ceftriaxone

Image:Цефтриаксон.JPG

Ceftriaxone and other third-generation cephalosporin antibiotics are used to treat organisms that tend to be resistant to many other antibiotics.{{Cite book | vauthors = Katzung B, Masters S, Trevor A |title = Basic and Clinical Pharmacology |publisher = McGraw-Hill|year = 2012|isbn = 978-0-07-176402-5|pages = 797–801 }} Due to emergent resistance, ceftriaxone should not be used for the treatment of Enterobacter infections. Before using ceftriaxone, it is important to determine the susceptibility of the bacteria.{{cite web | title=Ceftriaxone- ceftriaxone sodium injection, powder, for solution | website=DailyMed | date=31 December 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5cd2d96f-83e5-4326-ae87-d0ede4ba493a | access-date=1 February 2020|url-status = live|archive-url = https://web.archive.org/web/20151117032102/http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=61c6334c-d6fe-4663-ad29-eaee8dc169a6 |archive-date = 17 November 2015}} If sepsis is being considered, empiric therapy may be initiated prior to susceptibility testing.

Medical uses include:

• lower respiratory tract infections
• acute bacterial otitis media
• skin and skin structure infections
• urinary tract infections
• uncomplicated gonorrhea
• pelvic inflammatory disease
• bacterial sepsis
• intra-abdominal infections
• meningitis
• surgical prophylaxis
• Lyme disease

Ceftriaxone is also a choice drug for treatment of bacterial meningitis caused by pneumococci, meningococci, Haemophilus influenzae, and "susceptible enteric Gram-negative rods, but not Listeria monocytogenes."{{cite book| vauthors = Katzung B |title = Basic and Clinical Pharmacology, Eleventh Edition|date = 2009|publisher = McGraw-Hill|location = New York|isbn = 978-0-07-160405-5|pages = 783–784}}

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.{{cite journal | vauthors = St Cyr S, Barbee L, Workowski KA, Bachmann LH, Pham C, Schlanger K, Torrone E, Weinstock H, Kersh EN, Thorpe P | title = Update to CDC's Treatment Guidelines for Gonococcal Infection, 2020 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 69 | issue = 50 | pages = 1911–1916 | date = December 2020 | pmid = 33332296 | pmc = 7745960 | doi = 10.15585/mmwr.mm6950a6 }}

Like other third-generation cephalosporins, ceftriaxone is active against Citrobacter spp., Serratia marcescens, and beta-lactamase-producing strains of Haemophilus and Neisseria. However, unlike ceftazidime and cefoperazone, ceftriaxone does not have useful activity against Pseudomonas aeruginosa. It is generally not active against Enterobacter species, and its use should be avoided in the treatment of Enterobacter infections, even if the isolate appears susceptible, because of the emergence of resistance. Some organisms, such as Citrobacter, Providencia, and Serratia, have the ability to become resistant through the development of cephalosporinases (enzymes that hydrolyze cephalosporins and render them inactive).

Although not being used as first line therapy against Staphylococcus aureus, ceftriaxone retains activity against isolates of methicillin-susceptible S. aureus and is used in clinic for infections sustained by this bacterium. In this case the dose should be doubled (e.g. 2 g intravenously every 12 hours).{{Cite journal | vauthors = Di Bella S, Gatti M, Principe L |date=29 April 2023 |title=Ceftriaxone for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia: a matter of dosages? |journal=European Journal of Clinical Microbiology & Infectious Diseases |volume=42 |issue=7 |pages=917–918 |language=en |doi=10.1007/s10096-023-04612-x |pmid=37119346 |s2cid=258423746 |issn=1435-4373}}

