Potential for the use of macrolides in the antimicrobial therapy of severe community-acquired pneumonia in adults

Clinical Microbiology and Antimicrobial Chemotherapy. 2019; 21(3):217-223

​ Sinopalnikov A.I., Rachina S.A., Zakharenkov I.A.
10.36488/cmac.2019.3.217-223
community-acquired pneumonia antibacterial therapy macrolides immunomodulatory effects
Section
Antimicrobials
Type
Review
Publication
Clinical Microbiology and Antimicrobial Chemotherapy. 2019; 21(3):217-223

Abstract

This paper presents mechanism of action and antimicrobial spectrum of macrolides as well as the known acquired resistance mechanisms in the common pathogens causing community-acquired pneumonia, such as Streptococcus pneumoniae and Mycoplasma pneumoniae. Non-antimicrobial (anti-inflammatory and immunomodulatory) effects of macrolides that have been found in experimental and clinical studies are described in detail. Results of clinical studies and current practice guidelines which determine potential benefits and a role of macrolides in the antibacterial therapy of severe community-acquired pneumonia in adults are reviewed.

Alexander I. Sinopalnikov

Russian Medical Academy of Continuous Professional Education, Moscow, Russia

Svetlana A. Rachina

RUDN University, Moscow, Russia

Zakharenkov I.A.

