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Trends in Anaesthesia and Critical Care 2 (2012) 36e41

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Trends in Anaesthesia and Critical Care

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REVIEW

Infective endocarditis: An intensive care perspective

Vikram Sharma a, Luciano Candilio a, Derek J. Hausenloy*

The Hatter Cardiovascular Institute, University College London, 67 Chenies Mews, London WC1E 6HX, UK

Keywords:Infective endocarditisIntensive care unitNosocomial

Abbreviations: IE, infective endocarditis; NIE, nosoICU, intensive care unit; CT, computerized tomograpimaging; ACC, American College of Cardiology; AHA,ESC, European Society of Cardiology; TEE, transesophtransthoracic echocardiography.* Corresponding author. Tel.: þ44 (203) 447 9888;

E-mail addresses: drvikramsharma@hotmail.comuk (V. Sharma), luciano2108@hotmail.com (L. CandiliJ. Hausenloy).

a Tel.: þ44 (203) 447 9888; fax: þ44 (203) 447 95

2210-8440/$ e see front matter � 2011 Elsevier Ltd.doi:10.1016/j.tacc.2011.11.004

s u m m a r y

Infective endocarditis is a rising problem in the intensive care setting. Patients admitted to the intensivecare unit (ICU) are at a high risk of developing infective endocarditis because of the frequent use ofinvasive monitoring and therapeutic devices in the intensive care environment. In particular, cardiacsurgery patients are at a high risk of developing nosocomial infective endocarditis in the ICU. Staphy-lococci and Streptococci are the predominant organisms causing infective endocarditis in this setting,while fungal endocarditis remains a less frequent condition that may be on the rise. Infective endo-carditis in the intensive care can be challenging to diagnose and manage. Morbidity and mortality frominfective endocarditis can be high in the intensive care setting because of pre-existing pathologies inpatients as well as the more complex nature of the disease in patients who need admission to the ICU. Amultidisciplinary team approach is essential to improve clinical outcomes of patients with this condition.Particular emphasis has to be placed on the prevention of nosocomial endocarditis in the ICU through theuse of strict aseptic conditions during placement and manipulation of invasive devices as well asappropriate endocarditis prophylaxis in selected patients.

� 2011 Elsevier Ltd. All rights reserved.

1. Introduction

Infective endocarditis (IE) refers to an inflammation of theendocardium caused by infectious agents. IE was first described asa disease condition as early as in the 16th century.1 Since the firstdescriptions of IE, significant advances have been made in ourunderstanding of the disease, its prevention, diagnosis and treat-ment. A number of people have contributed to these advancesincluding Sir William Osler, who in 1885 drew a distinctionbetween “simple” and “malignant” forms of endocarditis, which wenow refer to as subacute and acute IE respectively.1,2

The incidence of IE has essentially remained unchanged overthe last two decades, ranging between 3 and 10 episodes/100,000 person-years.1,3 However, the epidemiological profile ofIE has changed dramatically in recent years with a large increase

comial infective endocarditis;hy; MRI, magnetic resonanceAmerican Heart Association;ageal echocardiography; TTE,

fax: þ44 (203) 447 9505., vikramsharma@doctors.org.o), d.hausenloy@ucl.ac.uk (D.

05.

All rights reserved.

in the proportion of cases with Staphylococcal IE due to intra-venous drug abuse, infection of prosthetic heart valves and theuse of invasive vascular devices.3 Nosocomial IE (NIE), which isdefined as infective endocarditis in patients admitted toa hospital at least 72 h prior to the onset of symptoms of IE or IEin patients with a history of an invasive procedure carried out ina recent hospital admission less than 8 weeks prior to onset ofsymptoms,4 has similarly increased in incidence and is a growingproblem.

The diagnosis and management of infective endocarditis in theICU setting can be quite challenging. ICU teams encounter patientswith IE who are hemodynamically unstable due to severe sepsis,heart failure or cardiogenic shock as well as patients who havesevere valvular pathology due to IE and require cardiac surgery.5

Patients are also admitted to the ICU after major cardiac surgeryfor post-operative care and are very susceptible to NIE and othernosocomial infections.6 Patients on ICU are in general moresusceptible to developing IE due to the widespread use of invasivemonitoring and therapeutic devices such as central venous lines,mechanical ventilation, in-dwelling urinary catheters, hemofiltra-tion devices and so on.

