THE GENUS THE GENUS

STREPTOCOCCUSSTREPTOCOCCUS

The genus The genus StreptococcusStreptococcus obtains grampositive obtains grampositive cocci, nonmotile, nonsporeforming, arranged cocci, nonmotile, nonsporeforming, arranged mostly in chains or in pairs. mostly in chains or in pairs. Most species are facultative anaerobes. Most species are facultative anaerobes. Some of streptococci are encapsulated.Some of streptococci are encapsulated.

The single scheme for differentiation of The single scheme for differentiation of streptococci is used in practise:streptococci is used in practise:– streptococci with complete (streptococci with complete () hemolysis) hemolysis– streptococci with incomplete (streptococci with incomplete () hemolysis ) hemolysis

(s.c. viridans streptococci)(s.c. viridans streptococci)– streptococci without hemolysisstreptococci without hemolysis

Streptococci • facultative anaerobe• Gram-positive• chains or pairs • catalase negative

Streptococci are widely distributed in nature.Streptococci are widely distributed in nature.

Some are members of the normal human microflora, Some are members of the normal human microflora, other are associated with important human diseases other are associated with important human diseases attributable in part to infection by streptococci, in part attributable in part to infection by streptococci, in part to sensitization to them.to sensitization to them.

Streptococci produce a variety of extracellular Streptococci produce a variety of extracellular substances and enzymes.substances and enzymes.

• The differentiation of streptococci according to The differentiation of streptococci according to serological properties (Lancefield groups A to V).serological properties (Lancefield groups A to V).

Streptococci, classified into different groups, posseStreptococci, classified into different groups, possesss group-s group-

specific antigens which are either cell wall carbohydrates (s.c. C specific antigens which are either cell wall carbohydrates (s.c. C

polysaccharides) or teichoic acid. polysaccharides) or teichoic acid.

• Other possibilities of differentiation of streptococci – Other possibilities of differentiation of streptococci – according to biochemical properties or clinical according to biochemical properties or clinical presentations.presentations.

Classification of streptococciClassification of streptococci- hemolysis on blood agar- hemolysis on blood agar

The type of hemolytic reaction displayed on blood agar has long been used to classify the streptococci. Beta -hemolysis is associated with complete lysis of red cells surrounding the colony, whereas alpha-hemolysis is a partial or "green" hemolysis associated with reduction of red cell hemoglobin. Nonhemolytic colonies have been termed gamma-hemolytic.

Group A streptococci are nearly always beta-hemolytic; related Group B can manifest alpha, beta or gamma hemolysis. Most strains of S. pneumoniae are alpha-hemolytic but can cause ß-hemolysis during anaerobic incubation. Most of the oral streptococci are non hemolytic. The property of hemolysis is not very reliable for the absolute identification of streptococci, but it is widely used in rapid screens for identification of S. pyogenes and S. pneumoniae.

Chemical structure Chemical structure and antigensand antigens

Cell wall polysaccharide CCell wall polysaccharide CPeptidoglycanPeptidoglycanLipoteichoic acidLipoteichoic acidM-proteinM-proteinT T substancesubstance and R protein and R proteinCapsuleCapsuleF proteinF protein

M proteinM protein This substance is major virulence factor of This substance is major virulence factor of S. pyogenesS. pyogenes. .

When M protein is present, the streptococci are virulent, When M protein is present, the streptococci are virulent, and in the absence of M type–specific antibodies, they and in the absence of M type–specific antibodies, they are able to resist phagocytosis by polymorphonuclear are able to resist phagocytosis by polymorphonuclear leukocytes.leukocytes.

M protein also promotes adherence to host epithelial M protein also promotes adherence to host epithelial cells. cells.

S. pyogenesS. pyogenes strains that lack M protein are not virulent. strains that lack M protein are not virulent.

T substanceT substance This antigen has no relationship to virulence of streptococci. This antigen has no relationship to virulence of streptococci.

Unlike M protein, T substance is acid-labile and heat-labile.Unlike M protein, T substance is acid-labile and heat-labile.

It is obtained from streptococci by proteolytic digestion.It is obtained from streptococci by proteolytic digestion.

T substance permits differentiation of certain types of T substance permits differentiation of certain types of streptococci by agglutination with specific antisera.streptococci by agglutination with specific antisera.

Another surface antigen has been called R protein.Another surface antigen has been called R protein.