Bryansk City Hospital #1, Bryansk, Russia

  • 1. Infectious morbidity in the Russian Federation. Available at: www.rospotrebnadzor.ru. Russian.
  • 2. The top 10 causes of death: 2018 update. World Health Organization. Available at: www.who.int.
  • 3. Ramirez J.A., Wiemken T.L., Peyrani P., Arnold F.W., Kelley R., Mattingly W.A., et al. Adults Hospitalized With Pneumonia in the United States: Incidence, Epidemiology, and Mortality. Clin Infect Dis. 2017;65(11):1806-1812. DOI: 10.1093/cid/cix647
  • 4. File T.M. Jr., Marrie T.J. Burden of community-acquired pneumonia in North American adults. Postgrad Med. 2010;122(2):130-141.
  • 5. Welte T., Torres A., Nathwani D. Clinical and economic burden of community-acquired pneumonia among adults in Europe. Thorax. 2012;67:71-79.
  • 6. Sinopalnikov A.I., Fesenko O.V. Community-acquired pneumonia in adults. In: Respiratory Medicine. 2 ed., Revised and supplemented. Ed. A.G. Chuchalin, M.: GEOTAR-Media. 2017. Vol. 2, pp. 29-67. Russian.
  • 7. Sligl W.I., Marrie T.J. Severe community acquired pneumonia. Crit Care Clin. 2013;29:563-601. DOI: 10.1016/j.ccc.2013.03.009
  • 8. Hoogewerf M., Oosterheert J.J., Hak E., Hoepelman I.M., Bonten M.J. Prognostic factors for early clinical failure in patients with severe community-acquired pneumonia. Clin Microbiol Infect. 2006;12(11):1097-1104. DOI: 10.1111/j.1469-0691.2006.01535.x
  • 9. Quah J., Jiang B., Tan P.C., Siau C., Tan T.Y. Impact of microbial aetiology on mortality in severe community-acquired pneumonia. BMC Infect Dis. 2018;18(1):451. DOI: 10.1186/s12879-018-3366-4
  • 10. Liapikou A., Rosales-Mayor E., Torres A. The management of severe community acquired pneumonia in the intensive care unit. Expert Rev Respir Med. 2014;8(3):293-303. DOI: 10.1586/17476348.2014.896202
  • 11. Müller-Redetzky H., Lienau J., Suttorp N., Witzenrath M. Therapeutic strategies in pneumonia: going beyond antibiotics. Eur Respir Rev. 2015;24(137):516-524. DOI: 10.1183/16000617.0034-2015
  • 12. Chuchalin A.G., Sinopalnikov A.I., Kozlov R.S., Avdeev S.N., Tyurin I.E., Rudnov V.A., et al. Clinical guidelines on diagnosis, treatment and prevention of severe community-acquired pneumonia in adults. Pul'monologija. 2014;14(4):13-48. Russian.
  • 13. Chuchalin A.G., Sinopalnikov A.I., Kozlov R.S., et al. Project: Clinical Guidelines “Community-acquired Pneumonia in Adults,” 2018. Available at: http://spulmo.ru/obrazovatelnye-resursy/federalnye-klinicheskie-rekomendatsii/. Russian.
  • 14. Boyles T.H., Brink A., Calligaro G.L., Cohen C., Dheda K., Maartens G., et al. South African guideline for the management of community- acquired pneumonia in adults. J Thorac Dis. 2017;9(6):1469-1502. DOI: 10.21037/jtd.2017.05.31
  • 15. Athlin S., Lidman C., Lundqvist A., Naucler P., Nilsson A.C., Spindler C., et al. Management of community-acquired pneumonia in immunocompetent adults: updated Swedish guidelines 2017. Infect Dis (Lond). 2018;50(4):247-272. DOI: 10.1080/23744235.2017.1399316
  • 16. Sivapalasingam S., Steigbigel N.H. Macrolides, clindamycin, and ketolides. In: G.L. Mandell, J.E. Bennett, R. Dolin, editors. Principles & Practice of Infectious Diseases. Churchill Livingstone, 6th ed., 2004, p. 396-417.
  • 17. Garnacho-Montero J., Barrero-García I., Gómez-Prieto M.G., Martín-Loeches I. Severe community-acquired pneumonia: current management and future therapeutic alternatives. Expert Rev Anti Infect Ther. 2018;16(9):667-677. DOI: 10.1080/14787210.2018.1512403
  • 18. Rachina S.A., Sudilovskaya N.N. Clinical pharmacology of macrolides. In: A Practical Guide to Anti-Infectious Chemotherapy. Ed. L.S. Stratchounsky, S.N. Kozlov, Yu.B. Belousov. Smolensk: IACMAC, 2007. P. 101-106. Russian.
  • 19. Kozlov S.N., Kozlov R.S. Contemporary Antimicrobial Chemotherapy: A Guide for Physicians. 3rd ed., Revised and supplemented. M.: MIA LLC, 2017. 400 p. Russian.
  • 20. Edelstein P.H. Pneumococcal resistance to macrolides, lincosamides, ketolides, and streptogramin B agents: molecular mechanisms and resistance phenotypes. Clin Infect Dis. 2004;38(Suppl 4):S322-327. DOI: 10.1086/382687
  • 21. Cornick J.E., Bentley S.D. Streptococcus pneumoniae: the evolution of antimicrobial resistance to beta-lactams, fluoroquinolones and macrolides. Microbes Infect. 2012;14(7-8):573-583. DOI: 10.1016/j.micinf.2012.01.012
