Lec7 các vi khuẩn thấp tim, nội tâm mạc, xét nghiệm vi sinh

Pyrogenic exotoxins Streptococcus pyogenes Cause various effects, including the rashes seen in scarlet fever and streptococcal toxic shock disease... 190 MEDICAL MICROBIOLOGYSummary: Str

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CÁC VI KHUẨN THƯỜNG GẶP GÂY THẤP TIM,

VIÊM NỘI TÂM MẠC VÀ CÁC XÉT NGHIỆM VI SINH CHẨN ĐOÁN

Phạm Hồng Nhung

Bộ môn Vi sinh, Đại học Y Hà Nội Khoa Vi sinh, Bệnh viện Bạch Mai

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1 Trình bày được đặc điểm sinh học, cơ chế gây thấp tim của S pyogenes.

2 Trình bày được xét nghiệm vi sinh sử dụng cho chẩn đoán thấp tim.

3 Trình bày được các căn nguyên gây viêm nội tâm mạc.

4 Phân tích được giá trị của các phương pháp chẩn đoán viêm nội tâm mạc.

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CĂN NGUYÊN GÂY THẤP TIM CÁC XÉT NGHIỆM VI SINH CHẨN ĐOÁN

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Thấp tim

hay nhiều đợt viêm họng hay sốt ban đỏ do nhiễm Streptococcus pyogenes không được điều trị hoặc điều trị không đúng cách

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Phân loại học streptococci

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• Dựa vào cấu trúc carbohydrate C ở vách

Phân loại học streptococci

Streptococcus pneumoniae

Streptococcus bovis

Streptococcus mutans

α α

C-Terminus

stance The clinically most important groups of β-hemolytic cocci are Types A and B (Figure 9.2) Commercial kits in which group- specific antisera are coupled to latex beads are now widely used for identification of β-hemolytic streptococci

strepto-III GROUP A β-HEMOLYTIC STREPTOCOCCI

S pyogenes, the most clinically important member of this group of positive cocci, is one of the most frequently encountered bacterial pathogens of humans worldwide It can invade apparently intact skin or mucous membranes, causing some of the most rapidly progressive infections known A low inoculum suffices for infection Some strains of

gram-S pyogenes cause postinfectious sequelae, including rheumatic fever and acute glomerulonephritis Nasopharyngeal carriage is common especially in colder months and particularly among children Unlike staphylococcal species, S pyogenes does not survive well in the environment Instead, its habitat is infected patients and also normal human carriers in whom the organism resides on skin and mucous membranes S pyogenes is usually spread person to person by skin contact and via the respiratory tract.

A Structure and physiology

S pyogenes cells usually form long chains when recovered from uid culture (see Figure 9.16), but may appear as individual cocci, pairs, or clusters of cells in Gram stains of samples from infected tissue Structural features involved in the pathology or identification of group A streptococci include:

connec-tive tissue, forms the outermost layer of the cell This capsule is not recognized as foreign by the body and, therefore, is nonimmunogenic The capsule is also antiphagocytic.

components Beginning with the outer layer of the cell wall, these components include the following (Figure 9.3):

protein M proteins extend from an anchor in the cell brane, through the cell wall and then the capsule, with the N- terminal end of the protein exposed on the surface of the bacterium M proteins are highly variable, especially the N-terminal regions, resulting in over 80 different antigenic types Thus, individuals may have many S pyogenes infections throughout their lives as they encounter new M protein types for which they have no antibodies M proteins are antiphagocytic and they form a coat that interferes with complement binding.

of rhamnose and N-acetylglucosamine [Note: All group A streptococci, by definition, contain this antigen.]

fibronectin in the pharyngeal epithelium M proteins and lipo teichoic acids also bind to fibronectin.

-Streptococci and enterococci

Clinical syndromes

Disease is caused by:

direct invasion and infl ammation local spread

distant spread distant toxin effects, e.g scarlet fever immune mechanisms, e.g rheumatic fever.

There is therefore a wide range of ical syndromes associated with streptococcal infections (see Table 4):

clin-Strep pyogenes: throat infections, wound

and burn infections, puerperal sepsis, scarlet fever, rheumatic fever, glomerulonephritis, septicaemia etc.

Strep agalactiae: neonatal pneumonia

and meningitis, puerperal sepsis enterococci: urinary tract and wound infections, endocarditis, septicaemia

Strep pneumoniae: bronchitis,

pneu-monia, bacteraemia, meningitis

Strep viridans group: caries,

endocar-ditis, bacteraemia.

Chemotherapy

In general, streptococci are very sensitive

to penicillin, while enterococci are quite resistant to most antibiotics, except ampicillin or vancomycin However, pneumococci with partial or complete resistance

to penicillin (p 127), and resistant enterococci, are increasingly common.

vancomycin-Control

A multivalent pneumococcal vaccine is used to protect those particularly at risk, including splenectomised and immunocompromised patients Locating carriers (nose, throat, skin or perineal carriage)

is important in controlling outbreaks, especially in hospitals or closed com- munities.

Table 2 Identifi cation of streptococci and enterococci

Organism Group Susceptibility to: CAMPa,b Hydrolysis of: Growth in:

Bacitracin Optochin test Hippurateb Aesculin Bile 6.5% NaCl

S, sensitive; R, resistant; +, present; −, absent.

aExtracellular protein giving synergistic haemolysis with b-haemolysin of Staph aureus.

bNow largely replaced by commercial latex or co-agglutination tests ( ) less common.

Table 3 Virulence factors of Strep pneumoniae and pyogenes

Virulence factor Actions

Strep pneumoniae

Capsular ‘C’ polysaccharides Inhibit phagocytosis and opsonisation

(the most important)

Pneumolysin Beta haemolytic, dermotoxic

Neuraminidase Splits membrane glycoproteins, may aid invasion and spread

Purpura-producing principle Active in animals, may be in humans

Strep pyogenes

Structural components

Capsule (if present) Not a virulence factor

M-protein Anti-phagocytic, anti-complementary (i.e blocks action of complement)

Lipoteichoic acid Adheres to epithelial cells

Toxins and enzymes

Streptolysin O (oxygen labile) Lyses red cells, white cells, tissue cells and platelets, releasing cell enzymes

Streptolysin S (oxygen stable) Action as for streptolysin O

DNAase, type B Depolymerises DNA in pus

Streptokinases Lyse clots, help bacterial spread

Hyaluronidases Solubilise collagen in tissues, may help bacterial spread

Erythrogenic toxins Mediate rash in scarlet fever

Table 4 Streptococcal organisms and associated clinical syndromes

Organism Direct invasion Local Distant Distant Immune

and infl ammation spread spread toxin effects mechanisms

Puerperal sepsis Enterococci Urinary tract Abscess Endocarditis

Group-specific carbohydrate

Fig 3 Structure of Strep pyogenes.

Streptococci and enterococci

Streptococci are Gram-positive cocci, usually growing in chains, facultative anaerobes, nutritionally fastidious and catalase negative.

Enterococci are more resistant than streptococci to bile, salt and antibiotics.

Identifi cation depends on Gram stain, haemolysis, biochemical tests and Lancefi eld grouping.

The complex cell wall and enzymes and toxins have important functions, including adhesion, virulence and spread.

Strep pyogenes and Strep pneumoniae are aggressive pathogens,

invasive and virulent even in normal hosts.