Extracellular productsExtracellular productsErythrogenic toxin (pyrogenic toxin)Erythrogenic toxin (pyrogenic toxin)

Streptolysin OStreptolysin O

Streptolysin SStreptolysin S

Hyaluronidase (spreading factor)Hyaluronidase (spreading factor)

StreptokinaseStreptokinase

Streptodornase (streptococcal deoxyribonuclease)Streptodornase (streptococcal deoxyribonuclease)

otherother

Erythrogenic toxin (pyrogenic toxin)Erythrogenic toxin (pyrogenic toxin)

This toxin is soluble and it is destroyed by boiling for This toxin is soluble and it is destroyed by boiling for 1 hour.1 hour.

It causes the rash that occurs in scarlet fewer. Only It causes the rash that occurs in scarlet fewer. Only S. S. pyogenespyogenes strains elaborating this toxin can cause strains elaborating this toxin can cause scarlet fewer.scarlet fewer.

A non-toxigenic strain, after lysogenic conversion A non-toxigenic strain, after lysogenic conversion will produce erythrogenic toxin.will produce erythrogenic toxin.

Erythrogenic toxin is antigenic.Erythrogenic toxin is antigenic.

Pyrogenic toxinPyrogenic toxin

superantigen

Streptolysin OStreptolysin O

Streptolysin O is a protein that is hemolytically Streptolysin O is a protein that is hemolytically active in the reduced state, but rapidly inactivated active in the reduced state, but rapidly inactivated in the presence of oxygen.in the presence of oxygen.

ASLO – appear in human following infection ASLO – appear in human following infection with any streptococci that produce streptolysin O.with any streptococci that produce streptolysin O.

Streptolysin Streptolysin SS

Streptolysin S is the agent responsible for Streptolysin S is the agent responsible for the hemolytic zones around streptococcal the hemolytic zones around streptococcal colonies growing on the surface of blood colonies growing on the surface of blood agar.agar.

It is not antigenic.It is not antigenic.

HyaluronidaseHyaluronidaseHyaluronidase splits hyaluronic acid, an important Hyaluronidase splits hyaluronic acid, an important

component of the ground substance of connective component of the ground substance of connective tissues.tissues.

Thus, hyaluronidase aids in spreading of infecting Thus, hyaluronidase aids in spreading of infecting microorganisms (spreading factor).microorganisms (spreading factor).

Hyaluronidases are antigenic and specific for each Hyaluronidases are antigenic and specific for each bacterial or tissue source.bacterial or tissue source.

Streptodornase Streptodornase (streptococcal deoxyribonuclease(streptococcal deoxyribonuclease))

Streptococcal deoxyribonuclease depolymerizes Streptococcal deoxyribonuclease depolymerizes DNA.DNA.

The enzymatic activity can be measured by the The enzymatic activity can be measured by the decrease in viscosity of known DNA solutions.decrease in viscosity of known DNA solutions.

StreptokinaseStreptokinase(fibrinylosin)(fibrinylosin)

Streptokinase is produced by many strains of group A Streptokinase is produced by many strains of group A beta-hemolytic streptococci. beta-hemolytic streptococci.

It transforms the plasminogen of human plasma into It transforms the plasminogen of human plasma into plasmin, an active proteolytic enzyme that digests plasmin, an active proteolytic enzyme that digests fibrin and other proteins.fibrin and other proteins.

Streptokinase has been given intravenously for Streptokinase has been given intravenously for treatment of pulmonary and of coronary artery and treatment of pulmonary and of coronary artery and venous thromboses.venous thromboses.

Classification of streptococci of Classification of streptococci of particular medical interestparticular medical interest

Streptococcus pyogenesStreptococcus pyogenesStreptococcus agalactiaeStreptococcus agalactiaebeta-hemolytic streptococci C, F, Gbeta-hemolytic streptococci C, F, GStreptococcus pneumoniaeStreptococcus pneumoniaeStreptococcus anginosusStreptococcus anginosusviridans streptococciviridans streptococciPeptostreptococcus Peptostreptococcus speciesspecies

The species The species Streptococcus pyogenesStreptococcus pyogenes Grampositive spherical cocci, 0.5 to 1.0 miGrampositive spherical cocci, 0.5 to 1.0 miccrometer in diameter rometer in diameter

arranged in chains (especially in liquid media and pathological arranged in chains (especially in liquid media and pathological specimens). specimens).

