Usage
Cefepime is a fourth-generation cephalosporin antibiotic prescribed for the treatment of moderate to severe bacterial infections. These infections include:
- Pneumonia (including nosocomial pneumonia)
- Febrile neutropenia (empiric therapy)
- Complicated and uncomplicated urinary tract infections (including pyelonephritis)
- Complicated intra-abdominal infections (in conjunction with metronidazole)
- Uncomplicated skin and skin structure infections
Its pharmacological classification is antibiotic.
Cefepime’s mechanism of action involves inhibiting bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs). This binding disrupts the cross-linking of peptidoglycans, leading to cell wall instability and bacterial lysis.
Alternate Names
Cefepime hydrochloride is the chemical name. Maxipime is a widely recognized brand name. Different brand names may exist regionally.
How It Works
Pharmacodynamics: Cefepime exerts its bactericidal effect by disrupting bacterial cell wall synthesis. It has a broad spectrum of activity against both Gram-positive and Gram-negative bacteria, including Pseudomonas aeruginosa.
Pharmacokinetics:
- Absorption: Cefepime is poorly absorbed from the gastrointestinal tract and is therefore administered intravenously (IV) or intramuscularly (IM). IV administration is the preferred route.
- Distribution: It achieves therapeutic concentrations in various tissues and body fluids, including cerebrospinal fluid. Protein binding is relatively low (around 20%).
- Metabolism: Cefepime is minimally metabolized.
- Elimination: Primarily eliminated by renal excretion, with a half-life of approximately 2 hours in patients with normal renal function.
Mode of Action: Cefepime binds to penicillin-binding proteins (PBPs), specifically PBP 3, which are essential for bacterial cell wall synthesis. This inhibits the transpeptidation and carboxypeptidation reactions necessary for peptidoglycan cross-linking, leading to cell wall instability and ultimately bacterial cell death. No significant enzyme inhibition or neurotransmitter modulation is associated with its mechanism.
Elimination Pathways: Primarily excreted unchanged via the kidneys.
Dosage
Standard Dosage
Adults:
- Mild to Moderate Infections: 0.5-1g IV/IM every 12 hours. IM administration is typically reserved for uncomplicated urinary tract infections (UTIs) caused by E. coli.
- Severe Infections: 1-2g IV every 8-12 hours. For Pseudomonas aeruginosa infections, 2g IV every 8 hours is recommended.
- Administration: IV infusions should be administered over approximately 30 minutes.
Children (2 months to 16 years):
- Most Infections: 50 mg/kg every 12 hours.
- Febrile Neutropenia or Severe Pneumonia (caused by P. aeruginosa): 50 mg/kg every 8 hours.
- Maximum Dose: Should not exceed the recommended adult dose.
Special Cases:
- Elderly Patients: Dose adjustment based on creatinine clearance (CrCl) is necessary. Monitor renal function closely.
- Patients with Renal Impairment: Dose adjustment is required based on CrCl (see dosage adjustments section).
- Patients with Hepatic Dysfunction: No dose adjustment is typically necessary.
- Patients with Comorbid Conditions: Carefully assess patients with conditions like diabetes, cardiovascular disease, and seizure disorders.
Clinical Use Cases
Dosing in specific clinical settings generally follows standard recommendations based on infection severity. Higher doses or more frequent administration might be necessary in critically ill patients. Consult local guidelines and expert advice for specific protocols.
Dosage Adjustments
Renal Impairment: Dose adjustments are necessary in adults and children with impaired renal function:
- CrCl >60 mL/min: Standard dosage.
- CrCl 30-60 mL/min: Reduce dosage or increase dosing interval.
- CrCl 11-29 mL/min: Further reduce dosage or increase dosing interval.
- CrCl <11 mL/min: Significant dose reduction or increase dosing interval.
- Hemodialysis: Administer after dialysis on dialysis days. Specific protocols exist (see source materials).
