1. Antibiotic Use In Dentistry Kevin Nakagaki, D.D.S. Director, Hospital Dental Clinic University of Minnesota

2. Writing Prescriptions Rx: Drug Name (can be generic) Unit Dose (ex: Pen V-K 500 mg, Elixer, Sol’n) Disp: # of pills, milliliters (ml) Sig: Directions for use. q24h (daily), q12h, q8h, q6h, q4h, prn pain, till gone Refills__Signature DEA # DEA #

3. General Rules  Write Legibly!!  Remember your audience (Generally non-docs) this will improve compliance.  Preferable to order specific hourly dosage time (q12h vs. bid, q8h vs. tid, etc.)  Sig: Specify # of pills to take each dose  Prescribe an endpoint. (prn pain, till gone)

5. Antibiotic Strategies  Cardinal Rules: 1) Use the right drug. 2) Use the right dose. 3) Use the correct dosing schedule. 4) Correct duration.  Hard and Fast—Especially early. Why?  Use a loading dose to rapidly achieve therapeutic blood levels.  Avoid combinations of bacteriostatic and bacteriocidal drugs.

6. Considerations  Gram Positive?  Gram Negative?  Mixed Infection?  Anaerobes?

7. Discussion: Antibiotic Choice  Narrow Spectrum?  Extended/Broad Spectrum?  Designer Antibiotics?  Anaerobes? Consider if the infection is present > 3days or if no improvement.

8. Narrow Spectrum Antibiotics  Specific for the pathogen.  Fewer disturbances of non-pathogenic bacteria.  Fewer side effects.  Rapid response for sensitive organisms.  Ex: Pen VK, Pen G, Erythromycin

9. Broad Spectrum Antibiotics  Affects both Gram + and Gram – bacteria, better for mixed infections.  May give up some effectiveness for Gram + to gain effectiveness for Gram -.  Examples: Amoxicillin, Ampicillin

10. Common Pathogens Necrotic pulp and apical abscesses Obligate anaerobic bacteria Gram negative rods Prevotella & porphyomonas spp. Fusobacterium spp. Campylobacter rectus Gram positive rods Eubacterium spp. Actinomycetes spp. Gram positive cocci Peptostreptococcus spp. Facultative anaerobic bacteria Gram positive cocci Strep and Entercoccus spp.

11. Common Pathogens  Periodontal Diseases Gingivitis Fuso, strep, & actinomycetes Adult peritonitis Bacteroides, porphyomonas, peptostreptococcus & prevotella Acute necrotizing ulcerative gingivitis Spirochetes, prevotella, fuso Localized juvenile periodontitis Actinobacillus

12. Common Pathogens Common Pathogens  Fungal Infections Candida spp. Mucorales spp.

13. Let’s Talk About Resistance   Three main types – –Chromosome mediated   Spontaneous mutations   Non-major form of drug resistance   Rarely lead to complete resistance – –Plasmid mediated (conjugation)   VERY important from clinical standpoint   Mostly gram negs   Mediate resistance to multiple drugs   High transfer rate from cell to cell – –Transposon (transduction and transformation)   Phage mediated   Clinically important for Gram +

14. Antibiotic Choices

15. ß-Lactams   Natural penicillins – –Pen VK and Pen G   MOA: Inhibit cell wall synthesis   Dose: 250-500 mg qid x 7-10 days   Contraindications: – –Allergies – –Poor renal fxn   Adverse events: GI upset   Drug interactions: oral contraceptives   Pregnancy category B

16. ß-Lactams   Natural penicillins – –Pen VK and Pen G   Bactericidal   Allergic reaction: rare (4 per 100,000)   Spectrum: – –Strep, staph, enterococcus, neiseria, treponema, listeria   Resistance: – –Mostly staph (>80%)

17. ß-Lactams   Amino-penicillins – –Amoxicillin, ampicillin   MOA: Inhibit cell wall synthesis   Dose: 250-500 mg q 8 h x 7-10 days   Contraindications: – –Allergies – –Poor renal fxn   Adverse events: GI upset   Drug interactions: oral contraceptives   Amoxicillin and clavulanic acid (Augmentin)

18. ß-Lactams   Amino-penicillins – –Amoxicillin, ampicillin   Bactericidal   “ampicillin” rash (4-10%)   Spectrum: – –Strep, staph, enterococcus, neiseria, treponema, listeria, E. coli, proteus, H. Flu, shigella, salmonella   Resistance: – –Entero, citro, serratia, proteus vulagris, provedincia, morganella, pseudomonas aeriginosa, acinetobacter

19. Cephalosporins   Cephalexin (Keflex) – –MOA: Inhibit cell wall synthesis – –Dose: 250-1000mg q 6 h x 7-10 days – –Contraindications:   Allergies   Poor renal fxn – –Adverse events: mild GI – –Drug interactions: probenecid – –Pregnancy category B

20. Cephalosporins   Cephalexin (Keflex) – –Bactericidal – –Spectrum:   Gram + – –Resistance:   Methicillin resistant gram + – –Low cross sensitivity with PCN

21. Lincosamides   Clindamycin (Cleocin) – –MOA: binds to the 50S ribosomal subunit and inhibits protein synthesis – –Dose: 100-450mg q 6 h x 7-10 days – –Precautions:   Poor hepatic fxn – –Adverse events: GI upset, pseudomembraneous colitis – –Drug interactions: neuromuscular blocking agents – –Pregnancy category B

22. Lincosamides   Clindamycin – –Bactericidal or static depending on concentration – – Spectrum:   Gram +, anaerobes, parasites – –Resistance   Enteroccocus *Clostridium diff. pseudomembranous colitis!!

