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Ceftriaxone, sold under the brand name Rocephin, is a third-generation cephalosporin antibiotic used for the treatment of a number of bacterial infections.
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Common side effects include pain at the site of injection and allergic reactions. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. Due to emergent resistance, ceftriaxone should not be used for the treatment of Enterobacter infections. If sepsis is being considered, empiric therapy may be initiated prior to susceptibility testing.
In combination with doxycycline or azithromycin, ceftriaxone used to be recommended by the United States Centers for Disease Control and Prevention (CDC) for the treatment of uncomplicated gonorrhea. Due to increased risk of developing azithromycin resistant strains and the high efficacy of higher doses of ceftriaxone the guidance has been updated to mono-antibiotic therapy with a higher dose of ceftriaxone.
Spectrum of activity
Like other third-generation cephalosporins, ceftriaxone is active against Citrobacter spp., Serratia marcescens, and beta-lactamase-producing strains of Haemophilus and Neisseria.
Available forms
Ceftriaxone is available for administration via the intramuscular or the intravenous routes. The solutions are pale yellowish in color, Diluents containing calcium are not used to reconstitute ceftriaxone, and it must not be administered in intravenous lines containing other calcium-containing solutions, as a ceftriaxone-calcium precipitate could form. This precipitation risk is particularly high in newborns (up to age 28 days), especially if they are premature or have impaired bilirubin binding.
Beyond the approved intramuscular and intravenous routes, ceftriaxone has also been administered off-label via the subcutaneous route. This practice has been reported in multiple clinical series, particularly in elderly, frail, or palliative-care patients and in those with difficult venous access. Pharmacokinetic data and clinical observations suggest that subcutaneous ceftriaxone provides adequate systemic exposure and is generally well tolerated, with reported clinical effectiveness comparable to intravenous administration in selected, non–critically ill patients.
Specific populations
Pregnancy
Ceftriaxone is pregnancy category B . The manufacturer recommends that caution be exercised when administering ceftriaxone to women who breastfeed. It has also been reported to cause post kidney failure in children. Like other antibiotics, ceftriaxone use can result in Clostridioides difficile-associated diarrhea ranging from mild diarrhea to fatal colitis. while ceftriaxone has a 45% biliary excretion
Contraindications
Ceftriaxone should not be used in those with an allergy to ceftriaxone or any component of the formulation. Although there is negligible cross-reactivity between penicillins and third-generation cephalosporins, caution should still be used when using ceftriaxone in penicillin-sensitive patients. Caution should be used in people who have had previous severe penicillin allergies. even if administered through different infusion lines due to rare fatal cases of calcium-ceftriaxone precipitations in neonatal lungs and kidneys.
Mechanism of action
Ceftriaxone is a third-generation antibiotic from the cephalosporin family of antibiotics. The peptidoglycan cell wall is made up of pentapeptide units attached to a polysaccharide backbone with alternating units of N-acetylglucosamine and N-acetylmuramic acid. PBPs act on a terminal D-alanyl-D-alanine moiety on a pentapeptide unit and catalyze the formation of a peptide bond between the penultimate D-alanine and a glycine unit on an adjacent peptidoglycan strand, releasing the terminal D-alanine unit in the process. It is not available orally.
Distribution
Ceftriaxone penetrates tissues and body fluids well, including cerebrospinal fluid to treat central nervous system infections. Ceftriaxone is reversibly bound to human plasma proteins and the binding of ceftriaxone decreases with increasing concentration from a value of 95% at plasma concentrations less than 25 mcg/mL to 85% at plasma concentration of 300 mcg/mL. Over a 0.15 to 3 g dose range in healthy adult subjects, the apparent volume of distribution ranged from 5.8 to 13.5 L. is excreted in the bile as unchanged drug which is ultimately excreted in feces as inactive compounds from hepatic and gut flora metabolism.
Elimination
The average elimination half-life in healthy adults is 5.8–8.7 (mean 6.5) hours, In people with renal impairment, the average elimination half-life increases to 11.4–15.7 hours.
The syn-configuration of the methoxy oxime moiety confers resistance to beta-lactamase enzymes produced by many Gram-negative bacteria.
Ceftriaxone seems to increase excitatory amino acid transporter-2 pump expression and activity in the central nervous system, so has a potential to reduce glutamatergic toxicity.
Ceftriaxone has been shown to have neuroprotective properties in a number of neurological disorders, including spinal muscular atrophy and amyotrophic lateral sclerosis (ALS). Despite earlier negative results in the 1990s, a large clinical trial was undertaken in 2006 to test ceftriaxone in ALS patients, but was stopped early after it became clear that the results would not meet the predetermined criteria for efficacy.