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ANTIBIOTIC PROPHYLAXIS IN DENTISTRY: Problems in Paradise

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ANTIBIOTIC PROPHYLAXIS IN DENTISTRY

“ANTIBIOTICS CURED

PATIENTS AND ANTIBIOTICS

PREVENTED INFECTIONS”.

In 1928, Fleming discovered that the fungus Penicillium notatum produced a substance

which killed the bacteria responsible for such infections. It was the first antibiotic and he

called it penicillin

Sir Alexander Fleming

Inside History

Definition of Antibiotics !

It is a chemical substance derivable from a mold or bacterium that kills micro-organisms and cures

infections.Antibiotics “Wonder Drugs” Antibiotics may be informally defined

as the sub-group of anti- infectives that are derived from bacterial sources and are used to treat bacterial infections

Antibiotic is a chemical substance produced by micro-organism having property of inhibiting the growth of or destroying other m/o in high dilution. Waksman in 1944

• Antibiotics are the substances produced by m/o, which suppress the growth of or kill other m/o at very low concentration.

Tripathi, 5th ed.

• Antibiotics are the substances produced by various species of m/o that suppress the growth of other m/o.

Goodman and Gillman’s Pharmacological Basis of Therapeutics, 10th ed.

Definition of Antibiotics !

How do Antibiotics work?

Define Antibiotic Prophylaxis:-

It is the use of antibiotics to prevent the infections and is based on the assumption that if antibiotics are useful in treating infections, then they will prevent the infections. Thomas J. Pallasch

It is defined as the use of an antimicrobial agent before any infection has occurred for the purpose of preventing a subsequent infection. Gerding DN, 1996

Uses of Antibiotic Prophylaxis:

USES

Principles of Antibiotic prophylaxis **

Acc. To Waddel TK et al., 1994

Cost-Benefit Ratios

High concentration at target site

Loading Dose

Active against single micro-organism

Continued as long as microbial contamination

Adverse effects of Antibiotic prophylaxis ---

Allergy and Toxicity Cutaneous eruptions (rash, urticaria, exfoliative

dermatitis) Serum sickness (immune complex reactions) Immediate hypersensitivity (penicillin anaphylaxis)

Super infections

Selection of Antibiotic Resistant micro-organisms

Induction of resistance gene transfer

Pallasch TJ et al, 2003

Contraindications:

Few Unusual Contraindications

Factors complicating antibiotic prophylaxis:

• No. of different organisms may be involved• Organisms involved have variable virulence• Organisms may originate from multiple sites• Organisms may have different sensitivity to

given antibiotics• Random physiologic bacteremia may occur• No controlled studies exist to show the

efficacy of antibiotic prophylaxis.

Thomas J Pallasch, 1989

AHA Recommendations:

In 1955 – Oral: Low Loading Dose Parenteral – Oral: None Parenteral: Single IM Injection Penicillin Allergy Protection:

None Special: None

IN 1943-------

250,000 U Pen G four times a day

AHA Recommendations:

In 1960 – Oral: None Parenteral – Oral: Oral, 2 days before, day of, 2 days following IM loading dose. Parenteral: IM Injections one on each of 2

days before and 2 days following IM loading dose on day of procedure. Penicillin Allergy Protection: Erythromycin Special: None

AHA Recommendations:

Oral: Start 1 hr before; Low dosage 3 days Parenteral – Oral: None Parenteral: Single IM Injection Penicillin Allergy Protection:

Erythromycin Special: None

In 1965 –

AHA Recommendations:

Oral: Start 1 hr before; Extra loading dose; Low dose 3 days following. Parenteral – Oral: None Parenteral: Three IM Injections, Reduced

aqueous dosage, 1 hr before and 2 days following. Penicillin Allergy Protection: Erythromycin Special: None

In 1972 -

AHA Recommendations:

Oral: High loading dose; Moderate dosage; About 2 days.

Parenteral – Oral: High IM loading dose; Moderate oral dose; About 2 days.

Parenteral: None Penicillin Allergy Protection: Erythromycin;

High loading dose; Moderate following dose. Special: IM penicillin & Streptomycin plus

penicillin IV or vancomycin plus oral erythromycin.

In 1977 -

1977 Recommendations:

High risk patientsNot allergic to penicillin.

