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Modern trends in identification of causative agents in infective endocarditis

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Advances in the diagnosis and treatment of patients with infectious endocarditis are limited by the high frequency of cases with an unknown etiology and imperfection of microbiological (cultural) methods. To overcome these problems new approaches to the identification of infectious endocarditis pathogens were introduced, which allowed achieving certain positive results. However, it should be noted that despite the wide variety of diagnostic tools currently used, there is no ideal method for etiological laboratory diagnosis of infectious endocarditis. The article discusses the features and place of immunochemical, molecular biological (MALDI-TOF MS, real-time PCR, sequencing, in situ fluorescence hybridization, metagenomic methods, etc.), immunohistochemical methods, and their advantages and limitations.

About the Authors

E. O. Kotova
Peoples’ Friendship University of Russia (RUDN)
Russian Federation

Elizaveta O. Kotova


eLibrary SPIN 6397-6480

E. A. Domonova
Central Research Institute of Epidemiology
Russian Federation

Elvira A. Domonova


eLibrary SPIN 1781-8807

Zh. D. Kobalava
Peoples’ Friendship University of Russia (RUDN)
Russian Federation

Zhanna D. Kobalava


eLibrary SPIN 9828-5409

J. L. Karaulova
Peoples’ Friendship University of Russia (RUDN)
Russian Federation

Yuliya L. Karaulova


eLibrary SPIN 8967-1163

A. S. Pisaryuk
Peoples’ Friendship University of Russia (RUDN); Moscow City Hospital named after V.V. Vinogradov
Russian Federation

Alexandra S. Pisaryuk


eLibrary SPIN 5602-1059

A. V. Balatskiy
Lomonosov Moscow State University
Russian Federation

Alexander V. Balatsky


eLibrary SPIN 3106-1840

V. G. Akimkin
Central Research Institute of Epidemiology
Russian Federation

Vasily G. Akimkin


eLibrary SPIN 4038-7455


1. Habib G., Lancellotti P., Erba P., et al., EURO-ENDO Investigators. Clinical presentation, aetiology and outcome of infective endocarditis. Results of the ESC-EORP EURO-ENDO (European infective endocarditis) registry: a prospective cohort study. Eur Heart J. 2019;40(39):3222-32. DOI:10.1093/eurheartj/ehz620.

2. Murdoch D., Corey G., Hoen B., et. all. Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century: the International Collaboration on Endocarditis-Prospective Cohort study. Arch Intern Med. 2009;169:463-73. DOI:10.1001/archinternmed.2008.603.

3. Shevchenko Yu.L., ed. Infective endocarditis, manual. Moscow: Geotar-Media; 2012 (In Russ.)

4. Danilov A.I., Alekseeva I.V., Asner T.V., et al. Real practice of therapy of infective endocarditis in the Russian Federation: intermediate results of the MAESTRO study. Clinical Microbiology and Antimicrobial Chemotherapy. 2013;15(2); suppl 1:18-9 (In Russ.)

5. Kotova E.O., Domonova E.A., Karaulova Yu.L., et al. Infective endocarditis: Importance of molecular biology techniques in the etiological diagnosis. Ter Arkhiv. 2016;88(11):62-7 (In Russ.) DOI:10.17116/terarkh2016881162-67.

6. Habib G., Lancellotti P., Antunes MJ., et al. 2015 ESC guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J. 2015;36:3075-128. DOI:10.1093/eurheartj/ehv319.

7. Morpeth S., Murdoch D., Cabell C., et. al. Non-HACEK gram-negative bacillus endocarditis. Ann Intern Med. 2007;147:829-35. DOI:10.7326/0003-4819-147-12-200712180-00002.

8. Korber F., Zeller M., Grünstäudl B., et. al. SeptiFast versus blood culture inclinical routine – A report on 3 years experience. Wien Klin Wochenschr . 2017;129:427-34. DOI:10.1007/s00508-017-1181-3.

9. Fukuchi T., Iwata K., Ohji G. Failure of early diagnosis of infective endocarditis in Japan - a retrospective descriptive analysis. Medicine (Baltimore). 2014;93:237. DOI:10.1097/MD.0000000000000237

10. Habib G., Hoen B., Tornos P., Thuny F., et al. Guidelines on the prevention, diagnosis and treatment of infective endocarditis (new version 2009): the Task Force on the Prevention, Diagnosis and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC), endorsed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the International Society of Chemotherapy (ISC) for Infection and Cancer. Eur Heart J. 2009;30:2369-413. DOI:10.1093/eurheartj/ehp285

11. Liesman R., Pritt B., Maleszewski J., Patel R. Laboratory diagnosis of infective endocarditis. J Clin Microbiol. 2017;55:259-2608. DOI:10.1128/JCM.00635-17.