Other streptococci are opportunistic pathogens, i.e normal fl ora that cause disease in abnormal sites or abnormal hosts.

Disease is caused by invasion and spread, toxin effects and immune mechanisms.

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Đặc điểm sinh học

• Hiếu kỵ khí tùy tiện

Streptococci and enterococci

Classifi cation and description

Streptococci and enterococci have tain characteristics that contribute to their ability to cause disease:

cer-the ability to live as normal fl ora on our skin and mucosal surfaces, mainly

in the nasopharynx, gut and vagina

Strep pyogenes and Strep pneumoniae

are aggressive pathogens with ous virulence factors, which give the ability to adhere, invade and damage tissues.

numer-other strains are ‘opportunistic gens’: normal fl ora that can become pathogenic in abnormal sites or in abnormal hosts

patho-infection is followed by spread locally,

to distant organs and to other people.

The description of these organisms is:

Gram-positive cocci (GPC), usually in chains, sometimes in pairs (Fig 1a, b) non-motile, non-sporing and may be capsulated (Fig 1c)

or other rich media, with some tant strains growing only in pyridoxal- rich media

impor-catalase negative, unlike staphylococci.

The classifi cation of streptococci is fusing, as three separate criteria are used:

con-biochemical into species serological into Lancefi eld groups based on specifi c polysaccharide antigens in the cell wall

haemolytic by the lysis seen when cultured on sheep blood agar: beta means a clear zone; alpha, a green zone (viridans means ‘making green’

in Latin) and gamma means no molysis (see Table 1 and Fig 2).

hae-Enterococci are now placed in a rate genus because of different characteristics, including resistance to bile, 6.5%

sepa-NaCl and antibiotics.

Streptococci that are obligate obes are also placed in a separate genus,

anaer-Peptostreptococcus (see p 55).

Cell structure and function

Streptococci have a complex cell wall (Fig 3) The biological principle that structure relates to function is illustrated

Lancefi eld group-specifi c carbohydrate protects peptidoglycan

linear peptidoglycan with cross-linking gives rigidity.

Confi rmatory tests

Clinical specimens (throat swabs, pus, sputum, etc.) are examined by:

Gram stain culture on sheep blood agar shows small colonies, usually glistening, mucoid if encapsulated, and with haemolysis as in Table 1

biochemical tests (Table 2), and Grouping

serology for the development of serum antibodies, i.e antistreptolysin O titre (ASOT) or antiDNAase B (Table 3).

Pathogenesis and virulence

Virulence factors (Table 3) are found in

the aggressive pathogens Strep pyogenes and Strep pneumoniae and are related to

surface antigens and extracellular ducts Some appear to help the spread of disease, but it is not yet possible to link every individual toxin with particular clinical infections.

in chains (a) and Strep pneumoniae in

pairs (b) and encapsulated (c).

(a)

(b)

(c)

Table 1 Classifi cation and normal habitat

Species Serologic Haemolysis on Normal fl ora (nf) or (biochemical) Lancefi eld group sheep blood agar asymptomatic carriage (ac)

Strep agalactiae B Beta (alpha, gamma) Vagina, gut (nf)

Strep bovis, equinus D Gamma (alpha) Gut, perineum (nf)

Strep pneumoniae Ungroupable Alpha Nasopharynx (ac)

Strep viridans group (Strep sanguis, Ungroupable Alpha (gamma) Mouth (nf)

salivarius, mitis, ‘milleri’, mutans)

of the area surrounding the colony and is termed α-hemolysis

(Figure 15-4).

When the RBCs immediately surrounding the colony are unaffected, the bacteria are described as nonhemolytic Some references term this result γ-hemolysis Because no lysis of the

RBCs occurs, however, the term γ-hemolysis is confusing and

is not recommended Some isolates belonging to the viridans group produce what is called wide-zone or α-prime hemolysis

The colonies are surrounded by a very small zone of no hemolysis and then a wider zone of β-hemolysis This reaction may be mistaken for β-hemolysis at first glance The use of a dissecting microscope or handheld lens reveals the narrow zone of intact RBCs and the wider zone of complete hemolysis.

CLINICALLY SIGNIFICANT STREPTOCOCCI AND

STREPTOCOCCUS -LIKE ORGANISMS

The role of the streptococci and enterococci in disease has been known for more than 100 years The range of infections caused by these organisms is wide and well studied As we have seen with other organisms, the previously unknown or poorly characterized species and the saprobes are playing more prominent roles in disease Some of the clinically important species and the diseases they cause are listed in Table

common C carbohydrate (polysaccharide), which can be used

to classify an isolate serologically This classification scheme

was developed in the 1930s by Rebecca Lancefield After first

recognizing the antigen in β-hemolytic streptococci,

Lance-field was able to divide the streptococci into serologic groups,

designated by letters Organisms in group A possess the same

antigenic C carbohydrate; those in group B have the same C

carbohydrate, and so on A schematic diagram of the

strep-tococcal cell wall is shown in Figure 15-2 Some species can

produce a type-specific polysaccharide capsule as well.

Hemolysis

The streptococci and similar organisms can produce a number

of exotoxins that damage intact red blood cells (RBCs) The

types of hemolysis are described in Table 15-1 When lysis of

RBCs in the agar surrounding the colony is complete, the

resulting area is clear; this is termed β-hemolysis (Figure 15-3)

Partial lysis of the RBCs results in a greenish discoloration

Capsule Teichoic acid Cell membrane

Peptidoglycan Group

carbohydrate Fimbriae

FIGURE 15-2 Schematic representation of streptococcal cell

Alpha (α) Partial lysis of red blood cells around colony

Greenish discoloration of area around colony Beta (β) Complete lysis of red blood cells around colony

Clear area around colony Nonhemolytic No lysis of red blood cells around colony

No change in agar Alpha-prime (α′)

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Yếu tố độc lực

also contributes to bacteremia and endocarditis E faecalis

is g-hemolytic and has been linked to colon carcinomas The bacterium S viridans is responsible for approximately half

of all cases of bacterial endocarditis Members of this group include S mutans, S sanguis, and S salivarius Although these organisms are normally found as oral bacterial flora, entry into the bloodstream can lead to fever and embolic events Group C streptococci (S equisimilis, S zooepidemi- cus, S equi, S dysgalactiae) primarily cause diseases of animals and pose little threat to immunocompetent hosts.

Likewise, groups E, F, G, H, and K to U species rarely cause pathogenic disease.

S pneumoniae (referred to as pneumococci) is a leading cause of pneumonia, often with onset after damage to the upper respiratory tract (e.g., following viral infection) Although

S pneumoniae is hemolytic, there is no group antigen and there are no main exotoxins that contribute to pathogenesis.

The organism often spreads, causing bacteremia and tis, and may also cause middle ear infections (otitis media).

meningi-S pneumoniae has an antiphagocytic capsule (antigenically effective as a vaccine target) and produces a pneumolysin that degrades red blood cells to allow productive spread from respiratory membranes to the blood It also produces an IgA protease that more readily allows colonization of respiratory mucosa Complement activation by teichoic acid may explain

the attraction of large numbers of inflammatory cells to the focal site of infection.

