Antibiotic Stewardship

The American Dental Association (ADA) supports the responsible use of antibiotics.¹ As part of this effort toward antibiotic stewardship, the ADA has adopted an evidence-based approach to guideline development, resulting in recommendations decreasing the indications for use of prophylactic antibiotics in people with heart conditions and those who have had joint replacements. Although there are some studies evaluating the appropriateness of antibiotic prescribing in dentistry, a recent paper in JADA suggests that “…it is likely that there are opportunities to improve prescribing practices.”² A 2013 survey³ of antibiotic prescribing by dentists found considerable geographic variability in prescribing practices and called for additional study to “better understand the reasons for this variability and identify areas of possible intervention and improvement.”

Antibiotic resistance—when bacteria no longer respond to antibiotics—is a growing problem.  According to the Centers for Disease Control and Prevention, at least 2 million people in the U.S. become infected with bacteria that are resistant to antibiotics and at least 23,000 people die each year as a direct result of these infections.⁴

Improving understanding of how antibiotics work will be helpful in preventing the spread of antibiotic-resistant bacteria.  Education regarding the responsible use of antibiotics will help practitioners to identify the circumstances when antibiotics are indicated, to choose the right antibiotic, and to prescribe it at the right dose for the right duration.

In addition to problems associated with antibiotic resistance, antibiotics are a major cause of adverse effects from systemically administered medications. A 2018 study found over 145,000 emergency hospital visits for systemically administered antibiotic adverse events in adults between 2011 and 2015 in the United States.⁵ More than half of the visits were from adults aged 20 to 50 years, and approximately 75% of the cases involved allergic reactions to antibiotics. Oral sulfonamides were the most frequent cause of adverse events, followed closely by penicillins, and, lastly, fluoroquinolones.⁵ These results were similar to a 2008 study that stated, “[m]inimizing unnecessary antibiotic use by even a small percentage could significantly reduce the immediate and direct risks of drug-related adverse events.”⁶

Clostridium difficile is spore-forming, Gram-positive anaerobic bacillus that is a cause of 15 to 25% of all episodes of antibiotic-associated diarrhea.⁷  It is commonly found at low levels within the commensal microbiota of the human gut.⁸  Among those organisms, it is considered to be pathobiont, meaning that within its indigenous community, it is benign; however, when homeostasis is disrupted, it acts as a pathogen.⁸ Factors that can alter this homeostatic balance include antibiotic treatment, tissue damage, changes to diet, and immune deficiencies.⁹

C. difficile infection (CDI) is increasing in both prevalence and severity. While the majority (56%) of reported cases are associated with a stay in a healthcare facility, the remaining (44%) cases, numbering 65.8 cases/1000 individuals, are considered community-associated CDI.¹⁰ Of these, it has been estimated that 65% of the community associated CDI occurred after the use of antibiotics.¹¹ Manifestations of CDI range from mild to life-threatening sequelae. CDI can result in pseudomembranous colitis, toxic megacolon, colon perforations, sepsis, and, rarely, death.⁷

Clinical factors associated with increased risk of CDI include age older than 65 years, the presence of underlying disease, and recent courses of antibiotics.¹¹ Dentists are estimated to prescribe 10% of outpatient antibiotics, so while they are not the sole source of these drugs in the community, they make a measurable contribution to it.³ There is some overlap among the antibiotics commonly prescribed by dentists and those reported to carry higher risk for CDI. Antibiotics associated with higher risk of CDI include clindamycin, the cephalosporins, and the fluoroquinolones,¹¹ which are reported to account for 14%, 5%, and less than 1% of the antibiotics prescribed by dentists, respectively.³

In 2004, the ADA Council on Scientific Affairs (CSA) issued a report¹² addressing the association between the overuse of antibiotics and the development of resistant bacteria. The CSA also presented a set of recommendations for dentists to consider when prescribing antibacterial drugs, as follows.

When prescribing antibiotics, practitioners should:

• make an accurate diagnosis;
• use appropriate antibiotics and dosing schedules;
• consider using narrow-spectrum antibiotics (Table 1) for simple infections to minimize disturbance of the normal microflora. Reserve the use of broad-spectrum antibiotics (Table 2) for more complex infections;¹³
• avoid unnecessary use of antibiotics for viral infections;
• if treating empirically, revise treatment regimen based on patient progress or test results;
• obtain thorough knowledge of the side effects and drug interactions of an antibacterial drug before prescribing it;
• educate the patient regarding the proper use of the drug and stress the importance of completing the full course of therapy.

