Ceftriaxone

Last updated

Ceftriaxone
Ceftriaxone-skeletal.svg
Ceftriaxone-from-PDB-6XQV-3D-bs-17.png
Clinical data
Pronunciation /ˌsɛftrˈæksn/
Trade names Rocephin, Epicephin, Wintriaxone, others
AHFS/Drugs.com Monograph
MedlinePlus a685032
License data
Pregnancy
category
Routes of
administration
Intravenous, intramuscular
Drug class Third-generation cephalosporin
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability n/a
Metabolism Negligible
Elimination half-life 5.8–8.7 hours [2]
Excretion 33–67% kidney, 35–45% biliary
Identifiers
  • (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
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.070.347 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C18H18N8O7S3
Molar mass 554.57 g·mol−1
3D model (JSmol)
  • O=C2N1/C(=C(\CS[C@@H]1[C@@H]2NC(=O)C(=N\OC)/c3nc(sc3)N)CS\C4=N\C(=O)C(=O)NN4C)C(=O)O
  • InChI=1S/C18H18N8O7S3/c1-25-18(22-12(28)13(29)23-25)36-4-6-3-34-15-9(14(30)26(15)10(6)16(31)32)21-11(27)8(24-33-2)7-5-35-17(19)20-7/h5,9,15H,3-4H2,1-2H3,(H2,19,20)(H,21,27)(H,23,29)(H,31,32)/b24-8-/t9-,15-/m1/s1 Yes check.svgY
  • Key:VAAUVRVFOQPIGI-SPQHTLEESA-N Yes check.svgY
   (verify)

Ceftriaxone, sold under the brand name Rocephin, is a third-generation cephalosporin antibiotic used for the treatment of a number of bacterial infections. [3] These include middle ear infections, endocarditis, meningitis, pneumonia, bone and joint infections, intra-abdominal infections, skin infections, urinary tract infections, gonorrhea, and pelvic inflammatory disease. [3] It is also sometimes used before surgery and following a bite wound to try to prevent infection. [3] Ceftriaxone can be given by injection into a vein or into a muscle. [3]

Contents

Common side effects include pain at the site of injection and allergic reactions. [3] Other possible side effects include C. difficile-associated diarrhea, hemolytic anemia, gall bladder disease, and seizures. [3] It is not recommended in those who have had anaphylaxis to penicillin but may be used in those who have had milder reactions. [3] The intravenous form should not be given with intravenous calcium. [3] There is tentative evidence that ceftriaxone is relatively safe during pregnancy and breastfeeding. [1] It is a third-generation cephalosporin that works by preventing bacteria from making a cell wall. [3]

Ceftriaxone was patented in 1978 and approved for medical use in 1982. [4] It is on the World Health Organization's List of Essential Medicines. [5] It is available as a generic medication. [3]

Medical use

A vial of ceftriaxone, manufactured and sold in Russia Tseftriakson.JPG
A vial of ceftriaxone, manufactured and sold in Russia

Ceftriaxone and other third-generation cephalosporin antibiotics are used to treat organisms that tend to be resistant to many other antibiotics. [6] Due to emergent resistance, ceftriaxone should not be used for the treatment of Enterobacter infections. [6] Before using ceftriaxone, it is important to determine the susceptibility of the bacteria. [7] If sepsis is being considered, empiric therapy may be initiated prior to susceptibility testing. [6]

Medical uses include: [7]

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 ." [8]

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. [9]

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 . [6] However, unlike ceftazidime and cefoperazone, ceftriaxone does not have useful activity against Pseudomonas aeruginosa . [6] 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. [6] 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). [6] Although not being used as first line therapy against Staphylococcus aures, 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). [10]

Available forms

Ceftriaxone is available for administration via the intramuscular or the intravenous routes. [7] 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). [11] The solutions are pale yellowish in color, [11] 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. [12] 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. [7] [13] This precipitation risk is particularly high in newborns (up to age 28 days), especially if they are premature or have impaired bilirubin binding. [14] [15]

Specific populations

Pregnancy

Ceftriaxone is pregnancy category B [ clarification needed ]. [7] [1] It has not been observed to cause birth defects in animal studies, but a lack of well-controlled studies done in pregnant women exists. [7]

Breastfeeding

Low concentrations of ceftriaxone are excreted in breast milk that are "not expected to cause adverse effects in breastfed infants." [16] [ failed verification ] The manufacturer recommends that caution be exercised when administering ceftriaxone to women who breastfeed. [7]

