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Cefepime
Cefepime is a fourth-generation cephalosporin antibiotic known for its broad-spectrum activity against both Gram-positive and Gram-negative bacteria. It is particularly effective against resistant pathogens and is widely used in hospital settings for severe infections. This article references the British National Formulary (BNF), Lippincott Textbook of Pharmacology, and Lange Basic & Clinical Pharmacology to provide a detailed overview of cefepime, including its mechanism of action, clinical uses, dosing guidelines, side effects, precautions, drug interactions, and generic names.
Cefepime exerts its bactericidal effect by inhibiting bacterial cell wall synthesis. According to the Lippincott Textbook of Pharmacology, cefepime binds to penicillin-binding proteins (PBPs) on the bacterial cell wall, disrupting peptidoglycan cross-linking. This weakens the cell wall, leading to osmotic instability and cell lysis.
The Lange Basic & Clinical Pharmacology emphasizes cefepime’s resistance to many beta-lactamases, including AmpC enzymes produced by Enterobacter and Citrobacter species. Its dual affinity for both Gram-positive and Gram-negative PBPs makes it effective against a wide range of pathogens.
Cefepime is indicated for:
- Severe Bacterial Infections:
- Respiratory Tract Infections: Pneumonia (community-acquired and hospital-acquired).
- Urinary Tract Infections (UTIs): Complicated pyelonephritis and cystitis.
- Intra-Abdominal Infections: Peritonitis, biliary tract infections (in combination with metronidazole).
- Skin and Soft Tissue Infections: Cellulitis, abscesses.
- Febrile Neutropenia: Empiric therapy in immunocompromised patients.
- Septicemia: Bloodstream infections caused by susceptible organisms.
The BNF highlights its role in treating infections caused by multidrug-resistant Gram-negative bacteria, particularly in critical care settings.
Dosing is tailored to infection severity, renal function, and patient age:
Adults:
- Moderate Infections: 1 g IV/IM every 12 hours.
- Severe Infections (e.g., febrile neutropenia): 2 g IV every 8 hours.
Children (>2 months):
- 30–50 mg/kg/day IV/IM in divided doses every 8–12 hours (max 6 g/day).
Renal Impairment:
- Creatinine Clearance (CrCl) 30–60 mL/min: Reduce dose by 25%.
- CrCl 10–30 mL/min: Reduce dose by 50%.
- CrCl <10 mL/min: Administer 25% of the standard dose.
Administration Tips:
- IV Infusion: Dilute in 50–100 mL of compatible fluid (e.g., 0.9% saline) and infuse over 30 minutes.
- IM Injection: Reconstitute with lidocaine or sterile water to reduce discomfort.
Cefepime is generally well-tolerated, but potential side effects include:
- Common:
- Gastrointestinal disturbances (nausea, diarrhea).
- Injection site reactions (pain, inflammation).
- Rash or pruritus.
- Serious (Rare):
- Neurotoxicity (seizures, encephalopathy) – particularly in renal impairment or overdose.
- Clostridioides difficile-associated diarrhea (CDAD).
- Hypersensitivity reactions (anaphylaxis, Stevens-Johnson syndrome).
- Hematologic effects (neutropenia, thrombocytopenia).
- Contraindications: Hypersensitivity to cephalosporins or severe beta-lactam allergy.
- Renal Impairment: Dose adjustment is critical to avoid neurotoxicity.
- Neurologic Monitoring: Monitor for seizures or confusion in patients with renal dysfunction or prolonged therapy.
- Pregnancy and Lactation: Use only if benefits outweigh risks (limited safety data).
- Cross-Reactivity: Low risk of cross-reactivity with penicillins (<1%), but caution is advised.
Key interactions per the BNF and Lange Basic & Clinical Pharmacology:
- Aminoglycosides: Synergistic against Gram-negative bacteria but may increase nephrotoxicity.
- Probenecid: Reduces renal excretion, increasing cefepime levels (avoid concurrent use).
- Oral Anticoagulants (e.g., warfarin): Enhanced anticoagulant effect (monitor INR).
- Loop Diuretics: May increase the risk of neurotoxicity.
- Generic: Cefepime hydrochloride.
- Brand Names: Maxipime®, Cepime®.
