REVIEW

C URRENT
OPINION Endocarditis in critically ill patients: a review
Wagner Nedel a,b, Marcio Manozzo Boniatti a,c,d and Thiago Lisboa a,d,e,f

Purpose of review
To summarize the advances in literature that support the best current practices regarding infective
endocarditis (IE) in critically ill patients.
Recent findings
IE due to rheumatic diseases has decreased significantly, and in fact, the majority of cases are associated
with degenerative valvopathies, prosthetic valves, and cardiovascular implantable electronic devices. The
Duke criteria were recently updated, addressing the increasing incidence of new risk factors for IE, such as
IE associated with the use of endovascular cardiac implantable electronic devices and transcatheter implant
valves. The presence of organ dysfunction, renal replacement therapies, or extracorporeal membrane
oxygenation should be considered in the choice of drug and dosage in critically ill patients with suspected
or confirmed IE. As highlighted for other severe infections, monitoring of therapeutic antibiotic levels is a
promising technique to improve outcomes in critically ill patients with organ dysfunction.
Summary
The diagnostic investigation of IE must consider the current epidemiological criteria and the diagnostic
particularities that these circumstances require. A careful evaluation of these issues is necessary for the
prompt clinical or surgical management of this infection.
Keywords
antibiotic, endocarditis, infectious endocarditis, sepsis, Staphylococcus

INTRODUCTION healthcare-associated infections [8]. These changes

Infective endocarditis (IE) is a severe condition char- have led to an increase in the proportion of Staph-
&

acterized by an infection of the endothelium of the
heart. Although it can occur on various endocardial
surfaces, the most commonly affected structures are
the heart valves. However, the infection can also
develop on mural endocardium, cardiac septal
defects, and intravascular devices. IE has an annual
incidence of 3 to 10 per 100,000 individuals per year
and up to 40–50% of affected patients require valve
surgery at some point during the clinical course,
with an overall mortality rate of 20–25% [1,2 ].
&
Endocarditis-related mortality is strongly linked to
a number of risk factors, including advanced age,
healthcare association, and failure to undergo sur-
gery when necessary [3,4].
EPIDEMIOLOGY
The incidence of IE related to rheumatic disease has
significantly declined in high-income countries,
and cases associated with degenerative valvulopa-
thies, prosthetic valves, and cardiovascular implant-
able electronic devices (CIEDs) have taken its place
[5–7]. As a consequence, patients diagnosed with IE
today are generally older and more susceptible to
ylococcus aureus and enterococcal IE [9,10 ,11]. In
recent years, Staphylococcus strains have emerged as
the predominant causative pathogens in patients
diagnosed with IE [8]. As the number of transcath-
eter aortic valve replacement (TAVR) cases is
expected to increase due to expanding indications,
Enterococcus spp.-related IE is anticipated to rise
further since it is the primary cause of IE in TAVR
cases [12,13].
Recently, there has been an increasing number
of IE patients who require admission to an intensive
care unit (ICU). The higher incidence of IE in older
patients with comorbidities, often caused by
a
Hospital de Clinicas de Porto Alegre, bHospital Nossa Senhora Con-
ceição, cPrograma de Pos-Graduação Cardiologia, UFRGS, dUniversi-
dade LaSalle, Canoas, ePrograma de Pos-Graduação Ciencias
Pneumológicas, UFRGS, Porto Alegre and fHospital Santa Rita, Com-
plexo Hospitalar Santa Casa de Porto Alegre, Brazil
Correspondence to Thiago Lisboa, Hospital de Clinicas de Porto Alegre,
Ramiro Barcelos 2350, Brazil. Tel: + 55 51 33598643;
e-mail: tlisboa@hcpa.edu.br
Curr Opin Crit Care 2023, 29:430–437
DOI:10.1097/MCC.0000000000001071

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KEY POINTS

Recently, there has been an increasing number of IE
patients who require admission to an intensive care
unit. The higher incidence of IE in older patients with
comorbidities, often caused by staphylococcal
infection, has led to a greater frequency of
critical illness.

