antibiotics in dentistry - chiang mai...
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Antibiotics in Dentistry
Outline: • ความรู้พื้นฐานเกีย่วกบัเชือ้โรค • ยาต้านจลุชพี
• ยาปฏิชีวณะ • จะเลือกใชอ้ยา่งไร
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เชื้อแบคทเีรีย :
เชื้อแบคทเีรีย :
• Cell Envelope • Protein Production • Reproduction
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เชื้อแบคทเีรีย : Cell Envelope
http://www.pc.maricopa.edu
เชื้อแบคทเีรีย : Cell Envelope
Liem Nguyen,Charles J. Thompson, Trends in Microbiology(2006)
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เชื้อแบคทเีรีย : Cell Envelope
www.cehs.siu.edu/fix/medmicro/
เชื้อแบคทเีรีย : Cell Envelope
NAM NAG NAM NAG
NAM NAG NAM NAG
NAM NAG NAM NAG
Penicillin-binding proteins (PBPs)
NAG
NAM
N-acetylmuramic acid
N-acetylglucosamine
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เชื้อแบคทเีรีย : Cell Envelope
เชื้อแบคทเีรีย : Protein Production
• Raw material : Oxygen consumption • Strict Aerobes : Mycobacterium tuberculosis
• Microaerophilic bacteria : Neisseria sp. • Strict anaerobes : Clostridium difficile • Facultative anaerobes : Staphylococcus aureus
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เชื้อแบคทเีรีย : Protein Production
http://academic.pgcc.edu
Antibacterial Agents
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Antibacterial agents :
•Agent grouping based on their mechanism •Damaging Cell envelop •Blocking protein synthesis •Blocking DNA or RNA replication
Antibacterial agents :
•Damaging Cell envelop • Inhibitors of peptidoglycan monomer synthesis : Fosfomycin, Fosmidomycin
• Inhibitors of peptidoglycan polymer synthesis : Vancomycin
• Inhibitors of peptidoglycan polymer crosslinking : Penicillins, Cephalosporins
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Antibacterial agents :
•Blocking protein synthesis • Target on the 50s ribosome :
•Macrolides : Erythromycin • Lincosamides : Clindamycin
• Target on the 30s ribosome : • Aminoglycosides: Streptomycin • Tetracyclines : Doxycycline
Antibacterial agents :
•Blocking DNA or RNA replication • Inhibitors of Topoisomerase:
•Quinolones : Ciprofloxacin • Inhibitors of transcription :
• Rifamicin : Rifampin
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Antibacterial Agents that attack cell
envelop
•beta-Lactam : Penicillins, Cephalosporins • Glycopeptides : Vancomycin •Daptomycin • Colistin
ABOs that target on Cell Envelop:
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•beta-Lactam : • Penicillins, Cephalosporins •Binding between PBPs andbeta-lactam ring inhibits new peptidoglycan synthesis
• Leading to lysis ofthe bacterium
C C
O C N
ABOs that target on Cell Envelop:
ABOs that target on Cell Envelop:
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•Penicillins •Natural : Pen V, Pen G • Antistaphylococcal : Dicloxacillin • Aminopenicillins : Amoxicillin, Ampicillin
• Aminopenicillins+beta lactamases inhibitors : Amox-clavulanate
ABOs that target on Cell Envelop:
Antibacterial agents : Bacteria Natural Anti-staph Aminopen
Aminopen + inhibitor
Extended Pen
extPen + inhibitor
G+ve +/- +/- +/- + +/- + G-ve - - +/- +/- +/- + Anaerobes +/- - +/- + +/- + Atypical - - +/- - - - On Chemist PenV Dicloxacillin Amoxi
Augmantin tab 500 + 125 mg
Piperacillin Ticarcillin
Piperacillin +Tazobactam
Price (฿) 1.50 1.87 1.60 8 - 588.50
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•Cephalosporins •From Cephalosporium acremonium •Target on Peptidoglycans •2 major advantages over Pen : More resistant to beta-
lactamases 2 side chain groups
ABOs that target on Cell Envelop:
•Cephalosporins •Broader activity against aerobic G-ve
•Limited activity against anaerobes
•Vary activity against G+ve
ABOs that target on Cell Envelop:
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Bacteria 1st 2nd 3rd 4th 5th
