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


Liem Nguyen,Charles J. Thompson, Trends in Microbiology(2006)

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www.cehs.siu.edu/fix/medmicro/


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 : 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


•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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•Blocking protein synthesis • Target on the 50s ribosome :

•Macrolides : Erythromycin • Lincosamides : Clindamycin

• Target on the 30s ribosome : • Aminoglycosides: Streptomycin • Tetracyclines : Doxycycline


•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



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•Penicillins •Natural : Pen V, Pen G • Antistaphylococcal : Dicloxacillin • Aminopenicillins : Amoxicillin, Ampicillin

• Aminopenicillins+beta lactamases inhibitors : Amox-clavulanate


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


•Cephalosporins •Broader activity against aerobic G-ve

•Limited activity against anaerobes

•Vary activity against G+ve


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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



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•Penicillins and Cephalosporins •Major interacting drug

• Allopurinol : Gout : allergic •Beta-blocker : HT : mast cell • Tetracyclines : reduce effectiveness


•beta-Lactam : Penicillins, Cephalosporins • Glycopeptides : Vancomycin •Daptomycin • Colistin


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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-.


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.


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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


•Macrolides and Ketolides : Azithromycin •Better penetrate through the outer membrane.

• Useful for treatment H.influenza infection.

• Slower released, longer therapeutic level.


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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


• 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


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•Tetracyclines •Major interacting drug

• Antacids : reduce GI resorption • Insulin : increase hypoglycemic eff. • Tetracyclines : reduce effectiveness


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


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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


Bacteria Metronidazole

G+ve - G-ve - Anaerobes + Atypical -

On Chemist Metronidazole Tab 200 mg

Price (฿) 0.37


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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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• 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.


• 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


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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 Sensitivity Testing - : Kirby-Bauer test Etest strip


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•Antibiotic Sensitivity Testing - :


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


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


Cavernous sinus thrombosis

Ludwig’s angina

DEATH !!!

Facial space infection

encyclopedia.com


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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


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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


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.


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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.


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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.


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


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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


Recommendations : If needed : Prophylacxis is implemented for : All dental procedures that involve

gingival tissue or periapical region or perforation of the oral mucosa


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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


Recommendations : Cardiac conditions related to IE: Prosthetic cardiac valve Previous IE Congenital heart disease


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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


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


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


Metronidazole 30-50 mg/kg/day (Max. 4 g/day)


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

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