Document

Report
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
7/18/2015
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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
Tetracycline
Clindamycin
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
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For cost information: www.drugstore.com
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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
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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


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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
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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



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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 metaanalysis
 14 trials
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What is the best antibiotic?
 Natural penicillin
 Coverage
 Gram +, anaerobes
 But no staph
 Products:




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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
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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

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
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
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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®), ampicillinsulbactam (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
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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
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
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
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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
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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
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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?
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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
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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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