Other Gram-Positive Cocci of Medical Importance

The Micrococcus spp include organisms that may produce thology in immunocompromised individuals (those with neutro- penia, severe combined immunodeficiency, or acquired immunodeficiency) Of these, Stomatococcus mucilaginosus, normally a soil-residing organism, may induce disease Pepto- streptococcus is an anaerobic counterpart of Streptococcus.

pa-Peptostreptococci are small bacteria that grow in chains; are ally nonpathogenic; and are found as normal flora of the skin, urethra, and urogenital tract Under opportunistic conditions, they can infect bones, joints, and soft tissue Peptostreptococcus magnus is the species most often isolated from infected tissues.

usu-l l l GRAM-NEGATIVE COCCI

Neisseria

The Neisseria genus consists of aerobic, non–spore-forming gram-negative diplococcobacilli that reside in mucous membranes They are nonmotile, oxidase-positive, glucose- fermenting microbes that require a moist environment and

Erythrogenic toxins(pyrogenic toxins)

Apoptosis inhibitsphagocytosis

Toxemia,skin rash

Tissuenecrosis Exotoxin B

Streptolysin O, S

Lysis of RBCs, WBCs, platelets

Dissolves fibrin inclots and thrombi

Streptokinase(fibrinolysin)

Streptococcus

Allows spreading insubcutaneous tissue

Hyaluronidase

Streptodornase(DNAase)

C5a peptidase

Exotoxins,superantigens(exotoxin A)

DepolymerizesDNA in necrotictissueInhibits complementanaphylatoxin

Prevents phagocytosis,allows attachment

to tissue

Mitogenic activator

of T cells

Capsule,M-protein

Toxins and Hemolysins

Inflammation and Immune Activation

Figure 12-2 Pathogenic mechanisms for group A streptococci (Streptococcus pyogenes) RBCs, red blood cells; WBCs, white blood cells.

Clinical Bacteriology 108

also contributes to bacteremia and endocarditis E faecalis

isg-hemolytic and has been linked to colon carcinomas Thebacterium S viridans is responsible for approximately half

of all cases of bacterial endocarditis Members of this groupinclude S mutans, S sanguis, and S salivarius Althoughthese organisms are normally found as oral bacterial flora,entry into the bloodstream can lead to fever and embolicevents Group C streptococci (S equisimilis, S zooepidemi-cus, S equi, S dysgalactiae) primarily cause diseases of ani-mals and pose little threat to immunocompetent hosts

Likewise, groups E, F, G, H, and K to U species rarely causepathogenic disease

S pneumoniae (referred to as pneumococci) is a leadingcause of pneumonia, often with onset after damage to the up-per respiratory tract (e.g., following viral infection) Although

S pneumoniae is hemolytic, there is no group antigen andthere are no main exotoxins that contribute to pathogenesis

The organism often spreads, causing bacteremia and tis, and may also cause middle ear infections (otitis media)

meningi-S pneumoniae has an antiphagocytic capsule (antigenicallyeffective as a vaccine target) and produces a pneumolysin thatdegrades red blood cells to allow productive spread from re-spiratory membranes to the blood It also produces an IgAprotease that more readily allows colonization of respiratorymucosa Complement activation by teichoic acid may explain

the attraction of large numbers of inflammatory cells to thefocal site of infection

Other Gram-Positive Cocci of Medical Importance

The Micrococcus spp include organisms that may produce thology in immunocompromised individuals (those with neutro-penia, severe combined immunodeficiency, or acquiredimmunodeficiency) Of these, Stomatococcus mucilaginosus,normally a soil-residing organism, may induce disease Pepto-streptococcus is an anaerobic counterpart of Streptococcus

pa-Peptostreptococci are small bacteria that grow in chains; are ally nonpathogenic; and are found as normal flora of the skin,urethra, and urogenital tract Under opportunistic conditions,they can infect bones, joints, and soft tissue Peptostreptococcusmagnus is the species most often isolated from infected tissues

Neisseria

The Neisseria genus consists of aerobic, non–spore-forminggram-negative diplococcobacilli that reside in mucousmembranes They are nonmotile, oxidase-positive, glucose-fermenting microbes that require a moist environment and

Erythrogenic toxins(pyrogenic toxins)

Apoptosis inhibitsphagocytosis

Toxemia,skin rash

Tissuenecrosis Exotoxin B

Streptolysin O, S

Lysis of RBCs, WBCs, platelets

Dissolves fibrin inclots and thrombi

Streptokinase(fibrinolysin)

Streptococcus

Allows spreading insubcutaneous tissue

Hyaluronidase

Streptodornase(DNAase)C5a peptidase

Exotoxins,superantigens(exotoxin A)

DepolymerizesDNA in necrotictissueInhibits complementanaphylatoxin

Prevents phagocytosis,allows attachment

to tissue

Mitogenic activator

of T cells

Capsule,M-protein

Toxins and Hemolysins

Inflammation and Immune Activation

Figure 12-2 Pathogenic mechanisms for group A streptococci (Streptococcus pyogenes) RBCs, red blood cells; WBCs, whiteblood cells

Clinical Bacteriology 108

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ELSEVIER’S INTEGRATED REVIEW IMMUNOLOGY ISBN: 978-0-323-07447-6AND MICROBIOLOGY, SECOND EDITION

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ELSEVIER’S INTEGRATED REVIEW

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3 Extracellular products: Like Staphylococcus aureus (see p 70),

S pyogenes secretes a wide range of exotoxins that often varyfrom one strain to another and that play roles in the pathogenesis

of disease caused by these organisms (Figure 9.4)

B Epidemiology

The only known reservoir for S pyogenes in nature is the skin andmucous membranes of the human host Respiratory droplets or skincontact spreads group A streptococcal infection from person to per-son, especially in crowded environments such as classrooms andchildren’s play areas

of distant sites, where cellulitis (acute inflammation of subcutaneoustissue), fasciitis (inflammation of the tissue under the skin that covers asurface of underlying tissue), or myonecrosis (death of muscle cells)may develop rapidly or insidiously However, direct inoculation of skinfrom another person's infection is probably more common as thepathogenesis of streptococcal skin and soft tissue infection

[Note: If a sunburnlike rash develops on the neck, trunk, andextremities in response to the release of pyrogenic exotoxin towhich the patient does not have antibodies, the syndrome is des-ignated scarlet fever.] Many strep throats are mild, and many sorethroats caused by viruses are severe Hence, laboratory confirma-tion is important for accurate diagnosis and treatment of streptococ-cal pharyngitis, particularly for the prevention of subsequent acuterheumatic fever and rheumatic heart disease

cases of impetigo (see p 72), S pyogenes is the classic cause ofthis syndrome The disease begins on any exposed surface (mostcommonly, the legs) Typically affecting children, it can causesevere and extensive lesions on the face and limbs (see Figure9.16) Impetigo is treated with a topical agent such as mupirocin, orsystemically with penicillin or a first-generation cephalosporin such

III Group A, β-Hemolytic Streptococci 81

Streptolysin S

Catalyzes conversion of plasminogen

to plasmin, causing lysis of clots, facilitating the rapid spread of organisms.

Disrupts the organization of ground substance, facilitating the spread of infection.

Streptodornases

Inactivates complement component C5a.

Pyrogenic exotoxins

Streptococcus pyogenes

Cause various effects, including the rashes seen in scarlet fever and streptococcal toxic shock disease.

Cytokines

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Summary of streptococcal disease.

