Ceftriaxone !

A third-generation cephalosporin given by injection that reaches the brain and lasts all day; a mainstay for gonorrhoea, meningitis and pyelonephritis.

Updated 2026-11-01

Class: Beta-lactams
Enzyme: Penicillin-binding protein 2 (PBP2) and other PBPs
ATC code: J01DD04
WHO Model List of Essential Medicines

Penicillin-binding protein 2 (PBP2) and other PBPsCeftriaxone

The figure shows the transpeptidase domain of PBP2 from Neisseria gonorrhoeae acylated by ceftriaxone: the opened drug is bonded to the active-site serine.

Target in 3D: Penicillin-binding protein 2 (PBP2) and other PBPs. PDB structure 6P54 (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Ceftriaxone acylates the PBPs and blocks peptidoglycan cross-linking, like the other β-lactams. It keeps activity in the presence of some β-lactamases (penicillinases and cephalosporinases), which gives it strong activity against gram-negatives such as gonococcus, meningococcus, H. influenzae and E. coli, and against pneumococcus and other streptococci.

Resists many β-lactamases and reaches the PBPs intact
Acylates PBP2 and other PBPs
Cell-wall cross-linking stops
The bacterium lyses; one daily dose keeps working

Pharmacokinetics

Absorption: Not absorbed by mouth; given IV or IM.
Distribution: Wide; penetrates inflamed meninges; largely and reversibly bound to plasma proteins.
Elimination: Two routes: a third to two-thirds unchanged in the urine, the rest in bile; for this reason kidney impairment alone usually needs no change, except when severe.
Half-life: About 6 to 9 hours in healthy adults, long for a β-lactam, which allows once-daily use.

Indications

Uncomplicated gonorrhoea: the recommended treatment, with surveillance for resistance. Gonorrhoea →
Bacterial meningitis caused by H. influenzae, meningococcus or pneumococcus. Bacterial meningitis →
Lower respiratory tract infections, including community-acquired pneumonia in hospital. Community-acquired pneumonia →
Complicated urinary tract infections such as acute pyelonephritis. Acute pyelonephritis →
Prevention in close contacts of meningococcal disease and before some surgeries.

Adverse effects

Common

Pain at the injection site
Diarrhoea
Rash
Raised liver enzymes and eosinophilia

Contraindications

Anaphylaxis to ceftriaxone or other β-lactams
Premature newborns and newborns with hyperbilirubinaemia
Newborns (28 days or younger) who need IV calcium-containing solutions

Key interactions

IV calcium-containing solutions: Ceftriaxone–calcium precipitates; never given at the same time, and avoided altogether in newborns who need calcium.
Vitamin K antagonists (warfarin): Higher bleeding risk; prothrombin time can change.

What is monitored

Right-upper-quadrant pain on long courses (biliary sludge)
Blood count and liver tests on long courses
Bilirubin in newborns

Test yourself

Think of the answer, then tap the question to see it.

A child on a long course of ceftriaxone develops right-upper-quadrant pain and ultrasound shows gallbladder sludge. What is the mechanism?

Ceftriaxone is partly excreted in bile, where it forms a calcium salt that precipitates (pseudolithiasis). It is transient and reverses after the drug is stopped.

Why is ceftriaxone avoided in jaundiced newborns?

It displaces bilirubin from albumin, raising free bilirubin and the risk of kernicterus.

Why can ceftriaxone usually be used without adjustment when only the kidneys are impaired?

It is cleared by two routes, urine and bile, so biliary excretion compensates; only severe kidney impairment calls for caution.

Why must ceftriaxone not be given at the same time as IV calcium-containing solutions?

The two form ceftriaxone–calcium precipitates; in newborns these have lodged in the lungs and kidneys, so the combination is contraindicated.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Ceftriaxone Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); DailyMed - CEFTRIAXONE injection, powder, for solution (DailyMed (U.S. National Library of Medicine), 2026); DailyMed - CEFTRIAXONE- ceftriaxone sodium injection, powder, for solution (DailyMed (U.S. National Library of Medicine), 2026); Gonococcal Infections Among Adolescents and Adults - STI Treatment Guidelines (Centers for Disease Control and Prevention (CDC), 2021).

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Representative model, for educational purposes only.