Topical issues concerning treatment of intracellular bacterial pathogens in children
DOI: 10.32364/2618-8430-2020-3-4-326-335
M.S. Savenkova1,2, M.P. Savenkov1
1Pirogov Russian National Research Medical University, Moscow, Russian Federation
2Morozov Children’s City Clinical Hospital, Moscow, Russian Federation
The article considers the issues of pharmacodynamics, clinical efficacy and safety of macrolide antibiotics. It also discusses the development of microorganisms resistance to macrolides. A number of studies in vivo and in vitro on various cellular and animal models have shown that macrolides have anti-inflammatory and immunomodulatory effects. The presence of these effects in macrolides may be especially relevant during the period of increasing incidence of influenza and the new COVID-19 coronavirus infection. It is known that the severity of viral infections is associated with the release of proinflammatory cytokines. Macrolides change the entire inflammatory response cascade by weakening the excess production of cytokines. Besides, macrolides can affect the activity of phagocytes, changing their function, including chemotaxis, phagocytosis, destroying bacteria and viruses. Earlier it was reported that macrolides (in particular, clarithromycin) can interfere with the replication cycle of the influenza virus, thus leading to its production inhibition by intracellular proteolysis of hemagglutinin. One of the commonly prescribed drugs in this group is clarithromycin. The article summarizes the literature data and presents the materials of our own clinical observations on the clarithromycin treatment of children with intracellular bacterial pathogens, the causative agents of which are Mycoplasma pneumoniae and Chlamydia pneumoniae.
Keywords: macrolides, clarithromycin, intracellular bacterial pathogens, children, antibacterial therapy.
For citation: Savenkova M.S., Savenkov M.P. Topical issues concerning treatment of intracellular bacterial pathogens in children. Russian Journal of Woman and Child Health. 2020;3(4):326–335. DOI: 10.32364/2618-8430-2020-3-4-326-335.
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28. Savenkova M.S., Abramova N.A., Abramov A.D. Features of the course and treatment of respiratory infections in children with allergies. Voprosy sovremennoy pediatrii. 2014;13(5):80–85 (in Russ.).
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32. Godron A., Pereyre S., Monet C. et al. Hemolytic uremic syndrome complicating Mycoplasma pneumoniae infection. Pediatr Nephrol. 2013;28(10):2057–2060. DOI: 10.1007/s00467-013-2541-5.
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46. Volberg W.A., Koci B.J., Su W. et al. Blockade of human cardiac potassium channel human ether-a-go-go-related gene (HERG) by macrolide antibiotics. Journal of Pharmacology and Experimental Therapeutics. 2002;302(1):320–327.
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2. Wei X., Jianbo S., Yu G. et al. Clinical and CT features in pediatric patients with COVID-19 infection: Different points from adults. Pediatr Pulmonol. 2020;55(5):1169–1174. DOI: 10.1002/ppul.24718.
3. Kanoh S., Rubin B.K. Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications. Clin Microbiol Rev. 2010;23(3):590–615. DOI: 10.1128/CMR.00078-09.
4. A practical guide to anti-infective chemotherapy. Ed. L.S. Strachunsky, Yu.B. Belousova, S.N. Kozlova. M.; 2002 (in Russ.).
5. Jin-Young M., Yоung Ju J. Macrolide Therapy Respiratory Viral Infections. Mediators Inflamm. 2012;2012:649570. DOI: 10.1155/2012/649570.
6. Tagaya E., Tamaoki J., Kondo M., Nagai A. Effect of a short course of clarithromycin therapy on sputum production in patients with chronic airway hypersecretion. Chest. 2002;122(1):213–218. DOI: 10.1378/chest.122.1.213.
7. Shimizu T., Shimizu S., Hattori R. et al. In vivo and in vitro effects of macrolide antibiotics on mucus secretion in airway epithelial cells. Am J Respir Crit Care Med. 2003;168(5):581–587. DOI: 10.1164/rccm.200212-1437OC.
8. Yamaryo T., Oishi K., Yoshimine H. et al. Fourteen-member macrolides promote the phosphatidylserine receptor-dependent phagocytosis of apoptotic neutrophils by alveolar macrophages. Antimicrob Agents Chemother. 2003;47(1):48–53. DOI: 10.1128/aac.47.1.48-53.2003.
9. Belser J.A., Zeng H., Katz J.M., Tumpey T.M. Infection with highly pathogenic H7 influenza viruses results in an attenuated proinflammatory cytokine and chemokine response early after infection. J Infect Dis. 2011;203(1):40–48. DOI: 10.1093/infdis/jiq018.
10. Woo P.C., Tung E.T., Chan K.H. et al. Cytokine profiles induced by the novel swine-origin influenza A/H1N1 virus: implications for treatment strategies. J Infect Dis. 2010;201(3):346–353. DOI: 10.1086/649785.
