Antibiotic in dental infections

Different dental infections and role, the role of amoxicillin and clavulanic acid combination, need for analgesics, aceclofenac role

1. Odontogenic Conditions Odonto- (from ancient Greek odous - "tooth") & -genic (from Greek genos - "birth“)

2. Common odontogenic conditions Am Fam Physician. 2008;77(5):797-802, 806 Pulpitis Pericoronitis Periodontitis Gingivitis Dry Socket

3. Prevalence of common odontogenic infections Periapical abscess 1  25% Pericoronitis 1  11% Periodontal abscess 1  7% Gingivitis 2 Frequency in school aged children 40-60% & 50% in adult Dry socket 3 : up to 30% Int J Dent. 2015;2015:472470. Dent Clin N Am 61 (2017) 217–233 Int J Dent. 2014; 2014: 796102.

4. Important features of common odontogenic conditions & management

5. Acute Apical Abscess Acute inflammation of the soft tissues immediately surrounding the tip of the root of a tooth, often caused by tooth decay and subsequent death of the pulp tissue Sign & Symptoms Pain & Fever Swelling of the gingiva, face or neck (due to abscess) Listlessness, lethargy, loss of appetite for children younger than 16 years old SDCEP: Scottish Dental Clinical Effectiveness Programme . Management of acute dental problems. Guidance for healthcare professionals. Available at: http://www.sdcep.org.uk/wp-content/uploads/2013/03/SDCEP+MADP+Guidance+March+2013.pdf . Last accessed: 23/04/2018

6. Acute Pericoronitis Infection under the operculum, i.e. the gingiva (gum) tissue covering a partially erupted tooth Pain associated with erupting teeth in children (both primary and permanent teeth) Sign & Symptoms Pain, f ever, nausea, fatigue Swelling of the gingiva around partially erupted tooth Discomfort with swallowing Limited mouth opening Unpleasant taste or odour SDCEP: Scottish Dental Clinical Effectiveness Programme . Management of acute dental problems. Guidance for healthcare professionals. Available at: http://www.sdcep.org.uk/wp-content/uploads/2013/03/SDCEP+MADP+Guidance+March+2013.pdf . Last accessed: 23/04/2018

7. Management of Acute Apical Abscess & Acute Pericoronitis Analgesic treatment (NSAIDs) Antibiotics if there are signs of spreading infection (e.g. facial or neck swelling), systemic infection Acute Apical Abscess Acute Pericoronitis Relieving occlusion on the affected tooth Extracting the tooth NSAIDs to control post-operative pain Mouth rinsing with chlorhexidine Extract the tooth if there are repeated episodes of Pericoronitis associated with the same tooth SDCEP: Scottish Dental Clinical Effectiveness Programme . Management of acute dental problems. Guidance for healthcare professionals. Available at: http://www.sdcep.org.uk/wp-content/uploads/2013/03/SDCEP+MADP+Guidance+March+2013.pdf . Last accessed: 23/04/2018

8. Acute Periodontal Conditions Necrotising gingivitis and necrotising periodontitis Severe inflammatory conditions of the gingiva (gum) caused by pathogenic bacteria ( Fusiform bacteria and Spirochetes) Necrotising gingivitis  lesions limited to gingival tissue Necrotising periodontitis  loss of attachment Sign & Symptoms Pain Swelling Bleeding Halitosis Ulcerated gingival tissue Loss of attachment Malaise Fever SDCEP: Scottish Dental Clinical Effectiveness Programme . Management of acute dental problems. Guidance for healthcare professionals. Available at: http://www.sdcep.org.uk/wp-content/uploads/2013/03/SDCEP+MADP+Guidance+March+2013.pdf . Last accessed: 23/04/2018

