Effect of Antibiotic Therapy on the Sensitivity of Etiological Diagnostic Methods in Patients with Infective Endocarditis after Surgery

Aim. Assessment of impact  of the duration  of preoperative  antimicrobial  therapy  (AMT) on the sensitivity  of microbiological examination and polymerase  chain reaction (PCR) of blood/tissues of resected valves in operated patients with infective endocarditis  (IE).

Materials and methods. 52 operated patients with active IE were included prospectively (Duke criteria, 2015). All patients underwent microbiological examination of blood  before  admission  to the cardiac  surgery  hospital,  as well as parallel  simultaneous microbiological examination and  PCR  of blood/tissues of excised  valves,  followed  by Sanger  sequencing. The duration  of preoperative  treatment  was  calculated  from the first day of AMT according to IE diagnosis to the day of surgery.

Results. The causative agent of IE was established in 84.6% (n=44) patients by means of complex etiological diagnosis. A significant  decrease in the sensitivity of microbiological examination of venous blood was revealed when performed  in the period before and after hospitalization to a surgical hospital (up 44.2% to 17.3%, p<0.05). When comparing microbiological examination of blood/tissues of resected valves and PCR of blood/tissues of resected valves, molecular biological  methods demonstrated the greatest sensitivity, with a great advantage when examining the tissues of resected valves (17.3% and 19.2% vs. 38.5% and 75.0%, respectively;  p<0.001). The microbiological examination of venous blood performed  at an early date before admission  to the cardiac  surgery  hospital was comparable in sensitivity to the PCR blood test performed  at a later date after prolonged AMT,  and significantly less sensitive in relation to the PCR of resected valve tissues [44.2% and 38.5% (p>0.05) vs. 75.0% (p<0.05)]. In course of AMT 1-28 days,  there were comparable results of microbiological examination with PCR blood examination and significantly better results of PCR of resected valve tissues [31.0% and 34.5% and 41.4% (p>0.05) vs 72.4% (p<0.001), respectively], and with AMT ≥ 29 days, microbiological examination of any biological  material was negative  in all patients,  and PCR of blood/tissues of resected valves retained high sensitivity (0% and 0% vs. 34.8% and 78.3%, respectively; p<0.01).

Conclusion. Long-term preoperative AMT significantly reduced the sensitivity of microbiological examination of resected valve blood/tissue in operated patients with IE, whereas PCR of resected valve blood/tissue was highly sensitive even with preoperative AMT for more than 29 days.

1. Cahill TJ, Prendergast BD. Infective endocarditis. Lancet. 2016;387(10021):882-93. DOI:10.1016/S0140-6736(15)00067-7.

2. Korber F, Zeller I, Grünstäudl M, et al. SeptiFast versus blood culture in clinical routine - A report on 3 years experience. Wien Klin Wochenschr. 2017;129(11-12):427-34. DOI:10.1007/s00508-017-1181-3.

3. Murdoch DR, Corey GR, Hoen B, et al. 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(5):463-73. DOI:10.1001/archinternmed.2008.603.

4. Moreillon P, Que YA. Infective endocarditis. Lancet. 2004;363(9403):139-49. DOI:10.1016/S0140-6736(03)15266-X.

5. Kim MS, Chang J, Kim MN, et al. Utility of a Direct 16S rDNA PCR and Sequencing for Etiological Diagnosis of Infective Endocarditis. Ann Lab Med. 2017;37(6):505-10. DOI:10.3343/alm.2017.37.6.505.

6. Casalta JP, Gouriet F, Roux V, et al. Evaluation of the LightCycler SeptiFast 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.

7. Voldstedlund M, Nørum Pedersen L, Baandrup U, et al. Broad-range PCR and sequencing in routine diagnosis of infective endocarditis. APMIS. 2008;116(3):190-8. DOI:10.1111/j.1600-0463.2008.00942.x.

8. Halavaara M, Martelius T, Järvinen A, et al. Impact of pre-operative antimicrobial treatment on microbiological findings from endocardial specimens in infective endocarditis. Eur J Clin Microbiol Infect Dis. 2019;38(3):497-503. DOI:10.1007/s10096-018-03451-5.

9. Armstrong C, Kuhn TC, Dufner M, et al. The diagnostic benefit of 16S rDNA PCR examination of infective endocarditis heart valves: a cohort study of 146 surgical cases confirmed by histopathology. Clin Res Cardiol. 2021;110(3):332-42. DOI:10.1007/s00392-020-01678-x.

10. Peeters B, Herijgers P, Beuselinck K, et al. Added diagnostic value and impact on antimicrobial therapy of 16S rRNA PCR and amplicon sequencing on resected heart valves in infective endocarditis: a prospective cohort study. Clin Microbiol Infect. 2017;23(11):888.e1-888.e5. DOI:10.1016/j.cmi.2017.06.008.