1S pyogenes has not acquired resistance to

penicillin G

3For penicillin-allergic patient

4All isolates remain sensitive to penicillin G and ampicillin

5In life-threatening infections, an glycoside can be added to the regimen

amino-6Penicillin G has been the drug of choice, but resistant strains are regularly seen

7Most resistant strains remain sensitive

anaerobes because the grow fermentatively even

in the presence of oxygen

• Diabetic foot infections

• Acute bacterial pneumonia

• Otitis media

• Meningitis

Facial erysipelas Impetigo Streptococcal pharyngitis

β- Hemolytic streptococci

on blood agar

α- Hemolytic streptococci

2Clindamycin may be added to pencillin G for soft tissue infection such as necrotizing fasciitis

Figure 9.16

Summary of streptococcal disease.

1S pyogenes has not acquired resistance to

penicillin G.

3For penicillin-allergic patient.

4All isolates remain sensitive to penicillin G and ampicillin.

5In life-threatening infections, an glycoside can be added to the regimen.

amino-6Penicillin G has been the drug of choice, but resistant strains are regularly seen.

7Most resistant strains remain sensitive

or chains

• Nonmotile, catalase negative

• Most are aerotolerant anaerobes because the grow fermentatively even

in the presence of oxygen

• Culture on blood agar

• Diabetic foot infections

• Acute bacterial pneumonia

• Otitis media

• Meningitis

β- Hemolytic streptococci

on blood agar

α- Hemolytic streptococci

1 Indicates first-line drugs; indicates alternative drugs 2

2Clindamycin may be added to pencillin G for

soft tissue infection such as necrotizing fasciitis.

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zygosity and concordance was strong, with an odds ratio of 6.4 (95% CI 3.4 to 12.1) (Engel, Stander, Vogel, Adeyemo, & Mayosi, 2011).

It is most likely that susceptibility to ARF is polygenic Polymorphisms in several genes coding for immune proteins have been associated with ARF susceptibility Several studies have reported genetic associations related to class II human leukocyte (HLA) molecules (Anastasiou-Nana, Anderson, Carlquist, & Nanas, 1986; Ayoub, Barrett, Maclaren, & Krischer, 1986; Carlquist, et al., 1995; Hafez, et al., 1985), while others have reported associations with non-HLA related immune proteins (Bryant, Robins-Browne, Carapetis,

& Curtis, 2009) Large-scale genome wide association studies of rheumatic heart disease

in multiple populations in over 20 countries, including in Africa, the Pacific, and northern Australia are currently underway.

Figure reproduced with permission from (Carapetis, et al., 2016).

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Chẩn đoán

• Chẩn đoán trực tiếp: Nuôi cấy, phân lập

Streptococci and enterococci have tain characteristics that contribute to

cer-their ability to cause disease:

the ability to live as normal fl ora on our skin and mucosal surfaces, mainly

are aggressive pathogens with ous virulence factors, which give the

numer-ability to adhere, invade and damage tissues.

other strains are ‘opportunistic gens’: normal fl ora that can become

patho-pathogenic in abnormal sites or in abnormal hosts

infection is followed by spread locally,

Gram-positive cocci (GPC), usually in chains, sometimes in pairs (Fig 1a, b)

non-motile, non-sporing and may be capsulated (Fig 1c)

Confi rmatory tests

Fig 1 Gram stain showing Strep pyogenes

(a)

(b)

(c)

Strep agalactiae B Beta (alpha, gamma) Vagina, gut (nf)

Strep bovis, equinus D Gamma (alpha) Gut, perineum (nf)

Strep viridans group (Strep sanguis, Ungroupable Alpha (gamma) Mouth (nf)

Trang 12

Specimen Containing ASO

+

Trang 13

Giá trị của ASO

viêm mủ da không tăng cao

đặc hiệu cho nhiễm S pyogenes.

Trang 14

Ngưỡng trên bình thường của hiệu giá ASO

Người lớn/người già: ≤ 200 IU/ml

6-15 tuổi: 240 – 320 IU/mL

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Figure 2 Common antigenic proteins of S pyogenes used for diagnostic and typing purposes.

Typing of Streptococcus pyogenes

In most clinical cases of acute infections, subtyping of group A streptococcal strains has

no immediate diagnostic or therapeutic consequences Such typing is typically performed

by reference laboratories for epidemiologic surveys or in outbreak situations, and may provide important information about the evolutionary relatedness of various strains Although classical antibody-dependent typing systems of surface proteins have been used for many years, molecular methods have become more and more prevalent, since they do not require the maintenance of rarely used large antibody panels or the establishment of specialized techniques As an additional advantage, the determination of DNA sequences

is independent from culture conditions and gene expression.

Conventional typing of S pyogenes is based upon the antigenic specificity of the expressed T and M proteins (Johnson & Kaplan, 1993) The trypsin-resistant T protein is part of the pilus structures (Mora, et al., 2005) T type identification can be achieved by

Anti Dnase B

ngoài da.

hiện anti Dnase B.

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Đặc điểm đề kháng kháng sinh

• S pyogene vẫn được coi là hoàn toàn còn nhạy cảm với β-lactam từ 1940.

nhiên.

• Các vi khuẩn khác tiết β-lactamase bảo vệ cho S pyogenes

• Có sự phối hợp M catarrhalis và S pyogenes giúp S pyogenes dễ dàng bám vào tế

bào biểu mô

Trang 17

190 MEDICAL MICROBIOLOGY

Summary: Streptococcus pyogenes (Group A)

BOX 19-1

Biology, Virulence, and Disease

Rapidly growing gram-positive cocci arranged in chains;

group-specific carbohydrate (A antigen) and type-specific

proteins (M protein) in cell wall

Virulence determined by ability to avoid phagocytosis

(mediated primarily by capsule, M and M-like proteins,

C5a peptidase), adhere to and invade host cells (M

protein, lipoteichoic acid, F protein), and produce toxins

(streptococcal pyrogenic exotoxins, streptolysin S,

streptolysin O, streptokinase, DNases)

Responsible for suppurative diseases (pharyngitis,

soft-tissue infections, streptococcal toxic shock) and

nonsuppurative diseases (rheumatic fever,

glomerulonephritis)

Epidemiology

Transient colonization in upper respiratory tract and skin

surface with disease caused by recently acquired strains

(before protective antibodies are produced)

Pharyngitis and soft-tissue infections typically caused by

strains with different M proteins

Person-to-person spread by respiratory droplets

(pharyngitis) or through breaks in skin after direct

contact with infected person, fomite, or

arthropod vector

Individuals at higher risk for disease include children 5 to

15 years old (pharyngitis); children 2 to 5 years old with

poor personal hygiene (pyoderma); patients with

soft-tissue infection (streptococcal toxic shock

syndrome); patients with prior streptococcal pharyngitis

(rheumatic fever, glomerulonephritis) or soft-tissue

A antigen) Antistreptolysin O test is useful for confirming rheumatic fever or glomerulonephritis associated with streptococcal pharyngitis; anti-DNase B test should be performed for glomerulonephritis associated with pharyngitis or

soft-tissue infections

Treatment, Prevention, and Control

Penicillin V or amoxicillin used to treat pharyngitis; oral cephalosporin or macrolide for penicillin-allergic patients;

intravenous penicillin plus clindamycin used for systemic infections

Oropharyngeal carriage occurring after treatment can be re-treated; treatment is not indicated for prolonged asymptomatic carriage because antibiotics disrupt normal protective flora

