Major Aspects of Detection and Monitoring of Adverse Reactions Associated with Cephalosporin Antibiotic Treatment

Widespread use of cephalosporin antibiotics in clinical practice calls for greater attention to the risk of adverse drug reactions. Information on serious or unexpected adverse events reported during post-marketing experience is submitted to national and international pharmacovigilance databases. Analysis of these reports helps to identify new adverse drug reactions.

The aim of the study was to analyse the safety profile of cephalosporin antibiotics based on spontaneous reports in the international VigiBase database.

Materials and methods: the analysis of the adverse reaction profile of cephalosporin antibiotics was based on MedDRA system organ classes and included spontaneous reports submitted to VigiBase from the moment of its creation until August 2020.

Results: the authors identified the most clinically significant adverse reactions for different cephalosporin generations. They compared and analysed information on adverse events in VigiBase and in patient information leaflets of medicinal products authorised in the Russian Federation. It was demonstrated that some serious events described in VigiBase spontaneous reports for V-generation cephalosporins are not included in the “Side effects” section of the patient information leaflets. According to VigiBase, the use of ceftaroline was associated with the development of generalised exfoliative dermatitis, Stevens–Johnson syndrome, tubulointerstitial nephritis, while the use of ceftolozane was associated with acute kidney injury, renal insufficiency, sepsis, pneumonia, and respiratory insufficiency.

Conclusion: reporting of unexpected and serious adverse drug reactions to cephalosporin antibiotics is an important task of healthcare practitioners. Availability of information on class-specific and generation-specific serious adverse reactions will help predict and prevent their development.

1. Kuzmina AV, Polivanov VA, Asetskaya IL, Zyryanov SK. Safety issues with the use of antimicrobials in current clinical practice. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya = Clinical Microbiology and Antimicrobial Chemotherapy. 2015;17(2):146–56 (In Russ.)

2. Nikolaeva TN, Romanova SV, Romanov BK, Alyautdin RN. Analysis of safety data of clinical trials in Russia in 2012–2016. Meditsinskaya etika = Medical Ethics. 2017;5(1):60–2 (In Russ.)

3. Glagolev SV, Gorelov KV, Chizhova DA. Development of the pharmacovigilance system in the Russian Federation. Vestnik Roszdravnadzora = Bulletin of Roszdravnadzor. 2019;(2):72–8 (In Russ.). https://doi.org/10.21518/1561-5936-2019-03-8-14

4. Dash CH. Penicillin allergy and the cephalosporins. J Antimicrob Chemother. 1975;1(3 Suppl):107–18. https://doi.org/10.1093/jac/1.suppl_3.107

5. Moreno E, Macías E, Dávila I, Laffond E, Ruiz A, Lorente F. Hypersensitivity reactions to cephalosporins. Expert Opin Drug Saf. 2008;7(3):295–304. https://doi.org/10.1517/14740338.7.3.295

6. Yakovlev SV. The current significance of cephalosporins in the treatment of infections in a hospital. RMZh = RMJ. 2005;(10):720 (In Russ.)

7. Demko IV. Medication allergy. Sibirskoe meditsinskoe obozrenie = Siberian Medical Review. 2013;(4):83–7 (In Russ.)

8. Payne LE, Gagnon DJ, Riker RR, Seder DB, Glisic EK, Morris JG, Fraser GL. Cefepime-induced neurotoxicity: a systematic review. Crit Care. 2017;21(1):276. https://doi.org/10.1186/s13054-017-1856-1

9. Grill MF, Maganti R. Cephalosporin-induced neurotoxicity: clinical manifestations, potential pathogenic mechanisms, and the role of electroencephalographic monitoring. Ann Pharmacother. 2008;42(12):1843–50. https://doi.org/10.1345/aph.1L307

10. Dickson SD, Salazar KC. Diagnosis and management of immediate hypersensitivity reactions to cephalosporins. Clin Rev Allergy Immunol. 2013;45(1):131–42. https://doi.org/10.1007/s12016-013-8367-x

11. Uri JV, Parks DB. Disulfiram-like reaction to certain cephalosporins. Ther Drug Monit. 1983;5(2):219–24. https://doi.org/10.1097/00007691-198306000-00013

12. Mergenhagen KA, Wattengel BA, Skelly MK, Clark CM, Russo TA. Fact versus fiction: a review of the evidence behind alcohol and antibiotic interactions. Antimicrob Agents Chemother. 2020;64(3):e02167-19. https://doi.org/10.1128/AAC.02167-19

13. Park GH, Kim S, Kim MS, Yu YM, Kim GH, Lee JS, Lee E. The association between cephalosporin and hypoprothrombinemia: a systematic review and meta-analysis. Int J Environ Res Public Health. 2019;16(20):3937. https://doi.org/10.3390/ijerph16203937

14. Mylonakis E, Ryan ET, Calderwood SB. Clostridium difficileassociated diarrhea: a review. Arch Intern Med. 2001;161(4):525– 33. https://doi.org/10.1001/archinte.161.4.525