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1
Good Morning
MOHD.SIBGHATULLAH KHATIB
1ST YEAR PG STUDENT
ANTIBIOTICS IN ENDODONTICS
2
CONTENTS
• INTODUCTION
• HISTORY
• CLASSIFICATION OF
ANTIBIOTICS
• SELECTION OF
ANTIMICROBIALAGENTS
• BACETRIOLOGY
• ODONTOGENIC INFECTION
• COMMONLY USE ANTIIBIOTIC
IN ORAL INFECTION
• COMPLICATION OF ANTIBIOTIC
THERAPY
• FASCIAL SPACE INFECTION
• MANAGEMENT OF ABSSCESS
AND CELLULITIS
• ANTIBIOTIC PROPHYLAXIS
• RESISTANCE
• ANTIBIOTIC DOSAGE
• USE OF ANTIBIOTIC AS AN INTRA
CANAL MEDICAMENT
• MYTHS
• CONCLUSION
• REFRENCES
3
• Antibiotics-These are substances produced by
microorganisms, which selectively suppress the growth of or
kill other microorganisms at very low concentrations
• Antimicrobial agent (AMA)-synthetic as well as naturally
obtained drugs that attenuate microorganisms
• Chemotherapy-Treatment of systemic infections with specific
drugs that selectively suppress the infecting microorganism
without significantly affecting the host
4
3 phases:
Empirical phase Ehrlich's phase
The modem era of
chemotherapy
5
History
Empirical phase
• Mouldy curd by Chinese on boils
• Chaulmoogra oil for leprosy,
• Chenopodium by Aztecs for intestinal worms,
• Mercury by Paracelsus (16th century) for syphilis,
• Cinchona bark (17th century) for fevers.
6
Ehrlich's phase (1890-1935)
• Ehrlich given the idea that if certain dyes could selectively stain microbes,
they could also be selectively toxic to these organisms. He tried
methyleneblue, trypan red, etc
• He developed arsphenamine in 1906 and neoarsphenamine in 1909 for
syphilis.
• He coined the term 'chemotherapy'
7
Modern era
• Domagk (1935) - The therapeutic effect of Prontosil.
• Pasteur (1877) - Demonstrated the phenomenon of antibiosis :
growth of anthrax bacilli in urine was inhibited by air-borne
bacteria.
8
• Fleming (1929) - Discovered penicillin .
• Chain and Florey (1941)- Clinical use of penicillin .
• Waksman and his colleagues (1944)- Discovered
streptomycin
9
10
Golden era in antibiotic discovery
CLASSIFICATION OF ANTIBIOTIC
11
• Based on
A. Chemical structure
B. Mechanism of action
C. Type of organism against which primarily active
D. Spectrum of activity
E. Type of action
TRIPATHI 6TH EDITION
MECHANISM OF ACTION
12
• Inhibit cell wall synthesis
– Penicillin
– Cepholosporin
– Vancomycin
– Bacitracin
• Cause leakage from cell
membrane
– Polypeptide: polymixin, Colistin
– Polyenes:Amp-B,nystatin
• Inhibit protein synthesis
– Tetracycline
– Chloramphenicol
– Macrolides
• Mis-reading of m-RNA
– Aminoglycosides
• Inhibit DNA gyrase
– Fluoroquinolones
• Interfere with DNA function
– Rifampicin
– Metronidazole
• Interfere with DNA
synthesis
– Acylovir
– Zidovudine
– Idoxuridine
• Interfere with
intermediatory metabolism
– Sulfonamide
– Ethambutol
13
TRIPATHI 6TH EDITION
ANTIBIOTICS
 BACTERIOSTATIC
• Sulfonamides
• Erythromycin
• Tetracyclines
• Ethambutol
• Chloramphenicol
• Clindamycin
 BACTERICIDAL
• Penicillins
• Cephalosporins
• Aminoglycosides
• Vancomycin
• Metronidazole
• Cotrimoxazole
14
TRIPATHI 6TH EDITION
Spectrum of activity
 Narrow-spectrum
• Penicillin G
• Streptomycin
• Erythromycin
 Broad-spectrum
• Tetracyclines
• Chloramphenicol
15
Extended-spectrum
•Ampicillin
•Amoxycillin
Lippincotts pharmacology 5th edition
SELECTION OF ANTIMICROBIALAGENTS
 The organism’s identity
 Patient factors
 The site of the infection
 The organism’s susceptibility to a particular agent
 The safety of the agent
 The cost of therapy
16
Lippincotts pharmacology 5th edition
BACTERIOLOGY
17
• The pulpodentin complex is sterile.
• Bacterial invasion of dentinal tubules occurs more
rapidly in nonvital teeth than in vital ones.
18
COHEN 10TH EDITION
19
ENDODONTICS
INFECTION
INTRARADICULAR
PRIMARY SECONDARY PERSISTANT
EXTRARADICULAR
COHEN 10TH EDITION
20
Siquiera jr et al : update endodontic microbiology 2008
ODONTOGENIC INFECTION
21
PULPITIS
Apical periodontitis
PERIAPICAL ABSCESS
PERIAPICAL GRANULOMA
PERIODONTAL CYST
OSTEOMYELITIS
PERIOSTEITIS
CELLULITIS ABSCESS
ACUTE CHRONIC
ACUTE CHRONIC
ACUTE CHRONIC
FOCAL DIFFUSE
Reversible Irreversible
When do you need the drugs to kill the bugs?
• Fever > 100° F
• Malaise
• Lymphadenopathy
• Trismus
• Increased Swelling
• Cellulitis
• Osteomyelitis
• Persistent Infection
22
American Association of Endodontists, 2006
Just say NO! Kill the bugs without the drugs
Irreversible pulpitis,
Acute apical periodontitis,
Draining sinus tracts,
After endodontic surgery,
To prevent flare-ups,
After incision for drainage of a localized swelling
(without cellulitis, fever, or lymphadenopathy)
23
COHEN 10th edition
COMMONLY USED ANTIBIOTIC IN ORAL
INFECTION
24
Antibiotics for odontogenic infections
25
DOSAGE
26
Antibiotic Dosage Duration
Penicllin V 250mg/500mg Every4-6hours/5-7days
Amoxicillin /
Amoxicillin with clavulanate
250mg/500 mg Every 8 hours/5-7 days
Clindamycin 300 mg/600mg Every 6 hours/5-7 days.
