Prophylaxis against Endocarditis: A Brave New World

Transcription

1 Prophylaxis against Endocarditis: A Brave New World Ann Bolger MD FACC FAHA University of California, San Francisco Nothing to disclose

2 PREVENTION OF INFECTIVE ENDOCARDITIS: GUIDELINES FROM THE AMERICAN HEART ASSOCIATION A guideline from the American Heart Association s Rheumatic Fever, Endocarditis and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and The Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group The Council on Scientific Affairs of the American Dental Association has approved the guideline as it relates to dentistry. In addition, this guideline has been endorsed by the Infectious Diseases Society of America and by the Pediatric Infectious Diseases Society.

3 Mission of IE Prophylaxis to target predictable bacteremias with organisms that can cause endocarditis in patients with more than baseline risk of infection Does prophylaxis decrease bacteremia? Does prophylaxis avoid IE? Do the benefits of prophylaxis outweigh the risks?

4 Year Primary Regimens for Dental Procedures 1960 Step I Prophylaxis two days before surgery with 600,000 units of procaine penicillin intramuscularly on each day. Step II Day of surgery: 600,000 units procaine penicillin intramuscularly supplemented by 600,000 units of crystalline penicillin intramuscularly one hour before surgical procedure. Step III For two days after surgery: 600,000 units procaine penicillin intramuscularly each day.

5 Year Primary Regimens for Dental Procedures 1997 Amoxicillin two grams orally one hour before procedure.

6 Cardiac Conditions Associated with the Highest Risk of Adverse Outcome from Endocarditis for Which Prophylaxis with Dental Procedures Is Recommended (Class IIb LOE B) Prosthetic cardiac valve Previous infective endocarditis Congenital heart disease (CHD)* --Unrepaired cyanotic congenital heart disease, including those with palliative shunts and conduits --Completely repaired CHD with prosthetic material or device either by surgery or catheter intervention during the first six months after the procedure** --Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization) Cardiac transplantation recipients who develop cardiac valvulopathy * Except for the conditions listed above, antibiotic prophylaxis is no longer recommended for any other form of congenital heart disease **Prophylaxis is recommended because endothelialization of prosthetic material occurs within 6 months after the procedure

7 The truth(s) of it. IE carries a high morbidity Bacteremia with organisms known to cause IE occurs commonly in association with dental, GI, or GU procedures Most cases are not related to an invasive procedure There are significant costs and risks of overuse of antibiotics

8 Outcome of Endocarditis Native valve endocarditis 70% cured with antibiotics 60% will require late valve surgery because of valve damage from infection Prosthetic valve endocarditis % over the first year

9 Dilemmas IE is rare Changing demographics Denominator Indications for prophylaxis are common (really?) Almost all supportive data comes from animal models with little semblance to human disease Few data exist to show that current regimens are highly effective There is a spectrum of underlying diseases

10 Endocarditis is a Rare Disease Rate per 100,000 Patient Years General population 5.0 Mitral valve prolapse No murmur 4.6 Murmur 52 Congenital heart disease Pulmonary stenosis 20 Aortic stenosis 180 VSD Corrected.. 60 Uncorrected. 220 Rheumatic heart disease Prosthetic valve Mechanical 308 Bioprosthesis Steckelberg IDCNA 7:9-19, 1993

11 Incidence of Endocarditis Per 1000 Medicare Beneficiaries v Device Infections Endocarditis Year Cabell CH, et al. Am Heart J 2004;147:

12 The Risks of Developing Endocarditis Bacteremia characteristics + Patient propensity Endothelial Substrate: Platelet aggregation Exposed fibrin Surface irregularity Artificial Materials Flow Substrate: High shear stress Shear stress gradients Turbulence Eddies Flow separation Stagnation points

13 Steady Laminar Flow is Protective Traub ATVB 1998; 18:677

14 Turbulent/Oscillatory flow: Promotion of Atherosclerosis and Thrombosis Traub ATVB 1998; 18:677

15 Dynamic Flow Conditions: Stagnation, Eddy Zones and Turbulence S C

16 Definition of Patients at Risk, 1997 and 2007 No Increased Risk: Isolated Secundum ASD ASD, VSD or PDA 6 months post-repair if no residua Previous CABG, Cardiac Pacemaker or Implanted Defibrillator MVP, Previous Kawasaki Disease, or Previous Rheumatic Fever if no insufficiency is present

17 84 year old Male Atrial Septal Defect Areas at risk?

