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A review of the American Heart Association revised guidelines for the prevention of infective endocarditis.

Introduction

In our careers as physicians, it is not often that we experience a significant change in the therapies or preventive measures for diseases we learned in medical school and residency training. Several examples of these include the routine use of screening colonoscopy for colon cancer, the use of ICDs for patients with low ejection fractions, and the development of a vaccine for certain types of human papillomavirus for cervical cancer prevention.

In April 2007, the American Heart Association published revised recommendations for the guidelines for infective endocarditis (IE) prophylaxis. One may think that this revision does not impact clinical practice to the same effect as the examples listed above. However, for over 50 years, physicians and patients have closely abided by the prophylactic measures previously recommended for a frightening condition, and now those recommendations have been modified. Although physicians may find this transition to a more simplified approach to prophylactic measures appealing, patients may be more reluctant to accept this perspective. This difficulty in acceptance is partly the consequence of our impact as physicians. For the last half-century, we have emphasized to our patients the importance of antibiotic prophylaxis prior to dental procedures in order to prevent the rare, but life-threatening infective endocarditis. We gave them cards to put in their wallets indicating their need for antibiotics prior to procedures. After these interventions, it is understandable that a patient may find it difficult to do away with this ritual and accept the risk we present to them. In order to understand the progression of this change in preventive medicine, we need to review the background and development of guidelines through the years.

Background

The earliest report of endocarditis was in 1554 in the book Medicini by Jean Francois Fernel. After several hundred years of theory development and research by scientists around the world, the American Heart Association (AHA) published the first document recommending prophylaxis against bacterial endocarditis. This historic year was 1955. What was the rationale for prophylaxis? Endocarditis generally follows bacteremia. If bacteremia is caused by certain procedures, then antibiotics should be given to those patients with predisposing heart conditions prior to those procedures. (12) The first recommendations for prophylaxis were for patients with rheumatic or congenital heart disease undergoing dental procedures or oral manipulation. The drug of choice was penicillin given prior to the procedure and for the following five days. This was also suggested for patients having GI or GU surgery. (4)

Over the last 50 years, changes have been made to these recommendations most often involving the duration of prophylactic therapy. Penicillin/ amoxicillin remains the ideal antibiotic for those without sensitivity. In 1997, the AHA provided a more detailed set of recommendations dividing the types of underlying heart diseases into high risk, moderate risk and negligible risk categories as well as specifying which procedures were high, intermediate, or low risk. They used these divisions and the planned procedure (dental, respiratory, GI or GU) to determine the specific prophylactic recommendations. Included in this recommendation was also limiting the administration of antibiotics to simply prior to the procedure. (2)

Present Day

In May of 2007, the AHA reviewed the principles behind the recommendation for IE prophylaxis and the literature to support them. According to their official report, there were five basic principles for formulation of their guidelines. They included: 1) IE is uncommon, but life threatening and prevention is preferable to treatment. 2) There are certain underlying cardiac diseases that predispose to IE. 3) The bacteria known to cause IE occurs commonly in association with invasive dental, GI, or GU tract procedures.

4) Antimicrobial prophylaxis was proven to be effective for prevention of experimental IE in animals. 5) Antimicrobial prophylaxis was thought to be effective in humans for prevention of IE associated with dental, GI, or GU procedures. (1) They felt that the first four of these principles held true today; however, there was no clear scientific evidence to support the fifth.

Discussion

When trying to understand the risk of bacteremia that may lead to IE, they found that the transient bacteremia exposure during a brief dental procedure was a much lower risk to patients than the more frequent bacteria exposure we experience on a daily basis from routine activities. A study from Roberts, estimates that brushing teeth two times per day for one year had a 154,000 times greater risk of exposure to bacteremia than that resulting from tooth extraction. (7) Guntherwoth quantifies the time of exposure risk by pointing out that there is a cumulative exposure of 5370 minutes of bacteremia over a one month period in dentulous patients, resulting from random bacteremia from daily measures (such as chewing, tooth brushing, flossing) compared with a 6-20 minute duration associated with tooth extraction8. Durack points out that the bacteremia related to procedures is short-lived. The detection of positive blood cultures is highest 30 seconds after a tooth extraction and most episodes of bacteremia associated with dental procedures last less than 10 minutes. If patients develop symptoms of endocarditis following a procedure, the interval of symptom onset should be short, within 2 weeks. Those patients who have a longer incubation period probably did not develop endocarditis as a direct result of the procedure. Nonetheless, the true upper limit of incubation period is not known for certain. (12)

