MICROBIOLOGYCARDIOVASCULAR INFECTIONS

INFECTIVE ENDOCARDITIS

Infective endocarditis (IE) is a serious infection involving the interior of the heart, most commonly the heart valves. It is predominantly bacterial.

Bacteria are the most common cause of IE with Staphylococcus aureus the most common causative agent worldwide. Other causes include streptococci, enterococci, viruses, fungi, rickettsia, and parasites.

Microorganisms That Cause Infective Endocarditis

INFECTIVE ENDOCARDITIS

“Few diseases present greater difficulties in the way of diagnosis than malignant endocarditis, difficulties which in many cases are practically insurmountable” (William Osler in the Gulstonian Lectures on Malignant Endocarditis, 1885).

Risk Factors

intravenous (IV) drug abusepoor dentitionvalvular heart diseasecongenital heart diseaseprosthetic heart valvesindwelling linespacemakerspast history of infective endocarditischronic hemodialysis

Pathogenesis of Infective Endocarditis.

IE Symptoms

Fever is the most common presenting symptom (up to 90%) and is often associated with chills, fatigue, and malaise.

A heart murmur is present in up to 85% of patients.

Patients may also develop myalgia, arthralgia, splinter hemorrhages, septic emboli, petechiae, splenomegaly, cough, weight loss, and/or glomuleronephritis.

Janeway lesions, Osler nodes, and Roth spots are highly suggestive of bacterial endocarditis.

Janeway lesions

Janeway lesions are rare, non-tender, small erythematous or haemorrhagic macular, papular or nodular lesions on the palms or soles only a few millimeters in diameter that are associated with infective endocarditis and often indistinguishable from Osler's nodes.

Janeway lesions

Osler’s nodes

Osler's nodes are painful, red, raised lesions found on the hands and feet. They are associated with a number of conditions, including infective endocarditis, and are caused by immune complex deposition.

Osler’s nodes

Roth spots

Roth's spots, also known as Litten spots or the Litten sign, are non-specific red spots with white or pale centres, seen on the retina and although traditionally associated with infective endocarditis, can occur in a number of other conditions including hypertension, diabetes, Collagen vascular disease, extreme hypoxia, leukemia and HIV.

Roth spots

IE Diagnosis - History

Nonspecific symptoms usually begin 2 weeks after initial bacteremia.

On average, diagnosis takes 5 weeks from onset of symptoms.

Low-grade fever is most common, may be accompanied by night sweats.

Fatigue, malaise, generalized weakness, anorexia, and weight loss are common; mimics cancer.

Myalgias and arthralgias may suggest a connective tissue disease.

Low back pain can be the initial primary complaint. Consider endocarditis, epidural abscess, and osteomyelitis when back pain is accompanied by fever.

Infective endocarditis must be excluded in all cases of embolic cerebrovascular accident, particularly in younger patients.

In acute endocarditis, fever is high (40 ︎C range), and the patient appears acutely ill.

IE Diagnosis - Lab tests

Blood culture (3 separate sets)

C-reactive protein (CRP)

Total blood count: neutrophil leucocytosis

Elevated erythrocyte sedimentation rate (ESR)

+ Rheumatoid factor (RF)

Serum antibodies. Most helpful to identify the cause of culture-negative endocarditis for Bartonella spp, Coxiella spp, Chlamydia spp, Tropheryma whipplei, and Brucella spp.

IE Diagnosis - Treatment

Vancomycin and ceftriaxone or gentamycin are good first-line agents.

Surgery:

1. Heart failure2. Uncontrolled infection despite maximal medical therapy 3. Infection with particular pathogens: Pseudomonas, Brucella, or Coxiella 4. Fungal infection

MYOCARDITIS

An inflammatory disease of the myocardium, which may be caused by a variety of infectious and non-infectious causes. May be acute, subacute, or chronic, and focal or diffuse.

In many cases, myocarditis fails to produce specific cardiovascular symptoms or electrocardiographic abnormalities, and recovery is usually spontaneous and without residual defects.

