appraisal and Julian
Frieden
Frankhn Lo-fly, .H).* Neal H. Steigbigel, M.D. F.A.G.P. New
York,
IV. Ei.
While antibiotic therapy of infective endocarditis has dramatically improved patient survival, the morbidity and mortality of this infection remains clinical studies appreciable.‘-” Well-controlled investigating the effectiveness of antibiotics in preventing the development of infective endocar.&is are not availa.ble. Therefore, the present recommendations for antibiotic prophylaxis have been based on extrapolations from several types of data: (1) the pathogenesis of infective endocarditis often involves implantation of the causative organism on damaged cardiac valves during transient bacteremia4; (2) the transient bacteremia often follows particular mechanical procedures”. j; (3) the species of organisms isolated during these bacteremias and those which frequently cause endocarditis have relatively predictable antibiotic susceptibilities”; (4) knowledge of the bactericidal activity and clinical pharmacology of antibiotics suggests prophylactic The actual risk of an individual with valvular heart disease developing endocarditis following a particular procedure is unknown. Hook and Xaye” roughly estimated the risk to be 1 in 533 (0.19 per cent) per tooth extraction. TaraniG had
prosthetic
heart
valves;
iac disorders Warrantii~g antimicrobial ~ro~by~axis of infective e~~oca~~~~~is --I____ Rheumatic v&alar disease Congenital heart disease (except urtcomplicated secundum atria1 septal defect) Prosthetic heart valves Idiopathic hypertrophic subaortic stenosis Previous episode of infective endocarditis Other acquired v&alar heart disease (e.g., :~yphilitic, artherosclerotic) Patients on hemodiaiysis” Mitral valve prolapse* Patients with pacemakers*
four cases a,f ~~docarditis Ln .350 hzclren with rheumatic valvular disease follnwing toot extractions, while Schwartz and Salman” noted no cases following 403 tooth extractions in 98 patients with rheumatic heart disease. The risk of endocarditis undoubtedly varies for a. num reasons incl~d~~~ the type of ~al~rslar disease, the age of the patient, the organism involved, and the level of batter ia. Bt should be noted for comparison, that ificidel,m of anaphylactic reactions caused by penicillin is reported to be 8.04 to 0.11 per cent, a risk similar
Lowy and Steigbigel
IV. Antimicrobial endocarditis
Table
1.
prophylaxis
of infective
Dental procedures and upper respiratory procedures’ Parenteral: A. Aqueous crystalline penicillin G 1 million units plus procaine penicillin G 600,000 units IM S-1 hour before the procedure, then penicillin V 500 mg. p.o. q6h for 4-8 doses. B. Regimen A plus streptomycin 1 Gm. IM given g-1 hour before the procedure* C. Vancomycin 1 Gm. IV over S-1 hour, given g-1 hour prior to the procedure’, 3 Oral: D. Penicillin V 2 Gm. p.o. S-1 hour prior to the procedure, then 500 mg. p.o. q6h for 8 doses E. Erythromycin 1 Gm. p.o., l-2 hours before the procedure, then 500 mg. p.o. q6h for 8 doses3
2.
Gastrointestinal
and genitourinary
procedures”
Parenteral: F. Ampicillin 1-2 grams IM or IV (or aqueous crystalline penicillin G 1-2 million units IM or IV) plus streptomycin 1.0 gram IM (or gentamicin 1.5 mg./kg. IM). Both antibiotics to be given g-1 hour before the procedure and repeated at 12 and 24 hours with the penicillin-streptomycin regimen and every 8 h for 24h with the penicillin-gentamicin regimen G. Vancomycin 1 Gm. IV over S-1 hour starting S-1 hour prior to the procedure plus streptomycin 1 Gm. IM. Both drugs may be repeated at 12 hours3 Oral: No oral regimen has been demonstrated to provide satisfactory protection ‘All dental procedures including cleaning, but not including orthodontic adjustments. The need for prophylaxis following tonsillectomy or bronchoscopy is uncertain. ‘These regimens are considered the most effective and are recommended for patients with prosthetic heart valves, and for individuals on long term penicillin prophylaxis for rheumatic fever. 3These regimens may be used in penicillin allergic patients. The parenteral regimen is preferred. ‘Prophylaxis is recommended for all genitourinary procedures, including urethral catheter insertion and removal. It is also recommended for gall bladder and bowel surgery. It is not routinely recommended for sigmoidoscopy, barium enema, liver biopsy or upper g.i. endoscopy, except perhaps for patients with prosthetic heart valves. SDosage of streptomycin and gentamicin should be modified in the presence of renal insufficiency.
