MORBIDITY & MORTALITY CONFERENCE

MORBIDITY & MORTALITY CONFERENCE
Department of Medicine Grand Rounds MORBIDITY & MORTALITY CONFERENCE Presenter: Jorge L. Morales-Estrella, MD Firm A Chief Medical Resident Department of Medicine

DISCLOSURES No conflicts of interest

Emergency Department (ED)
A 47-year-old lady presented to the ED with 1 week of: Generalized body aches Fever Chills ROS: productive cough, fatigue, nausea

Emergency Department Past medical history: Past social history:
Hypertension on enalapril Diabetes mellitus on metformin Morbid obesity (BMI 45) Iron deficiency anemia Past social history: Denied tobacco, alcohol or drugs history Married; 4 children

Emergency Department Examination: Plan: CBC, BMP, urinalysis
Fever (101.5 °F) Tachycardia (HR 107 beats/min) Systolic ejection murmur Clear lungs Normal joints Plan: CBC, BMP, urinalysis Urine, sputum and blood cultures Chest x-ray and EKG

Emergency Department Results: UA: CXR: normal EKG: sinus tachycardia
CBC: Stable microcytic anemia Normal white blood cell count BMP: Na 129 Glucose 286 UA: Pyuria (WBC 39) RBC 4 Few bacteria

Emergency Department Patient was discharged home with diagnoses of:
Viral upper respiratory infection Urinary tract infection Ciprofloxacin for 3 days Instructions to follow up with PCP

Next Day ID Bacteremia Surveillance Blood cultures:
Gram positive cocci (GPC) in clusters (½ culture set) Patient was asked to return to the ED Keep it brief WAS

Day prior to return to ED
Blood cultures: Methicillin-susceptible Staphylococcus aureus (MSSA) isolated Urine culture: MSSA

Day 1: ED Return “Persistent fever and chills” Normal exam
Blood and urine culture: MSSA Similar laboratory results Repeat blood cultures  Admit for observation

Day 2: Wards Admitting team:
“Recent flu and UTI” “Denies frank dysuria” Normal exam “+UA and blood culture…likely a contaminant”  “Will start fluids…on exam she is mildly dehydrated” Question: “real infection vs. contamination?” take off senior team Question (no S)

Overnight Fever (103°F) Tachycardia (HR 121 beats/min) Started on ceftriaxone Infectious diseases (ID) is consulted for next morning

Day 3: Wards ID “Loud holosystolic murmur heard throughout precordium, best in apex” Osler’s node, left palm Janeway lesions, right hand and bilateral foot Splinter hemorrhage, left 5th fingernail Probable MSSA native valve infective endocarditis (NVIE) with metastatic seeding Stop the ceftriaxone and start oxacillin Don’t say where No need to say TTE

Day 3: Wards Trans-thoracic echocardiogram (TTE)
Large, irregular, echogenic, mobile vegetation 1.8 x 1.2 cm on the left ventricular aspect of the aortic valve Eccentric regurgitation Markedly increased transaortic velocity Trans-esophageal echocardiogram (TEE) Large, irregular, echogenic, mobile mass, measuring 1.8 cm x 1.5 cm on the left coronary cusp Vegetation causing significant LV outflow obstruction

Day 3: CCU transfer CCU team
“Decreased exercise tolerance from baseline 1 block to few steps over the last 2 weeks” 3/6 holosystolic murmur Not in florid heart failure and hemodynamically stable “This is a large AV vegetation causing severe obstruction”

Day 4: CCU CCU team Warrants urgent surgical evaluation
Concerned “about this patient's significant risk of systemic embolization considering this large AV vegetation” Warrants urgent surgical evaluation Cardiothoracic (CT) surgery consulted

Day 5: CCU CT surgery attending
“By echocardiogram she is hyper-dynamic if anything and no annular abscess” Agreed “should operate sooner rather than later”  Plan for OR in 3 days

Day 8: CCU Planned OR day Surgery was postponed for next day due to an emergent case 5 days since last positive blood culture CT of the head, spine, abdomen and pelvis showed no evidence of metastatic seeding