9. Periodontal abscess Perio-endo abscesses (endodontic and periodontal lesions) Periodontal breakdown occurs whilst there is marginal closure of deep periodontal pocket occluding drainage (Abscesses develop in deep periodontal pockets) Affect a single tooth leading to abscess formation Sign & Symptoms Pain & tenderness swelling of gingival tissue Increased tooth mobility Fever & swollen or lymph nodes Suppuration from gingiva Sign & Symptoms Localized pain Swelling with or without suppuration on palpation Deep pocketing to root apex with bleeding on probing SDCEP: Scottish Dental Clinical Effectiveness Programme . Management of acute dental problems. Guidance for healthcare professionals. Available at: http://www.sdcep.org.uk/wp-content/uploads/2013/03/SDCEP+MADP+Guidance+March+2013.pdf . Last accessed: 23/04/2018

10. Management Pain management  NSAIDs Antibiotics  signs of spreading infection, systemic infection, or for an immunocompromised patient if there are signs of necrotizing disease Acute periodontal conditions Necrotising periodontal disease Periodontal abscess Perio-endo lesions Scaling teeth as effectively as symptoms allow Prescribing chemical plaque control Oral hygiene instruction & smoking cessation Scaling & irrigating periodontal pocket & Extraction Root canal treatment or retreatment SDCEP: Scottish Dental Clinical Effectiveness Programme . Management of acute dental problems. Guidance for healthcare professionals. Available at: http://www.sdcep.org.uk/wp-content/uploads/2013/03/SDCEP+MADP+Guidance+March+2013.pdf . Last accessed: 23/04/2018

11. Alveolar Osteitis (Dry Socket) Osteitis (inflammation) of a socket after a tooth is extracted, most common after molar extraction Sign & Symptoms Management Pain Swelling Unpleasant taste or odour Analgesic treatment (NSAIDs) Irrigating with saline Applying a suitable material to dress the socket, e.g. Alvogy Antibiotics  if there are signs of spreading infection (e.g. facial, limited mouth opening), systemic infection SDCEP: Scottish Dental Clinical Effectiveness Programme . Management of acute dental problems. Guidance for healthcare professionals. Available at: http://www.sdcep.org.uk/wp-content/uploads/2013/03/SDCEP+MADP+Guidance+March+2013.pdf . Last accessed: 23/04/2018

12. Antibiotics in odontogenic infections

13. Antibiotics: An empirical therapy in dental infections Microorganism culture are not commonly preferred to identify infection Based on clinical & bacterial epidemiological data the types of pathogen responsible for infection are suspected Treatment is dependant on Presumptive Fundamental Probabilistic Int Dent J. 2015 Feb;65(1):4-10.

14. Common odontogenic pathogens Int J Med and Dent Sci 2014; 3(1):303-313

15. Common odontogenic pathogens Int J Med and Dent Sci 2014; 3(1):303-313

16. Rationale for antibiotic usage Human oral cavity contains >500 different species Bacteria generally cause odontogenic infection are ‘Saprophytes’ (microorganism that lives on dead or decaying organic matter) Involves Multiple microorganism with different characteristics Presence of anaerobic & aerobic species Dental caries  bacteria penetrates in dentinal tubules Mainly facultative anaerobes (Streptococcus spp., staph spp., lactobacillus spp.) Necrosed pulp  bacteria advance through pulp canal  periapical inflammation Warrants antibiotic Int Dent J. 2015 Feb;65(1):4-10.

17. Prophylactic use of antibiotic To reduce the likelihood of postoperative Local complication: Infection or dry socket Serious complication: Infective endocarditis In surgical excision of benign tumors In immunocompromised patients Risk of infection after extracting wisdom teeth from healthy young people  10% 25% in patients with sickness or low immunity Do the drugs work? Cochrane evidence on antibiotics in dentistry. Posted on 11/14/2017. Available at: https://cochraneohg.wordpress.com/2017/11/14/do-the-drugs-work-cochrane-evidence-on-antibiotics-in-dentistry/#more-1558 . last accessed: 19/04/2018

