History of Endocarditis and Antibiotic Prophylaxis

Antibiotic prophylaxis to prevent IE began in 1955 based on some limited animal data, but primarily on the assumption that if antibiotics treat infections, they surely must prevent them. IE prophylaxis arose from the observation that dental treatment was associated with an increase in bacteremia rates, although it was well known at that time that daily living activities also produced bacteremias at roughly the same intensity as dental treatment. This emphasis on possible prevention was understandable considering that in the preantibiotic era, IE in all its forms (acute, subacute, and chronic) was universally fatal, with the only question being how soon the patient would die.

Currently, most studies on antibiotic prophylaxis given before dental treatment have been shown to reduce, but not eliminate, these bacteremias. It is still unknown how many bacteria (inoculum size) are necessary to induce IE. It was also assumed that if the bacteremias were reduced, endocarditis would be prevented. There have never been any data to support this assumption; however, thousands of lawsuits have been filed alleging negligence against dentists with millions of dollars transferred from them and their insurance carriers to the dental patient allegedly developing IE. This hypothesis was expanded to promote antibiotic prophylaxis to prevent orthopedic joint prosthesis infections. Many other alleged metastatic diseases have supported the 100-year-old observation that: “Previously sclerosed endocarditis was in most cases due to mouth organisms.”⁸

This theory that metastatic bacteremias were the cause of anatomically distant diseases was embodied in the focal infection theory. At the turn of the 20th century, the focal infection theory proposed that a focus of infection (a confined area that contained bacteria) disseminated these microorganisms and their products in blood to distant body sites where a new infection arose.⁵⁹ These foci of infection were primarily located in the mouth, tonsils, and gallbladder and were allegedly responsible for myriad diseases, including arthritis, neuralgias, myalgias, asthma, cancer, pancreatitis, thyroid disease, and “nervous diseases of all kinds.”⁵⁹ After the loss of millions of teeth, tonsils, and gallbladders, the focal infection theory faded away in the 1930s and 1940s, only to be resurrected today with alleged causation of sarcoidosis, multiple sclerosis, amyotrophic lateral sclerosis, myasthenia gravis, Tourette’s syndrome, and other diseases by focal infections. The “oral-systemic connection” is another resurrection of the focal infection theory with as much “evidence” as in the past but with an ever-expanding group of associated diseases, including cardiovascular disease, preterm birth, diabetes mellitus, and Alzheimer’s disease.⁵⁹

IE is a bacterial or fungal infection of one or more of the cardiac valves (aortic, mitral, tricuspid, or pulmonary) or the mural endocardium. The primary pathology is the formation of valvular vegetations composed of fibrin and platelets resulting from abnormal jets of blood that damage the valves over time and lead to the vegetations, which become infected by microorganisms in the blood (bacteremias, fungemias). Most IE is caused by staphylococci and streptococci owing to their ability to attach to surfaces using various adhesion molecules.⁹³

The rationale for antibiotic prophylaxis to prevent IE with cardiac valvulopathy has been that (1) certain cardiac defects predispose to endocarditis, (2) most microbes causing IE are susceptible to antibiotics, (3) the risk of bacteremias is increased by certain invasive medical and dental procedures, (4) antibiotic prophylaxis reduces the incidence and magnitude of such bacteremias, and (5) antibiotics prevent bacterial attachment to damaged cardiac valves or their multiplication after they become attached.^57,58,93 These suppositions remain valid for the greater risk of IE in individuals with damaged cardiac valves, but it is becoming increasingly obvious that routine bacteremic sensitivity to antibiotics is now unlikely, that it does not follow that reducing bacteremias reduces IE, and that bacteremias associated with daily living are much more likely to produce IE than a few dental appointments in a given year. The lack of evidence for dental treatment being the cause of IE, prosthetic joint infections (PJIs), brain abscesses (BAs), and other potentially bacteremic infections has been challenged since the mid-1970s by numerous individuals,⁵⁵ and this has resulted in the new guidelines by the AHA, BSAC, and NICE. Reason and science have finally prevailed after 100 years.