Metronidazole 200mg/400 mg Every 8 hours/5-7 days.
Azithromycin 250mg/500mg Once a day /5-7 days.
American Association of Endodontists 2006
27
COMPLICATIONS OF ANTIBIOTIC THERAPY
• Hypersensitivity
• Direct toxicity
• Superinfections
28
lippincotts pharmacology 5th edition
THE FASCIAL SPACES
The mandible and
below
The buccal
vestibule
Body of the
mandible
The mental space
The submental
space
The sublingual
space
Submandibular
space
The cheek and
lateral face
The buccal
vestibule of the
maxilla
The buccal space
The submasseteric
space
The temporal space
The pharyngeal and
cervical areas
The pterygo-
mandibular space
The para-
pharyngeal
spaces
The cervical
spaces
The
midface
The palate
The base of
the upper
lip
The canine
spaces
The
periorbital
spaces
29
Management of Abscesses and Cellulitis
• Correct diagnosis
• Removal of the cause
• Incision for drainage is indicated for any infection marked
by cellulitis. It is important to provide a pathway of
drainage to prevent further spread of the abscess and/or
cellulitis.
30
COHEN 10th edition
Systemic Antibiotics for Endodontic Infections
• Selection of antibiotics-
– Empirical
– based on the results of microbial susceptibility tests.
• For diseases with known microbial causes, empirical
therapy may be used.
• Most of the bacterial species involved with endodontic
infections, including abscesses, are susceptible to
penicillins .
31
COHEN 10TH EDITION
32
33
• Managment
 Amoxicillin (500 mg, orally) at
intervals of 8 h for 7 days and
dexamethasone (4 mg, intramuscularly)
at intervals of 24 h for 3 days
 2% chlorhexidine gel applied with a 5-
ml syringe
TOOTH AVULSION
• Systemic administration of antibiotics is generally
recommended in order to prevent the harmful effects of
bacterial contamination.
• Antibiotics decrease the incidence of inflammatory root
resorption but have a limited, or no, effect on the pulp
34
Australian Dental Journal Endodontic Supplement 2007
• Gram-negative obligate anaerobic rods
– Porphyromonas spp.
– Prevotella spp.
• Prophylactic use of antibiotic to decrease incidence of
flare up Controversy.
Flare-Up’s
Cohen pathways of pulp : 10 th edition 35
ANTIBIOTIC PROPHYLAXIS
36
Infective Endocarditis (IE)
• A life threatening disease with substantial morbidity and
mortality which affects individuals with underlying
structural cardiac defects who develop bacteremia.
37
38
JADA, Vol. 131, March 2000
39
JADA, Vol. 131, March 2000
40
JADA, Vol. 131, March 2000
• The French agency for Health Product Health Safety
advices against or contraindicates
– Dental facial surgery,
– Bone surgery,
– Periodontal surgery,
– Root canal treatment in these patients except under emergency
situations,
As these patients are prone to high risk of infection.
41
Asian Pac J Trop Biomed 2012; 2(9): 749-754
42
American Heart Association, 2007; 116: 1736-1754
PREGNANCY
• Any drug used during pregnancy should be taken
only under the supervision of the patient’s
physician.
43
lippincotts pharmacology 5th edition
44
CATEGORY DESCRIPTION DRUS
A No human fetal risk or
remote possibility of fetal
harm
B No controlled studies show
human risk;
animal studies Suggest
potential Toxicity
β-Lactams,β-Lactams with inhibitors,
Cephalosporins, Aztreonam , Clindamycin,
Erythromycin, Azithromycin, Metronidazole
Nitrofurantoin. Sulfonamides
C Animal fetal toxicity
demonstrated; human risk
Undefined
Chloramphenicol, Fluoroquinolones,
Clarithromycin, Trimethoprim, Vancomycin
Gentamicin, Trimethoprim-sulfamethoxazole
D Human fetal risk present,
but benefits
Mayoutweigh Risks
Tetracyclines, Aminoglycosides
(except gentamicin)
X Human fetal risk present
but does not
Outweigh benets;
contraindicated in
pregnancy
United States FDA categories of antimicrobials and fetal risk.
lippincotts pharmacology 5th edition
Partial List of Drugs Usually Compatible With Both
Pregnancy and Breast-Feeding
• Local anesthetics including lidocaine , etidocaine , and
prilocaine
• Penicillins- 250mg/500mg(Every 8 hours)
• Clindamycin- 300/600mg(6 hrs)
• Azithromycin- 250/500mg(OD)
• Acyclovir
• Prednisone
45
COHEN 10TH EDITION
ANTIBIOTICS AND DOSAGES
46
Antibiotic Dosage Trade name Brand name Cost
AMOXICILLIN
250mg/500mg
(Every 8 hours)
AMOXIL 500 mg
CAP.
ZYDUS CADILA
Rs32.5
(10 cap)
AMOXIL250 mg
CAP.
ZYDUS CADILA
Rs20
(10 cap)
NOVAMOX
500 mg CAP.
CIPLA
Rs105.68
(15 cap)
WYMOX 500 mg
CAP.
PFIZER LTD
Rs147.0
(15 cap)
BLUMOX 500 mg
CAP.
BLUE CROSS
LAB. LTD
Rs70.0
(10 cap)
CIPMOX 500 mg
CAP.
CIPLA
Rs105.81
(10 cap)
47
Antibiotic Dosage Trade name Brand name Cost
Amoxicillin
With
lactobacillus
spores
250mg/500mg
(Every 8 hours)
NOVAMOX LB 500
CAP
CIPLA
Rs116.5
(6 cap.)