Side Effects
Common Side Effects:
- Diarrhea
- Nausea and vomiting
- Rash
- Headache
- Pain, redness, or swelling at the injection site
- Fever
Rare but Serious Side Effects:
- Clostridium difficile associated diarrhea (CDAD)
- Seizures (especially in patients with renal impairment receiving high doses)
- Severe allergic reactions (anaphylaxis)
- Stevens-Johnson Syndrome
- Toxic epidermal necrolysis
- Neutropenia
- Thrombocytopenia
- Renal dysfunction
Long-Term Effects: Long-term use of cefepime can lead to:
- Development of antibiotic resistance
- Superinfection with resistant organisms (e.g., fungal infections).
Adverse Drug Reactions (ADR): Clinically significant ADRs include:
- Anaphylaxis
- Stevens-Johnson syndrome/Toxic epidermal necrolysis
- Pseudomembranous colitis
- Drug-induced nephritis
Contraindications
- Absolute: Known hypersensitivity to cefepime, other cephalosporins, penicillins, or any component of the formulation.
- Relative: History of non-severe hypersensitivity to beta-lactam antibiotics, asthma, allergic diathesis, seizure disorders.
Drug Interactions
- Aminoglycosides: Increased risk of nephrotoxicity.
- Probenecid: Increased cefepime serum levels.
- Anticoagulants (e.g., warfarin): Enhanced anticoagulant effect.
- Other nephrotoxic drugs: Additive nephrotoxic effects.
Pregnancy and Breastfeeding
- Pregnancy: Cefepime crosses the placenta. Limited human data available, animal studies have not shown adverse effects. Use only if clearly needed.
- Breastfeeding: Cefepime is present in human milk in low concentrations. Exercise caution when administering to breastfeeding women.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial cell wall synthesis by binding to PBPs.
- Side Effects: Diarrhea, rash, nausea, vomiting, headache, injection site reactions. Serious side effects include seizures, CDAD, and allergic reactions.
- Contraindications: Hypersensitivity to cefepime or other beta-lactam antibiotics.
- Drug Interactions: Aminoglycosides, probenecid, anticoagulants.
- Pregnancy & Breastfeeding: Use with caution; limited data in humans.
- Dosage: Varies depending on the infection and renal function.
- Monitoring Parameters: Renal function (serum creatinine, CrCl), complete blood count, signs of superinfection, clinical response.
Popular Combinations
- Cefepime and metronidazole for intra-abdominal infections.
Precautions
- Renal function monitoring is essential.
- Monitor for allergic reactions.
- Assess for signs of superinfection.
- Consider age-related dose adjustments in elderly patients.
- Caution in patients with a history of seizures.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Cefepime?
A: Dosage varies depending on the infection, severity, and patient-specific factors like age and renal function. See the detailed dosage section above.
Q2: What are the common side effects of Cefepime?
A: Common side effects include diarrhea, nausea, vomiting, rash, headache, and injection site reactions.
Q3: Is Cefepime safe to use during pregnancy?
A: Limited human data are available. Animal studies have not shown adverse effects. Use only if the potential benefit outweighs the potential risk to the fetus.
Q4: How is Cefepime administered?
A: Cefepime is administered intravenously (IV) or intramuscularly (IM). IV administration is the preferred route.
Q5: How does Cefepime work?
A: Cefepime inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins.
Q6: What infections is Cefepime used to treat?
A: Cefepime is used to treat a variety of bacterial infections, including pneumonia, urinary tract infections, skin and skin structure infections, and intra-abdominal infections.
Q7: Does Cefepime interact with other medications?
A: Yes, cefepime can interact with other medications such as aminoglycosides, probenecid, and anticoagulants.
Q8: What should I monitor in patients receiving Cefepime?
A: Monitor renal function, complete blood count, signs of superinfection, and clinical response.
Q9: What is the difference between Cefepime and other cephalosporins?
A: Cefepime is a fourth-generation cephalosporin with broader spectrum activity, particularly against Pseudomonas aeruginosa, compared to earlier generations.
Q10: Are there any contraindications to using Cefepime?
A: Cefepime is contraindicated in patients with a known hypersensitivity to cefepime, cephalosporins, or penicillins.