18 Definition of Patients at Risk, 1997 and 2007 Highest Risk Category: Prosthetic Cardiac Valves Previous Bacterial Endocarditis Complex Cyanotic Congenital Heart Disease, with surgically constructed systemicpulmonary shunts or conduits Transplant recipients with valvular insufficiency (added in 2007 guidelines)

19 55 year old Male Mitral Valve Prosthesis Areas at risk

20 Definition of Patients at Risk, 1997 Moderate Risk Category: Most Other Congenital Cardiac Malformations Acquired Valvular Dysfunction Hypertrophic Cardiomyopathy Mitral Valve Prolapse with Insufficiency and/or Thickened Leaflets

21 History of the Denominator: Mitral Valve Prolapse 1970 s: 10% of young men and women with MVP, based on M-mode and any two dimensional view 1990 s: Changes in diagnostic criteria 2mm displacement Visible in more than apical 4 and 2 chamber views 5 mm thickness Incidence of MVP: 2%

22 Framingham Heart Study MVP Prevalence, % Freed JACC 2002 Any Echo Criteria Leaflet displacement Leaflet displacement Leaflet thickening > Mild MR Leaflet thickening Leaflet displacement

23 History of the Denominator: Mitral Valve Prolapse Currently: Better defined high risk features: More than mild valvular insufficiency Older age Male gender Prevalence of high risk MVP is low, however: MVP is the most common etiology requiring mitral valve replacement MVP is the most common underlying cardiac condition in patients with IE

24 27 year-old Female Mitral Valve Prolapse with Murmur Mild to moderate regurgitation No leaflet thickening

25 27 year-old Female Mitral Valve Prolapse with Murmur Mild to moderate regurgitation No leaflet thickening Areas at risk

26 Hypertrophic Cardiomyopathy 64 year old Male

27 64 year old Male Hypertrophic Cardiomyopathy Areas at risk

28 The Costs of Prophylaxis Adverse antibiotic reactions Inconvenience Expense Microbial resistance False confidence?

29 The Risks of Endocarditis Patient Risks: Risk of contracting the disease Risk of morbidity from the disease Procedure Risks: Risk of causing bacteremia with organisms likely to cause endocarditis

30 International Endocarditis Workshop Chicago May 7-9, 2004 Director: Walter Wilson, MD (Mayo Clinic) Co-sponsored by AHA and ADA International experts: from UK, Canada, France, Spain, Switzerland, S. Korea, Netherlands & USA Multidisciplinary: adult and pediatric cardiologists, adult and pediatric ID specialists, dentists, epidemiologists Later input from GI and GU specialists

31 Bacteremia in Dental Procedures Transient bacteremia is common with manipulation of the teeth and periodontal tissues with wide variation in reported frequencies. Tooth extraction (10-100%) Periodontal surgery (36-88%) Scaling and root planing (8-80%) Teeth cleaning (up to 40%) Endodontic procedures (up to 20%) Roberts GJ et al: Pediatr Cardiol1997;18:24

32 Bacteremia in Daily Activities Transient bacteremia also occurs during routine daily activities Tooth brushing and flossing (20-68%) Use of wooden toothpicks (20-40%) Water irrigation devices (7-50%) Chewing food (7-51%) Cobe HM et al: Oral Surg 1954;7:609 Sconyers JR et al: J Dental Assn 1973;87:616 Forner L, et al: J. Clin Peridontol 2006;33:401

33 Physiologic versus Dental Procedure Related Bacteremia Random bacteremias from chewing, tooth brushing & flossing add up to 5370 minutes over 1 month. Bacteremia due to a single tooth extraction lasts 6-30 minutes. (Guntheroth) Tooth brushing 2 times daily for 1 year had a 154,000 times greater risk of bacteremia than a single tooth extraction. (Roberts) Cumulative exposure in 1 year to bacteremia from all routine, daily activities may be 5.6 million times greater than that resulting from a single tooth extraction. (Roberts)

34 Is the Magnitude of Bacteremia Important? The magnitude of bacteremia from a dental procedure is relatively low ( < 10 4 CFU/mL) Bacteremia from routine daily activities are of similar magnitude Experimental IE in animals require CFU/mL There are no data demonstrating relationship between magnitude of bacteremia and likelihood of IE in humans Durack DT et al: Br J Exp Pathol 1972;53:50 Roberts GJ et al: Heart 2006;92:1274 Lucas VS et al: J Clin Microbiol 2002;40:3416

35 Is Oral Hygiene a Factor? In patients with poor oral hygiene, the frequency of positive blood cultures just prior to dental extraction may be similar to that following extraction Poor oral hygiene increased risk of spontaneous bacteremia Roberts GJ Pediatr Cardiol. 1999;20:317 Hockett RN, et al. Arch Oral Biol. 1977;22:91 Thayer W Hopkins Hospital Report. 1926;22:1

36 Is Bleeding a Factor? No data to support that visible bleeding during a dental procedure is a reliable predictor for bacteremia Roberts GJ Pediatr Cardiol 1999;20:317

37 Do Antibiotics Reduce Bacteremia? Amoxicillin therapy causes significant reduction but does not eliminate bacteremia. (Lockhart) Penicillin or ampicillin compared with placebo diminished the percentage of viridans group streptococci and anaerobes in culture, but no significant difference in the percentage of pts with positive cultures 10 minutes after tooth extraction. (Hall) Erythromycin: (1) Post-procedure bacteremia reduced by erythromycin (Shannon) (2) Erythromycin or clindamycin did not reduce bacteremia (Hall)