NOVAMOX LB 250
CAP
CIPLA
Rs57.62
(10 cap)
Amoxicillin and
clavulanic acid 500mg+125mg
AMOXYCLAV
500/125MG TAB.
ABBOTT INDIA LTD
Rs51.25
(6 tab)
MOXIKIND-CV 625
TAB.
MANKIND PHARMA
LTD
Rs82.76
(6 tab)
CIPMOX CV 500/125
MG TAB.
CIPLA LTD
Rs79.68
(6 tab)
AUGMENTIN 625
DUO TAB
GSK
Rs259.73
(10 tab)
Amoxicillin and
cloxacillin
250mg+250mg/
125mg+125mg
NATACLOX 250 MG
CAP
SUN PHARMA
Rs31.37
(10 cap)
48
Antibiotic Dosage Trade name Brand name Cost
CEFADROXIL
125mg/250mg/
500mg
(every 12 hrs)
ODOXIL DT-250 LUPIN LTD Rs26 (10 tab)
CEFADUR
250MG TAB
CIPLA LTD Rs 26.0 (10 tab)
CEFOXID 250
MG TAB
ALKEM LAB.
LTD
Rs153.05 (10 tab)
CEFUROXIME 125 mg
(every 12 hrs)
CEFAKIND
125MG TAB
MANKIND
PHARMA LTA
Rs69.0 (10 tab)
CEFIXIME 200mg (bid)
TAXIM O
400MG TAB
ALKEM LAB
LTD
Rs345 (10 tab)
CEFIX 400MG CIPLA LTD Rs115.57 (4 tab)
CLINDAMYCIN 300/600mg(6 hrs)
DALCINEX
300MG CAP
CIPLA LTD Rs176.0 (10 cap)
CLINDAMITE
300MG CAP
MANKIND
PHARMA LTD
Rs143.0 (10 cap)
49
Antibiotic Dosage Trade name Brand name Cost
TETRACYCLINE 500mg
(every 8 hrs)
RESTECLIN
500mg CAP
ABBOTT INDIA
LTD
Rs16.9 (10 CAP)
NICOCYCLINE
500mg CAP
ABBOTT INDIA
LTA
Rs16.25 (10 CAP)
ALCYCLIN 500
mg CAP
ALEMBIC
PHARMA LTD
Rs17.71 (10 CAP)
DOXYCYCLINE 100mg
(every 12 hrs)
NICODOXY 100
mg CAP
ABBOTT INDIA
LTD
Rs9.57 (10CAP)
DOXICIP 100 mg
CAP
CIPLA LTD Rs10.87 (10 CAP)
TATRADOX
100mg CAP
RANBAXY LAB
LTD
Rs41.02 (10 CAP)
50
Antibiotic Dosage Trade name Brand name Cost
Ciprofloxacin 250-750 mg
(twice daily)
CIPROBID
500 TAB
ZYDUS
CADILA
Rs42.05
(10 TAB)
CIPRACT
250 mg TAB
RANBAXY
LAB LTD
Rs13.0
(10 TAB)
CIPLOX 250 mg
TAB
CIPLA LTD Rs24.46
(10 TAB)
Ciprofloxacin
+
Tinidazole
500/600 mg
(twice daily)
CIFRAN CT
500 mg/600mg
TAB
RANBAXY
LAB LTD
Rs107.0
(10 TAB)
51
Antibiotic Dosage Trade name Brand name Cost
METRONIDAZOLE 200-400mg
(every 8 hrs)
FLAGYL
200 mg TAB
ABBOTT
INDIA LTD
Rs6.77
(10 TAB)
METROGYL
200 mg TAB
JB CHEMICAL Rs6.77
(10 TAB)
52
Good Morning
MOHD.SIBGHATULLAH KHATIB
1ST YEAR PG STUDENT
53
RESPONSIBLE USE OF ANTIBIOTICS IN ENDODONTIC
THERAPY
54
LOCAL DRUG DELIVERY
• Bacteria located inside dentinal tubules are protected from
host defence cells, systemic antibiotics and
chemomechanical preparation.
• Therefore, endodontic medicaments must be able to
penetrate into dentinal tubules and kill bacteria within
them.
55
Australian Dental Journal Endodontic Supplement 2007;52:1.
Grossman Polyantibiotic Paste
Tetracycline
Ledermix
Septomixine Forte
MTAD
Tetraclean
Triple antibiotic Paste
Clindamycin
Odontopaste
56
LOCAL DRUG DELIVERY
Grossmann Poly Antibiotic Paste
• The first reported local use of an antibiotic in endodontic treatment
was in 1951
• When Grossman used a polyantibiotic paste known as PBSC
(penicillin, bacitracin, streptomycin, and caprylate sodium).
Australian Dental Journal Endodontic supplement :2007
57
• All compounds were all suspended in a silicone vehicle.
• The composition was ineffective against anaerobic species
58
Australian Dental Journal Endodontic Supplement 2007;52:1.
Penicillin Gram-positive organisms
Bacitracin For penicillin-resistant strains
Streptomycin Gram-negative organisms
Caprylate sodium Yeasts
Septomixine Forte
• Contains two antibiotics –
 Neomycin
Polymixin B sulphate
59
 Gram-negative bacilli Neomycin X Bacteroides , fungi
 Gram-positive bacteria Polymyxin B sulphate
International Journal of Pharmacy and Pharmaceutical Sciences Vol 6, Issue 3, 2014
Ledermix paste
TRIAMCINOLONE
• Anti-inflammatory action
• Concentration of 1.0%
• Inhibits clastic cells
(osteoclasts, cementoclasts and
dentinoclasts)
DEMECLOCYCLINE
• Anti microbial action
• concentration of 3.21%
60
Australian Dental Journal Endodontic supplement :2007
• Ledermix:
Effective in preventing inflammatory resorption in
avulsed teeth
 Pain management
Australian Dental Journal Endodontic supplement :2007
61
Ledermix paste + Calcium hydroxide
An intracanal dressing
Pulp necrosis and infection with incomplete root formation
Perforations
Inflammatory root resorption
Inflammatory periapical bone resorption
The treatment of large periapical radiolucent lesions
62
Australian Dental Journal Endodontic supplement :2007
TRIPLE ANTIBIOTIC PASTE
• Metronidazole + Ciprofloxacin + Minocycline.
