Preview

Safety and Risk of Pharmacotherapy

Advanced search

Risk Factors and Characteristics of Adverse Reactions Associated with the Use of Beta-Lactam Antibiotics in Older Patients

https://doi.org/10.30895/2312-7821-2021-9-3-128-135

Abstract

The frequency of adverse drug reactions (ADRs) in older patients is approximately 11.0%, according to scientific literature. Antibiotics are the third largest group (19.5%) of medicinal products in terms of ADR frequency in geriatric patients. Beta-lactam antibiotics are the empiric treatment of choice for older outpatients and inpatients with community-acquired pneumonia. The mortality in this group of patients accounts for 85% of the overall mortality from community-acquired pneumonia. The aim of the study was to analyse scientific data on risk factors and characteristics of adverse drug reactions associated with the use of beta-lactam antibiotics in older patients. Specificity of ADRs to beta-lactam antibiotics in this group of patients is due to age-related changes in pharmacokinetics and pharmacodynamics as well as polymorbidity and polypharmacy. The analysis of scientific literature demonstrated that there have not been so many pharmacoepidemiological studies in this group of patients, and their results have been inconsistent. The frequency, causes, and clinical manifestations of ADRs in geriatric patients are diverse and differ considerably from those in younger patients. Of the most widely used antibiotics, ceftriaxone and cefaclor exhibited a statistically lower risk of ADRs in older patients than in younger patients. At the same time, ceftriaxone was associated with a relatively higher frequency of serious ADRs in older patients as compared to younger patients, whereas the frequency of serious ADRs was lower with cefaclor. The likelihood of nephrotoxic, neurotoxic, and hepatotoxic ADRs associated with the use of beta-lactam antibiotics is becoming more and more obvious but it is still underestimated in clinical and geriatric practice. Safety monitoring, therapeutic drug monitoring with due consideration of ADR risk factors in older patients, and inclusion of older patients in clinical trials of antimicrobial drugs, would improve efficacy and safety of antibiotic treatment.

About the Authors

E. A. Sokova
Scientifc Centre for Expert Evaluation of Medicinal Products
Russian Federation

Elena A. Sokova, Cand. Sci. (Med.), Associate Professor

8/2 Petrovsky Blvd, Moscow 127051, Russian Federation



V. V. Arkhipov
Scientifc Centre for Expert Evaluation of Medicinal Products
Russian Federation

Vladimir V. Arkhipov, Dr. Sci. (Med.), Associate Professor

8/2 Petrovsky Blvd, Moscow 127051, Russian Federation



O. A. Demidova
Scientifc Centre for Expert Evaluation of Medicinal Products
Russian Federation

Olga A. Demidova, Cand. Sci. (Pharm.)

8/2 Petrovsky Blvd, Moscow 127051, Russian Federation



I. A. Mazerkina
Scientifc Centre for Expert Evaluation of Medicinal Products
Russian Federation

Irina A. Mazerkina, Cand. Sci. (Med.)

8/2 Petrovsky Blvd, Moscow 127051, Russian Federation



T. V. Alexandrova
Scientifc Centre for Expert Evaluation of Medicinal Products
Russian Federation

Tatiana V. Alexandrova, Cand. Sci. (Med.)

8/2 Petrovsky Blvd, Moscow 127051, Russian Federation



M. V. Zhuravleva
Scientifc Centre for Expert Evaluation of Medicinal Products; I. M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Marina V. Zhuravleva, Dr. Sci. (Med.), Professor

8/2 Petrovsky Blvd, Moscow 127051, Russian Federation

8/2 Trubetskaya St., Moscow 119991, Russian Federation



References

1. Silva C, Ramalho C, Luz I, Monteiro J, Fresco P. Drug-related problems in institutionalized, polymedicated older patients: opportunities for pharmacist intervention. Int J Clin Pharm. 2015;37(2):327–34. https://doi.org/10.1007/s11096-014-0063-2

2. Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. Lancet. 2000;356(9237):1255–9. https://doi.org/10.1016/S0140-6736(00)02799-9