Oral Parenteral & Oral

2gm Pen. V 30-60 mins 1million U Aq. Pen. Gbefore procedure. 600,000 U Procaine Pen. G 1 gm Streptomycin 500 mg Pen. V every 500mg Pen. V every 6hrs6 hrs for 8 doses.

Allergic to Pen1gm Vancomycin i/v over 30 mins period just before procedure. 500 mg Erythromycin every 6 hrs for 8 doses.

AHA Recommendations:

Oral: High loading dose; Single following dose; Less than 1 day.

Parenteral – Oral: None Parenteral: High IM loading dose

followed by IM dose 6hrs later; Only aqueous.

Penicillin Allergy Protection: Erythromycin; High loading dose; Single following dose; Less than one day.

Special: IM or IV ampicillin, gentamycin plus single-dose oral penicillin; IV vancomycin only.

In 1984 -

1984 Recommendations:

Patients who cannot take oral penicillin• Low moderate risk 2 million U Aq. Pen G i/m 30-60 mins before

followed by 1 million units of Aq. Pen G i/m 6 hrs later

• High risk 1-2 gm Ampicillin i/m or i/v 1 hr. before followed by

1gm Pen V orally 6 hrs later

AHA Recommendations:

Oral: High loading dose; Single following dose; Less than 1 day.

Parenteral – Oral: None Parenteral: None Penicillin Allergy Protection:

Clindamycin or Erythromycin; High loading dose; Single following dose less than one day.

Special: IM or IV ampicillin, gentamycin plus single following dose oral penicillin; IV vancomycin only

In 1990 -

AHA Recommendations:

In 1990 –

Erythromycin ethylsuccinate 800mg initial oral dose followed 6hrs

later by 400mg.Erythromycin stearate 1gm initial oral dose followed by 6hrs later by

500mg.

Patients unable to tolerate erythromycin Clindamycin 300mg 1hr before and

150mg 6hrs after the procedure.

AHA Recommendations:

Most cases of endocarditis are not attributable to invasive dental proceduresCommittee stated that approach for

endocarditis prophylaxis should consider• Level of risk• Risk of bacteremia• Adverse reactions with antibiotic selected• Cost-benefit aspects

In 1997 -

Conditions considered for Antibiotic Prophylaxis by AHA:

High Risk Conditions

Prosthetic cardiac valves

Bioprosthetics Homograft Previous Bacterial

Endocarditis Complex cyanotic

CHD Surgically constructed

systemic pulmonary shunts

Moderate Risk Conditions

Other congenital cardiac malformations

Acquired valve dysfunction

Hypertrophic cardiomyopathy

Mitral Valve prolapse with valvar regurgitation

Antibiotic prophylaxis recommended

Circulation 1997; 96: 358-66.

Conditions considered for Antibiotic Prophylaxis by AHA:

Low or Negligible Risk Conditions :

Isolated scundum atrial septal defect Ventricular septal defect Patent ductus arteriosus Previous coronary artery bypass graft surgery Mitral valve prolapse without valvar

regurgitations Physiologic, functional, or innocent heart

murmurs Previous Kawasaki disease without valvar

dysfunction Previous rheumatic fever without valvar

dysfunction Cardiac pacemakers and implanted defibrillators

Antibiotic prophylaxis recommended

Circulation 1997; 96: 358-66.

Recommendations by AHA regarding dental procedures and antibiotic prophylaxis:

Endocarditis prophylaxis recommended:

• Dental extractions• Periodontal Surgery, scaling, root planning,

probing and recall maintenance• Placement of dental implants• Reimplantation of avulsed teeth• Endodontic instrumentation or surgery only

beyond the apex of teeth• Subgingival placement of orthodontic

fibers/strips• Initial placement of orthodontic bands but not

brackets• Intraligamentary local anesthetic injections• Prophylactic cleaning of teeth or implants

where bleeding is anticipatedCirculation 1997; 96: 358-66.

Recommendations by AHA regarding dental procedures and antibiotic prophylaxis:

Endocarditis prophylaxis not recommended:

• Restorative dentistry• Local anesthetic injections• Intracanal endodontic treatment, post placement,

and crown build up• Placement of rubber dams• Post operative suture removal• Placement of removable prosthodontic or

orthodontic appliances• Taking oral impressions• Fluoride treatments• Taking oral radiographs• Orthodontic appliance adjustment• Shedding of primary teeth

Circulation 1997; 96: 358-66.