Despite advances in diagnosis and treatment along withimproved antimicrobial treatments and potentially curativesurgery, infective endocarditis continues to cause significantmorbidity and mortality.3,7e9 Mortality from IE is particularly highin ICU patients ranging from 29 to 54%.10e12 This review article will

Table 1Common presentations of infective endocarditis in the ICU.

Pyrexia of unknown causePeripheral thromboembolismNeurological complications such as stroke or intracranial hemorrhageHypotensionNew or changing cardiac murmurTachycardiaHeart failureUnexplained rise in inflammatory markersAcute kidney injuryAnemia

V. Sharma et al. / Trends in Anaesthesia and Critical Care 2 (2012) 36e41 37

provide a concise overview of the pathophysiology, diagnosis andmanagement of IE and provides a specific update on recentdevelopments in all aspects of IE in the ICU setting.

2. Causative organisms

There is limited data on the causative organisms for IE in ICUpatients. A few data series available in literature on patients with IEin the ICU setting have found Staphylococci to be the mostcommonly isolated organisms9e11 with Streptococci being thesecond most common. In a study of 90 ICU patients with IE, Moulyet al. reported that majority (44%) of the cases were caused byStaphylococci, followed by Streptococci which were responsible for25% cases.9 Methicillin Resistant Staphylococcus aureus (MRSA)were seen in 4% cases. Streptococcal species isolated were Strep-tococcus bovis and Enterococci. Staphylococci were also thepredominant organisms responsible for NIE in these patientsaccounting for 74% of all nosocomial endocarditis. A small numberof patients (3.3% of all cases) had fungal endocarditis with 2 cases ofCandida and 2 cases of Aspergillus endocarditis. There was 1 caseeach of endocarditis with gram negative bacilli and HACEK (Hae-mophilus, Actinobacillus, Cardiobacterium hominis, Eikenella corro-dens, Kingella kingae) group of organisms. In another series fromFrance involving 228 patients with endocarditis in the intensivecare setting, Staphylococci were again the most commonly isolatedorganisms10 and were responsible for 50% of all cases and themajority of nosocomial IE cases. MRSA were seen in 11% of totalcases. 4% of cases had fungal endocarditis and in 5% of the casesgram negative bacilli were isolated. Staphylococci were also thepredominant organisms in patients with endocarditis secondary tointravenous drug use admitted to the ITU in a series reported fromUSA.11 Fungal endocarditis and in particular Candida endocarditis,although still uncommon, is a rising problem in the ICU setting.Candida endocarditis is ten times more common in the ICU ascompared to general hospital patients.13,14 Candida nosocomialendocarditis has also been reported in neonatal intensive caresetting, where morbidity and mortality in patients with Candidaendocarditis is very high.15,16 Hence in patients with endocarditis inthe ICU setting, there should be a high index of suspicion for fungalendocarditis especially in patients not responding to empiricalantibiotics.

3. Pathophysiology

The endothelium represents the internal lining of heart valvesand cavities. In normal conditions it forms a continuous smoothsurface which, if subjected to injury, can become susceptible tofibrin and platelet deposits leading to the formation of sterilemicro-vegetations.1,12 This endothelial injury can occur as a resultof high-velocity turbulent blood flow associated with certainvalvular pathologies like aortic incompetence, mitral incompetenceand ventricular septal defects17 or due to intra-cardiac deviceinsertion. These sterile micro-vegetations constitute an idealenvironment for colonisation and infection by microorganisms.Endocardial inflammation itself, which can occur as a result ofendothelial injury, promotes bacterial colonisation which may leadto infective endocarditis.18 Prosthetic heart valves also providea suitable environment for microbial colonisation in the presenceof bacteremia.

Trauma to skin and mucosal linings as seen with dental proce-dures involving manipulation of the gingival surface,17 intravenousdrug abuse and insertion of invasive vascular devices or theirmanipulation can provide an opportunity for microbes to enter thecirculation and cause IE.1,12,18 Once established, IE can lead toperforation, obstruction or incompetence of heart valves, abscess

formation and valve dehiscence (in cases of prosthetic heartvalves). Vegetations on valve leaflets can also cause the formationof micro-thrombi which can then embolise to the brain, kidney,spleen, peripheral vasculature and so forth,1 or induce septicemboli with subsequent metastatic infection, as in the case ofpulmonary abscesses seen in patients with tricuspid valveendocarditis.

