Antimicrobial Prophylaxis

Antimicrobial Prophylaxis Against Acute Rheumatic Fever and Spontaneous Bacterial Endocarditis David Kramer, M.D.

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Rheumatic Fever: Secondary Prophylaxis

Secondary rheumatic fever prophylaxis. You all should know what primary rheumatic fever prophylaxis is. That occurs of course to accurate diagnosis and treatment of acute streptococcal pharyngi-

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Indicated for patients with previous acute rheumatic fever (ARF) and/or

ary rheumatic fever prophylaxis, that is which is for patients who

rheumatic heart disease (RHD)

have been identified of having had a previous episode of rheumatic

Prophylaxis is continuous because subclinical Group A beta-hemolytic

fever and/or have been identified to have the presence of rheumatic

streptococcal pharyngitis can trigger recurrent ARF €

tis to prevent a first episode of rheumatic fever. However, second-

heart disease. So that if you identify someone who appears to have rheumatic heart disease, but don’t have a clear history of rheumatic

Risk of recurrence is greatest in first 5 years after ARF and in those with

episodes, you still want to institute rheumatic prophylaxis. Rheu-

RHD; the risk is 50% per episode of streptococcal pharyngitis

matic fever prophylaxis is continuous and the reason is because you can not really rely only upon prior treatment of clinically apparent strep pharyngitis in order to prevent rheumatic fever. One third of rheumatic fever episodes may follow subclinical, in clinically apparent streptococcal pharyngitis, and therefore this should be continued prophylaxis to prevent all those streptococcal infections. The risk of recurring episodes of rheumatic fever is greatest in the first five years after a rheumatic fever episode. And it also greatest in the first five years after a rheumatic fever episode, and it also greatest in individuals who have had heart disease. And if you take individuals at risk who have developed a streptococcal pharyngitis. I gather in time another episode of rheumatic fever will assume, all odds of sorts with increased heart disease, or other developments of first-time heart disease. And that is why this is such an important intervention. A common question is how long do you get rheumatic fever prophylaxis? The best and most considerate opinion is that the Committee of the American Heart Association has recommended, and it’s recommendations published in 1995, and contained in the Red Book. Patients who have persistent rheumatic heart disease should receive at least ten years of prophylaxis and should be at least until they are 40 years of age, because that gets them through the period of time when they are most likely to encounter young children who have streptococcal pharyngitis. And I think really that a patient who has significant rheumatic heart disease, doesn’t mean he has a life long list of recurrent episodes of rheumatic fever after streptococcal pharyngitis infection and lifelong infection ought to be considered in those individuals.

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Rheumatic Fever Prophylaxis Duration

The patient who has an episode of acute rheumatic fever with cardiac involvement, but then the cardiac involvement has resolved

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Persistent RHD:

Prophylaxis is provided for at least 10 years

and echo findings are no longer apparent in those patients. The recommendation is that ten years of prophylaxis. And the reason

and at least until age 40; lifelong prophylaxis

that these are long recommendations is that the consequences are

should be considered

more obviously severe in the categories of patients considering an episode of rheumatic fever. In patients who have had an episode of

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rheumatic fever without any cardiac involvement, their recommen-

RF with carditis

10 years, or well into adulthood

dation is that they should receive five years of therapy or at least

without residual RHD:

(whichever is longer)

until the age of 21. The specifically recommended regimens for rheumatic fever prophylaxis are Penicillin given monthly, the dose

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is 600,000 units for children under 60 pounds or 1.2 million units

RF without carditis:

5 years, or until age 21

for individuals over 60 pounds, and then some kind of a regimen

(whichever is longer)

every 3 week or every 4 week should be recommended. In the United States every 4 week administration is perfectly fine. There are of course, three acceptable oral agents, the third recommended is Penicillin G at 250 mg twice daily. But for the individual who can not tolerate these drugs, erythromycin seems to be the idea for the standard recommendation.

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Rheumatic Fever Prophylaxis Regimens Cardiac conditions that the Heart Association has recommended.

