Analysis of fatal outcomes associated with ceftriaxone treatment from the Russian database of spontaneous reports

Clinical Microbiology and Antimicrobial Chemotherapy. 2023; 25(2):159-164

​ Klabukova D.L., Titova A.R., Krysanov I.S., Polivanov V.A., Krysanova V.S., Ermakova V.Yu.
10.36488/cmac.2023.2.159-164
ceftriaxone fatal outcome anaphylactic shock local anesthetics pharmacovigilance spontaneous reports
Section
Antimicrobials
Type
Original Article
Publication
Clinical Microbiology and Antimicrobial Chemotherapy. 2023; 25(2):159-164

Objective.

To analyze spontaneous reports (SRs) from the Russian database of adverse reactions (Automated information system «Pharmacovigilance» of Roszdravnadzor), containing information on fatal outcomes during ceftriaxone treatment, and to identify factors associated with an increased risk of death with ceftriaxone use.

Materials and Methods.

The study included 122 SRs concerning fatal cases during ceftriaxone therapy. All SRs were submitted to the Russian pharmacovigilance database from 06 May 2019 to 23 November 2022. A retrospective analysis of fatal adverse reactions cases in ceftriaxone treatment was carried out according to the following parameters: gender, age, drug intake and route of administration, clinical symptoms of anaphylaxis. Additionally, indications for the simultaneous use of drugs for local anesthesia as a solvent were evaluated.

Results.

A total of 86 SRs (70.5%) were primary and relevant for further analysis. 16 SRs (18.6%) were registered in the database for 8 months of 2019, 25 (29.1%) – for 2020, 15 (17.4%) – for 2021, for less than 11 months 2022 received 30 reports (34.9%). The number of adverse reactions reports in male and female patients was similar. Among the age groups, the largest number of SRs was observed in middleaged and elderly patients – 27 (31.4%) and 23 (26.7%) reports, respectively, 8 cases (9.3%) were registered in pediatric population. The development of fatal adverse reactions in the hospital was reported in 50 (58.1%) SRs, in outpatient setting – in 31 (36.1%) SRs. 18 SRs were identified with an indication of the patient’s self-treatment, which is 20.9% of all primary reports. Clinical symptoms of anaphylactic shock were noted in 63 reports (73.3%). Additional analysis of the combined use of ceftriaxone and local anesthetics cases revealed a range of medical errors.

Conclusions.

Ceftriaxone treatment was associated with a high risk of anaphylactic shock. The use of this antibiotic in outpatient setting, especially as self-treatment is an additional risk factor for death. Inappropriate use of local anesthetics in combination with ceftriaxone is an additional serious risk factor for fatal outcome.

Daria L. Klabukova

A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia
Scientific and Practical Center for Clinical and Economic Analysis of the Ministry of Healthcare of Moscow Region, Krasnogorsk, Russia

Titova A.R.

Information and Methodological Center for Evaluation, Accounting and Analysis of Circulation of Medicinal Products, Moscow, Russia

Krysanov I.S.

A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia
Medical Institute of Continuous Education at the “Russian Biotechnological University”, Moscow, Russia

Polivanov V.A.

Information and Methodological Center for Evaluation, Accounting and Analysis of Circulation of Medicinal Products, Moscow, Russia

Krysanova V.S.

Medical Institute of Continuous Education at the “Russian Biotechnological University”, Moscow, Russia

Ermakova V.Yu.

LLC “Institute of Clinical and Economic Expertise and Pharmacoeconomics”, Mytishchi, Russia
I.M. Sechenov First Moscow State Medical University, Moscow, Russia