A multimodal diagnostic strategy should be necessary
in IE, especially in investigation of prosthetic valves or
in patients using cardiovascular implantable devices.

Duke diagnostic criteria was recently updated, but their
diagnostic accuracy was lower in patients with
suspected right-sided native valve IE, prosthetic valve IE,
and pacemaker or defibrillator lead IE. It is still too
early to assess the impact of these changes on
diagnostic accuracy, however.

Rational for prompt antibiotic initiation and blood
cultures sampled before first antibiotic doses is the
same for septic patients. In patients with septic shock,
urgent introduction of empirical antibiotics is
recommended, and this recommendation should
therefore also apply to patients with known or
suspected IE and septic shock.
staphylococcal infection, has led to a greater fre-
quency of critical illness. Moreover, critically ill
patients have a higher risk of developing IE due to
their pro-inflammatory states and the prevalence of
indwelling catheters, which increase the risk of
infection [14,15].
PATHOPHYSIOLOGY
Endocarditis is extremely difficult to induce in lab-
oratory animals without causing structural changes
that compromise endocardial integrity [16,17]. Such
changes result in turbulent blood flow, which can
mechanically stress the wall and ultimately damage
the endothelium. This damage promotes the depo-
sition of fibrin and platelets, creating a nidus for
vegetation [18]. Recently, experimental endocardi-
tis has been induced in structurally healthy, but
inflamed valves [19], which might explain why
individuals infected with virulent bacteria like S.
aureus can develop endocarditis in previously
healthy hearts [7].
The second phase in the pathophysiological
process of IE is bacterial adherence. After the endo-
thelial lesion is created, the expression of fibronec-
tin and the release of inflammatory cytokines linked
to tissue factors enhance bacterial adherence, lead-
ing to the formation of a thrombus composed of
platelets and fibrin [20,21]. The same organisms that
are detected more frequently in IE patients highlight
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Endocarditis in critically ill patients Nedel et al.
the importance of bacterial components that facil-
itate adherence to the lesion [22,23]. These organ-
isms possess adhesins on their surfaces that promote
adhesion to the vegetation and might control
inflammation. Microbial surface component react-
ing with adhesive matrix molecules (MSCRAMMs) is
the collective name for these adhesins [24].
MSCRAMMs can identify integrins, specific ligands
present on the surface of damaged or swollen endo-
thelium.
The development of fibrin-platelet aggregates,
which group with bacteria to form vegetation, is the
final significant pathogenic event in IE. Within this
structure, microorganisms can survive and thrive as
biofilms by modifying their function and metabo-
lism to a self-made matrix [25]. This biofilm serves as
a habitat for the bacteria and contributes to their
resistance to antibiotics, making them more chal-
lenging to treat [26,27]. Vegetation is a pathological
characteristic of IE and is associated with several
clinical symptoms, including: (1) growth of a septic
thrombus, aided by the activation of hemostasis by
cytokines, resulting in continuous bacteremia and
high inoculum that can seed distant septic meta-
stases; (2) valve changes and perivalvular changes
caused by the destruction of the extracellular matrix
by proteolytic enzymes released by microorganisms
and inflammatory cells; and (3) autoimmune lesions
caused by immune complexes in circulation as a
result of immune system activation [28].
DIAGNOSIS OF INFECTIVE ENDOCARDITIS
Electrocardiography and chest radiography should
always be performed as part of the initial evaluation
of patients with suspected IE. The presence of a heart
block or conduction delay on baseline electrocar-
diography may be indicative of a paravalvular exten-
sion of the infection. Moreover, myocardial
ischemia may suggest the occurrence of septic
emboli in the coronary arteries. Chest radiography
may reveal the presence of septic pulmonary emboli
or potential alternative causes of fever and systemic
symptoms [29].
&&
The Duke criteria were recently updated [30 ],
addressing the increasing incidence of new risk
factors for IE, such as IE associated with the use of
endovascular cardiac implantable electronic devices
and transcatheter implanted valves. These changes
are listed in Table 1. The Duke criteria were devel-
oped for the evaluation of patients with left-sided
native valve IE, and their diagnostic accuracy was
lower in patients with suspected right-sided native
valve IE, prosthetic valve IE, and pacemaker or
defibrillator lead IE [31]. The diagnostic sensitivity
of the modified Duke criteria for right-sided/CIED-IE
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Severe infections