to that of endocarditis following tooth extraction.48, 49 The recommendations for antibiotic prophylaxis for endocarditis have been extensively revised based on experimental studies using a rabbit endocarditis model. Endocarditis is produced in the rabbit by passing a polyethylene catheter across the aortic or tricuspid valves and
692
giving an intravenous injection of organisms after a period of 1 to 2 days.50,j1 Mechanical trauma to the valve leads to formation of a platelet-fibrin thrombus which serves as the nidus for infection. The virulence of the organism correlates with the likelihood of establishing an infection, following the “transient” bacteremia. Durack and Petersdo@ have studied the more commonly recommended regimens for prophylaxis using this model. Antibiotics were given one-half hour prior to the injection of organisms. Rabbits were killed at 24 hours, at which time bacterial colony counts of valvular vegetations were performed. Their studies of streptococcus viridans endocarditis demonstrated that vancomycin alone, or a combination of penicillin G and streptomycin, were the most effective regimens. When a lower initial bacterial inoculum was used, erythromcyin was shown to have some protective value; however, primarily bacteriostatic drugs such as tetracycline, clindamycin, or erythromycin were generally ineffective.8, 9 Similar studies were performed in rabbits inoculated with enterococci.10 Vancomycin alone and vancomycin or ampicillin plus streptomycin were all effective regimens. There was considerable variation in response depending on the strain of enterococcus; these variations were not always predicted by in vitro sensitivity tests.lO The studies in the rabbit model provide important data for selecting an appropriate prophylactic regimen, but with some appreciable limitations. The pharmacokinetics of antibiotics in the rabbit are different from those in man. Endocarditis is produced in the rabbit by leaving a foreign body, the catheter, across the cardiac valve. Finally, a high inoculum of bacteria, lo8 colony forming units/ml., is used compared to the 10f to lo* colony forming units/ml. generally encountered in the bacteremia following dental procedures.‘, 23The high inoculum assures that a higher percentage of animals will be infected; however, it provides a greater challenge for the prophylactic regimen, making some drugs such as erythromycin, which are effective at a lower inoculum, appear inadequate. Therefore, regimens shown to be effective using this experimental model probably provide a wide margin of safety. Nevertheless, some have suggested that antibiotic dosages for prophylaxis should be the same as those used for treatment of endocarditis.”