Day 9: OR Operative findings:
Large vegetation extending into the annulus and commissure (abscess), tracking into the free-wall of the LV, down to the papillary muscle Contained LV free-wall rupture eroding into the main pulmonary artery

Day 9: OR and SICU Operative procedures:
Radical debridement and extensive reconstruction Repair of LV, annulus and aorta with root enlargement Long CPB time (9.5 hours) and edema: the chest was left open with wound vacuum  SICU on 5 vasopressors Cardiogenic shock and multiorgan failure

Day 11: SICU POD #2: Patient expires after withdrawal of care

Morbidity and mortality: hindscope
Delay to recognize S. aureus bacteremia and diagnosis of infective endocarditis  3 days Delay to effective treatment of S. aureus bacteremia  3 days Delay of surgical intervention from diagnosis of infective endocarditis  5 days

Delay to recognize S. aureus bacteremia and diagnosis of infective endocarditis  3 days Delay to effective treatment of S. aureus bacteremia  3 days Delay of surgical intervention from diagnosis of infective endocarditis  5 days I’ll like to work it backwards by looking at the indications of and timing of surgery

Surgery in NVIE: Indications
Left-sided IE Valve dysfunction causing HF (I) Resistant organism (S. aureus, fungi) (I) Heart block, abscess, fistula (I) Persistent infection (I) Recurrent emboli and persistent vegetation despite antibiotics (IIA) Large (10 mm) mobile vegetation (IIB) Right-sided IE Reasonable for patients with certain complications (IIA) Because majority are due to IVDU, the general approach is avoidance of valve prosthesis Valve repair rather than replacement should be performed when feasible IIA: reasonable IIB: may be considered Baddour LM, Wilson WR, Bayer AS, et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation 2015; 132:1435 Habib G, Lancellotti P, Antunes MJ, et al ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J 2015; 36:3075. Nishimura RA, Otto CM, Bonow RO, et al AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice. J Am Coll Cardiol 2014;63:2438–88

Surgery in NVIE: Timing
EMERGENT (<24 hours) Refractory pulmonary edema or cardiogenic shock (IB) URGENT (days) Persisting congestive heart failure or sepsis (IB) Signs of poor hemodynamic tolerance (IB) Abscess (IB) Large vegetation (10 mm) with an embolic event (IB) Very large vegetation: >15 mm (IIB), >30mm (IIA) EARLY ELECTIVE (1-2 wk.) HF with good response to medical therapy (IB) Resistant organisms (S. aureus, fungi) (IB) Persistent bacteremia/fever (>5-7 days) (IB) DELAYED (>4 wks) Major ischemic stroke or intracranial hemorrhage (IIA) Prendergast BD, Tornos P. Surgery for infective endocarditis: who and when? Circulation 2010; 121:1141 Baddour LM, Wilson WR, Bayer AS, et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation 2015; 132:1435 Habib G, Lancellotti P, Antunes MJ, et al ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J 2015; 36:3075. Nishimura RA, Otto CM, Bonow RO, et al AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice. J Am Coll Cardiol 2014;63:2438–88

Surgery in NVIE: Timing
URGENT (days) Persisting congestive heart failure or sepsis (IB) Signs of poor hemodynamic tolerance (IB) ✔? Abscess (IB) ✔ Large vegetation (10 mm) with an embolic event (IB) Very large vegetation: >15 mm (IIB), >30mm (IIA) ✔ EARLY ELECTIVE (during hospital stay after 1-2 weeks of antibiotics) HF with good response to medical therapy (IB) ✔? Resistant organisms (S. aureus, fungi) (IB) ✔ Persistent bacteremia/fever (>5-7 days) (IB) Prendergast BD, Tornos P. Surgery for infective endocarditis: who and when? Circulation 2010; 121:1141 Baddour LM, Wilson WR, Bayer AS, et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation 2015; 132:1435 Habib G, Lancellotti P, Antunes MJ, et al ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J 2015; 36:3075. Nishimura RA, Otto CM, Bonow RO, et al AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice. J Am Coll Cardiol 2014;63:2438–88

