Infective Endocarditis in Icu

8/13/2019 Infective Endocarditis in Icu

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I n f e c t i v e E n d o c a rd i t i s i n t h eIntensive Care Unit

Yoav Keynan, MDa,b,c,*, Rohit Singal, MDd,e, Kanwal Kumar, MDd,Rakesh C. Arora, MD, PhDd,e,f,g, Ethan Rubinstein, MDa,b

The true incidence of endocarditis is difficult to estimate; various figures are based on

diverse study designs, settings, and variable case definitions. In developed countries,

the incidence is approximately 5 to 7.9 cases per 100,000 persons/y. An estimated

10,000 to 15,000 new cases of infective endocarditis (IE) are diagnosed in the United

States each year.1,2 These rates vary between geographic regions, and publications

regarding the epidemiology are affected by referral bias, with a tendency for reporting

from larger centers.3,4 In addition to the range of incidence rates, the underlying con-ditions such as rheumatic heart disease, injection drug use, prosthetic devices, and

Disclosures: The authors have nothing to disclose.a Department of Internal Medicine, University of Manitoba, Manitoba, Canada; b Departmentof Medical Microbiology, University of Manitoba, Manitoba, Canada; c Department of Commu-nity Health Sciences, University of Manitoba, Manitoba, Canada; d Department of Surgery, Uni-versity of Manitoba, Manitoba, Canada; e Manitoba Cardiac Sciences Program, University ofManitoba, Manitoba, Canada; f Department of Anesthesia, University of Manitoba, Manitoba,

Canada;

g

Department of Physiology, University of Manitoba, Manitoba, Canada* Corresponding author. Department of Internal Medicine, Medical Microbiology and Commu-nity Health Sciences, University of Manitoba, Rm 507, 745 Bannatyne Avenue, Winnipeg,Manitoba R3E 0J9, Canada.E-mail address: [email protected]

KEYWORDS

Endocarditis Diagnosis Infection site ICU Echocardiography

KEY POINTS

Infective endocarditis (IE) is a disease with many facets and various expressions depend-

ing on the site of infection, microorganism, underlying heart lesion, immune status of thehost, and remote effects such as emboli, organ dysfunction, and the general condition of

the host.

Diagnosis is the first crucial step, which depends on meticulous clinical examination,

blood cultures, results, and echocardiographic findings.

The management of the patient with endocarditis in the intensive care unit is complex and

needs a multidisciplinary team, including the intensivist, a cardiologist, an experienced

echocardiologist, an infectious diseases specialist, and a cardiac surgeon.

The medical and surgical management of such patients is complex, and timely decisions

are important.

Crit Care Clin 29 (2013) 923951http://dx.doi.org/10.1016/j.ccc.2013.06.011 criticalcare.theclinics.com0749-0704/13/$ see front matter 2013 Elsevier Inc. All rights reserved.
mailto:[email protected]://dx.doi.org/10.1016/j.ccc.2013.06.011http://criticalcare.theclinics.com/http://criticalcare.theclinics.com/http://dx.doi.org/10.1016/j.ccc.2013.06.011mailto:[email protected]


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immunosuppression have changed over time. The incidence seems to be increasing

because of greater number of indwelling devices and prosthetic materials and higher

levels of immune suppression.

IE is no longer commonly associated with rheumatic heart disease in developed

countries, and it is more common in older adults.57 In a study reporting 203 IE epi-

sodes among 193 patients,5 the median age was 67 years, one-third were nosocomial

and one-third involved a prosthetic valve. The other trend observed is the increase in

Staphylococcus aureus (SA), which may also be related to prosthetic devices. SA is

the most common pathogen associated with IE and has a predilection for individuals

with intravascular devices, hemodialysis, and diabetes.68 In a report of the results of

the ICE-PCS (International Collaboration on Endocarditis-Prospective Cohort Study),

patients in the United States were likely to be hemodialysis dependent, to have dia-

betes, to harbor an intravascular device and were more likely to be infected with

methicillin-resistant SA (MRSA), and to receive vancomycin.8 These underlying

comorbidities resulted in an increased severity of illness manifested as higher mortality

and higher incidence of embolic events and central nervous system (CNS) events, as

well as higher rates of surgery.6,7 A recent study noted a trend toward an increase in

SA and a significant increase in the subgroup of patients without known underlying

valvular disease.9 A population-based study reported an incidence of 33.8 cases

per million, highest among men aged 75 to 79 years, most of whom had no previously

identified predisposing heart disease. Staphylococci were the most common causal

agents, accounting for 36.2% of cases, and of those, SA accounted for more than a

quarter, whereas coagulase-negative staphylococci (CONS) caused nearly 10%.

Health careassociated IE accounted for 26.7% of cases. SA was the most important

factor associated with in-hospital mortality forinfections originating in the communityas well as for nosocomially acquired cases.10

IE can be caused by many microorganisms; however, staphylococci and strepto-

cocci account for most cases (Table 1).

The higher incidence of SA compared with viridans group streptococci (VGS) is

probably because this study was conducted in large tertiary-care centers, which

may not reflect the epidemiology of uncomplicated IE in rural settings. This hypothesis

is supported by a population-based survey using the Rochester Epidemiology Project

of Olmsted County, Minnesota, in which VGS were the most common cause.11 The

same group reported a more recent accumulation of 150 patients with IE, with VGS

accounting for 40% and SA for 26.7%.12

SA epidemiology is changing, with increasingincidence and prevalence of MRSA. The emergence of community-associated MRSA

Table 1

Cause of IE in 2781 patients with definite endocarditis from 25 countries, ICE-PCS

Causative Organism

Overall

Rate (%)

Native Valve (Excluding

Drug Abusers) (%)

Prosthetic

Valve (%)

SA 1743 (31) 28 23

VGS 926 (17) 21 12Enterococci 1013 (11) 11 12

CONS 713 (11) 9 17

Streptococcus bovisand other streptococci 815 14 10

Data fromMurdoch DR, Corey GR, Hoen B, et al. Clinical presentation, etiology, and outcome ofinfective endocarditis in the 21st century: the International Collaboration on Endocarditis-Prospective Cohort Study. Arch Intern Med 2009;169(5):466.

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and its invasion into hospitals created a mixture of distinct SA pathogens that are

capable of causing bacteremia and IE.

