cefepime
Brand: Maxipime
Prototype: ceftriaxone
Drug Class: antibiotic
Drug Family: antibiotic
Subclass: fourth-generation cephalosporin / beta-lactam
Organ Systems: infectious-disease
Mechanism of Action
Fourth-generation cephalosporin with expanded spectrum; zwitterionic structure enables penetration through outer membrane of gram-negatives more efficiently; maintains activity against AmpC-expressing Enterobacteriaceae and has antipseudomonal activity; does not cover MRSA or enterococci.
penicillin-binding proteins (PBPs)
Indications
- hospital-acquired pneumonia / ventilator-associated pneumonia
- febrile neutropenia
- complicated UTI (Pseudomonas)
- intra-abdominal infections (with metronidazole)
- empiric therapy for severe gram-negative infections
Contraindications
- cephalosporin or severe penicillin allergy
Adverse Effects
Common
- diarrhea
- nausea
- rash
- elevated LFTs
Serious
- neurotoxicity / encephalopathy (especially in renal impairment — dose-dependent accumulation)
- C. difficile colitis
- anaphylaxis
- seizures (in renal failure with inadequate dose adjustment)
Pharmacokinetics (ADME)
| Absorption | IV or IM |
| Distribution | Protein binding 20%; good CNS penetration |
| Metabolism | Minimal |
| Excretion | Renal; significant dose reduction required for CrCl <60 mL/min |
| Half-life | 2 hours |
| Onset | End of infusion |
| Peak | End of infusion |
| Duration | 8–12 hours |
| Protein Binding | 20% |
| Vd | ~0.28 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| aminoglycosides | additive nephrotoxicity; separate IV lines | moderate |
Nursing Considerations
- Strict renal dosing is critical — cefepime neurotoxicity (encephalopathy, myoclonus, seizures) occurs when doses are not adjusted for CrCl; obtain renal function before and during therapy
- Cefepime neurotoxicity can be mistaken for worsening septic encephalopathy in ICU patients — suspect cefepime as cause in any ICU patient with unexplained neurological deterioration
- Monitor renal function (SCr, BUN) every 48–72 hours in ICU patients; adjust dose proactively as renal function changes
- EEG may show triphasic waves consistent with metabolic encephalopathy during cefepime neurotoxicity; treatment is discontinuation and supportive care
Clinical Pearls
- Cefepime neurotoxicity (CEFNE) is increasingly recognized in the ICU — it is dose-dependent, occurs most often in patients with renal impairment receiving standard doses, and manifests as confusion, myoclonus, and non-convulsive status epilepticus
- Unlike third-generation cephalosporins, cefepime is stable to AmpC beta-lactamases (produced by chromosomal derepression in Enterobacter, Citrobacter, Serratia), making it the preferred agent when these organisms are suspected
Safety Profile
Pregnancy generally-safe
Lactation safe
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
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