Furthermore, “the diagnosis and antibiotic selection should be based on a thorough history (medical and dental) to reveal or avoid adverse reactions such as allergies and drug interactions.”

Table 1. Narrow-Spectrum Antimicrobial Agents Encountered in Dentistry
(adapted from 2004 CSA Report¹²)

Generic Name and Characteristics*	Common Indications for Use**
Clindamycin Bacteriostatic (bactericidal at higher doses); active against some aerobic gram-positive cocci (including Staphylococcus aureus, S. epidermidis, streptococci and pneumococci), some anaerobic gram-negative bacilli, many anaeorbic gram-positive non-spore-forming bacilli, many anaerobic gram-positive cocci and clostridia	Indicated for the treatment of infections caused by susceptible microorganisms; used as a prophylactic antibiotic in high-risk patients allergic to penicillin for the prevention of bacterial endocarditis
Metronidazole Bactericidal; active against most anaerobic cocci and both gram-negative bacilli and gram-positive spore-forming bacilli	Has been used as adjunct in treatment of periodontitis and acute necrotizing ulcerative gingivitis; commonly coprescribed with amoxicillin (Note: its combined use with amoxicillin or amoxicillin/clavulanic acid has not been approved by the U.S. Food and Drug Administration)
Penicillin V Potassium Bactericidal; cell-wall synthesis inhibitor that is active primarily against gram-positive cocci (including S. aureus), gram-positive and gram-negative bacilli, and spirochetes	Use is limited to treatment of minor infections such as ulcerative gingivostomatitis, and the treatment of streptococcal infections

 ^{"Narrow-spectrum" is defined as active against a small number of organisms
Adapted, in part, from Ciancio13
*Bactericidal drugs directly kill an infecting organism; bacteriostatic drugs inhibit the proliferation of bacteria by interfering with an essential metabolic process.
**Common indications have been modified to exclude uses not currently supported by evidence}

Table 2. Broad-Spectrum Antimicrobial Agents Encountered in Dentistry (adapted from 2004 CSA Report¹²)