Antibiotic prophylaxis Guidelines for the Prevention of Bacterial Endocarditis:

Standard Regimen (Oral)AdultsAmoxicillin 2g, 1hr before procedure.ChildrenAmoxicillin 50mg/kg, 1 hr before procedure.

Penicillin Allergy (Oral)AdultsClindamycin 600mg, 1 hr before procedure.Cephalexin or Cefadroxil 2g, 1 hr before procedure.Clarithromycin or Azithromycin 500mg, 1 hr before

procedure.

JAMA 277: 1794-1801, 1997.

Antibiotic prophylaxis Guidelines for the Prevention of Bacterial Endocarditis:

Penicillin Allergy (Oral)ChildrenClindamycin 20mg/kg, 1 hr before procedure.Cephalexin or Cefadroxil 50mg/kg, 1 hr before

procedure.Clarithromycin or Azithromycin 15mg/kg, 1 hr

before procedure.

Unable to Take Oral MedicationsAdultsAmpicillin 2g IM or IV 30 min before procedure.Children50mg/kg IM or IV 30 min before procedure.

JAMA 277: 1794-1801, 1997.

Antibiotic prophylaxis Guidelines for the Prevention of Bacterial Endocarditis:

Penicillin Allergy and Unable to take Oral Medications:

Adults Clindamycin 600 mg IV 30 min before

procedure Cefazolin 1g IM or IV 30 min before

procedure Children Clindamycin 20mg/kg IV 30 min before

procedure Cefazolin 25mg/kg IM or IV 30 min before

procedure

JAMA 277: 1794-1801, 1997.

After the AHA recommendations in 1997 were published number of questions arose regarding some of the specifics that could not be included in original document; these questions were answered in 1999??

QUESTIONS ????

Answers ……

• Procedures associated with significant bleeding

• If large no. of sutures are involved• Dental matrix bands and gingival retraction

cords• If patients forget to take the antibiotics• If dentist did not anticipate significant

bleeding• A 9-14 interval is advised between

appointments• If only short interval exists between

appointments• If multiple appointments are necessary

Therapeutic Guidelines 2000

• Standard Oral Amoxicillin orally 1 hr preop Adult 2gm Child 50mg/kg• Parenteral Ampicillin/Amoxicillin IV immediately or IM 30 min preop Adult 2gm Child 50mg/kg• Non-penicillin Oral Clindamycin orally 1 hr preop Adult 600mg Child 10mg/kg Cephalexin orally 1 hr preop Adult 2gm Child 50mg/kg

Spicer J et al 2000

ADA Recommendations

• Non-penicillin Parenteral Clindamycin IV infused over 30min preop Adult 600mg Child 10mg/kg Lincomycin IV immediately Adult 600mg Child 15mg/kg Tiecoplanin IV immediately preop Adult 400mg Child 10mg/kg Vancomycin IV infused over 30 min preop Adult 1gm Child 20mg/kg

Spicer J et al 2000

Therapeutic Guidelines 2000ADA Recommendations

Rationale behind recommendations:

Both ADA and AHA recommend • Amoxicillin as drug of first choice• Use of Amoxicillin 1 hr preoperatively• Reduced dose of Amoxicillin from 3gms to 2gms• 2nd dose of Amoxicillin 6hrs post operatively• In patients allergic to Amoxicillin, Clindamycin is

recommended• Erythromycin no longer used………..

Rouse MS et al, 1997

Rationale behind recommendations:

Both ADA and AHA recommend

• Clarithromycin and Azithromycin as Amoxicillin alternatives

• Cephalexin………• Cephalosporins should not be given to patients with

history of immediate Type 1 hypersensitivity • No longer recommend combination of Amoxycillin

and Gentamycin…… Morreilon P et al, 1996• AHA no longer recommends Vancomycin but

however ADA recommends Vancomycin for Pen allergic patients unable to take oral medication

Review-

2

6

8

10

12

4

14

2 gm Amoxicillin600mg ClindamycinMIC 90

Adapted by Dajani 1997 Vermot 1996

mg/L

Hours1 6

Serum conc. following 2gm oral Amoxicillin and 600mg ClindamycinMIC 90 - Minimum inhibitory serum conc. effective against 90% of m/o exposed to antimicrobials.

