Infection of the Cardiovascular System Rizalinda 2016

8/18/2019 Infection of the Cardiovascular System Rizalinda 2016

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After presenting this lecture, the students

must be able to explain about the

characteristics, virulence factors, pathogenesis

of microbial infection causing cardiovascular

disorder, clinical manifestation, laboratoric

diagnosis and the treatment for cardiovascular

infectious diseases.


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After the lecture students must be able to :

1. Describe the characteristics of microbes causing

cardiovascular diseases

2. Describe the virulence factors including the effects

towards host

3. Describe the pathogenesis of cardiovascular disease

4. Mention the clinical manifestation & the causativemicrobes

5. Explain laboratory diagnosis

6. Know the antibiotic used for therapy


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Infections of the cardiovascular

system: Myocarditis

Pericarditis

Endocarditis


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INFECTIOUSMYOCARDITIS


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Myocarditis

Myocarditis is an inflammation of themyocardium, may be caused by:◦ infectious agents (bacterial, mycotic, viral, parasitic)

◦ allergic reaction

◦ drug reaction◦ associated with systemic inflammatory disease

Acute Myocarditis: symptoms ranges from anasymptomatic illness with reversible changes tofulminant myocardial necrosis and death

Chronic Myocarditis: lymphocytic infiltration of themyocardium may cause subacute/chronicdeterioration of cardiac function


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Incidence of myocarditis

Incidence is unknown

Often follows an upper Resp Infection

Children and young adults are more

prevalent than older adults

Major cause of sudden cardiac death in a

person under 40 years old


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Clinical Features of Myocarditis

Asymptomaticprogressive myocardialdisfunction death

Symptomatic fever, fatigue, malaise,chest pain, dyspnea, palpitation, arthralgia,

upper respiratory tract symptoms

Diagnosis is often difficult.Diagnosis is suggested for an acute febrile illness

with unexplained heart failure or malignantarythmia

•Physical examination: Tachycardia, fever, hypotension

•Signs of left-sided or biventricular congestive heart failure

•S3 gallop


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Features for Diagnosis of

Myocarditis

Recent-onset congestive heart failure and

a history of antecedent viral infection

Elevated ESR (Eryth. sed. rate) & LDH

(lactate dehydrogenase)

Echocardiography shows dilated LV with

global hypokinesia

Elimination of other causes of LV

dysfunction


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Clinical history

New-onset congestive heart failure

No previous history of heart disease

Preceding symptoms of fever and chills

(antecedent viral illness)

May have chest pains and gastrointestinal

symptoms

Unexplained tachycardia

Syncope or presyncope


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Differential Diagnosis

Ischemia

Primary pulmonary disease

Primary congenital disease

Rheumatologic disease

Endocrinopathies

Electrolyte disturbances

Toxin exposure (ethanol, cocaine, heavy

metals)


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Diagnostic tests

1. Blood examination: CK-MB, increase liver enzymes, ESR,LDH, leukocyte count

2. Electro Cardio Graphy:a. non specific changes

b. Sinus tachycardia or atrial fibrillation

c. ST-T wave changes including pesudoinfarction patternd. Intraventricular conduction delay or LBBB

e. AV blocks or repolarization abnormalities

3. Chest X-ray: mild-moderate cardiomegaly with venouscongestive stages

4. Echocardiography: global LV dysfunction or globalhypokinesia

Definitive diagnosis by endomyocardial biopsy


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Microorganisms causing Myocarditis

Virus

Fungi

Bacteria

◦ Bacterial toxins (diphteria toxin)

◦ The Spirochetes (Borrelia burgdorferi causingtick born Borrelia Lyme myocarditis)

◦ Rickettsiae (Rickettsia ricketsii ) Parasites (toxoplasmosis, Trypanosoma

Cruzi)


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Infectious causes of MyocarditisRegion Normal host Immunocompromised

DevelopedWorld

C omm

on

VIRUSES: Coxsackie A and B, echovirus,

CMV, EBV, HHV-6, Influenza virus A andB, adenovirus, Parvovirus, HBV, HCV

BACTERIA: diphteria, Lyme disease,

organisms associated with IE

PARASITES: American Trypanosomiasis,

trichinosis

VIRUSES: HIV, CMV, EBV,

VZV, adenovirus,parvovirus

FUNGI: Candidiasis,

aspergillosis,

cryptococcosis

PARASITES:toxoplasmosis,

American trypanosomiasis Un c omm on

VIRUSES:Adenovirus, Parvovirus,

Respiratory syncitial virus, HBV, HCV

BACTERIA:Staphylococci,

Streptococci, meningococci,

Salmonellae, listeria, clostridia,rickettsia, bartonellosis, ehrlichiosis

FUNGI:

histoplasmosis,

blastomycosis,

coccidioidomycosis,

zygomycosis

Developing

World

VIRUSES: poliovirus, mumps, rubella, arenaviruses, dengue,

rabies, chikungunya, ebola virus, yellow fever

BACTERIA: leptospirosis

PARASITES:American Trypanosomiasis, African Trypanosomiasis


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Non infectious etiology ofmyocarditis:

◦ Unknown/idiopathic

◦ Toxin

◦ Hypersensitivity

◦ Autoimmune


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Viral cause of Myocarditis

Viral myocarditis:◦ Usually mild or asymptomatic

◦ Cardiac Signs: due damage to the myocard

(cardiomegaly, short breath, palpitations,arythmia)

◦ Non-cardiac signs: rash, fever, sore throat

◦

Chest pain


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Treatment of myocarditis

Treat the underlying infectious orinflammatory process

Supportive treatment (bed rest, oxygen,

antipyretic) Control congestive heart failure with

diuretics and Ace-inhibitors

Steroids (controversial!!)


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PERICARDITIS


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Pericarditis

Pericarditis: injury to the pericardium causingcellular infiltration, fibrin deposition andoutpouring of pericard fluid.

The cause of pericarditis:◦

Infectious agents◦ Non-infectious: Acute MI, Uremia, neoplasm,

myxedema, cholesterol, trauma, aortic aneurism (withleakage to peric.sac), radiation, assoc with severechronic anemia, infectious mononucleosis, sarcoidosis,postcardiac surgery, acute idiopathic.

◦ Hypersensitivity /autoimmunity: RF, collagen vasculardisease (SLE, RA, scleroderma), drug-induced(procainamid, hidralazin), Post MI (Dressler’ssyndrome, postpericardiotomy)


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Infectious Agents causing Pericarditis

◦ VIRAL

◦ BACTERIAL: pyogenic or syphilitic

◦ TUBERCULOUS

◦

MYCOTIC◦ PARASITIC


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Infectious causes of pericarditis

Viruses (most common cause of

idiopathic Pericarditis)

Mycobacteria

CMV,

Herpes simplex virus,Coxsackie A, B,

Echovirus,

Epstein Barr virus,

adenovirus,

Influenza,

Mumps, VZV, EBV, and HIV

Mycobacterium tuberculosis ,

Mycobacterium chelonae, Mycobacterium aviumcomplex

Spirochetes

Borrelia burgdorferi

Bacteria Mycoplasma

Streptococcus pneumoniae ,

Streptococcus spp., Staphylococcus

aureus , Neisseria meningitidis* ,

Listeria monocytogenes, Hemophilusinfluenzae, Francisella tularensis, Brucella

melitensis, Enteric Gram negative rods,

Actinomyces spp., Nocardia asteroides,

legionella pneumophila, Tropheryma

whippelii, Salmonella spp., Campylobacterspp., Rickettsia/Q fever

Mycoplasma pneumoniae, Ureaplasma

urealyticum, Mycoplasma hominis

Fungi

Histoplasma capsulatum, Coccidioides immitis,Cryptococcus neoformans, Blastomyces dermatitidis,

Candida spp., Aspergillus fumigatus

Parasites

Toxoplasma gondii, Entamoeba histolityca,

Echinococcus granulosus, Schistosoma spp


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Bacterial causative of pericarditis

Bacteria spread to the pericard through:◦ Hematogenous seeding during bacteremia (esp Mtb)

◦ Extension of infection from a contiguous focus in thechest (complication postoperative or post-traumatic)or from a subdiaphragmatic abscesses

◦ Invasive bacterial infection (staphylococcalendocarditis)

Pathologic changes in the pericardium which are causedby immune complex deposition sterile exudates

Most effusions resolve without specific therapy

Most common bacteria: streptococci (S.pnie, S. Vir.)**and staphylococci


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*


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**


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Other causes may be....

Mycoplasma causing pericarditis(Fournier et al, 2001)Treat with

doxycyclin after drainage

Mycobacteria: important cause indeveloping countries; 1-8% cases among

pulmonary tuberculosis patients.

Histoplasma capsulatum; 6% ofsymptomatic histoplasmosis


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Clinical Classification of pericarditis

I. Acute pericarditis (6 months)

I. ConstrictiveII. Effusive

III. Adhesive (nonconstrictive)


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Clinical Features of acute pericarditis

Chief manifestation: chest pain – precordial/retrosternal, radiates to the trapeziusridge or neck, worsen when supine, coughing ordeep inspiration. Relieved when sitting uprightor forward.

Pericardial friction rub (on auscultation):pathognomonic finding of acute pericarditis

Fever (common) ESR usually elevated

ECG: ST segment elevation with assoc PR

depression


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Clinical History of pericarditis

1. Acute presentation (


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Diagnosis of pericarditis

Pericardiocentesis Pericardial biopsy Characteristic ECG changes Echocardiography: sign of effusion

Effusion are subjected to microbial analysis: cultures foraerobic, anaerobic bacteria, detection of viruses,chlamydiae, mycoplasmas, fungi and mycobacteria

However, since specific etiology of pericarditis is notapparent, and because of their brief and benign course – full diagnostic evaluation becomes not appropriate.