There are several case control studies looking at the efficacy of prophylactic antibiotics; however, they provide conflicting results. One study found a protective efficacy of 91% for prophylaxis; however, this study included only 8 case patients over a period of 6 years. This may have made the time relation between procedure and diagnosis difficult to assess. In addition, the prophylaxis was defined by patient's recall, not by evidence that an antibiotic regimen recommended by the AHA was given. (10,12) A second case control study in the Netherlands concluded that prophylaxis was probably not effective and even if it was, it would do little to decrease the total number of cases of endocarditis. (3,12) Furthermore, one must take into account the associated risk of antibiotic administration including hypersensitivity reactions and other adverse events. There is also possible occurrence of drug-resistant organisms. (3) There are no randomized controlled trials to prove the effectiveness of endocarditis prophylaxis. To perform this kind of trial would require large numbers. It also may be considered unethical because antibiotic prophylaxis, though not validated by strong scientific evidence, is regarded as standard of care. (12)

The AHA presented this research in its guidelines to support the change in their recommendations. They shifted from focusing on prophylactic therapy for those patients with the highest predisposition to the acquisition of endocarditis to those with the highest risk of adverse outcome from IE. Table 1 reviews the cardiac conditions in which prophylaxis continues to be recommended. They include prosthetic cardiac valves, previous IE, certain congenital heart disease conditions, and cardiac transplant patients with valvulopathy. Conditions excluded from these recommendations include aortic stenosis or regurgitation, mitral valve prolapse, ASD, VSD, and several others. Table 2 explains the dental procedures for which prophylaxis is reasonable. The medical regimens are included in Table 3. (1)

In regards to other procedures, the AHA states that antibiotic prophylaxis is reasonable for procedures on the respiratory tract or infected skin, skin structures or musculoskeletal tissue for patients with those underlying cardiac conditions listed in Table 3 as these are patients with the highest risk of adverse outcome from IE.

There has been limited research in the association of GI and GU tract procedures and IE. There are few cases reported of IE temporally associated with a GI or GU tract procedures, and there are no studies to show a clear link between the two. There has also been an increase in antimicrobial-resistant strains of enterococci. Therefore, antibiotic prophylaxis solely to prevent IE is no longer recommended by the AHA for GI or GU tract procedures. (1)

Conclusion

So, what is the take home message from the AHA's latest revision? For those patients who previously required prophylaxis as well as those who continue to need it based on the new guidelines, the emphasis of prevention should be on good daily oral hygiene. The important preventive measures include brushing teeth, flossing and seeing a dentist for regular check-ups. (13) These are the points that should be discussed with patients. For primary care providers, these are already part of routine health maintenance concerns. One should continue to offer prophylaxis to those patients at highest risk of adverse outcome (see Table 1). As discussed above, one may find that both adult patients and the parents of pediatric patients have difficulty in discontinuing the prophylactic antibiotic if they no longer fit the criteria. In this case, one has to consider the risk versus benefit of taking an antibiotic prior to procedures. Most often, this decision will be made on an individual basis. One may consider reviewing the article's main points with the patient and use a shared decision making process to determine what is best for that patient. In looking to the future, the importance of prophylaxis for IE remains, as does the need for further research and prospective trials. There shall continue to be ongoing evolution of this issue as is the case in many aspects of medicine; however, the unchanging and common thread among all practitioners continues to be doing what is best for patients and society as a whole, especially in matters of the heart.

References

(1.) Wilson W, et al. 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. Circulation. 2007 Oct 9;116(15):1736-54. Epub 2007 Apr 19.

(2.) Dajani AS, et al. Prevention of bacterial endocarditis: recommendations by the American Heart Association. JAMA. 1997;277:1794-1801.

(3.) Strom BL, Abrutyn E, Berlin JA, Kinman JL, Feldman RS, Stolley PD, Levison ME, Korzeniowski OM, Kaye D. Dental and cardiac risk factors for infective endocarditis: a population-based, case-control study. Ann Intern Med. 1998;129:761-769.

(4.) Jones TD, Baumgartner L, Bellows MT, Breese BB, Kuttner AG, McCarty M, Rammelkamp CH (Committee on Prevention of Rheumatic Fever and Bacterial Endocarditis, American Heart Association). Prevention of rheumatic fever and bacterial endocarditis through control of streptococcal infections. Circulation. 1955;11:317-320.

(5.) Committee on Prevention of Rheumatic Fever and Bacterial Endocarditis, American Heart Association. Prevention of rheumatic fever and bacterial endocarditis through control of streptococcal infections. Circulation. 1960;21:151-155.