Newborns

Hyperbilirubinemic neonates are contraindicated for the use of ceftriaxone. [7] It can compete with bilirubin and displace it from binding to albumin, increasing the risk of bilirubin encephalopathy. [7]

Elderly

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." [7]

Adverse effects

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. [17]

Incidence of adverse effects greater than 1%:

Some less frequently reported adverse events (incidence < 1%) include phlebitis, itchiness, fever, chills, nausea, vomiting, elevations of bilirubin, elevations in creatinine, headache and dizziness. [17]

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. [18] [19] [20] It has also been reported to cause post kidney failure in children. [21] Like other antibiotics, ceftriaxone use can result in Clostridioides difficile-associated diarrhea ranging from mild diarrhea to fatal colitis. [17] 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 [22] while ceftriaxone has a 45% biliary excretion [23]

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, [8] [24] caution should still be used when using ceftriaxone in penicillin-sensitive patients. [17] Caution should be used in people who have had previous severe penicillin allergies. [17] 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 [25] even if administered through different infusion lines due to rare fatal cases of calcium-ceftriaxone precipitations in neonatal lungs and kidneys. [17] [26]

Mechanism of action

Ceftriaxone is a third-generation antibiotic from the cephalosporin family of antibiotics. [6] 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. [27] 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. [28] [29] 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. [27] [29] 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. [27] 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. [27]

Pharmacokinetics

Absorption: Ceftriaxone can be administered intravenously and intramuscularly, and the drug is completely absorbed. [7] [30] It is not available orally. [31] [32]

Distribution: Ceftriaxone penetrates tissues and body fluids well, including cerebrospinal fluid to treat central nervous system infections. [7] [33] 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. [7]

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. [7] The rest [34] is excreted in the bile as unchanged drug [35] which is ultimately excreted in feces as inactive compounds from hepatic and gut flora metabolism. [7] [36] [37]

Elimination: The average elimination half-life in healthy adults is 5.8–8.7 (mean 6.5) hours, [2] with some reviews estimated half-life up to 10 hours. [38] In people with renal impairment, the average elimination half-life increases to 11.4–15.7 hours. [7]

Chemistry

Ceftriaxone is commercially available as a white to yellowish-orange crystalline powder for reconstitution. [7] 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. [7] To reduce pain with intramuscular injections, ceftriaxone may be reconstituted with lidocaine. [39]

The syn-configuration of the methoxy oxime moiety confers resistance to beta-lactamase enzymes produced by many Gram-negative bacteria. [27] The stability of this configuration results in increased activity of ceftriaxone against otherwise resistant Gram-negative bacteria. [27] In place of the easily hydrolyzed acetyl group of cefotaxime, ceftriaxone has a metabolically stable thiotriazinedione moiety. [27]

Research

Ceftriaxone has also been investigated for efficacy in preventing relapse to cocaine addiction. [40]

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. [41] [42]

Ceftriaxone has been shown to have neuroprotective properties in a number of neurological disorders, including spinal muscular atrophy [43] and amyotrophic lateral sclerosis (ALS). [44] 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. [45]

Related Research Articles

<span class="mw-page-title-main">Beta-lactamase</span> Class of enzymes

Beta-lactamases (β-lactamases) are enzymes produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems (ertapenem), although carbapenems are relatively resistant to beta-lactamase. Beta-lactamase provides antibiotic resistance by breaking the antibiotics' structure. These antibiotics all have a common element in their molecular structure: a four-atom ring known as a beta-lactam (β-lactam) ring. Through hydrolysis, the enzyme lactamase breaks the β-lactam ring open, deactivating the molecule's antibacterial properties.

<span class="mw-page-title-main">Penicillin</span> Group of antibiotics derived from Penicillium fungi

Penicillins are a group of β-lactam antibiotics originally obtained from Penicillium moulds, principally P. chrysogenum and P. rubens. Most penicillins in clinical use are synthesised by P. chrysogenum using deep tank fermentation and then purified. A number of natural penicillins have been discovered, but only two purified compounds are in clinical use: penicillin G and penicillin V. Penicillins were among the first medications to be effective against many bacterial infections caused by staphylococci and streptococci. They are still widely used today for different bacterial infections, though many types of bacteria have developed resistance following extensive use.

