Antibiotic Use In Dentistry Kevin Nakagaki, D.D.S. Director, Hospital Dental Clinic University of Minnesota 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 # 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) Barry Brainfart Dental Clinic 666 Bite Me Ln Crossbyte Falls, MN Ph: 555-YOU-HURT Pt. Name: Rx: Disp: Sig: Refill____ Address: DOB: Date: Barry Brainfart, DDS DEA:______________________ 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. Considerations Gram Positive? Gram Negative? Mixed Infection? Anaerobes? Discussion: Antibiotic Choice Narrow Spectrum? Extended/Broad Spectrum? Designer Antibiotics? Anaerobes? Consider if the infection is present > 3days or if no improvement. 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 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 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. 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 Common Pathogens Fungal Infections Candida spp. Mucorales spp. 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 + Antibiotic Choices 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 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%) 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) 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 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 Cephalosporins Cephalexin (Keflex) – Bactericidal – Spectrum: Gram + – Resistance: Methicillin resistant gram + – Low cross sensitivity with PCN 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 Lincosamides Clindamycin – Bactericidal or static depending on concentration – Spectrum: Gram +, anaerobes, parasites – Resistance Enteroccocus *Clostridium diff. pseudomembranous colitis!! 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 Macrolides Azithromycin, clarithromycin – Bactericidal – Spectrum: Gram +, gram -, anaerobes – Resistance: B. fragilis, and strep pneumo 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 Tetracyclines Doxycycline – Bacteriostatic – Spectrum: Broad, Gram +, -, anaerobes, aerobes, and spirochetes – Resistance: Widespread, cross resistance – PHOTO SENSITIVITY!!! 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 Nitroimidazoles Metronidazole – Bactericidal – Spectrum: Gram - anaerobes – Resistance: Rare, H. Pylori? – Unpleasant metallic taste 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 Fluoroquinolones Ciprofloxacin – Bactericidal – Spectrum: Very broad except B. frag – Resistance: MRSA, MRSE 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 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 ADA/AAOS Advisory Statement July 1997 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. 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 AAOS recommendations Prophylaxis antibiotic recommendations – Same as AHA OR – No specific regimen recommended – Keflex is often the first drug of choice 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. 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. In Summary…. Principles of Antibiotic Therapy Therapeutic effectiveness – Clinical indications Pharmcodynamics, pharmacokinetics – Age and extent of infection Patient factors Age, allergies, compliance, pregnancy risk Patient function – Renal, hepatic, immunosuppresion, route applicability Cost – Brand name, length of course, alternatives? Cost Drug Name Cost of Therapy $ (~10 Days) Generic if Available Pen VK 6.81 Amoxicillin 8.41 Ampicillin 12.45 Cephalexin 15.65 Clindamycin 38.45 Azithromycin 41.52 Clarithromycin 74.45 Augmentin 76.82 Doxycycline 5.15 Metronidazole 9.65 Ciprofloxacin 76.65 Nystatin 9.86 Clotrimazole 97.05 Ketoconazole 30.69 Fluconazole 116.25 Dental Infection Acute—Rapid growth < 3 days Chronic > 3 days Pen VK 500mg q6h or Amox 500mg q8h or Cephalosporin Think Anaerobes Add Metronidazole 250-500mg To PCN, Amox, or Ceph Allergic to PCN Clindamycin 300mg q8h Clindamycin 300mg q8h or Cephalosporin (check allergic Rxn) or Azith or Clarithromycin