18. Indications for performing culture & Sensitivity tests No improvement in symptoms despite adequate local debridement & antibiotic coverage Possible causes Unusual species of virulent bacteria, multidrug resistant bacteria or fungal infection Immune deficiency Uncontrolled diabetes Penicillin allergy or history of C. difficile infection 2017 AAE Guidance on the Use of Systemic Antibiotics in Endodontics . AAE Position Statement. Available at: www.aae.org . last accessed: 19/04/2018

19. Indications for performing culture & Sensitivity tests 2017 AAE Guidance on the Use of Systemic Antibiotics in Endodontics . AAE Position Statement. Available at: www.aae.org . last accessed: 19/04/2018

20. Most commonly used antibiotic Int Dent J. 2015 Feb;65(1):4-10

21. Antibiotics in odontogenic infections Benefits Prevention of infection Resolution of infection Prevention of spread of disease Minimization of serious complications Risk GI disturbance: Nausea, vomiting, diarrhea & stomach cramps Resistance 2017 AAE Guidance on the Use of Systemic Antibiotics in Endodontics . AAE Position Statement. Available at: www.aae.org . last accessed: 19/04/2018

22. Efficacy of commonly used antibiotic ENDODONTICS: Colleagues for Excellence by American Association of Endodontists . Antiobiotics and the treatment of endodontic infection. 2006. Available at: https://www.aae.org/specialty/wp-content/uploads/sites/2/2017/07/summer06ecfe.pdf . last accessed: 23/04/2018

23. Unlike others Amoxicillin/ clavulanate sensitive to all common pathogens Odontoestomatol 2006; 22-1: 69-94

24. Sensitivity antibiotic to common odontogenic pathogen Antibiotic Aerobic (%) Anaerobic (%) Amoxicillin/Clavulanic acid 80.3 92.3 Azetreonam 4.5 - Ampicillin 13.6 - Cephalothin 53 100 Cephalexin 53 100 Ciprofloxacin 7.7 Gentamycin 19.7 15.4 Clindamycin 37.8 100 Erythromycin 53 100 Linezolid 53 100 Methicillin 42.4 15.4 Ticarcillin /Clavulanic acid 57.5 25.6 Pipercillin / Tazobactam 53 100 Vancomycin 47.1 100 Int J Med and Dent Sci 2014; 3(1):303-313

25. First line agent for odontogenic infections Penicillin such as amoxicillin is the first-line drug for odontogenic infections Amoxicillin Most common semi synthetic penicillin is drug of choice in treating dental infections In penicillin resistant cases beta- lactamase -stable antibiotics like amoxicillin with clavulanic acid should be prescribed As per American Heart Association (AHA) amoxicillin is first choice for prophylaxis against Endocarditis and prosthetic joint replacement therapy associated with dental procedures J Antimicro.2016. 2: 117

26. WHO: Antibiotic resistance: Enormous threat worldwide Antibiotic resistance 500 000 people worldwide Resistant to at least one commonly used antibiotic in different country is 0-82% Penicillin up to 51% Ciprofloxacin 8-85% Common strains exhibiting resistance Escherichia coli ,  Klebsiella pneumoniae ,  Staphylococcus aureus , &  Streptococcus pneumoniae , followed by  Salmonella   spp WHO. High levels of antibiotic resistance found worldwide, new data shows . January 2018. Available at: http://www.who.int/mediacentre/news/releases/2018/antibiotic-resistance-found/en/. Last accessed: 20/04/2018

27. An elevated cefaclor resistance rate of 12.8%, for 240 isolates of H. influenzae Determined through SENTRY surveillance program Antimicrobial Agents and Chemotherapy 1999 Observed hrough susceptibility surveillance observed Antimicrobial Agents and Chemotherapy 1999 An ever increasing resistance to Penecillin with 60% S. pneumoniae isolates resistant Confirmed through J. Antimicrob Chemotherapy 2005 global surveillance study Cefuroxime resistance of 46%, for 1,113 Streptococcus pneumoniae isolates 1) Journal of Antimicrobial Chemotherapy (2005) 56, S2, ii3-ii21 2) Antimicrobial Agents and Chemotherapy, September 1999, 3(9); 2236-2239 3) Antimicrobial Agents and Chemotherapy, February 1999, 43(2); 357-359 Penicillin 60% resistance C efaclor 12.8% resistance Cefuroxime 46% resistance Antibiotic resistance