Delay to recognize S. aureus bacteremia and diagnosis of infective endocarditis  3 days Delay to effective treatment of S. aureus bacteremia  3 days Delay of surgical intervention from diagnosis of infective endocarditis  5 days

Bacteremia: appropriateness of antibiotic therapy
Appropriate empiric and culture-directed antibiotic therapy results in decreased mortality and improved outcomes This patient was started on ceftriaxone which is an inappropriate antibiotic. Other authors have looked into this in the past. Weinstein MP, Towns ML, Quartey SM, et al. The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. Clin Infect Dis. 1997;24:584-60

After susceptibility test results, 25% of all patients were receiving antibiotic agents judge to be superfluous Early 1990’s2 7.6% of septicemic patients received inappropriate therapy even after susceptibilities were reported Pien et al (2010): About 11% of all bloodstream infections were associated with inappropriate or non- susceptible antibiotics at 2 decision points Weinstein MP, Murphy JR, Reller LB, Lichtenstein KA. The clinical significance of positive blood cultures: a comprehensive analysis of 500 episodes of bacteremia and fungemia in adults. II. Clinical observations, with special reference to factors influencing prognosis. Rev Infect Dis. 1983;5:54-70. Weinstein MP, Towns ML, Quartey SM, et al. The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. Clin Infect Dis. 1997;24:584-60 . Pien BC, Sundaram P, Raoof N, et al. The clinical and prognostic importance of positive blood cultures in adults. Am J Med 2010; 123:81

REFERENCES CFR: case fatality ratio Weinstein MP, Towns ML, Quartey SM, et al. The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. Clin Infect Dis. 1997;24:584-60

SAB: treatment GPCs isolated
 empiric antimicrobial therapy with MRSA coverage (vancomycin) should be instituted immediately Should be continued until culture and susceptibility become available If MSSA is isolated  preference is a beta-lactam antibiotic (cefazolin, nafcillin or oxacillin) REFERENCE Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011; 52:e18.

SAB: treatment duration
Uncomplicated SAB  14 days of IV therapy from the first negative blood culture Requires (all): Exclusion of endocarditis No implanted prostheses Follow-up cultures of blood samples drawn 2–4 days after the initial set that do not grow MRSA Defervescence within 72 h of therapy No evidence of metastatic sites of infection Complicated SAB  prolonged IV antibiotic course Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011; 52:e18. Petti CA, Fowler VG. Staphylococcus aureus bacteremia and endocarditis. Infect Dis Clin N Am.2002;16(2):413. doi: /S (01)

SAB: treatment Infectious disease (ID) consultation is a well-established tenet of SAB management Higher rates of compliance with critical components of high-quality SAB care

Delay to recognize S. aureus bacteremia and diagnosis of infective endocarditis  3 days Delay to effective treatment of S. aureus bacteremia  3 days Delay of surgical intervention from diagnosis of infective endocarditis  5 days Now I want to focus on what I think was the main cause of poor outcomes in this patient, which is the….

Delay to recognize S. aureus bacteremia Undifferentiated febrile illness incorrectly attributed to a simultaneous URI and UTI  premature closure Possibly an insufficient review of systems Murmur identified on the very first examination was overlooked Classic Oslerian manifestations of IE were missed by several physicians - and likely not sought after -

Diagnosis of SAB Interpretation of positive blood cultures
Recognition of S. aureus bacteremia (SAB) as an almost invariable cause of true bloodstream infection Discussing the epidemiological and clinical implications of SAB Distinguishing uncomplicated from complicated SAB Role of physical examination in excluding IE Role of echocardiography in excluding IE To dissect reasons for the delay further, I will be talking about SAB. I will cover….

