Antimicrobial Prophylaxis

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

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Rheumatic Fever: Secondary Prophylaxis
. Indicated for patients with previous acute rheumatic fever (ARF) and/or
rheumatic heart disease (RHD)
. Prophylaxis is continuous because subclinical Group A beta-hemolytic
streptococcal pharyngitis can trigger recurrent ARF
. Risk of recurrence is greatest in first 5 years after ARF and in those with
RHD; the risk is 50% per episode of streptococcal pharyngitis
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 pharyngitis
to prevent a first episode of rheumatic fever. However, secondary
rheumatic fever prophylaxis, that is which is for patients who
have been identified of having had a previous episode of rheumatic
fever and/or have been identified to have the presence of rheumatic
heart disease. So that if you identify someone who appears to have
rheumatic heart disease, but don’t have a clear history of rheumatic
episodes, you still want to institute rheumatic prophylaxis. Rheumatic
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
. Persistent RHD: Prophylaxis is provided for at least 10 years
and at least until age 40; lifelong prophylaxis
should be considered
. RF with carditis 10 years, or well into adulthood
without residual RHD: (whichever is longer)
. RF without carditis: 5 years, or until age 21
(whichever is longer)
The patient who has an episode of acute rheumatic fever with
cardiac involvement, but then the cardiac involvement has resolved
and echo findings are no longer apparent in those patients. The
recommendation is that ten years of prophylaxis. And the reason
that these are long recommendations is that the consequences are
more obviously severe in the categories of patients considering an
episode of rheumatic fever. In patients who have had an episode of
rheumatic fever without any cardiac involvement, their recommendation
is that they should receive five years of therapy or at least
until the age of 21. The specifically recommended regimens for
rheumatic fever prophylaxis are Penicillin given monthly, the dose
is 600,000 units for children under 60 pounds or 1.2 million units
for individuals over 60 pounds, and then some kind of a regimen
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
. IM Benzathine Pen G 1.2 M units IM Q3-4 wk
or
. P.O. Penicillin V 250 mg BID
or
. P.O. Sulfadiazine 0.5-1.0 gm QD
or
. P.O. Erythromycin 250 mg BID
Cardiac conditions that the Heart Association has recommended.
I think it would be a good idea to have a clear idea of this group of
patients. Clearly we all know that patients with prosthetic heart
valves are at very high risk. There is also a group of patients who
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
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
has had a previous episode of endocarditis is considered to be a
high risk for future episodes.

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Infective Endocarditis Prophylaxis
. Goal is to prevent infective endocarditis in susceptible patients (with
underlying structural cardiac disease) when undergoing procedures that are
likely to induce transient bacteremia
. Coverage is provided for the procedure
. No controlled data support efficacy; recommendations are based on in vitro
susceptibility data
Then we have identified the moderate risk group of patients who
have unreformed heart disease, in whom prophylaxis is recommended,
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
they have acquired valvular heart disease, such as rheumatic heart
disease where the patients are getting continuous rheumatic fever
prophylaxis that needs in addition while ongoing a procedure for
example. We have ultimately decided that these patients should be
divided into those that have micro-prolapse with regurgitation, and
those that have micro-prolapse that may be associated with thicker
leaflets, this is something that occurs as folks get older, in the 50s
and 60s. So from the pediatric perspective, the findings of micro-
regurgitation 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
. Cardiac Conditions
Highest-Risk Patients (Recommended)
Prosthetic heart valves
Previous IE
Complex cyanotic congenital lesions
Surgical systemic-pulmonary shunts or conduits
. Moderate-Risk Patients (Recommended)
Acquired valve dysfunction (eg, RHD)
Hypertrophic cardiomyopathy
Most other congenital heart disease not included in categories I or III
Mitral prolapse with MR and/or thickened leaflets
. Negligible-Risk Patients (Not recommended)
Isolated secundum ASD
Surgically repaired ASD, VSD or PDA (without residua >6 months
post-op)
Previous CABG
Mitral prolapse without regurgitation
Functional murmurs; previous Kawasaki disease or rheumatic fever
without valve dysfunction
Pacemakers and defibrillators
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
orthodontic bands with associated bleeding, and lots of trauma,
and as in contrast to the adjustment of orthodontic appliances. So
that the general rule is patients who have first time placement of
their orthodontia, they should be prophylaxis. Root canal surgery,
if it extended beyond the apex, is associated with bacteremia.
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
suture removal interestingly, has not been associated with
bacteremia, and therefore we would not generally recommend
prophylaxis. In addition to dental procedures, there are a number
of nondental procedures involving the oral cavity and upper
respiratory tract, and of course the GI and GU tract.

