227

Antibiotic Prophylaxis for Medical-Risk Patients* Thomas J. Pallasch and J0rgen Slots

The three current regimens for the prevention of infective endocarditis are discussed and compared along, with at-risk patients and dentally-induced bacteremias. The principles of antibiotic prophylaxis, and other medical conditions where antibiotic prophylaxis is controversial or inadequately documented is critically analyzed. / Periodontol 1991;

61:227-231.

Key Words: Antibiotic prophylaxis; endocarditis, infective subacute bacterial/prevention; risk factors; amoxicillin/therapeutic use; erythromycin/therapeutic use; clinada-

mycin/therapeutic use; ampicillin/therapeutic use; gentamicin/therapeutic use; vancomycin/ therapeutic use. There exists an empirical consensus that high-risk patients for metastatic bacteremic infections may benefit from antibiotic prophylaxis prior to dental procedures that are invasive and induce bleeding. High-risk patients include subjects with previous infective endocarditis (IE), coarctation of the aorta, cardiac valve prosthesis, rheumatic heart disease (even after valvular surgery), mitral valve prolapse (MVP) with régurgitation, hypertrophie cardiomyopathy, ventriculoatrial shunts for hydrocephalus, idiopathic hypertrophie subaortic stenosis and various forms of congenital heart disease1'2 (Table 1). Those patients at no or low-risk (no antibiotic prophylaxis required) include isolated secundum atrial septal defect, coronary bypass surgery, coronary artery disease, congenital pulmonary stenosis, MVP without régurgitation (except possibly those with redundant and/or thickened valves particularly males age 45 or over), previous Kawasaki disease without valvular dysfunction, previous rheumatic fever without valvular dysfunction, cardiac pacemakers and implanted defibrillators, physiologic, functional or innocent heart murmurs, and those having had surgical repair without residual effects of certain congenital heart defects1'2 (Table

Table 1: Medical Conditions Classified

Prophylaxis Requirements1'2

Prophylaxis

Recommended

Previous infective endocarditis Coarctation of the aorta Cardiac valve prosthesis Rheumatic heart disease

Hypertrophie cardiomyopathy

Ventriculoatrial shunts for

hydrocephalus prolapse with régurgitation

Mitral valve

Mitral valve surgery

Idiopathic hypertrophie aortic stenosis

Indwelling vascular catheter (right heart) Renal dialysis with A-V shunt appliance Congenital Heart Disease Ventricular septal defect Patent ductus arteriosus

Tetralogy of Fallot Complex cyanotic heart disease Systemic pulmonary artery

shunt Aortic stenosis

According to Antibiotic

Prophylaxis Not Recommended Secundum atrial septal defect Coronary bypass surgery Congenital pulmonary stenosis

Previous rheumatic fever without valvular dysfunction Coronary artery disease Mitral valve prolapse without re-

gurgitation (except possibly

with thickened and/or redundant valves particularly in males age 45 or older) Previous Kawasaki disease without valvular dysfunction Cardiac pacemakers and implanted defibrillators Physiologic, functional, or innocent heart murmurs Six months or longer after surgery for: Ligated ductus arteriosus Secundum atrial septal defect Ventricular septal defect Autogenous arterial grafts

1)·

The need for antibiotic prophylaxis is unsettled for patients with impaired host defenses (may be indicated with white cell counts less than 2500) or indwelling catheters (may be indicated).1 Patients with orthopedic prosthetic de-

vices are at a very-low to no-risk from dentally-induced bacteremias and antibiotic prophylaxis may not be required.3 Such patients should not receive penicillin prophylaxis as the risk-benefit ratio is poor (greater risk of death from penicillin allergy than death from infected prostheses).4 If prophylaxis is advised by the orthopedic surgeon, a ceph-

*Department of Periodontology, School of Dentistry, University of SouthCalifornia, Los Angeles, CA.