Interpreting positive blood cultures
The most important step in the interpretation of any positive blood culture is differentiating between: True bacteremia vs. Contaminant Identification of the organism requires several steps dispersed in time Gram staining  speciation  antibiotic susceptibilities REFERENCE

The two most valuable aids for determining clinical significance are: the number of culture sets positive (as a function of the number of sets obtained) the identity of the microorganism itself Bates, D. W., T. H. Lee Rapid classification of positive blood cultures. Prospective validation of a multivariate algorithm. JAMA 267: 1962–1966 Hall KK1, Lyman JA. Updated review of blood culture contamination. Clin Microbiol Rev. 2006;19: 788–802 Weinstein MP et al. The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. Clin Infect Dis. 1997;24: Weinstein MP, Doern GV A critical appraisal of the role of the clinical microbiology laboratory in the diagnosis of bloodstream infections. J Clin Microbiol 2011;49:S26-9.

Some species are always important clinical pathogens

Staphylococcus aureus  93% Streptococcus pneumoniae  100% Group A streptococci  97% Enterobacteriaceae  % Represent TRUE bloodstream infection1: Pseudomonas aeruginosa  96% Klebsiella pneumoniae  95% Bacteroidaceae  97% Candida spp.  100% Mycobacterium spp.  100% . Pien BC, Sundaram P, Raoof N, et al. The clinical and prognostic importance of positive blood cultures in adults. Am J Med 2010; 123:81

When isolated, these organisms - including S. aureus - almost always represent true bloodstream infection and should be treated as such . Pien BC, Sundaram P, Raoof N, et al. The clinical and prognostic importance of positive blood cultures in adults. Am J Med 2010; 123:81

Clinical findings (fever, leukocytosis, imaging studies, etc.) Hypothermia (<36°C) or marked fever (>40°C) WBC <4,000 or >20,000 Hypotension Take Weinstein down Weinstein et al. found that some findings predicted true infection Weinstein MP, Doern GV A critical appraisal of the role of the clinical microbiology laboratory in the diagnosis of bloodstream infections. J Clin Microbiol 2011;49:S26-9.

However, other studies1 have shown that clinical variables, including fever, do not help differentiate between contaminants and true bacteremias Hall KK1, Lyman JA. Updated review of blood culture contamination. Clin Microbiol Rev. 2006;19: 788–802

S. aureus in urine One-third of patients with S. aureus bacteriuria have concomitant bacteremia1 It may be an indicator of bacteremia, particularly in the absence of an urinary catheter In SAB, S. aureus bacteriuria is associated with increased mortality, complications and poor outcomes2-3 Muder RR, Brennen C, Rihs JD, et al. Isolation of Staphylococcus aureus from the urinary tract: association of isolation with symptomatic urinary tract infection and subsequent staphylococcal bacteremia. Clin Infect Dis 2006; 42:46. Perez-Jorge EV, Burdette SD, Markert RJ, Beam WB Staphylococcus aureus bacteremia (SAB) with associated S. aureus bacteriuria (SABU) as a predictor of complications and mortality. J. Hosp. Med. 5: 208–211 Huggan PJ, Murdoch DR, Gallagher K, Chambers ST. Concomitant Staphylococcus aureus bacteriuria is associated with poor clinical outcome in adults with S. aureus bacteraemia. J Hosp Infect. 2008;69(4):345–9. Chihara S, Popovich KJ, Weinstein RA, Hota B Staphylococcus aureus bacteriuria as a prognosticator for outcome of Staphylococcus aureus bacteremia: a case-control study. BMC Infect. Dis. 10: 225

Staphylococcus aureus bacteremia (SAB)
The primary step in evaluating every patient with SAB is to identify complications and the extent of infection Approximately one-third of patients with SAB develop one or more complications Acute systemic (ie. sepsis) and/or localized (ie. IE) Now with an understanding of how to interpret BCx, lets focus on the management of SAB Petti CA, Fowler VG. Staphylococcus aureus bacteremia and endocarditis. Infect Dis Clin N Am.2002;16(2):413

More than one metastatic site of infection is present in 50% of cases
SAB: complications Common sites of localized/metastatic disease include: Joints (36%) Lungs (15%) Kidneys (29%) Hepatosplenic (13%) CNS (28%) Bone (11%) Skin (16%) Heart valves Intervertebral disk (15%) Add reference (Petti – 7) More than one metastatic site of infection is present in 50% of cases Lautenschlager S, Herzog C, Zimmerli W. Course and outcome of bacterernia due to Staphylococcus aureus: evaluation of different clinical case definitions. Clin Infect Dis 1993;16:567-73