The rates of other causes vary greatly between geographic regions, with HACEK

organisms being uncommon inNorth America and Bartonella and Coxiella reported

mostly from centers in Europe.13 In the Middle East, Brucella is an important cause

of IE.14,15 The role of CONS is being increasingly appreciated, in part because of multi-

center studies providing an opportunity to study less frequent causative agents. In

recent multicenter studies, it has become the third most common causative agent

overall, with a growing appreciation as a pathogen in the context of native valve

IE.13,16 More cases of a more virulent CONS, Staphylococcus lugdunensis, have

been reported in recent years, and this frequent colonizer of the groin, perineum,

and long-term indwelling catheters has been shown to account for predominantly

native valve endocarditis (NVE), responsible for up to 18% of CONS endocarditis

cases.17,18

IE IN THE INTENSIVE CARE UNIT SETTING

It is difficult to estimate the proportion of patients with IE requiring admission to the

intensive care unit (ICU). Many of those requiring surgery go through the ICU at

some stage of their hospital admission. In addition, the associated cardiac and extrac-

ardiac complications of IE may necessitate management in the ICU setting. Among the

systemic complications are hemodynamic instability caused by sepsis, cardiogenic

shock or a combination of the 2, embolization of infected materials, with resulting

end-organ damage, sepsis, septic shock, and so forth. The causes for requiring ICU

admission were reported in a study of 4106 patients admitted to 4 medical ICUs, of

whom 33 had a complicated IE. More than half had IE diagnosed before ICU admission,whereas the remaining 15 were diagnosed while in the ICU. The most common reason

for ICU admission was congestive heart failure (CHF), in almost two-thirds of cases;

septic shock accounted for 21% cases and the third most common was neurologic

deterioration in 15%. Seventy-nine percent required mechanical ventilation, 73%

were on ionotropic support, and 39% suffered from renal failure, renal failure was

the only independent risk factor for mortality in a multivariate analysis.19 SA was the

most common causative agent.

NEUROLOGIC COMPLICATIONS

Neurologic complications of IE are common among patients with IE admitted to ICU.

The mechanisms that lead to these complications include embolic occlusion of cere-

bral arteries; cerebral hemorrhage; infection of the brain parenchyma (septic purulent

encephalitis) or meninges and mycotic aneurysms. Several of these complications

may be present together in a given patient and can be accompanied by sepsis-

related encephalopathy, leading to acute delirium and fluctuating level of conscious-

ness; these factors may make the diagnosis of focal neurologic deficits even more

difficult. Sonneville and colleagues20 recently reported a series of 198 left-sided IE

from 33 ICUs in France. Neurologic complications occurred in 55% of the patients.

These complications included, in order of frequency, ischemic strokes, cerebral hem-orrhages, meningitis, brain abscesses, and mycotic aneurysms. The risk factors for

these neurologic complications were SA as the cause of IE; mitral valve endocarditis;

and embolic events elsewhere. Meningitis is not uncommon and may be caused by

presence of bacteria in the cerebrospinal fluid (CSF) or represent an inflammatory

reaction to a nearby parenchymal infection or ischemia; it occurs in 2% to 20% of

patients with IE and up to 40% of those with neurologic complications. However, in

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most cases, the organisms are not recovered from the CSF because of absence, or

transient presence only, with the notable exception ofStreptococcus pneumoniae.

CNS embolization is frequent and may range from subclinical to catastrophic. The

incidence of neurologic embolic events complicating IE varies between series and is

probably higher among patients reported from referral centers, because they tend to

be overrepresented in large multicenter studies. The importance of CNS emboli is

shown by older studies of autopsies of patients succumbing to IE. In some, the pres-

ence of brain lesions is reported to occur in up to 90% of patients.21 In most series

that are based on clinical manifestations, CNS involvement during the course of IE oc-

curs in 20% to 40% of cases. In a Finnish teaching hospital, one-quarter of cases

were associated with neurologic complications, and SA was 2 to 3 times more likely

to be associated with their presence.22 A recent series from France reported lower

occurrence of strokes (17%) among 264 IE cases caused by staphylococci or strep-

tococci23; similar rates were observed among 513 episodes of complicated, left-sided

native valve IE, from the United States.24 In the ICE database,13 which reported on

2781 patients from 58 hospitals in 25 countries, identical incidence of strokes was

found. The use of computed tomography (CT) or magnetic resonance imaging (MRI)

results in detection of some clinically silent embolic events. A study from France25

identified cerebrovascular complications in 22.2% of patients with IE. CT led to iden-

tification of 17 (3.8%) additional unsuspected emboli (453 CT scans, 496 patients).

Even more dramatic discrepancies were reported by Cooper and colleagues,26 who

studied 56 patients with definite left-sided IE. Clinical stroke was present in 25%.

Forty patients underwent MRI, and the incidence rates of subclinical brain emboliza-

tion and acute brain embolization were 48% and 80%, respectively. Patients with any

stroke (clinical and subclinical) were more likely to have IE caused by SA (56% vs13%). Some rarer pathogens such asStreptococcus agalactiaeand fungi are associ-

ated with even higher rates of systemic and CNS embolization, attributed to the larger

vegetation size that they cause. Although these pathogens lead to a higher proportion

of embolic complications, because of their relative rarity, they account for a smaller

absolute number.27,28 The proportion of neurologic events is increased among individ-

uals with IE requiring admission to the ICU as a result of selection of more severe

cases with higher rates of comorbid conditions. The initiation of appropriate antimi-

crobial therapy leads to a precipitous decline in embolic complications evident as

early as after the first week of therapy,29 with further decreases in incidence in the

ensuing weeks.

THE ROLE OF ECHOCARDIOGRAPHY IN DIAGNOSIS AND MANAGEMENT OF IE

Echocardiography is a cornerstone in the diagnosis of IE. Both the American Society

of Echocardiography30 and the European Association of Echocardiography31 have

provided guidelines for the appropriate use of transthoracic echocardiography (TTE)

or transesophageal (TEE) echocardiography in patients with suspected IE. Echocardi-

ography must be performed early in patients with suspected IE. Echocardiography is

the preferred imaging modality to detect vegetations on cardiac valves and show

lesions as small as 1 to 2 mm. In addition, two-dimensional imaging can showintracardiac abscesses and with the use of color Doppler, abnormal blood flow

patterns (Box 1).

TTE OR TEE?

Both TTE and TEE have a role in the diagnosis of IE. Because of the noninvasive nature

of TTE, it is the first-line technique, because it can provide useful information on the

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diagnosis and severity of the disease.32 TTE generally has a lower sensitivity

compared with TEE (46% vs 93%); however, both are highly specific (95% vs

96%).33A good-quality, negative TTE examination and a low clinical index of suspicion

of IE should prompt clinicians to seek alternate diagnosis. However, an equivocal (ie,

suboptimal examination) or a negative TTE examination in the setting of high pretest

probability (ie, positive blood cultures, type of organism, presence of known IE riskfactors, or new murmur) does not exclude the diagnosis of IE. TEE is required to

show the cardiac lesion(s) consistent with IE and to further characterize the extent

of perivalvular disease (ie, severity of regurgitation, valve leaflet perforation, aneurysm,

and abscess formation). Furthermore, even with positive TTE, examining the extent of

disease by the TEE may assist the surgical team in planning their operative manage-

ment. An algorithm for suggested use of TTE/TEE is shown in Fig. 1. The use of TTE in

patients admitted to the ICU may be even less sensitive because of the need of me-

chanical ventilation and suboptimal positioning of the patient for examination. In a

multicenter review of echocardiographic examination in ICU patients,34 TTE was

diagnostic in only 33% and a subsequent TEE was required in 91% to confirm the

diagnosis or fully to delineate the extent of disease. Others have reported sensitivity

of TTE and TEE for endocarditis detection is 58% to 62% and 88% to 98%,

respectively.35,36

The presence of prosthetic heart valve, particularly mechanical valves, can make

the visualization more challenging, particularly with examination performed by the

transthoracic technique. A study by Palraj and colleagues37 reported the poor sensi-

tivity (


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potential progression of vegetation may be warranted depending on the clinical status

of the patient. Second, an echocardiographic false-positive diagnosis of IE may occur

in certain patients. Examples of potential confounders include variants of normalcardiac structures (ie, Lambl excrescences), noninfective lesions (ie, marantic endo-

carditis), or cardiac tumors. It is not possible to echographically distinguish infective

from noninfective lesions, and repeat echocardiographic examination needs to be

considered on an individual basis.