Ceftriaxone is available for administration via the intramuscular or the intravenous routes. Ceftriaxone is stored as a dry powder in a vial, and is reconstituted (dissolved) immediately before use. The solution is used promptly after preparation, still, reconstituted solutions retain their physical and chemical stability for 24 hours at 25°C (or for 3 days when stored between 2 and 8°C).{{cite web |archive-url=https://web.archive.org/web/20231206072711/https://www.medsafe.govt.nz/profs/datasheet/c/ceftriaxoneinjDEVA.pdf |url=https://www.medsafe.govt.nz/profs/datasheet/c/ceftriaxoneinjDEVA.pdf |archive-date=6 December 2023 |title=Ceftriaxone New Zealand Data Sheet |publisher=Devatis Limited |date=October 2023}} The solutions are pale yellowish in color, but the change of color to amber or reddish suggests hydrolysis of the amide bond of the β-lactam ring, thereby affecting the antimicrobial activity of the antibiotic.{{cite journal |vauthors=Palzkill T |title=Metallo-β-lactamase structure and function |journal=Ann N Y Acad Sci |volume=1277 |issue= 1|pages=91–104 |date=January 2013 |pmid=23163348 |pmc=3970115 |doi=10.1111/j.1749-6632.2012.06796.x|bibcode=2013NYASA1277...91P }} 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.{{cite web |archive-url=https://web.archive.org/web/20230813180009/https://www.pbm.va.gov/PBM/vacenterformedicationsafety/nationalpbmbulletin/CeftriaxoneNationalPBMBulletin.pdf |archive-date=13 August 2023 |url=https://www.pbm.va.gov/PBM/vacenterformedicationsafety/nationalpbmbulletin/CeftriaxoneNationalPBMBulletin.pdf |title=National PBM Bulletin - Ceftriaxone (Rocephin) and Calcium Interaction |date=28 September 2007}} This precipitation risk is particularly high in newborns (up to age 28 days), especially if they are premature or have impaired bilirubin binding.{{cite web | url=https://www.gov.uk/drug-safety-update/ceftriaxone-rocephin-incompatible-with-solutions-containing-calcium | archive-url=https://web.archive.org/web/20231208090719/https://www.gov.uk/drug-safety-update/ceftriaxone-rocephin-incompatible-with-solutions-containing-calcium | archive-date=8 December 2023 | title=Ceftriaxone (Rocephin): Incompatible with solutions containing calcium }}{{cite web |archive-url=https://web.archive.org/web/20240222194630/https://www.hpra.ie/docs/default-source/Safety-Notices/ceftriaxone---march-2010---final.pdf |url=https://www.hpra.ie/docs/default-source/Safety-Notices/ceftriaxone---march-2010---final.pdf |archive-date=22 February 2024 |title=Ceftriaxone - Contraindication in newborns and risk of calcium-ceftriaxone precipitation when administered/mixed with solutions containing calcium |publisher=Irish Medicines Board |date=March 2010}}

Ceftriaxone is pregnancy category B {{clarify|date=February 2024}}. It has not been observed to cause birth defects in animal studies, but a lack of well-controlled studies done in pregnant women exists.

Low concentrations of ceftriaxone are excreted in breast milk that are "not expected to cause adverse effects in breastfed infants."{{Cite web|title = TOXNET|url = http://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+lactmed:@term+@DOCNO+57|website = toxnet.nlm.nih.gov|access-date = 4 November 2015|url-status = dead|archive-url = https://web.archive.org/web/20170908213423/https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+lactmed%253A%2540term+%2540DOCNO+57|archive-date = 8 September 2017}}{{Failed verification|date=May 2020}} The manufacturer recommends that caution be exercised when administering ceftriaxone to women who breastfeed.

Hyperbilirubinemic neonates are contraindicated for the use of ceftriaxone. It can compete with bilirubin and displace it from binding to albumin, increasing the risk of bilirubin encephalopathy.

According to the package insert, clinical studies did not

show differences in efficacy and safety of ceftriaxone in geriatrics compared to younger patients but "greater sensitivity of some older individuals cannot be ruled out."

Although generally well tolerated, the most common adverse reactions associated with ceftriaxone are changes in white blood cell counts, local reactions at site of administration, rash, and diarrhea.