Confirming a particular viral agent is not necessary (costly)and retrospective diagnostic does not affect treatment.


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Laboratory Findings and Diagnostic

Studies VIRAL PERICARDITIS:

◦ Clinical

◦ Leukocytosis

◦ Rising titer in paired sera rarely done

TUBERCULOUS PERICARDITIS:

Inferred diagnosis if AFB is found

elsewhere. BACTERIAL PERICARDITIS:

pericardiocentesis


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Management of pericarditis

Hospitalization to relief symptoms,evaluate diagnosis and observecomplications

Specific treatment depends on theetiology

To reduce symptoms in idiopathic or viralpericarditis: Aspirin 2-6g/day or use other

NSAIDS Appropriate intravenous antibiotics and

surgical drainage


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INFECTIVEENDOCARDITIS


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Infective Endocarditis

Inflammation or infection of the endocard including the valve

caused by microorganisms

preexisting tissue damage

frequently fatal

And Nonvalvular areas or implanted mechanical devices

-Artific.Heart valve

-Pacemakers

-Implantable defibrillators


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KEY POINTS

Infective endocarditis (IE) remains universallylethal if not aggressively treated

Medical progress has altered the epidemiologyof IE

Healthcare-associated IE has become a majorissue in industrialized countries

Prophylaxis for IE has been questioned and

new guidelines have been proposed Successful therapy for IE is being challenged by

the development of antibiotic resistance


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Epidemiology of IE

Relatively rare – due to lacking report? In developing countries - before year 1950 -

IE was a complication of Rheumatic Heart

Disease and poor dentition. Antibiotic use demoraphic pattern changed from

30-40 in the preantibiotic era to 47-69 in the 1st

decade of the 21st century.

Aging more Degeneration Heart Valve diseasemore use of heart planted substitutes and intracardiac

devices.

Predisposing chronic comorbidities (diabetes, HIV, renal

disease, nosocomial bacteremia).


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IE is IMPORTANT because of its seriouscomplications:

◦ Stroke

◦ Requires open heart surgery◦ Death


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Pathogenesis of IE

Persistent endocardial infectioncontinous bacteremia

Is uncommon due to transient bacteremia.


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Physical findings

Congestive heart failure Neurologic findings: cerebral emboli,

encephalopathy, mycotic aneurism leak,

meningitis, brain abscess Chorioretinitis, endophtalmitis

Systemic embolization


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Diagnostic Criteria for IE

Blood Culture: to find the causativemicroorganism in blood

Bacterial and Fungal

Fungal Modified Duke criteria


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Infective Endocarditis

Risk factors:◦ acquired valvular disease (eg. chronic rheumatic heart

disease)

◦ cardiac structural abnormalities (eg. artificial (prosthetic)heart valve, including bioprosthetic and homograft valves,

previous bacterial endocarditis, certain congenital heartdiseases, Heart valve disease that develops after hearttransplantation, Hypertrophic cardiomyopathy (HCM),Mitral valve prolapse with valve regurgitation (leaking)and/or thickened valve leaflets

◦

immunosuppressed status◦ prolonged surgery, reoperation

◦ catheter related bacteremia

◦ sternal wound infection


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Classification of IE

Based on clinical symptoms Based on the host

Based on the causative microorganism


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Endocarditis

Based on clinical symptoms Acute Bacterial Endocarditis – acute and fulminant

Caused by Staphylococcus aureus

Virulent May even affect healthy valves

Subacute Bacterial Endocarditis

Caused by Streptococcus viridans

Clinical symptoms unnoticable/More Insidious

Usually affect already damaged valves

Recently, due to lack of clinical importance to distinguish acute and sub acute,

now this classification is not further discussed. ,


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Based on the host◦ Native valve endocarditis (NVE):

Streptococcus viridans, Group D streptococcus,

S.aureus, Enterococci and HACEK (Haemophylus

aphrophilus, Actinobacillus actinomycetencomitan,

Cardiobacterium hominis, Eikenella corrodens).

◦ Prosthetic valve endocarditis (PVE)

Staphylococcus epidermidis◦ Drug Addicted persons endocarditis (IVDA) usually Staphylococcus aureus or fungi


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Echocardiography helps to

visualize the heart valves and

deformities.

Vegetations growing on the

valve may damage the function

of the valve.