SUPPORTIVE AND ANTIMICROBIAL MANAGEMENT

The reader is also referred to articles by Keynan and colleagues elsewhere in this issue

dealing with specific organisms. IE, which was formerly an invariably fatal disease, is

associated with a 20% mortality. In IE caused by virulent organisms like SA, the mor-tality is still w30%, with many of the patients dying during their first hospitalization.8

CRITICAL CARE MANAGEMENT

Patients with IE can progress to critical illness requiring an admission to an ICU.

Diligent clinical assessment, augmented with continuous invasive, and noninvasive

ICU monitoring, are the cornerstones to effective management. Standard continuous

monitoring includes electrocardiography, arterial pressure, and pulse oximetry. Al-

though the use of pulmonary artery catheters remains of uncertain benefit,3740 central

venous monitoring may be of value in central venous gas assessment and guiding fluidadministration.41

Mourvillier and colleagues42 reported a larger retrospective review of 228 consecu-

tive patients meeting the Duke criteria for IE admitted to 2 regional, tertiary ICUs from

1993 to 2000. Approximately 64% of these patients (n 5 146) suffered from NVE, with

the remaining patients (n 5 82) admitted with PVE. Approximately 50% of patients

with NVE and 40% of patients with PVE were managed medically. SA was the most

Fig. 1. An algorithm for the use of echocardiography in the diagnosis and assessment ofextensiveness of IE disease; *denotes the need to consider additional TEE on the individualbasis of the clinical context of the patient. (Adapted fromHabib G, Badano L, Tribouilloy C,et al. Recommendations for the practice of echocardiography in infective endocarditis. Eur JEchocardiogr 2010;11(2):203; with permission.)

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common cultured microbe (50%). Significant complications occurred frequently, with

neurologic injury being the most frequent (40% of cases). The overall mortality was

high in this cohort, at 45% (108/228). Clinical factors in patients with NVE who were

independently associated with in-hospital mortality included (in descending strength

of association) septic shock (odds ratio [OR] 4.81), cerebral emboli (OR 3.00), and

immunocompromised state (OR 2.88). The investigators emphasized that cardiac

surgery was protective (OR 0.475). In patients with prosthetic valve IE, the factors

associated with mortality were septic shock (OR 4.07), neurologic complications

(OR 3.1), and immunocompromised state (3.46), with higher survival rates with surgery

compared with medical management alone.

TREATING SEVERE SEPSIS OR SEPTIC SHOCK IN THE PATIENT WITH IE

The patient with IE who is admitted to ICU requires prompt and protocolized care to

maximize survival. In 2008, the update to the international guidelines for management

of severe sepsis and septic shock provided the contemporary framework for manage-ment of patients with IE requiring admission to the ICU.43 The key principles are: (1)

Goal-directed resuscitation; (2) Diagnosis, including echo; (3) initiation of appropriate

antimicrobial therapy; and (4) source control.

Goal-directed resuscitation: the current recommendation is that hypotension is

treated aggressively once hypoperfusion is recognized. During the initial first 6 hours

of resuscitation, the clinician should seek to achieve all of the following hemodynamic

and clinical goals44:

Central venous pressure 8 to 12 mm Hg

Mean arterial pressure 65 mm Hg Urine output 0.5 mL/kg/h

Central venous (superior vena cava) or mixed venous oxygen saturation 70% or

65%, respectively.45

The early initiation of antimicrobial therapy42 and surgical consideration of repair/

replacement of infected cardiac valves are necessary to improve outcomes in patients

with IE.46

NATURAL VALVE IE

Results of blood cultures for accurate diagnosis are usually available within 1 to 3 days.Blood cultures are positive in most patients, and empirical antibiotic therapy should be

administered only after at least 2 (preferably 3) sets of blood cultures have been

obtained from separate venipunctures, and ideally spaced over 30 to 60 minutes.

Empirical therapy pending blood culture results should cover methicillin-susceptible

SA (MSSA) and MRSA as well as streptococci and enterococci. Appropriate agents

are either vancomycin 30 mg/kg/24 h in 2 divided doses or a single daily dose of

daptomycin 10 to 12 mg/kg. Most patients become afebrile within 3 to 5 days of appro-

priate therapy. Patients with SA IE may remain febrile for 5 to 7 days. Right-sided

endocarditis with septic pulmonary emboli can lead to a longer febrile period. The initial

microbiologic response to therapy should be assessed by repeat blood cultures 48 to72 hours after antibiotics are begun. Thereafter, regular examinations should be per-

formed to search for heart failure, emboli, and other complications. The length of

therapy for patients with native valve IE depends on the organism and valve involved

as well as on the presence of complications. Two-week therapy is suitable for patients

with right-sided endocarditis and for patients with highly susceptible VGS (minimum

inhibitory concentration [MIC]


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combination therapy. Most other patients are treated with 4 to 6 weeks of intravenous

(IV) therapy. Patients with complications or when therapy has started late benefit from

prolonged courses of IV therapy (6 weeks).

Combination therapy using a b-lactam agent, such as penicillin, with an aminoglyco-

side has been shown to be highly effective in streptococcal and enterococcal endo-

carditis, and of equivocal efficacy in patients with staphylococcal endocarditis.

Combination therapy with a penicillin and an aminoglycoside or ceftriaxone and an

aminoglycoside for 2 weeks is highly effective in carefully selected patients with Strep-

tococcus viridansendocarditis.47

Combination therapy with nafcillin or oxacillin or cloxacillin and an aminoglycoside

for 2 weeks has been shown to be effective in patients with right-sided endocarditis

caused by SA.6 In contrast, combined therapy with vancomycin and an aminoglyco-

side administered for 2 weeks does not seem to be effective in these patients. In

addition, combined therapy with nafcillin and an aminoglycoside is not effective in

left-sided endocarditis if treatment is given for only 2 weeks.48

VIRIDANS STREPTOCOCCI AND STREPTOCOCCUS GALLOLYTICUS (FORMERLYSTREPTOCOCCUS BOVIS)

Members of the viridans group (VGS) are responsible for half of all community-

acquired mitral valve endocarditis; other members of the VGS include Streptococcus

mitis, Streptococcus mutans, Streptococcus oralis, Streptococcus sanguinis, Strepto-

coccus sobrinus, and the Streptococcus milleri group (Streptococcus anginosus,

Streptococcus constellatus, and Streptococcus intermedius). Most VGS are highly

penicillin susceptible, defined as an MIC of 0.12 mg/mL or less. Occasional strainshave intermediate susceptibility to penicillin (MIC >0.12 mg/mL and 0.5 mg/mL),

and rare strains are considered to be fully resistant, with a penicillin MIC greater

than 0.5 mg/mL. For the VGS and Streptococcus gallolyticus IE treatment consists

of crystalline penicillin G 12 to 18 million units/24 h divided into 4 or 6 equal doses

for 4 weeks if the causative pathogen has an MIC less than 0.12 mg/mL. Ceftriaxone

2 g IV/24 h can substitute penicillin for the same treatment duration.