Starting antibiotic therapy within 10 days in patients with pharyngitis prevents rheumatic fever

For patients with a history of rheumatic fever, antibiotic prophylaxis is required before procedures (e.g., dental) that can induce bacteremias leading to endocarditis For glomerulonephritis, no specific antibiotic treatment or prophylaxis is indicated

Streptococcal Diseases: Clinical Summaries

BOX 19-2

Streptococcus pyogenes (Group A)

Suppurative Infections

Pharyngitis: reddened pharynx with exudates generally

present; cervical lymphadenopathy can be prominent

Scarlet fever: diffuse erythematous rash beginning on the

chest and spreading to the extremities; complication of

streptococcal pharyngitis

Pyoderma: localized skin infection with vesicles progressing

to pustules; no evidence of systemic disease

Erysipelas: localized skin infection with pain, inflammation,

lymph node enlargement and systemic symptoms

Cellulitis: infection of the skin that involves the

subcutaneous tissues

Necrotizing fasciitis: deep infection of skin that involves

destruction of muscle and fat layers

Streptococcal toxic shock syndrome: multiorgan systemic

infection resembling staphylococcal toxic shock

syndrome; however, most patients bacteremic and with

evidence of fasciitis

Other suppurative diseases: variety of other infections

recognized including puerperal sepsis, lymphangitis, and pneumonia

Nonsuppurative Infections

Rheumatic fever: characterized by inflammatory changes of

the heart (pancarditis), joints (arthralgias to arthritis), blood vessels, and subcutaneous tissues

Acute glomerulonephritis: acute inflammation of the renal

glomeruli with edema, hypertension, hematuria, and proteinuria

Streptococcus agalactiae (Group B)

Early-onset neonatal disease: within 7 days of birth,

infected newborns develop signs and symptoms of pneumonia, meningitis, and sepsis

Late-onset neonatal disease: more than 1 week after birth,

neonates develop signs and symptoms of bacteremia with meningitis

Infections in pregnant women: most often present as

postpartum endometritis, wound infections, and urinary

BOX 19-1

group-specific carbohydrate (A antigen) and type-specific proteins (M protein) in cell wall

Virulence determined by ability to avoid phagocytosis (mediated primarily by capsule, M and M-like proteins, C5a peptidase), adhere to and invade host cells (M protein, lipoteichoic acid, F protein), and produce toxins (streptococcal pyrogenic exotoxins, streptolysin S,

streptolysin O, streptokinase, DNases) Responsible for suppurative diseases (pharyngitis, soft- tissue infections, streptococcal toxic shock) and nonsuppurative diseases (rheumatic fever,

glomerulonephritis)

Epidemiology

Transient colonization in upper respiratory tract and skin surface with disease caused by recently acquired strains (before protective antibodies are produced)

Pharyngitis and soft-tissue infections typically caused by strains with different M proteins

Person-to-person spread by respiratory droplets (pharyngitis) or through breaks in skin after direct contact with infected person, fomite, or

arthropod vector Individuals at higher risk for disease include children 5 to

15 years old (pharyngitis); children 2 to 5 years old with poor personal hygiene (pyoderma); patients with

soft-tissue infection (streptococcal toxic shock syndrome); patients with prior streptococcal pharyngitis (rheumatic fever, glomerulonephritis) or soft-tissue

( L -pyrrolidonyl arylamidase) reaction, susceptibility to bacitracin, and presence of group-specific antigen (group

BOX 19-2

chest and spreading to the extremities; complication of streptococcal pharyngitis

infection resembling staphylococcal toxic shock syndrome; however, most patients bacteremic and with evidence of fasciitis

BOX 19-1

Virulence determined by ability to avoid phagocytosis (mediated primarily by capsule, M and M-like proteins, C5a peptidase), adhere to and invade host cells (M

protein, lipoteichoic acid, F protein), and produce toxins (streptococcal pyrogenic exotoxins, streptolysin S,

glomerulonephritis)

Epidemiology

( L -pyrrolidonyl arylamidase) reaction, susceptibility to bacitracin, and presence of group-specific antigen (group

Penicillin V or amoxicillin used to treat pharyngitis; oral cephalosporin or macrolide for penicillin-allergic patients; intravenous penicillin plus clindamycin used for systemic infections

For patients with a history of rheumatic fever, antibiotic prophylaxis is required before procedures (e.g., dental) that can induce bacteremias leading to endocarditis

For glomerulonephritis, no specific antibiotic treatment or prophylaxis is indicated

BOX 19-2

BOX 19-1

Virulence determined by ability to avoid phagocytosis (mediated primarily by capsule, M and M-like proteins, C5a peptidase), adhere to and invade host cells (M protein, lipoteichoic acid, F protein), and produce toxins (streptococcal pyrogenic exotoxins, streptolysin S,

glomerulonephritis)

Epidemiology

BOX 19-2

Trang 18

CĂN NGUYÊN GÂY VIÊM NỘI TÂM MẠC CÁC XÉT NGHIỆM VI SINH CHẨN ĐOÁN

Trang 19

Định nghĩa

Trang 20

Yếu tố nguy cơ VNTM do vi khuẩn

• Thủ thuật răng miệng

• Bệnh lý răng miệng (sâu răng, abscess)

• Nhiễm trùng ngoài tim (phổi, tiết niệu, da, xương)

• Dụng cụ can thiệp (đường tiết niệu, tiêu hoá, tĩnh mạch)

• Phẫu thuật tim

• Sử dụng thuốc đường tiêm

• Không rõ

Trang 21

Các căn nguyên từ vãng khuẩn huyết

Đánh răng

Ăn/Nhai

Thủ thuật răng miệng

Streptococci tan máu alpha từ vi hệ họng miệng

Trang 22

Căn nguyên gây bệnh

• Căn nguyên thường gặp

(đường vào)

Thomas J Cahill, Bernard D Prendergast

Infective endocarditis occurs worldwide, and is defi ned by infection of a native or prosthetic heart valve, the endocardial surface, or an indwelling cardiac device The causes and epidemiology of the disease have evolved in recent decades with a doubling of the average patient age and an increased prevalence in patients with indwelling cardiac devices The microbiology of the disease has also changed, and staphylococci, most often associated with health-care contact and invasive procedures, have overtaken streptococci as the most common cause of the disease Although novel diagnostic and therapeutic strategies have emerged, 1 year mortality has not improved and remains at 30%, which is worse than for many cancers Logistical barriers and an absence of randomised trials hinder clinical management, and longstanding controversies such as use of antibiotic prophylaxis remain unresolved In this Seminar, we discuss clinical practice, controversies, and strategies needed to target this potentially devastating disease.

Introduction

The challenges associated with infective endocarditis are greater than ever The patients aﬀ ected are older and

Virulent staphylococci have eclipsed penicillin-sensitive streptococci as the most common cause in many

and health-care-associated staphylococcal bacteraemia,

a precursor to infective endocarditis, is a challenge

has become one of the greatest threats to modern

At the bedside, the variability of disease presentation

evidence base for clinical practice, although clearly presented by international guidelines, is derived predominantly from observational cohort studies rather

abound Patients with infective endocarditis need prompt diagnosis and a rapid response from several specialists including cardiologists, cardiothoracic sur- geons, infectious disease specialists, and radiologists

The delivery of high-level coordinated care remains diﬃ cult, even in health-care systems of high-income countries, and is frequently impossible in low-income countries In this context, we provide an update and overview of best clinical practice in infective endocarditis, highlighting controversies and new research fi ndings.