ADA Risk Categories:

At-risk patient

• All acquired Valvular heart diseases • Hypertrophic Cardiomyopathy • Mitral valve prolapse with regurgitation• Most congenital heart diseases• Prosthetic heart valve• Previous episode of IE• Surgically constructed shunts

Aust. Dent. J 2001; 46(3): 220-5

ADA Risk Categories:

Non-risk patients

• Coronary bypass• Isolated atrio-ventricular defects • Kawasaki disease without Valvular dysfunction• Mitral valve prolapse without regurgitation• Pacemakers and implanted defibrillators• Physiological/innocent heart murmur• Rheumatic fever without Valvular dysfunction • Surgical repair of heart defects after six months

Aust. Dent. J 2001; 46(3): 220-5

ADA Risk Procedures:

1. Dental prophylaxis2. Endodontic surgery3. Extractions 4. Implant placement5. Instrumentation beyond the apex6. Intra- ligamentary injections7. Osteotomy8. Periodontal procedures9. Placing orthodontic bands10.Reimplantation of avulsed teeth11. Surgical drainage of abscess12.Surgical repair of jaw fracture

RISK PROCEDURES

Aust. Dent. J 2001; 46(3): 220-5

1. Exfoliation of deciduous teeth2. Intra-canal instrumentation3. Local anaesthesia (except intra-ligamentary )4. Orthodontic adjustments5. Radiographs6. Removal of sutures7. Restorative dental procedures8. Rubber dam placement9. Taking impressions

NON-RISK PROCEDURES

Aust. Dent. J 2001; 46(3): 220-5

ADA Risk Procedures:

Clinical Situations considered for Antibiotic Prophylaxis:

Prevention of metastatic infections Bacterial Endocarditis Surgical Antibiotic Prophylaxis Potential Antibiotic Prophylaxis Situations Prosthetic joints Brain Abscess Nonvalvular cardiovascular devices Hemodialysis Solid organ transplants Diabetes Immunocompromised patients Collagen Diseases and other disorders

Pharmacology & Therapeutics for Dentistry, 5th ed.

Clinical Situations considered for Antibiotic Prophylaxis:

• Infective Endocarditis• Dwelling catheters, neurosurgical

shunts and other implants• Prevention of local infection in

surgical or operative sites in the mouth

• Prevention of generalized spread of infections in patients with compromised immune system

JADA 2000; 131: 366-374

Exudative and Proliferative inflammatory alteration of the endocardium.

FIRST SUGGESTION OF THE LINK BETWEEN IE AND ORAL BACTERIA WAS RAISED IN 1909 BY HORDER TJ.

IE is uncommon with prevalence rate of 15-30 cases per1 million per year.

Certain studies challenge the practice of antibiotic prophylaxis to prevent IE:

Vandermeet JT et al, 1992 Storm BL et al 1998

Infective Endocarditis:

Certain controversies regarding association of Dentistry with IE :

Is IE caused by dental procedure-induced bacteremia or from spontaneous bacteremia ?

Which patients are at risk of IE ? Which procedures require antibiotic coverage

? Are the risk of providing such coverage

greater than the risk for contracting IE ? Are antibiotic regimens effective ?

DCNA 2002; 46: 635-51

Infective Endocarditis:

Antibiotic prophylaxis to prevent endocarditis 1955

Bacteremia and Oral Cavity

Incidence of Bacteremia

Dental Extraction 40%-89%Periodontal Surgery 36%-88%Simple Prophylaxis 0%-40%Buccal Anesthetic Injection 16%Intraligamentary Injection 97%Rubber Dam/Matrix/Wedge 9%-32%Non-Surgical Endodontic t/t 0%-15%

Infective Endocarditis:

Incidence of Bacteremia

Activities of Daily Living

Tooth Brushing : 0%-26%Dental Flossing : 20%-58%Wooden Cleansing Devices :20%-40%Water Irrigation Devices : 7%-50%Mastication : 17%-51%

Int J Oral Max Surg 1995; 24(3): 239-242.DCNA 2003; 47: 665-79.