4. Clinical features

IE may present with a variety of clinical manifestationsincluding atypical symptoms, particularly in patients on ICU.Common presentations on the ICU are pyrexia of unknown origin;peripheral thromboembolism; neurological complications such asstroke or intracranial hemorrhage; hypotension; new or changingcardiac murmur; tachycardia; heart failure; unexplained rise ininflammatory markers; acute kidney injury and anemia8,19,20

(please see Table 1).The classical manifestations of IE are not usually seen in criti-

cally ill patients, making it difficult to diagnose in the ICU envi-ronment. Central nervous system signs of IE can often be blunted bysedation given to intensive care patients. Fever and bacteremia canfrequently be attributed to other possible co-existing hospital-acquired infections and acute kidney injury is common due to co-existing pathologies. Hence, the timely diagnosis of IE requiresa high index of suspicion particularly in patients more predisposedto IE such as in patients with prosthetic valves, post-cardiac surgeryand with long-term in-dwelling invasive monitoring or therapeuticdevices.

5. Predictors of outcome

Various clinical factors have been associated with higher overallmortality in patients with IE and the majority of these factors arecommonpredictors of outcome in ICU patients as well as in patientsin general. These factors include older age,21 presence of heartfailure, presence of severe sepsis, immunocompromised status,presence of acute kidney injury5,8,9,12,22,23 and antimicrobial treat-ment failure.24 Other factors linked with increased mortality areprosthetic valve infection9,25 and neurological complications.10 Inpatients undergoing heart valve surgery for infective endocarditispredictors for mortality were higher age, severity of sepsis, acutekidney injury and hemodynamic instability8,26 (please see Table 2).In patients undergoing aortic root replacement surgery for IE,patients with prosthetic valves have higher mortality as comparedwith those having native valves.27 Staphylococcal,21 fungal andgram negative IE are also associated with poorer outcome.23

Certain echocardiographic features are associated with highermortality. These include large vegetation size, severe prostheticvalve dysfunction, severe left sided regurgitant lesions, peri-annular complications such as abscesses and left ventricular

Table 2Predictors of outcome in patients with infective endocarditis.

AgePre-existing heart pathologies: valve lesions, prosthetic heart valves, congenitalheart diseaseHeart failureAcute kidney injuryNeurological complicationsValve surgery for endocarditisAntimicrobial treatment failureStaphylococcal, fungal or gram negative endocarditisECHO features such as large vegetations, severe valve dysfunction, prostheticvalve dehiscence

V. Sharma et al. / Trends in Anaesthesia and Critical Care 2 (2012) 36e4138

dysfunction.23 Closer monitoring and attention may reducemorbidity and mortality in these high-risk patient groups.

6. Diagnosis

The diagnosis of IE is derived from a combination of clinicalfindings, laboratory investigations and imaging data. The ModifiedDuke’s Criteria can be used for the diagnosis of IE,28,29 althoughthese have not been specifically validated for the diagnosis of IE inthe ICU setting (please see Table 3).

Essentially, diagnosis is based on strength of clinical suspicion inconjunction with evidence from blood cultures and imaging

Table 3Modified Duke’s criteria for Infective endocarditis.29

Major criteriaMicrobiological evidence of infective endocarditis

- Positive blood cultures (typical organisms consistent with infectiveendocarditis isolated from 2 separate blood cultures; microorganismsconsistent with IE isolated from at least 2 blood culture done more than12 h apart or all of 3 or majority of �4 separate blood cultures spreadover more than 1 h; single positive blood culture for Coxiella burnetii orantiphase I IgG titer .1:800)

Evidence of endocardial involvement

- Echocardiogram positive for infective endocarditis (oscillating mass onvalves or supporting structures, in path of regurgitant jets or unex-plained mass on implanted material; abscess; new prosthetic valvedehiscence)

- New valve regurgitation

Minor criteria- Predisposing heart condition or history of intravenous drug abuse- Fever> 38 degree Celsius- Vascular phenomena (such as major arterial emboli, septic pulmonaryinfarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hae-morrhages, Janeway’s lesions)

- Immunologic phenomena (such as glomerulonephritis, Osler’s nodesRoth’s spots, positive rheumatoid factor)

