Antibiotic Prophylaxis: A Literature Review

Infective endocarditis (IE) is considered a life-threatening condition. Some cardiac diseases predispose a patient to IE. Invasive dental procedures can induce transient bacteremia, and antibacterial prophylaxis is thought to be effective.¹ Therefore, it is important for dental professionals to be current on guidelines for prophylaxis coverage.

The American Heart Association’s recommendations for antibiotic prophylaxis were published in 1955.² In 1960, children were included in the recommendation for prophylaxis. The possibility that oral microflora could develop penicillin resistance was proposed at the same time.³

In 1965, the AHA Committee on Prevention of Rheumatic Fever and Bacterial Endocarditis published the incidence of enterococci following gastrointestinal (GI) and genitourinary (GU) procedures.⁴ The American Dental Association’s involvement began in 1972, emphasizing the importance of oral hygiene.⁵ Antibiotic prophylaxis was recommended for GI and GU procedures at this time.⁶

The prophylaxis recommendation was revised in 1977 by categorizing the procedures and patients into low- and high-risk groups. After 1977, several changes were made to simplify the prophylactic regimens due to the complex nature of the previous document. The penicillin doses, route of administration, and procedure lists were changed with various revisions to the previous recommendations. The previously proposed recommendations were suggested as guidelines. In 2007, the ADA and AHA again made significant revisions in order to simplify the recommendations based on evidence-based practice.⁷ These recommendations for IE prophylaxis have been based on clinical experiences, expert opinion, and published studies over past decades.

IE occurs at sites of endothelial cell damage in the heart as a result of an interaction between platelet and matrix molecules and the pathogen from the bloodstream at the damaged site. Turbulent blood flow caused by congenital or acquired cardiac disease—such as blood flow from a high- to low-pressure chamber or across a narrow orifice—traumatizes the endothelium. Nonbacterial thrombotic endocarditis (NBTE) may result if platelets and fibrins are deposited on the damaged endothelial surface. Infective endocarditis occurs if NBTE is colonized by pathogens of the transient bacteremia from invasive procedures, including dental procedures.⁸ Streptococci viridans is present in the normal flora of the skin, oral cavity, respiratory, and GI tracts. It is responsible for at least 50% of the IE cases in the nonintravenous drug-addicted population.⁹ Transient bacteremia following manipulation of teeth and dental procedures have been reported in the literature.^10-13 Procedures included tooth extraction (10% to 100%), periodontal surgeries (35% to 88%), scaling and root planing (80% to 98%), teeth cleaning (up to 40%), and endodontic procedures (up to 20%). Transient bacteremia also happens during routine daily activities, including tooth brushing and flossing (20% to 68%), use of wooden toothpicks (20% to 40%), water irrigation (7% to 50%), and chewing food (7% to 51%).^10-19 Therefore, occurrence of bacteremia following daily activities is far more frequent than bacteremia following dental visits twice per year.

The reported frequency of endocarditis following dental or medical procedures varies from 3% to 62%.²⁰ Studies suggest that more than 700 species of bacteria—including aerobic and anaerobic gram-positive and gram-negative microorganisms—are living in the oral cavity, particularly on the teeth and in the gingival crevices. The Streptococci viridans group accounts for approximately 30% of the gingival crevice flora. More than 80 years ago, it was suggested that poor oral hygiene and dental diseases were a greater factor as a cause of IE than were dental procedures.²¹ Later studies have focused instead on the risks of bacteremia associated with dental procedures. The ability of antibiotic therapy to prevent or reduce the frequency, magnitude, or duration of bacteremia associated with a dental procedure is controversial.⁷ Some studies reported that antibiotics administered before a dental procedure reduced the frequency, nature, or duration of bacteremia,^22,23 while others did not.^24,25 Literature suggests that the use of antibiotic prophylaxis does not eliminate bacteremia but reduces the incidence, nature, and duration of bacteremia from dental procedures.²⁶ However, no data shows that such a reduction as a result of amoxicillin therapy reduces the risk of or prevents IE. There are no prospective randomized placebo-controlled studies on the efficacy of antibiotic prophylaxis to prevent IE in patients who undergo a dental procedure.⁷ Van der Meer and colleagues reported that dental or other procedures probably caused only a small fraction of cases of IE and that prophylaxis would prevent only a small number of cases, even if it were 100%. In a 2-year case-control study, Van der Meer and colleagues reported that five out of 20 cases developed IE despite receiving antibiotic prophylaxis.²⁰ In 1998, Strom and colleagues evaluated the dental prophylaxis and cardiac risk factors in a multicenter case-control study. The authors reported that dental treatment was not a risk factor for IE, even in patients with valvular heart disease.¹ Roberts et al estimated that tooth brushing twice daily for 1 year had a 154,000 times greater risk of exposure to bacteremia than that resulting from a single tooth extraction.^27,28