Table 1. New modifications in Duke criteria for infective endocarditis

Microbiologic criteria
Imaging
Surgical evidence
New minor evidence
Recent genetic, molecular and tissue staining techniques by which etiologic microorganisms can be detected
were incorporated, including PCR, and fluorescence in situ hybridization.
Additional bacteria were added to the ‘typical microorganism’ group to reflect recent epidemiologic data, such
as Streptococcus pneumoniae, Staphylococcus lugdunensis, Enterococcus faecalis and Streptococcus
pyogenes.
CT was included as an additional imaging modality, due to its higher sensitivity for the detection of paravalvular
lesions.
PET CT was included as an imaging modality, because it overcomes the diagnostic limitations of
echocardiography when evaluating prosthetic material.
Intraoperative evidence of IE (abscess, vegetations, valvular destruction, dehiscence) were included as a new
major criteria.
Splenic abscess and cerebral abscess were recognized as additional vascular phenomenon.

IE, infective endocarditis; PCR, polymerase chain reaction; PET CT, positron emission tomography and computed tomography.

is lower, as audible murmurs, peripheral emboli, and
immunological and vascular phenomena are usu-
ally absent. Extending these criteria to a clinical
practice setting has been somewhat more difficult
[32], and this effort to update the diagnostic criteria
is an attempt to minimize these limitations. How-
ever, it is still too early to assess the impact of these
changes on diagnostic accuracy.
IE of the left-sided native valve should be sus-
pected in patients with relevant cardiac risk factors
(e.g., preexisting valvular or congenital heart dis-
ease), prior IE, and other predisposing conditions,
including intravenous drug use, immunosuppres-
sion, recent dental or surgical procedures, an
indwelling cardiac device, or an intravenous cathe-
ter. Intravenous drug use and septic pulmonary
emboli, especially in the lungs, are important clues
for right-sided IE [33]. New onset of heart failure
symptoms is a relevant clue for this diagnosis in
both right- and left-sided IE.
At least three sets of blood cultures should be
obtained at 30 min intervals from separate veni-
puncture sites, preferentially before starting antibi-
otic therapy and from peripheral veins.
Contamination likelihood is reduced when the
microorganism is found in multiple blood cultures
obtained from different venipuncture sites [34].
Most clinically significant bacteremias caused by
typical pathogens are usually detected within
48 h. The time to positivity of a blood culture is
rarely greater than 5 days [35]. In patients with
negative blood cultures after 5 days of incubation
and subculturing using standard methods, blood
culture-negative IE should be suspected. Culture-
negative IE may be caused by previous antibiotic
therapy, fungi, or fastidious intracellular bacteria
that require specialized culture media and grow
relatively slowly [36].
Echocardiography is the first-line imaging
modality in IE and should be performed in all
patients with fever and positive blood culture and
at higher-risk of IE either on native-valve and pro-
thesis/CIED-based clinical presentation and risk fac-
tors [37]. Both transthoracic echocardiography
(TTE) and transoesophageal echocardiography
(TEE) provide complementary information, and
TTE should be performed initially in all suspected
IE cases. When TTE results are negative and clinical
suspicion remains low, other clinical entities should
be considered. If TTE shows vegetation but the like-
lihood of complications is low, then subsequent TEE
is unlikely to alter the initial medical management.
On the other hand, if the clinical suspicion of IE or
its complications is high (e.g., prosthetic valve or
new atrioventricular block), then a negative TTE will
not definitely rule out IE or its potential complica-
tions, and TEE should be performed first. Currently,
the sensitivity of TTE for detecting vegetation on
native valves is approximately 70% [38]. This is
reduced to 50% in patients with prosthetic valves
and is lower in patients with implanted electronic
devices ([38,39]. Where TTE is nonconfirmatory and
the microbiology is clinically suggestive of IE, a
repeat TTE may be appropriate at an interval of 5
to 7 days [40].
TEE has a sensitivity and specificity exceeding
90% for vegetation [41]. TEE is performed to confirm
the diagnosis of IE in the context of nondiagnostic
TTE and a high clinical suspicion of endocarditis,
when prosthetic or device-related endocarditis is
suspected, and when IE-related complications have
occurred (heart block, new murmur, persistent
fever, embolism, and intracardiac abscess) [38].
TEE should also be performed in patients with pos-
itive TTE results to rule out local complications.
Repeat imaging is generally not required during
the treatment course of IE unless clinical deteriora-
tion or complications are suspected.
Identification of vegetation may be difficult in
the presence of preexisting valvular lesions (mitral