12. Spicyn A.N., Utkin D.V., Kuklev V.E., et al. Application of MALDI mass spectrometry in the diagnosis of especially dangerous infectious diseases: current state and prospects. Problems of Especially Dangerous Infections. 2014; 3:77-82 (In Russ.) DOI:10.21055/0370-1069-2014-3-77-82.

13. Lim D., Simpson J., Kearns E., Kramer M. Current and Developing technologies for monitoring agents of bioterrorism and biowarfare. Clin Microbiol Rew. 2005;18(4):583-607. DOI:10.1128/CMR.18.4.583-607.2005.

14. Peruski A.H., Peruski L.F.Jr. Immunological Methods for Detection and Identification of Infectious Disease and Biological Warfare Agents. Clin Diagn Lab Immunol. 2003;10(4):506-13. DOI:10.1128/cdli.10.4.506-513.2003.

15. Raoult D., Casalta J., Richet H., et al. Contribution of systematic serological testing in diagnosis of infective endocarditis. J Clin Microbiol. 2005;43:5238-42. DOI:10.1128/JCM.43.10.5238-5242.2005.

16. Houpikian P., Raoult D. Blood culture-negative endocarditis in a reference center: etiologic diagnosis of 348 cases. Medicine (Baltimore). 2005;84:162-73. DOI:10.1097/

17. Maurin M., Eb F., Etienne J., Raoult D. Serological cross-reactions between Bartonella and Chlamydia species: implications for diagnosis. J Clin Microbiol. 1997;35:2283-7. DOI:10.1128/jcm.35.9.2283-2287.1997.

18. Baddour L., Wilson W., Bayer A., et al. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association. Circulation. 2015;132:1435-86. DOI:10.1161/CIR.0000000000000296.

19. Jenkins C., Ling L.C., Ciesielczuk H.L., et al. Detection and identification of bacteria in clinical samples by 16S rRNA gene sequencing: comparison of two different approaches in clinical practice. J Med Microbiol. 2012;61:483-8. DOI:10.1099/jmm.0.030387-0.

20. Tattevin P., Revset M., Lefort A., Michelet C., Lortholary O. Fungal endocarditis: current challenges. Int J Antimicrobiol Agents. 2014;44:290-4. DOI:10.1016/j.ijantimicag.2014.07.003.

21. Mongelli G., Romeo M. A., Denaro C., et al. Added value of multi-pathogen probe based real-time PCR SeptiFast in the rapid diagnosis of bloodstream infections in patients with bacteraemia. J Med Microbiol. 2015;64(7):670-5. DOI:10.1099/jmm.0.000074.

22. Suberviola B., Márquez-López A.,, Castellanos-Ortega A., et al. Microbiological diagnosis of sepsis: polymerase chain reaction system versus blood cultures. Am J Crit Care. 2016;25(1):68-75. DOI:10.4037/ajcc2016728.

23. Casalta J., Gouriet F., Roux V., et al. Evaluation of the Light Cycler Septi Fast test in the rapid etiologic diagnostic of infectious endocarditis. Eur J Clin Microbiol Infect Dis. 2009;28(6):569-73. DOI:10.1007/s10096-008-0672-6.

24. Shrestha N., Ledtke C., Wang H., et al. Heart valve culture and sequencing to identify the infective endocarditis pathogen in surgically treated patients. Ann Thorac Surg. 2015;99:33-7. DOI:10.1016/j.athoracsur.2014.07.028.

25. Cheng J., Hu H., Kang Y., et al. Identification of pathogens in culture-negative infective endocarditis cases by metagenomic analysis. Ann Clin Microbiol Antimicrob. 2018;17(1):43. DOI:10.1186/s12941-018-0294-5.

26. Cheng J., Hu H., Fang W., et al. Detection of pathogens from resected heart valves of patients with infective endocarditis by next-generation sequencing. Int J Infect Dis. 2019;83:148-53. DOI:10.1016/j.ijid.2019.03.007.

27. Popov D.A., Ovseenko S.T., Vostrikova T.Ju. Express-identification of positive blood cultures using the direct MALDI-TOF mass spectrometry method. Anesthesiology and Reanimatology. 2015;60(5):71- 5 (In Russ.)

28. Maneg D., Sponsel J., Muller I., et al. Advantages and limitations of direct PCR amplification of bacterial 16S-rDNA from resected heart tissue or swabs followed by direct sequencing for diagnosing infective endocarditis: a retrospective analysis in the routine clinical setting. BioMed Res Int. 2016;2016:e7923874. DOI:10.1155/2016/7923874.