  • 22. Sader H.S., Flamm R.K., Streit J.M., Carvalhaes C.G., Mendes R.E. Antimicrobial activity of ceftaroline and comparator agents tested against organisms isolated from patients with communityacquired bacterial pneumonia in Europe, Asia, and Latin America. Int J Infect Dis. 2018;77:82-86. DOI: 10.1016/j.ijid.2018.10.004
  • 23. Kuzmenkov A.Yu, Trushin I.V, Avramenko A.A., et al. AMRmap: an online platform for monitoring antibiotic resistance. Klinicheskaja mikrobiologija i antimikrobnaja himioterapija. 2017;19(2):84-90. Russian.
  • 24. Averbuch D., Hidalgo-Grass C., Moses A., Engelhard D., NirPaz R. Macrolide resistance in Mycoplasma pneumoniae, Israel, 2010. Emerg Infect Dis. 2011;17(6):1079-1082. DOI: 10.3201/eid/1706.101558
  • 25. Edelstein I.A., Edelstein M.V., Romanov A.V., Zaitsev A.A., Rakovskaya I.V., Barkhatova O.I., et al. Four cases of resistance mutations in 23S rRNA gene in Mycoplasma pneumoniae isolated from the hospitalized military personnel. Klinicheskaja mikrobiologija i antimikrobnaja himioterapija. 2017;19(3):248-253. Russian.
  • 26. Bébéar C.M., Pereyre S. Mechanisms of drug resistance in Mycoplasma pneumoniae. Curr Drug Targets Infect Disord. 2005;5(3):263271. DOI: 10.2174/1568005054880109
  • 27. Waites K.B., Xiao L., Liu Y., Balish M.F., Atkinson T.P. Mycoplasma pneumoniae from the Respiratory Tract and Beyond. Clin Microbiol Rev. 2017;30(3):747-809. DOI: 10.1128/CMR.00114-16
  • 28. Edelstein I., Romanov A., Edelstein M., Otvagina M.I., Kozlov R.S. Development and application of real-time PCR assay for detection of mutations associated with macrolide resistance in Mycoplasma pneumoniae directly in clinical specimens. Proceedings of 27th European Congress of Clinical Microbiology and Infectious Diseases, Vienna, Austria. April 22-25, 2017. P#1604.
  • 29. Zarogoulidis P., Papanas N., Kioumis I., Chatzaki E., Maltezos E., Zarogoulidis K. Macrolides: from in vitro antiinflammatory and immunomodulatory properties to clinical practice in respiratory diseases. Eur J Clin Pharmacol. 2012;68(5):479-503. DOI: 10.1007/s00228-011-1161-x
  • 30. Labro M.T., Abdelghaffar H. Immunomodulation by macrolide antibiotics. J Chemother. 2001;13:3-8. DOI: 10.1179/joc.2001.13.1.3
  • 31. Tamaoki J. The effects of macrolides on inflammatory cells. Chest. 2004;125:41S-51S. DOI: 10.1378/chest.125.2_suppl.41s
  • 32. Plewig G., Schopf E. Anti-inflammatory effects of antimicrobial agents: an in vivo study. J Invest Dermatol. 1975;65(6):532-536. DOI: 10.1111/1523-1747.ep12610281
  • 33. Woo P.C., Lau S.K., Yuen K.-Y. Macrolides as immunomodulatory agents. Antiinflamm Antiallergy Agents Med Chem. 2002;1:131-141. DOI: 10.2174/1568014023355944
  • 34. Demartini G., Esposti D., Marthyn P., Lapidari A, Fraschini F, Scaglione F. Effect of multiple doses of clarithromycin and amoxicillin on IL-6, IFNgamma and IL-10 plasma levels in patients with community acquired pneumonia. J Chemother. 2004;16:82-85. DOI: 10.1179/joc.2004.16.1.82
  • 35. Zimmermann P., Ziesenitz V.C., Curtis N., Ritz N. The Immunomodulatory Effects of Macrolides – A Systematic Review of the Underlying Mechanisms. Front Immunol. 2018; 9:302. DOI: 10.3389/fimmu.2018.00302.
  • 36. Tamaoki J., Takeyama K., Tagaya E., Konno K. Effect of clarithromycin on sputum production and its rheological properties in chronic respiratory tract infections. Antimicrob Agents Chemother. 1995;39:1688-1690. DOI: 10.1128/aac.39.8.1688
  • 37. 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;122:213-218. DOI: 10.1378/chest.122.1.213
  • 38. Molinari G., Guzman C.A., Pesce A., Schito G.C. Inhibition of Pseudomonas aeruginosa virulence factors by subinhibitory concentrations of azithromycin and other macrolide antibiotics. J Antimicrob Chemother. 1993;31:681-688. DOI: 10.1093/jac/31.5.681
  • 39. KawamuraSato K., Iinuma Y., Hasegawa T., Yamashino T., Ohta M. Postantibiotic suppression effect of macrolides on the expression of flagellin in Pseudomonas aeruginosa and Proteus mirabilis. J Infect Chemother. 2001;7:51-54. DOI: 10.1007/s1015610070051
  • 40. Wozniak D.J., Keyser R. Effects of subinhibitory concentrations of macrolide antibiotics on Pseudomonas aeruginosa. Chest. 2004;125:62S-69S. DOI: 10.1378/chest.125.2_suppl.62s
