Prophylaxis for Antibiotic Endocarditis By JAMES A. LYON, MARK E. THOMPSON, and GEORGE J. PAZIN Bacterial endocarditis is a lifethreatening infection of the inside lining (endocardium) of the heart, usually on or near one of the valves. NIH estimates that it kills only 650 people each year. Yet 2.2 million Americans are at high risk. Generally any medical or dental procedure-even as simple a procedure as dental cleaning-that exposes patients with rheumatic or congenital heart disease to bacteremia places them at immediate and usually fatal risk. The infection usually develops in relation to an abnormal heart valve. The abnormalities increase the turbulence of blood, which in turn results in the development of plateletfibrin thrombi on the endocardial surface. If the patient experiences bacteremia while the platelet-fibrin thrombi are present, they may become infected, resulting in endocarditis. Investigators believe that agglutinating antibodies to the bacteria in the blood may contribute to this sequence of events. Although the frequency of bacterial endocarditis appears low, the life-threatening nature of the infection has prompted new recommendations, which can be followed only if pharmacists, physicians, and dentists are prepared. Earlier (1971) recommended regimens for bacterial endocarditis prophylaxis have recently been found inadequate in experimental animal models. Although these models seem excessively demanding of antibiotic regimens, clinical studies have not been feasible for obvious ethical and statistical reasons. James A. Lyon, PharmD, is assistant professor of pharmacy at the University of Pittsburgh School of Pharmacy, Pittsburgh, PA 15261. Mark E. Thompson, MD, and George]. Pazin, MD, are associate professors of cardiology and infectious diseases, respectively, at the University of Pittsburgh School of Medicine.
American Pharmacy Vol. NS 19, No.6, June 1979/317
Based on the animal models, new recommendations for prophylaxis were developed in 1977 by the American Heart Association Committee on Prevention of Endocarditis. These recommendations, intended to provide physicians and dentists with prophylactic guidelines based on current knowledge, have been adopted by AHA and the American Dental Association for prophylaxis in known heart patients. In studying the new recommendations, however, we became aware that parenteral formulations of the required antibiotics are not immediately available in community pharmacies or dental offices. Although benzathine penicillin may be available in stock, practitioners are less likely to have penicillin procaine, aqueous crystalline penicillin, or streptomycin on hand. Patients with a known history of heart defects should have patient records in the offices of the physician and dentist indicating the diagnosis and appropriate prophylaxis for bacterial endocarditis. We have developed two patient schedules
based on the AHA/ADA recommendations, and the American Pharmaceutical Association has agreed to print and distribute these schedules upon request.* The schedules can be distributed by pharmacists to dentists and physicians in your area, along with the offer to supply or prepare the necessary medications for use by these practitioners. The sample chart with instructions was designed individually for both adults and children. It includes our condensation and simplification of the 1977 AHA/ADA recommendations for the prevention of endocarditis, along with a series of reminders relevant to the general concept of antibiotic prophylaxis of bacterial endocarditis. We trust that after reviewing the critical need for preventing this serious infection, the health care professionals in your community will support and follow these guidelines. (Chart on page 38) *Copies of this article and the schedule are available from: Order Desk, American Pharmaceutical Association, 2215 Constitution Avenue, NW, Washington, DC 20037. Cost: $3.00/100, prepaid.
Latest Research Findings On Antibiotic Endocarditis Therapy New research on the treatment of antibiotic endocarditis is reported in the April 27 issue of the journal of the American Medical Association. Researchers report tests on single versus combination antibiotic therapy on a number of patients. In a report from Boston, researchers suggested that treatment with high-dose parenteral penicillin or a bactericidal penicillin substitute will yield cure rates and relapse rates comparable with those with penicillin-streptomycin regimens. A report from New Haven, CT, reviewed a 14-year experience and also concluded that for therapy of
antibiotic endocarditis caused by penicillin-susceptible organisms, single-agent treatments for a prolonged period were indicated. In a detailed and referenced editorial, however, two physicians from the University of Chicago came out strongly for continuation of combination therapy for the disease. "It remains important to remember that bacterial endocarditis is still too often a fatal disease," Drs. Lawrence Resnick and Louis Cohen wrote. "It is thus considered advisable to take the added small risk of combination therapy unless absolutely contraindicated."
