Komzifti
Komzifti
Generic Name
Komzifti
Brand Names
*Komzi*) is a novel, broad‑spectrum, orally‑administered β‑lactam/β‑lactamase inhibitor combination approved for the treatment of complicated intra‑abdominal infections (cIAI), acute bacterial skin and skin structure infections (ABSSSI), and polymicrobial urinary tract infections (UTIs).
Mechanism
- Dual‑mechanism design:
- Komzilin (the β‑lactam core) binds covalently to penicillin‑binding proteins (PBPs 2a, 2b, 3), inhibiting cell‑wall transpeptidation and causing bacterial lysis.
- Zitivin (the novel β‑lactamase inhibitor) occupies the active site of class A (TEM, SHV, CTX‑M), class C (AmpC), and recently identified class D KPC β‑lactamases, thereby protecting Komzilin from enzymatic degradation.
- Resulting efficacy: Rapid bactericidal activity against both Gram‑positive and Gram‑negative pathogens, including ESBL‑producing Enterobacterales and *Pseudomonas aeruginosa* susceptible strains.
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Pharmacokinetics
| Parameter | Typical values (single oral dose, 500 mg) |
| Absorption | ~ 80 % bioavailability; peak plasma concentration (*Tmax*) 1–2 h |
| Distribution | Volume of distribution 0.75 L/kg; moderate protein binding (≈40 % for Komzilin) |
| Metabolism | Minimal hepatic metabolism; 10 % renal tubular secretion; 90 % excreted unchanged |
| Elimination | *t½* 2.0–3.0 h; mean renal clearance 7.5 mL/min/1.73 m² |
| Drug–Drug Interaction | No clinically significant P‑gp or CYP450 modulation; caution with nephrotoxic agents due to shared excretion pathways |
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Indications
- Complicated intra‑abdominal infections (cIAI) – including peritonitis, appendicitis with abscess, or diverticulitis requiring antimicrobial coverage.
- Acute bacterial skin and skin structure infections (ABSSSI), including cellulitis, erysipelas, and wound infections.
- Polymicrobial urinary tract infections (UTIs) where empirical coverage against ESBL producers is warranted.
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Contraindications
- Known hypersensitivity to β‑lactam antibiotics, β‑lactamase inhibitors, or any excipient (e.g., polyethylene glycol).
- Severe renal impairment (eGFR < 15 mL/min/1.73 m²) – dose adjustment or alternative therapy recommended.
- Pregnancy & lactation – data limited; contraindicated unless benefits outweigh risks.
- Cross‑reactivity with penicillin – evaluate for risk before use.
Warnings:
• Allergic reactions: anaphylaxis, severe skin reactions (Stevens–Johnson, toxic epidermal necrolysis).
• Nephrotoxicity: monitor renal function, avoid concomitant nephrotoxic drugs.
• Neurological: rare seizures reported, monitor in patients with pre‑existing CNS disease.
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Dosing
| Condition | Adult Dose | Child Dose (≥ 2 yrs) | Route | Frequency |
| cIAI | 500 mg oral q12h | 10 mg/kg q12h (max 500 mg) | PO | 2 days IV (if available) → 7 days PO |
| ABSSSI | 500 mg PO q12h | 12.5 mg/kg q12h (max 500 mg) | PO | 7 days |
| Polymicrobial UTI | 500 mg PO q12h | 10 mg/kg q12h (max 500 mg) | PO | 7 days |
• Administration: Take with or without food.
• Loading dose: not required in a 500 mg formulation.
• Maintenance: Continue until clinical resolution of signs/symptoms.
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Adverse Effects
Common (≤ 10 %)
• Diarrhea (12 %)
• Nausea (8 %)
• Headache (5 %)
• Dysgeusia (3 %)
Serious (≤ 1 %)
• Hypersensitivity/anaphylaxis (0.3 %)
• Stevens–Johnson syndrome / toxic epidermal necrolysis (0.1 %)
• Seizures (0.05 %)
• Acute kidney injury (0.07 %)
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Monitoring
| Parameter | Frequency | Rationale |
| Serum creatinine/eGFR | Baseline; weekly during therapy | Adjust dose in renal impairment |
| Complete blood count | Baseline; every 10 days | Detect neutropenia or thrombocytopenia |
| Prothrombin time/INR | Baseline; if on anticoagulation | β‑lactams may potentiate warfarin |
| Signs of hypersensitivity | During each clinic visit | Early detection of serious reactions |
| Urine analysis | Baseline; every 2–3 days | Monitor for hematuria/nephritis |
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Clinical Pearls
- Quick coverage of ESBL pathogens: Komzifti’s Zitivin component neutralizes most ESBL enzymes, making it a frontline choice in regions with high ESBL prevalence.
- One‑dose intravenous option: For patients unable to take oral meds, a 1‑hour IV loading dose (500 mg) equivalent ensures adequate plasma levels before transitioning to PO.
- Avoid concomitant PPIs: Proton‑pump inhibitors significantly reduce oral bioavailability (≈ 20 %); co‑administration should be avoided or staggered > 2 h.
- Patient education: Emphasize full 7‑day course even if symptoms resolve early to prevent resistance.
- Use in pregnancy with caution, but can be life‑saving: Data suggest low teratogenic risk; weigh benefits vs. risk in septic pregnant patients.
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• *Komzifti* continues to demonstrate robust activity against resistant Gram‑negative organisms while maintaining a favorable safety profile, making it an essential tool in contemporary antimicrobial stewardship.