Oral Microorganisms and Endocarditis:

• S. Viridans– Most common causative organism

• Gram negative bacilli– Neonates and Immunocompromised patients

• Prosthetic valves– Within first year of surgery: Coag-negative staph– After first year: similar to native valve endocarditis

• HACEK organisms– Hemophilus, Actinobacillus, Cardiobacterium,

Eikenella, Kingella Frequently affect damaged valves and can cause emboli

Oral Microorganisms and Endocarditis:

25% cases by VGS Cabell CH et al., 2002102 cases by A.

actinomycetemcomitans Paturel L et al., 20032 cases by P. oralis Quaglio G et al., 19995 cases by Veillonella Houston S et al., 19971 case by P. bivia, B. melaninogenicus Kentos A et al., 1994

Risk of Endocarditis due to dental procedures:

8% cases by periodontal/other dental diseases

Drangshott MT et al., 199819% to 35% by dental treatment procedures Droz D et al., 1997 No association between dental treatment

and endocarditis Strom BL et al., 1998 Houston S et al., 1997 Lacassin F et al., 1995 “Blaming a dentist for endocarditis would be like blaming the cardiologist for myocardial infarction.” Guntheroth, 1984

Infective Endocarditis:

Evertt ED et al., 1977

Bender IB et al., 1984Guntherhoth WG et al., 1984

Roberts GJ et al., 1999

Dentists are Innocent! “Everyday” bacteremia is the real culprit.

DCNA 2003; 47: 665-79.

Infective Endocarditis:

AHA recommendations significantly changed in respect to various cardiac conditions Understanding of disease process

Amoxicillin dosage reduced from 3gm to2gm.

recommending that follow up dose should be discontinued and replacement of

erythromycin.

Committee stated that:Wynn R. et alGen Dent 1997; 45: 426-34

Antibiotic Prophylaxis and Bacteremia Reduction:

Pallash TJ et al., 2000 antibiotic prophylaxis reduces

bacteremias after onset of dental treatment.

No explanation as to how drugs that work so slowly eliminate bacteremia so quickly?

Durack DT et al., 1995 & Hall G et al., 1996- Lysis filtration method- Preventing the adherence of

microbes to the valvular vegetations

Other conditions requiring antibiotic prophylaxis:

• Prosthetic Joint replacements: Jacobson JJ et al., 1988 CONTENTIOUS ISSUE!!

- Does dental induced bacteremia cause hematogenous infections in patients with joint prosthesis?

- Does antibiotic prophylaxis prevent such infections?

- What is the cost-risk benefit to provide such cover?

In the current consensus, ADA have recommended the use of antibiotic prophylaxis only patients with total joint replacements and compromised immune system.

R.A. Seymour et al 2003

Patients at Risk Include:

JADA 1997; 128(7): 1004-8

Suggested Antibiotic Prophylaxis Regime:

JADA 1997; 128(7): 1004-8

Hip and Joint Prosthesis:

• Early Infections Surgical Procedures• Late infections Hematogenous

Spread Is there any evidence ?? Ainscow DAP et al., 1984 Thyne GM et al., 1991 Deacon JM et al., 1996

Guidelines from Professional Bodies:• BSAC in 1992• ADA/AAOS in 1997• BOA

Overview:

Synopsis of evidence to date Staphylococcal origin Joint infection arising spontaneously from patient’s oral hygiene No evidence to support efficacy of antibiotic prophylaxis Risk with antibiotic prophylaxis is high Patients dentally fit Limited evidence…………..

Any perceived potential benefit of antibiotic prophylaxis must be weighed against the known

risks of antibiotic toxicity; allergy; and development, selection and transmission of

microbial resistance.

Patients with Renal diseases :

• Arteriovenous shunts and fistulas are commonly used to access the patient's bloodstream in hemodialysis.

• Carl and Wood (1976) suggested that patients receive dental treatment just before undergoing hemodialysis since they are free of anticoagulants at that time and at decreased risk of bleeding.

Common infectious agents are staphylococcal and streptococcal species.

Contaminate dialysis vascular access sites/infection in immunocompromised transplant patients

Arterio-Venous Connections

On one hand, patients with central lines and synthetic grafts for haemodialysis

Infection at the access site

Bacteremia and possible endocarditis

The synthetic graft or

catheter can be colonized and thus become a subsequent source for bacteremia.

