What is the recommended use and dosage of Cefepime for treating severe or complicated infections in patients with varying ages and renal function, including those with a history of allergy to cephalosporins or penicillins?

Cefepime: Recommended Use and Dosing for Severe and Complicated Infections

Primary Indications and Standard Dosing

Cefepime is indicated for moderate-to-severe pneumonia, complicated urinary tract infections, skin/soft tissue infections, complicated intra-abdominal infections (with metronidazole), and febrile neutropenia, with standard adult dosing of 1-2g IV every 8-12 hours depending on infection severity and pathogen. 1

Adult Dosing by Infection Type (Normal Renal Function, CrCl >60 mL/min)

• Moderate to severe pneumonia: 1-2g IV every 8-12 hours for 10 days 1

  • For Pseudomonas aeruginosa specifically: 2g IV every 8 hours 1

• Febrile neutropenia: 2g IV every 8 hours for 7 days or until neutropenia resolves 1

• Complicated urinary tract infections:

  • Mild to moderate: 0.5-1g IV every 12 hours for 7-10 days 1
  • Severe: 2g IV every 12 hours for 10 days 1

• Skin and soft tissue infections: 2g IV every 12 hours for 10 days 1

• Complicated intra-abdominal infections: 2g IV every 8-12 hours for 7-10 days (must combine with metronidazole for anaerobic coverage) 1

Multidrug-Resistant Organism Coverage

• For carbapenem-resistant Pseudomonas aeruginosa (CRPA) susceptible to cefepime: 2g IV every 8-12 hours for 5-14 days depending on infection site 2

  • Urinary tract infections: 5-10 days 2
  • Pneumonia or bloodstream infections: 10-14 days 2

• Cefepime is NOT recommended for difficult-to-treat Pseudomonas (DTR-PA) where newer agents like ceftolozane/tazobactam or ceftazidime/avibactam are preferred 2

Pediatric Dosing (Ages 2 Months to 16 Years, Normal Renal Function)

• Standard dose: 50 mg/kg IV every 12 hours (maximum 2g per dose) 1

• Febrile neutropenia: 50 mg/kg IV every 8 hours 1

• For Pseudomonas infections: 50 mg/kg IV every 8 hours (maximum 2g per dose) 2

• Neonatal dosing varies by gestational and postnatal age:

  • Gestational age <36 weeks: 30 mg/kg IV every 12 hours 2
  • Gestational age ≥36 weeks: 50 mg/kg IV every 12 hours 2

Critical Care and Pharmacodynamic Optimization

In critically ill patients with preserved renal function, higher doses of 2g every 8 hours are required due to increased clearance and volume of distribution, particularly for sepsis or high-MIC pathogens. 3

Extended Infusion Strategies

• Standard infusion: Administer over approximately 30 minutes 1

• Extended infusion (3-4 hours): Consider for severe infections with high-MIC organisms (MIC ≥4 mg/L), particularly Pseudomonas, to optimize time above MIC 3

• Continuous infusion: May provide additional benefit in critically ill septic patients, with loading dose given as rapid bolus followed by continuous infusion 3

Monitoring in Critical Illness

• Therapeutic drug monitoring should be considered in critically ill patients, especially those with fluctuating renal function 3

• Risk of neurotoxicity increases when trough concentrations exceed 8× MIC, emphasizing need for monitoring 3

• 37-44% of ICU patients fail to achieve therapeutic targets with standard dosing, highlighting need for dose adjustments 3

Renal Impairment Dosing

Dose adjustment is mandatory for patients with CrCl ≤60 mL/min to prevent neurotoxicity. 1

• Specific renal dosing adjustments are required but vary by creatinine clearance—consult FDA labeling for precise adjustments 1

Allergy Considerations

Penicillin Allergy Cross-Reactivity

Cefepime can be safely administered to most patients with unverified penicillin allergy, as cross-reactivity risk is extremely low (0.7-0.8%) when penicillin allergy is unconfirmed. 2

• For patients with confirmed penicillin allergy, cross-reactivity to cefepime remains low at approximately 2.11% for low-similarity-score cephalosporins like cefepime 2

• Cefepime has unique R1 side chains that differ from most penicillins, reducing cross-reactivity risk 2

Absolute Contraindications

Cefepime is contraindicated in patients with prior immediate hypersensitivity reactions to cefepime, other cephalosporins, or severe delayed immunologic reactions to beta-lactams. 1

• Do NOT use in patients with history of:
  • Stevens-Johnson syndrome or toxic epidermal necrolysis (SCARs) 2
  • Drug-induced hemolytic anemia 2
  • Drug-induced liver injury 2
  • Acute interstitial nephritis from beta-lactams 2

Practical Allergy Management Algorithm

• Unverified penicillin allergy: Administer cefepime without skin testing 2

• Confirmed penicillin allergy with non-severe reaction: Consider cefepime with monitoring for first dose 2

• Multiple drug allergies or severe reactions: Skin testing may be advisable, though not routinely recommended 2

• Anaphylaxis to penicillin: Evaluate for specific side chain cross-reactivity; cefepime remains low-risk but consider alternatives if multiple beta-lactam allergies exist 2

Critical Safety Warnings

Neurotoxicity Risk

Neurotoxicity may occur, especially in patients with renal impairment receiving unadjusted doses—if neurotoxicity develops (confusion, encephalopathy, myoclonus, seizures), discontinue cefepime immediately. 1, 3

Clostridioides difficile Risk

Evaluate for C. difficile-associated diarrhea if diarrhea develops during or after cefepime therapy. 1

Drug Interactions

• Aminoglycosides: Increased risk of nephrotoxicity and ototoxicity when combined 1

• Potent diuretics (furosemide): Nephrotoxicity reported with concomitant use 1

Clinical Efficacy Evidence

Cefepime demonstrates 90-97% clinical cure rates for serious bacterial infections including pneumonia, urinary tract infections, skin/soft tissue infections, and bacteremia. 4, 5

• Comparable efficacy to ceftazidime for pneumonia, urinary tract infections, and skin infections in multiple randomized trials 6, 5, 7

• Microbiological eradication rates exceed 90% for most pathogens including Pseudomonas aeruginosa 5

• Effective for infections failing previous beta-lactam therapy due to stability against many beta-lactamases 7

Common Pitfalls to Avoid

• Do not use standard dosing in critically ill patients—they require higher doses (2g every 8 hours) due to altered pharmacokinetics 3

• Do not forget renal dose adjustment—failure to adjust for CrCl ≤60 mL/min significantly increases neurotoxicity risk 1

• Do not use cefepime alone for intra-abdominal infections—must combine with metronidazole for anaerobic coverage 1

• Do not assume coverage of MRSA, Enterococcus, or ESBL-producing organisms—cefepime lacks activity against these pathogens 8

• Do not use for nosocomial infections without susceptibility data—resistance patterns may require broader coverage 8