Generic Name and Characteristics*	Common Indications for Use**
Amoxicillin (Semisynthetic Penicillin) Bactericidal; active against many gram-negative and gram-positive organisms; not effective against β-lactamase-producing bacteria	Commonly used as an empirical antibiotic for oral infections, sinusitis and skin infections; used as a prophylactic antibiotic in high-risk patients for the prevention of bacterial endocarditis
Amoxicillin with Clavulanic Acid Bactericidal; active against a wide spectrum of gram-negative and gram-positive organisms, including β-lactamase-producing bacteria	Used for the treatment of sinus, oral and respiratory infections
Ampicillin (Semisynthetic Penicillin) Bactericidal; active against many gram-negative and gram-positive organisms; not effective against β-lactamase-producing bacteria	Commonly used as an empirical antibiotic for oral infections, sinusitis and skin infections; used as a prophylactic antibiotic in high-risk patients unable to take oral medication for the prevention of bacterial endocarditis
Cefadroxil (First-Generation Cephalosporin) Bactericidal; active against β-hemolytic streptococci, staphylococci, Streptococcus pneumoniae, Escherichia coli, Proteus mirabilis, Klebsiella and Moraxella	Indicated for the treatment of infections caused by susceptible microorganisms; used as a prophylactic antibiotic in high-risk patients for the prevention of bacterial endocarditis; caution should be exercised when prescribing cephalosporins for patients sensitive to penicillin***
Cefazolin (First-Generation Cephalosporin) Bactericidal; active against group A β-hemolytic streptococci, Haemophilus influenzae, S. pneumoniae, E. coli, Enterobacter aerogenes, P. mirabilis and Klebsiella	Used for treatment of respiratory, urinary tract, skin and biliary infections and for the treatment of septicemia and endocarditis; used as a prophylactic antibiotic in high-risk patients who are unable to take oral medications for the prevention of bacterial endocarditis; caution should be exercised when prescribing cephalosporins for patients sensitive to penicillin***
Cephalexin (First-Generation Cephalosporin)	Indicated for the treatment of infections caused by susceptible microorganisms; used as a prophylactic antibiotic in high-risk patients for the prevention of bacterial endocarditis; caution should be exercised when prescribing cephalosporins for patients sensitive to penicillin***
Cephradine (First-Generation Cephalosporin; Note: no longer commercially available in the U.S.) Bactericidal; active against group A β-hemolytic streptococci, H. influenza, S. pneumoniae, E. coli, E. aerogenes, P. mirabilis and Klebsiella	Used as a prophylactic antibiotic in high-risk patients for the prevention of bacterial endocarditis; caution should be exercised when prescribing cephalosporins for patients sensitive to penicillin***
Azithromycin (Macrolide) Bactericidal; active against a wide range of aerobic gram-negative and gram-positive organisms	Indicated for the treatment of mild-to-moderate infections caused by susceptible microorganisms; used as a prophylactic antibiotic in high-risk patients allergic to penicillin for the prevention of bacterial endocarditis
Clarithromycin (Macrolide) Bactericidal; active against a wide spectrum of aerobic and anaerobic gram-positive and gram-negative organisms	Indicated for the treatment of mild-to-moderate infections caused by susceptible microorganisms; used as a prophylactic antibiotic in high-risk patients allergic to penicillin for the prevention of bacterial endocarditis
Erythromycin (Macrolide) Bacteriostatic; active against gram-positive bacteria, particularly gram-positive cocci; provides limited activity against gram-negative bacteria	Indicated for the treatment of infections of upper and lower respiratory tract, skin and soft-tissue infections of mild-to-moderate severity; alternative to penicillin G and other penicillins for treatment of gram-positive coccoid infections in patients with hypersensitivity to penicillins
Tetracycline (Doxycycline, Minocycline) Bacteriostatic; active against gram-positive and gram-negative bacteria, mycoplasmas, rickettsial and chlamydial infections	Indicated for the treatment of periodontitis and acute necrotizing ulcerative gingivitis (Note: to avoid the gastrointestinal side effects of oral tetracyclines, localized delivery systems of doxycycline and minocycline are marketed for the treatment of periodontitis)

 ^{"Broad-spectrum" antibiotics are used empirically or when culture and sensitivity are not available.
Adapted, in part, from Ciancio13
*Bactericidal drugs directly kill an infecting organism; bacteriostatic drugs inhibit the proliferation of bacteria by interfering with an essential metabolic process.
**Common indications have been modified to exclude uses not currently supported by evidence
***Cross-hypersensitivity has been documented and will occur in up to 10% of patients who have a history of penicillin allergy}

As part of antibiotic stewardship, antibiotic prophylaxis should be reserved for patients who are at the greatest risk of post-treatment bacterial-related complications. The following are ADA resources related to antibiotic prophylaxis:

• An evidence-based clinical practice guideline for dental practitioners about antibiotics prior to dental work in patients who have joint replacements, published in the Journal of the American Dental Association (JADA), states that, in general, antibiotics are not recommended prior to dental procedures for patients with prosthetic joint implants.¹⁴
• A 2017 commentary¹⁵ published in the February 2017 issue of JADA written by ADA-appointed experts, offers guidance for using appropriate use criteria published by the American Academy of Orthopaedic Surgeons in January 2017¹⁶ that address managing care for patients with orthopedic implants undergoing dental procedures. The JADA editorial calls the appropriate use criteria "a decision-support tool to supplement clinicians in their judgment" and it emphasizes discussion of available treatment options between the patient, dentist and orthopedic surgeon, weighing the potential risks and benefits. The commentary encourages dentists to continue to use the 2015 guideline,¹⁴ consult the appropriate use criteria as needed, and respect the patient's specific needs and preferences when considering antibiotic prophylaxis before dental treatment. According to the ADA Chairside Guide, in cases where antibiotics are deemed necessary, it is most appropriate that the orthopedic surgeon recommend the appropriate antibiotic regimen and, when reasonable, write the prescription.
• Guidelines¹⁷ from the American Heart Association about the prevention of infective endocarditis approved by the ADA Council on Scientific Affairs as they relate to dentistry, were published in JADA and clarify the conditions for which prophylaxis should be considered, as well as the regimens that should be used, if indicated.