29. Harris K., Yam T., Jalili S., et al. Service evaluation to establish the sensitivity, specificity and additional value of broad-range 16S rDNA PCR for the diagnosis of infective endocarditis from resected endocardial material in patients from eight UK and Ireland hospitals. Eur J Clin Microbiol Infect Dis. 2014;33:2061-6. DOI:10.1007/s10096-014-2145-4.

30. Edouard S., Nabet C., Lepidi H., et al. Bartonella, a common cause of endocarditis: a report on 106 cases and review. J Clin Microbiol. 2015;53:824-9. DOI:10.1128/JCM.02827-14.

31. Varani S. et al. Diagnosis of bloodstream infections in immunocompromised patients by real-time PCR. J Infect. 2009;58(5):346-51. DOI:10.1016/j.jinf.2009.03.001.

32. Tsalik E., Jones D., Nicholson B., et al. Multiplex PCR to diagnose blood stream infections in patients admitted from the emergency department with sepsis. J Clin Microbiol. 2010;48(1):26-33. DOI:10.1128/JCM.01447-09.

33. Rovery C., Greub G., Lepidi H., et al. PCR detection of bacteria on cardiac valves of patients with treated bacterial endocarditis. J Clin Microbiol. 2005;43:163-7. DOI:10.1128/JCM.43.1.163-167.2005.

34. Imai A., Gotoh K., Asano Y., et al. Comprehensive metagenomic approach for detecting causative microorganisms in culture-negative infective endocarditis. Int J Cardiol. 2014;172:288-9. DOI:10.1016/j.ijcard.2013.12.197.

35. Speranskaya A.S. Sequencing Next Gen. Molecular diagnostics of infectious diseases. In: Pokrovsky V.I., Tvorogova M.G., Shipulina G.A., eds. Moscow: RIPOL classic; 2018: 145-71 (In Russ.)

36. Fukui Y., Aoki K., Okuma S., et al. Metagenomic analysis for detecting pathogens in culture-negative infective endocarditis. J Infect Chemother. 2015;21:882-4. DOI:10.1016/j.jiac.2015.08.007.

37. Costabile A., Santarelli S., Claus S.P., et al. Effect of breadmaking process on in vitro gut microbiota parameters in irritable bowel syndrome. PLoS One. 2014;9(10):e111225. DOI:10.1371/journal.pone.0111225.

38. Bruzzese E., Callegari M.L., Raia V., et al. Disrupted intestinal microbiota and intestinal inflammation in children with cystic fibrosis and its restoration with Lactobacillus GG: a randomised clinical trial. PLoS One. 2014;9(2):e87796. DOI:10.1371/journal.pone.0087796.

39. Barancevich E.P., Barancevich N.E. Application of MALDI-TOF mass spectrometry in clinical microbiology. Translational Medicine. 2014;(3):23-8 (In Russ.). DOI:10.18705/2311-4495-2014-0-3-23-28.

40. Malek-Elkowska M., Elikowski W., Lisiecka M., Szyszka A. Microbiological diagnostics of infective endocarditis in the light of the new guidelines of the European Society of Cardiology with particular focus on the molecular methods. Przegl Lek. 2016;73(7):525-9.

41. Croxatto A., Prod’hom G., Greub G. Applications of MALDI-TOF mass spectrometry in clinical diagnostic microbiology. FEMS Microbiol Rev. 2011;36:380-407. DOI:10.1111/j.1574-6976.2011.00298.x

42. Bader O., Weig M., Taverne-Ghadwal L., et al. Improved clinical laboratory identification of human pathogenic yeasts by matrix-assisted laser desorption ionization time-off light mass spectrometry. Clin Microbiol Infect. 2011; 17:1359–65. DOI:10.1111/j.1469-0691.2010.03398.x.

43. Kosikowska U., Stępień-Pyśniak D., Pietas-Ożga D., et al. Application of MALDI-TOF MS mass spectrometry in the identification of bacteria isolated from clinical materials from humans and animals. Diagn Lab. 2015;51:23-30 (In Polsk.)

44. De Carolis E., Vella A., Vaccaro L., et al. Development and Validation of an In-House Database for MatrixAssisted Laser Desorbtion Ionization-Time of Flight Mass Spectrometry-Based Yeast Identification Using a Fast Protein Extraction Procedure. J Clin Microbiol. 2014;52(5):1453-8. DOI:10.1128/JCM.03355-13.

45. Patel R. MALDI-TOF Mass Spectrometry: Transformative Proteomics for Clinical Microbiology. Clin Chem. 2013;59(2): 340-2. DOI:10.1373/clinchem.2012.183558.

