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Submitted: February 26, 2022 | Approved: April 04, 2022 | Published: April 05, 2022

How to cite this article: Bereda G. Ceftriaxone in pediatrics: Indication, adverse drug reaction, contraindication and drug interaction. J Addict Ther Res. 2022; 6: 007-009.

DOI: 10.29328/journal.jatr.1001021

Copyright License: © 2022 Bereda G. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords: Adverse drug reaction; Ceftriaxone; Contraindication; Drug interaction; Pediatrics; Indication

Abbreviations: Ca2: Calcium; Cacl2: Calcium Chloride; CSF: Cerebrospinal Fluid; GI: Gastrointestinal; IV: Iintravenous

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Ceftriaxone in pediatrics: Indication, adverse drug reaction, contraindication and drug interaction

Gudisa Bereda*

Department of Pharmacy, Negelle Health Science College, Guji, Ethiopia

*Address for Correspondence: Alembante Gudisa Bereda, Department of Pharmacy, Negelle Health Science College, Guji, Ethiopia, Email: gudisabareda95@gmail.com

Ceftriaxone is having many uses and useful “third-generation” cephalosporin that necessitates being given every day. Ceftriaxone acts as binds to one or many of the penicillin-binding proteins which inhibit the final transpeptidoglycan step of peptidoglycan synthesis in the bacterial cell wall, thus inhibiting biosynthesis and arresting cell wall assembly resulting in bacterial cell death.

Ceftriaxone-associated biliary adverse events in children less than eighteen years cause biliary pseudolithiasis and scarcely nephrolithiasis often happen in children less than eighteen years after receiving overdoses of ceftriaxone. Ceftriaxone perhaps binds with calcium and figure insoluble chelation leading to biliary pseudolithiasis. Cholelithiasis, increased biliary thickness, and pseudolithiasis rarely happen in a period of being a child, but there are two modes of distribu¬tion described by two peaks, the first being at an early stage of development and the second is a period of life when a child develops into an adult. Hyperbilirubinemia is significantly contraindicated for neonates administrated ceftriaxone, particularly premature neonates, because of the displacement of bilirubin from albumin-binding sites and increase in blood concentrations of free bilirubin. A child than one month old and a child less than twelve-month old in special are at great risk of poor results because of bilirubin encephalopathy. Coincident administrations of ceftriaxone with aminoglycosides such as gentamycin and loop diuretics (furosemide) perhaps increase the risk of nephrotoxicity (rapid degeneration in the kidney function to the toxic outcome of double or triple medications). Coincident administrations of ceftriaxone with anticoagulant medications such as warfarin are associated with bleeding due to increased prothrombin times, which is reversible with vitamin K.

Ceftriaxone is a parenteral cephalosporin with broad antimicrobial activity. Ceftriaxone is an antibiotic that is commonly used to treat infectious diseases caused by bacteria. Ceftriaxone is having many uses and useful “third-generation” cephalosporin that requires to be given every day. It commonly acts on significant gram-positive and most gram-negative bacteria [1]. Ceftriaxone is an injectable cephalosporin with a wide anti-infective spectrum and has a prolonged elimination half-life of eight hours [2]. Ceftriaxone is a bactericidal agent that acts by inhibiting bacterial cell wall secretion. Ceftriaxone has activity in the presence of certain beta-lactamases, both penicillinase, and cephalosporins, of Gram-negative and Gram-positive bacteria. Ceftriaxone acts as binds to one or many of the penicillin-binding proteins which inhibit the final transpeptidoglycan step of peptidoglycan synthesis in the bacterial cell wall, thus inhibiting biosynthesis and preventing cell wall assembly sequencing in bacterial cell death [1].

Indications

Ceftriaxone is used for the management of neonatal sepsis and meningitis caused by susceptible gram (-ve) microorganisms (e.g. E. coli, P. aeruginosa, Klebsiella, H. influenzae) and for the management of gonococcal infections. Ceftriaxone distributes broadly in CSF, bile, bronchial secretions, lung tissue, ascitic fluid, and the middle ear. Ceftriaxone is eliminated unchanged by dual biliary (40%) and renal mechanisms. Serum half-life in infants born before the normal time is five to sixteen hrs. Only infants who have hepatic and renal impairment concurrently seek dose adjustment significantly [3].

