Subject: MEDICINE II

Topic: 2.11 – Infective Endocarditis

Lecturer: Dr. Solante
Date: August 18, 2015

OUTLINE  Gradually progressive unless complicated by a major embolic

I. Classification event or a ruptured mycotic aneurysm
A. Acute Endocarditis
B. Subacute Endocarditis
II. Etiologies “To classify endocarditis, there is relationship between onset
A. Oral cavity, skin, upper respiratory tract of symptoms, the temporal profile, including the severity of
B. Gastrointestinal tract clinical presentation. That is why there’s acute endocarditis
C. Genitourinary tract and subacute endocarditis.
D. Healthcare-associated NVE
E. Injection drug use-associated endocarditis
III. Mechanism of Vegetation II. ETIOLOGIES
IV. Clinical Manifestations The microorganism will always be dependent on the site where the
A. Cardiac Manifestations source of embolization coming from a mucosal injury or a structural
B. Non-Cardiac Manifestations damage coming from the heart is.
C. Manifestations of Specific Predisposing Conditions
V. Diagnosis A. Oral cavity, skin, and upper respiratory tract
A. Imaging Studies  Commonly causes acute endocarditis
B. Laboratory Manifestations  Respective primary portals
C. Modified Duke Criteria  Viridians streptococci, staphylococci
D. Blood Culture  HACEK organisms (gram negative bacilli)
VI. Drugs o Haemophilus, Aggregatibacter actinomycetemcomitans,Cardio
A. Antimicrobial Therapy bacterium hominis, Eikenella corrodens, Kingella kingae
B. Streptococci
C. Staphylococci B. Gastrointestinal tract
D. Enterococci
 Associated with polyps and colonic tumors
E. HACEK Organisms
 Streptococcus gallolyticus (formerly S. bovis) from the
F. Monitoring Antimicrobial Treatment
gastrointestinal tract – most common
VII. Indications for Surgery
 You can also have viridans strep and staphylococci
A. Surgery required for optimal outcome
B. Surgery strongly considered for improved outcome  Once they go into bacteremia, they can also ascend to the heart
C. Timing of cardiac surgical intervention in patients with and cause vegetations
endocarditis
VIII. Prophylaxis C. Genitourinary tract
A. Antibiotic regimens for prophylaxis of endocarditis in adults  One of the underestimated causes of infective endocarditis
with high risk cardiac lesions  Common among elderly, patients on chronic catheter,
immunocompromised patients with degenerative heart condition
REFERENCES  Enterococci
th
Dr. Solante’s lecture and powerpoint, Harrison’s 18 ed o Normal flora of the gastrointestinal tract but usually
translocates in the genitourinary tract among patients who are
I. CLASSIFICATION OF ENDOCARDITIS immunocompromised
A. Acute endocarditis o One of the common reasons why patients on chronic
 Febrile illness that rapidly damages cardiac structures polycatheter will have endocarditis
 Seeds extracardiac sites – usually metastasize to other organs of
the body because of bacteremia D. Health care-associated
 If untreated, progresses to death within weeks  Native valve endocarditis (NVE)
 It comes with higher rate of mortality o Absence of prosthetic valve
 In most cases you will not be able to appropriately initiate o Staphylococcus aureus (most common), coagulase-negative
antimicrobial treatment for those patients whom you suspect with staphylococci (CoNS), and enterococci
acute endocarditis o Nosocomial onset (55%) – among patients already in the
 Need to give antimicrobial that usually fits the microorganism that hospital
is suspected in this group of patients o Community onset (45%) in patients who have had extensive
 Prognosis is very poor contact with the health care system over the preceding 90
days(e.g. hemodialysis unit)
B. Subacute endocarditis o Catheter-associated S. aureus bacteremia endocarditis
 Usually more than 2 weeks (indwelled for many weeks  contamination coming from the
skin)
 Indolent course
 Catheter must be removed to control infection and avoid
 Causes structural cardiac damage only slowly
being resistant with antimicrobial
 Rarely metastasizes

Trans Group: Quintay, Quizon, Racoma, Raga Page 1 of 11

Edited By: Aix and HP
 Prosthetic valve endocarditis (PVE)
o S. aureus (being a foreign body, always remember majority is
always S. aureus, gram positive!), CoNS, facultative gram-
negative bacilli, diphtheroids, and fungi
o Patients who are immunocompromised can have a mix of staph