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IM Benzathine Pen G 1.2 M units IM Q3-4 wk or

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P.O. Penicillin V

P.O. Sulfadiazine

250 mg BID

P.O. Erythromycin

have other kinds of prosthetic material in their heart. And one of the reasons that we have seen the highest patients is that they are probably more likely given this. The consequences in these kinds

0.5-1.0 gm QD

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patients. Clearly we all know that patients with prosthetic heart valves are at very high risk. There is also a group of patients who

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I think it would be a good idea to have a clear idea of this group of

of patients are much more serious, and therefore it behooves us to be as aggressive as we can to try to prevent this. An individual who

250 mg BID

has had a previous episode of endocarditis is considered to be a high risk for future episodes.

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Infective Endocarditis Prophylaxis

Then we have identified the moderate risk group of patients who have unreformed heart disease, in whom prophylaxis is recom-

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Goal is to prevent infective endocarditis in susceptible patients (with

mended, and we will get to some of the new odds between this group when we are ready. It is a moderate group of patients in that

underlying structural cardiac disease) when undergoing procedures that are

they have acquired valvular heart disease, such as rheumatic heart

likely to induce transient bacteremia

disease where the patients are getting continuous rheumatic fever prophylaxis that needs in addition while ongoing a procedure for

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Coverage is provided for the procedure

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No controlled data support efficacy; recommendations are based on in vitro

divided into those that have micro-prolapse with regurgitation, and

susceptibility data

those that have micro-prolapse that may be associated with thicker

example. We have ultimately decided that these patients should be

leaflets, this is something that occurs as folks get older, in the 50s and 60s. So from the pediatric perspective, the findings of microregurgitation is really once you determine whether a MVP patient is one from whom you should recommend prophylaxis. Now what we have done this time as a recommendation is to try to spell out a group of negligible risk patients who have prophylaxis, and these are patients we have considered to have no measurable risk over that of the general population in individuals who do not have any kind of heart disease. So these are kids who are supposed to have ASD, VSD or PDA presurgical repairs, who do not have any residual, cardiac disease, six months postoperative. To give it time for all the patches to become epithelialized, for every 6 months, no residual shunts.

Cardiac conditions the procedures that individuals are undergoing where we need to consider whether they should give prophylaxis. Some general principals are that procedures that are performed through surgically scrubbed skin, including cardiac catheter, angiography, are unlikely to be associated with bacteremia and therefore, are generally not situations where we recommend prophylaxis. In contrast, procedures that are done across mucosal surfaces are much more likely to induce bacteremia. Bacteremia is more common in the presence of poor dental hygiene than it is in patients who have good dental hygiene, and the intensity of the bacteremia in terms of the colony forming units, is much greater in those that have poor dental hygiene. A very good rule of thumb when it comes to speaking about dental procedures, is that procedures that induce bleeding, that is that there is significant trauma to the gingiva, are the ones that are most associated with bacteremia.

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Conditions Requiring Infective Endocarditis Prophylaxis

So recommended prophylaxis includes extracting, cleaning with bleeding. Cleaning typically induce bleeding, because then you can really get down into the gum line and there is scraping and bleeding. Very important to pediatrics, is the initial placement of

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Cardiac Conditions •

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orthodontic bands with associated bleeding, and lots of trauma, and as in contrast to the adjustment of orthodontic appliances. So

Highest-Risk Patients (Recommended)

that the general rule is patients who have first time placement of

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Prosthetic heart valves

their orthodontia, they should be prophylaxis. Root canal surgery,

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Previous IE

if it extended beyond the apex, is associated with bacteremia.

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Complex cyanotic congenital lesions

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Surgical systemic-pulmonary shunts or conduits

Moderate-Risk Patients (Recommended)

Periodontal

procedures

are

associated

with

bacteremia.