11. Lee S.M., Gardy J.L., Cheung C.Y. et al. Systems-level comparison of host-responses elicited by avian H5N1 and seasonal H1N1 influenza viruses in primary human macrophages. PLoS One. 2009;4(12): e8072. Published 2009 Dec 14. DOI: 10.1371/journal.pone.0008072.
12. Zhirnov O., Klenk H.D. Human influenza A viruses are proteolytically activated and do not induce apoptosis in CACO-2 cells [published correction appears in Virology. 2003 Dec 20;317 (2):383]. Virology. 2003;313(1):198–212. DOI: 10.1016/s0042-6822 (03) 00264-2.
13. Miyamoto D., Hasegawa S., Sriwilaijaroen N. et al. Clarithromycin inhibits progeny virus production from human influenza virus-infected host cells. Biol Pharm Bull. 2008;31(2):217–222. DOI: 10.1248/bpb.31.217.
14. Guidelines: Features of the clinical manifestations and treatment of the disease caused by a new coronavirus infection (COVI-19) in children. Version 2 (in Russ.). (Approved by the Ministry of Health of Russia). (Electronic resource). URL: https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/050/914/original/03062020_%D0%B4%D0%B5%D1%82%D0%B8_COVID-19_v2.Pdf. (Access date: 10.08.2020).
15. Temporary guidelines. Prevention, diagnosis and treatment of new coronavirus infection (COVID-19). Version 7 (06/03/2020). (Electronic resource). (in Russ.). URL: https://static-0.rosminzdrav.ru/system/attachments/attaches/000/050/584/original/03062020_%D0%9CR_COVID-19_v7.pdf. (Access date: 10.08.2020).
16. Beloborodova N.V. Clarithromycin in Pediatrics: Focus on Respiratory Tract Infections. Pediatriya. Prilozheniye k Consilium medicum. 2007;2:40–48 (in Russ.).
17. RLS. Medicines and substances. Clarithromycin instruction. (Electronic resource). (in Russ.). URL: https://www.risnet.ru/mnn index id 1759.htm. (Assecc date: 12.08.2020).
18. Clarithromycin. (Electronic resource). URL: https://www.drugs.com/monograph/clarithromycin.html (access date 15.07.2020).
19. Amado-Rodríguez L., González-López A., López-Alonso I. et al. Anti-inflammatory effects of clarithromycin in ventilator-induced lung injury. Respir Res. 2013;14(1):52. DOI: 10.1186/1465-9921-14-52.
20. Baranov A.A., Bogomilskiy M.R., Volkov I.K. et al. The use of antibiotics in children in outpatient practice. Practical advice. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya. 2007;9(3):200–210 (in Russ.).
21. Maltsev S.V., Mansurova G.Sh. What is biofilm? Prakticheskaya meditsina. Pediatriya. 2011;5(53):7–10 (in Russ.).
22. Savenkova M.S., Savenkov M.P. Chlamydial-mycoplasma infections in children. M.: Miklos; 2011 (in Russ.).
23. Abramova N.A., Savenkova M.S., Abramov A.D. The role of intrafamilial infection in frequently ill children. Detskiye infektsii. 2014;13(1):52–58 (in Russ.).
24. Savenkova M.S., Vrublevsky S.G., Koltunov I.E. et al. Destructive pneumonia in children: complex issues of diagnosis and choice of individual etiopathogenetic therapy. Farmateca. 2015;14:46–52 (in Russ.).
25. Savenkova M.S., Savenkov M.P., Samitova E.R. et al. Mycoplasma infection: clinical forms, course features, diagnostic errors. Voprosy sovremennoy pediatrii. 2013;12(6):108–114 (in Russ.).
26. Malakhov A.B., Zinkevich A.P., Aliskandiev A.M. et al. Community-acquired pneumonia in children, algorithms for diagnosis and antibiotic therapy. Prakticheskaya pul’monologiya. 2019;2:18–26 (in Russ.).
27. Fonseca-Aten M., Okada P.J., Bowlware K.L. et al. Effect of clarithromycin on cytokines and chemokines in children with an acute exacerbation of recurrent wheezing: a double-blind, randomized, placebo-conrtolled trial. Ann Allergy Asthma Immunol. 2006;97:457–463. DOI: 10.1016/S1081-1206 (10) 60935-0.
28. Savenkova M.S., Abramova N.A., Abramov A.D. Features of the course and treatment of respiratory infections in children with allergies. Voprosy sovremennoy pediatrii. 2014;13(5):80–85 (in Russ.).
29. Averyanov A.V. Chlamydial and mycoplasma infection in the pathology of the lower respiratory tract. Lechebnoye delo. 2009;4:52–62 (in Russ.).
30. Numazaki K., Sakamoto Y., Umetsu M. et al. Therapeutic effect of clarithromycin for respiratory-tract infections in children caused by Chlamydia pneumoniae. Int J Antimicrob Agents. 2000;13(3):219–222.
