Infective endocarditis is caused primarily by three groups of bacteria: staphylococci, streptococci, and enterococci. Together, these account for 80% to 90% of all cases. The specific species involved depends heavily on how the infection was acquired, whether you have a natural or prosthetic heart valve, and certain lifestyle factors.
The Three Most Common Bacterial Groups
Staphylococcus aureus is the single most common cause of endocarditis in the developed world, responsible for roughly 30% of cases. It’s also the most dangerous. A Swiss nationwide study found that S. aureus endocarditis carried the highest in-hospital mortality at nearly 20%, with six-month mortality reaching 30%. What makes this bacterium particularly aggressive is its ability to infect even healthy, undamaged heart valves. It binds to cells lining the heart, gets pulled inside them, and then hides from the immune system while releasing proteins that destroy surrounding tissue.
Viridans group streptococci cause about 20% of community-acquired infections. These bacteria live naturally in your mouth and are the same species responsible for dental cavities and gum infections. When oral infections or dental procedures allow them into the bloodstream, they can settle on heart valves. Viridans streptococcal endocarditis tends to develop more slowly than staphylococcal infections and generally carries a better prognosis.
Enterococci round out the top three, causing 15% to 18% of cases. Unlike the other two groups, enterococci show up at similar rates whether the infection started in a hospital or in the community. These bacteria normally live in the gastrointestinal and urinary tracts, and infections often follow procedures involving those areas.
How Bacteria Infect Heart Valves
The process almost always starts with damage to the inner lining of the heart. Minor injuries to valve surfaces cause platelets and a clotting protein called fibrin to collect at the damaged spot, forming a small, sterile clump. When bacteria enter the bloodstream, even briefly, they can latch onto this clump and begin multiplying.
As the bacteria grow, they trigger more clotting. Immune cells arrive but release inflammatory signals that paradoxically encourage further buildup. The result is a vegetation: a mass of bacteria, clotting material, and immune cells anchored to the valve. Bacteria grow both inside individual cells and within a protective fibrin matrix inside the vegetation, which shields them from the immune system and makes the infection extremely difficult to clear without prolonged treatment. These vegetations can also break off in fragments and travel through the bloodstream to other organs, causing secondary damage to the brain, lungs, kidneys, or spleen.
Bacteria Linked to IV Drug Use
People who inject drugs face a distinct pattern of endocarditis. S. aureus dominates even more heavily in this group, involved in 43% to 95% of first-episode cases. The infection also tends to strike a different part of the heart. While endocarditis in the general population usually affects the left-sided valves (mitral and aortic), injection drug use most commonly damages the tricuspid valve on the right side of the heart, in 58% to 77% of cases. Bacteria introduced directly into the venous bloodstream encounter the tricuspid valve first as blood passes through the right side of the heart on its way to the lungs.
Recurrent infections are common in this group, with S. aureus still the leading cause in 20% to 63% of repeat episodes.
Prosthetic Valve Infections: Early vs. Late
If you have an artificial heart valve, the bacteria most likely to cause endocarditis depend on how much time has passed since surgery. Early-onset prosthetic valve endocarditis, occurring within the first months after the procedure, is overwhelmingly caused by staphylococcal species, which were responsible for about 81% of early cases in one study. These infections are typically acquired during or shortly after surgery.
Late-onset prosthetic valve endocarditis, developing months to years later, shifts toward streptococcal species as the leading cause. This pattern more closely resembles endocarditis on native valves, since the bacteria enter the bloodstream from everyday sources like the mouth or gut rather than from the surgical environment. The updated 2023 diagnostic criteria for endocarditis now include an expanded list of bacteria considered “typical” causes specifically when prosthetic material is present.
The Mouth-to-Heart Connection
Viridans streptococci, particularly species like Streptococcus mutans and Streptococcus sanguinis, are the main link between oral health and endocarditis. These bacteria thrive in the mouth, where they cause cavities and gum disease. When gum tissue is inflamed or broken, or during dental procedures that disturb the gums, these bacteria can enter the bloodstream. In people with damaged or abnormal heart valves, this brief episode of bacteria in the blood is sometimes enough for organisms to colonize the valve surface and establish an infection.
This is why people with certain heart conditions are advised to take antibiotics before specific dental procedures. The goal is to kill oral bacteria in the bloodstream before they have a chance to reach the heart.
Less Common and Hard-to-Detect Causes
About 10% to 20% of endocarditis cases are caused by less typical organisms, some of which don’t grow in standard blood cultures. The HACEK group is a collection of five types of bacteria that normally live in the mouth and upper respiratory tract. The name is an acronym for Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella. These slow-growing organisms can cause endocarditis that takes weeks to diagnose because routine blood cultures may come back negative or take unusually long to show growth.
Other rare causes include Coxiella burnetii (the organism behind Q fever) and Bartonella species. The 2023 update to the Duke diagnostic criteria, the standard framework used to diagnose endocarditis, now incorporates newer testing methods like DNA sequencing and specific blood tests for Bartonella to catch these harder-to-detect infections. These advances are particularly important for culture-negative cases, where traditional blood cultures fail to identify the responsible organism despite a clear clinical picture of endocarditis.