Incidence of adverse effects greater than 1%:

• Eosinophilia (6%)
• Thrombocytosis (5.1%)
• Elevations in liver enzymes (3.1–3.3%)
• Diarrhea (2.7%)
• Leukopenia (2.1%)
• Elevation in BUN (1.2%)
• Local reactions: pain, tenderness, irritation (1%)
• Rash (1.7%)

Some less frequently reported adverse events (incidence < 1%) include phlebitis, itchiness, fever, chills, nausea, vomiting, elevations of bilirubin, elevations in creatinine, headache and dizziness.

Ceftriaxone may precipitate in bile, causing biliary sludge, biliary pseudolithiasis, and gallstones, especially in children. Hypoprothrombinaemia and bleeding are specific side effects. Haemolysis is reported.{{cite journal | vauthors = Shiffman ML, Keith FB, Moore EW | title = Pathogenesis of ceftriaxone-associated biliary sludge. In vitro studies of calcium-ceftriaxone binding and solubility | journal = Gastroenterology | volume = 99 | issue = 6 | pages = 1772–1778 | date = December 1990 | pmid = 2227290 | doi = 10.1016/0016-5085(90)90486-K }}{{cite journal | vauthors = Shrimali JD, Patel HV, Gumber MR, Kute VB, Shah PR, Vanikar AV, Trivedi HL | title = Ceftriaxone induced immune hemolytic anemia with disseminated intravascular coagulation | journal = Indian Journal of Critical Care Medicine | volume = 17 | issue = 6 | pages = 394–395 | date = November 2013 | pmid = 24501497 | pmc = 3902580 | doi = 10.4103/0972-5229.123465 | doi-access = free }}{{cite journal | vauthors = Guleria VS, Sharma N, Amitabh S, Nair V | title = Ceftriaxone-induced hemolysis | journal = Indian Journal of Pharmacology | volume = 45 | issue = 5 | pages = 530–531 | date = Sep–Oct 2013 | pmid = 24130395 | pmc = 3793531 | doi = 10.4103/0253-7613.117758 | doi-access = free }} It has also been reported to cause post kidney failure in children.{{cite journal | vauthors = Li N, Zhou X, Yuan J, Chen G, Jiang H, Zhang W | title = Ceftriaxone and acute renal failure in children | journal = Pediatrics | volume = 133 | issue = 4 | pages = e917–e922 | date = April 2014 | pmid = 24664092 | doi = 10.1542/peds.2013-2103 | s2cid = 2854637 | url = https://publications.aap.org/pediatrics/article-pdf/133/4/e917/1099407/peds_2013-2103.pdf | access-date = 22 February 2024 | archive-date = 22 February 2024 | archive-url = https://web.archive.org/web/20240222203721/https://publications.aap.org/pediatrics/article-pdf/133/4/e917/1099407/peds_2013-2103.pdf | url-status = live }} Like other antibiotics, ceftriaxone use can result in Clostridioides difficile-associated diarrhea ranging from mild diarrhea to fatal colitis. In this regard it has been reported that shifting from ceftriaxone to cefotaxime would have a lower impact on C. difficile infection rates, since cefotaxime is almost entirely excreted by the kidneys {{cite journal | vauthors = Patel KB, Nicolau DP, Nightingale CH, Quintiliani R | title = Pharmacokinetics of cefotaxime in healthy volunteers and patients | journal = Diagnostic Microbiology and Infectious Disease | volume = 22 | issue = 1–2 | pages = 49–55 | date = May 1995 | pmid = 7587050 | doi = 10.1016/0732-8893(95)00072-I }} while ceftriaxone has a 45% biliary excretion {{cite journal | vauthors = Guggenbichler JP, Allerberger FJ, Dierich M | title = Influence of cephalosporines III generation with varying biliary excretion on fecal flora and emergence of resistant bacteria during and after cessation of therapy | journal = Padiatrie und Padologie | volume = 21 | issue = 4 | pages = 335–342 | date = 1986 | pmid = 3562044 | url = https://pubmed.ncbi.nlm.nih.gov/3562044/ | access-date = 29 April 2023 | archive-date = 29 April 2023 | archive-url = https://web.archive.org/web/20230429154021/https://pubmed.ncbi.nlm.nih.gov/3562044/ | url-status = live }}