(6.) Lockhart PB, Brennan MT, Kent ML, Norton HJ, Weinrib DA. Impact of amoxicillin prophylaxis on the incidence, nature, and duration of bacteremia in children after intubation and dental procedures. Circulation. 2004;109: 2878-2884.

(7.) Roberts GJ. Dentists are innocent! "Everyday" bacteremia is the real culprit: a review and assessment of the evidence that dental surgical procedures are a principal cause of bacterial endocarditis in children. Pediatr Cardiol. 1999;20:317-325.

(8.) Guntheroth WG. How important are dental procedures as a cause of infective endocarditis? Am J Cardiol. 1984;54: 797-801.

(9.) Imperiale TF, Horwitz RI. Does prophylaxis prevent postdental infective endocarditis? A controlled evaluation of protective efficacy. Am J Med. 1990;88:131-136.

(10.) van der Meer, JT. Prophylaxis of endocarditis. Neth J Med. 2002 Dec;60(11):423-7. Review.

(11.) Beynon RP, Bahl VK, Prendergast, BD. Infective Endocarditis. BMJ. 2006 Aug 12;333(7563):334-9.

(12.) Durack, D. Prevention of Infective Endocarditis. NEJM. 1995, Jan 5. 332: 38-42.

(13.) Prendergast, BD. The changing face of infective endocarditis. Heart 2006;92;879-885. originally published online 10 Oct 2005.

Nasira Roidad, MD

Internal Medicine/Pediatrics Resident

Larry Rhodes, MD

Chief, Section of Pediatric Cardiology

Brad Warden, MD

Assistant Professor Department of Cardiology

All of WVU Morgantown
Table 1. Cardiac Conditions Associated With the Highest Risk of
Adverse Outcome From Endocarditis for Which Prophylaxis With Dental
Procedures Is Reasonable (1)

1. Prosthetic cardiac valve

2. Previous IE

3. Congenital heart disease (CHD) *

- Unrepaired cyanotic CHD, including palliative shunts and conduits

- Completely repaired congenital heart defect with prosthetic
material or device, whether placed by surgery or by catheter
intervention, during the first 6 months after the procedure ([dagger])

- Repaired CHD with residual defects at the site or adjacent to the
site of a prosthetic patch or prosthetic device (which inhibit
endothelialization)

4. Cardiac transplantation recipients who develop cardiac valvulopathy

* Except for the conditions listed, antibiotic prophylaxis is no
longer recommended for any other form of CHD.

([dagger]) Prophylaxis is recommended because endothelialization of
prosthetic material occurs within 6 months after the procedure.

Table 2. Dental Procedures for
Which Endocarditis Prophylaxis Is
Reasonable for Patients in Table 11

All dental procedures that involve
manipulation of gingival tissue or
the periapical region of teeth or
perforation of the oral mucosa

The following procedures and
events do not need prophylaxis:
routine anesthetic injections
through noninfected tissue, taking
dental radiographs, placement
of removable prosthodontic
or orthodontic appliances,
adjustment of orthodontic
appliances, placement of
orthodontic brackets, shedding
of deciduous teeth, and bleeding
from trauma to the lips or oral
mucosa.

Table 3. Regimens for a Dental Procedure. (1)

Situation Agent Adults Children

Oral Amoxicillin 2 g 50 mg/kg

Unable to take oral Ampicillin 2 g IM or IV 50 mg/kg
 OR 1 g IM or IV IM or IV
 Cefazolin or 50 mg/kg
 Ceftriaxone IM or IV

Allergic to Cephalexin * 2g 50 mg/kg
penicillin ([dagger]) OR 600 mg 20 mg/kg
 Clindamycin latest 500 mg 15 mg/kg
 OR
 Azithromycin
 or clarithromycin

Allergic to penicillins Cefazoilin 1g IM or 50 mg/kg
or ampicillin ceftriaxone 600 mg IM IV
unable to take oral ([dagger]) 20mg/kg
medication and and Clindamycin IM IV
 seeing

* Or other first or second generation oral cephalosporin in
equivalent adult or pediatric dosage

([dagger]) Cephalosporins should not be used in an individual
with a history of anaphylaxis, angioedema, or urticaria with
penicillins or ampicillin.
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Title Annotation:Scientific Article
Author:Roidad, Nasira; Rhodes, Larry; Warden, Brad
Publication:West Virginia Medical Journal
Article Type:Report
Geographic Code:1USA
Date:May 1, 2010
Words:2333
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