Usage
Cefepime + Sulbactam is a fixed-dose combination antibiotic indicated for the treatment of various severe infections caused by susceptible pathogens. These include:
- Lower Respiratory Tract Infections (LRTIs): Nosocomial and community-acquired pneumonia.
- Urinary Tract Infections (UTIs): Complicated UTIs, including pyelonephritis.
- Intra-abdominal Infections: Complicated intra-abdominal infections, including peritonitis.
- Septicemia: Mild to moderate bacterial septicemia.
- Skin and Skin Structure Infections.
- Acute Biliary Tract Infections (in adults).
Pharmacological Classification: Beta-lactam antibiotic (fourth-generation cephalosporin + beta-lactamase inhibitor).
Mechanism of Action: Cefepime exerts its bactericidal effect by inhibiting bacterial cell wall synthesis through binding to penicillin-binding proteins (PBPs). Sulbactam, a beta-lactamase inhibitor, protects cefepime from degradation by certain beta-lactamases produced by bacteria, thereby expanding its spectrum of activity.
Alternate Names
No widely recognized alternate names.
Brand Names:
- Quatam
- Supime
- Maxipime (Cefepime alone)
How It Works
Pharmacodynamics: Cefepime + Sulbactam disrupts bacterial cell wall synthesis, leading to bacterial cell death. Sulbactam enhances cefepime’s activity against bacteria that produce beta-lactamases.
Pharmacokinetics:
- Absorption: Cefepime is poorly absorbed orally and must be administered intravenously (IV) or intramuscularly (IM). Sulbactam is administered by IV.
- Distribution: Both drugs distribute widely into various tissues and body fluids.
- Metabolism: Cefepime undergoes minimal metabolism. Sulbactam is partially metabolized to inactive compounds.
- Elimination: Cefepime is primarily eliminated renally as unchanged drug. Sulbactam is also mainly excreted in the urine via glomerular filtration and tubular secretion, with some biliary excretion.
Mode of Action: Cefepime inhibits transpeptidases and carboxypeptidases (PBPs) involved in peptidoglycan synthesis. Sulbactam irreversibly inhibits beta-lactamases, widening cefepime’s spectrum.
Receptor binding, enzyme inhibition, or neurotransmitter modulation: Cefepime binds to PBPs, and Sulbactam inhibits beta-lactamases. High doses of cefepime may cause neurotoxicity through GABA antagonism.
Elimination pathways: Cefepime and Sulbactam are predominantly eliminated by renal excretion.
Dosage
Standard Dosage
Adults:
- Standard Dose: 1-2 g every 8-12 hours IV, infused over 30 minutes. Some literature suggests up to 6-9g of sulbactam daily for infections caused by multi-drug resistant organisms (MDROs).
- Maximum Dosage: Up to 9 g daily.
Children:
- Pediatric Dosing: Children 2 months to 16 years and < 40 kg: 50 mg/kg every 8-12 hours IV for UTIs, uncomplicated skin and skin structure infections, and pneumonia. Maximum dose: 2 g/dose. Consider renal function.
- Febrile neutropenia: 50mg/kg every 8 hours.
Special Cases:
- Elderly Patients: Adjust dose based on creatinine clearance <60 mL/min. Neurotoxicity risk is increased in elderly.
- Patients with Renal Impairment: Dosage adjustment necessary (see below).
- Patients with Hepatic Dysfunction: No dosage adjustment generally required for Cefepime.
- Patients with Comorbid Conditions: Evaluate patient-specific factors for dosage adjustments, especially in CKD.
Clinical Use Cases
- Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use: Follow standard adult dosing with renal adjustments and therapeutic drug monitoring as needed, especially for high doses.
- Emergency Situations (Sepsis): Initial dose may be higher (2 g every 8 hours) for severe infections or higher MIC organisms.
Dosage Adjustments
- Renal Impairment: Dosage adjustment is crucial. For adults, several regimens exist based on creatinine clearance (CrCl), infection severity, and desired dosing interval (see resources for specific examples).
- Hemodialysis patients: 1g loading dose, then 0.5-1g every 24 hours, administered after dialysis.