ern

alosporin is the drug of choice with erythromycin as a secondary agent.1,4 Orthopedic prosthesis patients presenting with an acute infection should receive therapeutic antibiotics along with treatment of the source of the oral infection.3 The American Heart Association (AHA) no longer requires parenteral antibiotic prophylaxis for patients with cardiac valve prostheses regardless of the dental procedure

performed.2 The oral route is now the method of choice unless the patient cannot take oral antibiotics.2 Previously the AHA allowed oral prophylaxis only for dental patients if good oral health was present and no gingival or oral surgical procedures were performed. The AHA now ree-

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ANTIBIOTIC PROPHYLAXIS FOR MEDICAL-RISK PATIENTS

ognizes that there are substantial logistic and financial barriers to parenteral antibiotics in such patients.2 The former AHA recommendations for parenteral antibiotics only served to relegate cardiac valve prosthesis patients to minimal dental care and likely poor oral health. Failures of oral antibiotic prophylaxis in cardiac valve prosthesis patients have not constituted a significant clinical problem.2 The British Society for Antimicrobial Chemotherapy (BSAC) has always allowed oral prophylaxis for cardiac prosthesis patients.5 The AHA now limits antibiotic prophylaxis in MVP patients only to those with mitral régurgitation with the notation that MVP patients with thickened and/or redundant valves may be at higher risk for IE particularly in males

age 45 or over2 who have a greater risk for eventual mitral valve replacement than females. A possible source of confusion is the various antibiotic regimens that have been proposed for antibiotic prophylaxis of high-risk patients by the American Heart Association,2 The Medical Letter on Drugs and Therapeutics,6 and the British Society for Antimicrobial Chemotherapy5 (Table 2). These recommendations have been recently revised: AHA (December 1990), The Medical Letter (December 1989) and the BSAC (January 1990). These regimens differ somewhat in the antibiotics of choice and the dosage and timing of antibiotic administration. All fulfill the necessary scientific, medical, and legal requirements for antibiotic prophylaxis in patients at high-risk for bacteremic infections. The new AHA guidelines entail substantial changes in drugs, dosages, and indications. Principally these include a change from penicillin V to amoxicillin for oral medication (with the provision that penicillin V is still rational and acceptable for viridans streptococci), the use of ethylsuccinate or stéarate erythromycin preparations (more rapidly and completely absorbed than erythromycin base), parenteral dosages only for those who may still wish to use them, the choice of Clindamycin (Cleocin) for patients who cannot take penicillin or erythromycin due to toxicity or allergy, the addition of hypertrophie cardiomyopathy as an indication for prophylaxis, the clarification of MVP prophylaxis, and the important elimination of parenteral antibiotics for cardiac valve prosthesis patients.2 The Medical Letter recommendations for oral amoxicillin are identical to those of the AHA6 while the BSAC employs a single 3 gram amoxicillin dose without a second dose.5 Each differs slightly in their erythromycin dosages and the AHA and BSAC in their Clindamycin regimens. The BSAC maintains that there is no documented evidence of pseudomembranous colitis following a single dose of

Clindamycin.5 The principles of antibiotic prophylaxis are well established: 1) the antimicrobial agent is chosen on the basis of the most likely microorganism to cause the infection; 2) an antibiotic loading dose should be employed; 3) the antibiotic should be present at sufficient concentration in the blood and target tissues prior to the dissemination of the offending organism; 4) the antibiotic should be continued

only as long as microbial contamination from the operative site persists; and 5) the benefit from the prophylaxis must outweigh the risk of antibiotic-induced allergy, toxicity, superinfections, and emergence of antibiotic-resistant