Data Included in the American Heart Association Guidelines

The 2007 AHA statement on the prevention of IE has been an extensively reviewed document. Twenty-three members of the Writing Group; several content and foreign reviewers; and all members of the AHA Science and Advisory Group encompassing some 70 experts, including cardiologists, infectious disease specialists, and dentists, were involved. The AHA statement has been endorsed by the American College of Cardiology, the Infectious Diseases Society of America, the American Academy of Dermatology, the American Academy of Pediatrics, the International Society of Chemotherapy for Infection and Cancer, the Pediatric Infectious Disease Society, and the American Dental Association.⁹³ The following discussion summarizes the findings of the AHA and presents relevant data.

An overriding concept that guided the development of the AHA 2007 endocarditis prevention guidelines was that prophylaxis should no longer be based on the lifetime risk of acquiring endocarditis but rather on the highest risk for an adverse outcome from IE. The risk of serious morbidity and higher mortality is much greater in a patient with a prosthetic heart valve than a patient with a bicuspid aortic valve infected with viridans group streptococci (VGS). This greater risk does not mean that antibiotic prophylaxis has a better chance of preventing IE in a patient with a prosthetic valve, only that the pathologic sequelae are greater, and that in the remote chance that prophylaxis would work, it is worth the attempt. This conclusion was based on a thorough review of the literature on IE regarding its etiology, causative factors, pathophysiology, and risk factors for acquisition. Particular emphasis was placed on the role of dental treatment bacteremias in IE causation and the role of antibiotic prophylaxis in its prevention. The document also included a thorough discussion of the various AHA recommendations over the years since 1955 and their progression to the present form.

Essentially, the guidelines state that there is no evidence that antibiotic prophylaxis is effective in preventing IE associated with dental treatment procedures, that the risk of bacteremias from daily living activities is magnitudes greater than that associated with dental treatment, and that such dental treatment procedures are a very small risk for IE. In addition, the guidelines clearly state the following: (1) there is no evidence that the incidence of IE is greater with a higher versus a lower magnitude of bacteremia, (2) the role of the duration of bacteremias is uncertain, (3) a presumed relationship between poor oral hygiene and IE risk is controversial, (4) bleeding from a dental procedure is an unreliable predictor of bacteremia, and (5) no data indicate that a reduction in bacteremia with amoxicillin reduces the risk of or prevents IE. The absolute risk rate for IE from a single dental procedure was between 100,000 and 1 million depending on the type and severity of the cardiac valvular pathology (Box 49-4).^56,59,93

The absolute risk rate for endocarditis from a dental treatment procedure is essential to the determination of a risk/benefit assessment of antibiotic prophylaxis to prevent IE.^56,59 One would need to premedicate 100,000 to 1 million patients to achieve one successful IE prevention, assuming that antibiotic prophylaxis works and dental treatment bacteremias cause 1% of VGS-induced IE (see Box 49-4).⁵⁶ Because the mortality rate from VGS-associated IE is less than 10%, and the rate of anaphylactic death from penicillin is at least 1 per 1 million, it is likely that the risk of death is greater from the prevention than the disease.^57,87

In 1975, Podgrell and Welsby⁶⁴ published an estimate of the odds of IE occurring after a single dental procedure as 1 per 140,000. These data remained unappreciated until the popularization of evidence-based medicine. More specifically, the concept of absolute risk rates for disease incidence and prevalence determination were used to determine how many in a given population actually get the disease or benefit from its treatment. Steckelberg and Wilson⁷⁸ published the absolute risk rates for IE in individuals with varying severity of cardiac valvular pathology. Using data from the United States about the annual dental visits per year (1.6), the annual incidence of community IE (11,200 cases), and the percent caused by VGS (25%), it was calculated that (1) the risk for VGS-caused IE in the general population, if all were caused by dental treatment–induced bacteremias, is 1 per 142,000 (very close to the Podgrell-Welsby estimate), and (2) if only 1% were caused by dental treatment, the odds were approximately 1 per 14 million.^56,59

The risk rate increased substantially depending on the severity of the cardiac pathology using the Steckelberg and Wilson criteria.⁷⁸ The odds for patients with (1) previous endocarditis are 1 per 95,000; (2) heart valve prostheses, 1 per 114,000; (3) rheumatic heart disease, 1 per 142,000; (4) congenital heart disease, 1 per 475,000; and (5) mitral valve prolapse with regurgitation, 1.1 per 1 million.^56,59,78 It has likewise been calculated that the risk for PJIs from dental treatment was 1 per 2.5 million, and for BAs the odds ranged from 1 per 1 million to 10 million dental procedures.