Cardiac conditions associated with the highest risk of an adverse outcome from endocarditis are listed in Table 1; antibiotic regimens are provided in Table 2.

Antibiotic prophylaxis is not required for the following procedures: routine anesthetic injections through noninfected tissue, the taking of dental radiographs, placement of removable prosthodontic or orthodontic appliances, adjustment of orthodontic appliances, and placement of orthodontic brackets. Nor is it required for shedding of deciduous teeth or bleeding from trauma to the lips or oral mucosa.⁷

Antibiotic prophylaxis is not required for the following devices: pacemakers and implantable cardioverter-defibrillators, prosthetic vascular grafts, hemodialysis prosthetic vascular grafts, intra-aortic balloon counterpulsation catheters, coronary angiography and percutaneous coronary artery intervention, coronary artery stents, vascular closure devices, Dacron carotid patches, vena cava filters, peripheral vascular stents, devices for patent ductus arteriosus, atrial septal defect, and ventricular septal defect occlusion, ventriculoatrial shunt infections, and cardiac suture line pledget infections.⁷

According to the AHA, antibiotic prophylaxis is not recommended after device placement for patients who undergo dental, respiratory, gastrointestinal, or genitourologic procedures, or after other invasive procedures in patients with in-dwelling devices. Based on the present evidence, coronary bypass graft surgery is not associated with long-term risk for infections. Therefore, there is no need for antibiotic prophylaxis for patients undergoing this surgery. Antibiotic prophylaxis is not recommended for patients with coronary artery stents.⁷ Current published AHA guidelines for antibiotic prophylaxis for congenital cardiac lesions remain applicable.

Although patients who are severely immunocompromised as a result of underlying disease or immunosuppressive treatment have an increased risk of infection, the antibiotic prophylaxis is not generally recommended, because immunosuppression is not an independent risk factor for nonvalvular device infections.⁷

Patients already taking antibiotics for another reason—particularly penicillin for rheumatic fever prophylaxis—should be given an agent from a different class for endocarditis prophylaxis, either clindamycin or azithromycin. If possible, it would be preferable to delay a dental procedure until at least 10 days after completion of the antibiotic therapy. This may allow time for the usual oral flora to be reestablished.^7,29

In 1997, the ADA, American Academy of Orthopaedic Surgeons (AAOS), and Infectious Disease Specialists Association (IDSA) together published the first antibiotic prophylaxis advisory statement for dental patients with prosthetic joints. In this statement, antibiotic prophylaxis was recommended for dental patients who have had total joint replacement to prevent hematogenous prosthetic joint infections. Previously, because the most critical period was up to 2 years after the joint replacement, antibiotic prophylaxis had been recommended for 2 years post-procedure. However, antibiotic prophylaxis was not recommended for patients with pins, plates, or screws. This statement was revised in 2003 for the dental patient risk categories, but not the antibiotic regimens.³⁰

In February 2009, the AAOS released an Information Statement entitled “Antibiotic Prophylaxis for Bacteremia in Patients with Joint Replacements.”³¹ In this document, the AAOS recommended lifelong use of antibiotic prophylaxis after joint replacement. AAOS concluded that “given the potential adverse outcomes and the cost of treating an infected joint replacement, AAOS recommends that clinicians consider antibiotic prophylaxis for all total joint replacement patients prior to any invasive procedure that may cause bacteremia.” The importance of antibiotic prophylaxis was emphasized for high-risk categories (Table 3).

