April 19,2007

Introduction Infective endocarditis ; uncommon but life- threatening condition High morbidity and mortality despite advance medical strategies Many questions about IE prophylaxis efficacy from 1997 AHA guidelines

Classification of recommendations

Level of evidence

1997 document notable Most case of IE attribute to daily activities bacteremias than invasive procedure Acknowledgment of possible IE prophylaxis failures Not well evidence-based(class2b, LOE C) Complicating

New IE prophylaxis guidelines from British Society for Antimicrobial Chemotherapy

Potential consequences of changes in recommendations Violate long-standing expectations and practice pattern Fewer patients eligible for IE prophylaxis Reduce malpractice claims related to IE prophylaxis Stimulate prospective studies on IE prophylaxis

Pathogenesis of IE Formation of nonbacterial thrombotic endocarditis (NBTE) ; turbulence flow  Flow from high to low chamber  Flow through narrow orifice Bacteremia  Mucosal injury Bacterial adherence to NBTE  FimA protein of viridans streptococci  Staphylococcal adhesins of staphylococcus Proliferation of bacteria within vegetation  Rapidly multiply ; left > right  More than 90% of mature organisms : inactive ; less response to ATB Host’s immune response contribute to clinical manifestations

Historical background Bacteremia causes endocarditis Viridans streptococci and enterococci are part of normal flora of oral cavity and GI,GU tract respectively Susceptible to ATB ATB prophylaxis prevent endocarditis due to streptococci and enterococci in animal models Large number, poorly documented case report of dental procedure and IE Temporally relationship between dental procedure and onset of IE Evidence of viridans streptococci bacteremia after dental procedure Low risk of ATB adverse reaction High morbidity and mortality for IE patients Lack of published data demonstrate prophylactic benefit

Rationale for or against prophylaxis of IE Bacteremia-producing dental procedures  Frequency, nature, magnitude and duration of bacteremia associated with dental procedure  Impact of dental disease, oral hygiene and type of dental procedure on bacteremia  Impact of ATB prophylaxid on bacteremia from dental procedure  Exposure over time of bacteremia from daily activities compare with dental procedures Results of clinical studies of IE prophylaxis for dental procedure Absolute risk of IE resulting from dental procedure Risk of adverse reactions and cost-effectiveness of prophylactic therapy Cardiac conditions and endocarditis  Highest predisposition of IE  Highest risk of adverse outcome from IE

Bacteremia-producing dental procedures Frequency, nature, magnitude and duration of bacteremia associated with a dental procedure  Wide variation of frequencies of bacteremia from dental procedure ; tooth extraction, periodontal surgery, scaling and root planing, teeth cleaning, rubber dam matrix/wedge placement, endodontic procedure  Transient bacteremia occurs frequently in daily activities ; tooth brushing, flossing, wooden toothpicks, water irrigation devices, chewing food  Bacteremia from daily activities >>>> dental procedures  Few published data exist on the magnitude of bacteremia from dental procedure or daily activities life  Relatively low bacteremia from dental procedure and daily activities, < 10 4 CFU/ml, less than experimental IE in animals, 10 6 to 10 9 CFU/ml  Majority of IE patients had no dental procedure in 2 weeks before onset of symptom  No certain role of bacteremia duration and risk of IE  No clinically significant different between dental procedure and daily activities

Bacteremia-producing dental procedures Impact of dental disease, oral hygiene and type of dental procedure on bacteremia  Controversial relationship between poor oral hygiene, extent of dental and periodontal disease, type of dental procedure and the frequency, nature, magnitude, duration of bacteremia  Available evidences support : good oral hygiene and eradicating dental disease to decrease the frequency of bacteremia from routine daily activities  Numerous dental procedure associated with bacteremia similar to tooth extraction  Bleeding procedure?  Lastest guidline : overemphasis ATB prophylaxis and underemphasis good oral hygiene and routine dental care

Bacteremia-producing dental procedures Impact of antibiotic therapy on bacteremia from a dental procedure  Controversial of ability of ATB to prevent or reduce frequency, magnitude, duration of bacteremia associated with dental procedure  Amoxicillin ; reduce but not eliminate bacteremia  No data of amoxicillin for reduce or prevent IE  Contradictory of efficacy of antiseptic

Bacteremia-producing dental procedures Cumulative risk over time of bacteremias from routine daily activities compared with the bacteremia from a dental procedure  Cumulative exposure during 1 year to bacteremia from routine daily activities may be as high as 5.6 million times greater than that resulting from a single tooth extraction

Result of clinical studies of IE prophylaxis for dental procedures No prospective, randomized, placebo-controlled studies about efficacy of ATB prophylaxis to prevent IE in patients who undergo a dental procedure Some retrospective studies : suggest a prophylactic benefit but a small in size and insufficient clinical data and prolonged onset of symptoms Van der Meer ; dental procedure probably caused only a small fraction of cases of IE and prophylaxis ATB would prevent a small number of cases Strom : dental treatment was not a risk factor for IE even in patients with valvular heart disease Huge number of prophylaxis doses would be necessary to prevent a very low number of IE cases