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valve prolapse and degenerative calcified lesions),
prosthetic valves, small vegetation (2–3 mm), recent
embolization, and nonvegetant IE [38]. Many find-
ings identified using TEE can also be detected using
TTE. Concurrent TTE images can serve as a baseline
for rapid and noninvasive comparison of vegetation
size, valvular insufficiency, or changes in abscess
cavities during the course of the patient’s treatment
should clinical deterioration occur [32]. For tricus-
pid vegetation or abnormalities of the right ventric-
ular outflow tract, visualization may be enhanced by
choosing TTE rather than TEE. TTE may be superior
to TEE for quantifying hemodynamic dysfunction
manifested by valvular regurgitation, ventricular
dysfunction, elevated left and right ventricular fill-
ing pressures, and pulmonary artery pressure [32].
Other imaging modalities, including magnetic
resonance (MR), CT, PET/CT, and single-photon
emission computed tomography (SPECT)/CT, are
aimed at evaluating cardiac involvement and
embolic events. The choice of a particular diagnostic
modality is guided by local availability and expertise
[31]. Cardiac CT may be considered in patients with
suspicion of IE when ultrasound examinations are
&&
nondiagnostic [30 ]. Although it is inferior to trans-
oesophageal echocardiogram (TOE) in detecting veg-
etation, cardiac CT is superior for the evaluation of
the paravalvular extension of infection [29]. Nuclear
medicine modalities may provide additional diag-
nostic and prognostic information for the diagnosis
of prosthetic valve endocarditis (PVE), with a high
specificity and sensitivity in suspected PVE, espe-
cially in case of inconclusive TTE [42]. These modal-
ities have high diagnostic accuracy in cardiac device-
related IE [42,43] Moreover, it has excellent diagnos-
tic value in the visualization of perivalvular abscesses
[44]. The diagnostic parameters in solely the native
valve IE group, however, have not been validated so
far [45].
DIAGNOSTIC CHALLENGE IN CRITICALLY
ILL PATIENTS
IE may manifest with various clinical presentations,
including atypical symptoms, particularly in ICU-
admitted patients. The Modified Duke’s Criteria can
be employed to diagnose IE, but their applicability in
the ICU setting remains unvalidated (Table 1) [46].
Common ICU presentations include pyrexia of
unknown origin, peripheral thromboembolism,
neurological complications like stroke or intracra-
nial hemorrhage, hypotension, changing cardiac
murmur, tachycardia, heart failure, inflammatory
marker rise, acute kidney injury, and anemia [46].
Critically ill patients typically do not exhibit classical
IE symptoms, posing challenges to their diagnosis.
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Endocarditis in critically ill patients Nedel et al.
Central nervous system (CNS) signs can be masked
by sedation administered to ICU patients, and brain
imaging is crucial to rule out other confounding
factors like septic encephalopathy [47]. Fever and
bacteremia can indicate coexisting infections, and
acute kidney injury is frequently observed due to
other pathologies. Thus, timely diagnosis requires a
high level of suspicion, particularly in patients with
prosthetic valves, postcardiac surgery, bloodstream
infection from S. aureus or Candida species, persistent
bloodstream infection from other bacteria or fungi,
or long-term invasive monitoring or therapeutic
devices. Critically ill IE patients exhibit specific fea-
tures such as higher S. aureus involvement, increased
rates of neurological complications, and long-term
mortality [47].
Embolic phenomena are relatively frequent in
IE, occurring in approximately 25% of the patients