28. ß- Lactamases  Cause of bacterial resistance Curr Issues Mol Biol. 2015;17:11-21

29. Mechanism of antibiotic resistance Antibiotic Pathogen Antibiotic inactivation Loss of antimicrobial action Bacterial Resistance

30. Combining β - lactam antibiotic with β - lactamase inhibitor “Combination of - lactam Antibiotic + - lactamases Inhibitor  most successful strategy to combat - lactamases - induced bacterial resistance” Drugs 2003;63:1511-1524

31. Clavulanic Acid-superior to other β - lactamases inhibitors 3.FEMS Microbial Lett 1999;176:11-5 4.Antimicrobial Agents Chemother 1994;38:767-72

32. Odontoestomatol 2006; 22-1: 69-94

33. Choice of antibiotic Should be broad spectrum Wide clinical spectrum, to cover greatest number of dental procedures Adequate pharmacokinetics and pharmacodynamics to allow use in wide dosing intervals in preventive, short-term treatment Adequate safety profile, including in paediatric & elderly populations Odontoestomatol 2006; 22-1: 69-94

34. Dental procedures & antibiotic recommendations

35. Odontoestomatol 2006; 22-1: 69-94

36. Odontoestomatol 2006; 22-1: 69-94

37. Efficacy of Amox/ Clav in odontogenic condition

38. Amoxicillin/Clavulanic Acid for Treatment of Odontogenic Infections: A Randomized Study Comparing Efficacy and Tolerability versus Clindamycin n = 471 Intervention: Amox/ Clav (875/125 mg) BID & Clindamycin 150 QID d = 5 - 7 days Condition: Acute odontogenic infections Periapical abscess, acute periodontitis, & pericoronitis Assessment: % of subjects achieving clinical success Composite measure of pain, swelling, fever & additional antimicrobial therapy required Int J Dent. 2015;2015:472470.

39. Clinical Success Compared to clindamycin efficacy of Amox/ Clav was higher at day 5 & comparable at day 7 Safety Diarrhea : 8% in Amox/ Clav & 12% in Clindamycin Headache: 3% in Amox/ Clav vs. 6% in Clindamycin Int J Dent. 2015;2015:472470.

40. Number of subjects: 47 Condition: Dental infections Dry socket Pericoronitis Cellulitis Periapical abscess Intervention: Amoxicillin + Clavulanic acid 1g BID Duration: 1 week J Med J 2010 ; 44 (3):305- 312

41. Clinical cure rate J Med J 2010 ; 44 (3):305- 312

42. Before After Periapical abscess Pericoronitis Dry socket Resolution of infection by Amox/ Clav J Med J 2010 ; 44 (3):305- 312

43. Sensitivity to both aerobes & anaerobes J Med J 2010 ; 44 (3):305- 312 Conclusions Overall cure rate ( 87%); cure rate was (94%) in acute infections and (86%) in chronic ones Amox/ Clav is effective against most of isolated dental microbes

44. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;100:E11-8 Parameters Details No. of Patients 494 Intervention Amoxicillin + Clavulanic acid 500/125 TID & Placebo Duration of intervention 4 days postoperatively Follow up 8 weeks

45. No. of Patients with postopertive infectious & inflammatory complications significantly less in Amox/ Clav group Conclusion: Amoxicillin/clavulanic acid is efficacious in reducing the incidence of IC following third molar extraction Postoperative infectious & inflammatory complications are between 2.9 & 19.9 times more frequent if antibiotics are not taken ( OR 7.6; CI 2.9-19.9; P < 0.001 ) Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;100:E11-8

46. n = 150 Azithromycin 500 mg OD n = 153 Amox/ Clav 500+125 TID 3-10 days J Int Med Res. 1998 Oct-Nov;26(5):257-65.