aureus and fungal infection (difficult to treat because fungi is
difficult to eradicate once inside the vegetation)
o Within 2 months of valve surgery – patients prone to develop
infection
o 68–85% of CoNS strains that cause PVE are resistant to
methicillin
 Pacemaker or implantable cardioverter-defibrillator related
endocarditis
o S. aureus and CoNS,
o both of which are commonly resistant to methicillin
o within 3 months of implantation
E. Injection drug use-associated endocarditis
 R-sided IVDU(most common): S. aureus (many strains are
methicillin resistant)
 L-sided IVDU: P.aeruginosa, Candida spp. – microorganisms are
difficult to treat
o 5-15% w/ CNIE
o Treat both of these infection (pseudomonas, candida) as well
as staphylococcus aureus
 With the use of contaminated needle, both gram positive and
gram negative can be acquired, including fungal microorganism
III. MECHANISM OF VEGETATION
Figure 1. Vegetations. – Either due to endothelial injury or mucosal
injury. In patients with endocarditis particulary those with prosthetic
valve or on polycatheter, the source is endothelial injury. This
endothelial injury can be a milieu for the growth of the
microorganism because it can attract your platelet- fibrin clot and at
the same time, it can cause non-bacterial thrombotic endocarditis
(NBTE). The other source of endocarditis is seen in patients with
concomitant valve abnormality. When they do manipulation of oral
cavity such as dental procedure or brushing of teeth, it can cause
mucosal injury. It can be an entry of the microorganism, which will go
down the heart and form vegetations.
*Most common is mucosal injury caused by organisms such as
viridians strep, which is an oral cavity microorganism.
IV. CLINICAL MANIFESTATIONS
 The clinical endocarditis syndrome is highly variable and spans a
continuum between acute and subacute presentations.
o Acute course → typically from infection with β-Hemolytic
streptococci, S. aureus, and pneumococci
o Subacute course → caused by viridans streptococci,
enterococci, CoNS, and the HACEK group
o Indolent course -> Bartonella species, T. whipplei, and C.
burnetti
 In patients with subacute presentations, fever is typically low
grade and rarely exceeds 39.4°C (103°F); in contrast,
temperatures of 39.4°–40°C (103°–104°F) are often noted in
acute endocarditis. Fever may be blunted in patients who are
elderly, are severely debilitated, or have renal failure.
(See Appendix for a table of Clinical Manifestations)
A. Cardiac Manifestations
 Heart murmurs are detected in 85% of acute endocarditis
involving a normal valve
o Usually indicative of the predisposing cardiac pathology
rather than of endocarditis
o Valvular damage and ruptured chordae may result in new
regurgitant murmurs.
 Congestive heart failure (CHF) develops in 30–40% of patients as
a consequence of valvular dysfunction
o Occasionally due to endocarditis-associated myocarditis or
an intracardiac fistula
o Heart failure due to aortic valve dysfunction progresses more
rapidly than does that due to mitral valve dysfunction.
 Perivalvular abscesses result from extension of infection beyond
valve leaflets into adjacent annular or myocardial tissue,
o In turn may cause intracardiac fistulae with new murmurs
o Abscesses may burrow from the aortic valve annulus through
the epicardium, causing pericarditis, or into the upper
ventricular septum, where they may interrupt the
conduction system, leading to varying degrees of heart
block.
o Mitral perivalvular abscesses, which are usually more distant
from the conduction system, only rarely cause conduction
abnormalities; if such abnormalities occur in this setting, the
conduction pathway is most likely disrupted near the
atrioventricular node or in the proximal bundle of His.
 Emboli to a coronary artery occur in 2% of patients and may
result in myocardial infarction.
B. Non-Cardiac Manifestations
 This is brought about by metastatic spread of the pathogen
coming from the heart. These manifestations present with
symptoms that involve the organ that is infected
 The classic nonsuppurative peripheral manifestations of
subacute endocarditis (e.g., Janeway lesions) are related to
prolonged infection; with early diagnosis and treatment, these
have become infrequent.
 Septic emboli – mimicking some of these lesions (subungual
hemorrhage, Osler’s nodes) is common in patients with acute S.
aureus endocarditis.