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,{{Cite web|title = The Use of Cephalosporins in Penicillin-allergic Patients|url = http://www.medscape.com/viewarticle/764042|website = www.medscape.com|access-date = 10 November 2015|url-status = live|archive-url = https://web.archive.org/web/20151114135258/http://www.medscape.com/viewarticle/764042|archive-date = 14 November 2015}} caution should still be used when using ceftriaxone in penicillin-sensitive patients.{{Cite web|url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/050585s061lbl.pdf|title = Rocephin Prescribing Information|access-date = 1 November 2015|publisher = Roche|url-status = live|archive-url = https://web.archive.org/web/20160304055415/http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/050585s061lbl.pdf|archive-date = 4 March 2016}} Caution should be used in people who have had previous severe penicillin allergies. It should not be used in hyperbilirubinemic neonates, particularly those who are premature because ceftriaxone is reported to displace bilirubin from albumin binding sites, potentially causing bilirubin encephalopathy. Concomitant use with intravenous calcium-containing solutions/products in neonates (≤28 days) is contraindicated {{cite web|url = http://healthcare.utah.edu/pharmacy/alerts/243.htm|title = FDA Updates warning on Ceftriaxone-Calcium injection|url-status = live|archive-url = https://web.archive.org/web/20091128093447/http://healthcare.utah.edu/pharmacy/alerts/243.htm|archive-date = 28 November 2009}} even if administered through different infusion lines due to rare fatal cases of calcium-ceftriaxone precipitations in neonatal lungs and kidneys.{{cite journal | vauthors = Bradley JS, Wassel RT, Lee L, Nambiar S | title = Intravenous ceftriaxone and calcium in the neonate: assessing the risk for cardiopulmonary adverse events | journal = Pediatrics | volume = 123 | issue = 4 | pages = e609–e613 | date = April 2009 | pmid = 19289450 | doi = 10.1542/peds.2008-3080 | s2cid = 22718923 | url = https://publications.aap.org/pediatrics/article-pdf/123/4/e609/1022852/zpe0040900e609.pdf | access-date = 22 February 2024 | archive-date = 22 February 2024 | archive-url = https://web.archive.org/web/20240222203720/https://publications.aap.org/pediatrics/article-pdf/123/4/e609/1022852/zpe0040900e609.pdf | url-status = live }}

Ceftriaxone is a third-generation antibiotic from the cephalosporin family of antibiotics. It is within the β-lactam family of antibiotics. Ceftriaxone selectively and irreversibly inhibits bacterial cell wall synthesis by binding to transpeptidases, also called transamidases, which are penicillin-binding proteins (PBPs) that catalyze the cross-linking of the peptidoglycan polymers forming the bacterial cell wall.{{Cite book|title = Foye's Principles of Medicinal Chemistry|publisher = Lippincott Williams & Wilkins|year = 2013|isbn = 978-1-60913-345-0|location = Philadelphia, PA|pages = 1093–1094, 1099–1100| veditors = Lemke TL, Williams DA |edition = Seventh}} 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.{{cite journal | vauthors = van Heijenoort J | title = Formation of the glycan chains in the synthesis of bacterial peptidoglycan | journal = Glycobiology | volume = 11 | issue = 3 | pages = 25R–36R | date = March 2001 | pmid = 11320055 | doi = 10.1093/glycob/11.3.25r | s2cid = 46066256 | doi-access = free }}{{cite journal | vauthors = Scheffers DJ, Pinho MG | title = Bacterial cell wall synthesis: new insights from localization studies | journal = Microbiology and Molecular Biology Reviews | volume = 69 | issue = 4 | pages = 585–607 | date = December 2005 | pmid = 16339737 | pmc = 1306805 | doi = 10.1128/MMBR.69.4.585-607.2005 }} 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. The structure of ceftriaxone mimics the D-alanyl-D-alanine moiety, and the PBP attacks the beta-lactam ring in ceftriaxone as if it were its normal D-alanyl-D-alanine substrate. The peptidoglycan cross-linking activity of PBPs is a construction and repair mechanism that normally helps to maintain bacterial cell wall integrity, so the inhibition of PBPs leads to damage and destruction of the cell wall and eventually to cell lysis.