Excised valve

Ref: Cabell , et al, 2003


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How IE occurs

At normal condition blood is clear of infectiousorganisms and endothelium is resistant tocolonization

Bacteria or fungi can enter the blood from othersites of the body or from wound, more common

among intravenous drug users Preexisting lesions of the layer of endothelial cells

covering the valve or endovascular surfaces(damaged surfaces) make it susceptible to

colonization of certain types of bacteria Once bacteria/fungi have colonized the heart

internal surface, the immune system cannot clearthem off


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Pathogenesis of IEInjured endocard surface

Sterile thrombus develops on the injured surface=vegetation = nonbacterial thrombotic endocarditis= NBTE

Bacterial entrance to the blood(after brushing teeth/injury/diagnostic procedure)

certain bacteria attaches to the injured surface

Fibrin and platelets deposited

Complications:

Mechanical cardiac injury, thrombotic/septic emboli, immune injury


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Lesions on the heart that predisposeEndocarditis

1. Rheumatic Valvular disease

2. Acquired valve lesions

3. Hypertrophic obstructive cardiomyopathy4. Congenital Heart disease (PDA, VSD, TF, Bicuspid aortic

valves)

5. Surgically implanted intravascular hardware, prosthetic

heart valves, pulmonary systemic vascular shunts,ventriculo-atrial shunts for hydrocephalus

6. Previous endocarditis

F h bl


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Factors that enables any

microorganism causing IE:

1. Ability to enters the circulation

2. Ability to survive in the blood

3. Ability to attach to the endocard


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Most common causing microorganismsare GRAM positives (90%)::

◦

Staphylococcus aureus & CoNS (coagulase negativestaphylococcus)

◦ Streptococcus spp.

◦ Enterococci Because of its resistance to elimination and it has dextran

component of the cell wall used for attachment to thrombus

Less common cause (10%):◦ Coxiella burnetii (Q fever)◦ Chlamydia spp

◦Legionella spp

◦ Bartonella spp

◦ Haemophylus◦ fungi

Why?


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Blood flow can clear bacteria within minutes and detoxifybacteria

How do Streptococci avoid clearance?

Secreted Platelet Aggregation Associated

Proteins induces platelet aggregation on

the surface of a heart valve especially on

injured heart valve

Upregulation of aII b63-integrin

binds fibrinogen, forming a thrombus .

Released adhesins allow adherence

to platelet’s membrane

Released ADP and serotoninallows recruitment of additional

platelets

The initial infecting

streptococci would be

trapped within the

thrombus.


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Subacute IE (=SBE) is caused by m.o.other than Staphylococcus aureus

Occurs from a few days to 5 weeks or

more between the identifiable eventproducing bacteremia (e.g. dentalprocedure) to the time of diagnosis

Low grade fever

Other non specific signs reflect theexistence of cardiac or peripheralcomplications


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Traditional Clasf of IE

Acute BacterialEndocarditis:

◦ Ec: S. aureus (virulent)

◦ Clin: High fever, acute

◦ Path: Normal valves,

murmur neg

◦ Progn: fatal in 6 weeks

if untreated

SBE:

◦ Ec. S.viridans,

enterococci (less vir)

◦ Low grade fever,

subacute course

◦ Path: damaged valves,

murmur pos

◦ Better prognosis


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Injecting Drug use

a1

S. aureus

Gram neg. rods

Enterococci

Candida

a2

Streptococci

Enterococci

S. aureus

a3

S. aureus

Enterococci

Streptococci

a4

S.epidermidis

Gram neg. Rods

S. aureus

Candida

a4a2 over time

Infective endocarditis

Native Valve endocarditis Prosthetic valve endocarditis

Categorization of microbial etiologies of

Non injecting drug use Early Late

Valvular heart

diseaseNormal valve


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Cutaneous and Ocular signs of SBE

Sign Site and appearancePetechiae

Splinter hemorrhages

Osler’s nodes

Janeway Lesions

Roth spots

Conjunctiva, oral cavity, skin

Linear subungual hemor that

do not reach the distal nail

bed

Small painful red nodules in

the distal phalanges

Small erythematous non

tender macules on th palms

and soles

Small white retinal infarcts

surrounded by hemorrhage


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The Duke Criteria

A

B


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>38.0)


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Interpretation of the Duke criteria

Definite pathologic diagnosis: either A or B of thepatologic findings of Duke’s criteria Definite clinical diagnosis: two major criteria, or 1

major and 3 minor or 5 minor criteria Possible diagnostic : findings consistent with IE,

including 1 major and 1 minor criteria, or 3 minorcriteria

Diagnosis is rejected when:◦ there is an alternative diagnosis for the clinical

manifestations◦ resolution of the disease within 4 days of antibiotics

◦ no pathologic evidence upon surgery or autopsy


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Treatment of IE

1. Appropriate antibiotics2. Bed rest

3. Treat heart failure and arrythmias as

needed4. Echocardiography (may prove beneficial)

5. Valvular replacement, if necessary

Microbiological methods to


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Microbiological methods to

diagnose infection

Bacterial detection:◦ Culture, isolation and identification of specimen◦ Serologic examination of serum (Antibody titer)◦ Molecular Polymerase Chain Reaction (PCR)

