10 Apr 2024 [148] Rethink clindamycin for dental patient safety

Jump to: Abstract | Full text | Plain Language Summary | References

Plain Language Summary
Is Clindamycin a Good Antibiotic for Dental Infections?

Background

Dentists sometimes prescribe the antibiotic drug clindamycin in British Columbia for dental infections, although it can cause serious harm. Sometimes it is even given to prevent infection before dental work is done. This Therapeutics Letter stresses patient safety when choosing the best antibiotic for dental care.

Why is clindamycin usually not the best drug for dental infections?

Most dental infections come from bacteria in the mouth. Clindamycin is not any better than other antibiotics at treating these dental infections and can cause more harms. Recent research shows that other antibiotics are just as good at healing dental infections.

What are the risks of using clindamycin?

Clindamycin can cause diarrhea, stomach inflammation, and other problems. The most serious risk is developing Clostridioides difficile colitis. This is a severe infection of the colon. Studies have found that clindamycin is much more likely to cause this infection than other antibiotics. Even a single dose can lead to serious reactions that can be life-threatening.

What about patients who say they are allergic to penicillin?

Many patients believe or were told as children that they are allergic to penicillin.  Many studies have shown they may not be truly allergic or have outgrown the allergy. Dentists should ask questions about allergies and consider using cefuroxime instead, which is safe for most people with a penicillin allergy.

Antibiotics are overused in dentistry

Research shows that antibiotics may be prescribed before dental procedures to try to make sure an infection does not start. Guidelines recommend against using antibiotics for this purpose. Whether antibiotics are really needed to prevent infections before dental work in patients with heart conditions has also been questioned.

Choosing the right antibiotic

The Bugs & Drugs program https://www.bugsanddrugs.org updates advice for antibiotic use in dental care. Dentists should avoid using clindamycin as the first choice for dental infections. Safer alternatives, like cefuroxime, should be used especially for patients with penicillin allergies.

Conclusion

To protect patients from possible harm, clindamycin for dental infections is not a good choice. Other antibiotics should be used, and only when necessary. For more guidance, visit the Bugs & Drugs website.

Abstract

Background: Clindamycin is frequently prescribed by dentists in British Columbia (BC) for dental infections despite its significant propensity for harm, particularly in causing Clostridioides difficile colitis. Clindamycin accounts for 12% of antibiotic prescriptions from BC dentists, compared to 5% in Australia and a mere 0.5% in the UK. These disparities cannot be explained solely by differences in dental health.

Aims: This Therapeutics Letter highlights the risks associated with clindamycin use in dental practice, provides guidance on antibiotic use in dental infections, and recommends alternatives for patients with reported penicillin allergies.

Recommendations: Dentists are advised against using clindamycin for prophylaxis or initial treatment of dental infections due to its high risk of causing Clostridioides difficile colitis, increased mortality compared to amoxicillin, and potential for severe adverse reactions. Given the high prevalence of reported penicillin allergies, dentists are encouraged to consider cefuroxime as a safe alternative for most patients. The Bugs & Drugs program offers updated guidance for pre-operative dental prophylaxis and treatment of active infections, aligned with the guidance from the American Dental Association (ADA) and other authoritative bodies.

Rethink clindamycin for dental patient safety 

Summary:

• Do not use clindamycin for prophylaxis or initial treatment of dental infections, because it has the highest propensity among antibiotics to cause Clostridioides difficile colitis.
• Clindamycin increases death, compared with amoxicillin.
• About 10% of people report penicillin allergy; but skin-testing and oral challenges show the true rate is less than 0.5%.
• Cefuroxime is a safe option for most patients who have true penicillin allergy.
• See Bugs & Drugs for recommendations for prophylaxis and treatment of dental infections: www.bugsanddrugs.org

This Letter provides guidance for antibiotic use to prevent and treat dental infections, with specific emphasis on patient safety. Because of its outsized harms, clindamycin is rarely the best antibiotic choice. However, dentists in British Columbia prescribe it frequently. Clindamycin comprises 12% of antibiotic prescriptions from dentists in BC, compared with 5% for dentists in Australia and 0.5% in the UK. Differences in dental health do not account for this disparity.¹

