Cefepime vs Ceftazidime for Severe Infections
For most severe infections requiring empiric broad-spectrum gram-negative coverage, cefepime is the preferred agent over ceftazidime due to its superior gram-positive activity (particularly against methicillin-sensitive Staphylococcus aureus), broader spectrum, reduced beta-lactamase induction potential, and more convenient twice-daily dosing.
Spectrum of Activity Considerations
Gram-Positive Coverage
- Cefepime provides clinically significant activity against MSSA, while ceftazidime does not 1, 2, 3
- When empiric MSSA coverage is needed (high mortality risk patients not receiving anti-MRSA therapy), guidelines specifically recommend cefepime, piperacillin-tazobactam, levofloxacin, imipenem, or meropenem—notably excluding ceftazidime from this list 1
- Cefepime has in vitro activity against penicillin-sensitive, -intermediate, and -resistant Streptococcus pneumoniae similar to cefotaxime and ceftriaxone, whereas ceftazidime lacks reliable pneumococcal coverage 3
Gram-Negative Coverage
- Both agents provide equivalent antipseudomonal activity 2, 3, 4
- Cefepime demonstrates superior stability against AmpC beta-lactamases and is a poor inducer of these enzymes, making it more reliable for infections with Enterobacter, Citrobacter, and Serratia species 2, 3, 4
- For third-generation cephalosporin-resistant Enterobacterales (3GCephRE), both agents are listed as options, but cefepime is generally not recommended due to concerns about treatment failure 1
Clinical Efficacy Data
Hospital-Acquired and Ventilator-Associated Pneumonia
- Guidelines list both cefepime and ceftazidime as acceptable options for HAP/VAP empiric therapy 1
- However, cefepime monotherapy is preferred when MSSA coverage is desired without adding vancomycin or linezolid 1
- Clinical trials demonstrate equivalent efficacy between cefepime (2g q8-12h) and ceftazidime (2g q8h) for pneumonia, with satisfactory clinical response rates of 71-86% 3, 5, 6
Febrile Neutropenia
- Cefepime and ceftazidime show therapeutic equivalence for empiric monotherapy in febrile neutropenic patients, with survival rates of 93% vs 97% and resolution without modification rates of 51% vs 55% respectively 7
- Both agents are dosed at 2g IV q8h for this indication 7
Intra-Abdominal Infections
- For health care-associated intra-abdominal infections, both cefepime and ceftazidime are listed as acceptable options when combined with metronidazole 1
- Critical caveat: Neither cefepime nor ceftazidime provides enterococcal coverage 8
- When anti-enterococcal therapy is needed (postoperative infections, prior cephalosporin exposure, immunocompromised patients, valvular heart disease), ampicillin must be added to either regimen 1, 8
- Cefepime plus metronidazole achieved 81% cure rates for complicated intra-abdominal infections 7
Dosing Advantages
- Cefepime is administered twice daily (1-2g q12h) for most indications, while ceftazidime requires three-times-daily dosing (1-2g q8h) 2, 3, 6
- This dosing convenience improves nursing workflow and may enhance compliance without compromising efficacy 6
- For severe infections or febrile neutropenia, both agents are dosed at 2g q8h 1, 7
Resistance and Stewardship Considerations
- Cefepime's reduced induction of AmpC beta-lactamases theoretically decreases selection pressure for resistant mutants, particularly with Enterobacter species 2, 3, 4
- For carbapenem-resistant Enterobacterales (CRE), neither agent is recommended as monotherapy; newer beta-lactam/beta-lactamase inhibitor combinations (ceftazidime-avibactam, meropenem-vaborbactam) are preferred 1
- For 3GCephRE infections, guidelines suggest avoiding both cefepime and ceftazidime in favor of carbapenems or, for non-severe infections, targeted older agents based on susceptibility 1
Safety Profile
- Both agents demonstrate comparable tolerability with primarily gastrointestinal adverse events 2, 5, 6
- Adverse event rates requiring discontinuation: 1.4% for cefepime ≤2g/day and 2.9% for >2g/day 2
- Clinical trials show minimal differences in adverse effects between the two agents, with none requiring dose reduction or discontinuation 5, 6
Clinical Algorithm for Selection
Choose Cefepime when:
- Empiric therapy requires both gram-negative and MSSA coverage 1
- Treating HAP/VAP in patients at high mortality risk without separate anti-MRSA therapy 1
- Suspected Enterobacter, Citrobacter, or Serratia infections where AmpC induction is a concern 9, 2, 3
- Twice-daily dosing is preferred for logistical reasons 6
Choose Ceftazidime when:
- Cefepime is unavailable or contraindicated
- Treating documented Pseudomonas infections with confirmed susceptibility to both agents
- Used in combination regimens where gram-positive coverage is provided by another agent 1
Avoid both agents when: