The Role of Polymerase Chain Reaction in the Management of Patients With Infective Endocarditis

The Role of Polymerase Chain Reaction in the Management of Patients With Infective Endocarditis: Modern Diagnostic and Therapeutic Concepts

The aim of this study is to prospectively investigate the additional diagnostic value of broad range PCR targeting the 16 ribosomal DNA in diagnosis and management of patients with infective endocarditis who are candidate for surgicaltherapy;

Study protocol is divided into four different phases:screening, pre-operative clinical assessment (T-1), cardiac surgery (T0) and follow-up period (T4 eT90). During the screening phase, patients will be assessed to determine whether they met the study inclusion/exclusion criteria. After signing the informed consent, patients will go through a preoperative clinical evaluation (T-1). The following assessments are carried out the day before surgery: recording patient's generality, present antibiotic therapy and possible results of blood cultures performed prior to recruitment; - Twelve-lead ECG; - chest X-ray - transthoracic echocardiogram (TTE); -. three pairs of blood cultures from three different blood sampling sites. In cases of complicated endocarditis, the presence and location of septic embolisms is recorded (using Total body CT scan imaging), signs of heart failure evaluated and operability criteria are assessed. On the day of cardiac surgery (T0), main intraoperative data (valve findings, type of prosthesis, surgery time, cardiopulmonary bypass time and aortic cross clamping time) will be gathered; the excised valve was sent partly to the microbiology laboratory for culture and molecular tests and partly to the pathology Laboratory. After cardiac surgery, patients continued to be monitored for a follow up at four (T4) and 90 (T90) days after surgery. During the follow-up period, information was collected on the patient's clinical status (vital parameters) and the antibiotic treatment performed. The same blood tests performed at T-1 are repeated at T4 and T90. All this data was recorded on a dedicated database.

Molecular diagnostic using a broad range PCR on obtained histological material (native valve/valve prosthesis/fragments of them)

number of patients with positive blood cultures vs number of patients with negative blood cultures but with positive molecular diagnostic tests

Number of patients with IE in which antibiotic therapy change because of the results of molecular diagnostic tests

Inclusion Criteria: patients older than 18 years, with diagnosis of IE on a native or prosthetic valve and with a surgical indication for heart valve replacement using extracorporeal circulation (CPB). patients who have signed informed consent to the partecipation of the study Exclusion criteria: patients younger than 18 years Failure to sign consent for personal data processing and/or study participation Participation in other experimental studies Patients who did not complete the examinations under study (culture test on blood and excised valve, molecular tests)

Cahill TJ, Baddour LM, Habib G, Hoen B, Salaun E, Pettersson GB, Schafers HJ, Prendergast BD. Challenges in Infective Endocarditis. J Am Coll Cardiol. 2017 Jan 24;69(3):325-344. doi: 10.1016/j.jacc.2016.10.066.

Habib G, Lancellotti P, Antunes MJ, Bongiorni MG, Casalta JP, Del Zotti F, Dulgheru R, El Khoury G, Erba PA, Iung B, Miro JM, Mulder BJ, Plonska-Gosciniak E, Price S, Roos-Hesselink J, Snygg-Martin U, Thuny F, Tornos Mas P, Vilacosta I, Zamorano JL; ESC Scientific Document Group. 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 Nov 21;36(44):3075-3128. doi: 10.1093/eurheartj/ehv319. Epub 2015 Aug 29. No abstract available.

Baddour LM, Wilson WR, Bayer AS, Fowler VG Jr, Tleyjeh IM, Rybak MJ, Barsic B, Lockhart PB, Gewitz MH, Levison ME, Bolger AF, Steckelberg JM, Baltimore RS, Fink AM, O'Gara P, Taubert KA; American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation. 2015 Oct 13;132(15):1435-86. doi: 10.1161/CIR.0000000000000296. Epub 2015 Sep 15. Erratum In: Circulation. 2015 Oct 27;132(17):e215. Circulation. 2016 Aug 23;134(8):e113. Circulation. 2018 Jul 31;138(5):e78-e79.

Pant S, Patel NJ, Deshmukh A, Golwala H, Patel N, Badheka A, Hirsch GA, Mehta JL. Trends in infective endocarditis incidence, microbiology, and valve replacement in the United States from 2000 to 2011. J Am Coll Cardiol. 2015 May 19;65(19):2070-6. doi: 10.1016/j.jacc.2015.03.518.

Habib G, Lancellotti P, Erba PA, Sadeghpour A, Meshaal M, Sambola A, Furnaz S, Citro R, Ternacle J, Donal E, Cosyns B, Popescu B, Iung B, Prendergast B, Laroche C, Tornos P, Pazdernik M, Maggioni A, Gale CP; EURO-ENDO Investigators. The ESC-EORP EURO-ENDO (European Infective Endocarditis) registry. Eur Heart J Qual Care Clin Outcomes. 2019 Jul 1;5(3):202-207. doi: 10.1093/ehjqcco/qcz018. Erratum In: Eur Heart J Qual Care Clin Outcomes. 2020 Jan 1;6(1):91.