November,
1978, Vol. 96, No. 5
r the
prevention
of
Despite some uncertainty about effectiveness, antibiotic prophylaxis for bacterial endocarditis is recommended in association with certain procedures. The morbidity and mortality of the disease outweighs concern for drug side effects and for the limited protection they may provide. Prophylactic regimens suggested for dental or oropharyngeal surgery are aimed especially against viridans streptococci, while those suggested for genito-urinary or gastrointestinal procedures are directed primarily against the enterococcus.li, j* There are several precautions that should be in individuals with underlying valvular e. Patients should be informed of the potential risks of dental, gastrointestinal or genitourinary procedures. Cardiac conditions which warrant prophylaxis are listed in Table III. Good dental care is particularly important in patients with valvular heart disease. The level of bacteremia is correlated with the extent of gum disease. Oral irrigation devices should generally be avoided in patients at high risk for endocarditis because of the increased incidence of bacteremia associated with their use.2’ Patients scheduled for elective valvular replacement should have any necessary dental work performed prior to cardiac surgery, since the risk of developing endocarditis in the immediate postoperative period is 2 to 4 per cent.? When procedures are performed on the genito-urinary or biliary systems, the incidence of bacteremia is reduced when the urine or bile are sterile.“” If tracheal intubation is required, the orotracheal approach causes lessbacteremia than the nasotraeheal approach.‘5 The antibiotic regimens listed in Table IV are based on the recently published recommendations of the American Heart Association5* and The Medical Letter on Drugs and Therapeutics.j3 Antibiotics given parenterally are probably more effective than those given by mouth. The recommendations represent an attempt to accommodate the practical problem created by giving parenteral therapy for outpatient procedures with the need for sustained antibiotic activity. The pare&era1 regimen using intramuscular penicillin G plus procaine penicillin is probably adequate for most cardiac patients undergoing dental procedures. However, patients taking oral penicillin prophylaxis for rheumatic fever have a
higher incidence of relatively penlclllan-~esistan^i streptococci in their oro~hary~~, so that coverage with vancomycin, or penicillin plus s~e~~~rny~i~ is advised. In addition, the recommended for patients wi Antibiotic coverage is recommended for mrgery on abscesses,or infected foci and for d~bridement of burned tissue. The antibiotic re instances shoul take account of (i.e., S. aureus) likely to be associated with bacteremia and e~do~arditis.~~
cardiac surgery even though large carefully controlled studies of the e~e~t~~e~e~s of such regimens are not available. A~~ibiot~~ coverall has been suggested because of the morality associated with early prosthetic v e~dQ~ar~~tis.j”. j5 The incidence of valvular ~~~~e~tio~sis relatively Iow,~~so that a large num would have to be incl ing the potential bene its. The incidence of prosthetic valve e~~~~~ar~i~ia rises in patients requiring piol ~ard~o~~lmonary bypass.jc Al nisms accounting for these i different i~stitutio~s~ the most, frequently isolated pathogens are S. e~~der?~~~~~,S. am-em, diptheroids, fungi (especially As~~.r~i~l~~ and Candida sp.) and Gram-negative rods.*“. 55 The patient’s skin, the operating room air, an cardiopulmonary bypass machines have ssible i~trao~era~~ve sources of intravenous and urinary ca.thee major postoperative ortals of entry for bacteremia.4:* ~3 x Two recently reported studies have compare regimens using antibiotic p~o~~y~a~~s ~~~ti~~e for 1 to 2 days versus 5 to 6 days surgery and found no significan incidence of serious infection groups.57.58 One study noted caused by resistant organisms with the longer regimen.j’ The increase in early ~ro~t~~~i~ valve infections caused by Grarn-~e~~t~~~ organisms and methi~il~i~-~esiatant S. e~~~e~?~~~~snoted recently may be a consequence of the selective pressure provided by pr~~hylac~i~ therapy.“” antibiotic coverage is ~~~e~~essar~for pace-
Lowy
and
Steigbigel
maker insertions, closed heart surgery, and cardiac catheterization.““, 56.6o It is suggested for open heart surgery when cardiopulmonary bypass is necessary. Although a penicillinase-resistant semisynthetic penicillin or a cephalosporin given parenterally for 48 hours is recommended, differing local patterns of antibiotic sensitivity may warrant additional or different antibiotic coverage.j’
17.
18.
19. 20.
21. REFERENCES
1. 2.
3.
4.
5. 6.
7.
8.
9.
10.
11.
12.
13.
14.
15. 16.