Penicillin-allergic patients can usually be treated with ceftriaxone, if their penicillin

allergy consists of rash without other signs of immediate-type hypersensitivity. Pa-

tients with histories of immediate-type hypersensitivity may either be treated with van-

comycin or desensitized to penicillin and treated with a standard regimen. Oncepenicillin therapy is stopped for more than 24 hours in desensitized patients, repeat

desensitization is required. In patients with streptococcal endocarditis and a history

of significant penicillin allergy, a combination of gentamicin with vancomycin (or teico-

planin) can be used.

For treatment of streptococci with intermediate penicillin susceptibility (MIC0.12

and0.5 mg/mL), and for nutritionally deficient streptococci, 24 million units daily either

continuously or in 4 to 6 equally divided doses) or ceftriaxone (2 g IV or intramuscularly

once daily) for a total of 4 weeks should be used, gentamicin should be added to this

regimen for the first 2 weeks.49 IE caused by strains of VGS and streptococcallike or-

ganisms (eg, Abiotrophia defectiva, Granulicatella spp, and Gemella spp) that havepenicillin MICs greater than 1 mg/mL are considered fully resistant to penicillin and

should be treated with regimens used to treat enterococcal endocarditis. Other strep-

tococcal species (eg, groups A, B, C, and G, andStreptococcus pneumoniae) should

be treated according to their susceptibility; most of these strains are highly susceptible

to penicillin, and an infectious diseases consultation is needed in such cases. Some

strains of group B, C, and G streptococci are more resistant to penicillin than

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Streptococcus pyogenes. Therefore, adding gentamicin to a penicillin or cephalo-

sporin for the first 2 weeks of a 4-week to 6-week course of therapy is recommended.50

Pneumococcal IE is usually fulminant and causes severe valve damage, and

embolic complications, valve perforation, and ring abscess are frequently detected.51

In penicillin-susceptible strains, high-dose penicillin (24 million/24 h) is recommended.

In other strains, therapy is similar to intermediate and resistant streptococci.

ENTEROCOCCAL IE

Members of the genus Enterococcusare all resistant to low concentrations of peni-

cillin. They are also relatively resistant to expanded spectrum penicillins (eg, ampi-

cillin, piperacillin), as well as to the cephalosporins. In addition, they are typically

resistant to aminoglycosides at concentrations achieved using standard dosing reg-

imens. However, many strains of enterococci are killed if penicillin, ampicillin, or

vancomycin, which exert only bacteriostatic activity, are combined with an amino-

glycoside such as gentamicin, the combination being bactericidal. However, thereare exceptions to this suggested therapy: some enterococci produce b-lactamase,

rendering them b-lactam resistant; others may have high-level resistance to amino-

glycosides (>1000 mg/mL), rendering them resistant to the cidal activity of the com-

bination. Some strains are vancomycin resistant; for more details the reader is

referred to the article on vancomycin-resistant enterococci (VRE) elsewhere in this

issue.

Most cases of enterococcal IE are caused by Enterococcus faecalis. Therapy forE

faecalis with low-level penicillin resistance consists of a combination of IV aqueous

penicillin G, or ampicillin, plus gentamicin. In penicillin-allergic patients, penicillin

should be substituted with vancomycin administered together with gentamicin.Gentamicin should be given in patients with normal renal function in a dose of

1 mg/kg every 8 hours to achieve peak levels of 3 to 4 mg/mL. Although ampicillin is

slightly more active than penicillin against E faecalis, clinical trials do not favor the

use of ampicillin for enterococcal IE, because its use is associated with a higher

rate of adverse events (mainly rash) than is penicillin. Antibiotic combination therapy

should be administered for 4 weeks. Patients with a history of penicillin allergy should

be treated with a combination of vancomycin (30 mg/kg/d) and gentamicin (3 mg/kg/d)

for 6 weeks or considered for desensitization. The reason for longer therapy with the

vancomycin combination is the decreased activity of vancomycin against enterococci,

compared with penicillin.36 Enterococcal IE caused by strains that are susceptible to

penicillin, vancomycin, and streptomycin but resistant to gentamicin can be treated

with ampicillin or penicillin plus streptomycin (15 mg/kg/d in 2 equally divided doses).

Patients who have enterococcal IE caused by ampicillin-susceptible (MIC 4 mg/L)

and high-level gentamicin and streptomycin resistance (MIC >128 mg/L) may be

treated with high-dose ampicillin monotherapy. Enterococcal IE caused by strains

with intrinsic high-level penicillin resistance (MIC >16 mg/mL) can be treated with a

combination of gentamicin plus either ampicillin-sulbactam (12 g per day in 4 equally

divided doses) (if the resistance is b-lactamase mediated) or vancomycin (30 mg/kg

daily given IV in 2 divided doses) for 6 weeks. IE caused by VRE is limited to isolatedcase reports; in such cases, an infectious diseases consult is needed. The reader is

also referred to the article on VRE elsewhere in this issue.

STAPHYLOCOCCAL IE

For a more detailed discussion of staphylococcal infections, the reader is referred to

the relevant article elsewhere in this issue.