Habib G, Erba PA, Iung B, Donal E, Cosyns B, Laroche C, Popescu BA, Prendergast B, Tornos P, Sadeghpour A, Oliver L, Vaskelyte JJ, Sow R, Axler O, Maggioni AP, Lancellotti P; 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 Oct 14;40(39):3222-3232. doi: 10.1093/eurheartj/ehz620. Erratum In: Eur Heart J. 2020 Jun 7;41(22):2091.

Dickerman SA, Abrutyn E, Barsic B, Bouza E, Cecchi E, Moreno A, Doco-Lecompte T, Eisen DP, Fortes CQ, Fowler VG Jr, Lerakis S, Miro JM, Pappas P, Peterson GE, Rubinstein E, Sexton DJ, Suter F, Tornos P, Verhagen DW, Cabell CH; ICE Investigators. The relationship between the initiation of antimicrobial therapy and the incidence of stroke in infective endocarditis: an analysis from the ICE Prospective Cohort Study (ICE-PCS). Am Heart J. 2007 Dec;154(6):1086-94. doi: 10.1016/j.ahj.2007.07.023. Epub 2007 Sep 12.

Nihoyannopoulos P, Oakley CM, Exadactylos N, Ribeiro P, Westaby S, Foale RA. Duration of symptoms and the effects of a more aggressive surgical policy: two factors affecting prognosis of infective endocarditis. Eur Heart J. 1985 May;6(5):380-90. doi: 10.1093/oxfordjournals.eurheartj.a061876.

Lodise TP, McKinnon PS, Swiderski L, Rybak MJ. Outcomes analysis of delayed antibiotic treatment for hospital-acquired Staphylococcus aureus bacteremia. Clin Infect Dis. 2003 Jun 1;36(11):1418-23. doi: 10.1086/375057. Epub 2003 May 20.

Shrestha NK, Ledtke CS, Wang H, Fraser TG, Rehm SJ, Hussain ST, Pettersson GB, Blackstone EH, Gordon SM. Heart valve culture and sequencing to identify the infective endocarditis pathogen in surgically treated patients. Ann Thorac Surg. 2015 Jan;99(1):33-7. doi: 10.1016/j.athoracsur.2014.07.028. Epub 2014 Oct 22.

Morris AJ, Drinkovic D, Pottumarthy S, Strickett MG, MacCulloch D, Lambie N, Kerr AR. Gram stain, culture, and histopathological examination findings for heart valves removed because of infective endocarditis. Clin Infect Dis. 2003 Mar 15;36(6):697-704. doi: 10.1086/367842. Epub 2003 Mar 4.

Lamas CC, Fournier PE, Zappa M, Brandao TJ, Januario-da-Silva CA, Correia MG, Barbosa GI, Golebiovski WF, Weksler C, Lepidi H, Raoult D. Diagnosis of blood culture-negative endocarditis and clinical comparison between blood culture-negative and blood culture-positive cases. Infection. 2016 Aug;44(4):459-66. doi: 10.1007/s15010-015-0863-x. Epub 2015 Dec 15.

Zegri-Reiriz I, de Alarcon A, Munoz P, Martinez Selles M, Gonzalez-Ramallo V, Miro JM, Falces C, Gonzalez Rico C, Kortajarena Urkola X, Lepe JA, Rodriguez Alvarez R, Reguera Iglesias JM, Navas E, Dominguez F, Garcia-Pavia P; Spanish Collaboration on Endocarditis-Grupo de Apoyo al Manejo de la Endocarditis infecciosa en Espana (GAMES). Infective Endocarditis in Patients With Bicuspid Aortic Valve or Mitral Valve Prolapse. J Am Coll Cardiol. 2018 Jun 19;71(24):2731-2740. doi: 10.1016/j.jacc.2018.03.534.

Fontana C, Favaro M, Pelliccioni M, Pistoia ES, Favalli C. Use of the MicroSeq 500 16S rRNA gene-based sequencing for identification of bacterial isolates that commercial automated systems failed to identify correctly. J Clin Microbiol. 2005 Feb;43(2):615-9. doi: 10.1128/JCM.43.2.615-619.2005.

Mignard S, Flandrois JP. 16S rRNA sequencing in routine bacterial identification: a 30-month experiment. J Microbiol Methods. 2006 Dec;67(3):574-81. doi: 10.1016/j.mimet.2006.05.009. Epub 2006 Jul 21.

Akram A, Maley M, Gosbell I, Nguyen T, Chavada R. Utility of 16S rRNA PCR performed on clinical specimens in patient management. Int J Infect Dis. 2017 Apr;57:144-149. doi: 10.1016/j.ijid.2017.02.006. Epub 2017 Feb 16.