214   SECTION III  Bacteriology

Answers REFERENCES
1. D 6. D 11. E Becker K, Ballhausen B, Kock R, Kriegeskorte A: Methicillin
2. E 7. E 12. A resistance in Staphylococcus isolates: the “mec alphabet” with
3. A 8. D 13. D specific consideration of mec, C a mec homolog associated with
4. C 9. D 14. C S. aureus lineages. Int J Med Microbiol 2014;304:794.
5. E 10. C 15. D Que YA, Moreillon P: Chapter 196, Staphylococcus aureus (includ-
ing staphylococcal toxic shock). In Bennett JE, Dolin R, Blaser
MJ (editors). Mandell, Douglas and Bennett’s Principles and
Practice of Infectious Diseases, 8th ed. Churchill Livingstone,
Elsevier, 2015.

Riedel_CH13_p205-p214.indd 214 05/04/19 4:36 PM

 14
C H A P T E R

The Streptococci, Enterococci,

and Related Genera

The streptococci, enterococci, and related organisms are the human-pathogenic species S. pyogenes, S. agalactiae, and
Gram-positive spherical bacteria that characteristically form S. dysgalactiae. The classification of hemolytic patterns is
pairs or chains during growth. They are widely distributed used primarily with the streptococci although other bacte-
in nature. Some are members of the normal human micro- ria that cause disease may also typically produce a variety of
biota; others are associated with important human diseases hemolysins.
attributable to the direct effects of infection or in other cases
to an immunologic response to them. Streptococci elaborate B. Group-Specific Substance
a variety of extracellular substances and enzymes. (Lancefield Classification)
The streptococci are a large and heterogeneous group
This carbohydrate is contained in the cell wall of many strepto-
of bacteria, and no one system suffices to classify them. Yet,
cocci and forms the basis of serologic grouping into Lancefield
understanding their taxonomy is key to understanding their
groups A–H and K–U. The serologic specificity of the group-
medical importance.
specific carbohydrate is determined by an amino sugar. For
group A streptococci, this is rhamnose-N-acetylglucosamine;
for group B, it is rhamnose-glucosamine polysaccharide; for
CLASSIFICATION OF STREPTOCOCCI group C, it is rhamnose-N-acetylgalactosamine; for group D,
The classification of streptococci into major categories has it is glycerol teichoic acid containing d-alanine and glucose;
been based on a series of observations over many years: (1) and for group F, it is glucopyranosyl-N-acetylgalactosamine.
colony morphology and hemolytic reactions on blood agar, Extracts of group-specific antigen for grouping strepto-
(2) serologic specificity of the cell wall group-specific sub- cocci are prepared by a variety of methods, including extrac-
stance (Lancefield antigens) and other cell wall or capsular tion of centrifuged culture treated with hot hydrochloric
antigens, (3) biochemical reactions and resistance to physical acid, nitrous acid, or formamide; by enzymatic lysis of strep-
and chemical factors, and (4) ecologic features. More recently, tococcal cells (eg, with pepsin or trypsin); or by autoclaving
molecular genetics have replaced phenotypic methods in the of cell suspensions. These extracts contain the carbohydrate
taxonomic assignment of these organisms. The classifica- group-specific substance that yields precipitin reactions
tion of streptococci of medical importance is summarized in specific antisera. This permits arrangement of many strep-
Table 14-1. tococci into groups A–H and K–U. Typing is generally done
only for groups A, B, C, F, and G (see Table 14-1), which cause
A. Hemolysis disease in humans and for which reagents are available that
allow typing using simple agglutination or color reactions.
Many streptococci are able to hemolyze red blood cells in
vitro in varying degrees. Complete disruption of erythro-
cytes with clearing of the blood around the bacterial growth C. Capsular Polysaccharides
is called β-hemolysis. Incomplete lysis of erythrocytes with The antigenic specificity of the capsular polysaccharides is
reduction of hemoglobin and the formation of green pigment used to classify S. pneumoniae into more than 90 types and to
is called α-hemolysis. Other streptococci are nonhemolytic type the group B streptococci (S. agalactiae).
(sometimes called γ- hemolysis).
The hemolysis patterns of the streptococci of medical D. Biochemical Reactions
importance to humans are shown in Table 14-1. Clini- Biochemical tests include sugar fermentation reactions,
cally important streptococci are traditionally differenti- tests for the presence of enzymes, and tests for susceptibil-
ated based on their hemolysis pattern, that is, β-hemolytic ity or resistance to certain chemical agents. Biochemical tests
vs non-hemolytic streptococci. Beta-hemolytic streptococci are most often used to classify streptococci after the colony
are also referred to as pyogenic streptococci, which include growth and hemolytic characteristics have been observed.