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 Can lodge in the blood vessels of brain, kidney, liver, spleen,
skeletal system, and meninges, and lower extremity vessels
o CVA, encephalopathy, meningitis, ICH
o Splenic, liver, renal abscess (have to find out if the source of
the abscess is secondary from the vegetation of
endocarditis)
 Flank pain, hematuria – from renal seeding
 Mycotic aneurysms – focal dilations of arteries occurring at
points in the artery wall that have been weakened by infection
in the vasa vasorum or where septic emboli have lodged):
manifests as back pain and severe abdominal pain
 Janeway lesions – non-tender erythematous macular lesions on
the palms or soles
 Osler’s nodes – subcutaneous nodules in the extensor surface of
the limbs; transient
 Splinter hemorrhages
 Arterial emboli are clinically apparent in up to 50% of patients
 Risk of embolization
o Endocarditis caused by S. aureus
o Vegetations >10 mm in diameter
o infection involving the mitral valve
 Cerebrovascular emboli presenting as strokes or as
encephalopathy complicate 15-35% of cases of endocarditis
 Microabscesses in brain and meninges occur commonly in S.
aureus endocarditis
 Immune complex deposition on the glomerular basement
membrane causes diffuse hypocomplementemic
glomerulonephritis and renal dysfunction
Figure 2. (Left) Septic emboli found in the sole of the foot with
hemorrhage and infarction from a Staphylococcus aureus
endocarditis infection. (Right) Petechiae on the toe with subacute
endocarditis.
Figure 3. (Left) Splinter hemorrhages, linear reddish-brown lesions
seen in the nail bed with bacterial endocarditis due to Grp. B
Streptococcus. (Right) Janeway lesion, a macular non-painful
erythematous lesion found in those with bacterial endocarditis due to
Grp. B Streptococcus bovis.
Figure 4. Osler’s nodes are tender papulopustules found on the pulp
of the finger in those with bacterial endocarditis caused by
Staphylococcus aureus.
C. Manifestations of Specific Predisposing Conditions
 Injecting drug use
o 50% are limited to the tricuspid valve and present with fever
o Faint or no murmur
 Septic emboli
o Cough, pleuritic chest pain, nodular pulmonary infiltrates
o Occasionally pyopneumothorax
 Infection of the aortic or mitral valves on the left side of the
heart presents with the typical clinical features of endocarditis
 Health care associated endocarditis
o Typical manifestation if not associated with retained
intracardiac device
 Transverse pacemaker associated endocarditis
o Associated with obvious or cryptic generator pocket
infection
o Fever, minimal murmur and pulmonary symptoms due to
septic emboli
V. DIAGNOSIS
A. Imaging Studies
 Echocardiography and Blood Culture and Sensitivity
o Allows anatomic confirmation of infective endocarditis, sizing
of vegetations, detection of intracardiac complications, and
assessment of cardiac function
o Cornerstone
o Confirms and measures vegetations
o Detect intracardiac complications
 Ruptured chordae tendinae
 Fistula
 Presence of perivalvular abscess
o Assesses cardiac function
 Baseline
 In patients whose cardiac function is initially
compromised, such as in the elderly with congestive heart
failure  poor prognosis
o Presence of vegetation will detect endocarditis
o For prognostication; for possible surgical intervention, you
have to measure the size of the vegetations
 There are vegetations that allows you to give your
antimicrobial to a particular period and there are also
some that even at a particular size, you cannot control the
infection with antibiotics alone such that surgery is
indicated
 Transthoracic Echocardiography
o Primary
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 o Non-invasive and exceptionally specific
o Limitations:
 Cannot image vegetations <2 mm in diameter
 In 20% of patients, it is technically inadequate because of
emphysema or body habitus
 Detects vegetations in only 65% of patients with definite
clinical endocarditis
 Not adequate for evaluating prosthetic valves or detecting
intracardiac complications
 Transesophageal Echocardiography
o Optimal method for the diagnosis of prosthetic valve
endocarditis, complicated endocarditis, detection of
myocardial abscess, valve perforation, or intracardiac fistulae
o Highly invasive
o Safe and detects vegetations in >90% of patients with definite
endocarditis
o Nevertheless, initial studies may be false negative in 6–18% of
endocarditis patients
o When endocarditis is likely, a negative TEE result does not
exclude the diagnosis but rather warrants repetition of the
study in 7–10 days
B. Laboratory Manifestations
 Many laboratory studies that are not diagnostic—i.e., complete
blood count, creatinine determination, liver function tests, chest
radiography, and electrocardiography—are nevertheless important
in the management of patients with endocarditis.
 The erythrocyte sedimentation rate, C-reactive protein level, and
circulating immune complex titer are commonly increased in
endocarditis. (See appendix)
 Cardiac catheterization is useful primarily to assess coronary artery
patency in older individuals who are to undergo surgery for
endocarditis.
 Since endocarditis is vascular phenomenon, most patients will
present with anemia, particularly those who will present will
subclinical manifestations more than 2 weeks.