G+ve +/- +/- +/- +/- + G-ve - +/- + + + Anaerobes - +/- - - +/- Atypical - - - - -
On Chemist Cefalexin
cap 500 mg Cefoxitin pwd 1 g
Cefotaxime pwd 1 g
Price (฿) 2.25 91 17
ABOs that target on Cell Envelop:
ABOs that target on Cell Envelop:
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•Penicillins and Cephalosporins •Major interacting drug
• Allopurinol : Gout : allergic •Beta-blocker : HT : mast cell • Tetracyclines : reduce effectiveness
ABOs that target on Cell Envelop:
•beta-Lactam : Penicillins, Cephalosporins • Glycopeptides : Vancomycin •Daptomycin • Colistin
ABOs that target on Cell Envelop:
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• ABOs that target on Cell Envelop • Glycopeptides : Vancomycin
• Preventing cell wall synthesis. • Poorly absorbed by GI tract. • IV only for systemic infections. • Against nearly all staph, strep • sterile pwdr 500 mg / 130-.
ABOs that target on Cell Envelop:
Antibacterial Agents that block
protein synthesis
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• Target on the 50s ribosome : •Macrolides : Erythromycin • Lincosamides : Clindamycin
• Target on the 30s ribosome : • Aminoglycosides: Streptomycin • Tetracyclines : Doxycycline
ABOs that block protein synthesis:
•Macrolides and Ketolides • Erythromycin, Azithromycin, Clarithromycin •Macrolide : Macrocyclic lactone ring •Bind to the 50s subunit of the bacterial ribosome.
ABOs that block protein synthesis:
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•Macrolides and Ketolides : Erythromycin • The oldest macrolides • Less effect on respiratory infection compared to the other macrolides, espicially H.influenza
•Being replaced by newer agents
ABOs that block protein synthesis:
•Macrolides and Ketolides : Azithromycin •Better penetrate through the outer membrane.
• Useful for treatment H.influenza infection.
• Slower released, longer therapeutic level.
ABOs that block protein synthesis:
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• Lincosamides : Clindamycin •Block peptide bond formation. • For serious anaerobic infections (Bacteroides)
• Good at against aerobic G+ve and anaerobic ; Stap ,Strep
•Most G-ve bacteria are resistant to Clindamycin
ABOs that block protein synthesis:
• Tetracyclines : Doxycycline, Minocycline •Bind to the 30s subunit of the bacterial ribosome.
• Prevent tRNA adding amino acids •Doxycycline : longer hafl-life •Minocycline : for staphylococcal infection
ABOs that block protein synthesis:
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•Tetracyclines •Major interacting drug
• Antacids : reduce GI resorption • Insulin : increase hypoglycemic eff. • Tetracyclines : reduce effectiveness
ABOs that target on Cell Envelop:
Bacteria Erythromycin Azithromycin Clindamycin Tetracyclines
G+ve +/- +/- +/- - G-ve +/- +/- - +/- Anaerobes - - +/- +/- Atypical +/- +/- - +
On Chemist Clarithromycin tap 500 mg
cap 250 mg Clindamycin cap 300 mg
Doxycycline cap 100 mg
Price (฿) 12.55 18.70 2.43 0.65
ABOs that block protein synthesis:
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Antibacterial Agents that block
DNA / RNA replication
•Metronidazole •Against anaerobic bacteria •Resistance is rare among obligate anaerobic bacteria
ABOs that target replication:
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•Metronidazole •Major interacting drug
• Ethanol : severe disulfiramlike react. • Lithium : •Benzodiazepines : • Carbamazepine : more toxicity • Cyclosporine : nephrotoxicity
ABOs that target on Cell Envelop:
Bacteria Metronidazole
G+ve - G-ve - Anaerobes + Atypical -
On Chemist Metronidazole Tab 200 mg
Price (฿) 0.37
Antibacterial agents :
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Antibacterial Agents, How to use them wisely
Put the like man in the right job.
