Our new Spotlight series uses case vignettes to explore diagnosis, pathophysiology, and management of a wide variety of diseases seen in the outpatient and inpatient settings. Articles in the Spotlight section contain clinical pearls that will be highlighted in the case discussion. While the occasional zebra may appear, the goal of the series is to provide clinically relevant information, and each case has been selected specifically for the relevance of its learning points rather than its rarity.
1. To describe the reasons why s. viridans has a predilection toward heart valves.
2. Does antibiotic prophylaxis prior to dental procedures decrease incidence of infectious bacterial endocarditis?
A 65-year-old man with hypertension, hypothyroidism and no known history of valvular heart disease presented to his primary care doctor with one month of generalized weakness and unintentional weight loss. The patient felt unwell, with neck and shoulder pain. He reported fever to 102 degrees Fahrenheit and cough at home. The patient had a dental procedure one month prior to admission. His blood work revealed white blood cells of 13.6mg/dL, hemoglobin of 13mg/dL, iron 27 ug/dl, TIBC 306 ug/dL with ferritin >800 ug/L and ESR 101mm/hr consistent with a systemic inflammatory state. A PET scan showed increased uptake in his spine involving multiple vertebral bodies. Blood cultures were positive for Streptococcus mitis, a species of the viridans group streptococcus and he presented to the hospital.
Physical exam at presentation to our hospital was notable for an elderly man who was alert and oriented. Vital signs were significant for an elevated temperature (100.2 F, BP 99/58, HR 89, RR 16, O2 98% RA). On cardiovascular exam, jugular venous distention was not present, and the patient was noted to have a regular rate and rhythm with normal S1/S2 but a harsh 2/4 short diastolic murmur. There were decreased breath sounds at the lung bases without bilateral lower extremity edema. A transthoracic echocardiogram revealed severe aortic insufficiency due to a 1.5cm aortic vegetation. He was treated with IV penicillin and gentamicin for two weeks followed by one month of ceftriaxone. He underwent aortic valve replacement given the risk of embolization with improvement in symptoms. The cause of his endocarditis was thought to be secondary to the dental procedure months before diagnosis; teeth #14 and #19 were found to have extensive carious lesions requiring extraction prior to surgery.
Why does Streptococcus viridans have a predilection toward heart valves in bacteremia?
In population studies, viridans group Streptococcus is among the most common cause of endocarditis. Both host and bacterial factors contribute to the pathogenesis of endocarditis. Host conditions include predisposing native valvular conditions, such as rheumatic heart disease, bicuspid aortic valves, prosthetic valves, intravenous drug use, intracardiac defibrillators, hemodialysis and advanced age[1,2].
Various factors make viridans streptococcus species well suited to causing endocarditis once it is in the bloodstream. First, viridans group streptococci can evade host immune surveillance by excreting a fibronectin binding protein to escape phagocytosis . Second, viridans group streptococci have a fimbrial adhesion protein (FimA), which is a lipoprotein receptor antigen that serves as a major adhesin, allowing it to firmly adhere to heart valves, especially damaged valves, as in the conditions listed above predisposing these high-risk patients to clot formation . As septic clusters flow through the bloodstream, they have a predilection to attach onto injured cardiac valves, already laden with platelet clots and unprotected by immune defenses, in which bacteria can colonize to form vegetations [4,5]. Viridans endocarditis can be difficult to treat as it is frequently associated with biofilm formation . This limits antibiotic activity against the bacteria. The persistent nature of biofilms also induces inflammation and contributes to chronic bacteremia and thromboembolic events. Platelet-fibrin clots contribute to oral streptococci colonization as well as vegetation formation because of the platelet-bacteria-biofilm interaction seen in rat models and in human imaging [4,6].
Though our patient did not have known valvular disease, he may have had an undetected predisposing condition that led to the large vegetation on his aortic valve. Unlike severe heart failure or failure to respond to therapy, there is no definitive data for surgery in the prevention of stroke. Our patient did have improvement in fatigue and has been doing well after bioprosthetic heart valve replacement.
Does antibiotic prophylaxis prior to dental procedures decrease incidence of infectious bacterial endocarditis?