 Leukocytosis – you will not expect this from immunocompromised
and the elderly; absence in these two populations does not rule
out IE
 Microscopic hematuria – due to embolization of the
microorganisms causing red blood cell injury
 Although non-specific, if you have an elevated ESR or C-reactive
protein, this indicates an acute inflammation. It can always elevate
with infection.
 Rheumatoid factor – in patients with rheumatic heart disease,
microorganism responsible are the streptococci. They can stay in
the heart as a colonizer but once the immune system goes down,
they can cause bacteremia.
C. Modified Duke Criteria (adapted from Li et al.)
 For the diagnosis of infective endocarditis (see appendix for bigger
table)
 For diagnosing possible or definite endocarditis
 MAJOR CRITERIA
1. Positive blood culture
Typical microorganism for infective endocarditis from two
separate blood cultures
 Viridans streptococci, Streptococcus gallolyticus, HACEK
group organisms, Staphyloccocus aureus, or
 Community-acquired enterococci in the absence of a
primary focus
or
Persistently positive blood culture, defined as recovery of a
microorganism consistent with infective endocarditis from:
 Blood cultures drawn >12 hours apart; or
 All of 3 or a majority of ≥4 separate blood cultures, with
first and last drawn at least 1 hour apart
or
Single positive blood culture for Coxiella burnetti or phase I
IgG antibody titer of >1:800
2. Evidence of endocardial involvement
Positive echocardiogram
 Oscillating intracardiac mass on valve or supporting
structures in the path of regurgitant jets or in implanted
material, in the absence of an alternative anatomic
explanation, or
 Abscess, or
 New partial dehiscence of prosthetic valve
or
New valvular regurgitation (increase or change in pre-existing
murmur not sufficient)
 MINOR CRITERIA
1. Predisposition: predisposing heart conditions or injection drug
use
2. Fever ≥38.0°C (≥100.4°F)
3. Vascular phenomena: major arterial emboli, septic pulmonary
infarcts, mycotic aneurysm, intracranial hemorrhage,
conjunctival hemorrhages, Janeway lesions
4. Immunologic phenomena: glomerulonephritis, Osler’s nodes,
Roth’s spots, rheumatoid factor
5. Microbiologic evidence: positive blood culture but not
meeting major criterion, as noted previously, or serologic
evidence of active infection with an organism consistent with
infective endocarditis
 In order to diagnose definitive IE you have to have:
o At least 2 major criteria
o 1 major or 3 minor criteria
o 5 minor criteria
 In order to diagnose possible IE you have to have:
o 1 major, 1 minor criteria
o 3 minor criteria
From Dr. Solante
In most of these cases, whether definite or possible IE,
we are always aggressive with treatment.
 The roles of bacteremia and echocardiographic findings in the
diagnosis of endocarditis are emphasized in the Duke criteria.
 The requirement for multiple positive blood cultures over time is
consistent with the continuous low-density bacteremia
characteristic of endocarditis.
 Among patients with untreated endocarditis who ultimately
have a positive blood culture, 95% of all blood cultures are
positive.
 To fulfill a major criterion, the isolation of an organism that
causes both endocarditis and bacteremia in the absence of
endocarditis must take place repeatedly and in the absence of a
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 primary focus of infection.
D. Blood Cultures
 In the absence of prior antibiotic therapy, three 2-bottle blood
culture sets, separated from one another by at least 1 h, should
be obtained from different venipuncture sites over 24 h.
o If the cultures remain negative after 48–72 h, two or three
additional blood culture sets should be obtained, and the
laboratory should be consulted for advice regarding optimal
culture techniques.
 Pending culture results, empirical antimicrobial therapy should
be withheld initially from hemodynamically stable patients with
suspected subacute endocarditis, especially those who have
received antibiotics within the preceding 2 weeks; thus, if
necessary, additional blood culture sets can be obtained without
the confounding effect of empirical treatment.
 Patients with acute endocarditis or with deteriorating
hemodynamics who may require urgent surgery should be
treated empirically immediately after three sets of blood
cultures are obtained over several hours.
VI. DRUGS
A. Antimicrobial Therapy
 It is difficult to eradicate bacteria from the vegetation because
local host defenses are deficient and because the largely non-
growing, metabolically inactive bacteria are less easily killed by
antibiotics.
 To cure endocarditis, all bacteria in the vegetation must be
killed; therefore, therapy must be bactericidal and prolonged.