Adverse drug reaction

The most common adverse drug reaction associated with administrating ceftriaxone involves allergic reactions (rash, eosinophilia, fever, anaphylactoid shock, etc), gastrointestinal disturbances, and temporary escalate in transaminases, nephrotoxicity, pseudomembranous colitis, blood dyscrasias, hematological anomalies (granu­locytopenia, thrombo-cytopenia, hemolytic anemia) and gallbladder deliverance inadequacy [4-6]. Certain side effects of ceftriaxone are illustrated beneath; Ceftriaxone-associated biliary adverse events in pediatrics are cause biliary pseudolithiasis and scarcely nephrolithiasis often happens in children less than eighteen years who receive overdoses of ceftriaxone [7]. Ceftriaxone-associated renal adverse events in pediatrics result in urolithiasis in children less than eighteen years, which could also cause acute kidney injury [8]. Ceftriaxone perhaps binds with calcium and figures insoluble chelation influencing biliary pseudolithiasis [9]. Cholelithiasis, escalated biliary thickness, and pseudolithiasis rarely happen in a period of being a child, but there are two modes of distribu­tion described by double peaks, the 1st being at an early stage of development and the 2nd in a period of life when a child develops into an adult [10,11]. Ceftriaxone-associated hemolysis in pediatrics due to the availability of a substance produced by the body to fight disease against ceftriaxone, and the judgment displaced immune complex type lysis of red blood cells with the liberation of hemoglobin [12]. Ceftriaxone displaces bilirubin from albumin attaching sites; ceftriaxone generated escalation of free bilirubin and erythrocyte-bound bilirubin and de-escalates unconjugated bilirubin. Ceftriaxone reveals a substantial replacing consequence at accumulations gathered among therapeutically used and should be used with precaution in more-risk jaundiced a very young child [13]. Determination of free bilirubin, erythrocyte-bound bilirubin, and unconjugated bilirubin was used to test the outcomes of ceftriaxone on the binding of bilirubin to albumin [14].

Contraindication
Hyperbilirubinemia is significantly contraindicated for neonates administrated ceftriaxone, particularly premature neonates, because of the displacement of bilirubin from albumin-binding sites and increase in blood concentra­tions of free bilirubin. A child than one month old and a child less than twelve months old in special are at great risk of poor results because of bilirubin encephalopathy [15-17]. Ceftriaxone for parenteral is not given for patients with a history of having cephalosporin category of antibiotics allergies [18]. Coadministration of ceftriaxone and calcium-containing solutions or products in a child less than a month old is contraindicated: ceftriaxone reacts to calcium-containing solution and it can chelate in lungs and kidneys of a child less than twenty-eight days years and this could be life-threatening. Consequently, ceftriaxone is also contraindicated in a child less than twenty-eight days years if they are anticipated to take any calcium-containing products. Coincident usage of IV ceftriaxone and calcium-containing solutions in neonates and young infants has been associated with calcium chelation. Ceftriaxone is discordant with theophylline, azithromycin, Cacl2, Ca gluconate, caspofungin, fluconazole, and vancomycin [19].
Drug interactions

Disulfiram-like reaction enclosing ceftriaxone in a child less than eighteen years patient: disulfiram-like reactions between ceftriaxone and ethanol have been well defined in the literature. The reaction’s mechanism involves disulfiram or the falling medication preventing aldehyde dehydrogenase, the enzyme responsible for converting acetaldehyde product of metabolism of ethanol to acetate. The sequencing increases in harmful blood acetaldehyde leads to clinical outcomes that categorize in severity and that are common to the amount of being exposed to alcohol and falling medicine. Rare reactions are clearly shown as vasodilation sequencing in flushing and headache, while moderate to severe reactions can develop from nausea and vomiting to hypotension, dysrhythmia, and death [20-22]. Disulfiram-like reactions among ceftriaxone and ethanol are extremely infrequent. Coincident administrations of ceftriaxone with aminoglycosides such as gentamycin and loop diuretics (furosemide) perhaps increase the risk of nephrotoxicity (rapid degeneration in the kidney function due to the toxic outcome of double or triple medications). Coincident administrations of ceftriaxone with anticoagulant medications such as warfarin are associated with bleeding due to increased prothrombin times, which is reversible with vitamin K [23,24].

