Clinical pattern of antibiotic-associated syndrome in children receiving different antibacterial therapy
DOI: 10.32364/2618-8430-2021-4-3-260-267
L.B. Golden1, A.A. Ploskireva2,3, E.V. Kanner2, I.D. Kanner4
1Infectious Clinical Hospital No. 2, Moscow, Russian Federation
2Central Research Institute of Epidemiology of the Russian Federal Service for Supervision
of Consumer Rights Protection and Human Well-Being, Moscow, Russian Federation
3Pirogov Russian National Research Medical University, Moscow, Russian Federation
4Lomonosov Moscow State University, Moscow, Russian Federation
Aim: to describe the clinical pattern of antibiotic-associated diarrhea (AAD) and extraintestinal manifestations of antibiotic-associated syndrome (AAS) in children receiving different antibacterial therapy.
Patients and Methods: this prospective clinical observational study was conducted in 2017–2019. The study included 231 children aged three months to 13 years admitted for community-acquired pneumonia and received antibacterial treatment. Clinical presentations of AAS (diarrhea, vomiting, dyspepsia, stomatitis) and extraintestinal presentations of AAS were evaluated in all children within a month after antibacterial treatment. In addition, clinical presentations of AAS were compared in children who received β-lactam antibiotics or macrolides.
Results: AAS symptoms were diagnosed in 64.5% of children, while diarrhea was observed in 25%. In patients who received β-lactam antibiotics, the most common gastrointestinal (GI) signs were diarrhea, dyspepsia, loss of appetite, and constipation. In children who received ampicillin, the rate of GI signs was lower. In total, GI signs in AAS were less common in children who received macrolides compared to children who received β-lactam antibiotics. Minimal symptoms were associated with clarithromycin.
Conclusion: AAS is one of the clinical manifestations of adverse effects of antibacterials on the human organism, including AAD and extraintestinal symptoms. The highest safety profile characterizes clarithromycin in terms of AAS.
Keywords: antibiotic-associated diarrhea, antibiotic-associated syndrome, adverse drug reactions, antibacterial treatment, macrolides, adverse effects, antibiotic-associated colitis.
For citation: Golden L.B., Ploskireva A.A., Kanner E.V., Kanner I.D. Clinical pattern of antibiotic-associated syndrome in children receiving different antibacterial therapy. Russian Journal of Woman and Child Health. 2021;4(3):260–267 (in Russ.). DOI: 10.32364/2618-8430-2021-4-3-260-267.
2. Максимов М.Л., Кулагина Л.Ю., Замалутдинова А.Г. и др. Клиническая фармакология антибактериальных препаратов: учеб. пособие. Под. ред. проф. М.Л. Максимова. Казань: ИД «МеДДоК»; 2021. [Maksimov M.L., Kulagina L.Yu., Zamalutdinova A.G. et al. Clinical pharmacology of antibacterial drugs: a tutorial. Under. ed. prof. M.L. Maximova. Kazan: Publishing House "MedDoK"; 2021 (in Russ.)].
3. Hedegaard H., Warner M., Minino A.M. Drug Overdose Deaths in the United States, 1999–2015. NCHS Data Brief. 2017;(273):1–8.
4. Trubiano J.A., Pai Mangalore R., Baey Y.W. et al. Old but not forgotten: Antibiotic allergies in General Medicine (the AGM Study). Med J Aust. 2016;204(7):273. DOI: 10.5694/mja15.01329.
5. Jose J., Rao P.G., Kamath M.S., Jimmy B. Drug safety reports on complementary and alternative medicines (ayurvedic and homeopathic medicines) by a spontaneous reporting program in a tertiary care hospital. J Altern Complement Med. 2009;15(7):793–797. DOI: 10.1089/acm.2008.0128.
6. Thompson D.F., Ramos C.L. Antibiotic-Induced Rash in Patients With Infectious Mononucleosis. Ann Pharmacother. 2017;51(2):154–162. DOI: 10.1177/1060028016669525.
7. Raizman M.B., Hamrah P., Holland E.J. et al. Drug-induced corneal epithelial changes. Surv Ophthalmol. 2017;62(3):286–301. DOI: 10.1016/j.survophthal.2016.11.008.
8. Москвичев В.Г. Ургентные состояния при опийной наркомании. Лечащий врач. 2006;5:72–76. [Moskvichev V.G. Urgent states in opium addiction. Lechashchiy vrach. 2006; 5: 72–76 (in Russ.)].