 Antibiotics are generally given parenterally to achieve serum
concentrations that, through passive diffusion, lead to effective
concentrations in the depths of the vegetation.
 To select effective therapy requires knowledge of the
susceptibility of the causative microorganisms.
 The decision to initiate treatment empirically must balance the
need to establish a microbiologic diagnosis against the potential
progression of disease or the need for urgent surgery.
 Simultaneous infection at other sites (such as meningitis),
allergies, end-organ dysfunction, interactions with concomitant
medications, and risks of adverse events must be considered in
the selection of therapy.
 Although given for several weeks longer, the regimens
recommended for the treatment of endocarditis involving
prosthetic valves (except for staphylococcal infections) are
similar to those used to treat NVE.
 Recommended doses and durations of therapy should be
adhered to unless alterations are required by end-organ
dysfunction or adverse events.
B. Streptococci
 Optimal therapy for streptococcal endocarditis is based on the
minimal inhibitory concentration (MIC) of penicillin for the
causative isolate.
 Penicillin-susceptible streptococci, S. gallolyticus (MIC, ≤0.1
μg/mL)
o Penicillin G (2–3 mU IV q4h for 4 weeks)
o Ceftriaxone (2 g/d IV as a single dose for 4 weeks)
o Vancomycin (15 mg/kg IV q12h for 4 weeks)
 Vancomycin dose is based on actual body weight. Adjust
for trough level of 10–15 μg/mL for streptococcal and
enterococcal infections and 15–20 μg/mL for
staphylococcal infections.
o Penicillin G (2–3 mU IV q4h) or ceftriaxone (2 g IV qd) for 2
weeks plus Gentamicin (3 mg/kg qd IV or IM, as a single dose
or divided into equal doses q8h for 2 weeks)
 Combination therapy lessens treatment duration but you
have to be careful in giving gentamicin due to its renal
toxicity
 Aminoglycosides should not be administered as single
daily doses for enterococcal endocarditis and should be
introduced as part of the initial treatment. Target peak
and trough serum concentrations of divided-dose
gentamicin 1 h after a 20- to 30-min infusion or IM
injection are ~3.5 μg/mL and ≤1 μg/mL, respectively;
target peak and trough serum concentrations of
streptomycin (timing as with gentamicin) are 20–35 μg/mL
and <10 μg/mL, respectively.
 Netilmicin (4 mg/kg qd, as a single dose) can be used in
lieu of gentamicin
o Can use ceftriaxone in patients with nonimmediate penicillin
allergy
o Use vancomycin in patients with severe or immediate B-lactam
allergy
o Avoid 2-week regimen when risk of aminoglycoside toxicity is
increased and in prosthetic valve or complicated endocarditis
 Relatively penicillin resistant streptococci (MIC, >0.1 μg/mL and
<0.5 μg/mL)
o Penicillin G (4 mU IV q4h) OR ceftriaxone (2 g IV qd) for 4
weeks PLUS Gentamicin (3 mg/kg qd IV or IM, as a single dose
or divided into equal doses q8h for 2 weeks)
 Penicillin alone at this dose for 6 weeks or with gentamicin
during initial 2 weeks preferred for prosthetic valve
endocarditis caused by streptococci with penicillin MICs of
≤0.1 μg/mL
 Gentamicin provides a synergistic action against strep
wherein it allows better penetration to the vegetation
area when added to Pen G or ceftriaxone
o Vancomycin (15 mg/kg) q 12H for 4 weeks – if monotherapy is
preferred and to avoid using gentamicin for patients with renal
conditions
 Moderately penicillin resistant streptococci (MIC, ≥0.5 μg/mL and
<8 μg/mL)
o Penicillin G (4–5 mU IV q4h) or ceftriaxone (2 g IV qd) for 6
weeks plus Gentamicin (3 mg/kg qd IV or IM as a single dose or
divided into equal doses q8h for 6 weeks)
 Preferred for prosthetic valve endocarditis caused by
streptococci with penicillin MICs of >0.1 μg/mL
o Vancomycin as noted above for 4 weeks
 The 2-week penicillin/gentamicin or ceftriaxone/gentamicin
regimens should NOT be used to treat complicated NVE or PVE.
B. Staphylococci
 The regimens used to treat staphylococcal endocarditis are based
not on coagulase production but rather on the presence or
absence of a prosthetic valve or foreign device, the native valve(s)
involved, and the susceptibility of the isolate to penicillin,
methicillin, and vancomycin.
 All staphylococci are considered penicillin-resistant until shown
not to produce penicillinase.