- Microbiological evidence: blood cultures not meeting major criteria orserological evidence of active infection with organisms consistent with IEbut excluding single positive cultures with coagulase negative staphylo-cocci and organisms not known to cause IE

Definite IE2 Major criteria; I major and 3 minor criteria or 5 minor criteria

Possible IE1 Major and 1 minor criteria or 3 minor criteria

No IEDefinite alternative diagnosis explaining findings, resolution of findings with�4days of antibiotics, absence of pathological evidence of IE at surgery or biopsywith antibiotic treatment� 4 days or not meeting criteria for possible IE

modalities such as echocardiography, CT and MRI. At least 3 sets ofblood cultures should be taken in patients with suspected infectiveendocarditis.3,19 The ACC/AHA guidelines also recommend bloodcultures to be taken in patients with any unexplained fever lastingmore than 48 h as well as prior to institution of antibiotics inpatients with known valve disease or prosthetic valves who haveunexplained pyrexia.

In patients with suspected IE, echocardiography is essential forthe detection of the presence, location and size of vegetations; theevaluation of valvular dysfunction and the detection of other intra-cardiac complications (e.g. abscess formation). Echocardiography isalso extremely crucial for the assessment of heart function, which isnot only a determinant of clinical outcome but also helps to decidethe need for valve surgery (see Fig. 1). Although transthoracicechocardiography (TTE) can be used as a screening tool for thesepurposes, transesophageal echocardiography (TEE) is the recom-mended investigation for patients with suspected IE in the ICUsetting because of its significantly higher sensitivity, specificity andaccuracy in detecting IE, identifying complications such as abscessformation, and assessing the severity of valve lesions as a result ofIE3,30,31 (see Fig. 2). In particular TEE is recommended in patientswith prosthetic heart valves30,32 as TTE can be less reliable in thesecases. TEE should also be done in all cases of IE being considered forsurgery.32 TEE can be a technically challenging procedure in criti-cally ill patients due to problems with accessing the esophagus inthe presence of nasogastric tubes and invasive ventilation. This isfurther confounded by the presence of pre-existing respiratory andcardiovascular compromise. However, complication rates with TEEin critically ill patients remain extremely low.31,33,34 TEE in ICUshould be carried out by a sufficiently skilled person and if possiblewith naso-endoscopy guidance to prevent injury to the esophagusor oropharynx. Patients should be fasting for at least 4e6 h prior toprocedure to prevent risk of aspiration.

New diagnostic modalities such as MRI, PET/CT scanning canalso be employed in the diagnosis of peripheral embolism ormetastatic infection in patients with infective endocarditis.35e40 Inparticular, MRI of the brain has been shown to detect cerebralemboli, even in asymptomatic patients. Hence MRI should beconsidered in patients with confirmed IE as the presence ofneurological sequelae can be an important indicator of diseaseseverity, treatment response and prognosis35e38 of IE.

Fig. 1. Transthoracic echocardiography view of a tricuspid valve vegetation. Trans-thoracic echocardiography can be used as a screening tool in patients with uncom-plicated native valve infective endocarditis and to assess left ventricular systolicfunction.

Fig. 2. Transesophageal image of a vegetation on the aortic valve e TEE has a muchhigher sensitivity and specificity for detecting infective endocarditis, for the assess-ment of vegetation size and the severity of valve lesions as well as for the detection ofabscesses and fistulae. TEE is much more reliable in the investigation of infectiveendocarditis in patients with prosthetic heart valves as well as in the presence ofcomplications such as perivalvular abscess formation and should be the imagingmodality of choice in these cases.

V. Sharma et al. / Trends in Anaesthesia and Critical Care 2 (2012) 36e41 39

7. Treatment

Treatment of IE includes antimicrobial therapy alone or incombination with surgery when indicated. The former should beinstituted early, after at least three sets of blood culture sampleshave been taken from peripheral venous sites.23 Empirical antibi-otics can be started based on local hospital policy and standardnational or international guidelines such as those issued by the ACCor ESC. The microbiology team should be consulted in all cases toguide treatment as per local protocols. The selection of antimicro-bial agents can then be adjusted based on antibiotic susceptibilitytesting after isolation of the causative microbe.

