Cloxacillin
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Cloxacillin: From Staphylococcal Infections to Chronic Rhinosinusitis
One-Sentence Summary
Cloxacillin is a penicillinase-resistant penicillin, originally used for staphylococcal infections such as Staphylococcus aureus infection, pharyngitis, staphylococcal pneumonia and sinusitis. The TxGNN model predicts it may be effective for chronic rhinosinusitis, but no clinical trials and no publications currently support this specific prediction, so it rests on model prediction alone.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Staphylococcus aureus infection, staphylococcal infection, pharyngitis, staphylococcal pneumonia, sinusitis (the approved indication text in the Singapore licences is blank, so these come from the knowledge graph) |
| Predicted New Indication | Chronic rhinosinusitis |
| TxGNN Prediction Score | 98.31% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 5 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, cloxacillin is a beta-lactamase-stable penicillin with an established role against staphylococcal infections, and mechanistically it may be applicable to staphylococcus-associated sinus disease.
Sinusitis is already one of cloxacillin's listed indications, so the prediction for the chronic form largely reflects closeness to that known use in the knowledge graph. The link is weak. Chronic rhinosinusitis is often polymicrobial and driven by inflammation, and cloxacillin has a narrow spectrum, so it would cover only the staphylococcal component.
Other predictions fall into three groups:
- Closely related to existing uses: chronic ethmoidal sinusitis, pneumonia, laryngitis and epiglottitis. Support is theoretical or indirect.
- Biologically implausible, likely false positives: paranasal sinus neoplasm, celiac trunk compression syndrome, abdominal cystic lymphangioma and abdominal ectopic pregnancy.
- Most evidence among the predictions: bacterial arthritis (rank 5). It is the only one with a clinical trial, and it has an animal study and a pharmacokinetic study of cloxacillin. It is mostly an extension of the existing staphylococcal infection indication.
Clinical Trial Evidence
Currently no related clinical trials are registered for chronic rhinosinusitis.
For reference, the only trial found among the predicted indications concerns bacterial arthritis (rank 5):
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT04141787 | Phase 4 | Unknown | 310 | Randomized non-inferiority trial of home IV ceftriaxone for deep-seated staphylococcal infections, including bone and joint. Ceftriaxone is the experimental arm and cloxacillin is probably the comparator, so it does not test cloxacillin as a repurposed drug. |
Literature Evidence
Currently no related literature is available for chronic rhinosinusitis.
For reference, the most relevant publications for the other predicted indications are:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 26695535 | 2016 | Animal study | Cellular Microbiology | Cloxacillin controlled experimental S. aureus arthritis and was associated with lower local and systemic cytokines (bacterial arthritis) |
| 10350394 | 1999 | Pharmacokinetic study | J Antimicrob Chemother | Cloxacillin 2 g IV reached bactericidal activity in synovial fluid against S. aureus isolates (bacterial arthritis) |
| 30772469 | 2019 | Review | Int J Infect Dis | Review of antibiotic penetration into bone and joint tissue (bacterial arthritis) |
| 3209935 | 1988 | Case series | J Laryngol Otol | 42 adults with acute epiglottitis in Singapore; indirect evidence only (epiglottitis) |
| 35228218 | 2022 | Case report | BMJ Case Reports | Glottic S. aureus infection in a patient with lupus (laryngitis) |
| 7102917 | 1982 | Case report | Am J Trop Med Hyg | Severe staphylococcal pneumonia treated with high-dose cloxacillin that still progressed to respiratory failure (pneumonia) |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15834P | MEIXAM POWDER FOR SOLUTION FOR INJECTION 500MG/VIAL | Powder for solution for injection | Not stated |
| SIN09934P | OXACIL GRANULES 125MG/5ML | Granule for suspension | Not stated |
| SIN05036P | CLOXACAP 250 CAPSULE 250 mg | Capsule | Not stated |
| SIN07168P | CLOXACILLIN PANPHARMA FOR INJECTION 500 mg/vial | Powder for solution for injection | Not stated |
| SIN08889P | CLOXACAP 500 CAPSULE 500 mg | Capsule | Not stated |
All five licences are valid single-ingredient products, available as injectable, oral capsule and granule forms.
Safety Considerations
- Contraindication-related diseases (from the knowledge graph, not label text): kidney disease, pyoureter, Clostridium difficile colitis, perinatal necrotizing enterocolitis, infectious mononucleosis, and chronic Epstein-Barr virus infection syndrome.
- Drug Interactions: 17 interactions were identified.
- Major: methotrexate.
- Moderate: doxycycline, tetracycline, minocycline, demeclocycline, balsalazide, picosulfuric acid, iodide I-131, iodide I-123, warfarin, proguanil, chloramphenicol, ethinylestradiol, mycophenolic acid and pemetrexed.
- Minor: clarithromycin and erythromycin.
Please refer to the package insert for warnings and label contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction for chronic rhinosinusitis is supported only by model scoring (L5), with no trials or literature. It largely duplicates the existing sinusitis indication, and cloxacillin's narrow spectrum fits poorly with the polymicrobial, inflammatory nature of chronic disease. Bacterial arthritis is the most plausible lead, but it is mostly an extension of the existing staphylococcal infection indication and has no direct clinical trial of cloxacillin.
To proceed, the following is needed:
- Package insert warnings and contraindications from HSA, which are needed before safety screening
- Mechanism of action data (for example from DrugBank)
- Clinical studies of cloxacillin in chronic rhinosinusitis, or a decision to prioritise the better-supported bacterial arthritis question
- The approved indication text for the Singapore licences, which is currently blank
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.