Absorption: Ceftriaxone can be administered intravenously and intramuscularly, and the drug is completely absorbed.{{cite journal | vauthors = Patel IH, Kaplan SA | title = Pharmacokinetic profile of ceftriaxone in man | journal = The American Journal of Medicine | volume = 77 | issue = 4C | pages = 17–25 | date = October 1984 | pmid = 6093513 }} It is not available orally.{{Cite book|title = Red Book: Pharmacy's Fundamental Reference|publisher = PDR Network, LLC.|year = 2010|isbn = 978-1-56363-751-3|edition = 114th}}{{Cite web|title = DailyMed – Search Results for ceftriaxone|url = http://dailymed.nlm.nih.gov/dailymed/search.cfm?query=ceftriaxone&searchdb=all&labeltype=all&sortby=rel&audience=professional&page=1&pagesize=100|website = dailymed.nlm.nih.gov|access-date = 4 November 2015|url-status = live|archive-url = https://web.archive.org/web/20160306075340/http://dailymed.nlm.nih.gov/dailymed/search.cfm?query=ceftriaxone&searchdb=all&labeltype=all&sortby=rel&audience=professional&page=1&pagesize=100|archive-date = 6 March 2016}}

Distribution: Ceftriaxone penetrates tissues and body fluids well, including cerebrospinal fluid to treat central nervous system infections.{{cite journal | vauthors = Nau R, Sörgel F, Eiffert H | title = Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nervous system infections | journal = Clinical Microbiology Reviews | volume = 23 | issue = 4 | pages = 858–883 | date = October 2010 | pmid = 20930076 | pmc = 2952976 | doi = 10.1128/CMR.00007-10 }} 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.

Metabolism: 33–67% of ceftriaxone is renally excreted as unchanged drug, but no dose adjustments are required in renal impairment with dosages up to 2 grams per day. The rest{{cite journal | vauthors = Arvidsson A, Alván G, Angelin B, Borgå O, Nord CE | title = Ceftriaxone: renal and biliary excretion and effect on the colon microflora | journal = The Journal of Antimicrobial Chemotherapy | volume = 10 | issue = 3 | pages = 207–215 | date = September 1982 | pmid = 6292158 | doi = 10.1093/jac/10.3.207 }} is excreted in the bile as unchanged drug{{cite journal | vauthors = Blumer J | title = Pharmacokinetics of ceftriaxone | journal = Hospital Practice | volume = 26 | issue = Suppl 5| pages = 7–13; discussion 52–4 | date = September 1991 | pmid = 1918224 | doi = 10.1080/21548331.1991.11707737 }} which is ultimately excreted in feces as inactive compounds from hepatic and gut flora metabolism.{{cite journal | vauthors = Balant L, Dayer P, Auckenthaler R | title = Clinical pharmacokinetics of the third generation cephalosporins | journal = Clinical Pharmacokinetics | volume = 10 | issue = 2 | pages = 101–143 | date = 1 April 1985 | pmid = 3888488 | doi = 10.2165/00003088-198510020-00001 | s2cid = 23478077 }}{{Cite book|title = Nursing Pharmacology Made Incredibly Easy!|url = https://books.google.com/books?id=NA41OnSGFWEC|publisher = Lippincott Williams & Wilkins|date = 7 March 2012|isbn = 978-1-4511-4624-0 |page = 496|url-status = live|archive-url = https://web.archive.org/web/20160603234922/https://books.google.com/books?id=NA41OnSGFWEC|archive-date = 3 June 2016}}

Elimination: The average elimination half-life in healthy adults is 5.8–8.7 (mean 6.5) hours, with some reviews estimated half-life is up to 10 hours.{{cite journal | vauthors = Klein NC, Cunha BA | title = Third-generation cephalosporins | journal = The Medical Clinics of North America | volume = 79 | issue = 4 | pages = 705–719 | date = July 1995 | pmid = 7791418 | doi = 10.1016/s0025-7125(16)30034-7 | doi-access = free }} In people with renal impairment, the average elimination half-life increases to 11.4–15.7 hours.