Ceftriaxone is having many uses and useful “third-generation” cephalosporin that requires to be given every day. Ceftriaxone acts as binds to one or many of the penicillin-binding proteins which inhibit the final transpeptidoglycan step of peptidoglycan synthesis in the bacterial cell wall, thus inhibiting biosynthesis and arresting cell wall assembly sequencing in bacterial cell death.

Ceftriaxone-associated biliary adverse events in children less than eighteen years cause biliary pseudolithiasis and scarcely nephrolithiasis often happen in children less than eighteen years after receiving overdoses of ceftriaxone. A child than one month old and a child less than twelve months old in special are at great risk of a poor outcome because of bilirubin encephalopathy. Coincident administrations of ceftriaxone with aminoglycosides such as gentamycin and loop diuretics (furosemide) perhaps escalate the risk of nephrotoxicity (rapid degeneration in the kidney functions due to the toxic outcome of double or triple medications). Coincident administrations of ceftriaxone with anticoagulant medications such as warfarin are associated with bleeding due to increased prothrombin times, which is reversible with vitamin K.

The author acknowledged to those all who support him during the preparation of this manuscript.

Data sources

Sources searched include Google Scholar, Research Gate, PubMed, NCBI, NDSS, PMID, PMCID, and Cochrane database. Search terms involved: indication, adverse drug reaction, contraindication, and drug interaction of ceftriaxone in pediatrics.

Availability of data and materials: The datasets generated amid the recent survey are available with the correspondent author.

Author’s contributions: GB contributed to preparing the first draft, reviewing and editing the draft, and finally reading and approving the manuscript.

