Ceftriaxone
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Ceftriaxone: From Bacterial Infections to Infectious Otitis Media
One-Sentence Summary
Ceftriaxone is a third-generation cephalosporin antibiotic, originally used for bacterial infections such as pneumonia, meningitis, gonorrhoea and salmonellosis. The TxGNN model's top-ranked prediction is polyclonal hyperviscosity syndrome, but it has no supporting evidence. The best-supported prediction is infectious otitis media, with 1 clinical trial (which does not test ceftriaxone) and 18 publications currently supporting this direction. Since otitis media is itself a bacterial infection, this is closer to an already-practised use than to novel repurposing.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the Singapore licence records. The knowledge graph lists streptococcal infection, bacterial pneumonia, bacterial meningitis, gonorrhoea, salmonellosis and bacterial arthritis, among others. |
| Predicted New Indication | Top-ranked by TxGNN: polyclonal hyperviscosity syndrome (no evidence). Best-supported: infectious otitis media (rank 4). |
| TxGNN Prediction Score | 99.39% (polyclonal hyperviscosity syndrome); 99.26% (infectious otitis media) |
| Evidence Level | L5 (polyclonal hyperviscosity syndrome); L4 (infectious otitis media) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 20 |
| Recommended Decision | Hold (polyclonal hyperviscosity syndrome); Proceed with Guardrails is not yet justified for otitis media, which remains a research question |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, ceftriaxone is a beta-lactam cephalosporin that kills susceptible bacteria by interfering with cell-wall synthesis. Its efficacy in bacterial infections of the respiratory tract, meninges and other sites is established.
The top-ranked prediction is not credible. Polyclonal hyperviscosity syndrome scores highest (99.39%), but ceftriaxone has no known effect on serum viscosity or polyclonal gammopathy. No trials or literature support it. The score reflects graph-based association only.
Infectious otitis media is the most plausible prediction. Ceftriaxone is active against the main pathogens of acute otitis media (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis). Single-dose intramuscular use is described in the literature, including a comparison with trimethoprim-sulfamethoxazole. Because the original indications are also bacterial infections, this is a natural extension rather than a new mechanism. Related predictions (suppurative otitis media, chronic otitis media, middle ear disease) share the same rationale, but their evidence largely overlaps and is weaker. In chronic suppurative disease, Pseudomonas aeruginosa, Staphylococcus aureus and biofilms may limit reliability.
Other predictions (hyperamylasemia, congenital analbuminemia, blood group incompatibility, premalignant haematological disease) have no mechanistic rationale. Otosalpingitis is anatomically plausible but has no evidence.
Clinical Trial Evidence
For infectious otitis media:
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02567825 | Not applicable | Completed | 250 | Tympanostomy tubes vs non-surgical management in children with recurrent acute otitis media. It does not test ceftriaxone, so it provides disease-context relevance only. |
No clinical trials are registered for the other predicted indications.
Literature Evidence
Selected publications for infectious otitis media and suppurative otitis media:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 8989332 | 1997 | Comparative trial (likely RCT; to be verified) | Pediatrics | Single intramuscular ceftriaxone dose vs 10 days of oral trimethoprim-sulfamethoxazole for acute otitis media |
| 11099083 | 2000 | Clinical study | Pediatr Infect Dis J | One-day vs three-day intramuscular ceftriaxone for nonresponsive acute otitis media in children |
| 9877360 | 1998 | Clinical study | Pediatr Infect Dis J | Bacteriologic efficacy of a three-day intramuscular ceftriaxone regimen in nonresponsive acute otitis media |
| 2523493 | 1989 | Clinical study (likely non-randomised) | Jpn J Antibiot | Ceftriaxone 1 g daily vs cefotiam in acute suppurative otitis media and acute exacerbation of chronic disease; efficacy 71% vs 86% |
| 35841649 | 2022 | Cohort | Int J Pediatr Otorhinolaryngol | Factors associated with ceftriaxone use for acute otitis media in US primary care |
| 10688388 | 2000 | Review | Clin Ther | Review of treatment recommendations for acute otitis media |
| 12166789 | 2002 | Consensus recommendations | Clin Pediatr | Consensus recommendations for managing acute otitis media |
| 20802367 | 2010 | Review | Otol Neurotol | Prevention and treatment of meningitis and otitis media in children with cochlear implants |
| 32796134 | 2020 | Case report | Eur J Microbiol Immunol | Chronic otitis media with Vibrio cholerae, treated with ciprofloxacin and ceftriaxone |
| 31315659 | 2019 | Microbiology study | BMC Res Notes | Prevalence and causative organisms of chronic suppurative otitis media in Tanzania |
For hyperamylasemia, the only ceftriaxone-specific paper (10458061, 1999) concerns infection prophylaxis after endoscopic papillosphincterotomy, not treatment of hyperamylasemia. For blood group incompatibility, the retrieved papers are about fetal cholelithiasis and ceftriaxone-resistant Salmonella Typhi, not therapeutic evidence.
Singapore Market Information
There are 20 valid single-ingredient registrations, all injectable powders for solution. The data compiled for this report contain no approved indication text. The main authorisations are:
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN00388P | ROCEPHIN FOR INJECTION 1 g/vial (intramuscular) | Powder for solution for injection | Not available |
| SIN00566P | ROCEPHIN FOR INJECTION 1 g/vial (intravenous) | Powder for solution for injection | Not available |
| SIN15008P | CEFTRIAXONE KABI 1 g/vial | Powder for solution for injection | Not available |
| SIN16822P | Ceftriaxone ADVAGEN 2 g/vial | Powder for solution for injection | Not available |
| SIN16289P | MEDAXONE 1 g/vial | Powder for solution for injection or infusion | Not available |
Safety Considerations
- Contraindication-related conditions (from the knowledge graph, not label text): liver disease, gallbladder disease, neonatal jaundice, Clostridium difficile colitis, perinatal necrotizing enterocolitis, hemolytic anemia.
- Drug Interactions (100 recorded; main ones shown):
- Major: calcium chloride, calcium glucoheptonate, calcium gluconate (calcium-containing products).
- Moderate: kanamycin, neomycin, streptomycin (aminoglycosides) and picosulfuric acid.
- Other recorded interactions have an unknown severity level.
Please refer to the package insert for warnings and contraindications, as label-based safety data were not available.
Conclusion and Next Steps
Decision: Hold
Rationale: The highest-scoring prediction (polyclonal hyperviscosity syndrome) has no mechanistic or clinical support. The most plausible indication, infectious otitis media, is an already-practised antibacterial use supported mainly by older studies, reviews and prescribing data. The only registered trial does not test ceftriaxone, and no confirmed Phase 3 RCT is available. Since the required safety screening cannot be completed without label data, it cannot yet move to a Go or Proceed with Guardrails decision.
To proceed, the following is needed:
- Singapore package insert warnings, contraindications and approved indication text
- Mechanism of action data
- Verification of PMID 8989332 as an RCT, and a review of other ceftriaxone otitis media trials for formal evidence grading
- Confirmation of whether otitis media is already within ceftriaxone's approved Singapore indications, which would make it a label extension question rather than repurposing
- Route compatibility assessment (the current injectable-only forms versus the needs of otitis media management)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.