Abstract
Introduction
Culture-negative infective endocarditis (IE) accounts for 7–31% of all cases. Metagenomics has contributed to improving the aetiological diagnosis of IE patients undergoing valve surgery. We assessed the impact of 16S ribosomal DNA gene polymerase chain reaction (16S rDNA PCR) in the aetiological diagnosis of culture-negative IE.
Methods
Between January 2016 and January 2020, clinical data from culture-negative IE patients were reviewed retrospectively. Identification of bacteria was performed using 16S rDNA PCR in heart valve specimens.
Results
36 out of 313 patients (12%) with culture-negative IE had their valve tissue specimens submitted for 16S rDNA PCR. 16S rDNA PCR detected and identified bacterial nucleic acid in heart valve tissue significantly more frequently compared to valve culture alone 25(70%) vs 5(12%); p < 0.05. Mean age was 57 years (SD 18) and 80% were male. Native and aortic valve were involved in 76% and 52% of cases, respectively. Streptococcus spp. (n 15) were the most commonly detected organisms, followed by bacteria of the HACEK group (Haemophilus parainfluenzae 2, Aggregatibacter actinomycetemcomitans 1), nutritionally variant streptococci (Abiotrophia defectiva 2), and one each of Staphylococcus aureus, Corynebacterium pseudodiphtheriticum, Helcococcus kunzii, Neisseria gonorrhoeae, Tropheryma whipplei.
Conclusion
16S rDNA PCR may be a useful diagnostic tool for the identification of the causative organism in culture-negative IE. Efforts towards a shorter turnaround time for results should be consider and further studies assessing the clinical impact of this technique in culture-negative IE are needed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Houpikian P, Raoult D. Blood culture-negative endocarditis in a reference center: etiologic diagnosis of 348 cases. Medicine. 2005;84:162–73.
Lamas CC, Eykyn SJ. Blood culture negative endocarditis: analysis of 63 cases presenting over 25 years. Heart. 2003;89:258–62.
Mylonakis E, Calderwood SB. Infective endocarditis in adults. N Engl J Med. 2001;345:1318–30.
Greub G, Lepidi H, Rovery C, Casalta JP, Habib G, Collard F, et al. Diagnosis of infectious endocarditis in patients undergoing valve surgery. Am J Med. 2005;118:230–8.
Imai A, Gotoh K, Asano Y, Yamada N, Motooka D, Fukushima M, et al. Comprehensive metagenomic approach for detecting causative microorganisms in culture-negative infective endocarditis. Int J Cardiol. 2014;172:e288–9.
Fukui Y, Aoki K, Okuma S, Sato T, Ishii Y, Tateda K. Metagenomic analysis for detecting pathogens in culture-negative infective endocarditis. J Infect Chemother. 2015;21:882–4.
Kim MS, Chang J, Kim MN, Choi SH, Jung SH, Lee JW, et al. Utility of a direct 16S rDNA PCR and sequencing for etiological diagnosis of infective endocarditis. Ann Lab Med. 2017;37:505–10.
Clarridge JE 3rd. Impact of 16S rRNA gene sequence analysis for identification of bacteria on clinical microbiology and infectious diseases. Clin Microbiol Rev. 2004;17:840–62 (Table of contents).
Sontakke S, Cadenas MB, Maggi RG, Diniz PP, Breitschwerdt EB. Use of broad range16S rDNA PCR in clinical microbiology. J Microbiol Methods. 2009;76:217–25.
Li JS, Sexton DJ, Mick N, Nettles R, Fowler VG Jr, Ryan T, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis. 2000;30:633–8.
Habib G, Lancellotti P, Antunes MJ, Bongiorni MG, Casalta JP, Del Zotti F, et al. 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.
Ellis ME, Al-Abdely H, Sandridge A, Greer W, Ventura W. Fungal endocarditis: evidence in the world literature, 1965–1995. Clin Infect Dis. 2001;32:50–62.
Pierrotti LC, Baddour LM. Fungal endocarditis, 1995–2000. Chest. 2002;122:302–10.
Corp I. IBM SPSS statistics for windows, version 21.0. Armonk: IBM Corp; 2012.
Fournier PE, Gouriet F, Casalta JP, Lepidi H, Chaudet H, Thuny F, et al. Blood culture-negative endocarditis: improving the diagnostic yield using new diagnostic tools. Medicine. 2017. https://doi.org/10.1097/MD.0000000000008392.
Siciliano RF, Mansur AJ, Castelli JB, Arias V, Grinberg M, Levison ME, et al. Community-acquired culture-negative endocarditis: clinical characteristics and risk factors for mortality. Int J Infect Dis. 2014;25:191–5.
Fournier PE, Thuny F, Richet H, Lepidi H, Casalta JP, Arzouni JP, et al. Comprehensive diagnostic strategy for blood culture-negative endocarditis: a prospective study of 819 new cases. Clin Infect Dis. 2010;51:131–40.
Lamas CC, Fournier PE, Zappa M, Brandão TJ, Januário-da-Silva CA, Correia MG, et al. Diagnosis of blood culture-negative endocarditis and clinical comparison between blood culture-negative and blood culture-positive cases. Infection. 2016;44:459–66.
Faraji R, Behjati-Ardakani M, Moshtaghioun SM, Kalantar SM, Namayandeh SM, Soltani M, et al. The diagnosis of microorganism involved in infective endocarditis (IE) by polymerase chain reaction (PCR) and real-time PCR: a systematic review. Kaohsiung J Med Sci. 2018;34:71–8.
Harris KA, Yam T, Jalili S, Williams OM, Alshafi K, Gouliouris T, 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 Clinmicrobiol Infect Dis. 2014;33:2061–6.
Breitkopf C, Hammel D, Scheld HH, Peters G, Becker K. Impact of a molecular approach to improve the microbiological diagnosis of infective heart valve endocarditis. Circulation. 2005;111:1415–21.
Cheng J, Hu H, Kang Y, Chen W, Fang W, Wang K, et al. Identification of pathogens in culture-negative infective endocarditis cases by metagenomic analysis. Ann Clin Microbiol Antimicrob. 2018;17:43.
Armstrong C, Kuhn TC, Dufner M, Ehlermann P, Zimmermann S, Lichtenstern C, 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;110:332–42.
Halavaara M, Martelius T, Järvinen A, Antikainen J, Kuusela P, Salminen US, et al. Impact of pre-operative antimicrobial treatment on microbiological findings from endocardial specimens in infective endocarditis. Eur J Clin Microbiol Infect Dis. 2019;38:497–503.
Rampini SK, Bloemberg GV, Keller PM, Büchler AC, Dollenmaier G, Speck RF, et al. Broad-range 16S rRNA gene polymerase chain reaction for diagnosis of culture-negative bacterial infections. Clin Infect Dis. 2011;53:1245–51.
Fox GEWJ, Jurtshuk P Jr. How close is close: 16S rRNA sequence identity may not be sufficient to guarantee species identity. Int J Syst Bacteriol. 1992;42:166–70.
Acknowledgements
The authors acknowledge the contribution of the BIDS 16s rDNA PCR service.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Anton-Vazquez, V., Dworakowski, R., Cannata, A. et al. 16S rDNA PCR for the aetiological diagnosis of culture-negative infective endocarditis. Infection 50, 243–249 (2022). https://doi.org/10.1007/s15010-021-01690-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s15010-021-01690-x