31. Esposito S., Tagliabue C., Bosis S., Principi N. Levofloxacin for the treatment of Mycoplasma pneumoniae-associated meningoencephalitis in childhood. Int J Antimicrob Agents. 2011;37(5):472–475. DOI: 10.1016/j.ijantimicag.2011.01.008.
32. Godron A., Pereyre S., Monet C. et al. Hemolytic uremic syndrome complicating Mycoplasma pneumoniae infection. Pediatr Nephrol. 2013;28(10):2057–2060. DOI: 10.1007/s00467-013-2541-5.
33. Scapini J.P., Flynn L.P., Sciacaluga S. et al. Confirmed Mycoplasma pneumoniae endocarditis. Emerg Infect Dis. 2008;14(10):1664–1665. DOI: 10.3201/eid1410.080157.
34. Kuvardina N.O., Kharlamova F.S., Polesko I.V. et al. The role of combined mycoplasma and herpesvirus infection in skin lesions in children. Detskiye infektsii. 2019;18(3):5–10 (in Russ.).
35. Instructions for the medical use of the medicinal product Klacid®, extended-release film-coated tablets, 500 mg. (Electronic resource).
(in Russ.). URL: https://grls.pharm-portal.ru/grls/053e4a4e-81c0–403a-853b-2ce5160e094e?filters%5Btrade_name%5D%5B0%5D%5Btext%5D=%D0%BA%D0%BB%D0% B0% D1% 86% D0% B8% D0% B4 and page = 3 and search =% D0% BA% D0% BB% D0% B0% D1% 86% D0% B8% D0% B4 # summary. (Access date: 02.08.2020).
36. Instructions for the medical use of the drug Klacid®, granules for suspension preparation, 250 mg / 5 ml. (Electronic resource). (in Russ.). URL: https://grls.pharm-portal.ru/grls/2e60c2de-31ce-4d0f-aded-ecc334ec330d?filters%5Btrade_name%5D%5B0%5D%5Btext%5D=%D0%BA%D0%BB%D0% B0% D1% 86% D0% B8% D0% B4 and page = 2 and search =% D0% BA% D0% BB% D0% B0% D1% 86% D0% B8% D0% B4 # dosageForms. (Access date: 02.08.2020).
37. 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. Published 2019 Mar 8. DOI: 10.2147/IDR.S187226.
38. Pereyre S., Pereyre S., Goret J., Bébéar C. Mycoplasma pneumoniae: Current Knowledge on Macrolide Resistance and Treatment. Front Microbiol. 2016;7:974. DOI: 10.3389/fmicb.2016.00974.
39. Ishiguro N., Koseki N., Kaiho M. et al. Regional Differences in Prevalence of Macrolide Resistance among Pediatric Mycoplasma pneumoniae Infections in Hokkaido, Japan. Jpn J Infect Dis. 2016;69(3):186–190. DOI: 10.7883/yoken.JJID.2015.054.
40. Bébéar C.M., Pereyre S. Mechanisms of drug resistance in Mycoplasma pneumoniae. Curr Drug Targets Infect Disord. 2005;5(3):263–271. DOI: 10.2174/1568005054880109.
41. Bébéar C., Pereyre S., Peuchant O. Mycoplasma pneumoniae: susceptibility and resistance to antibiotics. Future Microbiol. 2011;6(4):423–431. DOI: 10.2217/fmb.11.18.
42. Zhao F., Liu G., Wu J. et al. Surveillance of macrolide-resistant Mycoplasma pneumoniae in Beijing, China, from 2008 to 2012. Antimicrob Agents Chemother. 2013;57(3):1521–1523. DOI: 10.1128/AAC.02060-12.
43. Xin D., Mi Z., Han X. et al. Molecular mechanisms of macrolide resistance in clinical isolates of Mycoplasma pneumoniae from China. Antimicrob Agents Chemother. 2009;53(5):2158–2159. DOI: 10.1128/AAC.01563-08.
44. Kozlov R.S., Sivaya O.V., Krechikova O.I. and others. Dynamics of resistance of Streptococcus pneumoniae to antibiotics in Russia for the period 1999–2009. (Results of a multicenter prospective study PeGAS). Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya. 2010;12(4):329–341 (in Russ.).
45. Lazareva N.B., Rebrova E.V., Ryazanova A. Yu. and other Macrolides modern position in pulmonary practice. Prakticheskaya pul’monologiya. 2019;1:66–75 (in Russ.).
46. Volberg W.A., Koci B.J., Su W. et al. Blockade of human cardiac potassium channel human ether-a-go-go-related gene (HERG) by macrolide antibiotics. Journal of Pharmacology and Experimental Therapeutics. 2002;302(1):320–327.
47. Guo D., Cai Y., Chai D. et al. The cardiotoxicity of macrolides: a systematic review. Die Pharmazie. 2010;65(9):631–640.
48. Nightingale C.H. A survey of the quality of generic clarithromycin products from 18 countries. Clin Drug Investig. 2005;25(2):135–152. DOI: 10.2165/00044011-200525020-00006.
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