9. Cheng F., Li W., Wang X. et al. Adverse drug events: Database construction and in silico prediction. Journal of Chemical Information and Modeling. 2013;53(4):744–752. DOI: 10.1021/ci4000079.
10. Rathish D., Wijerathne B., Bandara S. et al. Pharmacology education and antibiotic self-medication among medical students: a cross-sectional study. BMC Res Notes. 2017;10(1):337. DOI: 10.1186/s13104-017-2688-4.
11. Hensgens M.P., Dekkers O.M., Demeulemeester A. et al. Diarrhoea in general practice: when should a Clostridium difficile infection be considered? Results of a nested case-control study. Clin Microbiol Infect. 2014;20(12):1067–1074. DOI: 10.1111/1469-0691.12758.
12. Croswell A., Amir E., Teggatz P. et al. Prolonged impact of antibiotics on intestinal microbial ecology and susceptibility to enteric Salmonella infection. Infect. Immun. 2009;77:2741–2753. DOI: 10.1128/IAI.00006-09.
13. Klemm E.J., Wong V.K., Dougan G. Emergence of dominant multidrug-resistant bacterial clades: Lessons from history and whole-genome sequencing. Proc Natl Acad Sci U S A. 2018;115(51):12872–12877. DOI: 10.1073/pnas.1717162115.
14. Elstner C.L., Lindsay A.N., Book L.S., Matsen J.M. Lack of relationship of Clostridium difficile to antibiotic-associated diarrhoea in children. Pediatr Inf Dis. 1983;2:364–366. DOI: 10.1097/00006454-198309000-00006.
15. Turck D., Bernet J.P., Marx J. et al. Incidence and risk factors of oral antibiotic-associated diarrhea in an outpatient pediatric population. J Pediatr Gastroenterol Nutr. 2003;37:22–26. DOI: 10.1097/00005176-200307000-00004.
16. Beaugerie L., Petit J.C. Microbial-gut interactions in health and disease. Antibiotic-associated diarrhea. Best Pract. Res Clin Gastroenterol. 2004;18:337–352. DOI: 10.1016/j.bpg.2003.10.002.
17. Clausen M.R., Bonnen H., Tvede M., Mortensen P.B. Colonic fermentation to short-chain fatty acids is decreased in antibiotic-associated diarrhea. Gastroenterology. 1991;101:1497–504. DOI: 10.1016/0016-5085(91)90384-w.
18. D’Argenio V., Salvatore F. The role of the gut microbiome in the healthy adult status. Clin Chim Acta. 2015;451(Pt A):97–102. DOI: 10.1016/j.cca.2015.01.003.
19. Петри А., Сэбин К. Наглядная медицинская статистика. М.: ГЭОТАР-Медиа; 2010. [Petri A., Sabin K. Visual medical statistics. M.: GEOTAR-Media; 2010 (in Russ.)].
20. Grasberger H., Gao J., Eaton K.A. et al. 126 Intestinal Epithelial Dual Oxidase 2 Expression Induced by Gut Dysbiosis Regulates Commensal-Mucosal Homeostasis by Restricting Bacterial Translocation in the Small Intestine. Intestinal Epithelial Dual Oxidase 2 Expression Induced by Gut Dysbiosis Regulates Commensal-Mucosal Homeostasis by Restricting Bacterial Translocation in the Small Intestine. Gastroenterology. 2015;148(4):S 33. DOI: 10.1016/s0016-5085(15)30115-3.
21. Liu R., Zhang C., Hu Z. et al. A five-microRNA signature identified from genome-wide serum microRNA expression profiling serves as a fingerprint for gastric cancer diagnosis. Eur J Cancer. 2011;47(5):784–791. DOI: 10.1016/j.ejca.2010.10.025.
22. Högenauer C., Langner C., Beubler E. et al. Klebsiella oxytoca as a causative organism of antibiotic-associated hemorrhagic colitis. N Engl J Med. 2006;355(23):2418–2426. DOI: 10.1056/NEJMoa054765.
23. Berdichevski T., Keller N., Rahav G. et al. The impact of pseudomembrane formation on the outcome of Clostridium difficile-associated disease. Infection. 2013;41(5):969–977. DOI: 10.1007/s15010-013-0473-4.
24. Sailhamer E.A., Carson K., Chang Y. et al. Fulminant Clostridium difficile colitis: patterns of care and predictors of mortality. Arch Surg. 2009;144(5):433–439. DOI: 10.1001/archsurg.2009.51.
