Tazobactam
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Tazobactam: From Beta-Lactamase Inhibitor (Combination Therapy) to Pneumonia
One-Sentence Summary
Tazobactam is a beta-lactamase inhibitor with no antibacterial activity on its own; it is always used in fixed combinations (e.g. Piperacillin-Tazobactam, Ceftolozane-Tazobactam) to restore the killing power of a partner beta-lactam against beta-lactamase-producing (including ESBL) bacteria. The TxGNN model predicts continued/expanded relevance for Pneumonia (including hospital-acquired and ventilator-associated pneumonia), with 57 clinical trials and 20 publications currently identified in this evidence pack supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | No standalone indication — Tazobactam is used only as the beta-lactamase-inhibitor component of combination antibiotics (e.g. Piperacillin-Tazobactam, Ceftolozane-Tazobactam) |
| Predicted New Indication | Pneumonia (incl. hospital-acquired / ventilator-associated pneumonia) |
| TxGNN Prediction Score | 99.46% |
| Evidence Level | L1 |
| South Africa Market Status | Not Marketed |
| Number of SAHPRA Registrations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data for Tazobactam itself is not available. Based on known pharmacology, Tazobactam is a beta-lactamase inhibitor that has no clinically meaningful antibacterial activity alone. It is always co-administered with a beta-lactam partner drug — most commonly piperacillin or ceftolozane — to inhibit bacterial beta-lactamase enzymes (including extended-spectrum beta-lactamases, ESBLs), thereby restoring the partner drug’s bactericidal activity against beta-lactamase-producing strains.
Pneumonia, particularly hospital-acquired and ventilator-associated pneumonia, is frequently caused by Gram-negative pathogens such as Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa — organisms commonly implicated in beta-lactamase-mediated resistance. This mechanistic profile aligns directly with the pathogen spectrum seen in nosocomial pneumonia.
Critically, this is not a novel repurposing hypothesis in the strict sense: Piperacillin-Tazobactam and Ceftolozane-Tazobactam are already established, guideline-referenced therapies for hospital-acquired and ventilator-associated bacterial pneumonia, and are used repeatedly as the active comparator arm in pivotal Phase 3 trials of newer beta-lactam/beta-lactamase-inhibitor combinations (e.g. imipenem/cilastatin/relebactam, ceftolozane/tazobactam vs. meropenem). This confirms the mechanistic and clinical plausibility of the TxGNN prediction.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT03583333 | Phase 3 | Completed | 274 | Multinational double-blind RCT: imipenem/cilastatin/relebactam vs. piperacillin/tazobactam in HABP/VABP; non-inferiority on 28-day all-cause mortality |
| NCT02493764 | Phase 3 | Completed | 537 | Double-blind active-comparator RCT: imipenem/cilastatin/relebactam vs. piperacillin/tazobactam in HABP/VABP |
| NCT02070757 | Phase 3 | Completed | 726 | Double-blind RCT: ceftolozane/tazobactam vs. meropenem in ventilated nosocomial pneumonia; non-inferiority on Day 28 all-cause mortality |
| NCT00253955 | Phase 3 | Completed | 460 | Open-label RCT: levofloxacin vs. piperacillin/tazobactam in mild-to-moderate hospital-acquired pneumonia |
| NCT01796717 | Phase 2/3 | Unknown | 50 | Prolonged vs. intermittent infusion of piperacillin/tazobactam for nosocomial pneumonia in ICU; clinical, bacteriologic and PK/safety endpoints |
| NCT01853982 | Phase 3 | Terminated | 4 | Randomized open-label study: IV ceftolozane/tazobactam vs. IV piperacillin/tazobactam in ventilator-associated pneumonia (terminated early, low enrollment) |
| NCT03897582 | N/A | Recruiting | 65 | Beta-lactam (incl. piperacillin/tazobactam) dosing in ICU pneumonia patients on continuous renal replacement therapy |
| NCT03581370 | Phase 3 | Recruiting | 80 | Short vs. prolonged infusion of ceftolozane-tazobactam in VAP due to Pseudomonas aeruginosa |
| NCT04223752 | Phase 1 | Completed | 41 | Safety, tolerability and PK of ceftolozane/tazobactam in pediatric nosocomial pneumonia |
| NCT04986254 | N/A | Completed | 179 | Individualised dosing regimens (incl. piperacillin/tazobactam) to maximise antibiotic effectiveness in ICU pneumonia |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 30208454 | 2018 | RCT | JAMA | Piperacillin-tazobactam vs. meropenem for 30-day mortality in ceftriaxone-resistant E. coli/K. pneumoniae bloodstream infection |
| 31563344 | 2019 | RCT | Lancet Infect Dis | ASPECT-NP: ceftolozane-tazobactam vs. meropenem for nosocomial pneumonia, Phase 3 non-inferiority trial |
| 39674398 | 2025 | RCT | Int J Infect Dis | Phase 3 non-inferiority trial: imipenem/cilastatin/relebactam vs. piperacillin/tazobactam in HABP/VABP |
| 32785589 | 2021 | RCT | Clin Infect Dis | RESTORE-IMI 2: randomized double-blind multicenter trial of imipenem/cilastatin/relebactam vs. piperacillin/tazobactam in HABP/VABP |
| 32662691 | 2020 | Review | Expert Rev Anti Infect Ther | Review of ceftolozane/tazobactam for treatment of hospital-acquired pneumonia |
| 38823453 | 2024 | Review | Clin Microbiol Infect | Systematic review and network meta-analysis of empiric antibiotic regimens in non-ventilator-associated HAP |
| 35488823 | 2022 | Review | Rev Esp Quimioter | Review of ceftolozane-tazobactam in nosocomial pneumonia |
| 38971203 | 2024 | Review | Int J Antimicrob Agents | Systematic review of PK/PD of novel beta-lactams and beta-lactam/beta-lactamase-inhibitor combinations in pneumonia from carbapenem-resistant Gram-negative bacteria |
| 39701120 | 2025 | Observational | Lancet Infect Dis | CACTUS: multicentre retrospective comparison of ceftazidime-avibactam vs. ceftolozane-tazobactam for MDR P. aeruginosa infections |
| 34598422 | 2021 | Review | Rev Esp Quimioter | When, how and why to use ceftolozane-tazobactam |
South Africa Market Information
Tazobactam has no active SAHPRA registrations and is currently classified as Not Marketed in South Africa (0 registered products in this evidence pack). No product name, dosage form, or approved indication text is available to report.
Safety Considerations
Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Multiple completed Phase 3 RCTs (e.g. NCT03583333, NCT02493764, NCT02070757, NCT00253955) establish beta-lactam/beta-lactamase-inhibitor combinations containing tazobactam as a validated, guideline-referenced comparator for hospital-acquired and ventilator-associated pneumonia, giving strong (L1) mechanistic and clinical evidence. However, Tazobactam has no current SAHPRA registration in South Africa, and TFDA/SAHPRA-level safety data (warnings, contraindications) and detailed MOA data are both marked as data gaps — one of them (PI warnings/contraindications) is classified as Blocking for safety pre-assessment.
To proceed, the following is needed:
- SAHPRA-approved Professional Information (PI) — warnings, precautions, and contraindications (Blocking data gap DG001)
- Detailed mechanism of action data from DrugBank (High-priority data gap DG002)
- Confirmation of regulatory pathway/status for tazobactam-containing combination products (e.g. Piperacillin-Tazobactam) intended for the South African market
- A drug-drug interaction (DDI) profile, currently unavailable (“not_found”)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.