Viral detection◦ Tissue culture◦ Serologic examination of serum◦ Molecular (PCR)

Fungal◦ Culture, isolation and identification

◦ Molecular (PCR)


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Blood Culture Requires +10 ml blood, collected 3 times within 24 hours and at least 1

hour apart; before antibiotics If clinically stable, stop antibiotics 2-3 days before collecting blood for

culture

Negative culture: Fungus previously treated with antibiotic

caused by fastidious m.o. (Legionella, Bartonella, abiotrophia) Bacteria can not grow in artificial media Slow grower bacteria

If negative Culture should order:◦ Serology

◦ tissue culture (for intracellular bacteria)

◦ immunohistology◦ or PCR detection

Tissue culture is intended for isolation of Coxiella burnetii, Chlamydia spp.,legionella spp., Bartonella spp..


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Serology tests

Agglutination test for Brucella melitensis Indirect fluorescense for L. pneumophila

ELISA for Mycoplasma pneumoniae

CF, ELISA and indirect IF for Chlamydiaspp..

Management:


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Management:

◦According to the causing bacteria: antibiotics 4-6weeks

◦ Surgery to remove infected tissues or correct thedamaged valve; the indications are:

Refractory cardiac failure

Persistent sepsis caused by a surgically removable focus

or a valvular ring or myocardial abscess

Persistent life-threatening embolization


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Clinical Course of endocarditis


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Clinical Course of endocarditis

Acute Rheumatic Fever and


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Acute Rheumatic Fever and

Rheumatic Heart Disease

Inflammatory disease affecting the heart,skin and soft tissues

Commonly attacks children or young

adults peak incidence at 5-15 y.o. As a complication (occurring 5 days-10 w;

usually 2-3 w) after pharyngitis which is

caused by Group A Streptococcus pyogenes

Diagnosis based on Jones Criteria and

confirmation of streptococcal infection


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Pathogenesis of ARF/RHD

Toxins secreted by Streptococci Autoimmune cross reactions between bacterial

antigens and endocard

Inflammation may affect pericard, myocard andendocard Scarred tissue (75-80% attacks themitral valve) deformity

Defect on valves do not appear until 10-30 years

(in developed country latency period is shorter) Recurrent in 10% more damage to the heart Prophylaxis is important

Below: Artist rendition of normal left heart anatomy,


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Ref: Seckeler MD, 2011

b) Two-dimensional echocardiogram of the left heart, demonstrating a

thickened anterior leaflet of the mitral valve.

c) Two-dimensional echocardiogram with color Doppler, demonstrating

moderate-to-severe mitral valve regurgitation (blue jet).

demonstrating the left atrium connected to the left

ventricle via a mitral valve.


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Symptoms of Acute carditis:◦ Tachycardy, reduced ventr.contractility, transient

mitral murmur, aortic regurgitation, pericardial frictionrub, diastolic murmur on the apex of the heart

Chronic phase after inflammation on the valve:

◦ Stenosis

◦ Valve regurgitation

◦

40% of RHD will develop Mitral Stenosis , 25% MS +Aort. Regurgitation or aort. Stenosis; Rarely affectstricuspid valve

Di i f ARF (J ’ C i i )


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Diagnosis of ARF (Jones’ Criteria)

MAJOR CRITERIA

(major manifestations)

MINOR CRITERIA

(minor manifestations)

EVIDENCE OF

GROUPA

STREPTOCOCCAL

INFECTION

1. Carditis

2. Polyarthritis

3. Sydenham’s

Chorea (involuntary

movements)

4. Erythemamarginatum (Skin

rash with advancing

edge and clearing

center

5. Subcutaneous

nodules

1. Migratory

arthralgia

2. Fever

3. Laboratoty findings:

Increased acute phase

reactants , Eryt SedRate, leucocytosis, C

reactive protein)

4. Prolonged PR Interval

on ECG

1. Antistreptolysin O

antibody and anti

DNase B rising or

elevated

2. Throat culture

positive for Group AStreptococci or

rapid streptococcal

antigen test positive

If proof of streptococcal infection is present , there is a high

probability of ARF if there are:

2 major manifestations or 1 major + 2 minor criteria


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definitions

Carditis:1. New significant murmur (usually mitral or

aortic regurgitation)

2. Pericardial friction rubs or signs ofpericardial effusion

3. Increased heart size

4. Congestive heart failure

Polyarthritis: arthritis in 2 or more joints

and migratory

Major manifestations of Jones criteria don’t occur as frequently in Asian countries

as compared to western countries

Strep infection

i h

Asymptomatic

t i f tisudden onset of sore throat

i ll i


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Hyaluronic acid

capsule

Antibioticsare required eventhoughsymptoms disappeared

Ongoing Ab producing

esp. anti M Ab

Infection of the pharynx

Ab to strept +

Infection subsided

Acute rheumatic fever

?PersistentStrep in the throat

with symptoms strep infectionpain on swallowingfeverheadache

red throat/tonsils

abdominal pain, nausea andvomiting, especially in children

Rheumatic Heart Disease &

Post streptococcal

Rheumatoid arthritis

Infectiousmaterials of

Group Astreptococci

streptokinase

streptolysin O (SLO)

