Usage
Ampicillin + Sulbactam is prescribed for a variety of bacterial infections. It’s effective against skin and skin structure infections, intra-abdominal infections, gynecological infections, and respiratory tract infections. This combination is particularly useful against bacteria producing beta-lactamase, an enzyme that can break down certain antibiotics like ampicillin.
Pharmacological Classification: Beta-lactam antibiotic (Penicillin class combined with a beta-lactamase inhibitor).
Mechanism of Action: Ampicillin inhibits bacterial cell wall synthesis, leading to bacterial cell death. Sulbactam, a beta-lactamase inhibitor, protects ampicillin from being deactivated by beta-lactamase enzymes produced by some bacteria, thus broadening its spectrum of activity.
Alternate Names
Sultamicillin (prodrug combination).
Brand Names: Unasyn.
How It Works
Pharmacodynamics: Ampicillin + Sulbactam exerts bactericidal activity by disrupting bacterial cell wall synthesis during active replication. Sulbactam, while having minimal intrinsic antibacterial activity, irreversibly binds to beta-lactamases, preventing them from inactivating ampicillin.
Pharmacokinetics:
- Absorption: After intravenous (IV) or intramuscular (IM) administration, ampicillin and sulbactam are rapidly absorbed and distributed widely in the body, reaching therapeutic levels in various tissues and fluids. Oral administration of sultamicillin, a prodrug of ampicillin/sulbactam, results in absorption and subsequent hydrolysis to release the active components.
- Metabolism: Minimal metabolism occurs for both drugs.
- Elimination: Primarily renal excretion. Ampicillin and sulbactam have similar elimination half-lives, which increase in patients with renal impairment.
Mode of Action: Ampicillin binds to penicillin-binding proteins (PBPs), enzymes crucial for the final cross-linking step of peptidoglycan synthesis in bacterial cell walls. This binding disrupts the cell wall integrity, leading to bacterial lysis and death. Sulbactam, by inhibiting beta-lactamases, protects ampicillin from degradation.
Elimination Pathways: Renal excretion is the primary elimination pathway.
Dosage
Standard Dosage
Adults:
1.5 g to 3 g (ampicillin + sulbactam) IV or IM every 6 hours. The maximum daily dose of sulbactam should not exceed 4 grams. Less severe infections may be treated with 1.5-3g every 12 hours. For oral administration (sultamicillin), 375-750 mg twice daily.
Children:
- Neonates (first week of life, especially preterm): 75 mg/kg/day (ampicillin + sulbactam) IV or IM divided every 12 hours.
- Infants and Children: 150 mg/kg/day (ampicillin + sulbactam) IV or IM divided every 6 or 8 hours.
- Children >1 year (skin infections): 300 mg/kg/day IV infused over 6 hours, divided every 6 hours for up to 14 days.
- Children ≥40 kg: Adult dose.
Special Cases:
- Elderly Patients: Dosage based on renal function.
- Patients with Renal Impairment: Adjust dose and frequency based on creatinine clearance (CrCl). For CrCl 15–29 mL/min, administer every 12 hours. For CrCl <15 mL/min, administer every 24 hours. Hemodialysis patients: administer 1.5 g - 3 g after dialysis.
- Patients with Hepatic Dysfunction: No dosage adjustment usually needed.
- Patients with Comorbid Conditions: Consider individual patient factors and adjust accordingly.
Clinical Use Cases
- Intubation, Surgical Procedures (Abdominal or Pelvic), Cesarean Section: 1.5 g to 3 g IV or IM at induction of anesthesia, then every 6-8 hours as needed. Discontinue 24 hours post-op unless therapeutically indicated.
- Mechanical Ventilation, ICU Use: Dose according to the infection being treated and renal function.
- Emergency Situations: Dose according to the infection being treated and renal function.
Side Effects
Common Side Effects:
Diarrhea, rash, pain at the injection site, nausea, vomiting.