• Used in - The revitalization regeneration procedures
63
COHEN 10TH EDITION
Avulsion
Application in large periradicular lesion
Application in primary teeth
Root fracture
65
DISADVANTAGES
It may cause bacterial resistance.
Use of minocycline can cause tooth discoloration
66
COHEN 10TH EDITION
TETRACYCLINES
 To remove the smear layer from instrumented root canal walls
 Irrigation of apical root-end cavities during periapical surgical
procedures
 As intracanal medicaments
Mohammadi etal: An update on the antibiotic-based root canal irrigation solutions:IEJ 2008
MTAD
• COMPOSITION-
3% Doxycycline hyclate + 4.25% Citric acid+0.5%
Polysorbate-80 (Tween 80) detergent.
68
COHEN 10TH EDITION
• MTAD is capable of
Removing the smear layer
Disinfecting the root canal system.
• Commercially available as BioPure MTAD
69
COHEN 10TH EDITION
• Tetraclean is another combination product similar to
MTAD.
• The use of tetraclean was able to reduce 90%
bacteric load after 5 minutes and 99.9% after 30
minutes of application.
70
MTAD TETRACLEAN
DOXYCYCLINE 150mg/5ml 50mg/5ml
Tween 80 Polypropylene glycol
JOE-2007
COHEN 10TH EDITION
MTAD has best antibacterial efficiency against E faecalis
when compared to 2.5% Sodium Hypochlorite and 2%
Chlorhexidine.
MTAD was effective in killing E. faecalis up to 200 x
dilution whereas NaOCl ceased to exert its antibacterial
activity beyond 32 x dilution
Torabinejad et al. (2003)
71
Journal of Dental and Medical SciencesVolume 5, Issue 3 (Mar.- Apr. 2013), PP 47-53
ODONTOPASTE
• Zinc oxide-based endodontic dressing
• COMPOSITION
Clindamycin hydrochloride- 5%
Triamcinolone acetonide - 1%
Calcium hydroxide- < 0.5%
72
Odontopaste is the most effective against Enterococcus
faecalis.
Propolis is partially effective against Candida albicans.
73
Journal of International Dental and Medical Research Volume ∙ 5 ∙ Number ∙ 1 ∙ 2012
BioPure (MTAD) is effective in removing the smear layer.
Ledermix help to reduce the periapical inflammatory reaction
including clastic-cell mediated resorption.
Clindamycin alone or in an ethylene vinyl acetate (EVA)
vehicle can reduce the bacterial load inside the root canal
system
74
International Endodontic Journal 2009
• The local application of antibiotics may be a more effective
than systemic routes.
• Tetracyclines –
remove the smear layer from instrumented root canal walls
for irrigation of apical root-end cavities during periapical surgical
procedures
intracanal medicament
• Substantivity of tetracyclines has been shown for up to at
least 12 weeks.
• BioPure (MTAD) is effective in removing the smear layer.
• Substantivity of MTAD has been shown to last for up to 4
weeks.
75
International Endodontic Journal 2009
YEA, BUT DO THEY REALLY KILL THE
BUGS?
76
Acquired resistance to PENICILLIN
• Resistance to penicillin is usually by three
mechanisms.
Decreased bacterial cell wall penetration,
Inability to bind to the penicillin binding proteins,
Production of ß-lactamase.
77
JOURNAL OF ENDODONTICS, JANUARY 2003
Beta-lactamase production
78
• Black-pigmented Prevotella
• Nonpigmented Prevotella species
• F. nucleatum,
• P. acnes,
• Actinomyces species,
• Peptostreptococcus species
• Capnocytophaga
• Neisseria species
COHEN 10TH EDITION
• Amoxicillin’s broad spectrum is more than is required for
endodontic needs, and its use in a healthy individual may contribute
to the global antibiotic resistance problem.
79
JAC 2013
Resistance Drugs
F. nucleatum Penicillin, amoxicillin, and metronidazole
P. intermedia Tetracycline and amoxicillin
A. actinomycetemcomitans Amoxicillin and azithromycin
Fusobacterium and nonpigmented Prevotella
species
Macrolides (erythromycin and azithromycin)
80
MYTHS
Antibiotics cure patients.
Antibiotics are substitutes for surgical intervention.
The most important decision is which antibiotic to
use.
Antibiotics increase the host’s defense to infection.
81
American Association of Endodontists, 2012
Multiple antibiotics are superior to a single antibiotic.
Bactericidal agents are always superior to
bacteriostatic agents.
Antibiotic dosages, dosing intervals and duration of
therapy are established for most infections.
Bacterial infections require a “complete course” of
antibiotic therapy.
82
MYTHS
American Association of Endodontists, 2012
CONCLUSION
• To sum up, the risk/benefit ratio should be always weighed
before prescribing antibiotics.
• Appropriately selected patients will benefit from
systemically administered antibiotics.
• A restrictive and conservative use of antibiotics is highly
recommended in endodontic practice, but indiscriminate
use is contrary to sound clinical practice
• Future generations will thank us for today’s conscientious
and judicious use of antibiotics.
83
REFERENCES
• Cohen 10th edition
• Tripathi 6TH EDITION
• Lippincotts pharmacology 5th edition
• Ingles endodontics - 6th ed.