3. Alhawassi TM, Krass I, Bajorek BV, Pont LG. A systematic review of the prevalence and risk factors for adverse drug reactions in the elderly in the acute care setting. Clin Interv Aging. 2014;9:2079–86. https://doi.org/10.2147/CIA.S71178

4. Pedros C, Formiga F, Corbella X, Arnau JM. Adverse drug reactions leading to urgent hospital admission in an elderly population: prevalence and main features. Eur J Clin Pharmacol. 2016;72(2):219–26. https://doi.org/10.1007/s00228-015-1974-0

5. Hailu BY, Berhe DF, Gudina EK, Gidey K, Getachew M. Drug related problems in admitted geriatric patients: the impact of clinical pharmacist interventions. BMC Geriatr. 2020;20(1):13. https://doi.org/10.1186/s12877-020-1413-7

6. Strachunsky LS, Belousov YB, Kozlov SN, eds. Practical guide to anti-infectious chemotherapy. Smolensk: MAKMAKH;2007 (In Russ.)

7. Zagaria MAE. Addressing challenges of infection: antibiotic adverse drug events in older adults. US Pharm. 2019;44(4):6–12.

8. Peyrani P, Mandell L, Torres A, Tillotson GS. The burden of community-acquired bacterial pneumonia in the era of antibiotic resistance. Expert Rev Respir Med. 2019;13(2):139–52. https://doi.org/10.1080/17476348.2019.1562339

9. Woo SD, Yoon J, Doo GE, Park Y, Lee Y, Lee SH, et al. Common causes and characteristics of adverse drug reactions in older adults: a retrospective study. BMC Pharmacol Toxicol. 2020;21:87. https://doi.org/10.1186/s40360-020-00464-9

10. van Marum RJ. Underrepresentation of the elderly in clinical trials, time for action. Br J Clin Pharmacol. 2020;86(10):2014–6. https://doi.org/10.1111/bcp.14539

11. Davies EA, O’Mahony MS. Adverse drug reactions in special populations — the elderly. Br J Clin Pharmacol. 2015;80(4):796–807. https://doi.org/10.1111/bcp.12596

12. Lee SJ, Walter LC. Prevention and screening. In: Halter JB, Ouslander JG, Studenski S, High KP, Asthana S, Supiano MA, Ritchie C, eds. Hazzard’s Geriatric Medicine and Gerontology. 7th ed. New York: McGraw-Hill Education; 2017.

13. Shi S, Klotz U. Age-related changes in pharmacokinetics. Curr Drug Metab. 2011;12(7):601–10. https://doi.org/10.2174/138920011796504527

14. Mangoni AA, Jackson SHD. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol. 2004;57(1):6–14. https://doi.org/10.1046/j.1365-2125.2003.02007.x

15. Perazella МА. Pharmacology behind common drug nephrotoxicities. Clin J Am Soc Nephrol. 2018;13(12):1897–908. https://doi.org/10.2215/CJN.00150118

16. Imani S, Buscher H, Marriott D, Gentili S, Sandaradura I. Too much of a good thing: a retrospective study of β-lactam concentration-toxicity relationships. J Antimicrob Chemother. 2017;72(10):2891–7. https://doi.org/10.1093/jac/dkx209

17. Gorbachev VI, Bragina NV. Blood-brain barrier from the point of view of anesthesiologist. Review. Part 1. Vestnik intensivnoy terapii im. A.I. Saltanova = Annals of Critical Care. 2020;(3):35–45 (In Russ.) https://doi.org/10.21320/1818-474X-2020-3-35-45

18. Bhattacharyya S, Darby R, Berkowitz AL. Antibiotic-induced neurotoxicity. Curr Infect Dis Rep. 2014;16(12):448. https://doi.org/10.1007/s11908-014-0448-3

19. Sutter R, Rüegg S, Tschudin-Sutter S. Seizures as adverse events of antibiotic drugs: a systematic review. Neurology. 2015;85(15):1332–41. https://doi.org/10.1212/WNL.0000000000002023

20. 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

21. Cock HR. Drug-induced status epilepticus. Epilepsy Behav. 2015;49:76–82. https://doi.org/10.1016/j.yebeh.2015.04.034

22. Appa AA, Jain R, Rakita RM, Hakimian S, Pottinger PS. Characterizing cefepime neurotoxicity: a systematic review. Open Forum Infect Dis. 2017;4(4):ofx170. https://doi.org/10.1093/ofid/ofx170