 Similarly, methicillin resistance has become so prevalent among
staphylococci that therapy should be initiated with a regimen for
methicillin-resistant organisms and subsequently revised if the
strain proves to be susceptible to methicillin.
 The addition of 3–5 days of gentamicin (if the isolate is
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 susceptible) to a β-lactam antibiotic to enhance therapy for native
mitral or aortic valve endocarditis has been optional.
o While the addition of gentamicin minimally hastens
eradication of bacteremia, it does not improve survival
rates, and even abbreviated gentamicin therapy may be
associated with nephrotoxicity and thus is not
recommended. Gentamicin generally is not added to the
vancomycin regimen in this setting.
 For treatment of endocarditis caused by methicillin-resistant S.
aureus (MRSA), vancomycin dosing to achieve trough
concentrations of 15–20 μg/mL is recommended, with the
recognition that this regimen may be associated with
nephrotoxicity.
 Methicillin-susceptible S. aureus endocarditis that is
uncomplicated and limited to the tricuspid or pulmonic valve—a
condition occurring almost exclusively in injection drug users—can
often be treated with a 2-week course that combines oxacillin or
nafcillin (but not vancomycin) with gentamicin.
 Patients with prolonged fever (≥5 days) during therapy or multiple
septic pulmonary emboli should receive standard therapy.
 Right-sided endocarditis caused by MRSA is treated for 4 weeks
with a standard vancomycin regimen or with daptomycin (6 mg/kg
as a single daily dose).
 Staphylococcal PVE is treated for 6–8 weeks with a multidrug
regimen.
o Rifampin is an essential component because it kills
staphylococci that are adherent to foreign material in a
biofilm.
o Take note that rifampin increases warfarin and dicumarol
requirements for anticoagulation.
o Two other agents (selected on the basis of susceptibility
testing) are combined with rifampin to prevent in vivo
emergence of resistance.
o Because many staphylococci (particularly MRSA and S.
epidermidis ) are resistant to gentamicin, susceptibility to
gentamicin or an alternative agent should be established
before rifampin treatment is begun.
o If the isolate is resistant to gentamicin, then another
aminoglycoside, a fluoroquinolone (chosen on the basis of
susceptibility), or another active agent should be
substituted for gentamicin.
 MSSA infecting native valves (no foreign devices)
o Nafcillin, Oxacillin or flucloxacillin (2 g IV q4h for 4–6 weeks)
o Cefazolin (2 g IV q 8H) x 4-6 weeks
 Can use penicillin (4 mU q4h) if isolate is penicillin-
susceptible (does not produce β-lactamase)
o Vancomycin (15 mg/kg) q 12H for 4-6 weeks
 Usually given for 6 weeks to prevent relapse
 Can use cefazolin regimen for patients with non-
immediate penicillin allergy
 Use vancomycin for patients with immediate (urticarial) or
severe penicillin allergy
 MRSA infecting native valves (no foreign devices)
o Vancomycin (15 mg/kg) q 8-12H for 4-6 weeks
 Frequency depends on patient’s renal condition; if good
renal function, drug is given q8h
 No role for routine use of rifampin
 MSSA infecting prosthetic valves
o Nafcillin, Oxacillin or flucloxacillin (2 g IV q4h for 6-8 weeks) +
gentamicin (1 mg/kg/d) q 8H for 2 weeks + rifampin 300 mg
PO q 8H for 6-8 weeks
 Use gentamicin during initial 2 weeks
 Determine susceptibility to gentamicin before initiating
rifampin
 If patient is highly allergic to penicillin, use regimen
 for methicillin-resistant staphylococci
 If β-lactam allergy is of the minor, nonimmediate type, can
substitute cefazolin for oxacillin/nafcillin
 MRSA infecting prosthetic valves
o Vancomycin (15 mg/kg) q 8-12H for 6-8 weeks + gentamicin (1
mg/kg/d) q 8H for 2 weeks + rifampin 300 mg PO q 8H for 6-8
weeks
 Use gentamicin during initial 2 weeks
 Determine susceptibility to gentamicin before initiating
rifampin
C. Enterococci
 Enterococci are resistant to oxacillin, nafcillin, and the
cephalosporins and are only inhibited—not killed—by penicillin,
ampicillin, and vancomycin.
 To kill enterococci requires the synergistic interaction of a cell
wall–active antibiotic (penicillin, ampicillin, or vancomycin) that is
effective at achievable serum concentrations and an
aminoglycoside (gentamicin or streptomycin) to which the isolate
does not exhibit high-level resistance.
