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Seek and Destroy: General Principles and Antibiotic Choices in Treating Dental Infections

Seek and Destroy: General Principles and Antibiotic Choices in Treating Dental Infections. Kelly W. Jones, Pharm.D., BCPS McLeod Family Medicine Center kjones@mcleodhealth.org. Two types of antibiotics. Time-dependent killers Penicillin, cephalosporin, imipenem

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Seek and Destroy: General Principles and Antibiotic Choices in Treating Dental Infections

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  1. Seek and Destroy:General Principles andAntibiotic Choices in Treating Dental Infections Kelly W. Jones, Pharm.D., BCPS McLeod Family Medicine Center kjones@mcleodhealth.org

  2. Two types of antibiotics • Time-dependent killers • Penicillin, cephalosporin, imipenem • clindamycin, macrolides, TMP/SMX, tetracyclines • Accumulation at the site of infection is important at inhibiting bacterial growth • Concentration-dependent killers • Quinolones, Aminoglycosides, Metronidazole • “qAm”

  3. Time-dependant Killers Macrolides Clindamycin Cephalosporin Tetracycline Penicillin MIC

  4. Concentration-dependant Killers Quinolones Metronidazole Aminoglycosides MIC

  5. Dosing Issues • Three times a day and four times a day dosing is a set up for adherence problems. • Use total daily dose twice a day. • Cephalexin (Keflex®) • 250 mg capsule (#30 cost $14) • 500 mg capsule (#30 cost $14) • 750 mg capsule (#30 cost $100) • 125 mg/5 ml; 250 mg/5 ml each in 100 and 200 ml • Each of these are ~$18 For cost information: www.drugstore.com

  6. Dosing Issues • Three times a day and four times a day dosing is a set up for adherence problems. • Use total daily dose twice a day. • Cephalexin (Keflex®) • 250 mg capsule (#30 cost $14) • 500 mg capsule (#30 cost $14) • 750 mg capsule (#30 cost $100) • 125 mg/5 ml; 250 mg/5 ml each in 100 and 200 ml • Each of these are ~$18

  7. Dosing Issues • Keflex® 750 mg is branded drug. • Why? • Has indication for BID use or as JCAHO wants you to write: twice daily use. • Therefore write: • Cefalexin 500 mg capsules, take 2 capsules twice daily. 1 gm twice a day! • You can do this with Penicillin

  8. You may be wondering? • Why can you give an antibiotic that is a time-dependent killer less often? • Pharmacokinetic principle: • As you increase the dose and the serum concentration, you can stay above the MIC until the next dose - dose dependent.

  9. Time-dependant Killers Cephalexin 1 gm 2nd dose MIC 12 hours

  10. Dosing Issues: Concentration Killers • “qAm” • More is better! • Examples: Fluoroquinolone • Levofloxacin • 250 mg (#10 cost $120) • 500 mg (#10 cost $168) • 750 mg (#10 cost $260) • 5 day therapy for CAP • Metronidazole for trichomonas infection • 2 gram single dose is better than 500 mg bid for 7 days

  11. Administration • IV • 100% bioavailable • Best for the sickest patient, they often poorly absorbs oral drugs • PO • Several classes of drugs have excellent bioavailability similar to their IV dose • TMP/SMX, FQ, metronidazole • Mayo Clin Proc 1998;73:995

  12. Research Question of 2010 • How long do we treat? • Otitis media • 5 days • Uncomplicated UTI’s • 3 days with all drugs • Uncomplicated pyelonephritis • 7 days with FQ • Strep throat • 10 days

  13. How long do we treat? • Prostatitis • 6 weeks with TMP/SMX; 2-4 weeks FQ • CAP • 7 to 14 days (14 if in hospital) • Bronchitis • 0 days, Do not treat! • Treatment is recommended for smokers and chronic lung disease patients

  14. Dental Infections • How long do we treat? • ???? • Treat as cellulitis - 7 to 10 days

  15. Common Oral Dental Antibiotics • Penicillin (Pen-Vee K®) • Amoxicillin (Amoxil®) • Amoxicillin/clavulanate (Augmentin®) • Clindamycin (Cleocin®) • Cephalexin (Keflex®) • What about cefdinir? • Erythromycin/Azithromycin/Clarithromycin • Metronidazole (Flagyl®) • IV • Ampicillin/Sulbactam (Unasyn®)

  16. How to select an antibiotic! • CSI-like • Where is the infection? • What are the bugs? • Guess the organism based on epidemiology research • What is the best antibiotic? • Initial antibiotic choice is always empiric therapy

  17. Where is the infection? • Mouth • Reversible pulpitis • Irreversible pulpitis • Absess • Cellulitis • Pericoronitis • Periodontal Disease • Antibiotic are best utilized in situations of regional spread

  18. What are the bugs? • Dominant isolates are anaerobic bacteria. • Streptococcus mutans • are thought to cause initial caries infection • Alpha-hemolytic streptococci, a.k.a. Streptococcus viridans • Can coexhist with staph • Streptococcus anginosis

  19. What are the bugs? • Others • Gram +: • Peptostreptococci • Gram negative: • Bacteroides • Prevotella (Bacteroidesmelaninogenicus) • Porphyromonas • Fusobacterium nucleatum • Infections through the fascial planes usually are polymicrobial (average 4-6 organisms).