694
Garvey, G. J., and Neu, H. C.: Infective endocarditis-an evolving disease, Medicine 57:105, 1978. Pelletier, L. L., Jr., and Petersdorf, R. G.: Infective endocarditis: a review of 125 cases from the University of Washington Hospitals, 1963-72, Medicine 56:287, 1977. Kaye, D.: Cure rates and long-term prognosis, in. Infective Endocarditis, D. Kaye, ed., Baltimore, 1976, University Park Press, p 201. Weinstein, L., and Schlesinger, J. J.: Pathoanatomic, pathophysiologic and clinical correlations in endocarditis, N. Engl. J. Med. 291:832, 1122, 1974. Hook, E. W., and Kaye, D.: Prophylaxis of bacterial endocarditis, J. Chronic Dis. 15:635, 1962. Matsen, J. M., and Coghlan, C. R.: Antibiotic testing and susceptibility patterns of streptococci, in Streptococci and Streptococcal Diseases: Recognition, understanding and management, L. W. Wannamaker, J. M. Matsen, eds., New York, 1972, Academic Press, p 189. Sipes, J. N., Thompson, R. L., and Hook, E. W.: Prophylaxis of infective endocarditis: a reevaluation, Ann. Rev. Med. 28:371, 1977. Pelletier, L. L., Jr., Durack, D. T., and Petersdorf, R. G.: Chemotherapy of experimental streptococcal endocarditis. IV. Further observations on prophylaxis, J. Clin. Invest. 56:319, 1975. Durack, D. T., and Petersdorf, R. G.: Chemotherapy of experimental streptococcal endocarditis. I. Comparison of commonly recommended prophylactic regimens, J. Clin. Invest. 52:592, 1973. Durack, D. T., Starkebaum, M. K., and Petersdorf, R. G.: Chemotherapy of experimental streptococcal endocarditis. VI. Prevention of enterococcal endocarditis, J. Lab. Clin. Med. 90:171, 1977. Denny, F. W., Wannamaker, L. W., Brink, W. R., Rammelkamp, C. H., Jr., and Custer, E. A.: Prevention of rheumatic fever: treatment of the preceding streptococtic infection. J.A.M.A. 143:151, 1950. Catanzaro, F. J., Rammelkamp, C. H., and Chamovitz, R.: Prevention of rheumatic fever by treatment of streptococcal infections. II. Factor responsible for failures, N. Engl. J. Med. 259:51, 1958. Rammelkamp, C. H.: Hemolytic streptococcal infections, in Principles of Internal Medicine, G. W. Thorn, R. D. Adams, E. Braunwald, K. J. Isselbacher, and R. G. Petersdorf, eds., New York, 1977, McGraw-Hill Company, Inc., p 819. American Heart Association Committee on Prevention of Rheumatic Fever: Prevention of rheumatic fever, Circulation 55:1, 1977. Lewis, T., and Grant, R. T.: Observations relating to subacute infective endocarditis, Heart 10:21, 1923. Lerner, P. I., and Weinstein, L.: Infective endocarditis in the antibiotic era, N. Engl. J. Med. 274:199,259,323,388, 1966.
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Kaye, D.: Prophylaxis of endocarditis, in Infective endocarditis, D. Kaye, ed., Baltimore, 1976, University Park Press, p 245. Okell, C. C., and Elliott, S. D.: Bacteremia and oral sepsis with special reference to the etiology of subacute endocarditis, Lancet 2:869, 1935. McEntegart, M. G., and Porterfield, J. S.: Bacteremia following dental extractions, Lancet 2:596, 1949. Crawford. J. J.. Sconvers. J. R.. Moriartv. J. D.. King. R. C., and West, ‘J. F.:‘Bacteremia after ‘tooth extraction studied with the aid of prereduced anaerobically sterilized culture media, Appl. Microbial. 27:927, 1974. DeLeo, A. A., Schoenknecht, F. D., Anderson, M. W., and Peterson, J. C.: The incidence of bacteremia following oral prophylaxis on pediatric patients, Oral Surg. 37:36, 1974. Hurwitz, G. A., Speck, W. T., and Keller, G. B.: Absence of bactermia in children after prophylaxis, Oral Surg. 322391, 1971. Sconyers, J. R., Crawford, J. J., and Moriarty, J. D.: Relationship of bacteremia to toothbrushing in patients with periodontitis, J. Am. Dent. Assoc. 