37
Patient Schedule for Prevention of Endocarditis Treatment
Congenital and valvular heart disease
Prosthetic heart valve
Preferred:
Regimen A 1 or B
Regimen B
Alternate:
Regimen Az
Regimen B
Name needs protection from bacterial endocarditis. Diagnosis
Regimen Cz Age~~ Penkillinallergy?OyesOno~_a_l_~_r~g~y_=~~~~~~~~~~~~~~~~~~~ A1 Az B C1 Cz D E For GI or GU procedures: D D Regimens recommended: For dental or upper respiratory procedures: 0 0 0 D 0 Penicillin
Regimen C 1 or C 2
Date _ _ _ _ __
Standard Regimens
Intensified Regimens
For patients with congenital heart disease, rheumatic or acquired valvular heart disease, and hypertrophic subaortic stenosis, who require prophylaxis for dental procedures, tonsillectomy, adenoidectomy, bronchoscopy, or esophagoscopy with biopsy.
For patients with prosthetic heart valves or previous endocarditis, are on rheumatic fever prophylaxis or who have severe gingival disease or poor dental hygeine.
ADULT 0 D Aqueous crystalline penicillin G, ADULT 2,000,000 units IM or IV, or ampicillin, 1.0 0 B Regimen A 1 plus streptomycin 1.0 g IM g IV or IM, plus gentamicin, 1.5 mg/kg, not at time of initial injections. to exceed 80 mg IV or IM, or streptomycin, 1.0 g IM only. Initial dose 1 hour before 0 C 2 for Patients Allergic to Penicillin: procedure. Repeat twice at 8-hour inVancomycin, 1.0 g IV, 1 hour before procetervals if regimen contains gentamicin, or dure over 45 minutes, then erythromycin, at 12-hour intervals if regimen contains 500 mg orally, every 6 hours for 8 doses (or streptomycin. NOTE: Follow-up doses may longer in case of delayed healing). have to be adjusted if renal function is compromised. (See Reminder No.8 below) 0 E for Patients Allergic to Penicillin: Vancomycin, 1.0 g IV, 1 hour before procedure over 45 minutes, plus streptomycin, 1.0 g I M only, or gentamicin, 1.5 mg/kg, not to exceed 80 mg IV or IM. Repeat 12 hours after major procedures.
ADULT 0 A 1 Parenteral-Oral: Aqueous crystalline penicillin G, 1,000,000 units, mixed with penicillin G procaine, 600,000 units IM, 1 hour before procedure, then penicillin V, 500 mg orally, every 6 hours for 8 doses (or longer in case of delayed healing).
0 A 2 Oral Penicillin: Oral penicillin V, 2.0 g orally, 1 hour before procedure, then 500 mg orally every 6 hours for 8 doses (or longer in case of delayed healing) . 0 C 2 for Patients Allergic to Penicillin: Erythromycin, 1.0 g orally, 1Vz-2 hours before procedure, then 500 mg orally every 6 hours for 8 doses (or longer in case of delayed healing). PEDIATRIC* Regimen A-Penicillin 0 A1 Parenteral-oral: Combined aqueous penicillin G, 30,000 units/kg IM, mixed with penicillin G procaine, 600,000 units IM, 1 hour before procedure, then penicillin V, 250 mg orally (for children weighing less than 60 pounds), or penicillin V, 500 mg orally (for children weighing more than 60 pounds), every 6 hours for 8 doses (or longer in case of delayed healing). 0 A 2 Oral Penicillin: Penicillin V, 2.0 g orally, 30-60 minutes before procedure, then 500 mg every 6 hours for 8 doses. For children weighing less than 60 pounds, use penicillin V, 1.0 g orally, 30-60 minutes prior to the procedure, then 250 mg orally every 6 hours for 8 doses (or longer in case of delayed healing).
0 C1 for .Patients Allergic to Penicillin: Erythromycin, 20 mg/kg orally, 1Vz-2 hours before procedure, then 10 mg/kg every 6 hours for 8 doses (or longer in case of delayed healing).
Augmented Regimens For patients requiring prophylaxis who are about to undergo lower gastrointestinal or genitourinary procedures, or have obstetrical infections or in whom one decides to "cover" during childbirth.
PEDIATRIC* 0 B Aqueous crystalline penicillin G, 30,000 units/kg IM mixed with penicillin G procaine, 600,000 units IM, plus streptomycin, 20 mg/kg IM, 30-60 minutes before procedure, then penicillin V, 500 mg orally, every 6 hours for 8 doses. For children weighing less than 60 pounds, use penicillin V, 250 mg orally, every 6 hours for 8 doses.