Occasionally, myocarditis is complicated by heart failure; in rare cases, it leads to cardiomyopathy.

MYOCARDITIS

Myocardial injury may be a consequence of direct cell damage by an infectious agent, by a circulating toxin, or by immune reactions following infection. the cause is not identified in most cases.

Viruses are the commonest agents in the developed world, e.g. measles, influenza, polio, mumps, adenovirus, and the group B Coxsackie viruses.

Bacterial infection may cause myocarditis through immunological mechanisms (e.g. Lyme disease, acute rheumatic fever) or through direct myocardial infection with associated inflammation (e.g. brucellosis, meningococcal, streptococcal, and staphylococcal sepsis, Legionella spp., M. pneumoniae, and Chlamydia psittaci infection). toxin-mediated damage is seen in infection by C. diphtheriae and C. perfringens.

MYOCARDITIS

Parasitic causes include trypanosomal disease, e.g. T. cruzi is a common cause in South america.

Disseminated infection in the immunocompromised may lead to myocarditis (e.g. Toxoplasma, Aspergillus, and Cryptococcus spp.).

MYOCARDITIS - SYPTOMS

Myocarditis may be asymptomatic or result in severe heart failure or sudden death.

Myocarditis should be considered in a young person developing cardiac abnormalities in the context of a recognized systemic illness or in an otherwise well individual developing unexpected heart failure or arrhythmias (e.g. supraventricular tachycardia (SVt) or extrasystoles).

MYOCARDITIS - SYPTOMS

Fever, malaise, upper respiratory tract symptoms, tachycardia, dyspnoea, and chest pain may precede Coxsackie virus myocarditis.

On examination, there may be cardiomegaly, murmurs, and signs of cardiac failure.

MYOCARDITIS - DIAGNOSIS

Elevated cardiac enzymes (troponins)

ECG changes are non-specific

Echocardiography

MRI scanning - detecting myocardial inflammation

Endomyocardial biopsy is considered the gold standard for diagnosis

Virus isolation; Serology (Lyme disease), Detecting organism (stool, blood)

MYOCARDITIS - TREATMENT

Directed to the causative agent

Resting

In some cases cardiac assist devices

Steroids are of no benefit

Immunoglobulins (CMV myocarditis)

Antivirals ???

MYOCARDITIS - COMPLICATIONS

Complications from myocarditis include ar- rhythmias, thromboembolism, chronic valvulitis (when disease results from rheu- matic fever), and recurrence of disease.

GENERAL MICROBIOLOGY

The Three-Domain System of Classification

KEY TERMS

Classification The process of arranging organisms into similar or related groups (taxa), primarily to provide easy identification and study.

Dichotomous Key Flowchart of tests used for identifying organisms

Domain A collection of similar kingdoms; there are three domains—Bacteria, Archaea, and Eucarya.

KEY TERMS

Genus A collection of related species.

Nomenclature The system of assigning names to organisms.

Signature Sequence Characteristic sequences in the ribosomal RNA genes, or their products, that can be used to classify or identify certain organisms.

Species A group of closely related isolates or strains; the basic unit of taxonomy.

Strain An isolate; subgroup within a species.

KEY TERMS

Taxonomy The science that studies organisms in order to arrange them into groups (taxa); involves three interrelated areas - identification, classification, and nomenclature.

Microbiology Tests

Microscopy: Most infectious agents are visible only when viewed through a microscope. Lacks sensitivity and specificity. Rapid and relatively inexpensive test method. Provides differentiation of organisms based on staining and morphological characteristics.

Types of microscopy

MicroscopyThe Phase-Contrast Microscope: amplifies the slight difference between the refractive index of cells and the surrounding medium, resulting in a darker appearance of the denser material. Special optical devices boost those differences, thereby increasing the contrast. Paramecium bursaria containing

endosymbiotic Chlorella (a green alga).

Microscopy

The Interference Microscope: causes the specimen to appear as a three-dimensional image. This microscope, like the phase-contrast microscope, depends on differences in refractive index as light passes through different materials.

Protozoan (Paracineta) attachedto a green alga (Spongomorpha).