[48]. Embolic phenomena are well described in
healthcare-associated IE and are associated with a
worse prognosis in this population [49]. The most
feared foci of embolization are the central nervous
system, where the presense of ischemic stroke is
associated with worse prognosis [47].
INVESTIGATION OF EI DURING
BACTEREMIA/FUNGEMIA COURSE
As the risk of IE in patients with bloodstream infec-
tions depends on the different bacterial species,
strategies should be put in place to identify the
subgroup of patients with high clinical risk [37].
For example, given the high incidence of IE (6–
32%) among patients with Staphylococcus aureus
bacteremia (SAB) [37], standard clinical practice is
to perform echocardiography in patients with SAB,
as a significant portion of these patients have endo-
carditis in the absence of clinical signs [50]. Scoring
systems have been developed to determine the
necessity for TEE. The best performance was
obtained from the VIRSTA score, with a high neg-
ative predictive value (>98%), but at the expense of
a high number of patients classified as high-risk,
thus requiring TEE [51]. Some risk factors had an
increased positive likelihood ratio (PLR) for IE devel-
opment: presence of embolic events (PLR 12.7),
pacemakers (PLR 9.7), prosthetic valves (PLR 5.7)
and intravenous drug use (PLR 5.2); the only clinical
factor with a clinically relevant negative likelihood
ratio (NLR), however, was the clearance of bacter-
emia within 72 h (NLR 0.32 to 0.35) [52]. In patients
with SAB and without any high-risk criteria defined
as community-acquired SAB, high-risk cardiac con-
ditions (prosthetic heart valve, prosthetic material,
congenital heart disease, cardiac transplantation,
prior IE, pacemaker, permanent pacemaker (PM),
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Severe infections
or implantable cardioverter defibrillator) and intra-
venous drug, a normal TTE could rule out IE with
high sensitivity (97%, 95% confidence interval [CI]
87 – 100%) and high negative predictive value
(99%, 95% CI 96%–100%) [53].
Candida endocarditis is an uncommon disease
[54]. Therefore, routine echocardiography is not
recommended in patients with positive blood cul-
tures for Candida. Currently, however, there is an
increased incidence of endocarditis due to Candida
species during candidemia; in some cases, associated
with prosthetic valves or cardiac devices [55]. Exist-
ing valvular heart disease is an independent variable
associated with IE [54]. The results of TTE suggest IE
in 2.9% of patients, and the result of TEE is positive
in 11.5% of patients in an unicentric study [56]. An
echocardiography-focused investigation should be
performed especially in those patients with persis-
tent (3 days) candidemia despite antifungal ther-
apy [57]. Coagulase-negative staphylococci (CoNS)
are not considered the typical microorganisms that
cause IE, except Staphylococcus lugdunensis, that has
an elevated incidence (14%) of IE postbacteremia
[58]. Few unicentric studies have explored the inci-
dence of IE in patients with CoNS bacteremia. The
incidence of IE is variable, as high as 11% in one
cohort [59], to 2% in Staphylococcus epidermidis bac-
teremia [58]. The presence of valve prostheses (odd
ratio [OR] 38.6) and persistent bacteremia (OR 2.6)
were independent risk factors for IE [59].
MANAGEMENT
Most IE management recommendations are sup-
ported by low quality evidence from observational
studies and expert opinion [32,38]. This issue was
recently revised in this Journal [60] and no new
breakthrough evidence was published since then.
Table 2 summarizes the antimicrobial options sug-
gested by most recently published guidelines.
Rational for prompt antibiotic initiation and blood