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MSSA

NVE caused by MSSA is best treated with a semisynthetic penicillin, such as nafcillin,

oxacillin, or flucloxacillin (12 g per day IV in 4 to 6 equally divided doses). Aminogly-

cosides should not be combined routinely with antistaphylococcal penicillins,

vancomycin, or daptomycin for treatment of SA bacteremia. Although in vitro andexperimental models of endocarditis have shown that combination therapy facilitates

more rapid killing of MSSA than monotherapy, the evidence for clinically significant

benefit is minimal and the potential for renal toxicity is substantial.52,53 In adults,

6 weeks of therapy is recommended for complicated right-sided IE and for all left-

sided IE; complicated IE is defined as metastatic infections or when the course is

otherwise complicated by secondary cardiac problems (eg, heart failure). In patients

with uncomplicated right-sided IE, the duration of therapy is 2 weeks if synergistic

therapy can be given. In children, 6 weeks of therapy is recommended regardless

of the site of infection or presence of complications. Patients allergic to penicillin

can be treated with a first-generation cephalosporin, such as cefazolin (2 g IV every8 hours), if there is no previous history of penicillin reaction that is typical of an

immediate-type allergy. Vancomycin and daptomycin are acceptable alternatives in

patients with immediate-type penicillin allergy; however, in MSSA, vancomycin is a

less effective antistaphylococcal antibiotic.49,54 Clindamycin and macrolides are

not acceptable alternatives, because the clinical relapse rate is high.49

Selected patients with native valve right-sided endocarditis caused by SA with no

evidence of renal failure, extrapulmonary metastatic infections, or simultaneous left-

sided valvular infection, may be successfully treated with 2-week regimens using

the combination of nafcillin/methicillin/oxacillin and gentamicin. Regimens that substi-

tute vancomycin or teicoplanin for nafcillin (eg, for penicillin-allergic patients) are notconsidered to be reliably effective if only 2 weeks of therapy are given.55

MRSA IE

The reader is referred to the article dealing with MRSA infections elsewhere in this

issue. NVE caused by either MRSA or CONS should be treated with vancomycin for

6 weeks. Gentamicin should not be combined with vancomycin for MRSA native valve

IE. The addition of rifampin to vancomycin has not been proved to be clinically bene-

ficial. Daptomycin is an acceptable alternative to vancomycin.56 In a randomized trial

of 246 patients, daptomycin (6 mg/kg IV per day) was not inferior to standard therapyfor SA bacteremia or right-sided endocarditis. Daptomycin resistance (MIC2 mg/mL)

developed in 6 patients. Randomized controlled trials of the effectiveness of linezolid,

telavancin, and quinupristin-dalfopristin in humans with IE have not yet been published

but isolated case reports have reported clinical success.5759

CONS

Treatment regimens for CONS are identical to those for coagulase-positive staphylo-

cocci. Most strains of CONS are methicillin resistant.

HACEK ORGANISMS

Organisms in this category include Haemophilus aphrophilus, Actinobacillus actino-

mycetemcomitans (subsequently called Aggregatibacter actinomycetemcomitans),

Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae. They usually

grow late in blood culture media and are responsible for 5% to 10% of IE cases. Treat-

ment of IE caused by these organisms should be 4 weeks of ceftriaxone.

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CULTURE-NEGATIVE ENDOCARDITIS

The main reasons for culture-negative endocarditis are previous administration of anti-

microbial agents, inadequate microbiological techniques, and infection with highly

fastidious bacteria (eg,Coxiella burnetti, Brucellae, Tropheryma whippelii), nonbacte-

rial pathogens (eg, fungi), or noninfectious causes. Empirical treatment of patients withculture-negative endocarditis should provide coverage for both gram-positive and

gram-negative organisms.

PVE

For optimal management of PVE a regimen with proven efficacy combined with under-

standing of the underlying cardiac disease are necessary. Surgical interventions are

frequently required in the context of complications, especially when infection extends

beyond the valve. Patients with hemodynamic instability or acute disease should

receive empirical antibiotics promptly after 3 sets of blood cultures have been ob-tained. Empirical antibiotic therapy should include vancomycin, gentamicin, and either

cefepime or a carbapenem. Subsequent therapy should be adjusted based on culture

results; if cultures remain negative, therapy as outlined for culture-negative PVE

should be used. The length of therapy for PVE has not been studied, but experts agree

that 6 weeks of therapy are needed.

STAPHYLOCOCCAL PVE

Antimicrobial treatment requires combination therapy. Major organizations (American

Heart Association [AHA] and the European Society of Cardiology [ESC]) recommend a

triple-drug regimen.

Nafcillin (or oxacillin) is the mainstay of therapy for isolates susceptible to methicillin

(MSSA). If the organism is susceptible to gentamicin, this should be the second agent,

with rifampin as the third agent. The aminoglycoside should be administered for the

initial 2 weeks of treatment, and the remaining 2 agents continued for at least 4 additional

weeks. If a fluoroquinolone is used in lieu of an aminoglycoside, the 3-drug regimen

should continue for the course of treatment. When the isolate is resistant to all aminogly-

cosides and fluoroquinolones, linezolid, ceftaroline, or trimethoprim-sulfamethoxazole

could be considered as a third drug for the initial 2 weeks of therapy.60,61

If breakthrough bacteremia or microbiologic failure occurs in patients receiving

vancomycin, the isolate recovered should be tested for the development of both

vancomycin and daptomycin resistance.

Optimal therapy for PVE caused by MRSA with reduced vancomycin susceptibility,

or when failing vancomycin therapy, has not been established. High-dose daptomycin

(if the isolate remains daptomycin susceptible), telavancin, ceftaroline, and linezolid is

often used, although clinical experience in the treatment of PVE is limited.

Rifampin has the unique ability to kill staphylococci that are adherent to foreign ma-

terial, and therefore is an essential component of the treatment of staphylococcal PVE.

However, resistance to rifampin may develop during therapy, and toxicity may be sig-

nificant. Susceptibility to rifampin should be reassessed when regimens containingrifampin fail.62

STREPTOCOCCAL PVE

Combination therapy with a b-lactam antibiotic and an aminoglycoside (if the isolate

does not show high-level resistance to the aminoglycoside) is the preferred regimen

for streptococcal PVE. Treatment is as delineated for native valve IE.



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ENTEROCOCCI

Treatment of enterococcal PVE requires the synergistic interaction of a cell wall active

agent (penicillin, ampicillin, or vancomycin) and an aminoglycoside in order to achieve

a synergistic effect. The organisms should be tested for high-level aminoglycoside

resistance. Cephalosporins are not active against enterococci and do not providebactericidal synergy when combined with an aminoglycoside. If the enterococcus

isolate has high-level resistance to streptomycin and gentamicin, synergy is not

feasible, and an aminoglycoside should not be administered. In these cases, a pro-

longed course of 8 to 12 weeks ofb-lactam or vancomycin should be administered

instead, but few cases are clinically successful. In such cases, the combination of

ampicillin (2 g every 4 hours) and ceftriaxone (2 g every 12 hours) for 6 weeks yielded

acceptable clinical results in nonprosthetic valve infections with these organisms.63 In

the setting of progressive nephrotoxicity, the duration of aminoglycoside administra-

tion may be reduced to less than 6 weeks with no decrease in cure rates.64

In PVE caused by vancomycin-resistantE faecium(VRE), organisms that are oftenalso resistant to penicillin and ampicillin, and highly resistant to gentamicin and strep-

tomycin, treatment options are few. The reader is referred to the article on VRE else-

where in this supplement. Surgical intervention during suppressive bacteriostatic

therapy should be strongly considered when PVE is caused by highly resistant

enterococci.

HACEK

See earlier discussion in the natural valve endocarditis section.

