ceftriaxone

Third-generation cephalosporin· Brands: Rocephin, CefaxoneIMIV

Mechanism of action

Ceftriaxone is a third-generation cephalosporin antibiotic that exerts a bactericidal effect by inhibiting bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs), particularly those involved in the transpeptidation step of peptidoglycan cross-linking. This inhibition disrupts the integrity of the cell wall, leading to osmotic lysis of the dividing bacterium. Its broad spectrum of activity results from differential affinity for various PBPs across gram-positive and gram-negative organisms. Like all beta-lactams, its action is most pronounced during active bacterial growth.

Pharmacokinetics

Ceftriaxone is administered parenterally, either intravenously or intramuscularly, as it is poorly absorbed from the gastrointestinal tract. It exhibits dose-dependent pharmacokinetics and has a long elimination half-life of approximately 6 to 9 hours, permitting once-daily dosing for many infections. The drug binds extensively to plasma albumin (85-95%), but this does not impair its distribution. It penetrates well into body fluids and tissues, including cerebrospinal fluid, particularly when the meninges are inflamed. Ceftriaxone is eliminated primarily by the kidneys (about 60%) and the remainder is excreted unchanged in the bile. Dosage adjustment is generally not required in renal impairment unless hepatic impairment coexists.

Indications & dosing

Community-acquired pneumonia

Consider local guidelines for choice based on severity.

adult · IV: 1–2 g once daily · Consider local guidelines for choice based on severity.

Bacterial meningitis

Give immediately if suspected; seek expert advice.

adult · IV: 2 g every 12 hours · Give immediately if suspected; seek expert advice.

Uncomplicated gonorrhoea

Also treat for Chlamydia co-infection if not excluded.

adult · IM: 1 g single dose · Also treat for Chlamydia co-infection if not excluded.

Intra-abdominal infection (peritonitis)

Use with metronidazole for anaerobic cover.

adult · IV: 2 g once daily · Use with metronidazole for anaerobic cover.

Complicated urinary tract infection

Once daily dosing may be used.

adult · IV: 1–2 g once daily · Once daily dosing may be used.

Typhoid fever (enteric fever)

Check local resistance patterns.

adult · IV: 1–2 g once daily · Check local resistance patterns.

Contraindications & precautions

Hypersensitivity to ceftriaxone or other cephalosporins · Cross-hypersensitivity with penicillins may occur.
Neonates with hyperbilirubinaemia · Ceftriaxone displaces bilirubin from albumin, risking bilirubin encephalopathy.
Concomitant intravenous calcium-containing solutions, particularly in neonates · Risk of fatal ceftriaxone-calcium precipitation.
History of severe penicillin hypersensitivity · Cross-allergy possible; use with caution.
Use with caution in patients with a history of penicillin allergy, as cross-hypersensitivity may occur.
Monitor for signs of Clostridioides difficile infection; discontinue if severe diarrhoea develops.
Use with caution in patients with severe renal and hepatic impairment, as dose adjustment may be required.
Caution in patients with gallbladder disease or impaired biliary flow, as biliary sludge may develop.
Monitor blood counts during prolonged therapy.

Adverse effects

Diarrhoea
Injection site reactions (pain, inflammation)
Rash
Anaphylaxisserious
Clostridioides difficile-associated colitisserious
Biliary pseudolithiasis (gallbladder sludge)
Blood dyscrasias (neutropenia, thrombocytopenia)serious

Renal & hepatic adjustment

eGFR 10–300: No dose adjustment required.
eGFR 0–9: Maximum dose 2 g daily. Use with caution and monitor closely.
Hepatic impairment (mild): No dose adjustment required.
Hepatic impairment (moderate): No dose adjustment required.
Hepatic impairment (severe): Use with caution. Monitor hepatic function and signs of adverse effects.

Monitoring, pregnancy & toxicity

Renal function (serum creatinine, eGFR) · Baseline and periodic
Hepatic function (liver function tests) · Baseline and periodic
Full blood count · Periodic
Prothrombin time · In patients at risk of vitamin K deficiency
Signs of hypersensitivity or superinfection · During therapy
Pregnancy: Ceftriaxone is generally considered safe in pregnancy; use when clearly indicated.
Toxicity: Hypersensitivity reactions (rash, fever, anaphylaxis) · Discontinue immediately and treat anaphylaxis with epinephrine, antihistamines, and corticosteroids as required.
Toxicity: Gastrointestinal effects (diarrhoea, nausea, Clostridium difficile-associated colitis) · Supportive care. Discontinue if severe; treat C. difficile infection with oral vancomycin or fidaxomicin.
Toxicity: Haematological effects (leukopenia, neutropenia, thrombocytopenia, haemolytic anaemia) · Monitor blood counts. Discontinue if severe or if haemolysis occurs.
Toxicity: Neurotoxicity in overdose (seizures, encephalopathy) · Symptomatic and supportive treatment. Ceftriaxone is not effectively removed by dialysis.

Clinical notes

Ceftriaxone is indicated for a broad range of infections, including community-acquired pneumonia, septicaemia, meningitis, and gonorrhoea, and is used for surgical prophylaxis. Its long half-life allows once-daily administration. It is contraindicated in neonates with hyperbilirubinaemia and in patients requiring intravenous calcium due to the risk of precipitation. Caution is warranted in patients with biliary obstruction, as bile sludging may occur. Resistance is a growing concern, and local susceptibility data and antimicrobial stewardship guidelines should inform prescribing. In severe hepatic and renal impairment, plasma levels should be monitored.

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BNF; local formulary