• Siquiera jr et al : update endodontic microbiology 2008
• Asian pac J trop biomed 2012; 2(9): 749-754
• J antimicrob chemother 2014
• American association of endodontists 2006
• International endodontic journal 2009
84
• JADA, vol. 131, march 2000
• American heart association, 2007; 116: 1736-1754
• Australian dental journal endodontic supplement 2007;52:1
• American association of endodontics 2012
• Journal of International Dental and Medical Research Volume
5 Number 2012
• ADA council 1997
• Journal of dental and medical sciencesvolume 5, issue 3 (mar.-
Apr. 2013), pp 47-53
• Journal of endodontics, january 2003
• International Journal of Pharmacy and Pharmaceutical
Sciences Vol 6, Issue 3, 2014
85
REFERENCES
86

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Antibiotic in endodontic

  • 3. CONTENTS • INTODUCTION • HISTORY • CLASSIFICATION OF ANTIBIOTICS • SELECTION OF ANTIMICROBIALAGENTS • BACETRIOLOGY • ODONTOGENIC INFECTION • COMMONLY USE ANTIIBIOTIC IN ORAL INFECTION • COMPLICATION OF ANTIBIOTIC THERAPY • FASCIAL SPACE INFECTION • MANAGEMENT OF ABSSCESS AND CELLULITIS • ANTIBIOTIC PROPHYLAXIS • RESISTANCE • ANTIBIOTIC DOSAGE • USE OF ANTIBIOTIC AS AN INTRA CANAL MEDICAMENT • MYTHS • CONCLUSION • REFRENCES 3
  • 4. • Antibiotics-These are substances produced by microorganisms, which selectively suppress the growth of or kill other microorganisms at very low concentrations • Antimicrobial agent (AMA)-synthetic as well as naturally obtained drugs that attenuate microorganisms • Chemotherapy-Treatment of systemic infections with specific drugs that selectively suppress the infecting microorganism without significantly affecting the host 4
  • 5. 3 phases: Empirical phase Ehrlich's phase The modem era of chemotherapy 5 History
  • 6. Empirical phase • Mouldy curd by Chinese on boils • Chaulmoogra oil for leprosy, • Chenopodium by Aztecs for intestinal worms, • Mercury by Paracelsus (16th century) for syphilis, • Cinchona bark (17th century) for fevers. 6
  • 7. Ehrlich's phase (1890-1935) • Ehrlich given the idea that if certain dyes could selectively stain microbes, they could also be selectively toxic to these organisms. He tried methyleneblue, trypan red, etc • He developed arsphenamine in 1906 and neoarsphenamine in 1909 for syphilis. • He coined the term 'chemotherapy' 7
  • 8. Modern era • Domagk (1935) - The therapeutic effect of Prontosil. • Pasteur (1877) - Demonstrated the phenomenon of antibiosis : growth of anthrax bacilli in urine was inhibited by air-borne bacteria. 8
  • 9. • Fleming (1929) - Discovered penicillin . • Chain and Florey (1941)- Clinical use of penicillin . • Waksman and his colleagues (1944)- Discovered streptomycin 9
  • 10. 10 Golden era in antibiotic discovery
  • 11. CLASSIFICATION OF ANTIBIOTIC 11 • Based on A. Chemical structure B. Mechanism of action C. Type of organism against which primarily active D. Spectrum of activity E. Type of action TRIPATHI 6TH EDITION
  • 13. • Inhibit cell wall synthesis – Penicillin – Cepholosporin – Vancomycin – Bacitracin • Cause leakage from cell membrane – Polypeptide: polymixin, Colistin – Polyenes:Amp-B,nystatin • Inhibit protein synthesis – Tetracycline – Chloramphenicol – Macrolides • Mis-reading of m-RNA – Aminoglycosides • Inhibit DNA gyrase – Fluoroquinolones • Interfere with DNA function – Rifampicin – Metronidazole • Interfere with DNA synthesis – Acylovir – Zidovudine – Idoxuridine • Interfere with intermediatory metabolism – Sulfonamide – Ethambutol 13 TRIPATHI 6TH EDITION
  • 14. ANTIBIOTICS  BACTERIOSTATIC • Sulfonamides • Erythromycin • Tetracyclines • Ethambutol • Chloramphenicol • Clindamycin  BACTERICIDAL • Penicillins • Cephalosporins • Aminoglycosides • Vancomycin • Metronidazole • Cotrimoxazole 14 TRIPATHI 6TH EDITION
  • 15. Spectrum of activity  Narrow-spectrum • Penicillin G • Streptomycin • Erythromycin  Broad-spectrum • Tetracyclines • Chloramphenicol 15 Extended-spectrum •Ampicillin •Amoxycillin Lippincotts pharmacology 5th edition
  • 16. SELECTION OF ANTIMICROBIALAGENTS  The organism’s identity  Patient factors  The site of the infection  The organism’s susceptibility to a particular agent  The safety of the agent  The cost of therapy 16 Lippincotts pharmacology 5th edition
  • 18. • The pulpodentin complex is sterile. • Bacterial invasion of dentinal tubules occurs more rapidly in nonvital teeth than in vital ones. 18 COHEN 10TH EDITION
  • 20. 20 Siquiera jr et al : update endodontic microbiology 2008
  • 21. ODONTOGENIC INFECTION 21 PULPITIS Apical periodontitis PERIAPICAL ABSCESS PERIAPICAL GRANULOMA PERIODONTAL CYST OSTEOMYELITIS PERIOSTEITIS CELLULITIS ABSCESS ACUTE CHRONIC ACUTE CHRONIC ACUTE CHRONIC FOCAL DIFFUSE Reversible Irreversible
  • 22. When do you need the drugs to kill the bugs? • Fever > 100° F • Malaise • Lymphadenopathy • Trismus • Increased Swelling • Cellulitis • Osteomyelitis • Persistent Infection 22 American Association of Endodontists, 2006
