Treatment of Gram-Negative Bacilli Infections: Ceftriaxone vs Ceftazidime
For most gram-negative bacilli infections, ceftriaxone (Rocephine) is the preferred first-line agent, while ceftazidime (Fortum) should be reserved specifically for suspected or confirmed Pseudomonas aeruginosa infections. 1, 2, 3
Clinical Decision Algorithm
When to Use Ceftriaxone (Rocephine)
Ceftriaxone is the appropriate choice for:
- HACEK group organisms causing endocarditis: 2g/day for 4 weeks in native valve endocarditis, 6 weeks in prosthetic valve endocarditis 1
- Community-acquired gram-negative infections including Enterobacteriaceae (E. coli, Klebsiella, Proteus, Enterobacter): 1-2g daily or divided twice daily 1, 3
- Gram-negative enteric bacilli pneumonia: 1-2g twice daily for 14-21 days 1
- Complicated intra-abdominal infections (mild-to-moderate severity): Third-generation cephalosporin plus metronidazole 1
- Meningitis due to H. influenzae, N. meningitidis, or susceptible gram-negative organisms 3
- Bacteremia/septicemia from susceptible gram-negative bacilli 3, 4
The clinical cure rate with ceftriaxone for gram-negative infections is 93%, with excellent bacteriological eradication 4. Ceftriaxone has superior activity against most Enterobacteriaceae compared to first and second-generation cephalosporins, though it has limited activity against Pseudomonas 5, 4.
When to Use Ceftazidime (Fortum)
Ceftazidime is specifically indicated when:
Pseudomonas aeruginosa is suspected or confirmed, particularly in:
Non-HACEK gram-negative endocarditis: Ceftazidime (or other extended-spectrum cephalosporin) plus aminoglycoside for minimum 6 weeks 1
Healthcare-associated infections with suspected resistant gram-negative organisms including Pseudomonas, Enterobacter, or Serratia 1
Ceftazidime demonstrates superior anti-pseudomonal activity compared to ceftriaxone and should be combined with gentamicin for serious Pseudomonas infections 2, 6.
Combination Therapy Considerations
For critically ill patients or severe infections:
- Add an aminoglycoside (gentamicin 3-5 mg/kg/day) to either cephalosporin for synergy against gram-negative bacilli 1
- Two-drug gram-negative coverage is mandatory for critically ill patients with suspected multidrug-resistant organisms, then de-escalate based on susceptibilities 1
- For intra-abdominal infections, add metronidazole to cover anaerobes including Bacteroides fragilis 1
Duration of Therapy
- Uncomplicated infections: 7 days 1
- Severe gram-negative pneumonia: 14-21 days 1
- Endocarditis (HACEK): 4 weeks for native valve, 6 weeks for prosthetic valve 1
- Non-HACEK gram-negative endocarditis: Minimum 6 weeks 1
- Catheter-related bloodstream infection: 7-14 days after catheter removal 1
Critical Pitfalls to Avoid
Do not use ceftriaxone as monotherapy for Pseudomonas aeruginosa infections - it has minimal activity and will result in treatment failure 2, 5, 4. Ceftazidime is required for anti-pseudomonal coverage 2.
Do not use ceftazidime when ceftriaxone would suffice - ceftazidime has a narrower spectrum against some Enterobacteriaceae and should be reserved for its specific anti-pseudomonal indication to preserve its utility 2.
Monitor for Enterobacter cloacae resistance - this organism may develop resistance to ceftriaxone during therapy; consider alternative agents if suspected 4.
Add anaerobic coverage for polymicrobial infections - neither cephalosporin adequately covers Bacteroides fragilis; metronidazole must be added for intra-abdominal or mixed aerobic-anaerobic infections 1, 3.
Ensure adequate dosing in severe infections - use 2g ceftriaxone twice daily or 2g ceftazidime three times daily for life-threatening infections rather than standard once-daily dosing 1, 2, 3.