S. pyogenesS. pyogenes likely as other streptococci does not produce likely as other streptococci does not produce catalase (in contrast to staphylococci).catalase (in contrast to staphylococci).

This species does not split ribose (in contrast to other This species does not split ribose (in contrast to other streptococci). streptococci).

It grows in white regular colonies about 1 mm in diameter, with It grows in white regular colonies about 1 mm in diameter, with a large zone of a large zone of -hemolysis on blood agar after 24 h-hemolysis on blood agar after 24 hourours of s of incubation.incubation.

 

The species The species Streptococcus pyogenesStreptococcus pyogenes

The metabolism of S. pyogenes is fermentative; the organism is a catalase-negative aerotolerant anaerobe (facultative anaerobe), and requires enriched medium containing blood in order to grow.

Group A streptococci typically have a capsule composed of hyaluronic acid and exhibit beta (clear) hemolysis on blood agar.

Group A streptococci are parasites of humans, and Streptococcus pyogenes is one of the most frequent pathogens of humans.

It is estimated that between 5-15% of normal individuals harbor Streptococcus pyogenes, usually in the respiratory tract, without signs of disease.

When the host defenses are compromised, or when the microorganism is able to exert its virulence, or when it is introduced to vulnerable tissues or hosts, an acute infection occurs.

Streptococcus pyogenes owes its major success as a pathogen to its ability to colonize and rapidly multiply and spread in its host while evading phagocytosis and confusing the immune system.

Acute diseases associated with Streptococcus pyogenes occur chiefly in the respiratory tract, bloodstream, or the skin. Streptococcal disease is most often a respiratory infection (pharyngitis or tonsillitis) or a skin infection (pyoderma). S. pyogenes is the leading cause of uncomplicated bacterial pharyngitis and tonsillitis.

S. pyogenes infections can also result in sinusitis, otitis, mastoiditis, pneumonia, joint or bone infections, necrotizing fasciitis and myositis, meningitis or endocarditis.

S. pyogenes also infects the skin. Infections of the skin can be superficial (impetigo) or deep (cellulitis).

Scarlet fever and streptococcal toxic shock syndrome are systemic responses to circulating bacterial toxins.

Two post streptococcal sequelae (rheumatic fever following respiratory infection and glomerulonephritis following respiratory or skin infection), occur in 1-3% of untreated infections.

There has been a recent increase in variety, severity and sequelae of Streptococcus pyogenes infections, and a resurgence of severe invasive infections, prompting descriptions of "flesh eating bacteria" in the news media.

A complete explanation for the decline and resurgence is not known. Today, the pathogen is of major concern because of the occasional cases of rapidly progressive disease and because of the risk of serious sequelae in untreated infections. These diseases remain a major worldwide health concern, and effort is being directed toward clarifying the risk and mechanisms of these sequelae and identifying rheumatogenic and nephritogenic strains of streptococci.

The most frequent etiologic agents of The most frequent etiologic agents of

bacterial tonsillitis and bacterial tonsillitis and

tonsillopharyngitis are tonsillopharyngitis are Streptococcus Streptococcus

pyogenespyogenes strains (80-90 %). strains (80-90 %).

Initial antibiotic therapy of bacterial Initial antibiotic therapy of bacterial tonsillitis and tonsillopharyngitistonsillitis and tonsillopharyngitis

Antibiotics of I. choiceAntibiotics of I. choice– penicillin (3-4 x daily)penicillin (3-4 x daily)– macrolides (in patients with allergy to macrolides (in patients with allergy to

penicillins)penicillins)

Etiology and treatment of Etiology and treatment of peritonsillar and tonsillar abscessperitonsillar and tonsillar abscess

Etiology:– Streptococcus pyogenes– anaerobic microbes

(Peptostreptococcus sp.)

ATB of I. choice:– penicillin

Alternative ATB:– clindamycin

Diagnostic methodsDiagnostic methods

microscopymicroscopycultivationcultivationbiochemical testsbiochemical testsserological examinserological examinaationtionothersothers

Streptococcus pneumoniaeStreptococcus pneumoniaePneumococci are alfa-hemolytic.Pneumococci are alfa-hemolytic.

Their growth is inhibited by optochin.Their growth is inhibited by optochin.

The pneumococci are grampositive diplococci, often The pneumococci are grampositive diplococci, often lancet-shaped or arranged in chains, possessing a lancet-shaped or arranged in chains, possessing a capsule of polysaccharide that permits typing with capsule of polysaccharide that permits typing with specific antisera.specific antisera.