<span class="mw-page-title-main">Beta-lactam antibiotics</span> Class of broad-spectrum antibiotics

β-lactam antibiotics are antibiotics that contain a beta-lactam ring in their chemical structure. This includes penicillin derivatives (penams), cephalosporins and cephamycins (cephems), monobactams, carbapenems and carbacephems. Most β-lactam antibiotics work by inhibiting cell wall biosynthesis in the bacterial organism and are the most widely used group of antibiotics. Until 2003, when measured by sales, more than half of all commercially available antibiotics in use were β-lactam compounds. The first β-lactam antibiotic discovered, penicillin, was isolated from a strain of Penicillium rubens.

<span class="mw-page-title-main">Ertapenem</span> Antibiotic medication

Ertapenem, sold under the brand name Invanz, is a carbapenem antibiotic medication used for the treatment of infections of the abdomen, the lungs, the upper part of the female reproductive system, and the diabetic foot.

<span class="mw-page-title-main">Methicillin</span> Antibiotic medication

Methicillin (USAN), also known as meticillin (INN), is a narrow-spectrum β-lactam antibiotic of the penicillin class.

<span class="mw-page-title-main">Cephalosporin</span> Class of pharmaceutical drugs

The cephalosporins are a class of β-lactam antibiotics originally derived from the fungus Acremonium, which was previously known as Cephalosporium.

<span class="mw-page-title-main">Aztreonam</span> Chemical compound

Aztreonam, sold under the brand name Azactam among others, is an antibiotic used primarily to treat infections caused by gram-negative bacteria such as Pseudomonas aeruginosa. This may include bone infections, endometritis, intra abdominal infections, pneumonia, urinary tract infections, and sepsis. It is given by intravenous or intramuscular injection or by inhalation.

<span class="mw-page-title-main">Cefazolin</span> Antibiotic medication

Cefazolin, also known as cefazoline and cephazolin, is a first-generation cephalosporin antibiotic used for the treatment of a number of bacterial infections. Specifically it is used to treat cellulitis, urinary tract infections, pneumonia, endocarditis, joint infection, and biliary tract infections. It is also used to prevent group B streptococcal disease around the time of delivery and before surgery. It is typically given by injection into a muscle or vein.

<span class="mw-page-title-main">Cefalexin</span> Beta-lactam antibiotic

Cefalexin, also spelled cephalexin, is an antibiotic that can treat a number of bacterial infections. It kills gram-positive and some gram-negative bacteria by disrupting the growth of the bacterial cell wall. Cefalexin is a β-lactam antibiotic within the class of first-generation cephalosporins. It works similarly to other agents within this class, including intravenous cefazolin, but can be taken by mouth.

<span class="mw-page-title-main">Cefuroxime axetil</span> Chemical compound

Cefuroxime axetil, sold under the brand name Ceftin among others, is a second generation oral cephalosporin antibiotic.

<span class="mw-page-title-main">Cefotaxime</span> Chemical compound

Cefotaxime is an antibiotic used to treat a number of bacterial infections in human, other animals and plant tissue culture. Specifically in humans it is used to treat joint infections, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, sepsis, gonorrhea, and cellulitis. It is given either by injection into a vein or muscle.

Ampicillin/sulbactam is a fixed-dose combination medication of the common penicillin-derived antibiotic ampicillin and sulbactam, an inhibitor of bacterial beta-lactamase. Two different forms of the drug exist. The first, developed in 1987 and marketed in the United States under the brand name Unasyn, generic only outside the United States, is an intravenous antibiotic. The second, an oral form called sultamicillin, is marketed under the brand name Ampictam outside the United States, and generic only in the United States. Ampicillin/sulbactam is used to treat infections caused by bacteria resistant to beta-lactam antibiotics. Sulbactam blocks the enzyme which breaks down ampicillin and thereby allows ampicillin to attack and kill the bacteria.

<span class="mw-page-title-main">Flucloxacillin</span> Penicillin

Flucloxacillin, also known as floxacillin, is an antibiotic used to treat skin infections, external ear infections, infections of leg ulcers, diabetic foot infections, and infection of bone. It may be used together with other medications to treat pneumonia, and endocarditis. It may also be used prior to surgery to prevent Staphylococcus infections. It is not effective against methicillin-resistant Staphylococcus aureus (MRSA). It is taken by mouth or given by injection into a vein or muscle.

<span class="mw-page-title-main">Dicloxacillin</span> Chemical compound

Dicloxacillin is a narrow-spectrum β-lactam antibiotic of the penicillin class. It is used to treat infections caused by susceptible (non-resistant) Gram-positive bacteria. It is active against beta-lactamase-producing organisms such as Staphylococcus aureus, which would otherwise be resistant to most penicillins. Dicloxacillin is available under a variety of trade names including Diclocil (BMS).