microorganisms.1

Based upon these principles, the recommendations of the AHA, Medical Letter, and BSAC are all reasonable with the qualification that risk-benefit determinations have been minimally addressed.1 All fulfill the medicolegal considerations in antibiotic prophylaxis for medical-risk patients exposed to dental treatment-induced bacteremias (directed principally against "viridans" streptococci). In view of the microbial etiology of infective endocarditis, the more rapid and less variable absorption of oral amoxicillin compared to penicillin V and equal efficacy against viridans streptococci, amoxicillin is the reasonable drug of choice. Amoxicillin is more expensive than penicillin V. The second dose recommendations of the AHA and The Medical Letter provide more prolonged blood drug levels but it is generally agreed that dentally-induced bacteremias are usually shortlived (15 to 30 minutes).1,2 The AHA recommends antibiotic prophylaxis only during the perioperative period (1 to 2 hours before the procedure and no longer than a total of 6 to 8 hours) with the provision that in delayed healing or a procedure involving infected tissue, it may be necessary to provide additional doses of antibiotics.2 The BSAC only requires antibiotic prophylaxis in highrisk patients for extractions and gingival scaling or surgical procedures.5 The Medical Letter does not list specific dental indications.6 The AHA recommends antibiotic prophylaxis for all dental procedures involving gingival or mucosal bleeding including professional cleaning, but allows for no prophylaxis in high-risk-patients for dental restorations above the gingival line, adjustment of orthodontic appliances and local anesthetic injections (except intraligamentary).2 In addition to systemic antibiotic prophylaxis, there is increasing evidence that the application of topical antiseptics immediately prior to the dental procedure can substantially reduce the incidence and severity of induced bacteremias.7,8 Chlorhexidine is the topical agent of choice (the AHA also lists povidone-iodine or iodine and glycerine) particularly in high-risk patients (i.e., cardiac valve prostheses) or those with poor oral hygiene. An appropriate procedure is the oral rinsing with Chlorhexidine for 1 to 2 minutes prior to the dental procedure. The AHA recommends irrigation of the gingival sulcus or painting on isolated or dried gingiva for 3 to 5 minutes before tooth extraction but does not address periodontal therapy.2 Local application of Chlorhexidine may itself induce a bacteremia and should only be used immediately before the dental procedure and after systemic prophylaxis is in place. Prolonged use of Chlorhexidine prior to the dental procedure is not recommended as this may result in the selection of antibioticresistant oral streptococci, enteric Gram-negative rods and

pseudomonads. The efficacy of antibiotic prophylaxis for the prevention

Volume 62 Number 3

PALLASCH, SLOTS

Table 2: Infective Endocarditis Antibiotic Prophylaxis Regimens for Dental Procedures According to the American Heart Association The Medical Letter on Drugs and Therapeutics,6 and the British Society for Antimicrobial Chemotherapy (BSAC)5 AHA

Medical Letter

Adults: 3 grams 1 hour prior to the procedure and 1.5 gram. 6 hours after the initial dose; Children: 50 mg/kg initially and 25 mg/kg 6 hours later (total dose not to exceed adult

Adults: 3 grams 1 hour prior to the procedure and 1.5 gram 6 hours later; Children: 50 mg/kg 1 hour before procedure and 25 mg/kg 6 hours later

Ethylsuccinate (800 mg) or stéarate (1 gm) 2 hours before procedure; Vi the first

Adults: 1 gram 2 hours before procedure and 500 mg 6 hours later; Children: 20 mg/kg 2 hours prior to procedure and 10 mg/kg 6 hours later

229

(AHA),2

BSAC

Oral Amoxicillin*

dose)

Adults: 3 grams 1 hour prior to the procedure; no second dose; Children: under age 10, 1/2 adult dose; under age 5, 1/4 adult dose

Erythromycin! Adults:

dose 6 hours after initial dose; Children: 20 mg/kg initially and 10 mg/kg 6 hours later (total dose not to exceed adult

Adults: 1.5 gram 1 to 2 hours before procedure, then 500 mg 6 hours later; Children: under age 10, 1/2 adult dose; under age 5, 1/4 adult dose

dose)

Clindamycin^ Adults: 300 mg 1 hour before procedure and 150 mg 6 hours after initial dose; Children: 10 mg/kg (total dose not to exceed adult dose);

