AMP case report: Culture-negative endocarditis due to Tropheryma whipplei

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Conclusions. Tropheryma whipplei is a rare cause of endocarditis and is a difficult organism to identify since it does not grow in culture media.^1-3 Whipple disease can present as isolated organ manifestations (migrating oligo/polyarthritis, acute gastroenteritis, pulmonary disease, endocarditis, or central nervous system involvement) or as the classical (systemic) form with aggravated diarrhea, malabsorption, weight loss, abdominal pain, migratory arthralgias of the large joints, and lymphadenopathy. Determining the causative agent of culture-negative endocarditis is extremely beneficial for patients. Whipple disease is fatal if untreated and requires close follow-up for signs of central nervous system involvement and possible relapse of the disease. Patients with Tropheryma whipplei are treated for a year or longer with antimicrobials since rates of relapse can be high. Initial therapy is intravenous ceftriaxone or penicillin G for two weeks with maintenance therapy of trimethoprim-sulfamethoxazole for one to two years.^4,5 More recent proposed therapy is oral doxycycline combined with hydroxychloroquine for 12 to 18 months.¹ Sequencing for 16S rRNA has been extremely beneficial in cases where bacterial infections are expected but cultures have been negative. The 16S rRNA gene has both conserved and variable regions; the conserved regions enable primers to bind to and amplify the variable regions of the gene.^6-8,10,11 The species-specific variable regions are used for identification by sequence alignment with the public database at the National Center for Biotechnology Information (BLAST).^6-8,10 Next-generation sequencing typically is used with either the Illumina or Ion Torrent platforms.

1. Dolmans RA, Boel CH, Lacle MM, Kusters JG. Clinical manifestations, treatment, and diagnosis of Tropheryma whipplei infections. Clin Microbiol Rev. 2017;30(2):529–555.
2. Dutly F, Altwegg M. Whipple’s disease and “Tropheryma whippelii.” Clin Microbiol Rev. 2001;14(3):561–583.
3. Fenollar F, Célard M, Lagier JC, Lepidi H, Fournier PE, Raoult D. Tropheryma whipplei endocarditis. Emerg Infect Dis. 2013;19(11):1721–1730.
4. Schneider T, Moos V, Loddenkemper C, Marth T, Fenollar F, Raoult D. Whipple’s disease: new aspects of pathogenesis and treatment. Lancet Infect Dis. 2008;8(3):179–190.
5. Pierce D, Calkins BC, Thornton K. Infectious endocarditis: diagnosis and treatment. Am Fam Physician. 2012;85(10):981–986.
6. Marchesi R, Sato T, Weightman AJ, et al. Design and evaluation of useful bacterium-specific PCR primers that amplify genes coding for bacterial 16S rRNA. Appl Environ Microbiol. 1998;64(2):795–799.
7. Shrestha N, Ledtke CS, Wang H, et al. Heart valve culture and sequencing to identify the infective endocarditis pathogen in surgically treated patients. Ann Thorac Surg. 2015;99(1):33–37.
8. Clarridge JE 3rd. Impact of 16S rRNA gene sequencing analysis for identification of bacteria on clinical microbiology and infectious diseases. Clin Microbiol Rev. 2004;17(4):840–862.
9. Biagi F, Badulli C, Feurle GE, et al. Cytokine genetic profile in Whipple’s disease. Eur J Clin Microbiol Infect Dis. 2012;31(11):3145–3150.
10. Salipante SJ, Kawashima T, Rosenthal C, et al. Performance comparison of Illumina and Ion Torrent next-generation sequencing platforms for 16S rRNA-based bacterial community profiling. Appl Environ Microbiol. 2014;80(24):7583–7591. Published correction appears in Appl Environ Microbiol. 2016;82(14):4453.
11. Salipante SJ, Sengupta DJ, Rosenthal C, et al. Rapid 16S rRNA next-generation sequencing of polymicrobial clinical samples for diagnosis of complex bacterial infections. PLoS One. 2013;8(5):e65226.

Dr. Stefaniuk is assistant professor and assistant clinical laboratory director, University of Cincinnati College of Medicine and University of Cincinnati Medical Center. Dr. Rhoads is assistant professor and section head of microbiology, Cleveland Clinic. Dr. Jacobs is professor emeritus, Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center.

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