  • 23. Just say NO! Kill the bugs without the drugs Irreversible pulpitis, Acute apical periodontitis, Draining sinus tracts, After endodontic surgery, To prevent flare-ups, After incision for drainage of a localized swelling (without cellulitis, fever, or lymphadenopathy) 23 COHEN 10th edition
  • 24. COMMONLY USED ANTIBIOTIC IN ORAL INFECTION 24
  • 26. DOSAGE 26 Antibiotic Dosage Duration Penicllin V 250mg/500mg Every4-6hours/5-7days Amoxicillin / Amoxicillin with clavulanate 250mg/500 mg Every 8 hours/5-7 days Clindamycin 300 mg/600mg Every 6 hours/5-7 days. Metronidazole 200mg/400 mg Every 8 hours/5-7 days. Azithromycin 250mg/500mg Once a day /5-7 days. American Association of Endodontists 2006
  • 27. 27
  • 28. COMPLICATIONS OF ANTIBIOTIC THERAPY • Hypersensitivity • Direct toxicity • Superinfections 28 lippincotts pharmacology 5th edition
  • 29. THE FASCIAL SPACES The mandible and below The buccal vestibule Body of the mandible The mental space The submental space The sublingual space Submandibular space The cheek and lateral face The buccal vestibule of the maxilla The buccal space The submasseteric space The temporal space The pharyngeal and cervical areas The pterygo- mandibular space The para- pharyngeal spaces The cervical spaces The midface The palate The base of the upper lip The canine spaces The periorbital spaces 29
  • 30. Management of Abscesses and Cellulitis • Correct diagnosis • Removal of the cause • Incision for drainage is indicated for any infection marked by cellulitis. It is important to provide a pathway of drainage to prevent further spread of the abscess and/or cellulitis. 30 COHEN 10th edition
  • 31. Systemic Antibiotics for Endodontic Infections • Selection of antibiotics- – Empirical – based on the results of microbial susceptibility tests. • For diseases with known microbial causes, empirical therapy may be used. • Most of the bacterial species involved with endodontic infections, including abscesses, are susceptible to penicillins . 31 COHEN 10TH EDITION
  • 32. 32
  • 33. 33 • Managment  Amoxicillin (500 mg, orally) at intervals of 8 h for 7 days and dexamethasone (4 mg, intramuscularly) at intervals of 24 h for 3 days  2% chlorhexidine gel applied with a 5- ml syringe
  • 34. TOOTH AVULSION • Systemic administration of antibiotics is generally recommended in order to prevent the harmful effects of bacterial contamination. • Antibiotics decrease the incidence of inflammatory root resorption but have a limited, or no, effect on the pulp 34 Australian Dental Journal Endodontic Supplement 2007
  • 35. • Gram-negative obligate anaerobic rods – Porphyromonas spp. – Prevotella spp. • Prophylactic use of antibiotic to decrease incidence of flare up Controversy. Flare-Up’s Cohen pathways of pulp : 10 th edition 35
  • 37. Infective Endocarditis (IE) • A life threatening disease with substantial morbidity and mortality which affects individuals with underlying structural cardiac defects who develop bacteremia. 37
  • 38. 38 JADA, Vol. 131, March 2000
  • 39. 39 JADA, Vol. 131, March 2000
  • 40. 40 JADA, Vol. 131, March 2000
  • 41. • The French agency for Health Product Health Safety advices against or contraindicates – Dental facial surgery, – Bone surgery, – Periodontal surgery, – Root canal treatment in these patients except under emergency situations, As these patients are prone to high risk of infection. 41 Asian Pac J Trop Biomed 2012; 2(9): 749-754
  • 42. 42 American Heart Association, 2007; 116: 1736-1754
  • 43. PREGNANCY • Any drug used during pregnancy should be taken only under the supervision of the patient’s physician. 43 lippincotts pharmacology 5th edition
  • 44. 44 CATEGORY DESCRIPTION DRUS A No human fetal risk or remote possibility of fetal harm B No controlled studies show human risk; animal studies Suggest potential Toxicity β-Lactams,β-Lactams with inhibitors, Cephalosporins, Aztreonam , Clindamycin, Erythromycin, Azithromycin, Metronidazole Nitrofurantoin. Sulfonamides C Animal fetal toxicity demonstrated; human risk Undefined Chloramphenicol, Fluoroquinolones, Clarithromycin, Trimethoprim, Vancomycin Gentamicin, Trimethoprim-sulfamethoxazole D Human fetal risk present, but benefits Mayoutweigh Risks Tetracyclines, Aminoglycosides (except gentamicin) X Human fetal risk present but does not Outweigh benets; contraindicated in pregnancy United States FDA categories of antimicrobials and fetal risk. lippincotts pharmacology 5th edition
  • 45. Partial List of Drugs Usually Compatible With Both Pregnancy and Breast-Feeding • Local anesthetics including lidocaine , etidocaine , and prilocaine • Penicillins- 250mg/500mg(Every 8 hours) • Clindamycin- 300/600mg(6 hrs) • Azithromycin- 250/500mg(OD) • Acyclovir • Prednisone 45 COHEN 10TH EDITION