The new AAOS recommendation for total joint replacement raised controversy among dental industry authorities. Among the concerns were: AAOS failed to provide enough scientific evidence to necessitate antibiotic prophylaxis; overuse of antibiotics might increase the possibility of developing antibiotic resistance; and, evidence that antibiotic prophylaxis is useful in preventing distant-site infections was unavailable.³² Additionally, it was thought that AAOS increased the use of antibiotic prophylaxis despite the fact that there was little, if any, scientific data supporting the connection between oral bacteria and joint infections. The AHA, conversely, had reduced the use of antibiotic prophylaxis by about 90% in 2007 in recognition that nearly 50% of IE cases are caused by oral microorganism.³³

In a position paper in Journal of the American Dental Association,³⁴ the American Academy of Oral Medicine (AAOM) stated that due to lack of evidence for antibiotic prophylaxis in patients with total joint replacement, dentists could discuss the situation with their patients’ orthopedic surgeons with regard to following the 2003 AAOS guideline33; orthopedic surgeons who opt to use the 2009 guidelines may prescribe the antibiotic for the patient. In 2010, several members of the AAOM sent letters to the authorities of the ADA, AAOS, and AAOM expressing their concern about this issue, including the lack of evidence for antibiotic prophylaxis in patients with total joint replacement.³³ The AAOS responded by welcoming the opportunity to formally work with ADA, AAOM, and IDSA to develop a more evidence-based approach to its recommendation. The AAOM maintains that, because the 2009 recommendation is an opinion rather than a guideline, dentists may follow the 2003 guideline since it was recommended by such relevant organizations as ADA, AAOS, and IDSA.

An evidence-based approach was the basis for AHA’s developing guidelines for antibiotic prophylaxis. The AHA Committee on Prevention of Rheumatic Fever and Bacterial Endocarditis reported that if prophylactic therapy was 100% effective, only a very small number of infective endocarditis cases would be prevented. Prophylaxis was not recommended based only on an increased lifetime risk of developing infective endocarditis. The potential benefit of antibiotic prophylaxis must be weighed against the known risks of antibiotic toxicity and allergy and the development of microbial resistance.

All oral healthcare professionals have a responsibility to promote the benefits of good oral health and eliminate oral diseases. They should remember that bacteremia occurs from everyday activities, including flossing and tooth brushing. Clinical guidelines are useful and beneficial for proper patient care but must be based on cause and effect. Therefore, all oral healthcare professionals need to evaluate and understand the rationale for implementing any clinical guideline.

Lida Radfar, DDS, MS
Associate Professor
Department of Oral Diagnosis and Radiology
University of Oklahoma
College of Dentistry
Oklahoma City, Oklahoma

Susan Settle, DDS
Associate Professor and Chair
Department of Oral Diagnosis and Radiology
University of Oklahoma
College of Dentistry
Oklahoma City, Oklahoma

Yavar Movaffagh, BS
Volunteer Research Assistant
Department of Oral Diagnosis and Radiology
University of Oklahoma
College of Dentistry
Oklahoma City, Oklahoma

Farah Masood, DDS, MS
Associate Professor and Director of Radiology
Department of Oral Diagnosis and Radiology
University of Oklahoma
College of Dentistry
Oklahoma City, Oklahoma

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In a letter to the Compendium editor dated March 1, 2013, from Eric T. Stoopler, DMD, FDS RCSEd, Associate Professor of Oral Medicine, Director, Postdoctoral Oral Medicine Program, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania, and Thomas P. Sollecito, DMD, FDS RCSEd, Professor and Chairman of Oral Medicine, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania, it was brought to our attention that an update should be noted regarding an article published online by Compendium. The article, “Antibiotic Prophylaxis: A Literature Review,” pp e33-e37, was part of the Compendium March Online Only issue.