Adults: No recommendation; Children: No recommendation

Adults: 600 mg 1 hour prior to the procedure; Children: Under age 10, 6 mg/kg 1 hour

prior to procedure

Parenteral

Ampicillin; Clindamycin; Ampicillin,

Gentamicin and Amoxicillin§ Adults: Ampicillin 2 grams IM or IV 30 minutes before procedure, then IM or IV 1 gm or oral amoxicillin 1.5 gm 6 hours after initial dose; Clindamycin 300 mg IV 30 minutes before procedure, then 150 mg IV or orally 6 hours after initial dose; Ampicillin 2 gm plus gentamicin 1.5 mg/kg (not to exceed 80 mg) IV or IM 30 minutes before procedure; then amoxicillin 1.5 gm orally 6 hours after initial dose; Children: Ampicillin (50 mg/kg); Clinda-

Ampicillin plus Gentamicin5 Adults: Ampicillin 2 grams and gentamicin 1.5 mg/kg IM or IV 30 minutes prior to procedure;

Children: Ampicillin 50 mg/kg and gentamicin 2 mg/kg IM or IV 30 minutes prior to

procedure

Amoxicillin5 Adults: Amoxicillin 1 gram in 2.5 ml of 1% lidocaine IM plus 120 mg gentamicin IM just before induction then 500 mg amoxicillin orally 6 hours later; Children: under age 10, 1/2 the adult dose of amoxicillin and gentamicin 2 mg/kg

mycin (10 mg/kg); gentamicin (2 mg/kg) not to exceed total adult dose; follow-up doses Vi initial dose.

Vancomycin' Adults: 1 gram IV given over 60 minutes and begun 1 hour prior to procedure; Children: 20 mg/kg IV over 60 minutes and begun 1 hour prior to procedure (not to exceed adult dose) 'Antibiotic of choice for most

Adults: 1 gram IV infused slowly over 1 hour beginning 1 hour prior to procedure; Children: 20 mg/kg infused slowly over 1 hour beginning 1 hour prior to procedure

patients; penicillin V is still

rational and

Adults: 1 gram by slow IV infusion over 1 hour followed by gentamicin 120 mg IV just before induction or 15 minutes before surgery; Children: under age 10, 20 mg/kg vancomycin and 2 mg/kg gentamicin IV

acceptable (AHA).

tFor patients allergic to penicillin or on continuous penicillin to prevent rheumatic fever (AHA). tFor patients unable to take penicillin or erythromycin due to allergy or toxicity. §For patients unable to take oral medications (ampicillin), allergic to penicillin, and unable to take oral medications (Clindamycin),

or not candidates for standard regimens (ampicillin, gentamicin, amoxicillin), amoxicillin not available in parenteral form in United States (AHA); for patients with prosthetic heart valves, previous endocarditis, and continuous penicillin for rheumatic fever prophylaxis (Medical Letter); only for patients undergoing general anesthesia who are not allergic to penicillin and have not had penicillin more than once in the previous month (BSAC). 'For high risk patients allergic to penicillin (AHA and Medical Letter), for patients undergoing general anesthesia allergic to penicillin, or undergoing general anesthesia who have received penicillin more than once in the previous month (BSAC).

of infective endocarditis and other metastatic microbial infections has never been proven in human clinical trials.1'2'9 The recommended guidelines are based on in vitro studies, clinical experience, animal models, and an assessment of bacteria likely to produce a bacteremia from a given site and most likely to produce infective endocarditis.2 The relevance of animal studies to the human disease has been seriously questioned as septicemia rather than bacteremia

and indwelling aortic catheters are generally required to induce experimental infective endocarditis.10 Antibiotic doses far greater than those employed in humans are required to prevent experimental IE in animals.11 Antibiotic prophylaxis in humans also may fail.2 It is also well established that dental treatment-induced bacteremias are responsible for 4% or less of infective endocarditis cases.12,13 Individuals are at far greater risk from

