ceftriaxone
Brand: Rocephin
Prototype Drug
Drug Class: antibiotic
Drug Family: antibiotic
Subclass: third-generation cephalosporin / beta-lactam
Organ Systems: infectious-disease
Mechanism of Action
Third-generation cephalosporin with expanded gram-negative coverage including Neisseria meningitidis, N. gonorrhoeae, Haemophilus influenzae, and most Enterobacteriaceae; poor anti-MRSA and anti-enterococcal activity; penetrates CSF well.
penicillin-binding proteins (PBPs)
Indications
- community-acquired pneumonia (hospitalized patients)
- bacterial meningitis
- gonorrhea (drug of choice — IM)
- Lyme disease (disseminated/severe)
- typhoid fever
- pelvic inflammatory disease
- spontaneous bacterial peritonitis prophylaxis/treatment
- sepsis (empiric)
Contraindications
- neonates with hyperbilirubinemia (displaces bilirubin from albumin)
- concurrent IV calcium in neonates (precipitation in lungs/kidneys)
Adverse Effects
Common
- diarrhea
- rash
- elevated LFTs
- biliary sludge (pseudolithiasis — especially with high doses/prolonged use)
Serious
- anaphylaxis
- C. difficile colitis
- hemolytic anemia (Coombs-positive)
- biliary sludge/cholelithiasis
- calcium-ceftriaxone precipitates in neonates
Pharmacokinetics (ADME)
| Absorption | IV or IM only |
| Distribution | Highly protein-bound (~93–96%); Vd ~0.12 L/kg; excellent CSF penetration in meningitis |
| Metabolism | Not significantly metabolized |
| Excretion | Dual — renal (~33–65%) and biliary (~35–45%); dose adjustment NOT typically required in renal failure (unlike most cephalosporins) |
| Half-life | 5–9 hours — allows once-daily dosing |
| Onset | End of infusion |
| Peak | End of infusion |
| Duration | 24 hours |
| Protein Binding | 93–96% |
| Vd | ~0.12 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| calcium-containing IV fluids (neonates) | calcium-ceftriaxone precipitation in lungs and kidneys — potentially fatal in neonates | major |
| warfarin | may prolong prothrombin time; monitor INR | moderate |
Nursing Considerations
- Reconstitute with appropriate diluent — do NOT use calcium-containing solutions (including Ringer's lactate) in neonates; may use in adults if infused at separate times
- Once-daily dosing (1–2 g q24h) is appropriate for most indications; bacterial meningitis requires 2 g q12h for adequate CSF concentrations
- Monitor for biliary sludge with prolonged use (>7–14 days) — present as RUQ pain; usually resolves after discontinuation
- For gonorrhea: current CDC guidelines recommend ceftriaxone 500 mg IM single dose (1 g if weight >150 kg) — azithromycin is no longer routinely added due to GC resistance
Clinical Pearls
- Ceftriaxone's unique dual hepatic-renal elimination means it does NOT require dose adjustment in renal failure alone — a key prescribing advantage over most beta-lactams
- Ceftriaxone remains first-line for bacterial meningitis (with dexamethasone) because of its excellent CSF penetration, once-daily dosing, and broad gram-negative coverage including N. meningitidis and H. influenzae
Safety Profile
Pregnancy generally-safe
Lactation safe
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.