Intraligamentary injections. Prophylaxis is not recommended for shedding of primary teeth. As I said it is the adjustment of the orthodontia, taking x-rays, fluoride treatments, and oral impressions. Local anesthesia, placement of a kind of rubber dam and

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Acquired valve dysfunction (eg, RHD)

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Hypertrophic cardiomyopathy

bacteremia, and therefore we would not generally recommend

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Most other congenital heart disease not included in categories I or III

prophylaxis. In addition to dental procedures, there are a number

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Mitral prolapse with MR and/or thickened leaflets

Negligible-Risk Patients (Not recommended) •

Isolated secundum ASD

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Surgically repaired ASD, VSD or PDA (without residua >6 months

suture removal interestingly, has not been associated with

of nondental procedures involving the oral cavity and upper respiratory tract, and of course the GI and GU tract.

post-op) •

Previous CABG

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Mitral prolapse without regurgitation

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Functional murmurs; previous Kawasaki disease or rheumatic fever without valve dysfunction

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Pacemakers and defibrillators

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IE Prophylaxis: Procedures

Prophylaxis is clearly recommending for the group of patients at high risk undergoing these kinds of procedures and will be optional for the much larger group of individuals who are on that list of

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Procedures (AHA, 1997) •

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moderateness. So you can see here that the compromise that was achieved was to make prophylaxis optional for the GI procedures,

Procedures through surgically scrubbed skin including routine cardiac cath and

accept for the very high-risk patients where we thought the risk

angiography are unlikely to induce bacteremia

really justified without a doubt, the treatment of prophylaxis. So in

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Trans-mucosal procedures more often induce bacteremia

this category then are recommended patients undergoing T&A.

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Bacteremia is more common in the presence of poor dental hygiene

Under the GI procedures, for high-risk patients it is definitely

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Procedures that induce bleeding are most commonly associated with bacteremia

Dental Procedures Prophylaxis Recommended

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recommended that optional moderate infection, esophageal dilatation, endoscopic retroperitoneal endoscopy. Under GU procedures recommended for patients undergoing prostatic surgery, got too many kids. So in this book we have simple

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Extractions

endotracheal intubation, flexible bronchoscopy, and that gets an

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Cleaning (with bleeding)

asterisk. GI procedures: Transesophageal echoes, only optional for

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Initial placement of orthodontic bands

certain patients otherwise they really are not any cases of hepatitis

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Root canal surgery (only beyond the apex)

associated with this procedure, although almost all of your patients

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Periodontal procedures

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Intraligamentary injections

have heart disease. Endoscopy. GU procedures: Vaginal delivery is actually a higher risk for bacteremia than C-sections, so that gets

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an asterisk. Hysterectomy gets an asterisk. If the patients have

Prophylaxis Not Recommended

nose infection, undergoing GU procedures such as urethral

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Shedding of primary teeth

catheterization of D&C, or circumcision, I strongly suspect that we

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Adjustment of orthodontic appliances

would not recommend prophylaxis. Then we have this latest group

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X-rays, fluoride treatments, oral impressions

of situations where we will not recommend prophylaxis:

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Restorative dentistry (filling cavities)

angioplasty, placement of a pacemaker, coronary stents.

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Local anesthetic; placement of dams

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Suture removal

Non-dental Procedures •

Prophylaxis Recommended -

Respiratory: Tonsillectomy and/or adenoidectomy surgery involving mucosa, rigid bronchoscopy

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GI*: sclerotherapy for varices, esophageal dilatation, endoscopic retrograde cholangiography with biliary obstruction, biliary tract surgery, surgery involving GI mucosa

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GU: prostatic surgery, cystoscopy, urethral dilatation

*Recommended for high-risk patients, optional for moderate risk •

Prophylaxis Not Recommended -

Respiratory: endotracheal intubation, flexible scope bronchoscopy (with or without biopsy*), tympanostomy tube placement

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GI: Transesophageal echocardiography*, endoscopy (with or without biopsy)

Genitourinary: Vaginal* or Cesarean delivery, hysterectomy*; in uninfected tissues: urethral catheterization, dilation and curettage, therapeutic abortion, sterilization procedures, insertion or removal of intrauterine devices, circumcision

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Miscellaneous: cardiac catheterization, balloon angioplasty, placement of pacemakers, defibrillators, or coronary stents, incision or biopsy of prepped skin * Prophylaxis optional for high-risk patients

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IE Prophylaxis for Dental, Oral, Respiratory Tract or Esophageal Procedures (AHA, 1997)

What are the now recommended prophylactic regimens? For dental, oral, respiratory or esophageal procedures. Prevents everything except lower GI and GU procedures, things have been simplified to the bottom line here, single dose, no second doses.