  • 47. Antibiotic Dosage Trade name Brand name Cost AMOXICILLIN 250mg/500mg (Every 8 hours) AMOXIL 500 mg CAP. ZYDUS CADILA Rs32.5 (10 cap) AMOXIL250 mg CAP. ZYDUS CADILA Rs20 (10 cap) NOVAMOX 500 mg CAP. CIPLA Rs105.68 (15 cap) WYMOX 500 mg CAP. PFIZER LTD Rs147.0 (15 cap) BLUMOX 500 mg CAP. BLUE CROSS LAB. LTD Rs70.0 (10 cap) CIPMOX 500 mg CAP. CIPLA Rs105.81 (10 cap) 47
  • 48. Antibiotic Dosage Trade name Brand name Cost Amoxicillin With lactobacillus spores 250mg/500mg (Every 8 hours) NOVAMOX LB 500 CAP CIPLA Rs116.5 (6 cap.) NOVAMOX LB 250 CAP CIPLA Rs57.62 (10 cap) Amoxicillin and clavulanic acid 500mg+125mg AMOXYCLAV 500/125MG TAB. ABBOTT INDIA LTD Rs51.25 (6 tab) MOXIKIND-CV 625 TAB. MANKIND PHARMA LTD Rs82.76 (6 tab) CIPMOX CV 500/125 MG TAB. CIPLA LTD Rs79.68 (6 tab) AUGMENTIN 625 DUO TAB GSK Rs259.73 (10 tab) Amoxicillin and cloxacillin 250mg+250mg/ 125mg+125mg NATACLOX 250 MG CAP SUN PHARMA Rs31.37 (10 cap) 48
  • 49. Antibiotic Dosage Trade name Brand name Cost CEFADROXIL 125mg/250mg/ 500mg (every 12 hrs) ODOXIL DT-250 LUPIN LTD Rs26 (10 tab) CEFADUR 250MG TAB CIPLA LTD Rs 26.0 (10 tab) CEFOXID 250 MG TAB ALKEM LAB. LTD Rs153.05 (10 tab) CEFUROXIME 125 mg (every 12 hrs) CEFAKIND 125MG TAB MANKIND PHARMA LTA Rs69.0 (10 tab) CEFIXIME 200mg (bid) TAXIM O 400MG TAB ALKEM LAB LTD Rs345 (10 tab) CEFIX 400MG CIPLA LTD Rs115.57 (4 tab) CLINDAMYCIN 300/600mg(6 hrs) DALCINEX 300MG CAP CIPLA LTD Rs176.0 (10 cap) CLINDAMITE 300MG CAP MANKIND PHARMA LTD Rs143.0 (10 cap) 49
  • 50. Antibiotic Dosage Trade name Brand name Cost TETRACYCLINE 500mg (every 8 hrs) RESTECLIN 500mg CAP ABBOTT INDIA LTD Rs16.9 (10 CAP) NICOCYCLINE 500mg CAP ABBOTT INDIA LTA Rs16.25 (10 CAP) ALCYCLIN 500 mg CAP ALEMBIC PHARMA LTD Rs17.71 (10 CAP) DOXYCYCLINE 100mg (every 12 hrs) NICODOXY 100 mg CAP ABBOTT INDIA LTD Rs9.57 (10CAP) DOXICIP 100 mg CAP CIPLA LTD Rs10.87 (10 CAP) TATRADOX 100mg CAP RANBAXY LAB LTD Rs41.02 (10 CAP) 50
  • 51. Antibiotic Dosage Trade name Brand name Cost Ciprofloxacin 250-750 mg (twice daily) CIPROBID 500 TAB ZYDUS CADILA Rs42.05 (10 TAB) CIPRACT 250 mg TAB RANBAXY LAB LTD Rs13.0 (10 TAB) CIPLOX 250 mg TAB CIPLA LTD Rs24.46 (10 TAB) Ciprofloxacin + Tinidazole 500/600 mg (twice daily) CIFRAN CT 500 mg/600mg TAB RANBAXY LAB LTD Rs107.0 (10 TAB) 51 Antibiotic Dosage Trade name Brand name Cost METRONIDAZOLE 200-400mg (every 8 hrs) FLAGYL 200 mg TAB ABBOTT INDIA LTD Rs6.77 (10 TAB) METROGYL 200 mg TAB JB CHEMICAL Rs6.77 (10 TAB)
  • 53. 53
  • 54. RESPONSIBLE USE OF ANTIBIOTICS IN ENDODONTIC THERAPY 54
  • 55. LOCAL DRUG DELIVERY • Bacteria located inside dentinal tubules are protected from host defence cells, systemic antibiotics and chemomechanical preparation. • Therefore, endodontic medicaments must be able to penetrate into dentinal tubules and kill bacteria within them. 55 Australian Dental Journal Endodontic Supplement 2007;52:1.
  • 56. Grossman Polyantibiotic Paste Tetracycline Ledermix Septomixine Forte MTAD Tetraclean Triple antibiotic Paste Clindamycin Odontopaste 56 LOCAL DRUG DELIVERY
  • 57. Grossmann Poly Antibiotic Paste • The first reported local use of an antibiotic in endodontic treatment was in 1951 • When Grossman used a polyantibiotic paste known as PBSC (penicillin, bacitracin, streptomycin, and caprylate sodium). Australian Dental Journal Endodontic supplement :2007 57
  • 58. • All compounds were all suspended in a silicone vehicle. • The composition was ineffective against anaerobic species 58 Australian Dental Journal Endodontic Supplement 2007;52:1. Penicillin Gram-positive organisms Bacitracin For penicillin-resistant strains Streptomycin Gram-negative organisms Caprylate sodium Yeasts
  • 59. Septomixine Forte • Contains two antibiotics –  Neomycin Polymixin B sulphate 59  Gram-negative bacilli Neomycin X Bacteroides , fungi  Gram-positive bacteria Polymyxin B sulphate International Journal of Pharmacy and Pharmaceutical Sciences Vol 6, Issue 3, 2014
  • 60. Ledermix paste TRIAMCINOLONE • Anti-inflammatory action • Concentration of 1.0% • Inhibits clastic cells (osteoclasts, cementoclasts and dentinoclasts) DEMECLOCYCLINE • Anti microbial action • concentration of 3.21% 60 Australian Dental Journal Endodontic supplement :2007
  • 61. • Ledermix: Effective in preventing inflammatory resorption in avulsed teeth  Pain management Australian Dental Journal Endodontic supplement :2007 61
  • 62. Ledermix paste + Calcium hydroxide An intracanal dressing Pulp necrosis and infection with incomplete root formation Perforations Inflammatory root resorption Inflammatory periapical bone resorption The treatment of large periapical radiolucent lesions 62 Australian Dental Journal Endodontic supplement :2007
  • 63. TRIPLE ANTIBIOTIC PASTE • Metronidazole + Ciprofloxacin + Minocycline. • Used in - The revitalization regeneration procedures 63 COHEN 10TH EDITION
  • 64.