46. Ferreira L., Vega Castaño S.V., Sánchez-Juanes F., et al. Identification of Brucella by MALDI-TOF Mass Spectrometry. Fast and Reliable Identification from Agar Plates and Blood Cultures. PLoS One. 2010;5(12):14235. DOI:10.1371/journal.pone.0014235.

47. Lista F., Reubsaet F., De Santis R., et al. Reliable identification at the species level of Brucella isolates with MALDI-TOF-MS. BMC Microbiology. 2011;11:267. DOI:10.1186/1471-2180-11-267.

48. Prod’hom G., Bizzini A., Durussel C., et al. Matrix-assisted laser desorption ionization-time of flight mass spectrometry for direct bacterial identification from positive blood culture pellets. J Clin Microbiol. 2010;48(4):1481-3. DOI:10.1128/JCM.01780-09.

49. Ferreira L., Sánchez-Juanes F., González-Avila M., et al. Direct identification of urinary tract pathogens from urine samples by matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol. 2010;48(6):2110-5. DOI:10.1128/JCM.02215-09.

50. Lominadze G.G., Semenova E.A., Motuzova O.V., et al. Using the MALDI-TOF mass spectrometry method to accelerate the identification of microorganisms in blood cultures of patients with suspected sepsis. Laboratory LPU. 2014;4:17-20 (In Russ.).

51. Wüppenhorst N., Consoir C., Lörch D., Schneider C. Direct identification of bacteria from charcoalcontaining blood culture bottles using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. Eur J Clin. Microbiol Infect Dis. 2012;31(10):2843-50. DOI:10.1007/s10096-012-1638-2.

52. Mestas J., Felsenstein S., Bard J.D. Direct identification of bacteria from positive BacT/ALERT blood culture bottles using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. Diagn Microbiol Infect Dis. 2014;80(3):193-6. DOI:10.1016/j.diagmicrobio.2014.07.008.

53. Monteiro J., Inoue F.M., Lobo A.P., et al. Fast and reliable bacterial identification direct from positive blood culture using a new TFA sample preparation protocol and the Vitek MS system. J. Microbiol. Meth. 2015;109:157-9. DOI:10.1016/j.mimet.2014.12.009

54. Machen A., Drake T., Wang Y. Same Day Identification and full panel antimicrobial susceptibility testing of bacteria from Positive blood culture bottles made possible by a combined lysis-filtration method with MALDI-TOF VITEK mass spectrometry and the VITEK2 system. PLoS One. 2014;9(2):e87870. DOI:10.1371/journal.pone.0087870

55. Hooff G.P., van Kampen J.J., Meesters R.J., et al. Characterization of β-lactamase enzyme activity in bacterial lysates using MALDI-mass spectrometry. J Proteome Res. 2012;11:79-84. DOI:10.1021/pr200858r.

56. Kostrzewa M., Sparbier K., Maier T., Schubert S. MALDI-TOF MS: an upcoming tool for rapid detection of antibiotic resistance in microorganisms. Proteom Clin. 2013;7(11-12):767-78. DOI:10.1002/prca.201300042.

57. Wallet F., Herwegh S., Decoene C., Courcol R.J. PCR-electrospray ionization time-of-flight mass spectrometry: a new tool for the diagnosis of infective endocarditis from heart valves. Diagn Microbiol Infect Dis. 2013;76:125-8. DOI:10.1016/j.diagmicrobio.2013.02.007.

58. Morris A.J., Drinkovic D., Pottumarthy S., et al. Gram stain, culture, and histopathological examination findings for heart valves removed because of infective endocarditis. Clin Infect Dis. 2003;36:697-704. DOI:10.1086/367842.

59. Moiseev V.S., Kobalava Z.D., Pisaryuk A.S., et al. Infective Endocarditis in Moscow General Hospital: Clinical Characteristics and Outcomes (Single-Center 7 Years’ Experience). Kardiologiia. 2018;58(12):62- 5 (In Russ.). DOI:10.18087/cardio.2018.12.10192.

60. Habib G., Lancellotti P., Erba PA. et al., EURO-ENDO Investigators. The ESC-EORP EURO-ENDO (European Infective Endocarditis) registry. European Heart Journal – Quality of Care and Clinical Outcomes 2019;5(3):202-7. DOI:10.1093/ehjqcco/qcz018.

For citation:

Kotova E.O., Domonova E.A., Kobalava Z.D., Karaulova J.L., Pisaryuk A.S., Balatskiy A.V., Akimkin V.G. Modern trends in identification of causative agents in infective endocarditis. Rational Pharmacotherapy in Cardiology. 2021;17(1):153-164. (In Russ.)

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