CORYNEBACTERIA (DIPHTHEROIDS)

If the strain is susceptible to gentamicin (MIC


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CULTURE-NEGATIVE

With onset within the first year after valve surgery, therapy should include vancomycin,

gentamicin, cefepime, and rifampin.49 For initial therapy for PVE with onset greater

than 1 year after surgery, the recommended treatment is with ampicillin-sulbactam

plus gentamicin or vancomycin, gentamicin, and ciprofloxacin.1,49,50

For patientswith onset of PVE more than 12 months after valve implantation in whom Bartonella

is suspected, treatment with ceftriaxone, gentamicin, and doxycycline should be

administered.49 If unexplained fever persists in the face of empirical therapy, surgery

to obtain a vegetation for microbiological evaluation should be considered (for

Coxiella,Bartonella, Trephomyra, and so forth).

INDICATIONS AND APPROACH TO THE SURGICAL MANAGEMENT OF IE

Surgical management of IE is challenging for the entire multidisciplinary team. One of

the most important considerations in management of IE relates to the indications forand timing of surgical intervention. The primary indications for surgical intervention

during antibiotic treatment of endocarditis (considered the active phase) relate to

prevention of deterioration as a result of worsening CHF, systemic embolism, or uncon-

trolled infection. The principles of surgical therapy involve the widespread debridement

of infected tissues with subsequent reconstruction and valve replacement. Choice of

prosthesis and the possibility of repair need to be planned, and in the cases of signif-

icant destruction, complex reconstruction may be required.

Indications for Surgical Intervention

The latest comprehensive guidelines addressing surgical intervention come from theAmerican College of Cardiology (ACC)/AHA and the ESC.70,71 The indications in these

documents are classified as I, II (a or b), and III according to the well-accepted system

of assessing relative usefulness (of the intervention) from supportive literature.

The guidelines are reasonably matched in their assessment of class I indications for

surgical intervention in IE (Table 2). The ESC guidelines are more explicit in their

breakdown of the recommendations into 3 categories of consideration, which include

heart failure, uncontrolled infection, and prevention of embolism. Furthermore, the

ESC guidelines assign a relative urgency to the indications, which include emergent

(surgery within 24 hours), urgent (surgery within a few days), and elective (surgery after

1 to 2 weeks of antibiotic therapy). The ACC/AHA guidelines do not address timing.Multiple publications have shown thatCHF is themost important predictor of mor-

tality both in-hospital and at 6 months.7,24,49,7274 Higher levels ofbrain natriuretic

peptide and troponin have been correlated with mortality as well.75 The presence of

heart failure is a class I indication in both sets of guidelines. The ESC suggests that

refractory pulmonary edema or shock constitute emergencies in terms of timing.

Furthermore, the ESC guidelines consider severe valve dysfunction without heart

failure to be a IIa indication for surgery. This subject is not mentioned in the ACC/

AHA guidelines. There is reasonable evidence to suggest that surgical intervention

carries a better prognosis for patients with CHF in IE compared with nonsurgical man-

agement, and it is the most common indication for surgical intervention, occurring60% to 70% of the time.74,7680

Periannular extension of IE can lead to many complications involving the destruction

of surrounding tissues, including abscess formation, pseudoaneurysms, fistulae, and

heart block.8183 Periannular extension and fistulas are more common in PVE than in

native valve IE, and in the aortic valve compared with the mitral.49,8385 Mortality for

patients with periannular extension is high at 40%, even with surgery.84,86 Both sets



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of guidelines list uncontrolled infection by way of annular abscess, destructive, or

penetrating lesions as class I indications for surgical intervention; however, the ESC

guidelines address persistent fever and positive blood cultures (>710 days) in this

category as well. Recently, an association between persistently positive blood cul-

tures at 48 to 72 hours and poorer survival has been observed.87 In such patients, it

is reasonable to diagnose and treat extracardiac infection (eg. septic joint, indwelling

lines) in case the persistent sepsis is on this basis; however, if vegetations are

increasing in size, heart block develops, or new abscesses or other periannular abnor-

malities develop, the source of the ongoing sepsis is likely uncontrolled intracardiacinfection.1,88 TEE has been shown to be the best imaging modality for detection of

these locally destructive complications of IE, especially when compared with TTE;

however, TEE is still not 100% sensitive for detection of abscesses, particularly of

the mitral valve.85,8992

Fungal or multiresistant organisms are considered to be class I indications for inter-

vention. An analysis of 270 cases of fungal endocarditis over 30 years showed a

Table 2

Indications for surgical intervention in IE according to the latest ESC and ACC/AHA guidelines

Indication for Surgical Intervention

Guidelines

Timing (ESC Only)ACC/AHA ESC

Heart failure indications

Refractory pulmonary edema or cardiogenicshock as a result of aortic or mitral IE causingsevere acute valve regurgitation, valveobstruction, or fistula into a cardiac chamber

X X Emergency

Persisting heart failure or echocardiographic signsof poor hemodynamic tolerance as a result ofaortic or mitral IE, causing severe acuteregurgitation or valve obstruction

X X Urgent

Uncontrolled infection

IE complicated by heart block, annular, or aorticabscess or destructive penetrating lesions (eg,fistula, false aneurysm)a

X X Urgent

IE with persisting fever and positive bloodcultures >710 d

X Urgent

IE caused by fungi or multiresistant organisms X X Urgent/elective

Prevention of embolism

Aortic or mitral IE with large vegetations(>10 mm) after 1 embolic episodes despiteappropriate antibiotic therapyb

X Urgent

a Heart block not specified by ESC guidelines.b Class IIa recommendation in ACC/AHA guidelines.

Data fromBonow RO, Carabello BA, Chatterjee K, et al. 2008 focused update incorporated intothe ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a reportof the American College of Cardiology/American Heart Association Task Force on Practice Guide-lines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients WithValvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society forCardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation2008;118(15):e596; and Vahanian A, Alfieri O, Andreotti F, et al. Guidelines on the managementof valvular heart disease (version 2012): the Joint Task Force on the Management of Valvular HeartDisease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur J Cardiothorac Surg 2012;42(4):S144.

Keynan et al936


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mortality of 72%.93 Improved survival rates are associated with combined surgical-

antifungal treatment. Thus surgical intervention is a standard in management of fungal

IE.94,95 Multidrug-resistant organisms such as MRSA and VRE require surgical inter-

vention because of the inadequacy of antimicrobial treatment.1,88 SA infections are

virulent, destructive, and associated with mortality of 30% to 40% and therefore

should be considered for early surgical intervention.77,9698

Risk, outcome, and prevention of embolism is a subject of great importance, likely

as a result of the greater level of equipoise of how and when to intervene for this indi-

cation when compared with CHF and periannular destruction. Embolic events occur in

22% to 50% of cases of IE, most commonly affect the CNS, and are associated with

increased mortality.22,25,72,99103 The most consistent and powerful predictor of risk of

embolism is the size of vegetation, which, when greater than 10 mm in diameter, are

associated with higher rates of embolism.72,91,104107 One study further stratifies a

higher incidence of embolism in 83% of patients with highly mobile vegetations of

greater than 15 mm compared with 60% in patients with vegetations greater than

10 mm.99 Other predictors of embolism include mitral location, enlarging vegetations

despite antibiotics and SA or Streptococcus gallolyticus organism.22,72,91,102,105,108,109