Surgery is required in about 50% of all cases of infective endo-carditis.41 Careful consideration has to be given to the need forsurgery and its appropriate timing. This decision has to be individ-ualized in each case and requires a multidisciplinary approachinvolving the cardiac surgical team. Heart failure is the mostcommon indication for surgery in patients with infective endo-carditis.41 Heart failure in the majority of patients with IE is a resultof severe valvular regurgitation. Other main indications for surgeryinclude uncontrolled infection, presence of perivalvular extensionsuch as abscess or fistula formation, large vegetation size and theprevention of systemic embolism (please see Table 4).32,41 Surgeryhas to be performed on an urgent basis in patients with persistentcardiogenic shock or pulmonary edema despite optimal medicaltherapy. In some cases of IE, surgery can be delayed if the valvular

Table 4Indications for surgery in patients with infective endocarditis.

Congestive heart failurePeri-annular complications (such as abscess or fistula formation)Severe valvular dysfunction (severe aortic or mitral regurgitation)Systemic emboliLarge vegetation sizeNeurological complicationsPersistent sepsisIsolation of difficult to eradicate organisms (such as Pseudomonas, Coxiella,Brucella, Candida, Aspergillus, S. lugdunensis)Prosthetic valve endocarditis (early prosthetic valve endocarditis, S. aureusprosthetic valve endocarditis, heart failure in prosthetic valve endocarditiscaused my mechanical failure such as dehiscence or obstruction)

regurgitant lesions are well tolerated in order to allow for completetreatment of IE (provided there are no other indications forsurgery).23 Surgery for the prevention of thromboembolism can beconsidered in patients with isolated vegetations> 15 mm in size aswell as in patients with aortic or mitral vegetations> 10 mm in sizeif one or more embolic episodes have occurred despite antibiotictherapy.23 Surgery is also indicated in cases of IE due to microor-ganisms which are difficult to treat or eradicate with antibiotics.These include IE caused by Pseudomonas aeruginosa, Coxiella bur-netii, Brucella, Staphylococcus lugdunensis, Candida or Aspergillus.Finally, surgery is also indicated in the majority of early prostheticvalve infections as well as late prosthetic valve infections caused byStaphylococciwhich can be difficult to treatwith antibiotics alone.32

In all of the above cases prompt surgical opinion should be sought.In some cases surgery has to be delayed despite indications,

such as in patients with intracranial hemorrhage where surgeryshould be postponed for at least 1 month.23,32 The ACC/AHAguidelines recommend surgery in patients with congestive cardiacfailure or cardiogenic shock caused by surgically treatable valvedisease with or without infective endocarditis, provided there isa reasonable prospect of recovery with satisfactory quality of life.19

Thus surgery may not be suitable in some patients with severeembolic brain injury or patients with significant comorbiditieswhere there is no prospect of recovery to a satisfactory quality oflife, even if the valve pathology is correctable by surgery.

Decisions such as appropriate antibiotics therapy, duration ofantibiotic therapy, need for surgery as well as its timing andappropriateness are complicated and hence need a multidisci-plinary approach involving the microbiology, cardiology andcardiothoracic surgery teams in addition to the ICU team.

8. Prevention

As previously highlighted nosocomial IE is a growing problemparticularly in the ICU. There is a clear need to have robust ICUprotocols to prevent infections such as IE occurring as a result ofinvasive devices.42 Central venous catheter associated blood streaminfections are common in the ICU setting and are known to cause IEin susceptible patients such as those with prosthetic valves, knownvalve disease or patients post-cardiac surgery.6,20,43e45 Adequateprecautions and care should be taken in these patients to preventnosocomial IE as a result of their ICU stay. In addition, local practiceshould be regularly monitored and reviewed to address the issue ofnosocomial infections in the ICU.

Both the American Heart Association and the European Societyof Cardiology have recently provided revised guidelines for IEprophylaxis for the general populationwhich are also applicable forthe ITU patients. Prophylaxis is now only recommended for those atthe highest risk of IE. These include patients with prosthetic heartvalves; patients with prosthetic materials used for valve repair;patients with previous IE and patients with cyanotic congenitalheart diseases without repair or with a persistent defect or pallia-tive shunt/conduit. Prophylaxis is also indicated in patients withcongenital heart diseases either fully repaired with a prostheticdevice (during first 6 months following implantation of prostheticdevice) or with a residual defect after repair. Prophylaxis is onlyindicated in patients undergoing dental procedures involvingmanipulation of the gingival or peri-apical region of teeth andperforation of oral mucosa. There is currently no recommendationfor prophylactic antibiotics in patients undergoing respiratory(unless involving incision of respiratory mucosa), gastrointestinal,genito-urinary, skin or musculoskeletal procedures.19,23

