Treatment of Gram-Negative Bacilli Infections with Rocephin (Ceftriaxone)
For infections caused by gram-negative bacilli, ceftriaxone is indicated for susceptible organisms including Escherichia coli, Klebsiella pneumoniae, Proteus species, Enterobacter species, Haemophilus influenzae, and Serratia marcescens, but is not recommended as monotherapy for Pseudomonas aeruginosa or multidrug-resistant gram-negative bacilli. 1
Susceptible Gram-Negative Organisms
Ceftriaxone is effective against many gram-negative bacilli, specifically:
- Escherichia coli - urinary tract, intra-abdominal, bloodstream infections 1
- Klebsiella pneumoniae - respiratory tract, urinary tract, bloodstream infections 1
- Proteus species (mirabilis, vulgaris) - urinary tract infections 1
- Enterobacter species - lower respiratory tract, bone and joint infections 1
- Haemophilus influenzae - respiratory infections, meningitis 1
- Serratia marcescens - lower respiratory tract, skin infections 1
- Morganella morganii - urinary tract, skin infections 1
Dosing Recommendations
The dosing of ceftriaxone depends on infection severity and site:
- For severe infections: 1-2 grams IV once daily or in divided doses twice daily 1
- For most infections: 1-2 grams IV once daily 1
- For meningitis: 100 mg/kg/day (not exceeding 4 grams daily) 1
- Maximum daily dose: 4 grams 1
- Duration: Generally 4-14 days; complicated infections may require longer therapy 1
Treatment Algorithm for Gram-Negative Bacilli Infections
1. For Third-Generation Cephalosporin-Susceptible Gram-Negative Bacilli:
- Use ceftriaxone 1-2 grams IV once daily for 7-14 days depending on infection site and severity 1, 2
- For uncomplicated urinary tract infections: Consider shorter courses (5-7 days) 3
- For meningitis: Use higher doses (100 mg/kg/day, not exceeding 4 grams) 1
2. For Third-Generation Cephalosporin-Resistant Enterobacterales (3GCephRE):
- Do not use ceftriaxone - it will be ineffective 4
- For bloodstream infections and severe infections: Use a carbapenem (imipenem or meropenem) 4
- For non-severe infections: Consider piperacillin-tazobactam, amoxicillin/clavulanic acid, or quinolones 4
- For complicated UTI without septic shock: Consider aminoglycosides or IV fosfomycin 4
3. For Carbapenem-Resistant Enterobacterales (CRE):
- Do not use ceftriaxone - it will be ineffective 4
- For severe infections: Use meropenem-vaborbactam or ceftazidime-avibactam if active in vitro 4
- For severe infections with metallo-β-lactamases: Consider cefiderocol 4
- For non-severe infections: Use an active older antibiotic based on susceptibility testing 4
4. For Carbapenem-Resistant Pseudomonas aeruginosa (CRPA):
- Do not use ceftriaxone - it has limited activity against Pseudomonas, even susceptible strains 2, 3
- For severe infections: Consider ceftolozane-tazobactam if active in vitro 4
- For severe infections treated with polymyxins, aminoglycosides, or fosfomycin: Use combination therapy with two active agents 4
Important Considerations and Caveats
- Always obtain cultures before starting therapy to confirm susceptibility 1
- Ceftriaxone has limited activity against Pseudomonas aeruginosa and should not be used as monotherapy for these infections 2, 3
- For multidrug-resistant gram-negative bacilli, ceftriaxone is typically ineffective and alternative agents should be used 4
- Do not mix ceftriaxone with calcium-containing solutions due to risk of precipitation 1
- Monitor for adverse effects including elevated liver enzymes (16%), thrombocytosis (16%), and eosinophilia (8%) 3
- Ceftriaxone has a long half-life allowing for once-daily dosing in most infections, which can provide cost and convenience benefits 5, 6
- For empiric therapy of suspected gram-negative infections, local antibiotic resistance patterns should guide initial treatment choices 1
Specific Infection Sites
- Lower respiratory tract infections: 1-2 grams IV once daily for 7-14 days 1, 7
- Urinary tract infections: 1-2 grams IV once daily for 5-14 days 1, 3
- Intra-abdominal infections: 1-2 grams IV once daily, often combined with metronidazole for anaerobic coverage 1, 7
- Skin and soft tissue infections: 1-2 grams IV once daily for 7-14 days 1, 7
- Meningitis: 100 mg/kg/day (not exceeding 4 grams daily) 1