Infective Endocarditis: What’s Changed and What’s the Same

“Few diseases present greater difficulties in the way of diagnoses than malignant [infective] endocarditis, difficulties which in many cases are practically insurmountable. It is no disparagement to the many skilled physicians who have put their cases upon record to say that in fully one-half the diagnosis was made post mortem.”

Sir William Osler, Goulstonian Lectures, London, 1885

“Knowledge about the origins of endocarditis stems from the work of Fernel in the early 1500s, and yet this infection still presents physicians with major diagnostic and management dilemmas.”

Beverly C. Miller and John E. Moore, “Emerging Issues in Infective Endocarditis,” CDC Stacks, June 2024. 

Infective endocarditis (IE) is a rare but life-threatening heart infection. It is the only bacterial infection that is 100% fatal without antibiotic treatment. (Rabies, a viral infection, and inhalational anthrax are the only other infectious diseases with that kind of staggering mortality.) And, despite major advances in microbiology, antibiotics, cardiac imaging, and cardiac surgery, IE remains one of the most challenging infections in clinical medicine.

Until recently, I had never considered writing a Germ Gems on IE as I thought it wouldn’t be of sufficient interest. Then I was hospitalized and treated for congestive heart failure. During my hospital stay, my physicians asked if I had had any dental procedures which could have caused an infection resulting in damage to my mitral valve. Upon hearing this, my adult children started to bombard me with questions about IE. As they expressed interest (albeit self-interest) in this infection, I thought this might be a good time for a short post on IE.

What is infective endocarditis (IE)? IE is a microbial infection of the endocardium (inner lining) of the heart. The pathogen, usually a bacterium but sometimes a fungus like Candida, enters the bloodstream then settles and multiples in the heart’s endocardium. While the pathogen can enter the bloodstream in several ways, e.g., skin conditions or infections, burns, and IV drug use,  “your teeth are the most common location for infection-causing bacteria to get inside your heart.” (Johnston, D.R., “What is Endocarditis?,” Northwestern Medicine, July 2024).

IE most commonly affects the heart valves but can also involve other parts of the heart’s inner lining including implanted cardiac devices. It is a potentially life-threatening disease characterized by infection and inflammation of heart valve tissue, with formation of infected vegetations, and sometimes destruction of the valve and surrounding cardiac structures. The mitral and aortic valves are most frequently affected, although right-sided endocarditis occurs, most commonly among people who inject drugs.

IE is rare. There are, however, factors that can increase your risk for IE. These include: an artificial heart valve, pace maker or defibrillator; certain heart conditions (heart valve disease, hypertrophic cardiomyopathy); diabetes; IV substance use; poor dental health; and a weakened immune system.

IE can be acute, that is, begin suddenly with a high fever and fast heart rate and can become life-threatening within days, or subacute, developing gradually over time. (https://my.clevelandclinic.org/health/diseseses/16957-endocarditis).

Symptoms can include:

• Chest pain

• Heart murmur

• Tachycardia (fast heart rate)

• Fatigue

• Fever

• Chills and night sweats

• Loss of appetite and weight loss

• Muscle and joint aches

• Dyspnea (shortness of breath)

• Skin rash

• Swelling in legs or abdomen

• Hematuria (blood in your urine).

  
  

IE is generally treated with IV antibiotics. The choice of antibiotic and the duration of therapy depends on the organism causing the infection, the valve involved and whether complications have developed. In some cases, surgery may be needed.

What’s changed? Although IE is still relatively uncommon, it is a substantial and growing global burden. In 2021, there were an estimated 1.04 million cases of IE and 77,840 estimated global deaths.

We have, however, moved from an illness of younger people to an illness increasingly infecting older adults. A century ago, young people with rheumatic or congenital heart disease were the big risk group for IE. Today, the mean patient age is 57 years, and there is no longer a single “typical” patient. The major risk groups now include older adults with degenerative valve disease, patients with prosthetic valves or implanted cardiac devises, IV drug abusers, and patients on hemodialysis or those with indwelling vascular catheters.

The microbiology has changed too. Staphylococcus aureus is now the leading cause of IE. (People with abnormal heart valves are predisposed to developing IE, and some microbes, like S. aureus, are notorious for also infecting normal heart valves.) Other major pathogens include viridans group streptococci, often from a dental source, Enterococcus faecalis, and HACEK organisms.

What’s the same? IE is a multidisciplinary disease requiring primary care physicians, infectious diseases specialists, cardiologists and cardiac surgeons—that has not changed. It is also still true that without prompt treatment with antibiotics, patients with IE will inevitably die.  The stakes remain that high.

An old question moving closer to an answer. The most important goal in managing patients with abnormal heart valves or with cardiac devices is to keep bacteria out of the bloodstream to begin with or to prevent the bacteria from  “setting up shop” on heart valves if they do gain access to the bloodstream. With this goal in mind, antibiotics are sometimes given prophylactically before procedures, such as dental work, to prevent IE. But, how long does one treat patients with established valve infections? While that question is still being debated, a randomized controlled study conducted in Denmark moves us closer to an answer.

In the POET II trial, Danish cardiologists enrolled 508 patients with left-sided IE and assigned them to standard-duration therapy or to a response-tailored antibiotic regimen that allowed the patients to be antibiotic-free earlier. (Bundgaard, H.,  et al.,  “Response-Tailored or Standard-Duration Antibiotic Treatment for Infective Endocarditis. New England Journal of Medicine, October 22, 2026). The response-tailored group spent more time alive without antibiotics and met the criterion for noninferiority with respect to safety, but they had a higher incidence of relapse of bacteremia or IE.

In my opinion, this trial was laudable but the results are unlikely to change the current practice of treating IE for a prolonged period of time, which in some cases may be longer than required.  Nonetheless, it is remarkable as this Danish study is the first randomized controlled trial to evaluate the duration of antibiotic therapy for IE, the single most life-threatening bacterial infection. Hats off to these Danes for beginning to provide an answer to an age-old question.