Clindamycin is not more effective

Most dental infections are polymicrobial, originating from endogenous oral flora. Clindamycin is active against certain aerobic gram-positive cocci (including some Staphylococci and Streptococci) and against anaerobic gram-negative rod-shaped bacteria (some Bacteroides and Fusobacteria). Clindamycin is not more efficacious than alternatives. A 2021 systematic review of antibiotics as adjuvants to dental procedures for management of acute dentoalveolar infections (with or without systemic signs and symptoms) found that all of the assessed treatment regimens – whether no antibiotic, narrow-spectrum antibiotics, broad-spectrum antibiotics, or clindamycin specifically – are equally likely to achieve clinical resolution.² The Australian authors recommend against broad-spectrum antibiotics like clindamycin as first-line therapy for non-severe infections in otherwise healthy patients. They also question whether antibiotics are required when drainage can be established surgically.

Clindamycin causes significant harm to patients, especially Clostridioides difficile

Clindamycin often causes diarrhea and gastritis, but its worst effect is to reduce the normal gut microbiome’s resistance to colonization by pathogens.³ A 2013 meta-analysis of observational studies in outpatients determined that clindamycin poses a relative risk for C. difficile infections that exceeds any other class of antibiotic: nearly 17-fold above baseline, 6-fold higher than penicillins, and 3-fold higher than cephalosporins.⁴ A 2022 retrospective cohort study of a US claims database showed that of the ten most frequently prescribed outpatient antibiotics, clindamycin was most strongly associated with C. difficile infection. Azithromycin, doxycycline, and penicillin VK were least associated.⁵

Even a single dose of antibiotics can cause significant harms. This includes death, and clindamycin is particularly concerning. Observational data from the Yellow Card adverse drug reaction (ADR) reporting system in England show that among nearly 3 million patients who received a single 2-gram dose of oral amoxicillin, there were no fatal reactions, and <23 non-fatal reactions per million prescriptions. In contrast, a single 600mg dose of oral clindamycin was reported to cause 13 fatal and 149 non-fatal reactions per million prescriptions, most of which were from C. difficile infections. ADRs from clindamycin were similar after single or multiple doses.⁶ In the United States, clindamycin carries a Black Box warning: “…Because [clindamycin] therapy has been associated with severe colitis which may end fatally, it should be reserved for serious infections where less toxic antimicrobial agents are inappropriate…”⁷

What to do when patients report a penicillin allergy?

First, question the allergy. Up to 10% of people report a penicillin allergy, but of these, more than 95% will test negative upon skin testing or oral challenge. Fewer than 0.5% of people have a true allergy.⁸ IgE-mediated hypersensitivity also declines substantially over time.⁹

Beta-lactam cross-reactivity between penicillin and cephalosporins depends on the similarity of side chain structure.¹⁰ Because its side chain does not resemble that of amoxicillin, cefuroxime is the recommended alternative for dental infections, as opposed to cephalexin.⁹ Very rare but severe reactions such as Stevens-Johnson syndrome remain contraindications to prescribing any beta-lactam. The Figure below offers a decision tree to help patients and clinicians (including dentists) navigate reported allergy status.

Figure: Decision tree for evaluation of penicillin allergy²¹

Antibiotics are overused for prophylaxis and as adjuvants for dental procedures

A retrospective cohort study of about 170,000 US dental visits between 2011 and 2015 found that 80% of prescriptions for antibiotics prior to dental procedures were unnecessary, when compared with recommendations in national guidelines.¹¹ The American Dental Association (ADA) has issued clear guidance against use of antibiotics for minor ailments such as toothache or localized dental abscess.¹² Four Cochrane reviews concluded that there is insufficient evidence to promote use of antibiotics as prophylaxis or adjuvant treatment for most dental procedures in healthy patients.^13-16 In a consensus statement, the Canadian Dental Association and partner organizations recommend against antibiotic prophylaxis for patients with prosthetic joints.¹⁷

Using antibiotic prophylaxis to prevent infective endocarditis (IE) arising from dental procedures in patients with cardiac comorbidities is now being questioned. The United Kingdom National Institute for Health and Care Excellence (NICE) recommended in 2008 against antibiotic prophylaxis for preventing IE in any patient, even people at high risk.¹⁸ Since then, prescriptions for single doses of amoxicillin and clindamycin have declined radically in the UK, without a convincing increase in incidence of IE or death associated with IE.¹⁹ In the 5 years after Sweden issued similar recommendations, there was no increase in cases of streptococcal IE (the principal organism of concern for dental procedures), even among high-risk individuals.²⁰

Which antibiotic, if any, is right for my patient?

