Usage
Cefoperazone + Sulbactam is prescribed for a wide range of bacterial infections, including:
- Respiratory Tract Infections (upper and lower)
- Urinary Tract Infections (upper and lower)
- Intra-abdominal Infections
- Septicemia
- Meningitis
- Skin and Soft Tissue Infections
- Bone and Joint Infections
- Endometritis and other infections of the genital tract
- Febrile Neutropenia
Pharmacological Classification: Cefoperazone + Sulbactam is a beta-lactam antibiotic combination. Cefoperazone is a third-generation cephalosporin antibiotic, and Sulbactam is a beta-lactamase inhibitor.
Mechanism of Action: Cefoperazone inhibits bacterial cell wall synthesis, leading to bacterial cell death. Sulbactam inhibits beta-lactamase enzymes produced by bacteria, which would otherwise inactivate Cefoperazone. This combination broadens Cefoperazone’s spectrum of activity against bacteria resistant to beta-lactam antibiotics.
Alternate Names
Cefoperazone sodium + Sulbactam sodium. Some common brand names include Sulperazon, Magnex, and Cefratam.
How It Works
Pharmacodynamics: Cefoperazone exerts its bactericidal effect by binding to penicillin-binding proteins (PBPs), crucial enzymes for bacterial cell wall synthesis. This binding disrupts cell wall integrity, causing bacterial cell lysis and death. Sulbactam does not have significant antibacterial activity on its own but irreversibly binds to and inhibits beta-lactamases, protecting Cefoperazone from degradation.
Pharmacokinetics:
- Absorption: Cefoperazone + Sulbactam is administered parenterally (IV or IM) and achieves therapeutic concentrations in various tissues and fluids.
- Metabolism: Cefoperazone undergoes minimal metabolism. Sulbactam is partly metabolized in the liver.
- Elimination: Cefoperazone is primarily excreted in bile, with a small portion eliminated renally. Sulbactam is mainly excreted renally. Dosage adjustments are necessary in patients with renal impairment, specifically for Sulbactam.
Elimination Pathways: Cefoperazone is primarily eliminated through biliary excretion, while Sulbactam is predominantly eliminated by the kidneys.
Dosage
Standard Dosage
Adults:
The usual adult dose is 2-4 g/day (1-2 g Cefoperazone activity) administered IV or IM every 12 hours. In severe infections, the dosage can be increased up to 8 g/day IV (4 g Cefoperazone activity) or 12 g/day of a 1:2 ratio preparation. The maximum daily dose of Sulbactam is 4 g.
Children:
The usual pediatric dose is 40-80 mg/kg/day (20-40 mg/kg/day Cefoperazone activity) administered every 6-12 hours, divided into 2-4 equal doses. In serious or refractory infections, this can be increased up to 160 mg/kg/day (80 mg/kg/day Cefoperazone) of the 1:1 ratio or 240 mg/kg/day (160 mg/kg/day Cefoperazone) of the 1:2 ratio in 2-4 divided doses. For neonates in the first week of life, administer every 12 hours. The maximum daily Sulbactam dose in pediatrics should not exceed 80 mg/kg/day. If higher doses are required, administer additional Cefoperazone separately.
Special Cases:
- Elderly Patients: Dosage adjustments are generally not needed but caution is advised in patients with renal impairment.
- Patients with Renal Impairment: Sulbactam dosage needs to be adjusted based on creatinine clearance. For creatinine clearance 15-30 ml/min, the maximum Sulbactam dose is 1 g every 12 hours. For creatinine clearance <15 ml/min, the maximum Sulbactam dose is 500 mg every 12 hours. Cefoperazone can be administered without adjustment.
- Patients with Hepatic Dysfunction: Dosage adjustments may be required in severe biliary obstruction or severe liver disease, especially in patients with concomitant renal impairment. Serum concentrations should be closely monitored, and the Cefoperazone dose should not exceed 2 g/day without close monitoring.
- Patients with Comorbid Conditions: Carefully evaluate patients with comorbidities, particularly those on anticoagulant therapy, due to potential bleeding risks. Vitamin K may be required.
Clinical Use Cases
Dosing for clinical use cases generally follows the standard adult recommendations with adjustments as needed based on severity of infection and patient-specific factors like renal and hepatic function. Consider local guidelines and recommendations in these settings.
- Intubation: Standard dosing with adjustments based on patient factors
- Surgical Procedures (prophylactic/therapeutic): Standard dosing with adjustments based on patient factors
- Mechanical Ventilation: Standard dosing with adjustments based on patient factors
- Intensive Care Unit (ICU) Use: Standard dosing with adjustments based on patient factors
- Emergency Situations: Standard dosing with adjustments based on patient factors
Dosage Adjustments:
Adjustments are based on creatinine clearance for renal impairment, severity of hepatic dysfunction, and presence of comorbid conditions. Therapeutic drug monitoring of cefoperazone serum levels may be beneficial in patients with hepatic and/or renal dysfunction.