Streptococcus pneumoniaeStreptococcus pneumoniae is very is very important etiologic agent of pneumoniaimportant etiologic agent of pneumonia

PneumoniaPneumoniatypical typical atypicalatypical

PneumoniaPneumoniacommunity-acquiredcommunity-acquiredhospital-acquired (nosocomial)hospital-acquired (nosocomial)

Etiology of pneumoniaEtiology of pneumonia

typical pneumoniatypical pneumonia Streptococcus pneumoniaeStreptococcus pneumoniae Haemophilus influenzae Haemophilus influenzae Moraxella (Branhamella) catarrhalisMoraxella (Branhamella) catarrhalisStaphylococcus aureus Staphylococcus aureus Klebsiella pneumoniaeKlebsiella pneumoniaeotherother

Etiology of pneumoniaEtiology of pneumonia

atypical pneumoniaatypical pneumonia Chlamydophila pneumoniaeChlamydophila pneumoniaeChlamydophila psittaciChlamydophila psittaciMycoplasma pneumoniaeMycoplasma pneumoniaeLegionella pneumophilaLegionella pneumophilaothersothers

Etiology of pneumonia in olomouc Etiology of pneumonia in olomouc region (CAP)region (CAP)

chlamydia12%

mycoplasma6%

mixed infections

6%

typical bacteria

34%

unknown etiology

42%

Initial antibiotic therapy of Initial antibiotic therapy of community-acquired pneumoniacommunity-acquired pneumonia

Drug ofDrug of I. I. choicechoice

– amoxicilamoxicilllinin

Alternative antibioticsAlternative antibiotics

– mamaccrolidrolideses ( (e.g. ce.g. claritlarithhromycinromycin, azithromycin, azithromycin))

– doxycycline (in adults and children older than 12 years)doxycycline (in adults and children older than 12 years)

Etiology and treatment of Etiology and treatment of otitis media acutaotitis media acuta

Etiology:– Streptococcus

pneumoniae– Haemophilus influenzae– Moraxella (B)

catarrhalis

Antibiotic of I. choice:– amoxicillin

Alternative antibiotic:– amoxicillin/clavulanic acid– ampicillin/sulbactam– cephalosporins II. gen.

(cefuroxime, cefprozil)– in patients with allergy to

penicilllins - macrolides

Bacterial etiology of acute otitis media Bacterial etiology of acute otitis media in in olomouc regionolomouc region

Streptococcus pneumoniae - 49%

Haemophilus influenzae - 21%

Moraxella (B)catarrhalis- 14%

others - 16%

Etiology and treatment of sinusitis acutaEtiology and treatment of sinusitis acuta

Etiology:– Streptococcus

pneumoniae Haemophilus influenzae

– Moraxella (B) catarrhalis

Antibiotic of I. choice:– amoxicillin

Alternative antibiotic:

– amoxicillin/clavulanic acid

– ampicillin/sulbactam

– cephalosporins II. gen. (cefuroxime,

cefprozil)

– in patients with allergy to penicilllins -

macrolides

Bacterial etiology of acute sinusitis Bacterial etiology of acute sinusitis in in olomouc regionolomouc region

Streptococcus pneumoniae - 61%

Haemophilus influenzae - 22%

Moraxella (B)catarrhalis - 5%

others - 12%

Streptococcus agalactiaeStreptococcus agalactiae These are the group B streptococci. These are the group B streptococci.

They are members of the normal flora of the female genital They are members of the normal flora of the female genital tract and an important cause of neonatal sepsis and meningitis.tract and an important cause of neonatal sepsis and meningitis.

They typically are beta-hemolytic.They typically are beta-hemolytic.

They have positive CAMP test.They have positive CAMP test.

Basing on results obtainedBasing on results obtained in in Neonatal department of Teaching Neonatal department of Teaching Hospital in Olomouc, Hospital in Olomouc, the the most frequent bacterial pathogensmost frequent bacterial pathogens of neonatal of neonatal sepsis aresepsis are Escherichia coli, Klebsiella pneumoniae, Streptococcus Escherichia coli, Klebsiella pneumoniae, Streptococcus agalactiae, Enterococcusagalactiae, Enterococcus sp. and sp. and Staphylococcus aureusStaphylococcus aureus..