  • 1. Tanno L.K., Chalmers R., Bierrenbach A.L., Simons F.E.R., Martin B., Molinari N., et al. Changing the history of anaphylaxis mortality statistics through the World Health Organization's International Classification of Diseases-11. J Allergy Clin Immunol. 2019;144(3):627-633. DOI: 10.1016/j.jaci.2019.05.013
  • 2. Fischer D., Vander Leek T., Ellis A., Kim H. Anaphylaxis. Allergy Asthma Clin Immunol. 2018;14(Suppl. 2):54. DOI: 10.1186/s13223-018-0283-4
  • 3. Panesar S.S., Javad S., de Silva D., Nwaru B.I., Hickstein L., Muraro A., et al. The epidemiology of anaphylaxis in Europe: a systematic review. Allergy. 2013;68(11):13531361. DOI: 10.1111/all.12272
  • 4. Pagani S., Lombardi N., Crescioli G., Vighi V.G., Spada G., Andreetta P., et al. Drug-related hypersensitivity reactions leading to emergency department: original data and systematic review. J Clin Med. 2022;11(10):2811. DOI: 10.3390/jcm11102811
  • 5. The selection and use of essential medicines: report of the WHO Expert Committee, 2017 (including the 20th WHO Model List of Essential Medicines and the 6th WHO Model List of Essential Medicines for Children). Geneva: World Health Organization; 2017 (WHO technical report series; no. 1006). Licence: CC BY-NC-SA 3.0 IGO.
  • 6. Temporary guidelines. Prevention, diagnosis and treatment of a new coronavirus infection. Version 16, August 18, 2022 Available at: https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/060/193/original/%D0%92%D0%9C%D0%A0_COVID-19_V16.pdf. Accessed April 2023. Russian.
  • 7. Kelkar P.S., Li J.T. Cephalosporin allergy. N Engl J Med. 2001;345(11):804-809. DOI: 10.1056/NEJMra993637
  • 8. Riezzo I., Bello S., Neri M., Turillazzi E., Fineschi V. Ceftriaxone intradermal test-related fatal anaphylactic shock: a medico-legal nightmare. Allergy. 2010;65(1):130131. DOI: 10.1111/j.1398-9995.2009.02088.x
  • 9. Imam E.A., Ibrahim M.I.M. Ceftriaxone-induced fatal anaphylaxis shock at an emergency department: a case report. J Pharm Pract Community Med. 2017;3(4):299301. DOI: 10.5530/jppcm.2017.4.75
  • 10. Puranik A. Ceftraixone induced anaphylaxis and death: a case report. Int J Basic Clin Pharmacol. 2021;10:442443. DOI: 10.18203/2319-2003.ijbcp20211030
  • 11. Ul Mustafa Z., Salman M., Raza M.H., Yasmin K., Shehzadi N., Hussain K., et al. Ceftriaxone induced cardiopulmonary arrest: a fatal case report. Arch Pharm Pract. 2021;12(1):115-117. DOI: 10.51847/JCBSlPKYby
  • 12. Calapai G., Imbesi S., Ventura-Spagnolo E., Cafeo V., Milone L., Navarra M., Gangemi S. Fatal anaphylactic shock ceftriaxone-induced in a 4-year-old child. Pediatr Emerg Care. 2016;32(1):32-33. DOI: 10.1097/PEC.0000000000000311
  • 13. Yao Y., Zhou R., Wang Y. Fatal adverse effects of injected ceftriaxone sodium in China. Pharmacoepidemiol Drug Saf. 2012;21(11):1197-1201. DOI: 10.1002/pds.3232
  • 14. Zhang Z., Lin Z., Tang L., Chen C. Analysis of severe adverse drug reactions caused by ceftriaxone sodium injection. China J Mod Med. 2010;20(14):2224-2227.
  • 15. Finucane B.Y., Ed. Complications of regional anesthesia. New York: Springer; 2007.
  • 16. Di Gregorio G., Neal J.M., Rosenquist R.W., Weinberg G.L. Clinical presentation of local anesthetic systemic toxicity: a review of published cases, 1979 to 2009. Reg Anesth Pain Med. 2010;35(2):181-187. DOI: 10.1097/aap.0b013e3181d2310b
  • 17. Dolginina S.I., Osadchiy I.A., Faerman K.M., Aleksankin A.V. A case of acute development of shock on the introduction of the drug ceftriaxone, complicated by acute coronary syndrome with ST segment elevation. Sibirskoe medicinskoe obozrenie. 2019;(4):99-102. Russian. DOI: 10.20333/2500136-2019-4-99-102
  • 18. Kuzmina A.V., Asetskaya I.L., Polivanov V.A., Zyryanov S.K., Glagolev S.V. Medication errors associated with the use of cephalosporins. Kliniceskaa mikrobiologia i antimikrobnaa himioterapia. 2017;19(1):18-24. Russian.
  • 19. Demchenkova E.Yu., Gorodetskaya G.I., Mazerkina I.A., Zhuravleva M.V., Kazakov A.S., Gorodetskiy M.V., Badriddinova L.Yu., Serebrova S.Yu. Major aspects of detection and monitoring of adverse reactions associated with cephalosporin antibiotic treatment. Safety and risk of pharmacotherapy. 2021;9(1):34-42. Russian. DOI: 10.30895/23127821-2021-9-1-34-42
  • 20. Good Pharmacovigilance Practice Rules of the Eurasian Economic Union. Approved by the Decision of the Council of the Eurasian Economic Commission dated November 3, 2016 No. 87 (as amended by the Decision of the Council of the Eurasian Economic Commission dated May 19, 2022 No. 81). Available at: www.rceth.by/Documents/9es10rsN8120220519.pdf. Accessed April 2023. Russian.
  • 21. Shalviri G., Yousefian S., Gholami K. Adverse events induced by ceftriaxone: a 10-year review of reported cases to Iranian Pharmacovigilance Centre. J Clin Pharm Ther. 2012;37(4):448-451. DOI: 10.1111/j.13652710.2011.01321.x
  • 22. Pawar A.M., Caffrey A.R. Anaphylaxis adverse events with 3rd generation cephalosporins: disproportionality analysis of the United States Food and Drug Administration Adverse Eevent Reporting system (FAERS). Value in health. 2014;17(3):A265. DOI: 10.1016/j.jval.2014.03.1544
  • 23. Cai Y., Yang L., Shangguan X., Zhao Y., Huang R. Status and safety signals of cephalosporins in children: a spontaneous reporting database study. Front Pharmacol. 2021;12:736618. DOI: 10.3389/fphar.2021.736618
  • 24. Matveev A.V., Krasheninnikov A.E., Belostotsky A.V., Andreeva D.M., Marchenko S.D., Egorova E.A. Drug anaphylactic shock. Obshhaja reanimatologija. 2020;16(3):76-84. Russian. DOI: 10.15360/1813-9779-2020-3-76-84
  • 25. Kuzmina A.V., Polivanov V.A., Asetskaya I.L., Zyryanov S.K. Medication errors associated with the use of penicillins. Kliniceskaa mikrobiologia i antimikrobnaa himioterapia. 2016;18(2):93-103. Russian.
  • 26. Letter from the Federal Service for Surveillance in Healthcare (Roszdravnadzor) on ensuring the safe use of local anesthetics. Available at: https://roszdravnadzor.gov.ru/i/upload/images/2015/11/2/1446468980.1342-1-12084.pdf. Accessed April 2023. Russian.
Views
0 Abstract
0 PDF
0 Crossref citations
Shared