87:616, 1973. Bereer. S. A.. Weitzman. S.. Edberz. S. C.. and Casev. J. I.: Bacteremia after the’use of an &al irrigation device, Ann. Intern. Med. 80:510, 1974. Berry, F. A., Blankenbaker, W. L., and Ball, C. G.: A comparison of bacteremia occurring with nasotracheal and orotracheal intubation, Anaesth. Analog (Cleveland) 52:873, 1973. Shull, H. J., Jr., Greene, B. M., Allen, S. D., Dunn, G. D., and Schenker, S.: Bacteremia with upper gastrointestinal endoscopy, Ann. Intern. Med. 83:-2i2, 1975. LeFrock. J. L.. Ellis. C. A.. Turchik. J. B.. and Weinstein. L.: Transient bacteremia associated with sigmoidoscopy; N. Engl. J. Med. 289:467, 1973. LeFrock, J. L., Ellis, C. A., Klainer, A. S., and Weinstein, L.: Transient bacteremia associated with barium enema, Arch. Intern. Med. 135:835, 1975. LeFrock, J. L., Ellis, C. A., Turchik, J. B., Zawacki, J. K., and Weinstein, L.: Transient bacteremia associated with percutaneous liver biopsy, J. Infect. Dis. 131 (Suppl):S104, 1975. Biorn, C. L., Browning, W. H., and Thompson, L.: Transient bacteremia immediately following transurethral prostatic resection, J. Urol. 63:155, 1950. Creevy, C. D., and Feeney, M. J.: Routine use of antibiotics in transurethral prostatic resection: a clinical investigation, J. Ural. 71:615, 1954. Slade, N.: Bacteremia and septicemia after urological operations, Proc. R. Sot. Med. 51:331, 1958. Sullivan. N. M.. Sutter. V. L.. Mims. M. M.. Marsh. V. H.. and Finegold, S. M.: Clinical aspects of bacteremia after manipulation of the genitourinary tract, J. Infect. Dis. 127:49, 1973. McCormack, W. M., Rosner, B., Lee, Y. H., Rankin, J. S., and Lin, J. S.: Isolation of genital mycoplasmas from bloqd obtained shortly after vaginal delivery, Lancet 1:596, 1975. Everett, E. D., Reller, L. B., Droegemueller, W., and Greer, B. E.: Absence of bacteremia after insertion or removal of intrauterine devices, Obstet. Gynecol. 47:207, 1976. Sande, M. A., Levinson, M. E., Lukas, D. S., and Kaye, D.: Bacteremia associated with cardiac catheterization, N. Engl. J. Med. 281:1104, 1969. Richards, J. H.: Bacteremia following irritation of foci of infection, J.A.M.A. 99:1496, 1932. Cobe, H. M.: Transitory bacteremia, Oral Surg. 7:609, 1954. I
I
I
November,
I
I
1978, Vol. 96, No. 5
39. 40.
41.
42. 43.
44. 45.
46. 47.
48.
49.
50.
for bacterial endocarWeinstein, L.: Chemoprophylaxis ditis (Letter), N. Engl. J. Med. 292:427, 1975. Gould, K., Ramirez-Ronda, C. H., Holmes, R. K., and Sanford, J. P.: Adherence of bacteria to heart valves in vitro, J. Clin. Invest. 56:1364, 1975. Gibbons, R. J.: Ecology and cariogenic potential of oral streptococci, in Streptococci and Streptococcal Diseases: Recognition, understanding and management, L. W. Wannamaker, J. M. Matsen, eds., New York, 1972, Academic Press, p 371. H&on, G. R. F.: Is chemoprophylaxis necessary? Proc. R. Sot. Med. 63:267, 1970. Harvey, W. P., and Capone, M. A.: Bacterial endocarditis related to cleaning and filling of teeth, Am. J. Cardiol. 7:793, 1961. Weinstein, L., and Rubin, R. H.: Infective endocarditis-1973, Progr. Cardiovasc. Dis. 16:239, 1973. &rack. D. T.. and Littler. W. A.: Failure of “adeauate” penicilhn therapy to prevent bacterial endocarditis after tooth extraction (Letter), Lancet 2:846, 1974. Tarac, L. M.: Rheumatic fever in its relation to dental disease, hi. Y. J. Dent. 14:107, 1944. Schwartz. S. P.. and Salman. I.: The effects of oral surgery on the course of patients with diseases of the heart, Am. J. Orthod. 28:331, 1942. Rudolph, A. H., and Price, E. V.: Penicillin reactions among patients in venereal disease clinics. J.A.M.A. 223:499, 3973. Brown, W. J., Simpson, W. G., and Price, E. V.: Reevaluation of reactions to penicillin in venereal disease clinic patients, Public Health Rep. 76:189, 1961. Garrison. 43. K.. and Freedman. L. R.: Experimental endocarditis in rabbits resulting from placement of a polyethylene catheter in the right side of the heart, Yale J. Biol. Med. 42:394, 1970.