<span class="mw-page-title-main">Penicillin-binding proteins</span> Class of proteins

Penicillin-binding proteins (PBPs) are a group of proteins that are characterized by their affinity for and binding of penicillin. They are a normal constituent of many bacteria; the name just reflects the way by which the protein was discovered. All β-lactam antibiotics bind to PBPs, which are essential for bacterial cell wall synthesis. PBPs are members of a subgroup of enzymes called transpeptidases. Specifically, PBPs are DD-transpeptidases.

<span class="mw-page-title-main">Oxacillin</span> Chemical compound

Oxacillin is a narrow-spectrum beta-lactam antibiotic of the penicillin class developed by Beecham.

<span class="mw-page-title-main">Cefoxitin</span> Chemical compound

Cefoxitin is a second-generation cephamycin antibiotic developed by Merck & Co., Inc. from Cephamycin C in the year following its discovery, 1972. It was synthesized in order to create an antibiotic with a broader spectrum. It is often grouped with the second-generation cephalosporins. Cefoxitin requires a prescription and as of 2010 is sold under the brand name Mefoxin by Bioniche Pharma, LLC. The generic version of cefoxitin is known as cefoxitin sodium.

Cephalosporins are a broad class of bactericidal antibiotics that include the β-lactam ring and share a structural similarity and mechanism of action with other β-lactam antibiotics. The cephalosporins have the ability to kill bacteria by inhibiting essential steps in the bacterial cell wall synthesis which in the end results in osmotic lysis and death of the bacterial cell. Cephalosporins are widely used antibiotics because of their clinical efficiency and desirable safety profile.

<span class="mw-page-title-main">Antibiotic resistance in gonorrhea</span>

Neisseria gonorrhoeae, the bacterium that causes the sexually transmitted infection gonorrhea, has developed antibiotic resistance to many antibiotics. The bacteria was first identified in 1879.

<span class="mw-page-title-main">Ceftolozane/tazobactam</span> Antibiotic

Ceftolozane/tazobactam, sold under the brand name Zerbaxa, is a combination antibiotic medication used for the treatment of complicated urinary tract infections and complicated intra-abdominal infections in adults. Ceftolozane is a cephalosporin antibiotic, developed for the treatment of infections with gram-negative bacteria that are resistant to conventional antibiotics. It was studied for urinary tract infections, intra-abdominal infections and ventilator-associated bacterial pneumonia.