23. Macrolides   Azithromycin (Zithromax), clarithromycin (Biaxin) – –MOA: bind to the 23S rRNA in the 50S subunit ribosome – –Dose: 250-500 mg/day x 5-10 days – –Precautions :   Poor hepatic fxn – –Adverse effects: GI – –Drug interactions: Cytochrome P-450 (Remember Seldane?) – –Pregnancy category B

24. Macrolides   Azithromycin, clarithromycin – –Bactericidal – –Spectrum:   Gram +, gram -, anaerobes – –Resistance:   B. fragilis, and strep pneumo

25. Tetracyclines   Doxycycline (Vibramycin) – –MOA: inhibit protein synthesis by preventing aminoacyl transfer RNA from entering the acceptor sites on the ribosome – –Dose: 100mg qd-bid x 7-14 days – –Contraindications:   Food   pregnancy – –Adverse events: GI – –Drug interactions: anti-epileptics – –Pregnancy category D

26. Tetracyclines   Doxycycline – –Bacteriostatic – –Spectrum:   Broad, Gram +, -, anaerobes, aerobes, and spirochetes – –Resistance:   Widespread, cross resistance – –PHOTO SENSITIVITY!!!

27. Nitroimidazoles   Metronidazole (Flagyl) – –MOA: reduced intermediate interacts and breaks the bacterial or parasitic DNA – –Dose: 250-1000 mg q 6-8 h x 7-10 days – –Precautions : poor hepatic fxn – –Adverse events: HA, N/V/D – –Drug interactions: EtOH, warfarin, Li+ – –Pregnancy category D

28. Nitroimidazoles   Metronidazole – –Bactericidal – –Spectrum:   Gram - anaerobes – –Resistance:   Rare, H. Pylori? – –Unpleasant metallic taste

29. Fluoroquinolones   Ciprofloxacin (Cipro) – –MOA: Inhibition of DNA gyrase, and Topo II – –Dose: 250-500 mg qd x 7-10 days – –Contraindications: <18 yrs old, pregnancy – –Adverse events: spontaneous tendon rupture – –Drug interactions: probenacid, warfarin – –Pregnancy category C

30. Fluoroquinolones   Ciprofloxacin – –Bactericidal – –Spectrum:   Very broad except B. frag – –Resistance:   MRSA, MRSE

31. Antifungals   Nystatin – –MOA: inhibit cell wall synthesis – –Dose: 5 ml swish and swallow q 4 h x 10-14 d – –GI upset – –Drug interactions: minor – –Pregnancy category C

32. Antifungals   Clotrimazole (Mycelex), ketoconazole (Nizoral), fluconazole (Diflucan) – –MOA: inhibit cell wall synthesis – –Dose: 200-800 mg qd x up to 12 months – –GI upset – –Drug interactions: major p-450 enzyme inhibitor, interactions with many drugs – –Pregnancy category C

33. ADA/AAOS Advisory Statement July 1997

34. AAOS Statement Antibiotic prophylaxis is NOT recommended for dental patients with plates, pins, or screws, nor is it routinely recommended for MOST dental patients with TOTAL JOINT REPLACEMENTS.

35. AAOS recommendations   Prophylaxis recommended – –Total joint replacement within the last two years AND:   Compromised immune system OR   Type 1 DM OR   Previous prosthetic joint infections OR   Malnourishment OR   Hemophilia

36. AAOS recommendations   Prophylaxis antibiotic recommendations – –Same as AHA OR – –No specific regimen recommended – –Keflex is often the first drug of choice

37. Legal Considerations  The dentist may not be aware of the patient’s medical condition.  Physician may not be aware of the advisory statements or of the dental procedure to be performed.  Vicarious Liability: “The devil made me do it”  “I forgot to take my antibiotic.”  Documentation.

38. Legal Considerations  I forgot my antibiotics!  Animal studies have shown antibiotics are effective up to 2 hours after the procedure.  Differentiate between prophylaxis vs. treatment of an early infection.  Take into consideration patient’s risk factors.  Legal twists.

39. In Summary….

40. Principles of Antibiotic Therapy   Therapeutic effectiveness – –Clinical indications   Pharmcodynamics, pharmacokinetics – –Age and extent of infection

41. Patient factors   Age, allergies, compliance, pregnancy risk   Patient function – –Renal, hepatic, immunosuppresion, route applicability   Cost – –Brand name, length of course, alternatives?

42. Cost Drug NameCost of Therapy $ (~10 Days) Generic if Available Pen VK6.81 Amoxicillin8.41 Ampicillin12.45 Cephalexin15.65 Clindamycin38.45 Azithromycin41.52 Clarithromycin74.45 Augmentin76.82 Doxycycline5.15 Metronidazole9.65 Ciprofloxacin76.65 Nystatin9.86 Clotrimazole97.05 Ketoconazole30.69 Fluconazole116.25

43. Dental Infection Acute—Rapid growth < 3 days Pen VK 500mg q6h or Amox 500mg q8h or Cephalosporin Allergic to PCN Clindamycin 300mg q8h or Cephalosporin (check allergic Rxn) or Azith or Clarithromycin Chronic > 3 days Think Anaerobes Add Metronidazole 250- 500mg To PCN, Amox, or Ceph Clindamycin 300mg q8h