Introduction
Cefepime is a fourth-generation cephalosporin antibiotic with broad-spectrum activity against both gram-positive and gram-negative bacteria. It belongs to the beta-lactam class of antibiotics and is classified as a semi-synthetic cephalosporin. Cefepime is particularly valued for its enhanced stability against beta-lactamases and its activity against Pseudomonas aeruginosa, making it a crucial agent in the management of serious infections in hospitalized patients.
Mechanism of Action
Cefepime exerts its bactericidal effect by inhibiting bacterial cell wall synthesis through binding to penicillin-binding proteins (PBPs). Like other beta-lactam antibiotics, it disrupts the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, leading to cell lysis and death. Its zwitterionic nature allows for improved penetration through the outer membrane of gram-negative bacteria, while maintaining good activity against gram-positive organisms. Cefepime demonstrates increased stability against chromosomal and plasmid-mediated beta-lactamases compared to earlier generation cephalosporins.
Indications
FDA-approved indications include:
- Moderate to severe pneumonia (including community-acquired and hospital-acquired)
- Complicated and uncomplicated urinary tract infections
- Complicated intra-abdominal infections (in combination with metronidazole)
- Febrile neutropenia
- Skin and skin structure infections
Cefepime is also commonly used off-label for:
- Meningitis caused by susceptible organisms
- Empirical therapy in critically ill patients with suspected multidrug-resistant infections
- Infections in immunocompromised hosts
Dosage and Administration
Standard dosing:- Adults: 1-2 g IV every 8-12 hours
- Duration: Typically 7-14 days depending on infection type and severity
- CrCl 30-60 mL/min: Maximum 2 g daily
- CrCl 11-29 mL/min: 500 mg every 24 hours
- CrCl ≤10 mL/min: 500 mg every 24 hours
- Hemodialysis: 1 g loading dose, then 500 mg after each dialysis session
- Elderly: Adjust based on renal function
- Pediatrics: 50 mg/kg every 8-12 hours (maximum adult dose)
- Hepatic impairment: No adjustment needed
- IV infusion over 30 minutes
- IM administration possible but less common
Pharmacokinetics
Absorption: Not orally bioavailable; administered parenterally Distribution: Widely distributed into body tissues and fluids- Volume of distribution: 18-20 L
- CSF penetration: Adequate in inflamed meninges (10-15% of serum levels)
- Protein binding: Approximately 20%
- Half-life: 2-2.3 hours in normal renal function
- Prolonged in renal impairment
Contraindications
- Known hypersensitivity to cefepime or other cephalosporins
- History of anaphylactic reaction to any beta-lactam antibiotic
- Cross-reactivity with penicillins: Contraindicated in patients with immediate hypersensitivity reactions to penicillins
Warnings and Precautions
Boxed Warning: Neurotoxicity including encephalopathy, myoclonus, seizures, and nonconvulsive status epilepticus have been reported, particularly in patients with renal impairment who received doses exceeding recommended guidelines. Additional precautions:- Clostridium difficile-associated diarrhea
- Development of drug-resistant bacteria
- Superinfections with fungi or resistant organisms
- Positive direct Coombs test may occur
- Prolonged use may result in fungal or bacterial superinfection
- Use caution in patients with history of gastrointestinal disease, particularly colitis
Drug Interactions
Significant interactions:- Aminoglycosides: Increased risk of nephrotoxicity
- Loop diuretics: Potential increased nephrotoxicity
- Probenecid: Decreases renal clearance of cefepime
- Chloramphenicol: Antagonistic effect in vitro
- Warfarin: Possible enhanced anticoagulant effect (monitor INR)
Adverse Effects
Common (≥1%):- Diarrhea (3%)
- Rash (2%)
- Nausea/vomiting (2%)
- Injection site reactions
- Headache
- Fever
- Seizures and neurotoxicity
- Anaphylaxis
- Stevens-Johnson syndrome
- Blood dyscrasias (neutropenia, thrombocytopenia)
- Hepatitis and cholestasis
- Acute kidney injury
- Clostridium difficile-associated diarrhea
- Interstitial nephritis
Monitoring Parameters
Baseline:- Complete blood count with differential
- Renal function tests (BUN, creatinine)
- Liver function tests
- Culture and sensitivity results
- Clinical response assessment
- Renal function (especially in elderly and critically ill)
- Signs of neurotoxicity (especially in renal impairment)
- Superinfection monitoring
- Diarrhea assessment for C. difficile
- Coagulation parameters if on concurrent anticoagulants
Patient Education
- Complete the full course of therapy even if feeling better
- Report any signs of allergic reaction immediately (rash, itching, swelling)
- Inform healthcare providers of any history of kidney problems
- Report any neurological symptoms (confusion, twitching, seizures)
- Notify provider if diarrhea develops during or after treatment
- Inform all healthcare providers of cefepime use
- Do not take any new medications without consulting healthcare provider
- Understand potential side effects and when to seek medical attention
References
1. FDA Prescribing Information: Cefepime hydrochloride injection 2. Gilbert DN, et al. The Sanford Guide to Antimicrobial Therapy. 2023 3. Lexicomp Online®. Cefepime monograph 4. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 9th edition 5. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing 6. Chow JW, et al. Enterobacter bacteremia: clinical features and emergence of antibiotic resistance during therapy. Ann Intern Med. 1991 7. Yahav D, et al. Efficacy and safety of cefepime: a systematic review and meta-analysis. Lancet Infect Dis. 2007
Note: This monograph provides general information and should not replace clinical judgment. Always consult current prescribing information and clinical guidelines for specific patient care decisions.