What is the coverage and dosing of cefepime for treating bacterial infections?

Cefepime Coverage and Dosing for Bacterial Infections

Cefepime is a fourth-generation cephalosporin with broad-spectrum activity against gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa, and is indicated for various bacterial infections with standard dosing of 1-2g IV every 8-12 hours for adults depending on infection severity.

Antimicrobial Spectrum

Cefepime has excellent coverage against:

Gram-Positive Organisms

• Staphylococcus aureus (methicillin-susceptible isolates only) 1
• Streptococcus pneumoniae (including penicillin-sensitive, intermediate, and resistant strains) 2
• Streptococcus pyogenes 1
• Viridans group streptococci 1

Gram-Negative Organisms

• Pseudomonas aeruginosa 1, 2
• Klebsiella pneumoniae 1
• Enterobacter species 1, 2
• Escherichia coli 1
• Proteus mirabilis 1
• HACEK group (when susceptible) 3

Key Advantages

• Stable against many common plasmid- and chromosome-mediated beta-lactamases 2
• Poor inducer of AmpC beta-lactamases 2
• Retains activity against Enterobacteriaceae resistant to third-generation cephalosporins 2
• Less susceptible to hydrolysis by extended-spectrum beta-lactamases (ESBLs) than third-generation cephalosporins 2

FDA-Approved Indications

Cefepime is indicated for the following infections 1:

1. Moderate to severe pneumonia
2. Empiric therapy for febrile neutropenic patients
3. Uncomplicated and complicated urinary tract infections (including pyelonephritis)
4. Uncomplicated skin and skin structure infections
5. Complicated intra-abdominal infections (in combination with metronidazole)

Dosing Recommendations

Adult Dosing 1

• Moderate to severe pneumonia: 1-2g IV every 8-12 hours for 10 days
• Febrile neutropenia: 2g IV every 8 hours for 7 days or until resolution of neutropenia
• Mild to moderate UTIs: 0.5-1g IV every 12 hours for 7-10 days
• Severe UTIs: 2g IV every 12 hours for 10 days
• Skin and skin structure infections: 2g IV every 12 hours for 10 days
• Complicated intra-abdominal infections (with metronidazole): 2g IV every 8-12 hours for 7-10 days
• Nosocomial endocarditis (with vancomycin and gentamicin): 100-150 mg/kg/day divided every 8-12 hours up to 6g/day 3

Pediatric Dosing 1

• Children up to 40kg: 50 mg/kg/dose every 12 hours (for most infections)
• For moderate to severe pneumonia due to P. aeruginosa or febrile neutropenia: 50 mg/kg/dose every 8 hours

Renal Adjustment

Dose adjustment is required for patients with creatinine clearance ≤60 mL/min 1.

Clinical Efficacy

Cefepime has demonstrated clinical efficacy comparable to:

• Ceftazidime, ceftriaxone, and cefotaxime in community-acquired and nosocomial pneumonia 2
• Imipenem/cilastatin in nosocomial pneumonia 2
• When combined with amikacin, as effective as ceftazidime plus amikacin 2

For ESBL-producing Enterobacteriaceae, carbapenems are generally preferred over cefepime, especially when cefepime MICs are elevated (4-8 μg/mL) 3, 4.

Special Considerations

Optimized Dosing for Resistant Organisms

• For gram-negative pathogens with MICs of 4 or 8 μg/mL, higher dosing regimens (2g every 8 hours or 1g every 6 hours) may be necessary to improve outcomes 4
• Extended infusion of cefepime (over 3-4 hours) may be considered for serious infections to improve pharmacodynamic exposure 5

Combination Therapy

• For nosocomial endocarditis associated with vascular cannulae or early prosthetic valve endocarditis, cefepime should be used in combination with vancomycin and gentamicin (with rifampin if prosthetic material is present) 3
• For complicated intra-abdominal infections, cefepime should be combined with metronidazole 1

Potential Pitfalls

1. Resistance concerns:

   • Monitoring local susceptibility patterns is crucial as resistance can develop
   • Cefepime may be less effective against ESBL-producing organisms with elevated MICs 3, 4

2. Dosing errors:

   • Underdosing for serious infections or resistant organisms
   • Failure to adjust for renal function 5

3. Inappropriate use:

   • Using cefepime as monotherapy for anaerobic infections
   • Using for MRSA infections (cefepime lacks activity against MRSA) 1

4. Adverse effects:

   • Most common: rash and diarrhea
   • Less common: pruritus, urticaria, nausea, vomiting, oral candidiasis, colitis, headache, fever, erythema, and vaginitis 2

Cefepime remains an important antibiotic option for serious bacterial infections, particularly when broad-spectrum coverage including Pseudomonas aeruginosa is needed, but should be used judiciously to prevent the emergence of resistant organisms.