  20. Efficacy • Bacteria associated with endodontic abscesses reported to be susceptible to several antibiotics (level 3 [lacking direct] evidence) • based on cultures of 98 species of bacteria aseptically aspirated by needle from endodontic abscesses • Amoxicillin 91% • Amoxicillin/clavulanate 100% • Clindamycin 96% • Penicillin V 85% • Metronidazole 45% • Metronidazole with penicillin V 93% • Metronidazole with amoxicillin 99% J Endod 2003 Jan;29(1):44

  21. Consensus Statement • no evidence to recommend one antibiotic regimen over another for management of systemic complications of acute apical abscess • Based on systematic review and meta-analysis • 14 trials

  22. What is the best antibiotic? • Natural penicillin • Coverage • Gram +, anaerobes • But no staph • Products: • IV - Aqueous Pen G, benzathine Pen G • PO - Pen VK, Vee Tids • Dose: 1 gram twice daily ( 2-500 mg tabs) • Children: 50 mg/kg/day divided into 2 doses

  23. Penicillinase-resistant penicillins • Examples: • IV - methicillin, nafcillin • PO - cloxacillin, dicloxacillin • Coverage • Gram + including staph, anaerobes

  24. Methicillin-resistant Staph Aureus • 95% of staph was resistant to penicillin by 1953 • MRSA was first isolated in 1968 • Methicillin was developed in 1960 • incidence of infection • MRSA has risen from < 10% of all infecting staph aureus infections in the hospital in 1983 to 64% in 2004 to 70% in the intensive care units in 2008 • MRSA is prevalent

  25. MRSA • Drugs for treatment of community-acquired MRSA • Tetracycline 500 mg qid • Doxycycline 100 mg bid • Minocycline 100 mg bid • TMP/SMX 320 mg bid of trimethoprim (2 DS bid) • Clindamycin 300 to 450 mg tid • Levofloxacin 750 mg daily • Moxifloxacin 400 mg daily • Linezolid 600 mg bid

  26. MRSA • You can always add a second antibiotic: • Synergy with: • Rifampin 300 mg twice daily • $65 for 30 caps

  27. Practice Recommendations • JFP 2008;57(9):588-2 • MRSA abscesses are best managed by incision and drainage alone (90% cure rate vs 84% with antibiotics, level A evidence). • If incision and drainage fail within 7 days, add an oral antibiotic. • Eradication of MRSA from the nasal passages is not useful in preventing the spread of the infection in communities (level B evidence). • In one military study, 121 men with MRSA colonization needed to be treated with nasal mupirocin to prevent one MRSA infection (Antimicrob Agents Chemother. 2007;51:3591-8)

  28. Extended-spectrum penicillin • Aminopenicillins • Examples: • IV - Ampicillin • PO - Ampicillin, amoxicillin • Coverage • Gram + (no staph), enterococcus, anaerobes, basic gram - • 34% of Prevotella species are resistant to amoxicillin

  29. Amoxicillin • Availability - should be $12 or less for most • 250 mg capsule • 500 mg capsule • 500 tablet • 875 mg tablet ($27 for #30) • Chewables 125 mg, 250 mg • Suspension • 250 mg/5 ml • 400 mg/5 ml

  30. New Drug Formulation • Amoxicillin (Moxatag®) • Once-daily form, for Strep pharyngitis and tonsillitis • Pulsys delivers stacccato pulses (3) over 6 hrs • 775 mg tablet • 1 immediate release, 2 delay-release • 10 day course is $90

  31. Extended-spectrum penicillin • Antipseudomonal penicillins • Examples: • IV - ticarcillin, pipercillin • PO - carbenicillin • Coverage • Gram + (no staph), broad gram neg, anaerobes

  32. Extended-spectrum penicillin • Beta-lactamase inhibitor penicillin • Examples: • IV - ticarcillin-clavulanate (Timentin®), pipercillin-tazobactam (Zosyn®), ampicillin-sulbactam (Unasyn®) • PO - Amoxicillin-clavulanate (Augmentin®) • Coverage • Gram +, broad gram -, anaerobes

  33. Augmentin® - now generic • Chewable 400-57mg ($60/#20) • Suspension (~$50 to $60) • 250-62.5mg/5ml 75ml, 100 ml, 150 ml Bottle • 600-42.9mg/5ml, 75ml Bottle • Tablets • 250-125mg ($100/#20) • 500-125mg ($46/#20) • 875-125mg ($32/#20)

  34. Cephalosporins • Minimal utility for dental infections • First generation • Examples: • IV - Cefazolin (Ancef®) • PO - Cephalexin (Keflex®) • Coverage • Broad Gram +, including staph • No anaerobe coverage

