Ceftriaxone

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Ceftriaxone
Ceftriaxone-skeletal.svg
Ceftriaxone ball-and-stick.png
Systematic (IUPAC) name
(6R,7R)-7-{[(2Z)-2-(2-amino-1,3-thiazol-4-yl)->2-(methoxyimino)acetyl]amino}-3-{[(2-methyl-5,6-dioxo-1,2,5,6-tetrahydro-1,2,4-triazin-3-yl)thio]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
Clinical data
Trade names Rocephin or Epicephin, Arixon, Elcefrin(LGls)
AHFS/Drugs.com monograph
Pregnancy cat. B1 (AU) B (US)
Legal status Prescription Only (S4) (AU)
Routes Intravenous, intramuscular
Pharmacokinetic data
Bioavailability n/a
Metabolism Negligible
Half-life 5.8–8.7 hours
Excretion 33–67% renal, 35–45% biliary
Identifiers
CAS number 73384-59-5 YesY
ATC code J01DD04
PubChem CID 5479530
DrugBank DB01212
ChemSpider 4586394 YesY
UNII 75J73V1629 YesY
KEGG D07659 YesY
ChEBI CHEBI:29007 YesY
ChEMBL CHEMBL161 YesY
Chemical data
Formula C18H18N8O7S3 
Mol. mass 554.58 g/mol
 YesY (what is this?)  (verify)

Ceftriaxone (INN) /ˌsɛftrˈæksn/ 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 Hoffmann-La Roche under the trade name Rocephin. Ceftriaxone is administered parenterally (via needle or cannula).

Clinical use[edit]

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 daily up to three days. It has also been used in the treatment of Lyme disease, typhoid fever, and gonorrhea.[1]

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. According to the Journal of Family Practice, Volume 60, NO 12, December 2011, the intramuscular dose of ceftriaxone (Rocephin) has been increased from 125 mg IM to 250 mg IM due to increasing resistance of the gonococcal bacteria. It is also recommended that 100 mg of doxycycline be given orally at the same time for dual treatment. This takes care of treatment of underlying chlamydia, since treatment for chlamydia infection is also recommended. It must not be mixed or administered simultaneously (within 48 hours) with calcium-containing solutions or products for patients younger than 28 days old,[2] even via different infusion lines (rare fatal cases of calcium-ceftriaxone precipitates in lung and kidneys in neonates have been described).[3]

To reduce the pain of intramuscular injection, ceftriaxone may be reconstituted with 1% lidocaine.[4]

Ceftriaxone has also been investigated for efficacy in preventing relapse to cocaine addiction.[5]

Ceftriaxone seems to increase EAAT2 pump expression and activity[6] in the central nervous system and has therefore a potential to reduce glutamatergic toxicity.[7]

Ceftriaxone has been shown to have neuroprotective properties in a number of neurological disorders, including spinal muscular atrophy[8] and amyotrophic lateral sclerosis.[9] 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 pre-determined criteria for efficacy. [10]

Mechanism of Action[edit]

Ceftriaxone inhibits bacterial cell wall synthesis by means of binding to the penicillin-binding proteins (PBPs). Inhibition of PBPs would in turn inhibit the transpeptidation step in peptidoglycan synthesis which is required for bacterial cell walls.[11]

Chemistry[edit]

Ceftriaxone is a white crystalline powder 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 resistance to β-lactamase enzymes produced by many Gram-negative bacteria. The stability of this configuration results in increased 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 effects[edit]

Hypoprothrombinaemia and bleeding are specific side-effects. Haemolysis is reported. Biliary sludging is another known though rare adverse effect that occurs primarily in neonates.[12]

References[edit]

  1. ^ Gladwin, Mark (2007). Clinical Microbiology Made Ridiculously Simple 4th ed. Miami, FL: MedMaster, Inc. p. 67. ISBN 0-940780-81-X. 
  2. ^ "FDA Updates warning on Ceftriaxone-Calcium injection". 
  3. ^ Bradley JS, Wassel RT, Lee L, Nambiar S (April 2009). "Intravenous ceftriaxone and calcium in the neonate: assessing the risk for cardiopulmonary adverse events". Pediatrics 123 (4): e609–13. doi:10.1542/peds.2008-3080. PMID 19289450. 
  4. ^ Schichor A, Bernstein B, Weinerman H, Fitzgerald J, Yordan E, Schechter N (January 1994). "Lidocaine as a diluent for ceftriaxone in the treatment of gonorrhea. Does it reduce the pain of the injection?". Arch Pediatr Adolesc Med 148 (1): 72–5. PMID 8143016. 
  5. ^ Knackstedt LA, Melendez RI, Kalivas PW (August 2009). "Ceftriaxone restores glutamate homeostasis and prevents relapse to cocaine-seeking". Biol Psychiatry 67 (1): 81–4. doi:10.1016/j.biopsych.2009.07.018. PMC 2795043. PMID 19717140. 
  6. ^ Pharmacological evaluation of glutamate transporter 1 (GLT-1)-mediated neuroprotection following cerebral ischemia/reperfusion injury. Eur J Pharmacol. 2010 Jul 25;638(1-3):65-71. Epub 2010 Apr 24.
  7. ^ Lee SG, Su ZZ, Emdad L, Gupta P, Sarkar D, Borjabad A, Volsky DJ, Fisher PB (2008). "Mechanism of Ceftriaxone Induction of Excitatory Amino Acid Transporter-2 Expression and Glutamate Uptake in Primary Human Astrocytes". The Journal of Biological Chemistry 283 (19): 13116–13123. doi:10.1074/jbc.M707697200. PMC 2442320. PMID 18326497. 
  8. ^ Hedlund, E. (2011). "The protective effects of beta-lactam antibiotics in motor neuron disorders". Experimental Neurology 231 (1): 14–18. doi:10.1016/j.expneurol.2011.06.002. PMID 21693120.  edit
  9. ^ Rothstein, J. D.; Patel, S.; Regan, M. R.; Haenggeli, C.; Huang, Y. H.; Bergles, D. E.; Jin, L.; Dykes Hoberg, M.; Vidensky, S.; Chung, D. S.; Toan, S. V.; Bruijn, L. I.; Su, Z. Z.; Gupta, P.; Fisher, P. B. (2005). "β-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression". Nature 433 (7021): 73–77. doi:10.1038/nature03180. PMID 15635412.  edit
  10. ^ "Statement on the Clinical Trial of Ceftriaxone". The Northeast ALS Consortium (NEALS). 8 August 2012. Retrieved 10 May 2013. 
  11. ^ Ceftriaxone: Drug information. Uptodate.com. Retrieved Oct 2013.
  12. ^ Shiffman ML, Keith FB, Moore EW (December 1990). "Pathogenesis of ceftriaxone-associated biliary sludge. In vitro studies of calcium-ceftriaxone binding and solubility". Gastroenterology 99 (6): 1772–8. PMID 2227290. 

External links[edit]