Ticarcillin
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
- Ticarcillin
- Ticarcillin: From Gram-Negative Bacterial Infections to Intra-Abdominal Infection / Peritonitis
Ticarcillin: From Gram-Negative Bacterial Infections to Intra-Abdominal Infection / Peritonitis
One-Sentence Summary
Ticarcillin is a broad-spectrum antipseudomonal penicillin historically used against serious gram-negative bacterial infections, including Pseudomonas aeruginosa. Among the top 10 TxGNN-predicted indications for this drug, 8 were flagged during evidence review as biologically implausible false positives with zero supporting literature or trials — the only candidate with real supporting evidence is Intra-Abdominal Infection / Peritonitis, backed by 20 publications (including one open-label clinical trial), though no clinical trials were retrieved automatically.
Screening note: TxGNN ranks 1–8 and 10 (e.g., lymph node palisaded myofibroblastoma, abdominal ectopic pregnancy, sacrum chordoma, pelvic varices) were explicitly assessed in the evidence pack itself as knowledge-graph noise with no mechanistic plausibility and no evidence — they are not reported further. Rank 9 (disease of peritoneum) is the only candidate that reached decision stage S2 (“Proceed with Guardrails”) and is the focus of this report.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Gram-negative bacterial infections, incl. Pseudomonas aeruginosa (general antibacterial class use — specific approved indication text not present in evidence pack) |
| Predicted New Indication | Intra-Abdominal Infection / Peritonitis (disease of peritoneum) |
| TxGNN Prediction Score | 99.81% |
| Evidence Level | L3 |
| India Market Status | Not Marketed |
| Number of Registrations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available (DrugBank MOA field is a data gap). Based on known pharmacological class information, Ticarcillin is a carboxypenicillin with an antipseudomonal spectrum. It kills susceptible gram-negative organisms — including Pseudomonas aeruginosa, E. coli, Klebsiella spp., and (when combined with clavulanic acid) anaerobes such as Bacteroides — by binding penicillin-binding proteins (PBPs) and inhibiting bacterial cell wall synthesis.
Intra-abdominal infections and peritonitis (postoperative, secondary, or pelvic) are typically polymicrobial, involving exactly the pathogen classes covered by ticarcillin’s spectrum. This is therefore not a novel mechanistic leap but a recognition of an already well-established clinical use pattern: multiple studies in the evidence set use the ticarcillin/clavulanate combination (marketed historically as BRL28500/Timentin) specifically for intra-abdominal sepsis, postoperative peritonitis, and pelvic abscess (e.g., Douglas’ abscess).
The remaining 9 TxGNN top-ranked predictions lack any biological rationale connecting an antibacterial mechanism to structural, oncologic, or vascular diseases (e.g., chordoma, ectopic pregnancy, varices), and are correctly excluded as embedding-similarity artifacts rather than genuine repurposing signals.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 3302345 | 1987 | Clinical Trial (open-label) | Jpn J Antibiot | BRL28500 (ticarcillin/clavulanate) treated 76 cases of intraperitoneal and biliary tract infection with documented ascites drug levels |
| 3499526 | 1987 | Clinical Trial | Jpn J Antibiot | BRL28500 evaluated in 18 patients with pelvioperitonitis / Douglas’ abscess |
| 2691475 | 1989 | Prospective Cohort | J Antimicrob Chemother | 50 consecutive patients with secondary peritonitis treated with ticarcillin/clavulanate as initial empirical therapy |
| 2024225 | 1991 | Cohort / Case Series | Surg Gynecol Obstet | Ticarcillin + clavulanic acid used for intra-abdominal sepsis in elderly patients, avoiding aminoglycoside nephrotoxicity |
| 31770083 | 2020 | Retrospective Cohort | Surgical Infections | Adequacy of empirical antibiotic therapy in post-operative peritonitis and its link to prognosis |
| 26485771 | 2014 | Retrospective Cohort | Arch Inst Pasteur Tunis | Bacteriological profile and antibiotic protocol for postoperative peritonitis over a 9-year period |
| 20008043 | 2010 | Prospective Cohort | J Antimicrob Chemother | Risk factors for multidrug-resistant bacteria in post-operative peritonitis requiring intensive care |
| 1734854 | 1992 | Guideline / Policy Statement | Arch Surg | Surgical Infection Society guideline on anti-infective agent selection for intra-abdominal infection |
| 9451930 | 1998 | Review | World J Surg | Review of antibiotic therapy strategy for abdominal infection |
| 367159 | 1978 | Case Series | Am J Med Sci | Carbenicillin/ticarcillin used successfully in 11 patients with serious anaerobic infections |
India Market Information
Ticarcillin currently holds no active registrations in India (Market Status: Not Marketed; Total Licenses: 0). No authorization records are available for this evaluation.
Safety Considerations
- Drug Interactions (23 total interactions on record; key items):
- Anticoagulants — Moderate interaction with Warfarin and Dicoumarol (potential enhanced bleeding risk); Minor interaction with Heparin
- Aminoglycosides — Moderate interactions with Gentamicin, Amikacin, Amikacin (liposome), Kanamycin, Streptomycin (risk of inactivation/synergy issues when co-administered, particularly in renal impairment)
- Tetracyclines — Moderate interactions with Doxycycline, Tetracycline, Minocycline, Demeclocycline, Oxytetracycline (potential antagonism of bactericidal activity)
- Radioactive iodine — Moderate interaction with Iodide I-123 and I-131 (may interfere with thyroid uptake studies)
- Hormonal therapy — Moderate interaction with Ethinylestradiol (potential reduced contraceptive efficacy)
- Macrolides — Minor interactions with Clarithromycin, Erythromycin
- Chloramphenicol — Moderate interaction (potential antagonism)
Key warnings and contraindications are not currently available in the evidence pack; please refer to the official package insert once obtained.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Ticarcillin’s antibacterial spectrum mechanistically overlaps with the typical polymicrobial pathogens of intra-abdominal infection/peritonitis, and this is corroborated by one open-label clinical trial and several cohort studies (L3 evidence) rather than TxGNN score alone. However, no clinical trial data was retrieved, the drug is not currently marketed in India, and core safety documentation (warnings/contraindications) and MOA are missing.
To proceed, the following is needed:
- India regulatory (CDSCO)-equivalent label text with warnings/contraindications (Blocking gap DG001)
- DrugBank-sourced mechanism of action confirmation (Gap DG002)
- Confirmation of import/supply pathway given current “Not Marketed” status in India
- Clarification of original approved indication text (original_indications field was empty in the evidence pack)
- Search for any regional/ICTRP trials specific to ticarcillin (or ticarcillin/clavulanate) in intra-abdominal infection to strengthen the S2 evidence base
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.