Absolute risk of IE resulting from a dental procedure No published data accurately determine the absolute risk of EI that result from a dental procedure. Time frame between bacteremia and the onset of symptoms of IE is usually 7-14 days Many cases report and reviews included cases with a remote preceding events ; 3 to 6 months Undetermined whether the bacteremia result from dental procedure or routine daily activities Exceeding small amount of calculated cases of dental procedure-related IE

Risk of adverse reactions and cost- effectiveness of prophylactic therapy Nonfatal adverse reaction (rash, diarrhea, GI upset) commonly occur, not severe and self limited In penicillin use and anaphylactic fatalities  36% in known allergy to penicillin  64% in no history of allergy Fatal anaphylaxis in cephalosporin : less common Fatal reaction to single dose of macrolide or clindamycin : extremely rare

Summary of bacteremia factors Lacking of scientific proof for IE due to dental procedure and efficacy of prophylaxis ATB in cardiac risk factors patients Extremely small number of IE caused by bacteremia-producing dental procedure Extremely small number of IE cases might be prevented by ATB prophylaxis even 100% effective Majority of IE : caused by oral microflora and random bacteremia caused by routine daily activites Dental disease may increase risk of bacteremia associated with routines activities Emphasis shift from previous dental procedure-related bacteremia and prophylacxis ATB to dental care and oral health

Cardiac conditions and endocarditis Underlying conditions over a lifetime that have the highest predispositon to the acquisition of endocarditis  Most common underlying condition for IE Developing countries : RHD Developed countries : MVP  Steckelberg and Wilson report risk of IE per 100,000 patient-year MVP without murmur 4.6 MVP with MR murmur 52 RHD380 – 440 Mechanical or bioprosthetic valve308 – 383 Valve replacement for native IE630 Previous IE 740 Valve replacement for prosthetic IE2160

Cardiac conditions and endocarditis Underlying conditions over a lifetime that have the highest predispositon to the acquisition of endocarditis  CHD Minor to severe, complex cyanotic heart disease Increase various intracardiac valvular prosthesis, graft, shunt and other devices Different level of risk for acquisition of IE

Cardiac conditions and endocarditis Cardiac conditions associated with the highest risk of adverse outcome from endocarditis  Viridans streptococcal IE mortality rate Native valve : ≤ 5% Prosthetic valve : ≥ 20%  Enterococcal IE mortality rate : prosthetic valve > native valve  Prosthetic IE take higher risk for : HF, cardiac valve replacement surgery, perivalvular extension of infection and other complications  Relapsing or recurrent IE : greater risk of CHF, cardiac valve replacement surgery, higher mortality  Multiple episodes of native or prosthetic valve IE : greater risk of additional episodes of IE and more serious complications  CHD : complex cyanotic heart disease and postoperative palliative shunts, conduits or other prostheses have a high lifetime risk of acquiring IE and risk for morbidity and mortality

1997 risk classifications

Cardiac conditions and endocarditis Should IE prophylaxis be recommended for patients with the highest risk of acquisition of IE or for patients with the highest risk of adverse outcome from IE?  “In patients with underlying cardiac conditions associated with the highest risk of adverse outcome from IE, IE prophylaxis for dental procedures may be reasonable, even though we acknowledge that its effectiveness is unknown (class 2b, LOE B)”

Regimens recommended General principles  Single dose before the procedure  Up to 2 hours administration after procedure if inadvertently not administrated before procedure  Beware IE in high risk patient who underwent the invasive procedure

Regimens for dental procedure Class 2b, LOE C (unknown effectiveness)

Exists evidences of drug-resistance strains

Regimens for respiratory tract procedures No published data conclusively demonstrate a link between RS procedure and IE ATB prophylaxis was recommend in  an invasive procedure involve incision of mucosa : tonsillectomy, adenoidectomy  Infection drainage : abscess, empyema No role of ATB prophylaxis in bronchoscope without incision of mucosa The same patient and regimen as dental procedure Beware staphylococcus

Recommendations for GI or GU tract procedures Enterococci infection : GI and GU tract No published data link between IE and GI, GU tracts procedures No studies exist demonstrate ATB prophylaxis prevent IE in GI, GU procedures Increase frequency of enterococci resistant to penicillin, vancomycin, aminoglycosides, but unknown significance about GI, GU tracts procedures IE prevention Prophylaxis ATB solely to prevent IE is not recommend  Diagnostic esophagogastroduodenoscopy  colonoscopy

Recommendations for GI or GU tract procedures Reasonable ATB prophylaxis in indicated patients with :  Established GI or GU tract infection or  Receive ATB to prevent wound infection or sepsis associated with GI or GU tract procedure ATB against entercocci : penicillin, ampicillin, piperacillin, vancomycin include in regimen No published studies demonstrate efficacy Class 2B, LOE B

Recommendations for GI or GU tract procedures Reasonable ATB to eradicate enterococci in indicated patient with :  Elective cystoscopy or  Other urinary tract manipulation Enterococcal urinary tract infection or colonization Reasonable empiric or specific ATB against enterococci in non-elective procedure Class 2B, LOE B

Recommendations for procedures on infected skin, skin structure, musculoskeletal tissue Reasonable therapeutic regimen active against staphylococci and β-hemolytic streptococci in indicated patients with :  Undergo surgical procedure that involves infected skin, skin structure, musculoskeletal tissue Class 2B, LOE C