cultures sampled before first antibiotic dosis is the
same for septic patients. In patients with septic
shock, urgent introduction of empirical antibiotics
is recommended, and this recommendation should
therefore also apply to patients with known or sus-
pected IE and septic shock [60,61]. It is crucial to give
appropriate antibiotic therapy empirically. Since
staphylococci and streptococci account for 80% of
cases of IE, initial antibiotic therapy should be active
against these pathogens [32,38,62]. Presence of organ
dysfunction, renal replacement therapies, or extrac-
orporeal membrane oxygenation (ECMO) should be
considered in the choice of drug and dosage in
critically ill patients with suspected or confirmed
infectiousendocarditis (EI). As highlighted for other
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severe infections, monitoring of therapeutic anti-
biotic levels is a promising technique to improve
outcomes in critically ill patients with organ dysfunc-
tion, although availability is still an issue [63,64].
Duration of therapy in EI is a challenge. Optimal
antimicrobial duration in sepsis is likely to remain
best determined through close collaboration between
intensivists, infectious disease and cardiology special-
ists, in order to weigh the relative contributions of
many aspects regarding pathogen, host response and
drug efficacy, as well as risk for embolic events or
local complications such large vegetations, abscesses,
false aneurysms or fistulas.
The accepted indications for urgent surgery in IE
are heart failure, along with uncontrolled infection
(ongoing bacteriemia, local abscesses and fistulae)
and emboli prevention (in cases of recurrent emboli
or large vegetations).
Patients with congestive heart failure caused by
IE benefit from valvular surgery. In patients with
New York Heart Association (NYHA) class I or II
heart failure, the mortality rate in surgically treated
patients was 8 vs. 15% in those not surgically treated
(P ¼ 0.03); for those with NYHA class III or IV heart
failure, corresponding mortality rates were 23.4 vs.
54.5%, respectively (P < 0.001) [62,65]. Also, cardiac
surgery may be performed safely after ischaemic
stroke, provided that the patient has no extensive
neurologic damage and no cerebral bleeding. How-
ever, timing is still an issue. Recently, Dashkevich
et al. [66] assessed the impact of operative timing in
IE with cerebral embolism and suggested that post-
poning surgery to achieve clinical stabilization and
better postoperative outcomes of IE patients with CE
is reasonable, however, worsening of the disease
process with deterioration and resulting heart fail-
ure during the first 3 weeks after CE results in a
significantly higher in-hospital mortality and infe-
rior long-term survival. Regarding ischemic stroke
treatment, as a frequent neurologic complication of
IE, a recent systematic review [67] suggested that
thrombectomy in IE associated stroke appears to be
safer than thrombolysis, or combined treatment,
but with a low quality of evidence supporting this
choice.
A multidisciplinary heart team plays an impor-
tant role in improving the management of patients
with cardiovascular diseases [68]. In the case of IE
this is not different. This serious and complex dis-
ease has a multisystemic extension with specific
diagnostic and therapeutic challenges [69]. There-
fore, implementation of endocarditis teams, prefer-
entially in reference centers, is recommended to
&
optimize the care of these patients [69,70 ]. The
implementation of multidisciplinary teams is asso-
ciated with reduced in-hospital mortality and 3-year
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 Endocarditis in critically ill patients Nedel et al.

