Sulbactam
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
- Sulbactam
- Sulbactam: From Bacterial Infections (Cholangitis, Staphylococcal and E. coli Infections) to Bacterial Arthritis
Sulbactam: From Bacterial Infections (Cholangitis, Staphylococcal and E. coli Infections) to Bacterial Arthritis
One-Sentence Summary
Sulbactam is a beta-lactamase inhibitor, originally used (usually combined with ampicillin) against bacterial infections such as cholangitis, Staphylococcus aureus infection and Escherichia coli infection. The TxGNN model predicts it may be effective for bacterial arthritis, but there are currently no registered clinical trials, and the 20 publications retrieved are mostly case reports, susceptibility data and older open-label studies.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Cholangitis, staphylococcal infection, E. coli infection (from the knowledge graph; the Singapore licence records contain no indication text) |
| Predicted New Indication | Bacterial arthritis |
| TxGNN Prediction Score | 99.79% |
| Evidence Level | L3 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| Recommended Decision | Hold (research question only; see note below) |
Note: The top-ranked indication is bacterial arthritis, so the overview follows it. Other predicted indications, particularly epiglottitis, sinusitis and infectious otitis media, have stronger supporting evidence and are summarised in the Conclusion.
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, sulbactam is an irreversible beta-lactamase inhibitor that is combined with ampicillin. It protects ampicillin from degradation and extends its coverage to beta-lactamase-producing S. aureus, streptococci, Enterobacteriaceae and anaerobes. Sulbactam also has intrinsic activity against Acinetobacter.
Staphylococcal infection is already among the original indications, and S. aureus and streptococci are the common pathogens of septic arthritis and bone/joint infection. The mechanistic link is therefore plausible and antibacterial in nature. However, the supporting evidence is largely case reports, susceptibility data and older open-label studies.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
The most relevant publications for bacterial arthritis (clinical studies prioritised over reviews and case reports):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 2677956 | 1989 | Randomised comparative study | Pediatr Infect Dis J | Ampicillin/sulbactam vs ceftriaxone in children with soft tissue infections, including 11 with suppurative arthritis and 9 with osteomyelitis |
| 3026009 | 1986 | Open, randomised comparative study | Rev Infect Dis | Sulbactam/ampicillin vs cefotaxime for bone, joint and soft-tissue infections; all 13 patients in the sulbactam/ampicillin group were cured or improved |
| 3026018 | 1986 | Clinical study | Rev Infect Dis | Nine children with osteomyelitis or septic arthritis treated with parenteral sulbactam/ampicillin followed by oral sultamicillin; all pathogens identified were susceptible |
| 3252119 | 1988 | Clinical trial | Mikrobiyol Bul | 84 patients with various infections, including 5 with septic arthritis or osteomyelitis, treated with ampicillin/sulbactam |
| 1745624 | 1991 | In vitro comparison and review | Pharmacotherapy | Compares in vitro activity of ampicillin-sulbactam and ticarcillin-clavulanate; extends coverage to beta-lactamase-producing staphylococci and anaerobes |
| 36804370 | 2023 | Review | Int J Antimicrob Agents | Off-label versus formally recommended antibiotic use for multidrug-resistant infections |
| 9263167 | 1997 | Case report | J Rheumatol | Pasteurella multocida arthritis after a cat bite, resolved with ampicillin/sulbactam, joint aspiration and intra-articular steroids |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN01949P | UNASYN 3000 FOR INJECTION | Injection, powder, for solution | Not stated in the licence data |
| SIN01948P | UNASYN 1500 FOR INJECTION | Injection, powder, for solution | Not stated in the licence data |
| SIN01950P | UNASYN 750 FOR INJECTION | Injection, powder, for solution | Not stated in the licence data |
All three are valid single-ingredient licences, manufactured by Haupt Pharma Latina S.r.L. The only registered route is injectable.
Safety Considerations
- Disease associations flagged in 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: No interaction records were found.
Please refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold (for bacterial arthritis, as a research question)
Rationale: The mechanistic link is plausible, but the evidence for bacterial arthritis is limited to small, older, mostly open-label studies and case reports, with no registered trials. Evidence is also graded L3 and the programme stage is S1. In addition, the safety review cannot proceed because the Singapore package insert warnings and contraindications have not been obtained.
Other predicted indications worth noting:
- Infectious otitis media (L2, Proceed with Guardrails): comparative clinical studies against amoxicillin and amoxicillin-clavulanate.
- Epiglottitis (L3, Proceed with Guardrails): reviews and a paediatric clinical study; airway management remains the priority.
- Sinusitis (L3, Proceed with Guardrails): clinical reviews and older studies; established first-line alternatives exist.
- Chronic otitis media (L3, research question), chronic rhinosinusitis and paratyphoid fever (L4, Hold): weak or indirect evidence.
- Chronic ethmoidal sinusitis, paranasal sinus neoplasm and diffuse scleroderma (L5, Hold): model prediction only, and no plausible mechanism for the neoplasm and scleroderma predictions.
To proceed, the following is needed:
- Singapore package insert warnings and contraindications (a blocking gap for safety screening)
- Detailed mechanism of action data
- Approved indication text for the Singapore licences
- Prospective or well-designed comparative data in bone and joint infection, and comparison with current standard-of-care regimens
- Local susceptibility data for the relevant pathogens
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.