Bugs & Drugs is a program supported by BC and Alberta public funds. It periodically updates recommendations for pre-operative dental prophylaxis in select populations. It also offers recommendations for treatment of active infections, concordant with the ADA guidance that drainage or other definitive tooth-preserving dental treatment is the mainstay of management. Antibiotics are indicated only for infections with systemic involvement.¹³ 

See the Bugs & Drugs website for detailed guidance, including for those with penicillin allergy.

Portrait

As part of a special project in collaboration with the BC Centre for Disease Control (BCCDC) and with funding from the BC College of Oral Health Professionals (BCCOHP), the Therapeutics Initiative mailed an individual Portrait on prescribing for dental infections to approximately 4,000 dentists in BC. Dentists were randomized to three groups to receive different combinations of individual prescribing portraits and this Therapeutics Letter. Dentists received one of two slightly different Portraits. The Portraits were mailed to the early group in October 2023 and to the delayed group in April 2024.

A sample Portrait (with fictitious data) is freely available at: https://ti.ubc.ca/portrait-dental

BC primary care physicians and nurse practitioners can sign up on a secure platform to access their own personalized prescribing Portraits (8 topics currently available and more are being produced). If you qualify and have already signed up, log in to view your Portraits.

The Therapeutics Letter is a member of the International Society of Drug Bulletins (ISDB), a world-wide network of independent drug bulletins that aims to promote international exchange of quality information on drugs and therapeutics.

