Ceftriaxone

Ceftriaxone (INN) is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, it has broad spectrum activity against Gram-positive and Gram-negative bacteria. In most cases, it is considered to be equivalent to cefotaxime in terms of safety and efficacy. Ceftriaxone sodium is marketed by Hoffman-La Roche under the trade name Rocephin.

Clinical use
Ceftriaxone is often used (in combination, but not direct, with macrolide and/or aminoglycoside antibiotics) for the treatment of community-acquired or mild to moderate health care-associated pneumonia. It is also a choice drug for treatment of bacterial meningitis. In pediatrics, it is commonly used in febrile infants between 4 and 8 weeks of age who are admitted to the hospital to exclude sepsis. The dosage for acute ear infection in the very young is 50 mg/kg IM, one dose only. It has also been used in the treatment of Lyme disease, typhoid fever and gonorrhea.

Intravenous dosages may be adjusted for body mass in younger patients and is administered every 12–24 hours, at a dose that depends on the type and severity of the infection.

For the treatment of gonorrhea, a single intramuscular injection is usually given. Treatment for chlamydia infection is also recommended (usually with azithromycin) unless it is specifically ruled out.

It must not be mixed or administered simultaneously (within 48 hours) with calcium-containing solutions or products for patients younger than 28 days old, even via different infusion lines (rare fatal cases of calcium-ceftriaxone precipitates in lung and kidneys in neonates have been described).

To reduce the pain of intramuscular injection, ceftriaxone may be reconstituted with 1% lidocaine.

Ceftriaxone has also been investigated for efficacy in preventing relapse to cocaine addiction.

Ceftriaxone seems to increase EAAT2 pump expression in central nervous system and has therefore a potential to reduce glutamatergic toxicity. Despite earlier negative results in 1990s, new, large clinical trials are underway to test its effacy in Amyotrophic lateral sclerosis (ALS) patients.

Chemistry
Ceftriaxone is a white crystalline powder which is readily soluble in water, sparingly soluble in methanol and very slightly soluble in ethanol. The pH of a 1% aqueous solution is approximately 6.7.

The syn-configuration of the methoxyimino moiety confers stability to β-lactamase enzymes produced by many Gram-negative bacteria. Such stability to β-lactamases increases the activity of ceftriaxone against otherwise resistant Gram-negative bacteria. In place of the easily hydrolysed acetyl group of cefotaxime, ceftriaxone has a metabolically stable thiotriazinedione moiety.

Adverse Effect
Hypoprothombinaemia and bleeding are specific side effects. Haemolysis is reported. Biliary sludging is another known though rare adverse effect which occurs primarily in neonates.