In particular, the risk decreases markedly from the first week to after the

second week.22,72 This situation was best identified by the ICE-PCS multicenter study

analyzing 1437 consecutive patients with left-sided endocarditis, which showed that

the incidence of embolism on appropriate antibiotics dropped from 4.82 per 1000 pa-

tient days in the first week to 1.71 per 1000 days in the second week and continued to

decrease after that.29 The ESC guidelines clearly categorize the presence of vegeta-

tions larger than 10 mm in the setting of 1 or more embolic episodes despite antibiotic

therapy as a class I indication for surgery, whereas this is classified as class IIa in theACC/AHA guidelines. Both sets consider large vegetations without clinical embolism

to constitute a class IIb indication (the ESC use 15 mm, whereas the ACC/AHA use

10 mm). This situation has remained as a class IIb recommendation because of

studies such as ICE and others, which have shown that antimicrobial therapy is an

important mainstay in prevention of embolism. One can best conclude that surgery

for prevention of embolism is likely to be most effective early in high-risk cases, as

further discussed in the following section on timing.

Timing of Surgical Intervention

As surgery became an important tool in the treatment of endocarditis, multiple obser-vational series were published that reported that patients who were operated on in an

earlier time frame had better outcomes; these reports are subject to the biases

inherent in analyses of retrospective cohorts.77,110112 Statistical methods including

propensity matching and correction for all biases have been used to help answer

the question.43,76,78,113118 These methods have been reviewed in 2 recent publica-

tions (Table 3); the impact of (early) surgery was positive in 5 studies and not beneficial

in the other 4.119,120 Both reviews conclude, based on analysis performed in the last

3 propensity studies, that the conflicting results of the earlier studies are most likely

a result of differences in statistical methods and failure to account for all the biases.

The largest and most recent of these studies is a multicenter analysis of 1238 patientsin the propensity-matched model, with maximum accounting for selection, treatment,

survivorship, and hidden biases, which found that early surgery conferred an in-

hospital mortality benefit (absolute risk reduction 10.9%).113 Benefits were most pro-

nounced in the patients with the highest propensity for systemic embolization, SA

infection, and stroke and seem to be derived mostly from patients in whom there is

less controversy about the need for urgent surgery. Therefore, although the notion



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Table 3

Review of studies examining the impact of early surgery on the prognosis of IE

Reference

Inclusion

Period Population

Number of

Patients

Proportion

Operated (%)

Outcome

Measured Bias Adjuste

Vikram et al,81

200319901999 Complicated,

left-sided NVE513; 218

propensity-matched

45 6-mo all-causemortality

Treatment sebias

Mourvillieret al,42 2004

19931999 NVE or PVEhospitalized inan ICU

228 NVE; 54propensity-matched

46 In-hospitalmortality

Treatment sebias

Cabellet al,119 2005

19851999 NVE 1516; 1497in thepropensitygroups


Treatment sebias

Wang et al,120

200519851999 PVE 355; 136

propensity-matched


Treatment sebias

Aksoy et al,83

200719962002 Left-sided NVE or

PVE withoutintracardiacdevice

333; 102propensity-matched

23 5-y all-causemortality

Treatment sebias


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Tleyjehet al,118

2007

19801998 Left-sided NVE orPVE

546; 186propensity-matched

24 6-mo all-causemortality

Treatment sebias; surviv

Bannayet al,117 2011

1999 Left-sided NVE orPVE

449 53 5-y all-causemortality

Treatment sebias; surviv

Sy et al,116

200919962006 Left-sided NVE or

PVE223 28 5.2-y all-cause

mortalityTreatment se

bias; surviv

Lalaniet al,115 2010

20002005 NVE 1552; 1238in thepropensitygroups


Treatment sebias; survivhidden bia

Abbreviations:?, not available;ARR, absolute risk reduction; CI, confidence interval; HR, hazard ratio.Data from Refs.42,76,78,113118; and Adapted from Delahaye F. Is early surgery beneficial in infective endocard

2011;104(1):37, with permission.


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of early surgery for endocarditis is supported by these analyses, their statistical ac-

counting does not generate data as robust as would be seen from a randomized

controlled trial.

In 2012, Kang and colleagues49 published Early surgery versus conventional treat-

ment for infective endocarditis, a randomized controlled trial in which patients with

left-sided endocarditis, severe valve disease, and large vegetations (>10 mm) either

underwent urgent early surgery (within 48 hours, 37 patients) or conventional treat-

ment (39 patients). The primary end point was a composite of in-hospital death and

embolic events occurring within 6 weeks of randomization. The major finding of the

study was an arrival at the end point in 23% of the conventional patients versus in

only 3% of the early surgery group. There was no difference in death, and the major

finding was driven by clinical embolic events. The investigators are careful not to

use their findings as justification for a recommendation for early surgery in the broader

population. This caveat is fair considering that the study was small, not blinded, did

not use systematic imaging in both groups (relying only clinical determination), did

not provide long-term disability or quality-of-life data, and 77% of patients in the con-

trol group required surgical intervention for complications of endocarditis or ongoing

symptoms. This last point suggests that, although the population fits a IIa or IIb recom-

mendation by the guidelines, they were a sick population, in whom some centers

would already be inclined to intervene.1,70 Decisions regarding the approach to large

vegetation size are confounded by the other important inclusion criterion; severe

valvular dysfunction. The timing of surgery with respect to patients having recent ce-

rebrovascular accidents (CVAs) is particularly challenging. Embolism on its own con-

fers an indication for surgery (if secondary to embolic phenomena) and yet raises a

concern for exacerbation or worsening of the neurologic status with surgery. In partic-ular, the massive dose of heparin required during surgery creates a concern about

hemorrhagic transformation of these lesions, but cardiac operations in general create

opportunities for additional injury to the vulnerable brain.49,121 Most groups would

attempt to wait 4weeks in the case of intracranial hemorrhage but ischemic events

are less clear.122 This situation is reflected in the literature: some groups have advo-

cated for early surgery based on their case series,whereas other groups have sug-

gested a waiting period of 2 to 4 weeks.72,123126 These studies are all limited by

their small numbers and retrospective nature and do not always use a time-

dependent analysis. For example, Thuny and colleagues reported a neurologic dete-

rioration in only 6% of patients (total 63 patients) with symptomatic CVAs in whom themedian time to surgery was 9 days, but the range is from 0 to 2146 days. No stratifi-

cation per amount of delay is offered.72Angstwurm and colleagues127 combined their

own patients with other groups to create a population of 240 patients with embolic

stroke preceding cardiac surgery. They concluded that the risk of deterioration is

20% to 50% with surgery in the first 2 weeks, but less than 10% after 14 days and

less than 1% after 4 weeks; and is likely the basis for many groups desire to wait 2

to 4 weeks before operating on these patients. Recently, the ICE investigators pub-

lished the data from their prospective registry including 198 patients who underwent

surgery after ischemic CVA related to IE.128 They analyzed the patients according to

early surgery (17 days after CVA, 58 patients) and late surgery (>7 days, 140 patients)and after adjusting for risk factors found no difference in mortality either in-hospital or

at 1 year. Although this study benefits from organized prospective data collection, the

investigators acknowledge that referral bias relating to their tertiary-care centers and

lack of preoperative data with respect to anatomy and severity of neurologic injury

weaken their conclusion that there is no survival benefit to delaying surgery in these

patients. Furthermore, no postoperative neurologic or quality of life data are

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presented. It becomes difficult, therefore, to make definitive recommendations, and

the chance of seeing a randomized trial in this particular subset of patients is low.