• The progression of most dental infections
G+ve aerobes
predominate
Anaerobes
absent
Early stage
(Acute infection)
G+ve
aerobes
decreasing
G+ve
aerobes
decreasing
Anaerobes
present
Anaerobes
increasing
Mixed stage
G+ve aerobes
decreasing
Anaerobes absent
Last stage
(Chronic infection)
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Put the like man in the right job.
• Why it is not effective !! ?? !!! • Patient compliance : • Ineffective antibiotic : check pt.comp first • Poor debridement : • Resistant organism : • Concentration did not reach the site of infection
• Host defense inadequate :
• 6 Pitfalls •Penetraion : •Porins : •Pumps : •Penicillinase : beta-lactamases •PBPs : •Peptidoglycans :
Antibiotic Resistance:
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Hauser AR., Antibiotic Basics for Clinicians.
Antibacterial agents :
• Intrinsic resistance : the structure or physiology of the bacterial sp.
• Acquired resistance : used to sensitive to an ABO, later not due to a mutation or exogenous genetic material
Antibiotic Resistance:
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•Antibiotic Sensitivity Testing - : • To determine the susceptibility of an isolate to a range of potential therapeutic agents. • measured by establishing the Minimum Inhibitory Concentration (MIC)
Antibiotic Resistance:
•Antibiotic Sensitivity Testing - : Kirby-Bauer test Etest strip
Antibiotic Resistance:
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•Antibiotic Sensitivity Testing - :
Antibiotic Resistance:
Etest gradient strip
Kirby-Bauer test
Indications for Antimicrobial agents
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welovelmc.com
reahim-minsk.com
ahmedabaddentalimplants.com
beauty-healthcare.blogspot.com
damarisdlgd8.blogspot.com
Put the like man in the right job.
Orofacial painful/inflammatory conditions: Reversible pulpitis Irreversible pulpitis Symptomatic periapical periodontitis Periodontal abscess Periodontitis, NUG Pericoronitis Cellulitis Sialadinitis
Indications:
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Periodontal diseases Dental caries
Periodontal abscess
Periapical diseases
Pulpal diseases
Dentoalveolar abscess Dry socket
Osteomyelitis Facial space infection Pericoronitis
Put the like man in the right job.
Cavernous sinus thrombosis
Ludwig’s angina
DEATH !!!
Facial space infection
encyclopedia.com
Put the like man in the right job.
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Penicillin is still the gold standard in treating dental infections.
No difference between pen V, amoxicillin, or amoxicillin and clavulanate. (Kuriyama, Br Dent J. 2005)
Therapeutic Indications:
Patient factor : Immunocompromised host Infection : Virulence and invasiveness : severity,
acuteness and spreading
Therapeutic Indications:
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Recommendations : Incisional drainage : SAP, localised abscess Severe infections such as cellulitis,
pericoronitis, periodontal abscess, and NUG : ABO should be presceibed as an initial treatment.
2 ABOs can be used to treat anaerobic bacterial infection
Therapeutic Indications:
Recommendations : Correct frequency, dose, and duration Prolonged courses of antibiotics destroy the
commensal flora. Longer durations of up to 21 days may
result in the selection of resistant strains.
Therapeutic Indications:
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to reduce the postoperative local complications : infection, dry socket, or infective endocarditis
For non-medically compromised patients, most dentoalveolar surgical procedures are not required.
Prophylactic Indications:
Recommendations : There is no consistent association between
having an intervention, dental or non-dental, and the development of IE.
Regular tooth brushing almost certainly presents a greater risk of IE than a single dental procedure because of repetitive exposure to bacteremia with oral flora.Longer durations of up to 21 days may result in the selection of resistant strains.