  • 41. Anderson R., Steel H.C., Cockeran R., Smith A.M., von Gottberg A., de Gouveia L., et al. Clarithromycin alone and in combination with ceftriaxone inhibits the production of pneumolysin by both macrolide-susceptible and macrolide-resistant strains of Streptococcus pneumoniae. J Antimicrob Chemother. 2007;59:224-229. DOI: 10.1093/jac/dkl479
  • 42. Marrie T.J., Lau C.Y., Wheeler S.L., Wong C.J., Vandervoort M.K., Feagan B.G. A controlled trial of a critical pathway for treatment of community-acquired pneumonia. CAPITAL Study Investigators. Community-Acquired Pneumonia Intervention Trial Assessing Levofloxacin. JAMA. 2000;283:749-755. DOI: 10.1001/jama.283.6.749
  • 43. Zaharenkov I.A, Ratchina S.A., Dekhnich N.N., et al. The practice of using antimicrobial agents in adults with severe community-acquired pneumonia. Klinicheskaja mikrobiologija i antimikrobnaja himioterapija. 2019;21(Suppl. 1):28-29. Russian.
  • 44. Lonks J.R., Garau J., Gomez L., Xercavins M., Ochoa de Echagüen A., Gareen I.F., et al. Failure of macrolide antibiotic treatment in patients with bacteremia due to erythromycin-resistant Streptococcus pneumoniae. Clin Infect Dis. 2002;35:556-564. DOI: 10.1086/341978
  • 45. Rodríguez A., Mendia A., Sirvent J.M., Barcenilla F., de la Torre-Prados M.V., Solé-Violán J., et al. Combination antibiotic therapy improves survival in patients with community-acquired pneumonia and shock. Crit Care Med. 2007;35:1493-1498. DOI: 10.1097/01.CCM.0000266755.75844.05
  • 46. Waterer G.W., Somes G.W., Wunderink R.G. Monotherapy may be suboptimal for severe bacteremic pneumococcal pneumonia. Arch Intern Med. 2001;161:1837-1842. DOI: 10.1001/archinte.161.15.1837
  • 47. Martínez J.A., Horcajada J.P., Almela M., Marco F., Soriano A., García E., et al. Addition of a macrolide to a beta-lactam-based empirical antibiotic regimen is associated with lower in-hospital mortality for patients with bacteremic pneumococcal pneumonia. Clin Infect Dis. 2003;36:389-395. DOI: 10.1086/367541
  • 48. Baddour L.M., Yu V.L., Klugman K.P., Feldman C., Ortqvist A., Rello J., et al. Combination antibiotic therapy lowers mortality among severely ill patients with Pneumococcal bacteraemia. Am J Respir Crit Care Med. 2004;170:440-444. DOI: 10.1164/rccm.200311-1578OC
  • 49. Gattarello S., Borgatta B., Solé-Violán J., Vallés J., Vidaur L., Zaragoza R., et al. Decrease in mortality in severe communityacquired pneumococcal pneumonia: impact of improving antibiotic strategies (2000-2013). Chest. 2014;146:22-31. DOI: 10.1378/chest.13-1531
  • 50. De la Calle C., Ternavasio-de la Vega H.G., Morata L., Marco F., Cardozo C., García-Vidal C., et al. Effectiveness of combination therapy versus monotherapy with a third-generation cephalosporin in bacteraemic pneumococcal pneumonia: A propensity score analysis. J Infection. 2018;76:342-347. DOI: 10.1016/j.jinf.2018.01.003
  • 51. Gattarello S., Lagunes L., Vidaur L., Solé-Violán J., Zaragoza R., Vallés J., et al. Improvement of antibiotic therapy and ICU survival in severe non-pneumococcal community-acquired pneumonia: a matched case-control study. Crit Care. 2015;19:335. DOI: 10.1186/s13054-015-1051-1
  • 52. Sligl W.I., Asadi L., Eurich D.T., Tjosvold L., Marrie T.J., Majumdar S.R. Macrolides and mortality in critically ill patients with community-acquired pneumonia: a systematic review and metaanalysis. Crit Care Med. 2014;42(2):420-432. DOI: 10.1097/CCM.0b013e3182a66b9b
  • 53. Martin-Loeches I., Lisboa T., Rodriguez A., Putensen C, Annane D, Garnacho-Montero J., et al. Combination antibiotic therapy with macrolides improves survival in intubated patients with community-acquired pneumonia. Intensive Care Med. 2010;36(4):612-620. DOI: 10.1007/s00134-009-1730-y
  • 54. Restrepo M.I., Mortensen E.M., Waterer G.W., Wunderink R.G., Coalson J.J., Anzueto A. Impact of macrolide therapy on mortality for patients with severe sepsis due to pneumonia. Eur Respir J. 2009;33(1):153-159. DOI: 10.1183/09031936.00054108
  • 55. Lee J.H., Kim H.J., Kim Y.H. Is β-Lactam Plus Macrolide More Effective than β-Lactam Plus Fluoroquinolone among Patients with Severe Community-Acquired Pneumonia?: a Systemic Review and Meta-Analysis. J Korean Med Sci. 2017;32(1):77-84. DOI: 10.3346/jkms.2017.32.1.77
  • 56. O’Brien M.E., Restrepo M.I., Martin-Loeches I. Update on the combination effect of macrolide antibiotics in communityacquired pneumonia. Respir Invest. 2015;53(5):201-209. DOI: 10.1016/j.resinv.2015.05.003
Views
0 Abstract
0 PDF
0 Crossref citations
Shared