215

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 216   SECTION III  Bacteriology

TABLE 14-1 Characteristics of Medically Important Streptococci

Group-
Specific Important Common and
Name Substancea Hemolysisb Habitat Laboratory Criteria Important Diseases

Pyogenic
Streptococci

Streptococcus A β Throat, skin Large colonies (>0.5 mm), PYRc Pharyngitis, impetigo,
pyogenes test positive, inhibited by deep soft tissue
bacitracin infections; bacteremia;
rheumatic fever,
glomerulonephritis,
toxic shock

Streptococcus B β Urogenital Hippurate hydrolysis, CAMP- Neonatal sepsis

agalactiae tract, factor positived and meningitis;
lower GI bacteremia, UTIs,e
tract meningitis in adults

Streptococcus A, C, G β (human) Throat Large (>0.5 mm) colonies Pharyngitis, pyogenic

dysgalactiae infections), infections similar to
subspecies α, none group A streptococci
equisimilis; others

Viridans
Streptococci

Streptococcus bovis D None Colon, biliary Growth in presence of bile, Endocarditis, common
groupf tree hydrolyze esculin, no growth blood isolate in colon
in 6.5% NaCl, degrades starch cancer, biliary disease

Streptococcus F (A, C, G) and α, β, none Throat, colon, Small (<0.5 mm) colony variants Pyogenic infections,
anginosus group untypeable urogenital of β-hemolytic species; group including brain, liver,
(S. anginosus, tract A are bacitracin resistant and lung abscesses
Streptococcus PYR negative; carbohydrate
intermedius, fermentation patterns;
Streptococcus arginine, esculin, VPg positive
constellatus)

Mutans group Usually not α, none Oral cavity Carbohydrate fermentation Dental caries
typed patterns; esculin, VP positive (Streptococcus
mutans), endocarditis;
abscesses (with
many other bacterial
species)

Mitis-Sanguinis
group

Streptococcus None° α Nasopharynx Susceptible to optochin; Pneumonia, meningitis,

pneumoniae colonies soluble in bile; bacteremia, otitis
quellung reaction positive media, sinusitis

Streptococcus mitis None α, none Oral cavity VP negativeg; carbohydrate Endocarditis;

fermentation patterns bacteremia, sepsis in
immunocompromised
patients; high-level
resistance to penicillin

Salivarius group None α, none Oral cavity VP positive; carbohydrate Bacteremia, endocarditis,
fermentation patterns meningitis

GI, gastrointestinal.
a
Lancefield classification.
b
Hemolysis observed on 5% sheep blood agar after overnight incubation.
c
Hydrolysis of l-pyrrolidonyl-β-naphthylamide (PYR).
d
CAMP, Christie, Atkins, Munch-Peterson.
e
UTIs, urinary tract infections.
Includes the human species: Streptococcus gallolyticus subspecies gallolyticus; Streptococcus gallolyticus subspecies macedonicus; Streptococcus gallolyticus subspecies
f

pasteurianus; Streptococcus infantarius subspecies infantarius.

g
VP, Voges Proskauer; all viridans group streptococci are VP positive except the mitis group.

