractive keratectomy. |
| 2707046 | 1989 | In vitro study | Curr Eye Res | Neomycin, gentamicin, tobramycin and amikacin were toxic to rabbit corneal epithelial cells in culture. |
| 17228760 | 2006 | In vitro study | Nippon Ganka Gakkai Zasshi | Compared MIC and post-antibiotic effect of antibiotic eye drops on isolates from infectious keratitis in Japan. |
| 14574976 | 2003 | Case report | Yan Ke Xue Bao | Paracentral corneal dellen as a rare sign of Graves ophthalmopathy. Marginal relevance. |
| 33847093 | 2021 | Veterinary case series | Pol J Vet Sci | Feline ocular toxoplasmosis. Not applicable to human exposure keratitis. |
No randomised or controlled human studies of tobramycin in exposure keratitis were found.
South Africa Market Information
| Registration Number | Product Name | Dosage Form |
|---|---|---|
| Reg. No. 49/15.3/0196 | Mydex | Drops |
| Reg. No. X/15.3/92 | Tobradex 3.5g | Eye ointment |
The approved indication text and Essential Medicines List status are not recorded for these registrations. Both registered forms are topical, and no systemic or inhaled tobramycin product appears in this dataset.
Safety Considerations
Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.
One point from the evidence gathered is directly relevant to this indication. Laboratory data show aminoglycoside toxicity to corneal epithelium (PMID 2707046), which could be a concern on an already damaged ocular surface.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is high, but no study has tested tobramycin in exposure keratitis. Both listed trials are unrelated to tobramycin, and the literature is limited to case reports and laboratory studies. Tobramycin’s potential corneal epithelial toxicity is a further reason for caution.
To proceed, the following is needed:
- The SAHPRA-approved Professional Information, for warnings and contraindications and the registered indication text.
- Mechanism-of-action data from DrugBank.
- Clinical data specific to exposure keratitis, for example comparative or observational studies of topical tobramycin in patients with incomplete eyelid closure.
- An assessment of whether the tobramycin products registered in South Africa (drops and eye ointment) match the route needed for this use.
Other TxGNN predictions for tobramycin have stronger support and may be better research priorities. These include inhaled tobramycin for Pseudomonas aeruginosa infection in bronchiectasis, which has Phase 3 and Phase 4 trials, and otitis externa. No inhaled product appears in the current South African registrations.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.