References

  1. 1 2 3 "Ceftriaxone (Rocephin) Use During Pregnancy". Drugs.com. 12 December 2019. Archived from the original on 23 August 2016. Retrieved 24 December 2019.
  2. 1 2 Beam TR (1985). "Ceftriaxone: a beta-lactamase-stable, broad-spectrum cephalosporin with an extended half-life". Pharmacotherapy. 5 (5): 237–253. doi:10.1002/j.1875-9114.1985.tb03423.x. PMID   3906584. S2CID   25559476.
  3. 1 2 3 4 5 6 7 8 9 10 11 "Ceftriaxone Sodium Monograph for Professionals". Drugs.com. Archived from the original on 31 May 2016. Retrieved 27 August 2016.
  4. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 495. ISBN   978-3-527-60749-5.
  5. World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl: 10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  6. 1 2 3 4 5 6 7 8 Katzung B, Masters S, Trevor A (2012). Basic and Clinical Pharmacology. McGraw-Hill. pp. 797–801. ISBN   978-0-07-176402-5.
  7. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 "Ceftriaxone- ceftriaxone sodium injection, powder, for solution". DailyMed. 31 December 2019. Archived from the original on 17 November 2015. Retrieved 1 February 2020.
  8. 1 2 Katzung B (2009). Basic and Clinical Pharmacology, Eleventh Edition. New York: McGraw-Hill. pp. 783–784. ISBN   978-0-07-160405-5.
  9. St Cyr S, Barbee L, Workowski KA, Bachmann LH, Pham C, Schlanger K, et al. (December 2020). "Update to CDC's Treatment Guidelines for Gonococcal Infection, 2020". MMWR. Morbidity and Mortality Weekly Report. 69 (50): 1911–1916. doi:10.15585/mmwr.mm6950a6. PMC   7745960 . PMID   33332296.
  10. Di Bella S, Gatti M, Principe L (29 April 2023). "Ceftriaxone for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia: a matter of dosages?". European Journal of Clinical Microbiology & Infectious Diseases. 42 (7): 917–918. doi:10.1007/s10096-023-04612-x. ISSN   1435-4373. PMID   37119346. S2CID   258423746.
  11. 1 2 https://web.archive.org/web/20231206072711/https://www.medsafe.govt.nz/profs/datasheet/c/ceftriaxoneinjDEVA.pdf
  12. Palzkill T (January 2013). "Metallo-β-lactamase structure and function". Ann N Y Acad Sci. 1277 (1): 91–104. Bibcode:2013NYASA1277...91P. doi:10.1111/j.1749-6632.2012.06796.x. PMC   3970115 . PMID   23163348.
  13. https://web.archive.org/web/20230813180009/https://www.pbm.va.gov/PBM/vacenterformedicationsafety/nationalpbmbulletin/CeftriaxoneNationalPBMBulletin.pdf
  14. "Ceftriaxone (Rocephin): Incompatible with solutions containing calcium". Archived from the original on 8 December 2023.
  15. https://web.archive.org/web/20240222194630/https://www.hpra.ie/docs/default-source/Safety-Notices/ceftriaxone---march-2010---final.pdf
  16. "TOXNET". toxnet.nlm.nih.gov. Archived from the original on 8 September 2017. Retrieved 4 November 2015.
  17. 1 2 3 4 5 6 7 "Rocephin Prescribing Information" (PDF). Roche. Archived (PDF) from the original on 4 March 2016. Retrieved 1 November 2015.
  18. 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): 1772–1778. doi:10.1016/0016-5085(90)90486-K. PMID   2227290.
  19. Shrimali JD, Patel HV, Gumber MR, Kute VB, Shah PR, Vanikar AV, Trivedi HL (November 2013). "Ceftriaxone induced immune hemolytic anemia with disseminated intravascular coagulation". Indian Journal of Critical Care Medicine. 17 (6): 394–395. doi: 10.4103/0972-5229.123465 . PMC   3902580 . PMID   24501497.
  20. Guleria VS, Sharma N, Amitabh S, Nair V (September–October 2013). "Ceftriaxone-induced hemolysis". Indian Journal of Pharmacology. 45 (5): 530–531. doi: 10.4103/0253-7613.117758 . PMC   3793531 . PMID   24130395.
  21. Li N, Zhou X, Yuan J, Chen G, Jiang H, Zhang W (April 2014). "Ceftriaxone and acute renal failure in children" (PDF). Pediatrics. 133 (4): e917–e922. doi:10.1542/peds.2013-2103. PMID   24664092. S2CID   2854637. Archived (PDF) from the original on 22 February 2024. Retrieved 22 February 2024.
  22. Patel KB, Nicolau DP, Nightingale CH, Quintiliani R (May 1995). "Pharmacokinetics of cefotaxime in healthy volunteers and patients". Diagnostic Microbiology and Infectious Disease. 22 (1–2): 49–55. doi:10.1016/0732-8893(95)00072-I. PMID   7587050.
  23. Guggenbichler JP, Allerberger FJ, Dierich M (1986). "Influence of cephalosporines III generation with varying biliary excretion on fecal flora and emergence of resistant bacteria during and after cessation of therapy". Padiatrie und Padologie. 21 (4): 335–342. PMID   3562044. Archived from the original on 29 April 2023. Retrieved 29 April 2023.
