1. Seek and Destroy: General Principles and Antibiotic Choices in Treating Dental Infections
Kelly W. Jones, Pharm.D., BCPS
McLeod Family Medicine Center
11/7/2018

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”
11/7/2018

3. Time-dependant Killers
Macrolides
Clindamycin
Cephalosporin
Tetracycline
Penicillin
MIC
11/7/2018

4. Concentration-dependant Killers
Quinolones
Aminoglycosides
Metronidazole
MIC
11/7/2018

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
11/7/2018
For cost information:

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
11/7/2018

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
11/7/2018

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.
11/7/2018

9. Time-dependant Killers
Cephalexin 1 gm
2nd dose
MIC
12 hours
11/7/2018

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
11/7/2018

11. Administration IV PO 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
11/7/2018

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
11/7/2018

13. How long do we treat? Prostatitis CAP Bronchitis
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
11/7/2018

14. Dental Infections How long do we treat? ????
Treat as cellulitis - 7 to 10 days
11/7/2018

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®)
11/7/2018

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
11/7/2018

17. Where is the infection? Mouth
Reversible pulpitis
Irreversible pulpitis
Absess
Cellulitis
Pericoronitis
Periodontal Disease
Antibiotic are best utilized in situations of regional spread
11/7/2018

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
11/7/2018

19. 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).
11/7/2018

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%
11/7/2018
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
11/7/2018

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 ( mg tabs)
Children: 50 mg/kg/day divided into 2 doses
11/7/2018

23. Penicillinase-resistant penicillins
Examples:
IV - methicillin, nafcillin
PO - cloxacillin, dicloxacillin
Coverage
Gram + including staph,
anaerobes
11/7/2018

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
11/7/2018

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
11/7/2018

26. MRSA You can always add a second antibiotic: Synergy with:
Rifampin 300 mg twice daily
$65 for 30 caps
11/7/2018

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)
11/7/2018

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
11/7/2018

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
11/7/2018

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
11/7/2018

31. Extended-spectrum penicillin
Antipseudomonal penicillins
Examples:
IV - ticarcillin, pipercillin
PO - carbenicillin
Coverage
Gram + (no staph), broad gram neg, anaerobes
11/7/2018

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
11/7/2018

33. Augmentin® - now generic
Chewable mg ($60/#20)
Suspension (~$50 to $60)
mg/5ml 75ml, 100 ml, 150 ml Bottle
mg/5ml, 75ml Bottle
Tablets
mg ($100/#20)
mg ($46/#20)
mg ($32/#20)
11/7/2018

34. Cephalosporins Minimal utility for dental infections First generation
Examples:
IV - Cefazolin (Ancef®)
PO - Cephalexin (Keflex®)
Coverage
Broad Gram +, including staph
No anaerobe coverage
11/7/2018

35. Cephalosporins Second generation Examples: Coverage
IV - cefuroxime (Zinacef®), cefoxitin (Mefoxin®)
PO - Cefaclor (Ceclor®), cefpodoxime proxetil, cefuroxime axetil, cefprozil, loracarbef
Coverage
Broad gram +, basic gram -
Some have minimal anaerobe coverage
11/7/2018

36. Cephalosporins Third generation Examples: Coverage
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
11/7/2018

37. Cephalosporins Fourth generation Examples: Coverage
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
11/7/2018

38. Dental Principle Cephalosporin - best for general cellulitis
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.
11/7/2018

39. Macrolides Examples: Coverage IV - azithromycin, erythromycin
PO - azithromycin, clarithromycin, erythromycin, dirithromycin
Coverage
Broad gram +, minimal gram - (h.flu?),
atypicals
no anaerobes
11/7/2018

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
11/7/2018

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
11/7/2018

42. Sulfonamides Examples: TMP/SMX Coverage
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
11/7/2018

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)
11/7/2018

44. You can always add….. Metronidazole Coverage Dose twice daily PO
Broad anaerobe coverage
Dose twice daily PO
Tablets ($12/#30)
250 mg
500 mg
750 mg ($200/#30) - 24 hour tablet
11/7/2018

45. Fluoroquinolones First generation quinolone
Nalidixic acid (NegGram)
Second generation fluoroquinolone
IV and PO - ciprofloxacin
Others - ofloxacin, norfloxacin, lomefloxacin, enoxacin
Coverage
Gram - only
11/7/2018

46. Fluoroquinolones Third generation fluoroquinolone IV and PO
Levofloxacin, {gatifloxacin}, gemifloxacin moxifloxacin (respiratory quinolone)
Coverage
Broad gram +
Broad gram -
NO anaerobes
11/7/2018

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
11/7/2018
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
11/7/2018

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.
11/7/2018

50. E-mail: kjones@mcleodhealth.org
Questions???
11/7/2018