However, on a broader scale, one may consider renal patients

Immunocompromised Argue

Antibiotic prophylaxis for dental procedures is not to cover a prosthesis or foreign material but to prevent systemic infection and sepsis in an immunocompromised individuals.

Controversy exists over the principles of antibiotic prophylaxis in renal patients:

Antibacterial Regime:

- Vancomycin (1.0 g) infused over one hour during dialysis the day before dental treatment

- Amoxicillin (3.0 g per mouth) one hour before the dental procedure; a second dose is not needed

- Erythromycin ethylsuccinate (800 mg) or erythromycin stearate (1.0 g by mouth) two hours before the dental procedure, then one-half the dose six hours after the initial dose

- Clindamycin (300 mg by mouth) one hour before the dental procedure, then 150 mg six hours after the initial dose

JADA 1996; 127: 211-19

Recent Study:

Forty-one per cent of clinicians do not routinely give antibiotic prophylaxis to haemodialysis patients prior to dental surgery, but a majority (53%) would consider antibiotic prophylaxis if the patient had a synthetic arteriovenous fistula. The majority of clinicians follow the American Heart Association (AHA) guidelines with a single oral preoperative dose of 2 g Amoxycillin or 600 mg clindamycin if patients are allergic to penicillin.

DARRYL C TONG Nephrology 2004; 9: 167-70

History of rheumatic fever is important…… Inflammatory Rheumatic Carditis

Cardiac Valve Damage

Mitral Valve Prolapse

With regurgitation Without regurgitation

Require Antibiotic Not required prophylaxis

Rheumatic Heart Disease:

AHA

Darryl C. Tong JADA 2000; 131: 366-74

SUGGESTED ANTIBIOTIC PROPHYLAXIS REGIMENS:

• Patients not allergic to penicillin: Cephalexin, Cephradine or Amoxicillin, 2 grams

orally, one hour before dental procedure• Patients not allergic to penicillin and unable to

take oral medications: Cefazolin (1 g) or Ampicillin (2 g)

intramuscularly or intravenously, one hour before dental procedure

• Patients allergic to penicillin: Clindamycin, 600 milligrams orally, one hour

before dental procedure• Patients allergic to penicillin and unable to take

oral medications: Clindamycin, 600 mg intravenously, one hour

before dental procedureJADA 1999; 130: 689-697

Nonvalvular Cardiovascular Devices:

Pacemakers, implantable cardioverter defibrillators, peripheral and cardiac vascular stents, prosthetic vascular grafts, and Dacron carotid patches.

Evidence for hematogenous infection with these devices is extremely rare, with no documentation of dental treatment causation.

AHA review concludes that……………………………

Baddour LM et alCirculation 108: 2015-31, 2003

Other conditions requiring antibiotic prophylaxis:

Prevention of local infection in surgical site

Clean Contaminated Highly contaminated- Routine exodontia - Periodontal

Surgery- Third molar surgery- Orthognathic surgeryPrevention of generalised spread of

infections in patients with compromised immune system At high risk of developing bacteremias Undergoing chemotherapy HIV infected patients Diabetics

Other Conditions:

• Brain Abscess: - 3rd metastatic infections after B.E. and

joint infections. - VGS likely causative agent - Rare, 1 per 10,000 hospital admissions - Absolute risk is 1 in 1 million to 10 million Pallasch TJ et al, 2003• Splenectomy No clinical studies evaluate the

efficacy of antibiotic prophylaxis prior to dental t/t in splenetic patients.

Waghorn DJ et al, 2001• Solid Organ Transplants Petri WA et al, 1994 Paterson DL et al, 1998

• Immunocompromised patients - HIV patients Pallasch TJ et al 1997- Darryl C Tong et al 2003- - Diabetic patients No data support use of antibiotic

prophylaxis in controlled non-ketotic diabetic patients.

Alexander RE et al, 1999

Lockhart PB et al 2002- Little JW et al 1993- - Neutropenic patients - Chronic I/V drug abusers

Other Conditions:

Associated Unsolved Problems ?

By Pallasch T J et al 2003

• High financial cost…………………………• Risk of Bacteremia…………………………• Extreme rarity of endocarditis…• Extremely low absolute risk…………• Dental Treatments rarely………………• Antibiotic prophylaxis does not significantly

reduce…• Contribution of Antibiotic

prophylaxis………………………• Mortality rate is greater………………………