DNAase

Hyaluronidasemajor surface protein,

M protein

Causing autoreactivity

feverpainful, tender, red swollen joints

pain in one joint that migrates to another one

heart palpitations

chest pain

shortness of breath

skin rashes

fatigue

small, painless nodules under the skin


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Diagnostic Tests for ARF

1. Blood examination: CBC, ASO titers,CRP, ESR

2. Throat cultures* for streptococci

3. ECG: check for heart blocks4. 2-D Echo with Doppler: check for

valvular dysfunction and pericardial

effusion

*Throat/nasopharyngeal culture swab is discussed in the respiratory system


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REVIEW ON MICROBIAL AGENTS

OF CARDIOVASCULARINFECTIONS

http://en.wikipedia.org/wiki/File:Streptococci.jpg


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Streptococcus

Family: Streptococcaceae

Genus: Streptococcus

Morphology:◦ Coccus, gram positive

◦ On solid media: circular colony, convex,translucent-opaque, pinpoint size (0.5-1 μm)

◦ Catalase test negative

◦ Requires enriched medium: blood agar 5%

◦ In broth medium, they grow in pairs or chains

Small colonies

appearance on Blood agar

http://en.wikipedia.org/wiki/File:Streptococci.jpg


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Virulence factor of Streptococcus

1. Produces hemolysin alpha and beta2. Leucocydin – to destroy phagocytes

3. Erythrogenic toxin ( in scarlet fever)

4. Hyaluronidase – hydrolyse tissuecement/hyaluronic acid

5. Streptokinase – fibrinolysin

6. Nuclease (ribonuklease,dioksiribonuklease) – destroys viscoustissue debris


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Cell structure of Streptococci

Streptococci cells viewed by


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Streptococci cells viewed by

Electron Microscope

Cl ifi i b d h l i


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Classification based on hemolysis

Hemolytic activity:◦ α hemolytic

◦ Β hemolytic

◦ γ hemolitic

Αl h h l i


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Αlpha hemolytic

incomplete hemolysis; green zone aroundcolony; oxydation of iron in hemoglobin

(Hb methHb)

e.g. Streptococcus viridans, usuallynonpathogenic but opportunistic, may

cause subacute endocarditis

Β h l i


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Βeta hemolytic

o Complete hemolysis of blood, clear zone aroundcolonies, 2-4 x larger the size of colony.

o Streptococcus pyogenes (member of GAS = Group Astreptococcus) – causing tonsillitis,bronchopneumonie, scarlet fever, erysipelas, cellulitis,glomerulonephritis, rheumatic fever

o Streptococcus betahemolytic among group B (GBS)are those found in vaginal mucosa causing puerperalinfection, neonatal meningitis, endocarditis

o Streptococcus betahemolytic among group C arethose causing erysipelas, puerperal fever, throatinfections


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Id ifi i f S i

http://en.wikipedia.org/wiki/File:Strep_Classification.svg


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Identification of S. pneumoniae OptochinTest

◦ Optochin lyses Streptococcus pneumoniae

◦ Streak streptococci on MHA

◦ Place Optochin disc on agar, incubate 24 hours

observe zone of growth inhibition (must be >14 mm)

Bile Solubility Test

◦ Differentiate S. pneumoniae from other alphahemolytic strains see also BA*plate

◦ Bile or Sodium desoxycholate (bile salt) reduces surface tension. Bacterialautolytic enzymes results in a faster lytic action because of the lowered

bacterial & medium’s surface tension Grow bacteria 13-24 hours (not longer or colonies grow old) on Blood agar Place a drop of 10% bile salt next to an isolated colony, or 2% bile salt if in test tube Gently allow liquid cover the colony, do not dislodge colony Incubate at 35oC, aerob, for 30 minutes

Observe lysis of colony

Differentiating Streptococcus


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g ppneumoniae from Streptococcus

viridans S.pneumoniae after 24-48 hours produce

indented surface; S.viridans’ surface

remains domed.

