Usage
Cefoperazone is a third-generation cephalosporin antibiotic used to treat a wide variety of bacterial infections. It is prescribed for infections caused by susceptible bacteria, including:
- Respiratory Tract Infections: Pneumonia, bronchitis, lung abscess.
- Urinary Tract Infections: Pyelonephritis, cystitis, urethritis.
- Intra-abdominal Infections: Peritonitis, cholecystitis, cholangitis.
- Septicemia: Bloodstream infections.
- Meningitis: Infection of the membranes surrounding the brain and spinal cord.
- Skin and Soft Tissue Infections: Cellulitis, abscesses, wound infections.
- Infections of Bones and Joints: Osteomyelitis, septic arthritis.
- Gonorrhea: Sexually transmitted infection.
- Surgical Prophylaxis: To prevent infections after surgery.
Pharmacological Classification: Cefoperazone is a beta-lactam antibiotic belonging to the cephalosporin class. More specifically, it is a third-generation cephalosporin.
Mechanism of Action: Cefoperazone inhibits bacterial cell wall synthesis by binding to and inactivating penicillin-binding proteins (PBPs). These proteins are essential for the cross-linking of peptidoglycans, which form the structural integrity of the bacterial cell wall. This disruption leads to cell lysis and bacterial death.
Alternate Names
Cefoperazone is the generic name. It is often marketed under various brand names globally, such as Cefobid and Magnemycin.
How It Works
Pharmacodynamics: Cefoperazone exerts its bactericidal effect by disrupting the synthesis of the bacterial cell wall.
Pharmacokinetics:
- Absorption: Cefoperazone is administered parenterally (intravenously or intramuscularly) as it is not well-absorbed from the gastrointestinal tract.
- Distribution: It achieves therapeutic concentrations in various tissues and fluids, including bile, where concentrations are significantly higher than serum levels.
- Metabolism: Cefoperazone is not extensively metabolized.
- Elimination: Primarily excreted in the bile, with a small portion eliminated through the kidneys. The serum half-life is typically 1.5 to 2.5 hours.
Mode of Action: Cefoperazone binds to specific PBPs within the bacterial cell wall, inhibiting the transpeptidation reaction necessary for cross-linking peptidoglycans. This weakens the cell wall, leading to cell lysis and bacterial death.
Elimination Pathways: Predominantly biliary excretion, with minimal renal excretion.
Dosage
Standard Dosage
Adults:
- Standard Dose: 2 to 4 grams daily, administered in equally divided doses every 12 hours, intravenously or intramuscularly.
- Severe Infections: Dosage may be increased up to 8 grams daily or even higher in exceptionally severe cases, divided and administered every 8 or 12 hours.
- Uncomplicated Gonorrhea: 500 mg as a single intramuscular dose.
Children:
- Dosage: 50 to 200 mg/kg/day, divided every 8 to 12 hours, intravenously or intramuscularly. The maximum dose should not exceed 12 grams/day.
- Neonates (less than 8 days old): Administer every 12 hours.
Special Cases:
- Elderly Patients: Dosage adjustments are generally not necessary unless renal or hepatic impairment exists.
- Patients with Renal Impairment: For patients with creatinine clearance less than 18 ml/min or serum creatinine greater than 3.5 mg/dL, the maximum dosage should be 4 grams/day.
- Patients with Hepatic Dysfunction: In severe biliary obstruction or hepatic disease, reduce the dose to a maximum of 2 grams/day and monitor serum concentrations closely. For patients with combined renal and hepatic impairment, even closer monitoring is needed.
- Patients with Comorbid Conditions: Adjust dosages based on the specific comorbidity and organ function.
Clinical Use Cases
Dosage in these settings follows the standard adult or pediatric recommendations, adjusting for severity and patient-specific factors:
- Intubation
- Surgical Procedures: 1-2 grams IV 30-90 minutes prior to surgery, repeated every 12 hours for no longer than 24 hours.