23. Kim S, Lee I, Park S, Lee J. Cefepime neurotoxicity in patients with renal insufficiency. Ann Rehabil Med. 2012;36(1):159–62. https://doi.org/10.5535/arm.2012.36.1.159

24. Charach G, Argov O, Nochomovich H, Geiger K, Charach L, Steinvil R, et al. Cephalosporin-induced neurological toxi­city in elderly patients with preserved renal function. Arch Med. 2016;(8):6. https://doi.org/10.21767/1989-5216.1000181

25. Putilina MV. Comorbidity in elderly patients. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2016;116(5):106–11 (In Russ.) https://doi.org/10.17116/jnevro201611651106-111

26. Anosova E, Filimonov M, Proschaev K, Romanchikov A. Polymorbidity — polypharmacy — deprescribing: current trends in pharmacotherapy of geriatric patients and its optimization. Vrach = Doctor. 2019;(6):17–23 (In Russ.) https://doi.org/10.29296/25877305-2019-06-04

27. Violan C, Foguet-Boreu Q, Flores-Mateo G, Salisbury C, Blom J, Freitag M, et al. Prevalence, determinants and patterns of multimorbidity in primary care: а systematic review of observational studies. PLoS One. 2014;9(7):е102149. https://doi.org/10.1371/journal.pone.0102149

28. Souza DLB, Oliveras-Fabregas A, Minobes-Molina E, de Camargo Cancela M, Galbany-Estragués P, Jerez-Roig J. Trends of multimorbidity in 15 European countries: a population-based study in community-dwelling adults aged 50 and over. BMC Public Health. 2021;21(1):76. https://doi.org/10.1186/s12889-020-10084-x

29. Leelakanok N, Holcombe AL, Lund BC, Gu X, Schweizer ML. Association between polypharmacy and death: a systematic review and meta-analysis. J Am Pharm Assoc. 2017;57(6):729–38. https://doi.org/10.1016/j.japh.2017.06.002

30. Oscanoa T, Lizaraso F, Carvajal A. Hospital admissions due to adverse drug reactions in the elderly. A meta-analysis. Eur J Clin Pharmacol. 2017;73(6):759–70. https://doi.org/10.1007/s00228-017-2225-3

31. Yu YM, Shin WG, Lee JY, Choi SA, Jo YH, Youn SJ, et al. Patterns of adverse drug reactions in different age groups: analysis of spontaneous reports by community pharmacists. PLoS One. 2015;10(7):e0132916. https://doi.org/10.1371/journal.pone.0132916

32. Ribeiro-Vaz I, Marques J, Demoly P, Polonia J, Gomes ER. Drug-induced anaphylaxis: a decade review of reporting to the Portuguese Pharmacovigilance Authority. Eur J Clin Pharmacol. 2013;69(3):673–81. https://doi.org/10.1007/s00228-012-1376-5

33. Moore VR, Glassman PA, Au A, Good CB, Leadholm TC, Cunningham FE. Adverse drug reactions in the Veterans Affairs healthcare system: Frequency, severity, and causative medications analyzed by patient age. Am J Health Syst Pharm. 2019;76(5):312–9. https://doi.org/10.1093/ajhp/zxy059

34. Wierenga PC, Buurman BM, Parlevliet JL, van Munster BC, Smorenburg SM, Inouye SK, de Rooij S. Association between acute geriatric syndromes and medication-related hospital admissions. Drugs Aging. 2012;29(8):691–9.


Supplementary files

Review

For citations:


Sokova E.A., Arkhipov V.V., Demidova O.A., Mazerkina I.A., Alexandrova T.V., Zhuravleva M.V. Risk Factors and Characteristics of Adverse Reactions Associated with the Use of Beta-Lactam Antibiotics in Older Patients. Safety and Risk of Pharmacotherapy. 2021;9(3):128-135. (In Russ.) https://doi.org/10.30895/2312-7821-2021-9-3-128-135

Views: 1370


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2312-7821 (Print)
ISSN 2619-1164 (Online)