Prophylactic Indications:
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Recommendations : There is no consistent association between
having an intervention, dental or non-dental, and the development of IE.
Regular tooth brushing almost certainly presents a greater risk of IE than a single dental procedure.
Prophylactic Indications:
Recommendations : The clinical effectiveness of antibiotic
prophylaxis is not proven. Antibiotic prophylaxis against IE may lead to
a greater number of deaths through fatal anaphylaxis.
Better control defects in aseptic clinical technique or improperly sterilized equipment
Prophylactic Indications:
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Recommendations : The clinical effectiveness of antibiotic
prophylaxis is not proven. Antibiotic prophylaxis against IE may lead to
a greater number of deaths through fatal anaphylaxis.
Better control defects in aseptic clinical technique or improperly sterilized equipment
Prophylactic Indications:
Recommendations : If needed : Prophylacxis is implemented for : All dental procedures that involve
gingival tissue or periapical region or perforation of the oral mucosa
Prophylactic Indications:
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Recommendations : If needed : Prophylacxis is not necessary for : Injections through noninfected tissues X-ray Removaable prosth or ortho. Appliances Shedding of decidous teeth Bleeding from traumatic ulcer
Prophylactic Indications:
Recommendations : Cardiac conditions related to IE: Prosthetic cardiac valve Previous IE Congenital heart disease
Prophylactic Indications:
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Recommendations : Cardiac conditions not related to IE: Mitral valve prolapse Rheumatic heart disease Bicuspid vale disease Calcified aortic stenosis Ventricular septal defect Atrial septal defect Hypertrophic cardiomyopathy
Prophylactic Indications:
ABOs for orofacial bactrial infections
Poveda RR, Med Oral Patol Oral Cir Bucal, 2007
Drug Commonly used Creatinin Clearance
10-50 ml/min.
Prophylacxis
1 hr before
Amoxicillin 500 mg/8 hr
1000 mg / 12 hr Every 8-12 hours
2g or
50 mg/kg
Amoxi-clav
(Augmentin)
250-500 mg/8 hr
500-875 m g / 12 hr Every 8 hours
Clindamycin 300 mg/8 hr No adjustment 600 mg or
20 mg/kg
Azithromycin 500 mg/24 hours
3 days No adjustment
500 mg or
15 mg/kg
Doxycycline 100-200 mg/day
PO in div. dose q12-24h
Metronidazole 500-750 mg/8 hr Every 8-12 hours
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ABOs for orofacial bactrial infections Drug Commonly used
Prophylacxis
1 hr before
Amoxicillin Age > 3 mth : 20-90 mg/kg/day
PO in divided dose q8-12h
2g or
50 mg/kg
Amoxi-clav
(Augmentin)
Weight < 40 kg : 25-45 mg/kg/day
PO in divided dose q8-12h
Using either 200 or 400 mg/5 ml
suspension
Clindamycin
8-20 mg/kg/day
PO as hydrochloride in divided dose
q6-8h
600 mg or
20 mg/kg
Doxycycline Age > 8 yrs. : 2.2-4.4 mg/kg/day
PO in divided dose q12-24h
Metronidazole 30-50 mg/kg/day (Max. 4 g/day)
PO in divided dose q6-8h
ABOs for orofacial bactrial infections PRECAUTIONS WITH ANTIBIOTIC USE : FDA categorized 4 levels of drug risk during pregnancy A. Can be used during pregnancy B. Can be used during pregnancy C. Can be used with caution D. Should be avoided X. COntraindicated Mosby’s Dental Drug Reference, 10th edition, 2012
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ABOs for orofacial bactrial infections
Mosby’s Dental Drug Reference, 10th edition, 2012
Generic name FDA Preg Risk
Category Breast-feeding use
Amoxicillin B Yes
Amoxi-clav B Yes
Azithromycin B Yes
Clindamycin B Yes
Cephalexin B Yes
Metronidazole B Caution
Ciprofloxacin C No
Doxycycline D No