SAB: IE The possibility of S. aureus IE arises in virtually every patient with SAB IE is one of the most devastating complications of SAB Overall mortality ranging from 19-65% Petti CA, Fowler VG. Staphylococcus aureus bacteremia and endocarditis. Infect Dis Clin N Am.2002;16(2):413

SAB: IE Unlike endocarditis caused by less virulent pathogens, S. aureus endocarditis is often characterized by: Rapid onset (acute IE) Frequent involvement of architecturally normal cardiac valves Absence of physical stigmata of the disease on initial presentation Saginur R, Suh KN (2008) Staphylococcus aureus bacteraemia of unknown primary source: where do we stand? Int J Antimicrob Agents 32(Suppl 1):S21–S25

SAB: IE Thus, distinguishing patients with S. aureus infective endocarditis from those with uncomplicated SAB is essential, but often difficult

SAB: IE Historically, the prevalence of infective endocarditis in patients with SAB has ranged from 3 to 64%1. Varies due to selection bias and differences in methods used to make the diagnosis Most recent data suggest that the true prevalence of IE in the SAB population is approximately 10–13%1-4 Include all the references or common denominator Palraj, B.R., Sohail, M.R. Appropriate use of echocardiography in managing Staphylococcus aureus bacteremia. Expert Rev Anti Infect Ther. 2012;10:501–508 Mylotte JM, McDermott C, Spooner JA. Prospective study of 114 consecutive episodes of Staphylococcus aureus bacteremia. Rev. Infect. Dis. 1987; 9(5), 891–907 Chang FY, MacDonald BB, Peacock JE Jr. et al. A prospective multicenter study of Staphylococcus aureus bacteremia: incidence of endocarditis, risk factors for mortality, and clinical impact of methicillin resistance. Medicine (Baltimore), 2003; 82(5), 322–332 Palraj BR et al. Predicting risk of endocarditis using a clinical tool (PREDICT): Scoring system to guide use of echocardiography in the management of Staphylococcus aureus bacteremia. Clin Infect Dis 2015 Jul 1; 61:1

SAB: IE Traditionally, acquisition of SAB in the community and unknown source/portal of primary infection (“primary bacteremia”) have been important predictors of IE in patients with SAB1-2 Nolan CM, Beaty HN. Staphylococcus aureus bacteraemia. Current clinical patterns. Am. J. Med. 60, 495–500 (1976) Palraj, B.R., Sohail, M.R. Appropriate use of echocardiography in managing Staphylococcus aureus bacteremia. Expert Rev Anti Infect Ther. 2012;10:501–508

SAB: IE In a prospective, multicenter study1 of 505 patients with SAB: Overall prevalence of endocarditis of 13% IE was present in: 21% in patients with community-acquired SAB 5% in hospital-acquired SAB 12% in hemodialysis-related SAB Chang FY,MacDonald BB, Peacock Jr JE, Musher DM, Triplett P, Mylotte JM, et al. A prospective multicenter study of Staphylococcus aureus bacteremia: incidence of endocarditis, risk factors for mortality, and clinical impact of methicillin resistance. Medicine (Baltimore) 2003;82:322–32.

SAB: predictors of IE Acquisition in the community
Persistent bacteremia Unknown portal IVDU Significant predictors were found to be… Chang FY,MacDonald BB, Peacock Jr JE, Musher DM, Triplett P, Mylotte JM, et al. A prospective multicenter study of Staphylococcus aureus bacteremia: incidence of endocarditis, risk factors for mortality, and clinical impact of methicillin resistance. Medicine (Baltimore) 2003;82:322–32.