  1. Bereda G. Clinical Pharmacology of Ceftriaxone in Paediatrics. J Biomed Bio Sci. 2022; 2: 1-8.
  2. Neonatal Formulary. Seventh edition. John Wiley & Sons, Ltd. The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK. 2015; 140-141.
  3. Lutsar I, Friedland IR. Pharmacokinetics and pharmacodynamics of cephalosporins in cerebrospinal fluid. Clin Pharmacokinet. 2000; 39: 335–343. PubMed: https://pubmed.ncbi.nlm.nih.gov/11108433/
  4. Young TE, Mangum B. NEOFAX twenty-third edition. Antimicrobials. Montvale NJ 07645. 2010; 32-33.
  5. European Medicines Agency. Annex III. Summary of product characteristics, labelling and package leaflet. 2015. http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Rocephin_30/WC500160113.pdf
  6. Gökçe S, Yildirim M, Erdoğan D. A retrospective review of children with gallstones: single-center experience from Central Anatolia. Turk J Gastroenterol. 2014; 25: 46–53. PubMed: https://pubmed.ncbi.nlm.nih.gov/24918130/
  7. Rivkin AM. Hepatocellular enzyme elevations in a patient receiving ceftriaxone. Am J Health Syst Pharm. 2005; 62: 2006–2010. PubMed: https://pubmed.ncbi.nlm.nih.gov/16174837/
  8. Biner B, Oner N, Celtik C, Bostancioğlu M, Tunçbilek N, et al. Ceftriaxone-associated biliary pseudolithiasis in children. J Clin Ultrasound. 2006; 34: 217-222. PubMed: https://pubmed.ncbi.nlm.nih.gov/16673364/
  9. Shen X, Liu W, Fang X, Jia J, Lin H, et al. Acute kidney injury caused by ceftriaxone-induced urolithiasis in children: a single-institutional experience in diagnosis, treatment and followup. Int Urol Nephrol. 2014; 46: 1909-1914. PubMed: https://pubmed.ncbi.nlm.nih.gov/24879561/
  10. Avci Z, Koktener A, Uras N, Catal F, Karadag A, et al. Nephrolithiasis associated with ceftriaxone therapy: a prospective study in 51 children. Arch Dis Child. 2004; 89: 1069-1072. PubMed: https://pubmed.ncbi.nlm.nih.gov/15499067/
  11. Gökçe S, Yildirim M, Erdoğan D. A retrospective review of children with gallstones: single-center experience from Central Anatolia. Turk J Gastroenterol. 2014; 25: 46–53. PubMed: https://pubmed.ncbi.nlm.nih.gov/24918130/
  12. Alehossein M, Sotoudeh K, Nasoohi S, Salamati P, Akhtare-Khavari H. Ceftriaxone induced biliary pseudocholelithiasis in children. Report of 14 cases. Iran J Pediatr. 2008; 18: 31-37.
  13. Citak A, Garratty G, Ucsel R, Karabocuoglu M, Uzel N. Ceftriaxone-induced haemolytic anaemia in a child with no immune deficiency or haematological disease. J Paediatr Child Health. 2002; 38: 209-210. PubMed: https://pubmed.ncbi.nlm.nih.gov/12031011/
  14. Pacifici GM. Clinical Pharmacology of Ceftriaxone in Infants and Children. J Target Drug Deliv. 2019; 3: 001-013.
  15. Maria Pacifici G, Marchini G. Clinical Pharmacology of Ceftriaxone in Neonates and Infants: Effects and Pharmacokinetics. Int J Pediatr. 2017; 5: 5751-5778.
  16. Gulian JM, Dalmasso C, Pontier F, Gonard V. Displacement effect of ceftriaxone on bilirubin bound to human serum albumin. Chemotherapy. 1986; 32: 399–403. PubMed: https://pubmed.ncbi.nlm.nih.gov/3757585/
  17. Abu Teir MM, Ghitan J, Abu-Taha MI, Darwish SM, Abu-Hadid MM. Spectroscopic approach of the interaction study of ceftriaxone and human serum albumin. J Biophys Struct Biol. 2014; 6: 1–12.
  18. Schaad UB, Tschäppeler H, Lentze NJ. Transient formation of precipi­tations in the gallbladder associated with ceftriaxone therapy. Pediatr Infect Dis. 1986; 5: 708–710. PubMed: https://pubmed.ncbi.nlm.nih.gov/3540889/
  19. Baddour LM, Wilson WR, Bayer AS, Fowler VG, Jr., Bolger AF, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the Infectious Diseases Society of America. Circulation. 2005; 11: e 394–433. PubMed: https://pubmed.ncbi.nlm.nih.gov/15956145/
  20. Young TE, Mangum B. NEOFAX. Antimicrobials. Penicillin G. 23rd edition 2010. Thomson Reuters. 2010; 32-33.
  21. Zindel LR, Kranzler HR. Pharmacotherapy of alcohol use disorders: seventy-five years of progress. J Stud Alcohol Drugs Suppl. 2014; 75: 79–88. PubMed: https://pubmed.ncbi.nlm.nih.gov/24565314/
  22. Dong H, Zhang J, Ren L, Liu Q, Zhu S. Unexpected death due to cefuroxime-induced disulfiram-like reaction. Indian J Pharmacol. 2013; 45: 399–400. PubMed: https://pubmed.ncbi.nlm.nih.gov/24014919/
  23. Cina SJ, Russell RA, Conradi SE. Sudden death due to metronidazole/ethanol interaction. Am J Forensic Med Pathol. 1996; 17: 343–346. PubMed: https://pubmed.ncbi.nlm.nih.gov/8947362/
  24. Zareh M, Davis A, Henderson S. Reversal of warfarin-induced hemorrhage in the emergency department. West J Emerg Med. 2011; 12: 386. PubMed: https://pubmed.ncbi.nlm.nih.gov/22224125/