51.
52.
53.
54.
55.
56. 57.
58.
59.
60.
Darack, D. T., and Beeson, P. 9.: Exnerim
Frieden
Frankhn Lo-fly, .H).* Neal H. Steigbigel, M.D. F.A.G.P. New
York,
IV. Ei.
While antibiotic therapy of infective endocarditis has dramatically improved patient survival, the morbidity and mortality of this infection remains clinical studies appreciable.‘-” Well-controlled investigating the effectiveness of antibiotics in preventing the development of infective endocar.&is are not availa.ble. Therefore, the present recommendations for antibiotic prophylaxis have been based on extrapolations from several types of data: (1) the pathogenesis of infective endocarditis often involves implantation of the causative organism on damaged cardiac valves during transient bacteremia4; (2) the transient bacteremia often follows particular mechanical procedures”. j; (3) the species of organisms isolated during these bacteremias and those which frequently cause endocarditis have relatively predictable antibiotic susceptibilities”; (4) knowledge of the bactericidal activity and clinical pharmacology of antibiotics suggests prophylactic The actual risk of an individual with valvular heart disease developing endocarditis following a particular procedure is unknown. Hook and Xaye” roughly estimated the risk to be 1 in 533 (0.19 per cent) per tooth extraction. TaraniG had
prosthetic
heart
valves;
iac disorders Warrantii~g antimicrobial ~ro~by~axis of infective e~~oca~~~~~is --I____ Rheumatic v&alar disease Congenital heart disease (except urtcomplicated secundum atria1 septal defect) Prosthetic heart valves Idiopathic hypertrophic subaortic stenosis Previous episode of infective endocarditis Other acquired v&alar heart disease (e.g., :~yphilitic, artherosclerotic) Patients on hemodiaiysis” Mitral valve prolapse* Patients with pacemakers*
four cases a,f ~~docarditis Ln .350 hzclren with rheumatic valvular disease follnwing toot extractions, while Schwartz and Salman” noted no cases following 403 tooth extractions in 98 patients with rheumatic heart disease. The risk of endocarditis undoubtedly varies for a. num reasons incl~d~~~ the type of ~al~rslar disease, the age of the patient, the organism involved, and the level of batter ia. Bt should be noted for comparison, that ificidel,m of anaphylactic reactions caused by penicillin is reported to be 8.04 to 0.11 per cent, a risk similar
Lowy and Steigbigel
IV. Antimicrobial endocarditis
Table
1.
prophylaxis
of infective
Dental procedures and upper respiratory procedures’ Parenteral: A. Aqueous crystalline penicillin G 1 million units plus procaine penicillin G 600,000 units IM S-1 hour before the procedure, then penicillin V 500 mg. p.o. q6h for 4-8 doses. B. Regimen A plus streptomycin 1 Gm. IM given g-1 hour before the procedure* C. Vancomycin 1 Gm. IV over S-1 hour, given g-1 hour prior to the procedure’, 3 Oral: D. Penicillin V 2 Gm. p.o. S-1 hour prior to the procedure, then 500 mg. p.o. q6h for 8 doses E. Erythromycin 1 Gm. p.o., l-2 hours before the procedure, then 500 mg. p.o. q6h for 8 doses3
2.