Per Drs. Stoopler and Sollecito, while the article provides valuable information to oral healthcare providers (OHCPs) about antibiotic prophylaxis with significant clinical implications, it is imperative for OHCPs to be aware of new guidelines concerning antibiotic prophylaxis for patients with orthopaedic implants undergoing dental procedures. These guidelines were issued jointly from the American Dental Association (ADA) and the American Academy of Orthopaedic Surgeons (AAOS) in 2012,¹ after the Compendium article had been scheduled for publication. These are the first jointly endorsed guidelines from the ADA and AAOS regarding orthopaedic implant prophylaxis for patients undergoing dental procedures since 2003.² Three major recommendations have been issued in the 2012 guidelines, and OHCPs must be familiar with these in order to provide the most current evidence-based information to their patients (see Table). It is also important for OHCPs to understand that the 2012 guidelines regarding this matter supercede all previous guidelines issued by these organizations.

1. American Academy of Orthopaedic Surgeons; American Dental Association. Prevention of orthopaedic implant infection in patients undergoing dental procedures: evidence-based guideline and evidence report. 1st ed. American Academy of Orthopaedic Surgeons; Rosemont, IL: 2012. https://www.aaos.org/research/guidelines/PUDP/PUDP_guideline.pdf. Accessed March 15, 2013.

2. American Dental Association; American Academy of Orthopedic Surgeons. Antibiotic prophylaxis for dental patients with total joint replacements. J Am Dent Assoc. 2003;134(7):895-899.

Table. Major Recommendations from the 2012 ADA – AAOS guidelines for prevention of orthopaedic implant infection in patients undergoing dental procedures^a

Recommendation 1
The practitioner might consider discontinuing the practice of routinely prescribing prophylactic antibiotics for patients with hip and knee prosthetic joint implants undergoing dental procedures.

Strength of Recommendation: Limited

A Limited recommendation means the quality of the supporting evidence that exists is unconvincing, or that well-conducted studies show little clear advantage to one approach versus another.

Practitioners should be cautious in deciding whether to follow a recommendation classified as Limited, and should exercise judgment and be alert to emerging publications that report evidence. Patient preference should have a substantial influencing role.

Recommendation 2
We are unable to recommend for or against the use of topical oral antimicrobials in patients with prosthetic joint implants or other orthopaedic implants undergoing dental procedures.

Strength of Recommendation: Inconclusive

An Inconclusive recommendation means that there is a lack of compelling evidence resulting in an unclear balance between benefits and potential harm. Practitioners should feel little constraint in deciding whether to follow a recommendation labeled as Inconclusive and should exercise judgment and be alert to future publications that clarify existing evidence for determining balance of benefits versus potential harm. Patient preference should have a substantial influencing role.

Recommendation 3
In the absence of reliable evidence linking poor oral health to prosthetic joint infection, it is the opinion of the work group that patients with prosthetic joint implants or other orthopaedic implants maintain appropriate oral hygiene.

Strength of Recommendation: Consensus

A Consensus recommendation means that expert opinion supports the guideline recommendation even though there is no available empirical evidence that meets the inclusion criteria.

Practitioners should be flexible in deciding whether to follow a recommendation classified as Consensus, although they may set boundaries on alternatives. Patient preference should have a substantial influencing role.

^a Adapted and modified from: American Academy of Orthopaedic Surgeons; American Dental Association. Prevention of orthopaedic implant infection in patients undergoing dental procedures: evidence-based guideline and evidence report. 1st ed. Published by the American Academy of Orthopaedic Surgeons; Rosemont, IL: 2012.