38 2-Year Prospective Study in the Netherlands 427 pts with definite late prosthetic valve or native valve IE 31 Excluded (non-oral bacteria) 29 Excluded (procedure w/ low bacteremia risk) 89 pts with IE onset within 180 days of dental/medical procedure 25 Native valve IE (not previously known) no abx 48 NVE (previously known) 8 (17%) received abx 16 prosthetic valve IE 9 (56%) received abx 45 of 89 developed IE within 30 days Prophylaxis might have prevented 23/427 (5.3%) of IE van der Meer et al: Arch Intern Med 152:1869, 1992

39 Population-Based Study in France Survey #1 Sample of 2805 adults from 2.3 million population Surveyed for pts w/ PCC* having at-risk procedure Survey #2 1-year French epidemiologic survey for no. cases IE among 16 million population Denominator Extrapolated To all of France Numerator [95% CI] Monte Carlo Simulation No. pts with predisposing cardiac condition No. pts undergoing at-risk dental procedure + antibiotic prophylaxis No. IE cases in each subgroup * PCC=Predisposing Cardiac Condition Duval X et al. Clin Infect Dis 2006;42:e102

40 Population-Based Study in France (39 Million Adults in 1999) Estimated 2.7 million at-risk dental procedures done in 1999 in France on pts with PCC 62% unprotected Estimated 1370 IE cases in 1 year (1 in 28,500 adults) 714 (52%) in pts with PCC 44 could have been related to at-risk dental procedures 37 unprotected, 7 protected Prophylaxis reduces IE prevalence in pts with PCC from 1/46,000 to 1/149,000 A huge number of doses of prophylaxis are needed to prevent a small number of cases. Duval X et al. Clin Infect Dis 2006;42:e102

41 2 Year Case-Control Study in the Netherlands 54 cases of IE vs 200 controls: same cardiac conditions same procedure no IE within 180 days 1 in 6 in both groups received prophylaxis Best estimate of prophylaxis efficacy: 49% Van der Meer JT et al. Lancet. Jan ;339:135

42 Case-Control Study in Delaware valley To evaluate dental prophylaxis and cardiac risk factors for community-acquired IE (N=273) vs controls matched for age, sex and residence. 1. Risk factors for IE: mitral valve prolapse (OR 19.4), congenital heart disease (OR 6.7), rheumatic heart disease (OR 13.4), and previous cardiac valve surgery. 2. Cases & Controls had similar exposures to dental work within 3 months. Only 6 cases and 2 controls received abx prophylaxis within 1 mo of study date. Strom BL et al. Ann Intern Med.1998;129:761

43 Case-Control Study in Delaware Valley 1. Dental treatment was not a risk factor for IE even in patients with valvular heart disease 2. Few cases of IE could be prevented with prophylaxis, even if it were 100% effective. Strom BL et al. Ann Intern Med.1998;129:761

44 IE Cases Possibly Related to Unprotected Procedures France 2.7% Duval X, et al. Netherlands 5% Van der Meer, et al. US 3% Strom, et al.

45 Estimated Risk of IE From Dental Procedures General population MVP 1 / 14 million 1 / 1.1 million CHD 1 / 475,000 RHD 1 / 142,000 Prosthetic cardiac valve 1 / 114,000 Previous IE 1 / 95,000

46 General Conclusions From Population-Based Studies These calculations of risk are estimates The number of cases of IE that result from a dental procedure is likely to be very small The number of cases that could be prevented by antibiotic prophylaxis, even if 100% effective, is small Effectiveness of prophylaxis would be considerably less than 100%

47 Primary Reasons for the 2007 Revision No data are available to link individual cases of IE to individual procedures IE is much more likely from frequent random bacteremias from daily activities Prophylaxis may prevent very few cases of IE in individuals who undergo dental, GI, or GU tract procedures The risk of antibiotic-associated adverse events exceeds the benefit Maintenance of good oral health and hygiene may reduce the incidence of bacteremia

48 What changes now? Many patients with known increased lifetime risk of IE will still know it Dental procedures will still be performed Strep viridans endocarditis will still occur without obvious inciting event Risk/Benefit decisions are still made from the individual patient s perspective

49 What changes now? Implement Guidelines against historical and individual practices Communication: Are you serious? Why were you so wrong in the first place? Did your wrong ideas cost me money? You mean I could have DIED from that amoxicillin?? I guess I m not at risk for heart infections after all. So I m at risk for heart infections, but there s nothing I can do about it?

50 What changes now? Education New evidence (not exactly) New look at the evidence Concern that antibiotics are becoming less useful because of overuse Other approaches to dealing with the risk of IE Commitment to vigilance Oral health Sources of Communication and Education Primary care provider Dental practitioner American Heart Association