  24. "The Use of Cephalosporins in Penicillin-allergic Patients". www.medscape.com. Archived from the original on 14 November 2015. Retrieved 10 November 2015.
  25. "FDA Updates warning on Ceftriaxone-Calcium injection". Archived from the original on 28 November 2009.
  26. Bradley JS, Wassel RT, Lee L, Nambiar S (April 2009). "Intravenous ceftriaxone and calcium in the neonate: assessing the risk for cardiopulmonary adverse events" (PDF). Pediatrics. 123 (4): e609–e613. doi:10.1542/peds.2008-3080. PMID   19289450. S2CID   22718923. Archived (PDF) from the original on 22 February 2024. Retrieved 22 February 2024.
  27. 1 2 3 4 5 6 7 Lemke TL, Williams DA, eds. (2013). Foye's Principles of Medicinal Chemistry (Seventh ed.). Philadelphia, PA: Lippincott Williams & Wilkins. pp. 1093–1094, 1099–1100. ISBN   978-1-60913-345-0.
  28. van Heijenoort J (March 2001). "Formation of the glycan chains in the synthesis of bacterial peptidoglycan". Glycobiology. 11 (3): 25R–36R. doi: 10.1093/glycob/11.3.25r . PMID   11320055. S2CID   46066256.
  29. 1 2 Scheffers DJ, Pinho MG (December 2005). "Bacterial cell wall synthesis: new insights from localization studies". Microbiology and Molecular Biology Reviews. 69 (4): 585–607. doi:10.1128/MMBR.69.4.585-607.2005. PMC   1306805 . PMID   16339737.
  30. Patel IH, Kaplan SA (October 1984). "Pharmacokinetic profile of ceftriaxone in man". The American Journal of Medicine. 77 (4C): 17–25. PMID   6093513.
  31. Red Book: Pharmacy's Fundamental Reference (114th ed.). PDR Network, LLC. 2010. ISBN   978-1-56363-751-3.
  32. "DailyMed – Search Results for ceftriaxone". dailymed.nlm.nih.gov. Archived from the original on 6 March 2016. Retrieved 4 November 2015.
  33. Nau R, Sörgel F, Eiffert H (October 2010). "Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nervous system infections". Clinical Microbiology Reviews. 23 (4): 858–883. doi:10.1128/CMR.00007-10. PMC   2952976 . PMID   20930076.
  34. Arvidsson A, Alván G, Angelin B, Borgå O, Nord CE (September 1982). "Ceftriaxone: renal and biliary excretion and effect on the colon microflora". The Journal of Antimicrobial Chemotherapy. 10 (3): 207–215. doi:10.1093/jac/10.3.207. PMID   6292158.
  35. Blumer J (September 1991). "Pharmacokinetics of ceftriaxone". Hospital Practice. 26 (Suppl 5): 7–13, discussion 52–4. doi:10.1080/21548331.1991.11707737. PMID   1918224.
  36. Balant L, Dayer P, Auckenthaler R (1 April 1985). "Clinical pharmacokinetics of the third generation cephalosporins". Clinical Pharmacokinetics. 10 (2): 101–143. doi:10.2165/00003088-198510020-00001. PMID   3888488. S2CID   23478077.
  37. Nursing Pharmacology Made Incredibly Easy!. Lippincott Williams & Wilkins. 7 March 2012. p. 496. ISBN   978-1-4511-4624-0. Archived from the original on 3 June 2016.
  38. Klein NC, Cunha BA (July 1995). "Third-generation cephalosporins". The Medical Clinics of North America. 79 (4): 705–719. doi: 10.1016/s0025-7125(16)30034-7 . PMID   7791418.
  39. 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?". Archives of Pediatrics & Adolescent Medicine. 148 (1): 72–75. doi:10.1001/archpedi.1994.02170010074017. PMID   8143016.
  40. Knackstedt LA, Melendez RI, Kalivas PW (January 2010). "Ceftriaxone restores glutamate homeostasis and prevents relapse to cocaine seeking". Biological Psychiatry. 67 (1): 81–84. doi:10.1016/j.biopsych.2009.07.018. PMC   2795043 . PMID   19717140.
  41. Verma R, Mishra V, Sasmal D, Raghubir R (July 2010). "Pharmacological evaluation of glutamate transporter 1 (GLT-1) mediated neuroprotection following cerebral ischemia/reperfusion injury". European Journal of Pharmacology. 638 (1–3): 65–71. doi:10.1016/j.ejphar.2010.04.021. PMID   20423712.
  42. Lee SG, Su ZZ, Emdad L, Gupta P, Sarkar D, Borjabad A, et al. (May 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.
  43. Hedlund E (September 2011). "The protective effects of β-lactam antibiotics in motor neuron disorders". Experimental Neurology. 231 (1): 14–18. doi:10.1016/j.expneurol.2011.06.002. PMID   21693120. S2CID   26353910.
  44. Rothstein JD, Patel S, Regan MR, Haenggeli C, Huang YH, Bergles DE, et al. (January 2005). "Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression". Nature. 433 (7021): 73–77. Bibcode:2005Natur.433...73R. doi:10.1038/nature03180. PMID   15635412. S2CID   4301666.
  45. "Statement on the Clinical Trial of Ceftriaxone". The Northeast ALS Consortium (NEALS). 8 August 2012. Archived from the original on 28 May 2013. Retrieved 10 May 2013.