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IE Prophylaxis: Procedures
. Procedures (AHA, 1997)
Procedures through surgically scrubbed skin including routine cardiac cath and
angiography are unlikely to induce bacteremia
Trans-mucosal procedures more often induce bacteremia
Bacteremia is more common in the presence of poor dental hygiene
Procedures that induce bleeding are most commonly associated with bacteremia
. Dental Procedures
Prophylaxis Recommended
Extractions
Cleaning (with bleeding)
Initial placement of orthodontic bands
Root canal surgery (only beyond the apex)
Periodontal procedures
Intraligamentary injections
Prophylaxis Not Recommended
Shedding of primary teeth
Adjustment of orthodontic appliances
X-rays, fluoride treatments, oral impressions
Restorative dentistry (filling cavities)
Local anesthetic; placement of dams
Suture removal
..Non-dental Procedures
Prophylaxis Recommended
Respiratory: Tonsillectomy and/or adenoidectomy surgery involving mucosa,
rigid bronchoscopy
GI*: sclerotherapy for varices, esophageal dilatation, endoscopic retrograde
cholangiography with biliary obstruction, biliary tract surgery, surgery involving
GI mucosa
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
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
Miscellaneous: cardiac catheterization, balloon angioplasty, placement of pacemakers,
defibrillators, or coronary stents, incision or biopsy of prepped skin
* Prophylaxis optional for high-risk patients
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
moderateness. So you can see here that the compromise that was
achieved was to make prophylaxis optional for the GI procedures,
accept for the very high-risk patients where we thought the risk
really justified without a doubt, the treatment of prophylaxis. So in
this category then are recommended patients undergoing T&A.
Under the GI procedures, for high-risk patients it is definitely
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
endotracheal intubation, flexible bronchoscopy, and that gets an
asterisk. GI procedures: Transesophageal echoes, only optional for
certain patients otherwise they really are not any cases of hepatitis
associated with this procedure, although almost all of your patients
have heart disease. Endoscopy. GU procedures: Vaginal delivery
is actually a higher risk for bacteremia than C-sections, so that gets
an asterisk. Hysterectomy gets an asterisk. If the patients have
nose infection, undergoing GU procedures such as urethral
catheterization of D&C, or circumcision, I strongly suspect that we
would not recommend prophylaxis. Then we have this latest group
of situations where we will not recommend prophylaxis:
angioplasty, placement of a pacemaker, coronary stents.

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IE Prophylaxis for Dental, Oral, Respiratory
Tract or Esophageal Procedures (AHA, 1997)
Standard PO Amoxicillin 50 mg/kg 1 hour before
(adults=2 gm)
Unable to take orally IM or IV Ampicillin 50 mg/kg 30 min before
(adults=2 gm)
Penicillin-allergic PO Clindamycin 20 mg/kg 1 hour before
(adults=600 gm)
or
PO Cephalexin* or
Cefadroxil* 50 mg/kg 1 hour before
(adults=2 gm)
or
PO Azithromycin or 15 mg/kg 1 hour before
Clarithromycin (adults=500 mg)
Penicillin-allergic and 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
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 recommendation is single dose therapy. The standard
here is a single oral amoxicillin dose. For adults it is 2 grams. For
children it is 50 mg per kg. For patients that can not take oral
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
Erythromycin has gotten in the past, standard recommendation. In
the larger group of moderate risk patients undergoing the
nonesophageal, GI plus GU procedures, we can give single dose
oral amoxicillin.

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

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Prophylaxis for Surgical Wounds
. Generally not indicated for clean wounds that do not involve mucosal
surfaces (exceptions: open heart surgery, placement of prosthetic device,
immunocompromise?, neonate?)
. Often utilized for clean-contaminated wounds (across mucosal surface)
. Universally utilized for contaminated or dirty/infected wounds (treatment,
not prophylaxis)
. A single dose shortly before surgery is generally adequate
. Directed against the most likely bacteria (staph for skin; gut flora, etc.)
Other circumstances of antibiotic prophylaxis. One of those is
prophylaxis of surgical wounds. Surgical wounds are divided into
clean, clean contaminated, and infected kinds of wounds. This is
preoperative, not postoperative. Generally surgical prophylaxis is
not indicated for cleaning wounds that do not involve mucosal
surfaces. There are specific exceptions. I think all of us would
agree that I think all of us would agree that patients undergoing
open-heart surgery, placement of a prosthetic device either cardiac
or orthopedic or some other device, is perhaps in compromised
individuals. For clean contaminated surgery across mucosal
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
. Observation of exposed household or child care/nursery contacts, with
prompt evaluation if fever develops
. Increased risk of invasive Hib in unvaccinated household contacts <4 years
old (perhaps also in child care contacts)
. Increased risk of Hib colonization among household contacts of all ages
(probably also in child care contacts)
. Risk for secondary cases among child care contacts is less than age-
susceptible household contacts: 2Ecases are rare when all contacts are >2
years old
. Prophylaxis is given as soon as possible because best prevention occurs
in first week after index case
Prophylaxis against H flu. There are some general principals that
is that if a case of invasive AIDS flu and we have exposed individuals,
those exposed are household and childcare and nursery
contact should be observed. There is an increased risk of invasive
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
household contacts of an invasive case of HIb, there is an increased
risk of HIb colonization among household contacts of all
ages. That is also probably true in daycare and childcare contact
as well. The risk for secondary cases occurring among childcare
contact is definitely less than the risk for aids through susceptible
household contact.
In a household setting, all household members of all ages should
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
. Indications for Vaccine
Control of outbreak
Travel to epidemic area
Military recruits
Functional or anatomic asplenia, terminal complement deficiency state
. Immunogenicity
Group A >3 months old
Groups C, Y, W-135 >18-24 months old
Protection lasts 3-5 years (or less)
Revaccination is probably indicated for those <4 years if still at risk