PEDIATRIC* 0 D Aqueous crystalline penicillin G, 30,000 units/kg IM or IV, or ampicillin, 50 mg/kg IM or IV, plus gentamicin, 2.0 mg/kg IM or IV, or streptomycin, 20 mg/kg IM. Initial doses 30-60 minutes before procedure. Repeat twice at. 8-hour intervals if regimen includes gentamicin, or at 12-hour intervals if regimen includes streptomycin. NOTE: Follow-up doses may have to be adjusted if renal function is impaired.
0
c2
for patients allergic to penicillin: Vancomycin, 20 mg/kg IM, over 30-60 minutes. Start infusion 30-60 minutes before procedure, then erythromycin, 10 mg/kg orally, every 6 hours for 8 doses.
0 E for patients allergic to penicillin: Vancomycin, 20 mg/kg IV over 30-60 minutes, plus streptomycin, 20 mg/kg IM. A single dose of these antibiotics is given 1 hour before procedure and may be repeated in 12 hours.
*Doses for children should not exceed recommendations for adults for a single dose or for a 24-hour period. The total dose of vancomycin for children should not exceed 44 mg/kg/24 hours.
Reminders 1. No prophylaxis is needed for: shedding of deciduous teeth; simple adjustment of orthodontic appliance; liver or bone marrow biopsy; cardiac catheterization or angiography; uncomplicated secundum ASD; patent ductus after surgical repair or postcoronary artery bypass without valvular heart disease. 2. Prophylaxis is optional for: pelvic examination; uncomplicated vaginal delivery; uterine dilation and curettage; uncomplicated IUD insertion or r~moval; G_I-endoscopy without biopsy; proctoscopy or sigmoidoscopy without b10psy; patients with mitral valve prolapse syndrome except in patients with prosthetic heart valves. 3. Patients at increased risk of infective endocarditis should not take anti-
biotics for minor illness and should have a blood culture done to exclude endocarditis before instituting antibiotic therapy of bacterial infection . 4. Patients with rheumatic heart disease should be on a regimen or prophy-
!axis for recurrent group A streptococcal pharyngitis in addition to these regimens (Circulation 55 .1A 1977) . 5. Maintenance of the highest level of oral health is important in patients at increased risk of endocarditis . Complete evaluation and dental restorations are indicated before prosthetic valve insertion. 6. Physicians must prepare in advance if they plan to use the preferred parenteral regimens because pharmacies do not usually stock aqueous crystalline penicillin G, penicillin G procaine, streptomycin, or gentamicin; pharmacies can obtain these drugs within 24-48 hours on request. 7. These recommendations are based on the 1977 statement of the Joint Committee [Circulation 56.139A, 1977; ]. Am. Dent. Assoc. , 95 , 600 (1977)] . 8. Patients with renal insufficiency should receive full dosages initially, followed by subsequent doses of vancomycin, streptomycin, or gentamicin reduced in direct proportion to the reduction in creatinine clearance to a maximum reduction in dosage of 80%.
American Pharmacy Vol. NS 19, No.6, June 1979/317
Based on the animal models, new recommendations for prophylaxis were developed in 1977 by the American Heart Association Committee on Prevention of Endocarditis. These recommendations, intended to provide physicians and dentists with prophylactic guidelines based on current knowledge, have been adopted by AHA and the American Dental Association for prophylaxis in known heart patients. In studying the new recommendations, however, we became aware that parenteral formulations of the required antibiotics are not immediately available in community pharmacies or dental offices. Although benzathine penicillin may be available in stock, practitioners are less likely to have penicillin procaine, aqueous crystalline penicillin, or streptomycin on hand. Patients with a known history of heart defects should have patient records in the offices of the physician and dentist indicating the diagnosis and appropriate prophylaxis for bacterial endocarditis. We have developed two patient schedules
based on the AHA/ADA recommendations, and the American Pharmaceutical Association has agreed to print and distribute these schedules upon request.* The schedules can be distributed by pharmacists to dentists and physicians in your area, along with the offer to supply or prepare the necessary medications for use by these practitioners. The sample chart with instructions was designed individually for both adults and children. It includes our condensation and simplification of the 1977 AHA/ADA recommendations for the prevention of endocarditis, along with a series of reminders relevant to the general concept of antibiotic prophylaxis of bacterial endocarditis. We trust that after reviewing the critical need for preventing this serious infection, the health care professionals in your community will support and follow these guidelines. (Chart on page 38) *Copies of this article and the schedule are available from: Order Desk, American Pharmaceutical Association, 2215 Constitution Avenue, NW, Washington, DC 20037. Cost: $3.00/100, prepaid.