47. Clinical Success: More in Amox/ Clav than Azithromycin J Int Med Res. 1998 Oct-Nov;26(5):257-65.

48. Subjects with absence or mild symptoms J Int Med Res. 1998 Oct-Nov;26(5):257-65.

49. Role of NSAIDs in Odontogenic infections

50. Conclusion Combination of amoxicillin & clavulanic has proven to be significantly more effective than amoxicillin after oral-surgical interventions Combination of amoxicillin and clavulanic acid is recommended for use in further practice Parameters Details No. of subjects 102 Condition Removal of impacted wisdom teeth, apicoectomy or complicated extractions, and odontogenic abscesses Intervention Amox/ Clav 500/125 mg TID (5-10 days) & Amoxicillin 500 mg QID (8-10 days) Results Efficacy appeared to be significantly more in combination group Pain & swelling significantly less in combination group

51. The ‘3-D’s’ principle: Pain management in dentistry D iagnosis Diagnosis of condition causing pain & identifying what caused that condition D ental treatment To remove cause of condition for rapid resolution of symptoms D rugs As an adjunct to dental treatment Eg . Non Narcotic analgesic (NSAIDs, Paracetamol etc mostly used); Narcotic analgesic (Opioids: due to potential side effects, reserved for severe pain only) Australian Dental Journal Medications Supplement 2005;50:4: S14-S22

52. Non Steroidal Anti-inflammatory Drugs Non-Selective COX-II inhibitors Selective COX-II inhibitors Preferential COX-II inhibitors Diclofenac, Ibuprofen, Naproxen, Piroxicam, indomethacin Celecoxib, Etoricoxib Aceclofenac, Etodolac Efficacy Comparable Comparable Comparable or slightly superior Safety High risk of GI & CV side effects High risk of CV side effects but low GI side effects than Non-Selective Low GI & CV side effects

53. Subjects: 966611 + 23 million Drug Saf. 2012 Dec 1;35(12):1127-46.

54. The risk of Upper GI complication: Lowest with Aceclofenac

55. Cardiac arrest risk was greatest with non-selective NSAIDs Use of diclofenac (odds ratio [OR], 1.50 [95% CI 1.23–1.82]) & ibuprofen [OR, 1.31 (95% CI 1.14–1.51)] was associated with a significantly increased risk of Cardiac Arrest Eur Heart J Cardiovasc Pharmacother . 2017 Apr 1;3(2):100-107.

56. BMJ. 2016 Sep 28;354:i4857. Current use of individual NSAI Ds and risk of hospital admission for heart failure, compared with past use of any NSAID

57. 50 subjects, (18-60 years) Surgical removal of impacted mandibular third molars Intervention Aceclofenac 100 mg BID Diclofenac 50 mg TID

58. Aceclofenac exerts superior efficacy & safety than diclofenac Onset of Analgesia Aceclofenac 30.6 minutes Diclofenac 73 minutes

59. Aceclofenac + Paracetamol – Synergistic Combination Parameters Aceclofenac Paracetamol MOA Preferential COX-II inhibitor COX-III inhibitor t max 1.25-3 hours 0.7 hour Onset of action 30 minutes 15 minutes Analgesic action Yes Yes Anti-inflammatory Action Yes No Antipyretic Mild Yes Paracetamol Central action Aceclofenac Peripheral action

60. Aceclofenac + Paracetamol more effective than Ketorolac Intervention Pain intensity at 3 h 8 h 19 h Zerodol P Lowest 3 & highest 6.5 Lowest 2 & highest 5.5 Lowest 1 & highest 3.5 Ketorolac Lowest 3.5 & highest 6.5 Lowest 2.5 & highest 5 Lowest 2 & highest 3.5 Oral Zerodol P shows better pain relief than Ketorolac