Ceftriaxone is commercially available as a white to yellowish-orange crystalline powder for reconstitution. Reconstituted ceftriaxone injection solutions are light yellow- to amber-colored depending on how long the solution had been reconstituted, the concentration of ceftriaxone in the solution, and the diluent used. To reduce pain with intramuscular injections, ceftriaxone may be reconstituted with lidocaine.{{cite journal | vauthors = Schichor A, Bernstein B, Weinerman H, Fitzgerald J, Yordan E, Schechter N | title = Lidocaine as a diluent for ceftriaxone in the treatment of gonorrhea. Does it reduce the pain of the injection? | journal = Archives of Pediatrics & Adolescent Medicine | volume = 148 | issue = 1 | pages = 72–75 | date = January 1994 | pmid = 8143016 | doi = 10.1001/archpedi.1994.02170010074017 }}

The syn-configuration of the methoxy oxime moiety confers resistance to beta-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 hydrolyzed acetyl group of cefotaxime, ceftriaxone has a metabolically stable {{chem name|thiotriazinedione}} moiety.

Ceftriaxone has also been investigated for efficacy in preventing relapse to cocaine addiction.{{cite journal | vauthors = Knackstedt LA, Melendez RI, Kalivas PW | title = Ceftriaxone restores glutamate homeostasis and prevents relapse to cocaine seeking | journal = Biological Psychiatry | volume = 67 | issue = 1 | pages = 81–84 | date = January 2010 | pmid = 19717140 | pmc = 2795043 | doi = 10.1016/j.biopsych.2009.07.018 }}

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.{{cite journal | vauthors = Verma R, Mishra V, Sasmal D, Raghubir R | title = Pharmacological evaluation of glutamate transporter 1 (GLT-1) mediated neuroprotection following cerebral ischemia/reperfusion injury | journal = European Journal of Pharmacology | volume = 638 | issue = 1–3 | pages = 65–71 | date = July 2010 | pmid = 20423712 | doi = 10.1016/j.ejphar.2010.04.021 }}{{cite journal | vauthors = Lee SG, Su ZZ, Emdad L, Gupta P, Sarkar D, Borjabad A, Volsky DJ, Fisher PB | title = Mechanism of ceftriaxone induction of excitatory amino acid transporter-2 expression and glutamate uptake in primary human astrocytes | journal = The Journal of Biological Chemistry | volume = 283 | issue = 19 | pages = 13116–13123 | date = May 2008 | pmid = 18326497 | pmc = 2442320 | doi = 10.1074/jbc.M707697200 | doi-access = free }}

Ceftriaxone has been shown to have neuroprotective properties in a number of neurological disorders, including spinal muscular atrophy{{cite journal | vauthors = Hedlund E | title = The protective effects of β-lactam antibiotics in motor neuron disorders | journal = Experimental Neurology | volume = 231 | issue = 1 | pages = 14–18 | date = September 2011 | pmid = 21693120 | doi = 10.1016/j.expneurol.2011.06.002 | s2cid = 26353910 }} and amyotrophic lateral sclerosis (ALS).{{cite journal | vauthors = Rothstein JD, Patel S, Regan MR, Haenggeli C, Huang YH, Bergles DE, Jin L, Dykes Hoberg M, Vidensky S, Chung DS, Toan SV, Bruijn LI, Su ZZ, Gupta P, Fisher PB | title = Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression | journal = Nature | volume = 433 | issue = 7021 | pages = 73–77 | date = January 2005 | pmid = 15635412 | doi = 10.1038/nature03180 | s2cid = 4301666 | bibcode = 2005Natur.433...73R }} 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.{{cite web|url = http://www.alsconsortium.org/news_ceftriaxone_announcement.php|title = Statement on the Clinical Trial of Ceftriaxone|date = 8 August 2012|publisher = The Northeast ALS Consortium (NEALS)|access-date = 10 May 2013|url-status = usurped|archive-url = https://web.archive.org/web/20130528204018/http://www.alsconsortium.org/news_ceftriaxone_announcement.php|archive-date = 28 May 2013}}

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