There is increasing evidence that early surgery is beneficial for patients with endo-

carditis. It is apparent that this complex population is difficult to characterize in 1 study

and that performance of randomized controlled trials is difficult. The randomized study

by Kang and colleagues49 is enlightening and yet generates more questions about

who benefits and how with early intervention. Nevertheless, the studies have

continued to push the notion, and it is becoming clear that patients with true indica-

tions for surgical treatment of IE need to be dealt with expeditiously. This time frame

is still not clear, but until more data are available, the recommendations by the ESC

with respect to timing (see Table 1) seem to be reasonable. There are a multitude

of factors surrounding these critically ill patients that require individualization of treat-

ment, but the plan must account for the urgency required to deal with the disease, and

arbitrary waiting no longer seems to be justified, except perhaps with respect to pa-

tients with preexisting embolic CVA in whom the risk of delay of 2 to 4 weeks has to

be balanced against the risk of early surgery. In these patients, features suggestive

of higher risk of recurrent embolism and other accepted class I indications for surgery

should likely be dealt with as soon as possible and even before 2 weeks, especially in

the context of silent or small neurologic events.

OPERATIVE PROCEDURES

Thorough valve exploration, aggressive debridement, reconstruction or replacement

choice, and adequate antimicrobial coverage remain the fundamental principles that

guide operations for IE.Although beneficial, preoperative optimization of patients with IE cannot always be

achieved.127 Ongoing heart failure, sepsis, and metabolic derangements can make the

intraoperative period challenging. Anesthetic and cardiopulmonary bypass (CPB) may

lead to significant hypotension. Patients may require complex surgical reconstruction

further prolonging their CPB time, which can make separation from the heart-lung ma-

chine difficult. As a result, these patients are often markedly, critically ill on return to

the ICU. With respect to coronary angiography, published guidelines suggest it should

be performed in men older than 40 years, postmenopausal women or patients with at

least 1 risk factor for or a history of coronary disease except if large aortic vegetations

are present. In cases of the latter, CT angiography is acceptable to screen for severeproximal disease.

When the infectious process is isolated to the aortic valve leaflets, completeexci-

sion of the leaflets with implantation of a prosthesis is the standard approach.129 There

is no good evidence to suggest that any particular artificial valve is superior with

respect to reinfection in the setting of isolated valvular endocarditis.130 The choice

between mechanical versus bioprosthetic depends on patient preference, age, and

suitability for lifelong anticoagulation. Depending on the extent of involvement, vege-

tectomy leaflet repair may also be feasible.131 When repair is required, autologous

pericardial patches are favored.

For mitral valve endocarditis, because of the anticoagulation issues associated withmechanical valves, and the poor durability of bioprosthetic valves, vegetectomy

repair has been advocated as the initial approach if feasible.132,133 Tricuspid valve

endocarditis has been associated with IV drug use.134 Depending on pulmonary pres-

sures, extent of involvement and patient profile, surgery can be performed in a staged

manner.135,136 The first stage involves valve excision to allow passive blood flow from

the heart to the lungs. After the infection has resolved and the patient rehabilitated, a



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second stage involving valve replacement can be performed months later. In sce-

narios in which the infectious process is limited, a less invasive approach with vege-

tectomy repair as seen with the mitral valve can also be performed.

If the infectious process involves the periannular regions such as a root abscess or

fistula, radical resection of the involved tissues is crucial.137,138 Depending on the

degree of debridement required, either autologous pericardium for small defects or

glutaraldehyde-fixed bovine pericardium for larger defects can be used for recon-

struction.139 If there is significant aortic root involvement, complete resection with im-

plantation of a homograft to aid with the reconstruction of the left ventricular outflow

tract is often used.140,141 Each operation must be tailored to the patient and the extent

of endocarditis.

POSTCARDIAC SURGERYGeneral Considerations

The first 12 to 24 hours after a cardiac surgical procedure is the usual time frame inwhich the postoperative patients with IE experience dynamic changes in cardiac

rhythm and hemodynamics.142,143 Identifying and correcting the cause of postopera-

tive hypoperfusion are tantamount to preserving organ function. Typical causes of hy-

potension and hypoperfusion in the postoperative patient with IE include (but are not

limited to) hypovolemia, bleeding, cardiac tamponade, arrhythmias, poor myocardial

contractility, new myocardial ischemia, and tension pneumothorax. Similarly, exces-

sive blood pressure may lead to bleeding and disruption of surgical anastamotic sites.

The establishment of appropriate hemodynamic and transfusion goals through a

team-based, formal handover from the operating room to the ICU teams may be of

benefit in these complex surgical patients.144146

Heart Rhythm

Injury to the conductive tissue may occur with extensive valve annulus debridement

during surgical management of IE cases. Subsequent alterations in heart rate or con-

duction may contribute to hypotension or hypoperfusion.143 Attainment of sinus

rhythm, or sinuslike rhythm with the dual-chamber pacing using epicardial-pacing

wires, placed in the operating room, is preferred to maintain the atrial contraction

contribution to cardiac output.

Bleeding

Postoperative bleeding via mediastinal and pleural drains needs to be monitored and

hemodynamically assessed because clinically important anemia may require further

medical (ie, blood product transfusion) or surgical (ie, mediastinal reexploration) ther-

apy. Postoperative coagulopathy may arise from a variety of potential mechanisms,

such as hypothermia, sepsis, hemodilution, and the use of CPB. Recommendations

on the appropriate blood product use for the postoperative cardiac surgery patient

were provided in 2007 by a joint practice guideline from the Society of Thoracic Sur-

gery and Society of Cardiovascular Anesthesiologists.147152

SUMMARY

IE is a disease with many facets and various expressions, depending on the site of

infection, microorganism, underlying heart lesion, immune status of the host, and

remote effects such as emboli, organ dysfunction, and the general condition of the

host. Diagnosis is the first crucial step, which depends on meticulous clinical exami-

nation, blood cultures results, and echocardiographic findings. The management of

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the patient with endocarditis in the ICU is complex and needs a multidisciplinary team,

including the intensivist, a cardiologist, an experienced echocardiologist, an infectious

diseases specialist, and a cardiac surgeon. The medical and surgical management of

such patients is complex, and timely decisions are important.

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