Rare but Serious Side Effects:
Allergic reactions (including anaphylaxis, Stevens-Johnson syndrome), seizures (with rapid IV infusion), Clostridium difficile associated diarrhea, pseudomembranous colitis, liver dysfunction (cholestatic jaundice).
Long-Term Effects:
C. difficile associated diarrhea can occur up to 2 months or more after treatment.
Contraindications
Hypersensitivity to penicillins, cephalosporins or sulbactam, history of cholestatic jaundice or hepatic dysfunction associated with ampicillin/sulbactam.
Drug Interactions
Allopurinol (increased risk of rash), probenecid (increased ampicillin/sulbactam levels), anticoagulants (altered coagulation tests), bacteriostatic antibiotics (decreased bactericidal effect), oral contraceptives (reduced effectiveness), methotrexate (decreased clearance, increased toxicity).
Pregnancy and Breastfeeding
Pregnancy: Pregnancy category B. Use only if potential benefit outweighs risk.
Breastfeeding: Ampicillin and sulbactam are excreted in breast milk. Monitor the infant for diarrhea.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial cell wall synthesis; sulbactam inhibits beta-lactamase.
- Side Effects: Diarrhea, rash, injection site pain, nausea, vomiting. Serious: allergic reactions, seizures, C. difficile diarrhea.
- Contraindications: Hypersensitivity to penicillins or sulbactam, previous cholestatic jaundice/hepatic dysfunction with this drug.
- Drug Interactions: Allopurinol, probenecid, anticoagulants, bacteriostatic antibiotics, oral contraceptives, methotrexate.
- Pregnancy & Breastfeeding: Category B; excreted in breast milk.
- Dosage: Adults: 1.5-3 g IV/IM q6h. Pediatrics: weight/age based. Renal adjustments needed.
- Monitoring Parameters: Renal function, liver function tests, signs of hypersensitivity, superinfection.
Popular Combinations
No specific information about popular combinations is available in the provided sources.
Precautions
- General Precautions: Evaluate renal and hepatic function before and during treatment, monitor for signs of hypersensitivity or superinfection.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ampicillin + Sulbactam?
A: Adults: 1.5-3 g IV/IM every 6 hours. Pediatric dosing varies by age/weight. Renal adjustments required.
Q2: What infections is Ampicillin + Sulbactam used to treat?
A: Intra-abdominal infections, gynecological infections, skin and skin structure infections, and respiratory tract infections caused by susceptible bacteria, including beta-lactamase producing strains.
Q3: What is the role of sulbactam in this combination?
A: Sulbactam is a beta-lactamase inhibitor that protects ampicillin from degradation by bacterial enzymes, thus broadening its effectiveness against beta-lactamase producing organisms.
Q4: What are the most common side effects?
A: Diarrhea, rash, and pain at the injection site are common.
Q5: Are there any serious side effects to be aware of?
A: Yes, serious side effects include severe allergic reactions (anaphylaxis, Stevens-Johnson Syndrome), seizures (with rapid IV infusion), Clostridium difficile-associated diarrhea, and liver dysfunction.
Q6: What are the contraindications to using Ampicillin + Sulbactam?
A: Known hypersensitivity to penicillins, cephalosporins, or sulbactam; history of cholestatic jaundice or hepatic dysfunction associated with this medication.
Q7: Does this medication interact with other drugs?
A: Yes, it interacts with several medications, including allopurinol, probenecid, anticoagulants, bacteriostatic antibiotics, oral contraceptives, and methotrexate.
Q8: Can Ampicillin + Sulbactam be used during pregnancy and breastfeeding?
A: It’s a pregnancy category B drug, meaning it should be used only if the potential benefit outweighs the potential risk to the fetus. It is excreted in breast milk, so monitor the infant for potential side effects like diarrhea.
Q9: What is the maximum daily dose of sulbactam?
A: The total daily dose of sulbactam should not exceed 4 grams.
Q10: How is dosage adjusted for patients with renal impairment?
A: The dose and/or frequency of administration needs to be reduced based on the degree of renal impairment, as assessed by creatinine clearance. Consult specific guidelines.
