What are the indications for Cefepime?

Cefepime Indications

Cefepime is FDA-approved for moderate to severe pneumonia (including Pseudomonas aeruginosa), empiric therapy in febrile neutropenic patients, complicated and uncomplicated urinary tract infections, uncomplicated skin and skin structure infections, and complicated intra-abdominal infections when combined with metronidazole. 1

FDA-Approved Indications

Respiratory Tract Infections

• Moderate to severe pneumonia caused by Streptococcus pneumoniae (including bacteremic cases), Pseudomonas aeruginosa, Klebsiella pneumoniae, or Enterobacter species 1
• Dosing: 2 g IV every 8 hours for Pseudomonas aeruginosa pneumonia 2
• Treatment duration: 10-14 days for hospital-acquired or ventilator-associated pneumonia 2

Febrile Neutropenia

• Empiric monotherapy for febrile neutropenic patients 1
• Important caveat: Monotherapy may be insufficient in high-risk patients (recent bone marrow transplant, hypotension at presentation, underlying hematologic malignancy, or severe/prolonged neutropenia) 1
• Cefepime remains acceptable despite past FDA meta-analysis concerns; subsequent comprehensive FDA review found no statistically significant increase in 30-day mortality (RR 1.20; 95% CI 0.82-1.76) 3

Urinary Tract Infections

• Uncomplicated and complicated UTIs (including pyelonephritis) caused by E. coli or K. pneumoniae when severe, or E. coli, K. pneumoniae, or Proteus mirabilis when mild to moderate 1
• Treatment duration: 7-10 days for complicated UTIs 2

Skin and Soft Tissue Infections

• Uncomplicated skin and skin structure infections caused by methicillin-susceptible Staphylococcus aureus or Streptococcus pyogenes 1

Intra-Abdominal Infections

• Complicated intra-abdominal infections in combination with metronidazole caused by E. coli, viridans group streptococci, P. aeruginosa, K. pneumoniae, Enterobacter species, or Bacteroides fragilis 1
• Alternative regimen for critically ill patients: Cefepime 2 g every 8 hours plus metronidazole 500 mg every 6 hours 3

Key Clinical Advantages

Spectrum of Activity

• Fourth-generation cephalosporin with broader spectrum than third-generation agents 4, 5
• Enhanced activity against Gram-positive organisms (similar to cefotaxime/ceftriaxone) while maintaining excellent Gram-negative coverage (similar to ceftazidime) 4
• Stable against many plasmid- and chromosome-mediated beta-lactamases 4
• Poor inducer of AmpC beta-lactamases, retaining activity against Enterobacteriaceae resistant to third-generation cephalosporins (particularly derepressed Enterobacter mutants) 4, 5

Resistance Considerations

• Effective against AmpC-producing organisms, making it particularly valuable for empiric therapy in intra-abdominal infections 3
• Less susceptible to hydrolysis by extended-spectrum beta-lactamases compared to third-generation cephalosporins, though not immune 4
• For carbapenem-resistant Pseudomonas aeruginosa susceptible to cefepime, consider 2 g IV every 8 hours, though newer agents (ceftolozane-tazobactam, ceftazidime-avibactam) are preferred for difficult-to-treat strains 2

Important Clinical Caveats

When NOT to Use Cefepime

• No anti-anaerobic activity: Must combine with metronidazole for empiric intra-abdominal infections 3, 1
• Not reliable as monotherapy for ceftazidime-resistant organisms in many centers due to decreasing potency and poor activity against some streptococci 3
• Avoid for ESBL-producing organisms despite in vitro susceptibility; carbapenems remain preferred for confirmed ESBL infections 3

Geographic and Institutional Considerations

• Quinolone resistance prevalence, ESBL-producing bacteria rates, and local carbapenem resistance patterns must guide empiric selection 3
• In Taiwan and similar regions where cefoperazone, moxalactam, and flomoxef remain available, ESBL testing should still be performed before using these agents 3

Combination Therapy Scenarios

• For severe Pseudomonas infections or difficult-to-treat strains, consider combination with amikacin 15 mg/kg IV daily 2
• Vancomycin is NOT routinely added to cefepime for empiric febrile neutropenia unless specific risk factors present (catheter-related infection, hemodynamic instability, mucositis, skin/soft tissue infection at catheter site, or colonization with resistant Gram-positive organisms) 3

Pharmacokinetic Profile

• Linear pharmacokinetics with elimination half-life of approximately 2 hours 6
• Primarily renally excreted as unchanged drug (>80%) 6
• Low protein binding (16-19%) with wide tissue distribution 6
• Requires dose adjustment in renal impairment 6
• Removed by hemodialysis (40-68% over 3 hours) and peritoneal dialysis (26% over 72 hours) 6