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Drug Name: Cefepime

Click on the titles below for drug details

  • Fourth Generation Cephalosporin
  • beta-lactam - binds penicillin-binding-proteins and subsequently impairs bacterial cell wall formation, leading to impaired cell structure and cell death
  • Bactericidal (but can have bacteriostatic effects depending on the amount of time the antibiotic concentration is above the MIC)
  • Parenteral (IV/IM) only
  • Traditional dosing (infants, children, adolescents): normal renal function
    • Febrile neutropenia: 50 mg/kg/dose q8hrs (max 2,000 mg/dose)
      • Patients with severe neutropenia (e.g., patients with oncologic disease) are at increased risk for invasive Pseudomonal infections
    • Severe/Pseudomonal infections: 50mg/kg/dose q8hrs (max 2,000 mg/dose)
  • Non-severe/non-Pseudomonal infections: 50mg/kg/dose q12hrs (max 2,000 mg/dose)
    • Caveat: Q12Hour dosing may be suboptimal for infections caused by bacteria with MIC ≥1 mg/L based on pharmacokinetic modeling. This may include bacteria other than Pseudomonas. CCHMC generally will dose at q8hrs empirically.
  • Patients with abnormal renal function (<60 mL/minute/1.73 m2) require renal dosing adjustment, generally extending the dosing interval. Talk to your friendly pharmacist.
  • Spectrum
    • Combines coverage of both first and third generation cephalosporins + extended coverage against resistant organisms
    • Excellent gram-positive coverage of MSSA, GAS/GBS, Streptococcus pneumoniae
    • Improved gram-negative coverage compared to other cephalosporin classes
      • Neisseria coverage
      • Provides extended spectrum coverage against many Amp-C producing gram negatives (such as Enterobacter, Citrobacter, E.coli, Klebsiella)
    • Provides pseudomonal coverage
    • Does NOT cover MRSA or Enterococcus
  • Indications:
    • Endocarditis with a prosthetic valve
    • Febrile neutropenia
    • Complicated intra-abdominal infection
    • Meningitis
    • Peritonitis in patients on peritoneal dialysis
    • Pseudomonal infections including UTIs, pneumonia
    • Acute pulmonary exacerbations in cystic fibrosis
      • Helpful in CF exacerbation given activity against Pseudomonas as well as other bacteria more specific to CF.
  • Hypersensitivity to cefepime or other cephalosporins
  • Hypersensitivity to penicillins or other beta-lactam antibiotics
  • Higher risk in kidney impairment and pre-existing brain injury
  • C. difficile infections
  • Hypersensitivity
    • Immediate
      • Rapid, IgE-mediated like anaphylaxis and angioedema, usually within 1 hour of administration (can be up to 6 hours later)
    • Delayed
      • Maculopapular reactions, 7-10 days after administration
      • Rarely can cause severe reactions such as DRESS or SJS
  • Neurotoxicity (This is still a source of debate for children; the vast majority of data is in adults; studies in pediatrics are ongoing, including at CCHMC)
    • Can be severe, including encephalopathy, aphasia, myoclonus, seizure, nonconvulsive status epilepticus
    • Usually occurs within 2-4 days of cefepime initiation and is more likely in the setting of renal impairment
  • Cefepime is 85% cleared by the kidneys, serum concentrations are affected by changes in renal clearance
  • Pulmonary
    • Penetrates into the epithelial lining of the respiratory system
    • One study showed that both normal and injured lungs achieve ~ 100% of serum concentrations within the lungs
  • Intra-abdominal
    • Concentration in peritoneal fluid is equivalent to serum concentrations 2hrs after administration
    • Also has good penetration into appendiceal tissue (for coverage of appendicitis)
  • CNS
    • Has good penetration into the CNS, particularly for treatment of bacterial meningitis in infants and children
    • Concentrations in the CNS after administration are well above the typical MIC for common causes of pediatric bacterial meningitis (Strep pneumoniae, Neisseria meningiditis)
  • Joint/bone
    • Rapid penetration into bone, generally approaches serum concentrations
  • Can sometimes cause a maculopapular rash up to 7-10 days after administration, most likely is not significant allergic reaction, but should be monitored for development of other allergic symptoms
  • Similar to other antibiotics, can cause mild GI upset / diarrhea