1. Palmer C. ADA News: ADA supports responsible antibiotic use. American Dental Association. June 15, 2015. Accessed February 26, 2019.
2. Fluent MT, Jacobsen PL, Hicks LA, OSAP. Considerations for responsible antibiotic use in dentistry. J Am Dent Assoc 2016.
3. Roberts RM, Bartoces M, Thompson SE, Hicks LA. Antibiotic prescribing by general dentists in the United States, 2013. J Am Dent Assoc 2017;148(3):172-78.e1.
4. Centers for Disease Control and Prevention. Antibiotic/Antimicrobial Resistance U.S. Department of Health & Human Services. Accessed February 26, 2019.
5. Geller AI, Lovegrove MC, Shehab N, et al. National Estimates of Emergency Department Visits for Antibiotic Adverse Events Among Adults-United States, 2011-2015. J Gen Intern Med 2018.
6. Shehab N, Patel PR, Srinivasan A, Budnitz DS. Emergency department visits for antibiotic-associated adverse events. Clin Infect Dis 2008;47(6):735-43.
7. Centers for Disease Control and Prevention. Frequently Asked Questions about Clostridium difficile for Healthcare Providers. U.S. Department of Health and Human Services. Accessed February 26, 2019.
8. Kamada N, Chen GY, Inohara N, Nunez G. Control of pathogens and pathobionts by the gut microbiota. Nat Immunol 2013;14(7):685-90. Accessed February 26, 2019.
9. Hajishengallis G, Lamont RJ. Dancing with the Stars: How Choreographed Bacterial Interactions Dictate Nososymbiocity and Give Rise to Keystone Pathogens, Accessory Pathogens, and Pathobionts. Trends Microbiol 2016;24(6):477-89.
10. Centers for Disease Control and Prevention. 2015 Annual Report for the Emerging Infections Program for Clostridium difficile Infection. National Center for Emerging and Zoonotic Infectious Diseases 2017.  Accessed February 26, 2019.
11. Rupnik M, Wilcox MH, Gerding DN. Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat Rev Microbiol 2009;7(7):526-36.
12. ADA Council on Scientific Affairs. Combating antibiotic resistance. J Am Dent Assoc 2004;135(4):484-7.
13. Ciancio SG. ADA Guide to Dental Therapeutics, 3rd ed. Chicago, IL: ADA Publishing; 2003.
14. Sollecito TP, Abt E, Lockhart PB, et al. The use of prophylactic antibiotics prior to dental procedures in patients with prosthetic joints: Evidence-based clinical practice guideline for dental practitioners--a report of the American Dental Association Council on Scientific Affairs. J Am Dent Assoc 2015;146(1):11-16 e8.
15. American Dental Association-Appointed Members of the Expert Writing and Voting Panels Contributing to the Development of American Academy of Orthopedic Surgeons Appropriate Use Criteria. American Dental Association guidance for utilizing appropriate use criteria in the management of the care of patients with orthopedic implants undergoing dental procedures. J Am Dent Assoc 2017;148(2):57-59.
16. Quinn RH, Murray JN, Pezold R, Sevarino KS. The American Academy of Orthopaedic Surgeons Appropriate Use Criteria for the Management of Patients with Orthopaedic Implants Undergoing Dental Procedures. J Bone Joint Surg Am 2017;99(2):161-63.
17. Wilson W, Taubert KA, Gewitz M, 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. J Am Dent Assoc 2008;139 Suppl:3S-24S.

• ADA Council on Scientific Affairs, Combating Antibiotic Resistance
• ADA Council on Scientific Affairs, Antibiotic Interference with Oral Contraceptives
• ADA Oral Health Topic: Antibiotic Prophylaxis Prior to Dental Procedures
• Search JADA for articles related to antibiotic stewardship
• Search the ADA Catalog for products related to antibiotic stewardship
• ADA Library Services

Centers for Disease Control and Prevention:

• Get Smart: Know When Antibiotics Work
• Antibiotic Use in the United States, 2017: Progress and Opportunities
• CDC Checklist for Antibiotic Prescribing in Dentistry