Antimicrobials

Active against:

• Most strains of E. coli, Klebsiella, Proteus mirabilis
• Many strains of Acinetobacter, Serratia
• Haemophilus influenzae
• Neisseria gonorrhoeae and Neisseria meningitidis
• Staphylococci (less active than cefazolin) and streptococci
• Oral anaerobes

Not active against:

• Methicillin-resistant S. aureus (MRSA)
• Enterococci
• B. fragilis
• Pseudomonas aeruginosa, Stenotrophomonas maltophilia
• Listeria

Appropriate Uses:

• Empiric therapy for bacterial meningitis (where Pseudomonas is not suspected)
• Empiric therapy for severe community-acquired pneumonia, in combination with a macrolide (azithromycin, clarithromycin)
• Empiric therapy for early onset (< 5 days hospital length of stay) nosocomial pneumonia
• Intra-abdominal infection, in combination with metronidazole
• Bone/joint infection due to susceptible organisms

Inappropriate Uses:

• Surgical prophylaxis
• Treatment of known or suspected Pseudomonas infections

• The potential for cross-reactivity exists among penicillins, cephalosporins and carbapenems
• There is potential for development of beta-lactamase resistance in "SPICE” organisms during therapy with ceftriaxone. The risk is greatest with Enterobacter spp.
• Pregnancy: not expected to increase risk of major congenital malformations
• Breastfeeding: considered safe during breastfeeding. Monitor nursing infant for GI symptoms.

• Hypersensitivity: drug fever, skin rash, urticaria, anaphylaxis
• Hematologic: positive Coombs test, rarely thrombocytopenia, leucopenia
• Hepatic/Renal: transient rise in AST, ALT, and urea nitrogen (no clinical evidence of renal impairment)
• Gastrointestinal: nausea, vomiting, diarrhea, oral candidiasis, rarely pseudomembranous colitis
• Rare cases of biliary sludge or stones after prolonged treatment with high doses (>2 g/day)

• Usual dosage: 1 g every 24 hours
• Endocarditis: 2 g every 12 – 24 hours
• Meningitis or CNS infection: 2 g every 12 hours
• Osteomyelitis: 2 g every 12 – 24 hours
• Renal insufficiency: no reduction required
• Note: For ward patients, orders specifying >1 g per day for indications other than those listed above will automatically be converted to 1 g every 24h hours
• Note: For ICU patients with sepsis and CrCl > 60 mL/min, consider increasing ceftriaxone dose to 2 g IV daily

• Direct Injection: not recommended (unless severe fluid restriction)
• Intermittent Infusion: infuse over 15 – 30 minutes
• Please refer to IV drug monograph on pharmacy intranet page for additional administration information.

• Dreesen, Erwin et al. “Ceftriaxone dosing based on the predicted probability of augmented renal clearance in critically ill patients with pneumonia.” The Journal of antimicrobial chemotherapy vol. 77,9 (2022): 2479-2488
• Ollivier, Julien et al. “Are Standard Dosing Regimens of Ceftriaxone Adapted for Critically Ill Patients with Augmented Creatinine Clearance?.” Antimicrobial agents and chemotherapy vol. 63,3 e02134-18. 26 Feb. 2019
• Ackerman, Andrew et al. “Comparison of Clinical Outcomes among Intensive Care Unit Patients Receiving One or Two Grams of Ceftriaxone Daily.” Antimicrobial agents and chemotherapy vol. 64,6 e00066-20. 21 May. 2020