Side Effects
Common Side Effects:
- Diarrhea
- Nausea and vomiting
- Rash
- Pain at the injection site
- Eosinophilia
Rare but Serious Side Effects:
- Pseudomembranous colitis
- Severe allergic reactions (anaphylaxis)
- Bleeding disorders (hypoprothrombinemia)
- Neutropenia
- Seizures (rare)
- Hepatotoxicity (rare)
Long-Term Effects:
- Superinfection (overgrowth of resistant organisms)
- Vitamin K deficiency
Adverse Drug Reactions (ADR):
Severe hypersensitivity reactions, bleeding manifestations, Clostridium difficile-associated diarrhea, and severe neutropenia require immediate intervention.
Contraindications
- Hypersensitivity to Cefoperazone, Sulbactam, or any other beta-lactam antibiotics.
Drug Interactions
- Anticoagulants: Cefoperazone can increase the risk of bleeding when used with anticoagulants like warfarin. Monitor INR closely.
- Probenecid: Can decrease renal excretion of Cefoperazone.
- Alcohol: Concomitant alcohol consumption may cause a disulfiram-like reaction.
- Aminoglycosides: Increased risk of nephrotoxicity. Monitor renal function if aminoglycosides are used concomitantly.
Pregnancy and Breastfeeding
Cefoperazone + Sulbactam crosses the placenta. Use cautiously during pregnancy, especially during the first trimester. It is excreted in breast milk; exercise caution while breastfeeding.
Drug Profile Summary
- Mechanism of Action: Cefoperazone: Inhibits bacterial cell wall synthesis; Sulbactam: Beta-lactamase inhibitor.
- Side Effects: Diarrhea, nausea, rash, injection site pain, eosinophilia. Serious side effects: C. difficile infection, bleeding, neutropenia, allergic reactions, seizures (rare), hepatotoxicity (rare).
- Contraindications: Hypersensitivity to beta-lactam antibiotics.
- Drug Interactions: Anticoagulants (increased bleeding risk), Probenecid, Alcohol.
- Pregnancy & Breastfeeding: Use with caution during pregnancy, especially in the first trimester. Exercise caution while breastfeeding.
- Dosage: Adults: 2-4 g/day IV/IM every 12 hours; Children: 40-80 mg/kg/day every 6-12 hours.
- Monitoring Parameters: Renal function (creatinine, BUN), liver function (AST, ALT, bilirubin), prothrombin time/INR (especially in patients with comorbid conditions), complete blood count (CBC) with differential.
Popular Combinations
No specific popular combinations are commonly recommended. Cefoperazone + Sulbactam often provides broad enough coverage as a monotherapy.
Precautions
- Assess renal and hepatic function before and during therapy.
- Monitor for signs and symptoms of bleeding, especially in patients with risk factors or on anticoagulant therapy.
- Monitor for signs of superinfection.
- Assess for allergy to beta-lactam antibiotics.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Cefoperazone + Sulbactam?
A: Adults: 2-4 g/day IV or IM every 12 hours. Children: 40-80 mg/kg/day every 6-12 hours.
Q2: How should the dosage be adjusted for renal impairment?
A: Adjust Sulbactam dosage based on creatinine clearance. Creatinine clearance 15-30 ml/min: Max 1 g Sulbactam every 12 hrs; Creatinine clearance <15ml/min: Max 500mg Sulbactam every 12 hours. Cefoperazone dose does not need adjustment.
Q3: What are the most common side effects?
A: Diarrhea, nausea, rash, and injection site pain.
Q4: What are the serious side effects to watch for?
A: Clostridium difficile infection, bleeding abnormalities (hypoprothrombinemia), severe allergic reactions, neutropenia, and rarely, seizures or hepatotoxicity.
Q5: Is Cefoperazone + Sulbactam safe to use during pregnancy?
A: Use cautiously during pregnancy, especially in the first trimester. Consult with a specialist to weigh risks and benefits.
Q6: Can I use Cefoperazone + Sulbactam while breastfeeding?
A: It is excreted in breast milk. Exercise caution and consult with a specialist to weigh risks and benefits.
Q7: How is Cefoperazone + Sulbactam administered?
A: Intravenously (IV) or intramuscularly (IM).
Q8: What should I monitor in patients receiving this medication?
A: Renal function, liver function, prothrombin time/INR (especially for those on anticoagulants), complete blood count (CBC) with differential.
Q9: What if a patient develops a rash while on Cefoperazone + Sulbactam?
A: Evaluate the rash to differentiate between a minor reaction and a serious allergic reaction. Discontinue the medication if a serious allergy is suspected.
Q10: Are there any dietary restrictions with this antibiotic?
A: Avoid alcohol as it can cause a disulfiram-like reaction.