 High-level aminoglycoside resistance
o An isolate's resistance to cell wall–active agents or its ability
to replicate in the presence of gentamicin at ≥500 μg/mL or
streptomycin at 1000–2000 μg/mL
o Indicates that the ineffective antimicrobial agent cannot
participate in the interaction to produce killing
o High-level resistance to gentamicin predicts that tobramycin,
netilmicin, amikacin, and kanamycin also will be ineffective.
o Even when enterococci are not highly resistant to gentamicin,
it is difficult to predict the ability of these other
aminoglycosides to participate in synergistic killing.
o Consequently, they should not in general be used to treat
enterococcal endocarditis.
 High concentrations of ampicillin plus ceftriaxone or cefotaxime,
by expanded binding of penicillin-binding proteins, kill E. faecalis
in vitro and in animal models of endocarditis.
 Enterococci causing endocarditis must be tested for high-level
resistance to streptomycin and gentamicin, β-lactamase
production, and susceptibility to penicillin and ampicillin (MIC,
<8 μg/ mL) and to vancomycin (MIC, ≤4 μg/mL).
 If the isolate produces β-lactamase, ampicillin/sulbactam or
vancomycin can be used as the cell wall–active component
o If the penicillin/ampicillin MIC is ≥8 μg/mL, vancomycin can
be considered
o If the vancomycin MIC is ≥8 μg/mL, penicillin or ampicillin
can be considered.
 In the absence of high-level resistance, gentamicin or
streptomycin should be used as the aminoglycoside.
 If there is high-level resistance to both these drugs, no
aminoglycoside should be given
o Instead, an 8- to 12-week course of a single cell wall–active
agent—or, for E. faecalis , high doses of ampicillin
combined with ceftriaxone or cefotaxime—is suggested.
o If this alternative therapy fails or the isolate is resistant to
all of the commonly used agents, surgical treatment is
advised.
 The role of newer agents potentially active against multidrug-
resistant enterococci [quinupristin/dalfopristin ( E. faecium
only), linezolid, and daptomycin] in the treatment of
Page 6 of 11
 endocarditis has not been established.
 Although the dose of gentamicin used to achieve bactericidal
synergy in treating enterococcal endocarditis is smaller than that
used in standard therapy, nephrotoxicity is not uncommon
during treatment for 4–6 weeks.
 Regimens in which the aminoglycoside component is
discontinued at 2–3 weeks because of toxicity have been
curative.
o Thus, discontinuation of the aminoglycoside is
recommended when nephrotoxicity develops in patients
who have responded satisfactorily to therapy.
 Alternatively, the ampicillin-ceftriaxone regimen can
be used to treat E. faecalis endocarditis if nephrotoxicity develops
or is exceptionally threatening.
 Penicillin G (4–5 mU IV q4h) PLUS Gentamicin (1 mg/kg IV q8h),
both for 4–6 weeks
o Can use streptomycin (7.5 mg/kg q12h) in lieu of
gentamicin if there is not high-level resistance to
streptomycin
 Ampicillin (2 g IV q4h) PLUS Gentamicin (1 mg/kg IV q8h), both for
4–6 weeks
 Vancomycin (15 mg/kg IV q12h) PLUS Gentamicin (1 mg/kg IV
q8h), both for 4–6 weeks
o Use vancomycin plus gentamicin for penicillin-allergic
patients, or desensitize to penicillin
D. HACEK Organisms
 Fastidious gram negative coccobacilli
 Haemophilus spp.
Aggregatibacter actinomycetemcomitans
Cardiobacterium hominis
Eikenella spp.
Kingella spp.
 Ceftriaxone (2 g/d IV as a single dose fo 4 weeks)
o Can use another third-generation cephalosporin at
comparable dosage
 Ampicillin/sulbactam (3 g IV q6h for 4 weeks)
E. Monitoring Antimicrobial Treatment
 Serum bactericidal titer
o The highest dilution of the patient's serum during therapy
that kills 99.9% of the standard inoculum of the infecting
organism
o No longer recommended for assessment of standard
regimens
o However, in the treatment of endocarditis caused by
unusual organisms, this measurement may provide a
patient-specific assessment of in vivo antibiotic effect.
 Serum concentrations of aminoglycosides and vancomycin
should be monitored.
 Antibiotic toxicities, including allergic reactions, occur in 25–40%
of patients and commonly arise during the third week of
therapy.
 Blood tests to detect renal, hepatic, and hematologic toxicity
should be performed periodically.