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J Periodontol March 1991

ANTIBIOTIC PROPHYLAXIS FOR MEDICAL-RISK PATIENTS

random, spontaneous bacteremias associated with normal

daily living (brushing, flossing, chewing), particularly in poorly maintained dentitions. It has been calculated that the

risk of a bacteremia from these oral functions is 1000 times greater than professional dental treatment.13 The AHA now recognizes that poor oral hygiene and periodontal and periapical infections may induce bacteremias in the absence of dental procedures.2 Dental treatment-induced bacteremias are rarely, if ever, responsible for orthopedic prosthesis

infections.3,14

patient risk-benefit ratios for antibiotic prophylaxis have been questioned.1'9-15 Penicillin propenicillin using phylaxis may be reasonable for patients at high-risk from The

bacteremic infections as listed above but the risk-benefit is unfavorable for those with moderate, low or no-risk medical conditions (i.e., MVP without thickened redundant valves and/or mitral régurgitation1-16'17 or orthopedic prosthetic devices3,14) where the likelihood of a serious or fatal allergic penicillin reaction is greater than any postulated benefit from the drug1,15 (Table 1). Antibiotic prophylaxis to prevent surgical infections or their sequellae have been proven effective only with a reasonable risk-benefit ratio in clean surgery (open heart surgery, major vascular reconstruction, orthopedic prosthetic joint replacement) where the risk of infection is slight, but its potential consequences grave or in clean-contaminated surgery (elective gastric, biliary, or colonie surgery) where the likelihood of infection is great but seldom fatal.18 The Medical Letter does not advocate antibiotic prophylaxis for head and neck surgical procedures.19 Repeated use of antibiotic prophylaxis may result in the emergence of antibiotic-resistant microorganisms in the oral cavity.1-20 For penicillin and erythromycin prophylaxis, resistance may occur within a few days or less and persist for months.1,20 If these agents are used, the dental procedures should probably not be more frequent than once every 2 to 3 weeks.1-21 The AHA now recommends an interval of at least 7 days between procedures and as much dental treatment completed as possible at each appointment.2 If shorter intervals are required, consideration should be given to alternating between several different antibiotic agents.1 Inherent resistance of some Actinobacillus actinomycetemcomitans strains to penicillin is of particular concern in periodontal therapy.22 Cases of A. actinomycetemcomitans endocarditis have developed after periodontal surgery or other dental procedures despite prophylactic administration of penicillin or erythromycin/vancomycin.23/lcrmo0aci7/i« actinomycetemcomitans is closely associated with localized juvenile Periodontitis and occurs in about one-third of advanced cases of adult Periodontitis.24 If culture shows high numbers of penicillin-resistant A. actinomycetemcomitans in endocarditis-susceptible individuals, systemic tetracycline (1 gram/day of tetracycline HCl or preferably metronidazole/Augmentin at 250 mg 3 times daily for 8 days) may be used to eradicate the organism prior to any dental procedure. After waiting 1 day, dental treatment should

then be carried out utilizing conventional prophylactic endocarditis regimens directed mainly against viridans

streptococci.

The most important means for reducing metastatic bacteremic infections from dental treatment or home oral hygiene procedures is the maintenance of excellent oral health particularly that of the periodontal tissues.2'6,17 Individuals at-risk for IE should establish and maintain the best possible oral health to reduce potential sources of bacteremia.2 The proper use of antibiotic prophylaxis only when indicated in patients at high-risk for bacteremic infections (acceptable risk-benefit ratios) will prevent needless antibiotic toxicity, allergy, and selection of antibiotic-resistant microorganisms resulting in greater patient safety and efficacy.

REFERENCES 1. Pallasch TJ. A critical

appraisal of antibiotic prophylaxis. Int Dent J

1989;39:183-196. 2.