Epidemiology

Infective endocarditis is rare, with a yearly incidence of

varies worldwide, with epidemiology in low-income countries similar to that of high-income countries during

the key risk factor for infective endocarditis in low-income

Patients are usually young adults and infection is caused predominantly by community-acquired, penicillin- sensitive streptococci entering via the oral cavity The prevalence of rheumatic heart disease has fallen in high-income countries because of improved living standards and availability of antibiotics for streptococcal

diabetes, cancer, intravenous drug use, and congenital heart disease have replaced rheumatic heart disease as the major risk factors for infective endocarditis Moreover, patients with infective endocarditis are older, with the average age, which was in the mid-40s during the early

This changing epidemiology of infective endocarditis

in high-income countries refl ects wide medical

(nosocomial or hospital-acquired, and non-nosocomial

or outpatient-acquired) accounts for 25–30% of

intravenous lines and invasive procedures has led to an upsurge in rates of staphylococcal bacteraemia, a

and indwelling cardiac devices (eg, permanent makers) are widely used and can act as a nidus for infection within the heart (fi gure 1) As indications for complex devices such as cardiac resynchronisation therapy and implantable cardioverter defi brillators

Infective endocarditis is rare in children, although improved survival in congenital heart disease (the most important risk factor) has resulted in increasing incidence

with cyanotic congenital heart disease, endocardial cushion defects, or high velocity jets (eg, in ventricular

Lancet 2016; 387: 882–93

Published Online

September 2, 2015 http://dx.doi.org/10.1016/

S0140-6736(15)00067-7

Department of Cardiology, Oxford University Hospitals, Oxford, UK (T J Cahill MRCP);

St Thomas’ Hospital, London SE1 7EH, UK

bernard.prendergast@gstt.

nhs.uk

Search strategy and selection criteria

We searched MEDLINE, Embase, and the Cochrane Library using the search terms “endocarditis” or “infective

endocarditis” together with “epidemiology”, “pathogenesis”,

“manifestations”, “imaging”, “treatment”, “surgery”, or

“device” We selected publications mostly from the past

10 years, but did not exclude widely referenced and highly regarded older publications We also searched the reference lists of articles identifi ed by this search strategy and selected articles that we judged relevant Recommended review

articles are cited to provide readers with more details and background references.

Seminar

882 www.thelancet.com Vol 387 February 27, 2016

Infective endocarditis

Thomas J Cahill, Bernard D Prendergast

Infective endocarditis occurs worldwide, and is defi ned by infection of a native or prosthetic heart valve, the endocardial surface, or an indwelling cardiac device The causes and epidemiology of the disease have evolved in recent decades with a doubling of the average patient age and an increased prevalence in patients with indwelling cardiac devices The microbiology of the disease has also changed, and staphylococci, most often associated with health-care contact and invasive procedures, have overtaken streptococci as the most common cause of the disease Although novel diagnostic and therapeutic strategies have emerged, 1 year mortality has not improved and remains at 30%, which is worse than for many cancers Logistical barriers and an absence of randomised trials hinder clinical management, and longstanding controversies such as use of antibiotic prophylaxis remain unresolved In this Seminar, we discuss clinical practice, controversies, and strategies needed to target this potentially devastating disease.

Introduction

The challenges associated with infective endocarditis are greater than ever The patients aﬀ ected are older and sicker than in the past, often with many comorbidities.1

Virulent staphylococci have eclipsed penicillin-sensitive streptococci as the most common cause in many high-income countries.2 The population at risk is growing and health-care-associated staphylococcal bacteraemia,

a precursor to infective endocarditis, is a challenge worldwide.3 Resistance to many antibiotics is rising and has become one of the greatest threats to modern health care.4

At the bedside, the variability of disease presentation and course presents diﬃ culties for clinicians.5 The evidence base for clinical practice, although clearly presented by international guidelines, is derived predominantly from observational cohort studies rather than randomised trials.6,7 Moreover, logistical challenges abound Patients with infective endocarditis need prompt diagnosis and a rapid response from several specialists including cardiologists, cardiothoracic sur-geons, infectious disease specialists, and radiologists

The delivery of high-level coordinated care remains diﬃ cult, even in health-care systems of high-income countries, and is frequently impossible in low-income countries In this context, we provide an update and overview of best clinical practice in infective endocarditis, highlighting controversies and new research fi ndings

Epidemiology

Infective endocarditis is rare, with a yearly incidence of about 3–10 per 100 000 people.1,2,8,9 The pattern of disease varies worldwide, with epidemiology in low-income countries similar to that of high-income countries during the early antibiotic era.10 Rheumatic heart disease remains the key risk factor for infective endocarditis in low-income countries and underlies up to two-thirds of cases.11,12

Patients are usually young adults and infection is caused predominantly by community-acquired, penicillin-sensitive streptococci entering via the oral cavity The prevalence of rheumatic heart disease has fallen in high-income countries because of improved living standards and availability of antibiotics for streptococcal pharyngitis.13 However, degenerative valve disease, diabetes, cancer, intravenous drug use, and congenital heart disease have replaced rheumatic heart disease as the major risk factors for infective endocarditis Moreover, patients with infective endocarditis are older, with the average age, which was in the mid-40s during the early 1980s, shifting to older than 70 years in 2001–06 (fi gure 1).14

This changing epidemiology of infective endocarditis

in high-income countries refl ects wide medical advances.15 Health-care-acquired infective endocarditis (nosocomial or hospital-acquired, and non-nosocomial

or outpatient-acquired) accounts for 25–30% of contemporary cohorts.1,2 Increasing use of long-term intravenous lines and invasive procedures has led to an upsurge in rates of staphylococcal bacteraemia, a precursor to infective endocarditis.16–18 Prosthetic valves and indwelling cardiac devices (eg, permanent pace-makers) are widely used and can act as a nidus for infection within the heart (fi gure 1) As indications for complex devices such as cardiac resynchronisation therapy and implantable cardioverter defi brillators expand, rates of cardiac device infection are rising.19,20

Infective endocarditis is rare in children, although improved survival in congenital heart disease (the most important risk factor) has resulted in increasing incidence

in recent decades.21 The highest risk arises in children with cyanotic congenital heart disease, endocardial cushion defects, or high velocity jets (eg, in ventricular septal defect).22 The risk of infective endocarditis is

Lancet 2016; 387: 882–93

September 2, 2015 http://dx.doi.org/10.1016/

S0140-6736(15)00067-7

Department of Cardiology, Oxford University Hospitals, Oxford, UK (T J Cahill MRCP);

St Thomas’ Hospital, London SE1 7EH, UK

bernard.prendergast@gstt.

nhs.uk

Search strategy and selection criteria

We searched MEDLINE, Embase, and the Cochrane Library using the search terms “endocarditis” or “infective endocarditis” together with “epidemiology”, “pathogenesis”,