Latest Research Findings On Antibiotic Endocarditis Therapy New research on the treatment of antibiotic endocarditis is reported in the April 27 issue of the journal of the American Medical Association. Researchers report tests on single versus combination antibiotic therapy on a number of patients. In a report from Boston, researchers suggested that treatment with high-dose parenteral penicillin or a bactericidal penicillin substitute will yield cure rates and relapse rates comparable with those with penicillin-streptomycin regimens. A report from New Haven, CT, reviewed a 14-year experience and also concluded that for therapy of
antibiotic endocarditis caused by penicillin-susceptible organisms, single-agent treatments for a prolonged period were indicated. In a detailed and referenced editorial, however, two physicians from the University of Chicago came out strongly for continuation of combination therapy for the disease. "It remains important to remember that bacterial endocarditis is still too often a fatal disease," Drs. Lawrence Resnick and Louis Cohen wrote. "It is thus considered advisable to take the added small risk of combination therapy unless absolutely contraindicated."
37
Patient Schedule for Prevention of Endocarditis Treatment
Congenital and valvular heart disease
Prosthetic heart valve
Preferred:
Regimen A 1 or B
Regimen B
Alternate:
Regimen Az
Regimen B
Name needs protection from bacterial endocarditis. Diagnosis
Regimen Cz Age~~ Penkillinallergy?OyesOno~_a_l_~_r~g~y_=~~~~~~~~~~~~~~~~~~~ A1 Az B C1 Cz D E For GI or GU procedures: D D Regimens recommended: For dental or upper respiratory procedures: 0 0 0 D 0 Penicillin
Regimen C 1 or C 2
Date _ _ _ _ __
Standard Regimens
Intensified Regimens
For patients with congenital heart disease, rheumatic or acquired valvular heart disease, and hypertrophic subaortic stenosis, who require prophylaxis for dental procedures, tonsillectomy, adenoidectomy, bronchoscopy, or esophagoscopy with biopsy.
For patients with prosthetic heart valves or previous endocarditis, are on rheumatic fever prophylaxis or who have severe gingival disease or poor dental hygeine.
ADULT 0 D Aqueous crystalline penicillin G, ADULT 2,000,000 units IM or IV, or ampicillin, 1.0 0 B Regimen A 1 plus streptomycin 1.0 g IM g IV or IM, plus gentamicin, 1.5 mg/kg, not at time of initial injections. to exceed 80 mg IV or IM, or streptomycin, 1.0 g IM only. Initial dose 1 hour before 0 C 2 for Patients Allergic to Penicillin: procedure. Repeat twice at 8-hour inVancomycin, 1.0 g IV, 1 hour before procetervals if regimen contains gentamicin, or dure over 45 minutes, then erythromycin, at 12-hour intervals if regimen contains 500 mg orally, every 6 hours for 8 doses (or streptomycin. NOTE: Follow-up doses may longer in case of delayed healing). have to be adjusted if renal function is compromised. (See Reminder No.8 below) 0 E for Patients Allergic to Penicillin: Vancomycin, 1.0 g IV, 1 hour before procedure over 45 minutes, plus streptomycin, 1.0 g I M only, or gentamicin, 1.5 mg/kg, not to exceed 80 mg IV or IM. Repeat 12 hours after major procedures.
ADULT 0 A 1 Parenteral-Oral: Aqueous crystalline penicillin G, 1,000,000 units, mixed with penicillin G procaine, 600,000 units IM, 1 hour before procedure, then penicillin V, 500 mg orally, every 6 hours for 8 doses (or longer in case of delayed healing).