The most recent American Heart Association guidelines regarding antibiotic prophylaxis prior to dental procedures recommend limiting this to high-risk patients, such as those with prosthetic cardiac valves, previous infective endocarditis, congenital heart disease, and cardiac transplant recipients (table 1) .
|Cardiac predisposition||Absolute risk|
|None, general population||1 in 14 million dental procedures|
|Mitral valve prolapse||1 per 1.1 million dental procedures|
|Congenital heart disease||1 per 475 000 dental procedures|
|Rheumatic heart disease||1 per 142 000 dental procedures|
|Prosthetic cardiac valve||1 per 114 000 dental procedures|
|Previous infectious endocarditis||1 per 95 000 dental procedures|
Table 1: Absolute risk of endocarditis in various conditions .
The consensus is that antibiotic prophylaxis leads to resistance as well as adverse reactions and that these costs outweigh any benefit. A study by the Mayo Clinic evaluating outcomes after reducing antibiotic prophylaxis revealed that the incidence of infective endocarditis caused by viridans group streptococci had not increased . In addition, experimental rat models show that virulent strains of oral streptococci are refractory to antibiotic prophylaxis possibly because platelets absorb penicillin, reducing its bactericidal activity and allowing septic vegetations to form . Though prophylaxis does not show a benefit in any group, in patients who are at high-risk there may be a theoretical justification for using antibiotics to prevent endocarditis; nonetheless it will be important to weigh the risks and benefits when prescribing.
Subacute endocarditis should be in the differential when patients present with weight loss, fever and chronic inflammation, especially when the work-up is inconsistent with the leading diagnosis. Host and bacterial factors contribute to the formation of vegetations, and damaged heart valves are especially susceptible.
Dr. Helen Ma, residency at NYU Langone Health
Peer reviewed by Stuart Dickerman, MD, Cardiologist, NYU Langone Health
Image courtesy of Wikimedia Commons
 Tleyjeh IM, Steckelberg JM. Changing epidemiology of infective endocarditis. CurrInfect Dis Rep. 2006 Jun;8(4):265-70. https://link.springer.com/article/10.1007/s11908-006-0070-0
 Correa de Sa DD, Tleyjeh IM, Anavekar NS, Schultz JC, Thomas JM, Lahr BD, Bachuwar A, Pazdernik M, SteckelbergJM, Wilson WR, Baddour LM. Epidemiological trends of infective endocarditis: a population-based study in Olmsted County, Minnesota. Mayo Clin Proc. 2010 May;85(5):422-6. doi: 10.4065/mcp.2009.0585. https://www.ncbi.nlm.nih.gov/pubmed/20435834
 Jung CJ, Zheng QH, Shieh YH, Lin CS, Chia JS. Streptococcus mutans autolysin AtlA is a fibronectin-binding protein and contributes to bacterial survival in the bloodstream and virulence for infective endocarditis. Mol Microbiol. 2009;74:888-902. https://www.ncbi.nlm.nih.gov/pubmed/19818020
 Jung CJ, Yeh CY, Hsu RB, Lee CM, Shun CT, Chia JS. Endocarditis pathogen promotes vegetation formation by inducing intravascular neutrophil extracellular traps through activated platelets. Circulation. 2015 Feb 10;131(6):571-81.
 Wilson W, Taubert KA, Gewitz M, Lockhart PB, Baddour LM, Levison M, Bolger A, Cabell CH, Takahashi M, Baltimore RS, Newburger JW, Strom BL, Tani LY, Gerber M, Bonow RO, Pallasch T, Shulman ST, Rowley AH, Burns JC, Ferrieri P, Gardner T, Goff D, Durack DT; American Heart Association Rheumatic Fever, Endocarditis and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young; Council on Clinical Cardiology; Council on Cardiovascular Surgery and Anesthesia; Quality of Care and Outcomes Research Interdisciplinary Working Group; American Dental Association. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. J Am Dent Assoc. 2007 Jun;138(6):739-45, 747-60.
 Jung CJ, Yeh CY, Shun CT, Hsu RB, Cheng HW, Lin CS, Chia JS. Platelets enhance biofilm formation and resistance of endocarditis-inducing streptococci on the injured heart valve. J Infect Dis. 2012 Apr 1;205(7):1066-75. https://www.ncbi.nlm.nih.gov/pubmed/22357661
 DeSimone DC, Tleyjeh IM, Correa de Sa DD, Anavekar NS, Lahr BD, Sohail MR, Steckelberg JM, Wilson WR, BaddourLM; Mayo Cardiovascular Infections Study Group. Incidence of Infective Endocarditis Due to Viridans Group Streptococci Before and After the 2007 American Heart Association’s Prevention Guidelines: An Extended Evaluation of the Olmsted County, Minnesota, Population and Nationwide Inpatient Sample. Mayo Clin Proc. 2015 Jul;90(7):874-81.