“manifestations”, “imaging”, “treatment”, “surgery”, or

“device” We selected publications mostly from the past

10 years, but did not exclude widely referenced and highly regarded older publications We also searched the reference lists of articles identifi ed by this search strategy and selected articles that we judged relevant Recommended review articles are cited to provide readers with more details and background references

Seminar

infective endocarditis in high-income countries and is reported in up to 30% of cases.1,2 Staphylococcal infective endocarditis extends beyond traditional at-risk groups such as patients on haemodialysis and intravenous drug users, and can aﬀ ect both native and prosthetic valves.36

Moreover, it has notorious propensity to acquire antibiotic resistance, and meticillin-resistant strains have emerged worldwide.37

Coagulase-negative staphylococci (eg, Staphylococcus

epidermidis, Staphylococcus lugdunensis, and Staphylococcus capitis) are ubiquitous skin commensals They colonise

indwelling lines and devices and are the most common isolate in early prosthetic valve endocarditis.38–40

Coagulase-negative staphylococci also frequently cause hospital-acquired native valve endocarditis.2,41,42 Biofi lm production, high rates of abscess formation, and multi-antibiotic resistance are characteristic features of these commensals.43

Streptococcal infective endocarditis caused by the oral viridans group remains most common in low-income countries.10 From the Latin term viridis, which means green (referring to the characteristic discoloration of

blood agar medium), this group includes Streptococcus

mutans, Streptococcus salivarius, Streptococcus anginosus, Streptococcus mitis, and Streptococcus sanguinis These

organisms are commensals of the oral, gastrointestinal, and urogenital tract Group D streptococci (eg,

Streptococcus gallolyticus, Streptococcus bovis) are notable

for causing infective endocarditis associated with an underlying colonic tumour, which provides the portal of entry Enterococci account for 10% of cases overall.1,2

Most isolates are Enterococcus faecalis, causing both

native valve endocarditis and prosthetic valve endocarditis in elderly or chronically ill patients

Enterococcus faecium carries increasing resistance to

vancomycin, aminoglycosides, and ampicillin.44

The remaining microbes that can cause infective endocarditis are a mixture of fastidious bacteria, zoonotic bacteria, and fungi The HACEK bacteria (haemophilus,

aggregatibacter, cardiobacterium, Eikenella corrodens,

kingella), which cause about 3% of cases, are slow-growing organisms that colonise the oropharynx.45

Zoonotic endocarditis is caused by Coxiella burnetii and

Brucella (from livestock), Bartonella henselae (from cats),

and Chlamydia psittaci (from parrots, pigeons) Other

rare causes include Gram-negative bacteria (eg,

Acinetobacter spp, Pseudomonas aeruginosa), and Legionella spp, Mycoplasma spp, and Tropheryma whippelii.46

Fungal endocarditis, usually Candida or Aspergillus, is

rare but often fatal, arising in patients who are immunosuppressed or after cardiac surgery, mostly on prosthetic valves.47

Clinical features

The clinical presentation of infective endocarditis is particularly diverse and non-specifi c In his seminal 1885 Gulstonian lectures, William Osler remarked, “Few diseases present greater diﬃ culties in the way of diagnosis than malignant endocarditis, diﬃ culties which

in many cases are practically insurmountable.”48 More than 100 years later, the diagnosis is still frequently missed or uncertain, delaying defi nitive management and contributing to mortality.

Infective endocarditis should be considered in anyone with sepsis of unknown origin, or fever in the presence

of risk factors The manifestations of sepsis can range from general malaise to shock, infl uenced by microbial virulence and the host immune response.28,49 Infective endocarditis can also present with a complication, particularly stroke or systemic embolism Irrespective of presentation, patients with a persistent unexplained bacteraemia should be investigated for infective

endocarditis In particular, S aureus bacteraemia is

associated with infective endocarditis in 25–30% of cases, and all patients should be examined with echocardiography.50,51

Initial clinical assessment of a patient with suspected infective endocarditis involves evaluation of risk factors and a search for a supportive history and examination

fi ndings Core cardiac risk factors are previous infective endocarditis, a prosthetic valve or cardiac device, and valvular or congenital heart disease Non-cardiac risk

Panel 1: Proportion of cases of infective endocarditis

caused by diﬀ erent microorganisms from a French population-based cohort of 497 patients2

HACEK (haemophilus, aggregatibacter, cardiobacterium,

Eikenella corrodens, kingella) microorganisms

*Includes small numbers of Enterobacteriaceae, Propionibacterium acnes, Pseudomonas

aeruginosa, Lactobacillus spp, Corynebacterium spp, Coxiella burnetii, Bartonella quintana, Tropheryma whipplei, Gordonia bronchialis, Bacillus spp, Erysipelothrix rhusiopathiae, Neisseria elongata, Moraxella catarrhalis, Veillonella spp, Listeria monocytogenes, Acinetobacter ursingii, Campylobacter fetus, Francisella tularensis, and Catabacter hongkongensi

Trang 23

Căn nguyên gây bệnh

Trang 24

VNTM van tim nhân tạo

Trang 25

Streptococci and enterococci have tain characteristics that contribute to their ability to cause disease:

cer-the ability to live as normal fl ora on our skin and mucosal surfaces, mainly

are aggressive pathogens with ous virulence factors, which give the ability to adhere, invade and damage tissues.

numer-other strains are ‘opportunistic gens’: normal fl ora that can become pathogenic in abnormal sites or in abnormal hosts

patho-infection is followed by spread locally,

Gram-positive cocci (GPC), usually in chains, sometimes in pairs (Fig 1a, b) non-motile, non-sporing and may be capsulated (Fig 1c)

Confi rmatory tests

Fig 1 Gram stain showing Strep pyogenes

(a)

(b)

(c)

Trang 26

STREPTOCOCCUS 189

shared antigens Although strains with both classes of antigens can cause suppurative infections and glomerulonephritis, only bacteria with class I (exposed shared antigen) M proteins cause rheumatic fever The epide-

miologic classification of S pyogenes is based on sequence analysis of the emm gene that encodes the M proteins.

Other important components in the cell wall of S

pyogenes include M-like surface proteins, lipoteichoic

acid, and F protein A complex of more than 20 genes

that comprise the emm gene superfamily encode the

M-like proteins as well as the M proteins and globulin (Ig)-binding proteins Lipoteichoic acid and F protein facilitate binding of host cells by complexing with fibronectin, which is present on the host cell surface.

immuno-Some strains of S pyogenes have an outer hyaluronic

acid capsule that is antigenically indistinguishable from

hyaluronic acid in mammalian connective tissues Because the capsule can protect the bacteria from phagocytic clearance, encapsulated strains are more likely to be responsible for severe systemic infections.

Pathogenesis and Immunity

The virulence of group A streptococci is determined by the ability of the bacteria to avoid opsonization and phagocytosis, adhere to and invade host cells, and produce a variety of toxins and enzymes.