 Blood cultures should be repeated daily until sterile, rechecked if
there is recrudescent fever, and performed again 4–6 weeks
after therapy to document cure.
 Blood cultures become sterile within 2 days after the start of
appropriate therapy when infection is caused by viridans
streptococci, enterococci, or HACEK organisms.
o In S. aureus endocarditis, β-lactam therapy results in sterile
cultures in 3–5 days
o In MRSA endocarditis, positive cultures may persist for 7–9
days with vancomycin treatment.
o MRSA bacteremia persisting despite an adequate dosage of
vancomycin may indicate infection due to a strain with
reduced vancomycin susceptibility and therefore may point
to a need for alternative therapy.
 When fever persists for 7 days despite appropriate antibiotic
therapy, patients should be evaluated for paravalvular abscess,
extracardiac abscesses (spleen, kidney), or complications
(embolic events).
 Recrudescent fever raises the question of these complications
but also of drug reactions or complications of hospitalization.
 Vegetations become smaller with effective therapy; however, 3
months after cure, 50% are unchanged and 25% are slightly
larger.
VII. INDICATIONS FOR SURGERY
A. Surgery required for optimal outcome
 Moderate to severe congestive heart failure due to valve
dysfunction
 Partially dehisced unstable prosthetic valve
 Persistent bacteremia
 Lack of microbicidal therapy (fungal, brucella endocarditis)
 S. aureus prosthetic valve endocarditis with intracardiac
complications
 Relapse of prosthetic valve endocarditis
B. Surgery strongly considered for improved outcome
 Perivalvular extension of infection
 Poorly responsive S. aureus endocarditis involving the aortic or
mitral valve
 Large (>10 mm in diameter) hypermobile vegetations with
increased risk of embolism
 Persistent unexplained fever (≥10 days) in culture-negative native
valve endocarditis
 Poorly responsive or relapsed endocarditis due to highly
antibiotic-resistant enterococci or gram-negative bacilli
C. Timing of cardiac surgical intervention in patients with
endocarditis
 Emergent (same day)
o Acute aortic regurgitation plus preclosure of mitral valve
o Sinus of Valsalva abscess ruptured into right heart
o Rupture into pericardial sac
 Urgent (within 1-2 days)
o Valve obstruction by vegetation Unstable (dehisced) prosthesis
o Acute aortic or mitral regurgitation with heart failure (NYHA
class III or IV)
o Septal perforation
o Perivalvular extension of infection with or without new
electrocardiographic conduction system changes
o Lack of effective antibiotic therapy
 Elective (earlier usually preferred
o Vegetation diameter >10 mm plus severe aortic or mitral valve
dysfunction
o Progressive paravalvular prosthetic regurgitation
o Valve dysfunction plus persisting infection after ≥7–10 days of
antimicrobial therapy
Page 7 of 11
VIII. PROPHYLAXIS
A. Antibiotic regimens for prophylaxis of endocarditis in adults with
high risk cardiac lesions
 Standard oral regimen
o Amoxicillin: 2 g PO 1 h before procedure
 Inability to take oral medication
o Ampicillin: 2 g IV or IM within 1 h before procedure
 Penicillin allergy
o Clarithromycin or azithromycin: 500 mg PO 1 h before procedure
o Cephalexin: 2 g PO 1 h before procedure
o Clindamycin: 600 mg PO 1 h before procedure
 Penicillin allergy, inability to take oral medication
o Cefazolin or ceftriaxone: 1 g IV or IM 30 min before procedure
o Clindamycin: 600 mg IV or IM 1 h before procedure

Figure 5. High Risk Cardiac Lesions for Which Endocarditis Prophylaxis

is Advised Before Dental Procedures

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 Subject: MEDICINE II
Topic: 2.11 – Infective Endocarditis
Lecturer: Dr. Solante
Date: August 18, 2015

APPENDIX

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Edited By: Aix and HP
 Subject: MEDICINE II
Topic: 2.11 – Infective Endocarditis
Lecturer: Dr. Solante
Date: August 18, 2015

The diagnostic use of transesophageal and transtracheal echocardiography (TEE and TTE, respectively).
†High initial patient risk for endocarditis as listed in Table 124-8 (see previous page) or evidence of intracardiac complications (new regurgitant
murmur, new electrocardiographic conduction
changes, or congestive heart failure).
∗ High-risk echocardiographic features include large vegetations, valve insufficiency, paravalvular infection, or ventricular dysfunction.
Rx indicates initiation of antibiotic therapy.

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