For patients undergoing implantation of a prosthetic valve orprosthetic material for valve repair, prophylaxis for CoagulaseNegative Staphylococci and S. aureus should be given just before the

V. Sharma et al. / Trends in Anaesthesia and Critical Care 2 (2012) 36e4140

procedure and continued up to 48 h after surgery. Any potentialsource of dental sepsis should be resolved at least 2 weeks prior toimplantation of any prosthetic material.23

9. Conclusions

IE is a condition which is increasingly encountered in the ICU.Mortality can be very high in this setting due to the highercomplexity of cases admitted to ICU and the co-existing patholo-gies. The ICU stay itself represents a risk factor for nosocomial IE insusceptible patients groups. Diagnosis involves the identification ofthe causative organism by serial blood cultures (which allows foreffective antibiotic therapy to be administered based on sensitiv-ities) along with imaging studies. Transesophageal echo is theinvestigation of choice for determining the presence of endocarditisas well to ascertain the severity of the disease. Newer imagingmodalities such as MRI and PET/CT can help to identify emboliccomplications arising from IE particularly in caseswith neurologicalcomplications due to IE, whichmay not be clinically apparent in theventilated ICU patient. Treatment involves a multidisciplinaryapproach comprising microbiologists, cardiologists and cardiotho-racic surgeons working in conjunction with the ICU team. IEpatients with evidence of heart failure, severe IE-related valvelesions, severe prosthetic valve dysfunction or dehiscence andpatients with large vegetations should be promptly referred forsurgery. Emphasis on preventing nosocomial infections for exampleby protocols aimed at reducing central venous catheter inducedblood stream infections along with endocarditis prophylaxis whereappropriate will help prevent IE in ICU patients, a challengingcondition often associated with poor clinical outcomes.

Conflict of interestThe authors have no conflicts of interest to declare.

References

1. Bashore TM, Cabell C, Fowler Jr V. Update on infective endocarditis. Curr ProblCardiol 2006;31:274e352.

2. Silverman ME, Upshaw Jr CB. Extracardiac manifestations of infective endo-carditis and their historical descriptions. Am J Cardiol 2007;100:1802e7.

3. Habib G. Infective endocarditis: what’s new? European Society of Cardiology(ESC) guidelines 2009 on the prevention, diagnosis and treatment of infectiveendocarditis. Presse Med 2010;39:704e9.

4. Peetermans WE, Hill EE, Herijgers P, Claus P, Herregods MC, Verhaegen J, et al.Nosocomial infective endocarditis: should the definition be extended to 6months after discharge. Clin Microbiol Infect 2008;14:970e3.

5. Karth G, Koreny M, Binder T, Knapp S, Zauner C, Valentin A, et al. Complicatedinfective endocarditis necessitating ICU admission: clinical course and prog-nosis. Crit Care 2002;6:149e54.

6. Bouza E, Hortal J, Munoz P, Perez MJ, Riesgo MJ, Hiesmayr M. Infectionsfollowing major heart surgery in European intensive care units: there is roomfor improvement (ESGNI 007 study). J Hosp Infect 2006;63:399e405.

7. Prendergast BD. The changing face of infective endocarditis. Heart2006;92:879e85.

8. Rostagno C, Rosso G, Puggelli F, Gelsomino S, Braconi L, Montesi GF, et al. Activeinfective endocarditis: clinical characteristics and factors related to hospitalmortality. Cardiol J 2010;17:566e73.

9. Mouly S, Ruimy R, Launay O, Arnoult F, Brochet E, Trouillet JL, et al. Thechanging clinical aspects of infective endocarditis: descriptive review of 90episodes in a French teaching hospital and risk factors for death. J Infect2002;45:246e56.

10. Mourvillier B, Trouillet JL, Timsit JF, Baudot J, Chastre J, Regnier B, et al. Infectiveendocarditis in the intensive care unit: clinical spectrum and prognostic factorsin 228 consecutive patients. Intensive Care Med 2004;30:2046e52.

11. Saydain G, Singh J, Dalal B, Yoo W, Levine DP. Outcome of patients withinjection drug use-associated endocarditis admitted to an intensive care unit.J Crit Care 2010;25:248e53.