Di i i hi S i


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Distinguishing S. pneumoniae

G A S


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Group A Streptococcus

Protein M (on the cell surface of most serotypes) virulence fc

SPE (Streptoccocal Pyrogenic Exotoxins)

Type A --- similar molecule as Staph TSST-1

Type B

Type C

Diseases caused by


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y

Group A Streptococcus

Weiss, 1996

Identification of group A


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g p

streptococci

BacitracinTest◦ Streak streptococci on MHA

◦ Place Bacitracin impregnated filter paper disc onagar, incubate 24 hours

Group A: observe zone of growth inhibition (=sensitive)

Antigenic-antibody reaction◦ Extract the specimen, react with latex particle

coated with antibody to streptococci, observeagglutination

Identification of group B


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g p

streptococci

CAMP substance is produced by group Bstreptococci that works sinergically withstrong betahemolysis of Staphylococcus aureus

Streptococci is streaked on to Blood agar

plate, adjacent to (at a right angle) to a

line streaking of Staphylococcus aureus (2

mm distance), incubate 37oC

If it is a Group B streptococcus: anarrowhead zone of increased hemolysis,

other group shows normal hemolisis

around colony

CAMP TEST L ti h


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CAMP TEST: Lytic phenomenon

S. agalactiae on CAMP test shows increasedhemolysis area when is near to S.aureus

1. Enterococcus faecalis

2. Streptococcus salivarius

3. Streptococcus

agalactiae

4. Enterococus durans

Reference: Christie, R., N. E. Atkins, and E. Munch-Peterson. 1944. A note on a lytic

phenomenon shown by group B streptococci. Aust. J. Exp. Biol. Med. Sci. 22:197-200.

Identification of group D


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g p

streptococci

Bile esculin test :streptococcus group Dhydrolyses esculin into6,7dihidroxycumarin,

resulting brownish black onthe bile esculinmedium.

Grows in 6.5% NaCl broth(broth turns cloudy).

Other groups do not.

Enterococcus faecalis positive

Streptococcus mitis negative

S.E.M of Streptococcus gallolyticus


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p g y

(Group D Streptococcus)

After overnight incubation in modified BHI. Bar = 1 uM

L. O’Donovan, 2001


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Diseases caused by Staphylococci:


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Diseases caused by Staphylococci:

Abscesses or minor skin inflammation Pneumoniae

Osteomyelitis

Endocarditis Cystitis

Pyelonephritis

Food intoxication

Toxic shock syndromeToxin-1 (TSST-1)

Staphylococcus scalded skin syndrome (SSSS)

Septicemia


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The genus comprises 50 taxons with 39

various types, and several subtypes Resistant to adverse environmental

conditions

Resist drying Resist high NaCl concentration


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S. aureus is normal flora in anterior nares andperineum nasal mucosa carrier rate 37.2%(Ref.Matouska, 2008)

S. epidermidis normal found in anterior naresanterior and the skin

S. saphrophyticus normal in the urinary tract Other Staphylococcus are common on other

parts of the human body*all staphs may colonize cathether

*Among staphs only S. aureus produces exotoxins andable to cause furuncles

*The exotoxins are the exfoliatin pyrogenic andsuperantigenik toxins

Metabolic end products of


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p

Staphylococci1. Coagulase (cause clot formation)

2. Hyaluronidase (spreading factor)

3. Leukocidin toxin (makes pores that cause lysis ofwhite blood cell) : eg. Panton Valentine Leucocidin orLuk PV which is produced by CA-MRSA

4. Haemolysin toxin5. Staphylococcal superantigens (toxin)

6. Enterotoxin (exotoxins secreted by some strains ofS. aureus)

7. Dnase, lipase, gelatinase, penicillinase – non toxigenic

8. Staphylokinase -- fibrinolysin


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Identification of Staphylococcus


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Identification of Staphylococcus

1. MSA test◦ Agar medium containing Mannitol and high

Salt concentration◦ S.aureus: yellow halo forms around the colony

2. Coagulase test

Coagulase converts fibrinogen to fibrin

specimen which is mixed with citrated-

plasma will result a coagulation


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3.Dioxyribonuklease test (DNase test)◦ Agar medium contains DNA

◦ Specimen is spread on agar, hydrolisis of DNA by theDNase is seen as pink halo (clear area around thecolony);

◦ If DNase is not present, HCL reacts with DNA in themedium and forms precipitation around the colony

4. Novobiocin sensitivity

◦ Able to distinguish : S. epidermidis from S. saphrophyticus

Str. viridans from other streptoccocci

◦ Requires Mueller Hinton Agar and novobiocin disc

Staphylococcus’ characteristics


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Staphylococcus characteristics

◦

No flagella◦ Non motile

◦ Non spore producing

Aerob metabolism; can also undergo

facultative anaerob metabolism Distinguishing Streptococcus from Staph

is by Staph’s ability to produce catalase

Streptococci are catalase and oxydasenegative and many are facultativeanaerobe

S aureus’ cell membrane:


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S. aureus cell membrane:

composed of a combination of peptidoglycan andteichoic-ribitol acid molecules, determinesantigenicity and relatively specific for S. aureus

majority of S. aureus possess peptidoglycan

covered by a protein A. protein A uniquely binds Fc part of IgG molecule,

thus leaving only Fab part of IgG free to bind withantigen S. aureus becomes more virulencebecause of its ability to deter opsonisation.