Table 2. The antibiotic regimens suggested in international guidelines (adapted from reference [60])

American Heart Association European Society of Cardiology (ESC)

(AHA) guidelines, 2015 [32] guidelines, 2015 [38]

Empirical treatment in the
ICU
Staphylococcal
endocarditis, native
valve(s)
Staphylococcal
endocarditis, prosthetic
valve(s)
Streptococcal endocarditis,
susceptible strains (MIC
penicillin < 0.25 mg/l)
Enterococcal endocarditis,
penicillin-susceptible
strains
Gram-negative HACEK-
related species
Gram-negative non-
HACEK-species
Fungi
To be adjusted based on clinical course and risk
factors
Methicillin-susceptible:
Antistaphylococcal penicillinv
Methicillin-resistant:
Vancomycin or daptomycin
Methicillin-susceptible:
Antistaphylococcal penicillin þ gentamicin þ
rifampicin
Methicillin-resistant:
Vancomycin or daptomycin þ Gentamicin þ
rifampin
Four-week course Penicillin G or ceftriaxone
Ampicillin þ ceftriaxone 6 weeks
Ceftriaxone 2 g/day for 4 weeks in NVE and for
6 weeks in PVE OR
Ampicillin (12g/day) OR
Ciprofloxacin (1000mg/24h orally or 800mg/24h
IV)
Cardiac surgery þ prolonged courses of combined
antibiotic therapy for most patients with IE
caused by non-HACEK Gram-negative aerobic
bacilli, particularly P aeruginosa.
Combination antibiotic therapy with a b-lactam þ
aminoglycoside or fluoroquinolone for 6 weeks
Fungal IE is a ‘‘stand-alone indication’’ for surgical
replacement of an infected valve; and
amphotericin B is the initial drug of choice for
fungal IE.
Antifungal therapy usually is given for >6 weeks.
If community-acquired:
Ampicillin þ (cl)oxacillin þ gentamicin
If nosocomial:
Vancomycin þ gentamicin  rifampicin
Methicillin-susceptible
Antistaphylococcal penicillin
Methicillin-resistant
Vancomycin or daptomycin
Methicillin-susceptible:
Antistaphylococcal penicillin þ gentamicin þ
rifampicin
Methicillin-resistant:
Vancomycin or daptomycin þ gentamicin þ
rifampin
Four-week course Penicillin G or ceftriaxone or
amoxicillin
Ampicillin þ ceftriaxone
Ceftriaxone 2 g/day for 4 weeks in NVE and for
6 weeks in PVE.
If they do not produce beta-lactamase, ampicillin
(12 g/day i.v. in four or six doses) plus
gentamicin (3 mg/kg/day divided into two or
three doses) for 4--6 weeks
Early surgery plus long-term (at least 6 weeks)
therapy with bactericidal combinations of beta-
lactams and aminoglycosides, sometimes with
additional quinolones or cotrimoxazole.
Antifungal therapy for Candida IE: Liposomal
amphotericin B (or other lipid formulations) with
or without flucytosine OR an echinocandin at
high doses;
Aspergillus IE: voriconazole is the drug of choice.

IE, infective endocarditis; NVE, native valve endocarditis; PVE, prosthetic valve endocarditis.

&
mortality in native valves and PVE [70 ]. Addition-
ally, the endocarditis teams were associated with
improvement in management processes, such as
the duration of antibiotic therapy, time to targeted
antibiotic therapy, time to surgery, and time to
&
perform echocardiography [70 ].
CONCLUSION
IE is a life-threatening infectious complication that
requires high clinical suspicion and systematic clin-
ical laboratory investigation for its diagnosis. In
recent years, we have come across a new epidemi-
ology of the disease, related to cardiac devices that
are increasingly used routinely, which requires new
diagnostic investigations and clinical-surgical treat-
ment that takes these particularities into account. A
multidisciplinary approach is essential because of
the complexity of the various steps involved in
diagnosis and treatment. These steps include differ-
ent diagnostic techniques, selection of appropriate
antimicrobials, consideration of extracardiac com-
plications, and determination of the necessity and
timing of cardiac surgery.
Acknowledgements
None.
Financial support and sponsorship
None.

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Severe infections
Conflicts of interest
There are no conflicts of interest.
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