12. McDonald JR. Acute infective endocarditis. Infect Dis Clin North Am2009;23:643e64.

13. De Rosa FG, Garazzino S, Pasero D, Di Perri G, Ranieri VM. Invasive candidiasisand candidemia: new guidelines. Minerva Anestesiol 2009;75:453e8.

14. Schelenz S, Gransden WR. Candidemia in a London teaching hospital: analysisof 128 cases over a 7-year period. Mycoses 2003;46:390e6.

15. Rangel-Frausto MS, Wiblin T, Blumberg HM, Saiman L, Patterson J, Rinaldi M,et al. National epidemiology of mycoses survey (NEMIS): variations in rates ofbloodstream infections due to Candida species in seven surgical intensive careunits and six neonatal intensive care units. Clin Infect Dis 1999;29:253e8.

16. Rodriguez D, Almirante B, Park BJ, Cuenca-Estrella M, Planes AM, Sanchez F,et al. Candidemia in neonatal intensive care units: Barcelona, Spain. PediatrInfect Dis J 2006;25:224e9.

17. Nishimura RA, Carabello BA, Faxon DP, Freed MD, Lytle BW, O’Gara PT, et al.ACC/AHA 2008 Guideline update on valvular heart disease: focused update oninfective endocarditis: a report of the American College of Cardiology/Amer-ican Heart Association task force on practice guidelines endorsed by theSociety of Cardiovascular Anesthesiologists, Society for Cardiovascular Angi-ography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol2008;52:676e85.

18. Widmer E, Que YA, Entenza JM, Moreillon P. New concepts in the patho-physiology of infective endocarditis. Curr Infect Dis Rep 2006;8:271e9.

19. Bonow RO, Carabello BA, Chatterjee K, de Jr LA, Faxon DP, Freed MD, et al. 2008Focused update incorporated into the ACC/AHA 2006 guidelines for themanagement of patients with valvular heart disease: a report of the AmericanCollege of Cardiology/American Heart Association task force on practiceguidelines (Writing Committee to revise the 1998 guidelines for the manage-ment of patients with valvular heart disease). Endorsed by the Society ofCardiovascular Anesthesiologists, Society for Cardiovascular Angiography andInterventions, and Society of Thoracic Surgeons. J Am Coll Cardiol2008;52:e1e142.

20. Haddad SH, Arabi YM, Memish ZA, Al Shimemeri AA. Nosocomial infectiveendocarditis in critically ill patients: a report of three cases and review of theliterature. Int J Infect Dis 2004;8:210e6.

21. Hill EE, Herijgers P, Claus P, Vanderschueren S, Herregods MC, Peetermans WE.Infective endocarditis: changing epidemiology and predictors of 6-monthmortality: a prospective cohort study. Eur Heart J 2007;28:196e203.

22. Netzer RO, Altwegg SC, Zollinger E, Tauber M, Carrel T, Seiler C. Infectiveendocarditis: determinants of long term outcome. Heart 2002;88:61e6.

23. Habib G, Hoen B, Tornos P, Thuny F, Prendergast B, Vilacosta I, et al. Guidelineson the prevention, diagnosis, and treatment of infective endocarditis (newversion 2009): the task force on the prevention, diagnosis, and treatment ofinfective endocarditis of the European Society of Cardiology (ESC). Endorsed bythe European Society of Clinical Microbiology and Infectious Diseases (ESCMID)and the International Society of Chemotherapy (ISC) for infection and cancer.Eur Heart J 2009;30:2369e413.

24. Oyonarte M, Rojo P, Estevez A, Solis I, Akel C, Klenner C, et al. Infectiousendocarditis: prognostic factors of mortality in 131 cases. Rev Med Chile1997;125:165e73.

25. Bouza E, Menasalvas A, Munoz P, Vasallo FJ, del Mar MM, Garcia Fernandez MA.Infective endocarditis e a prospective study at the end of the twentiethcentury: new predisposing conditions, new etiologic agents, and still a highmortality. Medicine (Baltimore) 2001;80:298e307.

26. Gaca JG, Sheng S, Daneshmand MA, O’Brien S, Rankin JS, Brennan JM, et al.Outcomes for endocarditis surgery in North America: a simplified risk scoringsystem. J Thorac Cardiovasc Surg 2011;141:98e106.