Side Effects
Common Side Effects:
- Nausea, vomiting, diarrhea
- Rash, itching
- Pain at injection site
- Headache
Rare but Serious Side Effects:
- Seizures
- Encephalopathy
- Clostridium difficile colitis
- Allergic reactions (anaphylaxis)
- Neutropenia
Long-Term Effects: Potential for renal dysfunction with prolonged use, especially at high doses and in patients with pre-existing renal impairment.
Contraindications
- Hypersensitivity to cefepime, sulbactam, or other cephalosporins.
Drug Interactions
- Aminoglycosides: Increased risk of nephrotoxicity.
- Probenecid: Decreased renal excretion of Cefepime.
- Anticoagulants: May increase bleeding risk.
Pregnancy and Breastfeeding
- Pregnancy: Limited human data. Cefepime is a former FDA Pregnancy Category B. Use with caution after careful risk-benefit assessment.
- Breastfeeding: Cefepime is excreted in breast milk. Caution is advised; monitor infant for diarrhea and thrush.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial cell wall synthesis, enhanced by beta-lactamase inhibition.
- Side Effects: Nausea, vomiting, diarrhea, rash, seizures, encephalopathy.
- Contraindications: Hypersensitivity to cephalosporins or sulbactam.
- Drug Interactions: Aminoglycosides, probenecid, anticoagulants.
- Pregnancy & Breastfeeding: Use with caution in pregnancy and breastfeeding.
- Dosage: Adults: 1-2 g every 8-12 hours IV. Children: 50 mg/kg every 8-12 hours IV. Renal dose adjustments necessary.
- Monitoring Parameters: Renal function (serum creatinine, creatinine clearance), neurologic status (especially in elderly and renally impaired), signs of superinfection (e.g., C. difficile).
Popular Combinations
Combination with metronidazole is used in intra-abdominal infections.
Precautions
- General Precautions: Assess renal function, monitor for neurologic signs, evaluate for drug allergies.
- Specific Populations: Use with caution in pregnancy and breastfeeding. Adjust dose in renal impairment and elderly patients. Monitor neonates exposed via breastfeeding.
- Lifestyle Considerations: No specific lifestyle restrictions.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Cefepime + Sulbactam?
A: Adults: 1-2g every 8-12 hours by IV infusion. Children: 50mg/kg every 8-12 hours by IV infusion. Dose adjustments are needed in patients with renal dysfunction, and elderly.
Q2: How is Cefepime + Sulbactam administered?
A: Cefepime + Sulbactam should be administered intravenously, typically over 30 minutes.
Q3: What are the common side effects?
A: The most common side effects are nausea, vomiting, diarrhea, rash, itching, and pain at the injection site.
Q4: What are the serious side effects?
A: Serious side effects can include seizures, encephalopathy, Clostridium difficile associated diarrhea, and serious allergic reactions.
Q5: What are the contraindications to using Cefepime + Sulbactam?
A: The main contraindication is a known hypersensitivity to cefepime, sulbactam, or any other cephalosporin antibiotics.
Q6: Does Cefepime + Sulbactam require dose adjustment in renal impairment?
A: Yes, dosage adjustments are crucial in patients with renal impairment. Dose reduction, extended dosing intervals or a combination of both are usually applied depending on the creatinine clearance.
Q7: Can Cefepime + Sulbactam be used in pregnancy?
A: Cefepime is a former FDA Pregnancy Category B. While not absolutely contraindicated, its use during pregnancy requires a careful risk-benefit assessment by the physician.
Q8: Is Cefepime + Sulbactam safe during breastfeeding?
A: Cefepime is excreted in breast milk. Caution is advised. The nursing infant should be monitored for potential side effects such as diarrhea and thrush.
Q9: What are the signs of Cefepime-induced neurotoxicity?
A: Signs can include decreased mental status, confusion, myoclonus, and seizures. This is more common in patients with renal impairment and the elderly.
Q10: How should Cefepime-induced neurotoxicity be managed?
A: Discontinue Cefepime immediately. Supportive care, including seizure management with benzodiazepines, may be necessary. Hemodialysis can be considered in severe cases.
