Unasyn
combination antibiotic
Generic Name
combination antibiotic
Mechanism
- Ampicillin:
- Inhibits bacterial cell‑wall synthesis by binding to penicillin‑binding proteins (PBPs).
- Induces cross‑linking defects → osmotic lysis (bactericidal).
- Sulbactam:
- Irreversibly inhibits class A β‑lactamases.
- Protects ampicillin from enzymatic degradation, extending spectrum to resistant strains such as certain *Staphylococcus aureus*, *Enterococcus*, and *Escherichia coli*.
Together, the combo achieves potent activity against both aerobic and facultative anaerobes, including *Staphylococcus aureus*, *Streptococcus spp.*, *Enterococcus spp.*, *E. coli*, *Klebsiella spp.*, *Proteus spp.*, and certain anaerobes such as *Bacteroides fragilis*.
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Pharmacokinetics
| Parameter | Value | Comments |
| Absorption | Oral bioavailability ~60 % | Dose adjustment needed in renal insufficiency. |
| Distribution | Vd ≈ 0.3 L/kg (ampicillin); 0.5 L/kg (sulbactam) | Penetrates pleural, peritoneal, and joint fluid. |
| Protein Binding | Ampicillin 0–10 % | Sulbactam ~10 % |
| Metabolism | Minimal hepatic metabolism | Sulbactam is partially hydrolyzed in plasma. |
| Elimination | Renal excretion (≈90 % unchanged) | Clearance ↓ in renal impairment → dose adjustment. |
| Half‑Life | Ampicillin 1.0–1.5 h (clear, normal renal function) | Sulbactam 1.0–1.7 h |
| Steady‑State | 3 h after IV loading dose 2 g | Oral attainment 4–6 h. |
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Indications
- Community‑acquired respiratory tract infections (bronchitis, sinusitis, pneumonia).
- Urinary tract infections (cystitis, pyelonephritis).
- Skin and soft tissue infections (cellulitis, abscesses).
- Intra‑abdominal and peritoneal infections (peritonitis, pelvic inflammatory disease).
- Bone and joint infections (osteomyelitis, septic arthritis).
- Endocarditis (combined with other agents).
- Intra‑uterine device (IUD)‑related infections.
- Pre‑operative prophylaxis in patients with β‑lactam allergy if tolerated.
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Contraindications
- Contraindications
- History of true allergy to β‑lactam antibiotics (anaphylaxis, urticaria, angioedema).
- Warnings
- Renal impairment: Dose adjustment required.
- Hepatic dysfunction: Monitor for drug accumulation.
- Pregnancy/Lactation: Category B. Safe use after benefit‑risk assessment.
- Pediatrics: Use only with age‑appropriate dosing.
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Dosing
| Population | Dose | Frequency | Route | Notes |
| Adults (normal renal function) | 1–2 g IV *or* PO per dose | q6–8 h | IV/PO | Loading dose 8–10 g IV over 30 min, then 2 g q8 h. |
| Adults (CrCl 30–60 mL/min) | 1.5 g IV/PO | q8 h | ||
| Adults (CrCl <30 mL/min) | 1 g IV/PO | q8 h | ||
| Pediatrics (≥3 y) | 10–50 mg/kg/dose | q6–8 h | IV/PO | Max 4 g per dose. |
| Infants <3 y | 10–25 mg/kg/dose | q6–8 h | IV | Height‑based dosing recommended. |
| Pregnancy | Same as adults | q6–8 h | ||
| Lactation | Same as adults | q6–8 h |
• Intravenous: Administer 1 h infusion unless higher potency needed, then 30 min.
• Oral: Tablets or suspension; crushable for pediatric use.
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Adverse Effects
Common (≤10 %)
• Diarrhea (sometimes antibiotic‑associated).
• Nausea/vomiting.
• Rash (maculopapular, mild).
• Mild fever.
Serious (≤1 %)
• Anaphylaxis or severe hypersensitivity reactions.
• Severe cutaneous adverse reactions (e.g., Stevens‑Johnson syndrome).
• Clostridioides difficile colitis (noted with many antibiotics).
• Hemolytic anemia (rare, with coexisting G6PD deficiency).
• Hepatotoxicity (elevated LFTs).
Dose‑related
• Neutropenia, thrombocytopenia.
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Monitoring
| Parameter | Frequency | Guidance |
| Renal function (CrCl) | Every 2–3 days (initiation) | Adjust dose if CrCl 8 µg/mL prudent. |
| Infection markers (CRP/ESR, fever) | Daily | Monitor clinical response. |
| Stool for C. difficile toxins | If watery diarrhea | Test promptly. |
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Clinical Pearls
- Synergistic Spectrum: Sulbactam’s inhibition of *Enterococcus* β‑lactamases enables activity against Enterococcus faecalis and some *Streptococcus pneumoniae***, making Unasyn a go‑to for polymicrobial abdominal infections.
- Rapid Loading: A 8–10 g IV loading dose (≈4 g ampicillin + 4 g sulbactam) achieves therapeutic levels quickly in severe infections—critical for septic patients.
- Pediatric Flexibility: Since Unasyn is available in capsule, tablet, and suspension, dose adjustments are straightforward for children across the age spectrum.
- Cross‑React: Remember that patients with a documented β‑lactam allergy are not candidates; de‑extensive cross‑reactivity assessment is essential before prescribing.
- Surgical Prophylaxis: In β‑lactam‑naïve adults, Unasyn can be used intra‑operatively for procedures at high risk of peritoneal contamination, but confirm no allergy first.
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