25. Pyakurel D. Pseudomembranous colitis. J Pathol Nep. 2019;9:1497–1501. DOI: 10.3126/jpn.v9i1.23378.
26. Schäffler H., Breitrück A. Clostridium difficile — From Colonization to Infection. Front. Microbiol. 2018:9;646. DOI: 10.3389/fmicb.2018.00646.
27. Zacharioudakis I. M., Zervou F. N., Pliakos E. E. et al. Colonization with toxinogenic C. difficile upon hospital admission, and risk of infection: a systematic review and meta-analysis. Am J Gastroenterol. 2015;110:381–390. DOI: 10.1038/ajg.2015.22.
28. Becattini S., Taur Y., Pamer E.G. Antibiotic-induced changes in intestinal microbiota and disease. Trends Mol Med. 2016;22(6):458–478. DOI: 10.1016 / j. molmed.2016.04.003.
29. Langner C., Dorlars D., Gross C., Rüschoff J. [Acute segmental hemorrhagic antibiotic-associated colitis]. Pathologe. 2001;22(5):339–342. DOI: 10.1007/s002920100474.
30. Tse H., Gu Q., Sze K.H. et al. A tricyclic pyrrolobenzodiazepine produced by Klebsiella oxytoca is associated with cytotoxicity in antibiotic-associated hemorrhagic colitis. J Biol Chem. 2017;292(47):19503–19520. DOI: 10.1074/jbc.M117.791558.
31. Haran J.P., Hayward G., Skinner S. et al. Factors influencing the development of antibiotic associated diarrhea in ED patients discharged home: risk of administering IV antibiotics. Am J Emerg Med. 2014;32(10):1195–1199. DOI: 10.1016/j.ajem.2014.07.015.
32. Turck D., Bernet J.P., Marx J. et al. Incidence and risk factors of oral antibiotic-associated diarrhea in an outpatient pediatric population. J Pediatr Gastroenterol Nutr. 2003;37(1):22–26. DOI: 10.1097/00005176-200307000-00004.
33. Aspin M.M., Hoberman A., McCarty J. et al. Comparative study of the safety and efficacy of clarithromycin and amoxicillin-clavulanate in the treatment of acute otitis media in children. J Pediatr. 1994;125(1):136–141. DOI: 10.1016/s0022-3476(94)70140-7.
34. Клацид® (Электронный ресурс.) URL: https://grls.rosminzdrav.ru/grls.aspx?s=%D0%BA%D0%BB%D0%B0%D1%86%D0%B8%D0%B4%20andm=tn (дата обращения: 15.08.2021). [Klacid®. (Electronic resource.) URL: https://grls.rosminzdrav.ru/grls.aspx?s=%D0%BA%D0%BB%D0%B0%D1%86%D0%B8%D0%B4%20andm=tn (access date: 15.08.2021) (in Russ.)].
35. Страчунский Л.С., Козлов С.Н. Макролиды в современной клинической практике. Смоленск: Русич; 1998. [Strachunsky L.S., Kozlov S.N. Macrolides in modern clinical practice. Smolensk: Rusich; 1998 (in Russ.)].
36. Davidson R.J. In vitro activity and pharmacodynamic/pharmacokinetic parameters of clarithromycin and azithromycin: why they matter in the treatment of respiratory tract infections. Infect Drug Resist. 2019;12:585–596. DOI: 10.2147/IDR.S187226.
37. Kastner U., Guggenbichler J.P. Influence of macrolide antibiotics on promotion of resistance in the oral flora of children. Infection. 2001;29(5):251–256. DOI: 10.1007/s15010-001-1072-3.
38. Kastner U., Guggenbichler J.P The influence of macrolide antibiotics on the fecal and oral flora. Infections in Medicine.1998;15:17–25.
39. Солдатский Ю.Л Возможности современных макролидов в лечении тонзиллита в детском возрасте. Лечащий врач. 2012;8:32–36. [Soldatskiy Y.L. Possibilities of modern macrolides in the treatment of tonsillitis in childhood. Lechashchiy vrach. 2012;8:32–36 (in Russ.)].
40. AMRmap. (Электронный ресурс.) URL: https://amrmap.ru (дата обращения: 15.08.2021). [AMRmap. (Electronic resource.) URL: https://amrmap.ru (access date: 15.08.2021) (in Russ.)].

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
