(Opsonisation is the binding of antibody to antigen which then willbe swallowed by phagocytes)

The growth of S aureus


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The growth of S. aureus

Characteristic growth of S. aureus may be viewedon medium containing 5% sheep’s blood 5 ml

of blood is added into 95ml autoclaved culture

medium at + 50o

C

poured into 5 sterilepetridishes

Most S. aureus produces beta hemolysis around

its colony (complete hemolysis)

After incubation overnight whitish colony is

formed with a tendency to turn to golden colour


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H MOLYSIS ß NON H MOLYSIS

Note that the agar mediumremained red because no lysis

occurred

On this agar cleared area can beseen around the bacterial colony


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White colony

no hemolisis

Yellow colony diameter 2 mm

With hemolisis surrounding the colony


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Toxins of S aureus


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Toxins of S. aureus

1. Alfa toxin2. Exfoliatin

3. Pyrogenic Toxin Superantigen

Alpha toxin


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Alpha toxin

All S. aureus produce Alpha toxin, exceptwhen it is one of a coagulase-negative strain.

Lyse sitoplasm membrane and form atransmembrane pore (reviewed in Bhadki S,

et al. Alpha toxin of S. aureus, MicrobiolReview, 1991;55: 733-751)

Alpha toxin acts similar with othercytolysins, such as the Streptolisin-O,

complements and protein effector ofcytotoxic T lymphocyte

Exfoliatin


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Exfoliatin

Degrades intercellular bonds thus causingthe separation of epidermal layer between

the stratum spinosum and stratum

granulosum Antigenic property:body produces

antibody against expholiatin

Pyrogenic Toxin Superantigen


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Pyrogenic Toxin Superantigen

PTSAg stimulates a systemic effect whenabsorbed from a S. aureus infected site

About 10% S. aureus cannot produce

PTSAg One strain may produce one or more of

the Sag toxin

Physically, chemically and biologically thePTSAg of staphylococcus is similar with

that of streptococcus

Staphylococcus epidermidis


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Normal flora on human skin, sometimes c/illness

Infection is assoc with cathethers, decreased

immunity, newborn, inplanted medical devices Multidrug resistant:

◦ Treat with Vancomycin, Rifampin and newer

quinolones◦ Remove medical devices as source of infection

Serious hospital infection



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Source of infection:◦ Skin: from venous cath (IV or Hemodialysis)

or peritoneal dialysis

◦ From cathethers in the UTI

◦ Prosthetic joints

◦ Vascular grafts

◦ Eyes infection/surgery

◦ Other implants


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On solid culture (plate or slant agar):small colony diameter ~ 1 µm (as

compared to S.aureus), white to cream

Grows best in Blood agar: non hemolytic Grows on other non selective media

Microscopy: Gram positive, single/in

pairs/short chains/in clusters A.k.a. Coagulase negative staphylococcus

METHICILLIN RESISTANT

STAPHYLOCOCCUS AUREUS


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STAPHYLOCOCCUS AUREUS

Methicillin-(and Oxacillin) resistant Staphylococcus aureus(MRSA) are strains resistant to all β-lactam agents,including cephalosporins and carbapenems.

PathogenicVirulence factors enable them to result indisease.

Important c/ of nosocomial infections worldwide. Outbreak : one strain is transmitted to other patients or

through close contacts of infected persons in thecommunity.◦ Hospital-associated MRSA (HA-MRSA) isolates are also

frequent causes of healthcare-associated bloodstream andcatheter-related infections.

◦ Community-associated MRSA (CA-MRSA) isolates areoften only resistant to beta-lactam agents and erythromycin

References:


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References:1. McPhee S.J. Et al in Current Medical Diagnosis and Treatment, 2011

2. Ruff CT et, al, in Hurst’s the Heart, Manual of Cardiology 12 ed, 20093. Manual of Cardiovascular Medicine, 3rd edition, Brian P Griffin and Eric J.

Topol, editors, Lippincott Williams and Wilkins, 2009.

4. Medical Microbiology, 3rd edition, Cedric Mims, et al (eds), Mosby, 2004.

5. Infectious Diseases, 2nd edition, Jonathan Cohen and William G. Powderly(eds)

6. Zinsser Microbiology, 20th edition7. Valvular Heart Disease, 3rd edition, Joseph S. Alpert, James E.Dalen,

Rahimtoola Shahbudin H., editors, Lippincott Williams and Wilkins, 2000

8. Bhadki S, etal. Alpha toxin of S. aureus, Microbiol Review, 1991;55: 733-751.

9. Patophysiology of Heart Diseases, 3rd edition, Lilly LS. (Ed), LippincottWilliams and Wilkins, 2003

10. Matouskova I, 2008, Current knowledge of MRSA and CA-MRSA, BiomedPap Med Fac Univ Palacky Otomouc Czech Repub, 2008, 152 (2): 191-202

11. Others as cited in this lecture slides.

Infection of the Cardiovascular System Rizalinda 2016

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