References

1. Thompson W, Teoh L, Hubbard CC, et al. Patterns of dental antibiotic prescribing in 2017: Australia, England, United States, and British Columbia (Canada). Infection Control & Hospital Epidemiology 2022; 43(2):191–198. DOI: 10.1017/ice.2021.87
2. Teoh L, Cheung MC, Dashper S, et al. Oral Antibiotic for Empirical Management of Acute Dentoalveolar Infections-A Systematic Review. Antibiotics 2021; 10(3):240. DOI: 10.3390/antibiotics10030240
3. Jernberg C, Lofmark S, Edlund C, Jansson JK. Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology 2010; 156(Pt 11):3216–3223. DOI: 10.1099/mic.0.040618-0
4. Brown KA, Khanafer N, Daneman N, Fisman DN. Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection. Antimicrobial Agents & Chemotherapy 2013; 57(5):2326–32. DOI: 10.1128/AAC.02176-12
5. Zhang J, Chen L, Gomez-Simmonds A, et al. Antibiotic-Specific Risk for Community-Acquired Clostridioides difficile Infection in the United States from 2008 to 2020. Antimicrobial Agents & Chemotherapy 2022; 66(12):e0112922. DOI: 10.1128/aac.01129-22
6. Thornhill MH, Dayer MJ, Prendergast B, et al. Incidence and nature of adverse reactions to antibiotics used as endocarditis prophylaxis. Journal of Antimicrobial Chemotherapy 2015; 70(8):2382-8. DOI: 10.1093/jac/dkv115
7. Federal Drug Administration. CLEOCIN HCl® clindamycin hydrochloride capsules. USP Monograph. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/050162s092s093lbl.pdf (accessed: July 2023)
8. Jeimy S, Ben-Shoshan M, Abrams EM, et al. Practical guide for evaluation and management of beta-lactam allergy: position statement from the Canadian Society of Allergy and Clinical Immunology. Allergy, Asthma & Clinical Immunology: Official Journal of the Canadian Society of Allergy & Clinical Immunology 2020; 16(1):95. DOI: 10.1186/s13223-020-00494-2
9. Patrick DM, Al Mamun A, Smith N, et al. Beta-lactam allergy: Benefits of de-labeling can be achieved safely. BC Medical Journal 2019; 61(9):350–351,361.
   https://bcmj.org/bccdc/beta-lactam-allergy-benefits-de-labeling-can-be-achieved-safely (accessed: July 2023)
10. Picard M, Robitaille G, Karam F, et al. Cross-Reactivity to Cephalosporins and Carbapenems in Penicillin-Allergic Patients: Two Systematic Reviews and Meta-Analyses. The Journal of Allergy & Clinical Immunology in Practice 2019; 7(8):2722-2738.e5. DOI: 10.1016/j.jaip.2019.05.038
11. Suda KJ, Calip GS, Zhou J, et al. Assessment of the Appropriateness of Antibiotic Prescriptions for Infection Prophylaxis Before Dental Procedures, 2011 to 2015. JAMA Network Open 2019; 2(5):e193909. DOI: 10.1001/jamanetworkopen.2019.3909
12. Lockhart PB, Tampi MP, Abt E, et al. Evidence-based clinical practice guideline on antibiotic use for the urgent management of pulpal- and periapical-related dental pain and intraoral swelling: A report from the American Dental Association. Journal of the American Dental Association 2019; 150(11):906-921.e12. DOI: 10.1016/j.adaj.2019.08.020
13. Cope AL, Francis N, Wood F, Chestnutt IG. Systemic antibiotics for symptomatic apical periodontitis and acute apical abscess in adults. Cochrane Database of Systematic Reviews 2018, Issue 9. Art. No.: CD010136. DOI: 10.1002/14651858.CD010136.pub3
14. Khattri S, Kumbargere Nagraj S, Arora A, et al. Adjunctive systemic antimicrobials for the non-surgical treatment of periodontitis. Cochrane Database of Systematic Reviews 2020, Issue 11. Art. No.: CD012568. DOI: 10.1002/14651858.CD012568.pub2
15. Rutherford SJ, Glenny A-M, Roberts G, et al. Antibiotic prophylaxis for preventing bacterial endocarditis following dental procedures. Cochrane Database of Systematic Reviews 2022, Issue 5. Art. No.: CD003813. DOI: 10.1002/14651858.CD003813.pub5
16. Agnihotry A, Thompson W, Fedorowicz Z, et al. Antibiotic use for irreversible pulpitis. Cochrane Database Systematic Reviews 2019, Issue 5. Art. No.: CD004969. DOI: 10.1002/14651858.CD004969.pub5
17. Canadian Dental Association. Consensus Statement: Dental Patients with Total Joint Replacement. July 2016. https://www.cda-adc.ca/en/about/position_statements/jointreplacement/ (accessed: July 2023)
18. National Institute for Health and Care Excellence. Prophylaxis against infective endocarditis: antimicrobial prophylaxis against infective endocarditis in adults and children undergoing interventional procedures. NICE Clinical Guidelines, No. 64. London, 2016 July. https://www.ncbi.nlm.nih.gov/books/NBK554353/ (accessed: July 2023)
19. Thornhill MH, Dayer MJ, Forde J, et al. Impact of the NICE guideline recommending cessation of antibiotic prophylaxis for prevention of infective endocarditis: before and after study.  BMJ 2011; 342:d2392. DOI: 10.1136/bmj.d2392
20. Vahasarja N, Lund B, Ternhag A, et al. Infective Endocarditis Among High-risk Individuals Before and After the Cessation of Antibiotic Prophylaxis in Dentistry: A National Cohort Study. Clinical Infectious Diseases 2022; 75(5):1171-1178. DOI: 10.1093/cid/ciac095
21. New Brunswick Anti-infective Stewardship Committee. Antimicrobial Treatment Guidelines for Common Infections. New Brunswick Provincial Health Authorities, October 2017. The Figure was adapted from these Guidelines. https://www.vitalitenb.ca/sites/default/files/documents/medecins/antimicrobial_treatment_guidelines_for_common_infections_-_octobre2017.pdf (accessed July 2023)