  35. Cephalosporins • Second generation • Examples: • IV - cefuroxime (Zinacef®), cefoxitin (Mefoxin®) • PO - Cefaclor (Ceclor®), cefpodoxime proxetil, cefuroxime axetil, cefprozil, loracarbef • Coverage • Broad gram +, basic gram - • Some have minimal anaerobe coverage

  36. Cephalosporins • Third generation • Examples: • IV - ceftriaxone, ceftizoxime, cefotaxime • PO - cefixime, ceftebutin, cefdinir (Omnicef®) • Coverage • Broad Gram +, broad gram - • Ceftazidime (Fortaz®) - only gram -, but includes pseudomonas • Oral drugs loose gram + reliability

  37. Cephalosporins • Fourth generation • Examples: • IV - cefepime (Maxipime®) • PO - none • Coverage • Broad Gram +, broad gram -, including pseudomonas • Poor anaerobe coverage • Fifth generation cephalosporin due out soon - ceftaroline • Added MRSA coverage

  38. Dental Principle • Cephalosporin - best for general cellulitis • PO • Cephalexin (Keflex®) • Cefdinir (Omnicef®) • 300 mg capsule - $36 for #20 • 125 mg/5 ml, 60 ml, $48 • IV or IM • Ceftriaxone (Rocephin®) • If you decide to use a cephalosporin, it is best to add metronidazole for anaerobe coverage.

  39. Macrolides • Examples: • IV - azithromycin, erythromycin • PO - azithromycin, clarithromycin, erythromycin, dirithromycin • Coverage • Broad gram +, minimal gram - (h.flu?), • atypicals • no anaerobes

  40. Azithromycin Review • Z-pak (generic $26) • Tri-pak ($44) • Zmax • 1 gm powder for oral suspension • Suspension • 100mg/5ml, 15 ml ($50 - brand name only) • 250 mg/5ml, 15 ml, 22.5 ml, 30 ml - $32 • 600 mg tablet

  41. Clarithromycin (Biaxin®) • Tablets • 250 mg ($100/#30) • 500 mg • 500 mg, 24 hr tablet ($160/#30) • Suspension • 125 mg/5 ml, 50 ml, 100 ml • 250 mg/5 ml, 50 ml ($40), 100 ml ($80) • New FDA alert: do not give with colchicine

  42. Sulfonamides • Examples: TMP/SMX • IV - trimethoprim/sulfamethoxazole • PO - trimethoprim/sulfamethoxazole, erythromycin/sulfamethoxazole (Pediazole®) • Coverage • Great staph drug, alternative for strep and does NOT cover S pyogenes (group A, beta-hemolytic) or enterococcus • Good gram - with some pseudomonal coverage • no anaerobes • Poor-man’s regimen - add metronidazole

  43. Clindamycin (Cleocin®) • Coverage • broad gram +, broad anaerobe • IV dose is larger than the oral dose • Great for the penicillin allergy patient • Dosing • PO • 150 mg capsule (generic $25/#30) • 300 mg capsule (generic $80/#30)

  44. You can always add….. • Metronidazole • Coverage • Broad anaerobe coverage • Dose twice daily • PO • Tablets ($12/#30) • 250 mg • 500 mg • 750 mg ($200/#30) - 24 hour tablet

  45. Fluoroquinolones • First generation quinolone • Nalidixic acid (NegGram) • Second generation fluoroquinolone • IV and PO - ciprofloxacin • Others - ofloxacin, norfloxacin, lomefloxacin, enoxacin • Coverage • Gram - only

  46. Fluoroquinolones • Third generation fluoroquinolone • IV and PO • Levofloxacin, {gatifloxacin}, gemifloxacin moxifloxacin (respiratory quinolone) • Coverage • Broad gram + • Broad gram - • NO anaerobes

  47. SBE Prophylaxis - In who? • ACC/AHA Task Force Update 2008 • Prosthetic cardiac valve • Previous infective endocarditis • Congenital heart disease (CHD) • Unrepaired cyanotic CHD, including palliative shunts and conduits • Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure • Prosthetic material for valve repair • Cardiac transplantation recipients who develop cardiac valvulopathy J Am Coll Cardiol 2008;52(8):676-85

  48. SBE Prophylaxis - Dental Procedure? • Dental procedures that involve manipulation of the gingival tissue • Periapical region of the teeth • Perforation of the oral mucosa • No longer required for: • Routine anesthetic injections • X-ray • Bleeding from trauma to the lips or oral mucosa

  49. SBE Prophylaxis - With what? • Adults • amoxicillin 2 g PO 1 hour before procedure. • Children • amoxicillin 50 mg/kg • If by IV, administer ampicillin 2 g for adults and 50 mg/kg for children within 30 minutes before the procedure. • For patients allergic to penicillin • Adult - Clindamycin 600 mg PO/IV 1 hour before the procedure. Children -Clindamycin 20 mg/kg PO/IV. • Alternatively, azithromycin or clarithromycin 500 mg PO 1 hour before the procedure may be administered for adults and 15 mg/kg PO may be administered for pediatric patients.

  50. Questions??? E-mail: kjones@mcleodhealth.org

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