IE: CA-SAB vs. HA-SAB Despite the higher prevalence of IE when SAB is acquired in the community, multiple studies have shown that the prevalence of IE in hospital acquired-SAB is still clinically significant1 Modified Duke criteria Inclusion of SAB as a major criterion, regardless of whether the infection is hospital acquired (with or without a removable source of infection) or community acquired Original Duke criteria Bacteremia resulting from SAB was considered to fulfill a major criterion only if it was community acquired Baddour LM, Wilson WR, Bayer AS, et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation 2015; 132:1435

SAB: IE Thus, SAB of any origin or setting is a strong risk factor for IE IE should always be considered and excluded SAB should prompt: Initiation of empiric therapy Careful clinical evaluation for metastatic complications (ie. IE)  physical examination and echocardiography Petti CA, Fowler VG. Staphylococcus aureus bacteremia and endocarditis. Infect Dis Clin N Am.2002;16(2):413

SAB: fast facts SAB almost always means TRUE bloodstream infection
Up to 1/3 of patients will have one or more complications In the setting of SAB, infective endocarditis is quite prevalent and often fatal

IE in SAB: Usual suspect?
Despite all of these, infective endocarditis is often unsuspected and therefore not detected in many patients with SAB

IE in SAB: Usual suspect?
: 32% of 260 patients with SA IE The diagnosis of IE was made only on post-mortem examination and, Was not clinically suspected in patients with SAB suspected in patients with SAB Roder BL et al. Clinical features of Staphylococcus aureus endocarditis: a 10-year experience in Denmark. Arch Intern Med 1999; 159:462–9

IE: physical exam Historically, clinicians distinguished uncomplicated SAB from IE by relying upon the presence of stigmata to IE (ie. changing or new murmur, splenomegaly, embolic lesions) Many of these manifestations are of great diagnostic value and strongly suggest endocarditis Now lets talk about the role of physical examination to distinguish complicated SAB Baddour LM, Wilson WR, Bayer AS, et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation 2015; 132:1435

IE: physical exam However, in most patients these “textbook” stigmata of IE can be few or absent on initial presentation1-3 In the setting of SAB, a murmur was absent on admission in 32% and 55% of patients with left-IE and right-IE, respectively3 Bayer et al. found echocardiographic evidence of IE in 18% of 33 consecutive adult patients with SAB but without stigmata of IE4 Baddour LM, Wilson WR, Bayer AS, et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation 2015; 132:1435 Petti CA, Fowler VG. Staphylococcus aureus bacteremia and endocarditis. Infect Dis Clin N Am.2002;16(2):413. doi: /S (01) Fernández-Guerrero M et al. Endocarditis caused by Staphylococcus aureus: a reappraisal of the epidemiologic, clinical, and pathologic manifestations with analysis of factors determining outcome. Medicine (Baltimore) 2009;88:1-22. Bayer AS, Lam K, Ginzton L, et al. Staphylococcus aureus bacteremia: clinical, serologic, and echocardiographic findings in patients with and without endocarditis. Arch Intern Med 1987;147:

IE: physical exam This is particularly true for S. aureus IE:
Evolves too quickly for the development of immunologic vascular phenomena Often in IVDU  right-sided valves (usually no peripheral emboli and immunologic phenomena) Baddour LM, Wilson WR, Bayer AS, et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation 2015; 132:1435

IE: physical exam The majority of patients with IE do not have clinically evident disease at the time of bacteremia1 Thus, in the setting of SAB, the absence of classic physical findings cannot exclude the diagnosis of IE Showler A, Burry L, Bai AD, et al. Use of transthoracic echocardiography in the management of low-risk Staphylococcus aureus bacteremia: results from a retrospective multicenter cohort study. J Am Coll Cardiol Img 2015;8:924–31

SAB: echo The role of echocardiography in patients with SAB should not be underestimated All practice guidelines1-5 endorse routine echocardiography for all cases of SAB Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009;49:1–45 Habib G, Lancellotti P, Antunes MJ, et al ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J 2015; 36:3075. Baddour LM, Wilson WR, Bayer AS, et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation 2015; 132:1435 Nishimura RA, Otto CM, Bonow RO, et al AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice. J Am Coll Cardiol 2014;63:2438–88 Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011; 52:e18.

SAB: TTE or TEE? Historically, the consensus ends when it comes to the technique: TTE or TEE?, both? Is TTE enough in some low-risk patients?