Initial Host-Parasite Interactions

S pyogenes has multiple mechanisms for avoiding

opso-nization and phagocytosis The hyaluronic acid capsule

is a poor immunogen and interferes with phagocytosis

The M proteins also interfere with phagocytosis by

blocking the binding of the complement component C3b, an important mediator of phagocytosis C3b may also be degraded by factor H, which binds to the cell surface of the M protein M-like proteins resemble M proteins in structure and are under the same regulatory control These proteins interfere with phagocytosis by binding either the Fc fragment of antibodies or fibronectin, which blocks activation of complement by the alter- nate pathway and reduces the amount of bound C3b

Organism Historical Derivation

Streptococcus streptus, pliant; coccus, grain or berry (a pliant

berry or coccus; refers to the appearance of long, flexible chains of cocci)

S agalactiae agalactia, want of milk (original isolate [called S

mastitidis] was responsible for bovine mastitis)

S anginosus anginosus, pertaining to angina

S constellatus constellatus, studded with stars (original isolate

embedded in agar with smaller colonies surrounding the large colony; satellite

formation does not occur around colonies on the surface of an agar plate)

S dysgalactiae dys, ill, hard; galactia, pertaining to milk (loss of

milk secretion; isolates associated with bovine mastitis)

S gallolyticus gallatum, gallate; lyticus, to loosen (able to digest

or hydrolyze methyl gallate)

S intermedius intermedius, intermediate (initial confusion about

whether this was an aerobic or an anaerobic bacterium)

S mitis mitis, mild (incorrectly thought to cause mild

infections)

S mutans mutans, changing (cocci that may appear rodlike,

particularly when initially isolated in culture)

S pneumoniae pneumon, the lungs (causes pneumonia)

S pyogenes pyus, pus; gennaio, beget or producing (pus

producing; typically associated with formation

of pus in wounds)

S salivarius salivarius, salivary (found in the mouth in saliva)

β-Hemolytic Streptococci

Group

Representative

A S pyogenes Pharyngitis, skin and soft-tissue

infections, bacteremia, rheumatic fever, acute glomerulonephritis

S anginosus group Abscesses

B S agalactiae Neonatal disease, endometritis,

wound infections, urinary tract infections, bacteremia,

pneumonia, skin and soft-tissue infections

C S dysgalactiae Pharyngitis, acute

glomerulonephritis

F, G S anginosus group Abscesses

S dysgalactiae Pharyngitis, acute

S oralis

Subacute endocarditis;

sepsis in neutropenic patients; pneumonia;

meningitis Mutans S mutans, S sobrinus Dental caries; bacteremia Salivarius S salivarius Bacteremia; endocarditis Bovis S gallolyticus subsp

gallolyticus, subsp

pasteurianus

Bacteremia associated with gastrointestinal cancer (subsp

gallolyticus); meningitis

(subsp pasteurianus)

streptococcal toxic shock syndrome

consists of two polypeptide chains complexed in an alpha

helix The protein is anchored in the cytoplasmic

mem-brane, extends through the cell wall, and protrudes

above the cell surface The carboxyl terminus, which is

anchored in the cytoplasmic membrane, and the portion

of the molecule in the cell wall are highly conserved (by

amino acid sequence) among all group A streptococci

The amino terminus, which extends above the cell

surface, is responsible for the antigenic differences

observed among the unique serotypes of M proteins M

proteins are subdivided into class I and class II

mole-cules The class I M proteins share exposed antigens,

whereas the class II M proteins do not have exposed

Streptococcus, Enterococcus, and Other Catalase-Negative Gram-Positive Cocci CHAPTER 15 333

proteins and fibronectin binding protein, secures the ment of streptococci to the oral mucosal cells The hyaluronic

attach-acid capsule of S pyogenes is weakly immunogenic The

capsule prevents opsonized phagocytosis by neutrophils or macrophages The capsule also allows the bacterium to mask its antigens and remain unrecognized by its host.

Other products produced by S pyogenes are streptolysin

O, streptolysin S, deoxyribonuclease (DNase), streptokinase, hyaluronidase, and erythrogenic toxin Although all of these products have been postulated to play a role in virulence, the

exact role each has in infection is not clear S pyogenes secretes

four different DNases: A, B, C, and D All strains produce

at least one DNase; the most common is DNase B These enzymes are antigenic, and antibodies to DNase can be detected following infection.

A hemolysin responsible for hemolysis on sheep blood agar

(SBA) plates incubated anaerobically is streptolysin O (SLO)

The O refers to this hemolysin being oxygen labile It is active

only in the reduced form, which is achieved in an anaerobic environment SLO lyses leukocytes, platelets, and other cells

as well as RBCs SLO is highly immunogenic, and the infected individual readily forms antibodies to the hemolysin These antibodies can be measured in the antistreptolysin-O (ASO) test to determine whether an individual has had a recent infec-

tion with S pyogenes Streptolysin S is oxygen stable, lyses

leukocytes, and is nonimmunogenic The hemolysis seen around colonies that have been incubated aerobically is due

because groups C and G also form streptokinase dase, or spreading factor, is an enzyme that solubilizes the

Hyaluroni-ground substance of mammalian connective tissues

(hyal-15-2 The clinically isolated streptococci have historically been separated into the β-hemolytic streptococci and the species that are non-β-hemolytic The β-hemolytic streptococci often

isolated from humans include S pyogenes, S agalactiae, S

dysgalactiae subsp equisimilis, and S anginosus group (some

species are α-hemolytic or nonhemolytic).

Streptococcus pyogenes

Antigenic Structure

Streptococcus pyogenes has a cell-wall structure similar to that

of other streptococci and gram-positive bacteria The group antigen is unique, placing the organism in Lancefield group

A M protein is attached to the peptidoglycan of the cell wall

and extends to the cell surface The M protein is essential for virulence.

Virulence Factors

The best-defined virulence factor in S pyogenes is M protein, encoded by the emm genes More than 80 different serotypes

of M protein exist, identified as M1, M2, and so on

Resis-tance to infection with S pyogenes appears to be related to

the presence of type-specific antibodies to the M protein This means that an individual with antibodies against M5 is pro-

tected from infection by S pyogenes with the M5 protein but

remains unprotected against infection with the roughly 80 remaining M protein serotypes The M protein molecule causes the streptococcal cell to resist phagocytosis and also plays a role in adherence of the bacterial cell to mucosal cells.

Additional virulence factors associated with group A streptococci are fibronectin-binding protein (protein F); lipoteichoic acid; hyaluronic acid capsule; and extracellular products, including hemolysins, toxins, and enzymes Lipoteichoic acid and protein F are adhesion molecules that mediate adherence to host epithelial cells Lipoteichoic acid, which is affixed to proteins on the bacterial surface, in concert with M

TABLE 15-2 Classification of Streptococcus and Enterococcus

S pyogenes A β* Group A strep Rheumatic fever, scarlet fever, pharyngitis,

glomerulonephritis, pyogenic infections

S agalactiae B β* Group B strep Neonatal sepsis, meningitis, puerperal

fever, pyogenic infections

S dysgalactiae, S equi C β Group C strep Pharyngitis, impetigo, pyogenic infections

S bovis group D α, none Nonenterococcus member of

group, mitis group, salivarius group

A, C, F, G, N, or

referred to as viridans strep)

Pyogenic infections, endocarditis, dental caries, abscesses in various tissues

*Occasionally isolates are found that are nonhemolytic.

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Gây bệnh

Trang 28

Staphylococcus spp

Tiêu đề	Các Vi Khuẩn Thường Gặp Gây Thấp Tim, Viêm Nội Tâm Mạc Và Các Xét Nghiệm Vi Sinh Chẩn Đoán
Tác giả	Phạm Hồng Nhung
Trường học	Đại học Y Hà Nội
Chuyên ngành	Vi sinh

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