MicroscopyThe Dark-Field Microscope: Organisms viewed through a dark-field microscope stand out as bright objects against a dark background. The microscope operates on the same principle that makes dust visible when a beam of bright light shines into a dark room. A special mechanism directs light toward the specimen at an angle, so that only light scattered by the specimen enters the objective lens. Volvox (sphere) and Spirogyra (filaments),

both of which are eukaryotes.

MicroscopyThe Fluorescence Microscope: used to observe cells or other materials that are either naturally fluorescent or have been stained or tagged with fluorescent dyes. A fluorescent molecule absorbs light at one wavelength (usually ultraviolet light) and then emits light of a longer wavelength.

A rod-shaped bacteriumtagged with fluorescent marker.

MicroscopyThe Confocal Scanning Laser Microscope: is used to construct a three-dimensional image of a thick structure such as a community of microorganisms. Lenses focus a laser beam to illuminate a given point on one vertical plane of a specimen. Mirrors then scan the laser beam across the specimen, illuminating successive regions and planes until the entire specimen has been scanned. Confocal photomicrography

of fava bean mitosis.

Electron Microscopy

Electron microscopy is in some ways comparable to light microscopy. Rather than using glass lenses, visible light, and the eye to observe the specimen, the electron microscope uses electro-magnetic lenses, electrons, and a fluorescent screen to produce the magnified image. These instruments can clearly magnify an image 100,000".

Microscopic Techniques:

Dyes and Staining

Dyes and StainingSimple Stains: Employ a basic dye to impart a color to a cell. Easy way to increase the contrast between otherwise colorless cells and a transparent background.

Differential Stains: Distinguish one group of microorganisms from another. - Gram stain: Used to separate bacteria into two major groups, Gram-positive and Gram-negative. The staining characteristics of these groups reflect a fundamental difference in the chemical structure of their cell walls. This is by far the most widely used staining procedure. - Acid-fast stain: Used to detect organisms that do not readily take up stains, such as members of the genus Mycobacterium.

Dyes and Staining

Dyes and Staining

Results of a Gram stain. The Gram-positive cells (purple) are Staphylococcus aureus; the Gram-negative cells (reddish-pink) are

Escherichia coli.

Dyes and StainingSpecial Stains: stain specific structures inside or outside of a cell.

- Capsule stain: capsule stains exploit the fact that viscous capsules do not readily take up certain stains; the capsules stand out against a stained background. This is an example of a negative stain.

- Endospore stain: stains endospores, a type of dormant cell that does not readily take up stains. These are produced by Bacillus and Clostridium species.

- Flagella stain: The staining agent adheres to and coats the otherwise thin flagella, making them visible with the light microscope.

Dyes and Staining

Dyes and Staining

Fluorescent Dyes and Tags: Fluorescent dyes and tags absorb ultraviolet light and then emit light of a longer wavelength. They are used in conjunction with a fluorescence microscope.

- Fluorescent dyes: Some fluorescent dyes bind to compounds found in all cells; others bind to compounds specific to only certain types of cells.

- Fluorescent tags: Antibodies to which a fluorescent molecule has been attached are used to tag specific molecules.

Dyes and Staining

Reference ListMicrobiology : a human perspective / Eugene W. Nester ... [et al.]. — 6th ed.

Willey, Joanne M. Prescott’s principles of microbiology / Joanne M. Willey, Linda M. Sherwood, Christopher J. Woolverton.— 1st ed.

Netter’s infectious diseases / [edited by] Elaine C. Jong, Dennis L. Stevens ; Illustrations by Frank H. Netter ; contributing Illustrators, Carlos A.G. Machado ... [et al.].

Graphic guide to infectious disease / Brian Kloss, Travis Bruce.

Microbiology and Infectious Diseases on the move. Thomas Locke, Sally Keat, Andrew Walker and Rory Mackinnon

Lippincott’s guide to infectious diseases.

MIMS’ PATHOGENESIS OF INFECTIOUS DISEASE. Sixth Edition: Copyright 2015 Elsevier