  • 65. Avulsion Application in large periradicular lesion Application in primary teeth Root fracture 65
  • 66. DISADVANTAGES It may cause bacterial resistance. Use of minocycline can cause tooth discoloration 66 COHEN 10TH EDITION
  • 67. TETRACYCLINES  To remove the smear layer from instrumented root canal walls  Irrigation of apical root-end cavities during periapical surgical procedures  As intracanal medicaments Mohammadi etal: An update on the antibiotic-based root canal irrigation solutions:IEJ 2008
  • 68. MTAD • COMPOSITION- 3% Doxycycline hyclate + 4.25% Citric acid+0.5% Polysorbate-80 (Tween 80) detergent. 68 COHEN 10TH EDITION
  • 69. • MTAD is capable of Removing the smear layer Disinfecting the root canal system. • Commercially available as BioPure MTAD 69 COHEN 10TH EDITION
  • 70. • Tetraclean is another combination product similar to MTAD. • The use of tetraclean was able to reduce 90% bacteric load after 5 minutes and 99.9% after 30 minutes of application. 70 MTAD TETRACLEAN DOXYCYCLINE 150mg/5ml 50mg/5ml Tween 80 Polypropylene glycol JOE-2007 COHEN 10TH EDITION
  • 71. MTAD has best antibacterial efficiency against E faecalis when compared to 2.5% Sodium Hypochlorite and 2% Chlorhexidine. MTAD was effective in killing E. faecalis up to 200 x dilution whereas NaOCl ceased to exert its antibacterial activity beyond 32 x dilution Torabinejad et al. (2003) 71 Journal of Dental and Medical SciencesVolume 5, Issue 3 (Mar.- Apr. 2013), PP 47-53
  • 72. ODONTOPASTE • Zinc oxide-based endodontic dressing • COMPOSITION Clindamycin hydrochloride- 5% Triamcinolone acetonide - 1% Calcium hydroxide- < 0.5% 72
  • 73. Odontopaste is the most effective against Enterococcus faecalis. Propolis is partially effective against Candida albicans. 73 Journal of International Dental and Medical Research Volume ∙ 5 ∙ Number ∙ 1 ∙ 2012
  • 74. BioPure (MTAD) is effective in removing the smear layer. Ledermix help to reduce the periapical inflammatory reaction including clastic-cell mediated resorption. Clindamycin alone or in an ethylene vinyl acetate (EVA) vehicle can reduce the bacterial load inside the root canal system 74 International Endodontic Journal 2009
  • 75. • The local application of antibiotics may be a more effective than systemic routes. • Tetracyclines – remove the smear layer from instrumented root canal walls for irrigation of apical root-end cavities during periapical surgical procedures intracanal medicament • Substantivity of tetracyclines has been shown for up to at least 12 weeks. • BioPure (MTAD) is effective in removing the smear layer. • Substantivity of MTAD has been shown to last for up to 4 weeks. 75 International Endodontic Journal 2009
  • 76. YEA, BUT DO THEY REALLY KILL THE BUGS? 76
  • 77. Acquired resistance to PENICILLIN • Resistance to penicillin is usually by three mechanisms. Decreased bacterial cell wall penetration, Inability to bind to the penicillin binding proteins, Production of ß-lactamase. 77 JOURNAL OF ENDODONTICS, JANUARY 2003
  • 78. Beta-lactamase production 78 • Black-pigmented Prevotella • Nonpigmented Prevotella species • F. nucleatum, • P. acnes, • Actinomyces species, • Peptostreptococcus species • Capnocytophaga • Neisseria species COHEN 10TH EDITION
  • 79. • Amoxicillin’s broad spectrum is more than is required for endodontic needs, and its use in a healthy individual may contribute to the global antibiotic resistance problem. 79 JAC 2013 Resistance Drugs F. nucleatum Penicillin, amoxicillin, and metronidazole P. intermedia Tetracycline and amoxicillin A. actinomycetemcomitans Amoxicillin and azithromycin Fusobacterium and nonpigmented Prevotella species Macrolides (erythromycin and azithromycin)
  • 80. 80
  • 81. MYTHS Antibiotics cure patients. Antibiotics are substitutes for surgical intervention. The most important decision is which antibiotic to use. Antibiotics increase the host’s defense to infection. 81 American Association of Endodontists, 2012
  • 82. Multiple antibiotics are superior to a single antibiotic. Bactericidal agents are always superior to bacteriostatic agents. Antibiotic dosages, dosing intervals and duration of therapy are established for most infections. Bacterial infections require a “complete course” of antibiotic therapy. 82 MYTHS American Association of Endodontists, 2012
  • 83. CONCLUSION • To sum up, the risk/benefit ratio should be always weighed before prescribing antibiotics. • Appropriately selected patients will benefit from systemically administered antibiotics. • A restrictive and conservative use of antibiotics is highly recommended in endodontic practice, but indiscriminate use is contrary to sound clinical practice • Future generations will thank us for today’s conscientious and judicious use of antibiotics. 83
  • 84. REFERENCES • Cohen 10th edition • Tripathi 6TH EDITION • Lippincotts pharmacology 5th edition • Ingles endodontics - 6th ed. • Siquiera jr et al : update endodontic microbiology 2008 • Asian pac J trop biomed 2012; 2(9): 749-754 • J antimicrob chemother 2014 • American association of endodontists 2006 • International endodontic journal 2009 84
  • 85. • JADA, vol. 131, march 2000 • American heart association, 2007; 116: 1736-1754 • Australian dental journal endodontic supplement 2007;52:1 • American association of endodontics 2012 • Journal of International Dental and Medical Research Volume 5 Number 2012 • ADA council 1997 • Journal of dental and medical sciencesvolume 5, issue 3 (mar.- Apr. 2013), pp 47-53 • Journal of endodontics, january 2003 • International Journal of Pharmacy and Pharmaceutical Sciences Vol 6, Issue 3, 2014 85 REFERENCES
  • 86. 86