SAB: TTE or TEE? Sensitivity (%) Specificity (%) TTE 70 ~90 TEE 96
TEE is deemed superior to TTE in detecting small vegetations, perforations, and periannular abscesses and in diagnosing IE that involves prosthetic valves or intra-cardiac device leads3-5 Habib G et al. Recommendations for the practice of echocardiography in infective endocarditis. Eur J Echocardiogr 2010;11:202–219 Mugge A, Daniel WG, Frank G, Lichtlen PR. Echocardiography in infective endocarditis: reassessment of prognostic implications of vegetation size determined by the transthoracic and the transesophageal approach. J Am Coll Cardiol 1989;14: 631–638 Reynolds HR, Jagen MA, Tunick PA, Kronzon I. Sensitivity of transthoracic versus transesophageal echocardiography for the detection of native valve vegetations in the modern era. J Am Soc Echocardiogr. 2003;16:67–70. doi: /mje Kaasch AJ, Michels G. Staphylococcus aureus Bloodstream Infection: When Is Transthoracic Echocardiography Sufficient?. JACC Cardiovasc Imaging Aug;8(8): doi: /j.jcmg Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011; 52:e18

SAB: TTE or TEE? AHA/IDSA 2015 IE guidelines1
Other guidelines suggest similar approach (TTETEE) For example, a patient with fever and a previously known heart murmur and no other stigmata of infective endocarditis (IE). †High initial patient risks include prosthetic heart valves, many congenital heart diseases, previous endocarditis, new murmur, heart failure, or other stigmata of endocarditis Baddour LM, Wilson WR, Bayer AS, et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation 2015; 132:1435 Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009;49:1–45 Habib G, Lancellotti P, Antunes MJ, et al ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J 2015; 36:3075. Nishimura RA, Otto CM, Bonow RO, et al AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice. J Am Coll Cardiol 2014;63:2438–88

SAB: TTE or TEE? “Cost-effectiveness calculations suggest that TEE should be the first examination in adults with suspected IE, particularly in the setting of staphylococcal bacteremia” ?Cost: TEE-approach vs. 4-weeks of IV antibiotics Baddour LM, Wilson WR, Bayer AS, et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation 2015; 132:1435 Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011; 52:e18.

SAB: TTE or TEE? 65% acquired SAB while in the hospital
88% had a known focus of infection Clinical evidence of IE was rare 7/103 (7%) 5 peripheral emboli 2 new murmurs TTE: NPV was only 81% Fowler VGJ, Li J, Corey GR, et al. Role of echocardiography in evaluation of patients with Staphylococcus aureus bacteremia: experience in 103 patients. J Am Coll Cardiol 1997;30:1072–8

SAB: TTE or TEE? Others1-2, including current guidelines for catheter-related infections and MRSA infections3-4, recommend at least 4 weeks of therapy for SAB because infective endocarditis is assumed to be present, unless TEE is negative TTE is insufficient to rule out infective endocarditis (A-II)3-4 Showler A, Burry L, Bai AD, et al. Use of transthoracic echocardiography in the management of low-risk Staphylococcus aureus bacteremia: results from a retrospective multicenter cohort study. J Am Coll Cardiol Img 2015;8:924–31 Palraj, B.R., Sohail, M.R. Appropriate use of echocardiography in managing Staphylococcus aureus bacteremia. Expert Rev Anti Infect Ther. 2012;10:501–508. Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009;49:1–45 Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011; 52:e18.

SAB: TTE or TEE? However, adherence to this recommendation is low
TEE is expensive, invasive and not universally available Whether TTE is sufficient to rule out IE in some patients with SAB continues to be a topic of ongoing debate and research Palraj, B.R., Sohail, M.R. Appropriate use of echocardiography in managing Staphylococcus aureus bacteremia. Expert Rev Anti Infect Ther. 2012;10:501–508.