0 A 2 Oral Penicillin: Oral penicillin V, 2.0 g orally, 1 hour before procedure, then 500 mg orally every 6 hours for 8 doses (or longer in case of delayed healing) . 0 C 2 for Patients Allergic to Penicillin: Erythromycin, 1.0 g orally, 1Vz-2 hours before procedure, then 500 mg orally every 6 hours for 8 doses (or longer in case of delayed healing). PEDIATRIC* Regimen A-Penicillin 0 A1 Parenteral-oral: Combined aqueous penicillin G, 30,000 units/kg IM, mixed with penicillin G procaine, 600,000 units IM, 1 hour before procedure, then penicillin V, 250 mg orally (for children weighing less than 60 pounds), or penicillin V, 500 mg orally (for children weighing more than 60 pounds), every 6 hours for 8 doses (or longer in case of delayed healing). 0 A 2 Oral Penicillin: Penicillin V, 2.0 g orally, 30-60 minutes before procedure, then 500 mg every 6 hours for 8 doses. For children weighing less than 60 pounds, use penicillin V, 1.0 g orally, 30-60 minutes prior to the procedure, then 250 mg orally every 6 hours for 8 doses (or longer in case of delayed healing).
0 C1 for .Patients Allergic to Penicillin: Erythromycin, 20 mg/kg orally, 1Vz-2 hours before procedure, then 10 mg/kg every 6 hours for 8 doses (or longer in case of delayed healing).
Augmented Regimens For patients requiring prophylaxis who are about to undergo lower gastrointestinal or genitourinary procedures, or have obstetrical infections or in whom one decides to "cover" during childbirth.
PEDIATRIC* 0 B Aqueous crystalline penicillin G, 30,000 units/kg IM mixed with penicillin G procaine, 600,000 units IM, plus streptomycin, 20 mg/kg IM, 30-60 minutes before procedure, then penicillin V, 500 mg orally, every 6 hours for 8 doses. For children weighing less than 60 pounds, use penicillin V, 250 mg orally, every 6 hours for 8 doses.
PEDIATRIC* 0 D Aqueous crystalline penicillin G, 30,000 units/kg IM or IV, or ampicillin, 50 mg/kg IM or IV, plus gentamicin, 2.0 mg/kg IM or IV, or streptomycin, 20 mg/kg IM. Initial doses 30-60 minutes before procedure. Repeat twice at. 8-hour intervals if regimen includes gentamicin, or at 12-hour intervals if regimen includes streptomycin. NOTE: Follow-up doses may have to be adjusted if renal function is impaired.
0
c2
for patients allergic to penicillin: Vancomycin, 20 mg/kg IM, over 30-60 minutes. Start infusion 30-60 minutes before procedure, then erythromycin, 10 mg/kg orally, every 6 hours for 8 doses.
0 E for patients allergic to penicillin: Vancomycin, 20 mg/kg IV over 30-60 minutes, plus streptomycin, 20 mg/kg IM. A single dose of these antibiotics is given 1 hour before procedure and may be repeated in 12 hours.
*Doses for children should not exceed recommendations for adults for a single dose or for a 24-hour period. The total dose of vancomycin for children should not exceed 44 mg/kg/24 hours.
Reminders 1. No prophylaxis is needed for: shedding of deciduous teeth; simple adjustment of orthodontic appliance; liver or bone marrow biopsy; cardiac catheterization or angiography; uncomplicated secundum ASD; patent ductus after surgical repair or postcoronary artery bypass without valvular heart disease. 2. Prophylaxis is optional for: pelvic examination; uncomplicated vaginal delivery; uterine dilation and curettage; uncomplicated IUD insertion or r~moval; G_I-endoscopy without biopsy; proctoscopy or sigmoidoscopy without b10psy; patients with mitral valve prolapse syndrome except in patients with prosthetic heart valves. 3. Patients at increased risk of infective endocarditis should not take anti-
biotics for minor illness and should have a blood culture done to exclude endocarditis before instituting antibiotic therapy of bacterial infection . 4. Patients with rheumatic heart disease should be on a regimen or prophy-
!axis for recurrent group A streptococcal pharyngitis in addition to these regimens (Circulation 55 .1A 1977) . 5. Maintenance of the highest level of oral health is important in patients at increased risk of endocarditis . Complete evaluation and dental restorations are indicated before prosthetic valve insertion. 6. Physicians must prepare in advance if they plan to use the preferred parenteral regimens because pharmacies do not usually stock aqueous crystalline penicillin G, penicillin G procaine, streptomycin, or gentamicin; pharmacies can obtain these drugs within 24-48 hours on request. 7. These recommendations are based on the 1977 statement of the Joint Committee [Circulation 56.139A, 1977; ]. Am. Dent. Assoc. , 95 , 600 (1977)] . 8. Patients with renal insufficiency should receive full dosages initially, followed by subsequent doses of vancomycin, streptomycin, or gentamicin reduced in direct proportion to the reduction in creatinine clearance to a maximum reduction in dosage of 80%.