27. Musci M, Weng Y, Hubler M, Amiri A, Pasic M, Kosky S, et al. Homograft aorticroot replacement in native or prosthetic active infective endocarditis: twenty-year single-center experience. J Thorac Cardiovasc Surg 2010;139:665e73.

28. Calandra T, Cohen J. The international sepsis forum consensus conference ondefinitions of infection in the intensive care unit. Crit Care Med2005;33:1538e48.

29. Li JS, Sexton DJ, Mick N, Nettles R, Fowler Jr VG, Ryan T, et al. Proposedmodifications to the Duke criteria for the diagnosis of infective endocarditis.Clin Infect Dis 2000;30:633e8.

30. Ansari A, Rigolin VH. Infective endocarditis: an update on the role of echo-cardiography. Curr Cardiol Rep 2010;12:265e71.

31. Karski JM. Transesophageal echocardiography in the intensive care unit. SeminCardiothorac Vasc Anesth 2006;10:162e6.

32. Prendergast BD, Tornos P. Surgery for infective endocarditis: who and when?Circulation 2010;121:1141e52.

33. Huttemann E. Transoesophageal echocardiography in critical care. MinervaAnestesiol 2006;72:891e913.

34. Huttemann E, Greim CA. Transesophageal echocardiography in critically illpatients e techniques, indications and possibilities. Anasthesiol IntensivmedNotfallmed Schmerzther 2008;43:500e12.

35. Azuma A, Toyoda K, O’uchi T. Brain magnetic resonance findings in infectiveendocarditis with neurological complications. Jpn J Radiol 2009;27:123e30.

36. Duval X, Iung B, Klein I, Brochet E, Thabut G, Arnoult F, et al. Effect of earlycerebral magnetic resonance imaging on clinical decisions in infective endo-carditis: a prospective study. Ann Intern Med 2010;152:497e504. W175.

37. Grabowski M, Hryniewiecki T, Janas J, Stepinska J. Clinically overt and silentcerebral embolism in the course of infective endocarditis. J Neurol 2011.

38. Snygg-Martin U, Gustafsson L, Rosengren L, Alsio A, Ackerholm P, Andersson R,et al. Cerebrovascular complications in patients with left-sided infective endo-carditis are common: a prospective study using magnetic resonance imagingand neurochemical brain damage markers. Clin Infect Dis 2008;47:23e30.

39. Van Riet J, Hill EE, Gheysens O, Dymarkowski S, Herregods MC, Herijgers P,et al. (18)F-FDG PET/CT for early detection of embolism and metastatic infec-tion in patients with infective endocarditis. Eur J Nucl Med Mol Imaging2010;37:1189e97.

V. Sharma et al. / Trends in Anaesthesia and Critical Care 2 (2012) 36e41 41

40. Simons KS, Pickkers P, Bleeker-Rovers CP, Oyen WJ, van der Hoeven JG. F-18-fluorodeoxyglucose positron emission tomography combined with CT incritically ill patients with suspected infection. Intensive Care Med2010;36:504e11.

41. Tornos P, Iung B, Permanyer-Miralda G, Baron G, Delahaye F, Gohlke-Barwolf C,et al. Infective endocarditis in Europe: lessons from the Euro heart survey.Heart 2005;91:571e5.

42. Timsit JF, Dubois Y, Minet C, Bonadona A, Lugosi M, Ara-Somohano C, et al. Newchallenges in the diagnosis, management, and prevention of central venouscatheter-related infections. Semin Respir Crit Care Med 2011;32:139e50.

43. Moreno CA, Rosenthal VD, Olarte N, Gomez WV, Sussmann O, Agudelo JG, et al.Device-associated infection rate and mortality in intensive care units of 9Colombian hospitals: findings of the International Nosocomial InfectionControl Consortium. Infect Control Hosp Epidemiol 2006;27:349e56.

44. Rosenthal VD, Maki DG, Salomao R, Moreno CA, Mehta Y, Higuera F, et al.Device-associated nosocomial infections in 55 intensive care units of 8developing countries. Ann Intern Med 2006;145:582e91.

45. Gualis J, Florez S, Tamayo E, Alvarez FJ, Castrodeza J, Castano M. Risk factors formediastinitis and endocarditis after cardiac surgery. Asian Cardiovasc ThoracAnn 2009;17:612e6.