SAB: TTE or TEE? Criteria identifying patients with uncomplicated SAB who may not require TEE have been proposed1-6 Bergin SP, Holland TL, Fowler VG Jr, Tong SY. Bacteremia, Sepsis, and Infective Endocarditis Associated with Staphylococcus aureus. Curr Top Microbiol Immunol Dec 8 Kaasch AJ, Fowler VG Jr., Rieg S, et al. Use of a simple criteria set for guiding echocardiography in nosocomial Staphylococcus aureus bacteremia. Clin Infect Dis 2011;53:1–9. Khatib R, Sharma M. Echocardiography is dispensable in uncomplicated Staphylococcus aureus bacteremia. Medicine (Baltimore) 2013;92:182–8. Joseph JP, Meddows TR, Webster DP, et al. Prioritizing echocardiography in Staphylococcus aureus bacteraemia. J Antimicrob Chemother 2013;68:444–9 Palraj BR et al. Predicting risk of endocarditis using a clinical tool (PREDICT): Scoring system to guide use of echocardiography in the management of Staphylococcus aureus bacteremia. Clin Infect Dis 2015 Jul 1; 61:1 Showler A, Burry L, Bai AD, et al. Use of transthoracic echocardiography in the management of low-risk Staphylococcus aureus bacteremia: results from a retrospective multicenter cohort study. J Am Coll Cardiol Img 2015;8:924–31

SAB: TTE or TEE? Based on the current evidence it may be reasonable to forgo TEE for circumstances in which all of the following conditions are met: Nosocomial acquisition of bacteremia Sterile follow-up blood cultures within four days after the initial positive culture Defervescence within 72 hours of initial positive blood culture No permanent intra-cardiac device No hemodialysis dependence No clinical signs of endocarditis or secondary foci of infection Prompt removal of removable focus of infection, if present Bergin SP, Holland TL, Fowler VG Jr, Tong SY. Bacteremia, Sepsis, and Infective Endocarditis Associated with Staphylococcus aureus. Curr Top Microbiol Immunol Dec 8 Fowler, VG; Sexton, DJ. Clinical approach to Staphylococcus aureus bacteremia in adults. In: UpToDate, Calderwood, SB (Ed), UpToDate, Waltham, MA, 2016

Take Home Points Isolation of Staphylococcus aureus in blood cultures almost always represents TRUE bloodstream infection Infective endocarditis is frequent in patients with SAB and often fatal In the setting of SAB, the absence of a murmur and classic physical findings is insufficient to rule out IE A normal TTE cannot rule out IE in the majority of patients with SAB

Final thoughts Why was the murmur missed on several examinations, including that of seasoned clinicians?

Emergency Department Examination: Fever (101.5 °F)
 medical student Examination: Fever (101.5 °F) Tachycardia (HR 107 beats/min) Systolic ejection murmur Clear lungs Normal joints

Final thoughts 1980’s: emergence of “medical-industrial complex”1
The era of high throughput Dr. William Osler (second from left) at the Johns Hopkins Hospital, Baltimore Goitein, Lara. "Training Young Doctors: The Current Crisis." The New York Review of Books. The New York Review of Books, 4 June Web. 7 Apr. 2016

Final thoughts “…much more to do, for more patients, in much less time” Teaching the least of priorities Dr. William Osler (second from left) at the Johns Hopkins Hospital, Baltimore Goitein, Lara. "Training Young Doctors: The Current Crisis." The New York Review of Books. The New York Review of Books, 4 June Web. 7 Apr. 2016

Medical training: a time for reflection?
Medical education is essentially a verbal tradition and demonstrated at the bedside “A resident may read extensively about endocarditis in a textbook, but this cannot replace the experience of watching an attending physician make this diagnosis” Dr. William Osler (second from left) at the Johns Hopkins Hospital, Baltimore Goitein, Lara. "Training Young Doctors: The Current Crisis." The New York Review of Books. The New York Review of Books, 4 June Web. 7 Apr. 2016

Urgency to restore protected time for good teaching and good patient care “Otherwise, not too long from now, we may hear Osler’s footsteps in the hospital hallway—but when we turn around he will not be there” Lara Goitein MD Dr. William Osler Goitein, Lara. "Training Young Doctors: The Current Crisis." The New York Review of Books. The New York Review of Books, 4 June Web. 7 Apr. 2016

MORBIDITY & MORTALITY CONFERENCE

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