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Bisno AL, Chung KY et al. Prevention of bacterial endocarditis: Recommendations by the American Heart Association. J Amer Med Assn 1990;264:2919-2922. Ching DWT, Gould IM, Rennte JAN, Gibson PH. Prevention of late haematogenous infections in major prosthetic joints. J Antimicrob Chemother 1989;23:676-680. Tsevat J, Durno-Zaleski I, Pauker SG. Cost-effectiveness of antibiotic prophylaxis for dental procedures in patients with artificial joints. Amer J Pub Health 1989;79:739-743. Antibiotic prophylaxis for infective endocarditis. Recommendations from the Endocarditis Working Party of the British Society for Antimicrobial Chemotherapy. Lancet 1990;335:88-89. Prevention of bacterial endocarditis. Med Lett Drugs Therap

Dajani AS,

1989;31:112. 7. Bender IB, Naidorf IJ, Garvey GJ. Bacterial endocarditis: A consideration for physician and dentist. J Amer Dent Assn 1984;109:415-

420. 8. Tzukert AA, Leviner E, Sella M. Prevention of infective endocarditis. Not by antibiotics alone. Oral Surg Oral Med Oral Pathol 1986;62:385388. 9. Pallasch TJ. Antibiotic prophylaxis: Theory and reality. J Calif Dent Assn 1989;17:27-39. 10. Glauser MP, Francioli P. Relevance of animal models to the prophylaxis of infective endocarditis. J Antimicrob Chemother 1987;20(Suppl

A):87-98. Wright AS,

Wilson WR. Experimental animal endocarditis. Mayo Clin Proc 1982;57:10-14. 12. Oakley CM. Controversies in the prophylaxis of infective endocarditis. J Antimicrob Chemother 1987:20(Suppl A):99-104. 13. Guntheroth WG. How important are dental procedures as a cause of infective endocarditis? Amer J Cardiol 1984;54:797-801. 14. Eskinazi D. Is systemic antibiotic prophylaxis justified in dental patients with prosthetic joints? Oral Surg Oral Med Oral Pathol 11.

1990;66:430-431.

15. Tzukert AA, Leviner E, Banoliel R, et al. Analysis of the American Heart Association's recommendations for prevention of infective endocarditis. Oral Surg Oral Med Oral Pathol 1986;62:276-279. 16. Devereux RB, Kramer-Fox R, Kligfield P. Mitral valve prolapse: Causes, clinical manifestations, and management. Ann Int Med

1989;111:305-317. Kaye D. Prophylaxis for infective endocarditis: An update. Ann Int Med 1986;104:419^123. 18. Stone HH. Basic principles in the use of prophylactic antibiotics. / Antimicrob Chemother 1984;14(Suppl B):33-37. 19. Antimicrobial prophylaxis in surgery. Med Lett Drugs Therap 1989;31:105-108. 17.

Volume 62 Number 3 20. Leviner E, Tzukert AA, Benoliel R, et al. Development of resistant oral viridans Streptococci after administration of prophylactic antibiotics: Time management in the dental treatment of patients susceptible to infective endocarditis. Oral Surg Oral Med Oral Pathol

1987;64:417-420. 21. Simmons NA, Cawson RA, Clark CA, et al. Prophylaxis of infective endocarditis (Letter). Lancet 1986;1:1267. 22. Slots J, Evans RT, Lobbins PM, Genco RJ. In vitro antimicrobial

susceptibility of Actinobacillus actinomyctemcomitans. Antimicrob Agents Chemother 1980;18:9-12. 23. Slots J, Rosling BG, Genco RJ. Suppression of penicillin resistant oral Actinobacillus actinomyctemcomitans with tetracycline: Considerations in endocarditis prophylaxis. JPeriodontol 1983;54:193-196. 24. Slots J, Feik D, Rams TE. Actinobacillus actinomyctemcomitans and

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Bacteroides intermedius in human Periodontitis: Age relationship and mutual association. / Clin Periodontol 1990;17:659-662.

Send reprint requests to Dr. Thomas J. Pallasch, Department of Periodontology, School of Dentistry, University of Southern California, Los Angeles, CA 90089-0641. Accepted for publication August 17, 1990. Drs. Slots and Pallasch were asked in August 1990 to write an editorial for the Journal of Periodontology on prophylactic/antibiotic use because of the variations in recommendations for prophylactic premedication. Since then, the American Heart Association published its newest recommendations in the Journal of the American Medical Association 1990;264:2919-2922. We asked Drs. Slots and Pallasch to expand their editorial into a short paper incorporating these changes and comparing all of the current recommendations, which we publish here.