• Standard

• Unable to take orally

PO Amoxicillin

IM or IV Ampicillin

50 mg/kg 1 hour before

PO Clindamycin

children it is 50 mg per kg. For patients that can not take oral

50 mg/kg 30 min before

medication, a single dose of Ampicillin, same dosage, given 30 minutes before food. Now we have had a problem with patients who are penicillin allergic, and you may remember that

20 mg/kg 1 hour before

Erythromycin has gotten in the past, standard recommendation. In

(adults=600 gm)

the larger group of moderate risk patients undergoing the nonesophageal, GI plus GU procedures, we can give single dose

or

oral amoxicillin.

PO Cephalexin* or Cefadroxil*

here is a single oral amoxicillin dose. For adults it is 2 grams. For

(adults=2 gm)

(adults=2 gm) • Penicillin-allergic

Standard recommendation is single dose therapy. The standard

50 mg/kg 1 hour before (adults=2 gm)

or PO Azithromycin or 15 mg/kg 1 hour before

• Penicillin-allergic and

Clarithromycin

(adults=500 mg)

IV Clindamycin

20 mg/kg within 30 min

unable to take orally before

(adults=600mg) or IV or IM Cefazolin* 25 mg/kg within 30 min before (adults=1gm)

* Avoid with immediate penicillin hypersensitivity All Regimens are Single Dose

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Prophylaxis for Genitourinary/gastrointestinal (Non-esophageal) Procedures (AHA, 1997) € High-risk Patients

IV or IM Ampicillin (50 mg/kg up to 2 gin) plus IV or IM Gentamicin (1.5 mg/kg up to 120 mg) within 30 min of starting procedure; 6 hours later, ampicillin (25 mg/kg IV or IM) or amoxicillin (25 mg/kg PO)

€ High Risk (Pen-allergic)

IV Vancomycin (20 mg/kg up to 1 gm) over 1-2 hr (1.5 mg/kg up to 120 mg) plus IV or IM Gentamicin within 30 min of starting procedure

€ Moderate Risk

PO Amoxicillin or IM or IV Ampicillin (50 mg/kg up to 2 gm) within 30 min. of starting procedure

€ Moderate Risk (Pen-allergic)

IV Vancomycin (20 mg/kg up to 1 gm) over 1-2 hrs., within 30 min of starting procedure

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Prophylaxis for Surgical Wounds Other circumstances of antibiotic prophylaxis. One of those is

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Generally not indicated for clean wounds that do not involve mucosal

prophylaxis of surgical wounds. Surgical wounds are divided into clean, clean contaminated, and infected kinds of wounds. This is

surfaces (exceptions: open heart surgery, placement of prosthetic device,

preoperative, not postoperative. Generally surgical prophylaxis is

immunocompromise?, neonate?)

not indicated for cleaning wounds that do not involve mucosal surfaces. There are specific exceptions. I think all of us would

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Often utilized for clean-contaminated wounds (across mucosal surface)

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Universally utilized for contaminated or dirty/infected wounds (treatment,

open-heart surgery, placement of a prosthetic device either cardiac

not prophylaxis)

or orthopedic or some other device, is perhaps in compromised

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A single dose shortly before surgery is generally adequate

individuals. For clean contaminated surgery across mucosal

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Directed against the most likely bacteria (staph for skin; gut flora, etc.)

agree that I think all of us would agree that patients undergoing

surfaces, a surgical incision is going to be across a normal mucosal surface, it clearly cannot be prepped in the same way that skin can be, and therefore is going to be contaminated. Most surgeons would use antibiotics and most time that is the reasonable thing to do. In individuals who have contaminated or dirty infected wounds, that incision has to be made, that is a third compound fracture contaminated with dirt. I think the key is to try to individualize surgical colleagues that when surgical wound prophylaxis is given, and is appropriately in judgement of the surgeon, it really should be a single dose, and should be given shortly before surgery because it is really critical to have a substantial level of antibiotics in the patients blood stream at the time of incision. Antibiotic surgical prophylaxis should be directed against the most likely bacteria, which would be staphylococci of the skin.