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations
Dosage Adjustments
Adjustments are based on creatinine clearance, hepatic function, and serum drug levels.
Side Effects
Common Side Effects:
- Pain at the injection site
- Diarrhea
- Nausea and vomiting
- Rash
- Eosinophilia (increased eosinophils)
Rare but Serious Side Effects:
- Allergic reactions (anaphylaxis)
- Clostridium difficile-associated diarrhea
- Neutropenia (low neutrophil count)
- Bleeding disorders
- Pseudomembranous colitis
- Jaundice
Long-Term Effects:
Limited data available.
Adverse Drug Reactions (ADR):
Similar to rare but serious side effects.
Contraindications
- Hypersensitivity to cefoperazone, other cephalosporins, or penicillins.
Drug Interactions
- Aminoglycosides: Increased risk of nephrotoxicity. Monitor renal function.
- Probenecid: May increase cefoperazone serum levels.
- Anticoagulants: May enhance anticoagulant effects. Monitor coagulation parameters.
- Alcohol: Avoid alcohol during and for 72 hours after cefoperazone therapy due to a disulfiram-like reaction in some patients.
Pregnancy and Breastfeeding
- Pregnancy: Cefoperazone crosses the placenta. Use with caution during pregnancy, especially in the first trimester.
- Breastfeeding: Cefoperazone is excreted in breast milk. Exercise caution when administering to breastfeeding women.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial cell wall synthesis by binding to PBPs.
- Side Effects: Injection site pain, diarrhea, nausea/vomiting, rash, eosinophilia. Serious side effects include allergic reactions, bleeding disorders, and Clostridium difficile-associated diarrhea.
- Contraindications: Hypersensitivity to cefoperazone, cephalosporins, or penicillins.
- Drug Interactions: Aminoglycosides, probenecid, anticoagulants, alcohol.
- Pregnancy & Breastfeeding: Use cautiously.
- Dosage: See detailed dosage section above.
- Monitoring Parameters: Renal function, liver function tests, prothrombin time/INR (especially with concurrent anticoagulant use), complete blood count, and signs of superinfection.
Popular Combinations
Cefoperazone is sometimes combined with sulbactam (a beta-lactamase inhibitor) to broaden its spectrum of activity against bacteria that produce beta-lactamases.
Precautions
- General Precautions: Assess renal and hepatic function, monitor for hypersensitivity reactions, and observe for signs of superinfection.
- Specific Populations: See the dosage section for special considerations for pregnant/breastfeeding women, children, and the elderly.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Cefoperazone?
A: See the detailed dosage section above.
Q2: How is Cefoperazone administered?
A: Intravenously (IV) or intramuscularly (IM).
Q3: What are the most common side effects of Cefoperazone?
A: Pain at the injection site, diarrhea, nausea, vomiting, and rash.
Q4: Is Cefoperazone safe to use during pregnancy?
A: Use with caution, especially during the first trimester. It crosses the placenta.
Q5: Can Cefoperazone be used in patients with renal impairment?
A: Yes, but dosage adjustments may be required, especially with severe impairment.
Q6: What are the signs of a serious allergic reaction to Cefoperazone?
A: Difficulty breathing, swelling of the face or throat, hives, severe itching, and rash. Seek immediate medical attention if these occur.
Q7: What should I do if a patient develops diarrhea while taking Cefoperazone?
A: Evaluate for Clostridium difficile-associated diarrhea. Diarrhea can range from mild to severe and may be a sign of a serious complication.
Q8: Can Cefoperazone be used to treat meningitis?
A: Yes, it can be used to treat bacterial meningitis caused by susceptible organisms.
Q9: How long should Cefoperazone treatment typically last?
A: Treatment duration varies depending on the infection being treated and the patient’s response. It can range from a few days to several weeks.
Q10: What drug interactions should I be aware of with Cefoperazone?
A: Be cautious with concurrent use of aminoglycosides, probenecid, and anticoagulants. Alcohol should be avoided.
