Ceftriaxone (Rocephin)

• Core Use: Parenteral third-generation cephalosporin with broad Gram-negative and Gram-positive coverage; workhorse once-daily IV agent for many community-acquired serious infections
• Coverage: Covers Streptococcus pneumoniae and many Enterobacterales, but no Pseudomonas and no atypical coverage
• Typical Dosing: Adults: 1–2 g IV q24h; meningitis and severe infections: 2 g IV q12h
• Key Advantage: Once- or twice-daily dosing with long half-life (~8 hours) and dual renal + biliary elimination; generally no dose adjustment needed in isolated renal impairment
• Key Dangers: Biliary sludging/pseudolithiasis (especially high doses), C. difficile infection risk, calcium-ceftriaxone precipitates in neonates

• Generic Name: Ceftriaxone
• Brand Names: Rocephin, generics

Third-generation cephalosporin; parenteral β-lactam antibiotic

Mechanism of Action:

• β-lactam antibiotic that binds to penicillin-binding proteins (PBPs) and inhibits the final transpeptidation step of peptidoglycan synthesis in the bacterial cell wall
• Disrupts cell wall cross-linking, leading to cell lysis and death (bactericidal) in actively dividing bacteria
• Time-dependent killing; efficacy best correlated with the time serum concentrations remain above MIC (T>MIC) during the dosing interval

Pharmacokinetics:

• Absorption: Given IV or deep IM; IM bioavailability is high, with slightly slower peak concentrations
• Distribution: Volume of distribution ~0.1–0.2 L/kg; good penetration into most tissues and fluids; achieves therapeutic CSF levels in meningitis when meninges are inflamed
• Protein Binding: 85–95% (concentration dependent); displacement interactions possible (e.g., bilirubin in neonates)
• Elimination Half-life: ~6–9 hours in adults with normal renal/hepatic function, allowing once-daily dosing for many indications
• Elimination: ~40–60% renal and the remainder biliary/fecal; accumulation primarily an issue in combined severe renal + hepatic impairment
• Dose Adjustment: No routine renal dose adjustment in adults with only renal impairment, though some protocols reduce dose when CrCl is extremely low or in dialysis with concurrent hepatic disease

• Empiric therapy for sepsis when community-acquired Gram-negative and pneumococcal coverage is needed, often combined with vancomycin ± metronidazole depending on source
• Community-acquired pneumonia (CAP) requiring IV therapy, often combined with a macrolide or doxycycline for atypical coverage
• Meningitis (typically with vancomycin ± ampicillin depending on age/risk) for coverage of S. pneumoniae, N. meningitidis, and some Gram-negative bacilli
• Pyelonephritis and complicated UTI, especially when ESBL risk is low and local susceptibility supports use
• Spontaneous bacterial peritonitis (SBP) and other intra-abdominal infections (often ceftriaxone + metronidazole for anaerobic coverage)
• Gonorrhea and some other sexually transmitted infections: single-dose IM ceftriaxone as part of combination therapy per STI guidelines

Available Forms:

• Vials for IV/IM injection: typically 250 mg, 500 mg, 1 g, or 2 g dry powder to be reconstituted with sterile water or compatible fluids
• Reconstituted concentration often 100 mg/mL (e.g., 1 g in 10 mL); for IV infusion, further diluted in 50–100 mL NS or D5W
• Deep IM injection often mixed with lidocaine for pain reduction (per labeling/institutional practice)

Dosing – Ceftriaxone (Adult):

Absolute Contraindications:

• Documented serious hypersensitivity (e.g., anaphylaxis, SCAR) to ceftriaxone or other cephalosporins
• Neonates (especially ≤28 days) with hyperbilirubinemia due to risk of bilirubin displacement and kernicterus
• Neonates requiring IV calcium-containing solutions (e.g., TPN, calcium infusions) due to risk of calcium–ceftriaxone precipitation

Major Precautions:

• History of β-lactam allergy: clarify reaction characteristics; many non-severe reactions may still allow ceftriaxone use with monitoring
• History of severe immediate-type hypersensitivity to penicillins where cross-reactivity is considered clinically unacceptable (use with caution and allergy input)
• Combined severe renal and hepatic dysfunction: drug accumulation may occur; consider lower doses and/or extended intervals and closer monitoring
• Risk of C. difficile infection with any broad-spectrum antibiotic; limit duration and de-escalate based on cultures
• May cause biliary sludging/pseudolithiasis, particularly at high doses or in pediatric patients; consider alternatives in patients with significant biliary disease or unexplained RUQ pain on therapy
• Use caution in patients with a history of ceftriaxone-associated hemolytic anemia; recurrent exposure can be severe or fatal

Common:

• Injection-site pain (IM) or phlebitis (IV)
• Mild GI upset: diarrhea, nausea, abdominal discomfort
• Mild transient elevations in liver enzymes
• Headache, rash, pruritus

Serious:

• Severe hypersensitivity reactions (anaphylaxis, angioedema, Stevens–Johnson syndrome, toxic epidermal necrolysis)
• Immune-mediated hemolytic anemia, sometimes severe or fatal (rare)
• Clostridioides difficile–associated colitis
• Biliary sludge/pseudolithiasis and cholecystitis-like symptoms, particularly with high doses or prolonged use
• Precipitation with calcium-containing solutions in neonates leading to fatal embolic events

Hepatic Impairment:

• Combined severe renal and hepatic dysfunction may require dose reduction
• Monitor closely for drug accumulation
• Consider alternative antibiotics in severe hepatic disease

Renal Impairment:

• No routine dose adjustment for isolated renal impairment
• Dual renal + biliary elimination provides safety margin
• Consider dose reduction only in severe renal impairment with concurrent hepatic dysfunction

Neonatal & Pediatric Considerations:

• Avoid in neonates with hyperbilirubinemia (kernicterus risk)
• Do NOT use in neonates receiving IV calcium-containing solutions
• Many institutions avoid ceftriaxone entirely in infants <28 days
• Higher risk of biliary sludging in pediatric patients

Pregnancy & Lactation:

• Generally considered safe in pregnancy when clinically indicated
• Category B: no evidence of risk in humans
• Benefits usually outweigh risks for serious bacterial infections

Clinical Monitoring:

• Clinical response: fever curve, WBC trend, hemodynamics, radiographic changes and overall sepsis parameters
• Signs and symptoms of hypersensitivity: rash, wheezing, angioedema, hypotension
• GI symptoms and stool pattern; evaluate for C. difficile in the setting of new/worsening diarrhea
• In pediatric or high-dose adult use, monitor for RUQ pain or biliary abnormalities if symptoms develop

Laboratory Monitoring:

• Renal function (SCr, BUN) and liver enzymes with prolonged therapy or in patients with existing organ dysfunction
• Consider monitoring CBC for signs of hemolytic anemia with prolonged use

• 1. Lexicomp. (2024). Ceftriaxone: Drug information. Wolters Kluwer.
• 2. Sanford Guide to Antimicrobial Therapy. (2023). Ceftriaxone. Antimicrobial Therapy, Inc.
• 3. Tamma, P. D., Holmes, A., & Ashley, E. D. (2014). Antimicrobial stewardship: Another focus for patient safety? Current Opinion in Infectious Diseases, 27(4), 348–355.
• 4. Workowski, K. A., & Bachmann, L. H. (2021). Sexually transmitted infections treatment guidelines, 2021. MMWR Recommendations and Reports, 70(4), 1–187.
• 5. Martin, E., Fanconi, S., Kälin, P., & Zwingelstein, C. (1984). Ceftriaxone-bilirubin-albumin interactions and the role of acidosis. The Pediatric Infectious Disease Journal, 3(4), 304–307.