11. Fournier PE, Gouriet F, Casalta JP, et al. Blood culture-negative endocarditis: Improving the diagnostic yield using new diagnostic tools. Medicine (Baltimore). 2017;96(47):e8392. DOI:10.1097/MD.0000000000008392.

12. Kotova EO, Domonova EA, Karaulova YuL, et al. Infective endocarditis: Importance of molecular biological techniques in etiological diagnosis. Therapeutic Archive. 2016;88(11):62-7 (In Russ.) DOI:10.17116/terarkh2016881162-67.

13. El-Kholy A, Gamal El-din El-Rachidi N, El-Enany M, et al. Impact of serology and molecular methods on improving the microbiologic diagnosis of infective endocarditis in Egypt. Infection. 2015;43(5):523-9. DOI:10.1007/s15010-015-0761-2.

14. Kühn C, Disqué C, Mühl H, et al. Evaluation of commercial universal rRNA gene PCR plus sequencing tests for identification of bacteria and fungi associated with infectious endocarditis. J Clin Microbiol. 2011;49(8):2919-23. DOI:10.1128/JCM.00830-11.

15. DeminAA, KobalavaZD, SkopinII, TyurinPV, etal. Infectious endocarditis and infection of intracardiac devices in adults. Clinical guidelines 2021. Russian Journal of Cardiology. 2022;27(10):5233. (In Russ.) DOI:10.15829/1560-4071-2022-5233.

16. Miller RJ, Chow B, Pillai D, et al. Development and evaluation of a novel fast broad-range 16S ribosomal DNA PCR and sequencing assay for diagnosis of bacterial infective endocarditis: multiyear experience in a large Canadian healthcare zone and a literature review. BMC Infect Dis. 2016;16:146. DOI:10.1186/s12879-016-1476-4.

17. 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(1):163-7. DOI:10.1128/JCM.43.1.163-167.2005.

18. Greub G, Lepidi H, Rovery C, et al. Diagnosis of infectious endocarditis in patients undergoing valve surgery. Am J Med. 2005;118(3):230-8. DOI:10.1016/j.amjmed.2004.12.014.

19. Lang S, Watkin RW, Lambert PA, et al. Evaluation of PCR in the molecular diagnosis of endocarditis. J Infect. 2004;48(3):269-75. DOI:10.1016/S0163-4453(03)00102-6.

20. Bosshard PP, Kronenberg A, Zbinden R, et al. Etiologic diagnosis of infective endocarditis by broad-range polymerase chain reaction: a 3-year experience. Clin Infect Dis. 2003;37(2):167-72. DOI:10.1086/375592.

21. Gauduchon V, Chalabreysse L, Etienne J, et al. Molecular diagnosis of infective endocarditis by PCR amplification and direct sequencing of DNA from valve tissue. J Clin Microbiol. 2003;41(2):763-6. DOI:10.1128/JCM.41.2.763-766.2003.

22. Rantakokko-Jalava K, Nikkari S, Jalava J, et al. Direct amplification of rRNA genes in diagnosis of bacterial infections. J Clin Microbiol. 2000;38(1):32-9. DOI:10.1128/JCM.38.1.32-39.2000.

23. Zeaiter Z, Fournier PE, Greub G, et al. Diagnosis of Bartonella endocarditis by a real-time nested PCR assay using serum. J Clin Microbiol. 2003;41(3):919-25. DOI:10.1128/JCM.41.3.919-925.2003.

24. Upton A, Drinkovic D, Pottumarthy S, et al. Culture results of heart valves resected because of streptococcal endocarditis: insights into duration of treatment to achieve valve sterilization. J Antimicrob Chemother. 2005;55(2):234-9. DOI:10.1093/jac/dkh527.

25. Kotilainen P, Heiro M, Jalava J, et al. Aetiological diagnosis of infective endocarditis by direct amplification of rRNA genes from surgically removed valve tissue. An 11-year experience in a Finnish teaching hospital. Ann Med. 2006;38(4):263-73. DOI:10.1080/07853890600622119.

26. Mekontso Dessap A, Zahar JR, Voiriot G, et al. Influence of preoperative antibiotherapy on valve culture results and outcome of endocarditis requiring surgery. J Infect. 2009;59(1):42-8. DOI:10.1016/j.jinf.2009.04.009.

27. Vollmer T, Piper C, Horstkotte D, et al. 23S rDNA real-time polymerase chain reaction of heart valves: a decisive tool in the diagnosis of infective endocarditis. Eur Heart J. 2010;31(9):1105-13. DOI:10.1093/eurheartj/ehp600.

28. Gisler V, Dürr S, Irincheeva I, et al. Duration of pre-operative antibiotic treatment and culture results in patients with infective endocarditis. J Am Coll Cardiol. 2020;76(1):31-40. DOI:10.1016/j.jacc.2020.04.075.

29. Muñoz P, Bouza E, Marín M, et al. Heart valves should not be routinely cultured. J Clin Microbiol. 2008;46(9):2897-901. DOI:10.1128/JCM.02173-07.