Gastrointestinal
and genitourinary
procedures”
Parenteral: F. Ampicillin 1-2 grams IM or IV (or aqueous crystalline penicillin G 1-2 million units IM or IV) plus streptomycin 1.0 gram IM (or gentamicin 1.5 mg./kg. IM). Both antibiotics to be given g-1 hour before the procedure and repeated at 12 and 24 hours with the penicillin-streptomycin regimen and every 8 h for 24h with the penicillin-gentamicin regimen G. Vancomycin 1 Gm. IV over S-1 hour starting S-1 hour prior to the procedure plus streptomycin 1 Gm. IM. Both drugs may be repeated at 12 hours3 Oral: No oral regimen has been demonstrated to provide satisfactory protection ‘All dental procedures including cleaning, but not including orthodontic adjustments. The need for prophylaxis following tonsillectomy or bronchoscopy is uncertain. ‘These regimens are considered the most effective and are recommended for patients with prosthetic heart valves, and for individuals on long term penicillin prophylaxis for rheumatic fever. 3These regimens may be used in penicillin allergic patients. The parenteral regimen is preferred. ‘Prophylaxis is recommended for all genitourinary procedures, including urethral catheter insertion and removal. It is also recommended for gall bladder and bowel surgery. It is not routinely recommended for sigmoidoscopy, barium enema, liver biopsy or upper g.i. endoscopy, except perhaps for patients with prosthetic heart valves. SDosage of streptomycin and gentamicin should be modified in the presence of renal insufficiency.
to that of endocarditis following tooth extraction.48, 49 The recommendations for antibiotic prophylaxis for endocarditis have been extensively revised based on experimental studies using a rabbit endocarditis model. Endocarditis is produced in the rabbit by passing a polyethylene catheter across the aortic or tricuspid valves and
692
giving an intravenous injection of organisms after a period of 1 to 2 days.50,j1 Mechanical trauma to the valve leads to formation of a platelet-fibrin thrombus which serves as the nidus for infection. The virulence of the organism correlates with the likelihood of establishing an infection, following the “transient” bacteremia. Durack and Petersdo@ have studied the more commonly recommended regimens for prophylaxis using this model. Antibiotics were given one-half hour prior to the injection of organisms. Rabbits were killed at 24 hours, at which time bacterial colony counts of valvular vegetations were performed. Their studies of streptococcus viridans endocarditis demonstrated that vancomycin alone, or a combination of penicillin G and streptomycin, were the most effective regimens. When a lower initial bacterial inoculum was used, erythromcyin was shown to have some protective value; however, primarily bacteriostatic drugs such as tetracycline, clindamycin, or erythromycin were generally ineffective.8, 9 Similar studies were performed in rabbits inoculated with enterococci.10 Vancomycin alone and vancomycin or ampicillin plus streptomycin were all effective regimens. There was considerable variation in response depending on the strain of enterococcus; these variations were not always predicted by in vitro sensitivity tests.lO The studies in the rabbit model provide important data for selecting an appropriate prophylactic regimen, but with some appreciable limitations. The pharmacokinetics of antibiotics in the rabbit are different from those in man. Endocarditis is produced in the rabbit by leaving a foreign body, the catheter, across the cardiac valve. Finally, a high inoculum of bacteria, lo8 colony forming units/ml., is used compared to the 10f to lo* colony forming units/ml. generally encountered in the bacteremia following dental procedures.‘, 23The high inoculum assures that a higher percentage of animals will be infected; however, it provides a greater challenge for the prophylactic regimen, making some drugs such as erythromycin, which are effective at a lower inoculum, appear inadequate. Therefore, regimens shown to be effective using this experimental model probably provide a wide margin of safety. Nevertheless, some have suggested that antibiotic dosages for prophylaxis should be the same as those used for treatment of endocarditis.”
