Seek and Destroy: General Principles and

							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
2/8/2012                                    1
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”
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Time-dependant Killers

           Cephalosporin      Macrolides     Clindamycin
                   Tetracycline        Penicillin
                                                       MIC




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Concentration-dependant Killers

                      Quinolones

           Aminoglycosides         Metronidazole




                                                   MIC




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 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
  2/8/2012                                                    5
                    For cost information: www.drugstore.com
 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
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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
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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.




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Time-dependant Killers

           Cephalexin 1 gm



                                 2nd dose
                                            MIC




                             12 hours
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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

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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

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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


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




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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®)

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

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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



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

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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%

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                                     J Endod 2003 Jan;29(1):44
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


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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

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Penicillinase-resistant penicillins
 Examples:
      IV - methicillin, nafcillin
      PO - cloxacillin, dicloxacillin
 Coverage
      Gram + including staph,
       anaerobes




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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

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




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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)

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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




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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
2/8/2012                                      29
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



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



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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

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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)

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

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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

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 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
 2/8/2012                                             36
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


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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.

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

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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
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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

2/8/2012                                        41
 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

 2/8/2012                                                   42
 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)



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 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

 2/8/2012                                            44
Fluoroquinolones
 First generation quinolone
      Nalidixic acid (NegGram)
 Second generation fluoroquinolone
      IV and PO - ciprofloxacin
      Others - ofloxacin, norfloxacin, lomefloxacin,
       enoxacin
      Coverage
            Gram - only



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


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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

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                              J Am Coll Cardiol 2008;52(8):676-85
 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

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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.


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




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