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Prophylaxis for H Influenzae: Principles Prophylaxis against H flu. There are some general principals that

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Observation of exposed household or child care/nursery contacts, with

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contact should be observed. There is an increased risk of invasive

Increased risk of invasive Hib in unvaccinated household contacts <4 years

HIb in unvaccinated, this really should be incompletely vaccinated, household contact who are under 40 years of age, and perhaps there is an increased risk also in childcare contact. Among

Increased risk of Hib colonization among household contacts of all ages

household contacts of an invasive case of HIb, there is an in-

(probably also in child care contacts)

creased risk of HIb colonization among household contacts of all

Risk for secondary cases among child care contacts is less than age-

ages. That is also probably true in daycare and childcare contact

susceptible household contacts: 2E cases are rare when all contacts are >2 €

als, those exposed are household and childcare and nursery

prompt evaluation if fever develops

old (perhaps also in child care contacts) €

is that if a case of invasive AIDS flu and we have exposed individu-

as well. The risk for secondary cases occurring among childcare contact is definitely less than the risk for aids through susceptible

years old

household contact.

Prophylaxis is given as soon as possible because best prevention occurs

In a household setting, all household members of all ages should

in first week after index case

be prophylaxed where there is at least one incompletely vaccinated contact for those of 48 months of age. For a definition of who is considered to be completely vaccinated, that is a child who has received at least one conjugated dose at the age of 15 months or greater, or has had two doses of vaccine if the child is between 1214 months. In any case, I think the key point is that if you have any one who is incompletely vaccinated under 4 years of age in a household, you should really give vaccines to everybody in the household, because of the concern about carriage. If you have a child under 12 months of age in the household, all the household members again of all ages ought to be prophylaxed, and the reason is because this child may be colonized because of the booster dose beyond 12 months. If it is in a childcare situation, it really gets sort of confusing. I have to admit this is not my major field of interest, but I will relay to you what the Red Book says. It indicates clearly that the risks in a childcare setting is lower than in households and secondary cases are less likely to occur in childcare settings than in households. Secondary cases are rare when all the people in the childcare center are over 2 years of age. And they have a definition of what is contact? What is sufficient contact? They define it as 25 hours of the week. In addition, the identification of a first case, whether or not they give prophylaxis is certainly enough to take the opportunity to bring everyone to a vaccine center today. Now if there is a second case of invasive HIb that occurs within 60 days in one of these centers, and there are many unvaccinated or incompletely vaccinated children present, the families should be given and all personnel, a dose as well. Unless, we have pregnant personnel, and there is a specific exclusion in the Red Book for pregnant personnel.

Prophylaxis is recommended for household and childcare and nursery contacts. You do not need a second case. If you have a case of pneumococcal disease. Whenever there is sharing of oral secretions, food, drink, kissing, household and childbed nursery contacts, clearly prophylaxis is indicated. Then, of course, medical personnel. It should be everyone in the hospital who has passed within 25 feet of the case, that is really where prophylaxis is recommend or medical personnel who have been exposed such as mouth-to-mouth resuscitation.

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Meningococcal Vaccine €

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Indications for Vaccine •

Control of outbreak

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Travel to epidemic area

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Military recruits

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Functional or anatomic asplenia, terminal complement deficiency state

Immunogenicity •

Group A >3 months old

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Groups C, Y, W-135 >18-24 months old

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Protection lasts 3-5 years (or less)

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Revaccination is probably indicated for those <4 years if still at risk

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