Based on Based on their resistance their resistance to antibiotics to antibiotics it can be concluded that it can be concluded that ampicillin in combination with ampicillin in combination with gentamicin/gentamicin/netilmicin is first choice netilmicin is first choice regimen. regimen.

In case of persisting signs of infection, it is necessary to consider the In case of persisting signs of infection, it is necessary to consider the etiological role of chlamydia, mycoplasma and ureoplasma and the etiological role of chlamydia, mycoplasma and ureoplasma and the therapy is to be changed by adding of macrolide. therapy is to be changed by adding of macrolide.

After the identification od bacterial pathogens and the resistance to After the identification od bacterial pathogens and the resistance to antibiotics the therapy should be focused on the aimed (causal) one.antibiotics the therapy should be focused on the aimed (causal) one.

Etiology of neonatal infections Etiology of neonatal infections in in Teaching Hospital in OlomoucTeaching Hospital in Olomouc

gram-negative bacteria 53 %

Escherichia coli 19 %

Klebsiella pneumoniae 16 %

Pseudomonas aeruginosa 7%

Enterobacter cloacae 6 %

Acinetobacter baumannii 5 %

gram-positive bacteria 43 %

Streptococcus agalactiae 15%

Enterococcus sp. 13 % (84 % is E. faecalis)

Staphylococcus aureus 9 %

Staphylococcus sp. (coagulase-negative) 6 %

Candida sp. ( 87 % is C. albicans) 4 %

Etiology of community-acquired Etiology of community-acquired urinary tract infectionsurinary tract infections

Escherichia coli

Proteus mirabilis

Enterococcus faecalis

Streptococcus agalactiae

others

Bacterial etiology of community-acquired Bacterial etiology of community-acquired urinary tract infections in urinary tract infections in olomouc regionolomouc region

E.coli68%

P.mirabilis11%

E.faecalis9%

S.agalactiae8%

others4%

Initial antibiotic therapy of community-Initial antibiotic therapy of community-acquired urinary tract infectionsacquired urinary tract infections

Drug of I. choiceDrug of I. choice– nitrofurantoin, amoxicillin, cotrimoxazol, nitrofurantoin, amoxicillin, cotrimoxazol,

trimethoprim, oxolinic acidtrimethoprim, oxolinic acid

Alternative antibioticsAlternative antibiotics– amoxicillin/clavulanic acidamoxicillin/clavulanic acid– ampicillin/sulbactamampicillin/sulbactam– cephalosporins II. gen. (cefuroxime, cefprozil)cephalosporins II. gen. (cefuroxime, cefprozil)

Streptococcus anginosusStreptococcus anginosus

Other species names for Other species names for S. anginosusS. anginosus are are S. S.

millerimilleri, , S. intermediusS. intermedius and and S. constellatusS. constellatus. These . These

streptococci are part of the normal flora.streptococci are part of the normal flora.

They may be beta, alpha or non-hemolytic.They may be beta, alpha or non-hemolytic.

Viridans streptococciViridans streptococci Viridans streptococci include Viridans streptococci include S. mitis, S. mutans, S. S. mitis, S. mutans, S.

salivarius, S. sanquissalivarius, S. sanquis and other. and other.

Typically they are alpha-hemolytic, but they may be non-Typically they are alpha-hemolytic, but they may be non-hemolytic.hemolytic.

The viridans streptococci are the most prevalent members The viridans streptococci are the most prevalent members of normal microflora of the upper respiratory tract and are of normal microflora of the upper respiratory tract and are important for healthy state of mucous membranes there.important for healthy state of mucous membranes there.

They may reach the bloodstream as a result of trauma and They may reach the bloodstream as a result of trauma and are a principal cause of endocarditis on abnormal heart are a principal cause of endocarditis on abnormal heart valves.valves.

Peptostreptococcus Peptostreptococcus speciesspeciesThese streptococci grow only under anaerobic conditions These streptococci grow only under anaerobic conditions

and variably produce hemolysins.and variably produce hemolysins.

They are part of the normal microflora of the mouth, upper They are part of the normal microflora of the mouth, upper respiratory tract, bowel, and female genital tract.respiratory tract, bowel, and female genital tract.

They often participate with many other bacterial species in They often participate with many other bacterial species in mixed anaerobic infections in the abdomen, pelvis, lung, or mixed anaerobic infections in the abdomen, pelvis, lung, or brain.brain.