November,
1978, Vol. 96, No. 5
r the
prevention
of
Despite some uncertainty about effectiveness, antibiotic prophylaxis for bacterial endocarditis is recommended in association with certain procedures. The morbidity and mortality of the disease outweighs concern for drug side effects and for the limited protection they may provide. Prophylactic regimens suggested for dental or oropharyngeal surgery are aimed especially against viridans streptococci, while those suggested for genito-urinary or gastrointestinal procedures are directed primarily against the enterococcus.li, j* There are several precautions that should be in individuals with underlying valvular e. Patients should be informed of the potential risks of dental, gastrointestinal or genitourinary procedures. Cardiac conditions which warrant prophylaxis are listed in Table III. Good dental care is particularly important in patients with valvular heart disease. The level of bacteremia is correlated with the extent of gum disease. Oral irrigation devices should generally be avoided in patients at high risk for endocarditis because of the increased incidence of bacteremia associated with their use.2’ Patients scheduled for elective valvular replacement should have any necessary dental work performed prior to cardiac surgery, since the risk of developing endocarditis in the immediate postoperative period is 2 to 4 per cent.? When procedures are performed on the genito-urinary or biliary systems, the incidence of bacteremia is reduced when the urine or bile are sterile.“” If tracheal intubation is required, the orotracheal approach causes lessbacteremia than the nasotraeheal approach.‘5 The antibiotic regimens listed in Table IV are based on the recently published recommendations of the American Heart Association5* and The Medical Letter on Drugs and Therapeutics.j3 Antibiotics given parenterally are probably more effective than those given by mouth. The recommendations represent an attempt to accommodate the practical problem created by giving parenteral therapy for outpatient procedures with the need for sustained antibiotic activity. The pare&era1 regimen using intramuscular penicillin G plus procaine penicillin is probably adequate for most cardiac patients undergoing dental procedures. However, patients taking oral penicillin prophylaxis for rheumatic fever have a
higher incidence of relatively penlclllan-~esistan^i streptococci in their oro~hary~~, so that coverage with vancomycin, or penicillin plus s~e~~~rny~i~ is advised. In addition, the recommended for patients wi Antibiotic coverage is recommended for mrgery on abscesses,or infected foci and for d~bridement of burned tissue. The antibiotic re instances shoul take account of (i.e., S. aureus) likely to be associated with bacteremia and e~do~arditis.~~
cardiac surgery even though large carefully controlled studies of the e~e~t~~e~e~s of such regimens are not available. A~~ibiot~~ coverall has been suggested because of the morality associated with early prosthetic v e~dQ~ar~~tis.j”. j5 The incidence of valvular ~~~~e~tio~sis relatively Iow,~~so that a large num would have to be incl ing the potential bene its. The incidence of prosthetic valve e~~~~~ar~i~ia rises in patients requiring piol ~ard~o~~lmonary bypass.jc Al nisms accounting for these i different i~stitutio~s~ the most, frequently isolated pathogens are S. e~~der?~~~~~,S. am-em, diptheroids, fungi (especially As~~.r~i~l~~ and Candida sp.) and Gram-negative rods.*“. 55 The patient’s skin, the operating room air, an cardiopulmonary bypass machines have ssible i~trao~era~~ve sources of intravenous and urinary ca.thee major postoperative ortals of entry for bacteremia.4:* ~3 x Two recently reported studies have compare regimens using antibiotic p~o~~y~a~~s ~~~ti~~e for 1 to 2 days versus 5 to 6 days surgery and found no significan incidence of serious infection groups.57.58 One study noted caused by resistant organisms with the longer regimen.j’ The increase in early ~ro~t~~~i~ valve infections caused by Grarn-~e~~t~~~ organisms and methi~il~i~-~esiatant S. e~~~e~?~~~~snoted recently may be a consequence of the selective pressure provided by pr~~hylac~i~ therapy.“” antibiotic coverage is ~~~e~~essar~for pace-
Lowy
and
Steigbigel
maker insertions, closed heart surgery, and cardiac catheterization.““, 56.6o It is suggested for open heart surgery when cardiopulmonary bypass is necessary. Although a penicillinase-resistant semisynthetic penicillin or a cephalosporin given parenterally for 48 hours is recommended, differing local patterns of antibiotic sensitivity may warrant additional or different antibiotic coverage.j’
17.
18.
19. 20.
21. REFERENCES
1. 2.
3.
4.
5. 6.
7.
8.
9.
10.
11.
12.
13.
14.
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