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 CHAPTER 14 The Streptococci, Enterococci, and Related Genera    217

Biochemical tests are used for species that typically do not

react with the commonly used antibody preparations for
the group-specific substances, groups A, B, C, F, and G. For
example, the viridans streptococci are α-hemolytic or non-
hemolytic and do not react with the antibodies commonly
used for the Lancefield classification. Speciation of the viri-
dans streptococci requires a battery of biochemical tests
(see Table 14-1). However, because biochemical reactions
are labor intensive and often unreliable, laboratories with
molecular capabilities, such as gene sequencing or that have
implemented mass spectrometry for organism identification
(matrix-assisted laser desorption ionization-time of flight
mass spectrometry [MALDI-TOF MS]), are replacing pheno-
typic tests with these methods when identification of virid-
ians streptococci is required.

STREPTOCOCCI, ENTEROCOCCI,
AND RELATED GENERA OF FIGURE 14-1 Streptococci grown in blood culture showing
Gram-positive cocci in chains. Original magnification × 1000.
PARTICULAR MEDICAL INTEREST
The following streptococci and enterococci are of particular than is generally appreciated and together with M protein
medical relevance. was believed to be an important factor in the resurgence of
rheumatic fever (RF) in the United States in the 1980s and
1990s. The capsule binds to hyaluronic-acid-binding protein,
STREPTOCOCCUS PYOGENES CD44, present on human epithelial cells. Binding induces
Most clinical isolates of streptococci that contain the group A disruption of intercellular junctions allowing microorgan-
antigen are S. pyogenes. It is a prototypical human pathogen. isms to remain extracellular as they penetrate the epithelium
It is used here to illustrate general characteristics of strepto- (see Stollerman and Dale, 2008). Capsules of other strepto-
cocci and specific characteristics of the species. S. pyogenes cocci (eg, S. agalactiae and S. pneumoniae) are different. The
is the main human pathogen associated with local or sys- S. pyogenes cell wall contains proteins (M, T, R antigens), car-
temic invasion and poststreptococcal immunologic disor- bohydrates (group specific), and peptidoglycans. Hairlike pili
ders. S. pyogenes typically produces large (1 cm in diameter) project through the capsule of group A streptococci. The pili
zones of β-hemolysis around colonies greater than 0.5 mm in consist partly of M protein and are covered with lipoteichoic
diameter. They are PYR-positive (hydrolysis of l-pyrrolidony acid. The latter is important in the attachment of streptococci
l-β-naphthylamide) and usually are susceptible to bacitracin. to epithelial cells.

B. Culture
Morphology and Identification Most streptococci grow in solid media as discoid colonies,
A. Typical Organisms usually 1–2 mm in diameter. S. pyogenes is β-hemolytic
Individual cocci are spherical or ovoid and are arranged in (Figure 14-2); other species have variable hemolytic charac-
chains (Figure 14-1). The cocci divide in a plane perpendicular teristics (see Table 14-1).
to the long axis of the chain. The members of the chain often
have a striking diplococcal appearance, and rodlike forms C. Growth Characteristics
are occasionally seen. The lengths of the chains vary widely Energy is obtained principally from the utilization of glucose
and are conditioned by environmental factors. Streptococci with lactic acid as the end product. Growth of streptococci
are Gram-positive; however, as a culture ages and the bac- tends to be poor on solid media or in broth unless enriched
teria die, they lose their Gram positivity and can appear to with blood or tissue fluids. Nutritive requirements vary
be Gram-negative; for some streptococci, this can occur after widely among different species. The human pathogens are
overnight incubation. most exacting, requiring a variety of growth factors. Growth
Most group A strains (see Table 14-1) produce capsules and hemolysis are aided by incubation in 10% CO2. Most
composed of hyaluronic acid. The capsules are most notice- pathogenic hemolytic streptococci grow best at 37°C. Most
able in very young cultures. They impede phagocytosis. The streptococci are facultative anaerobes and grow under aero-
hyaluronic acid capsule likely plays a greater role in virulence bic and anaerobic conditions.

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 218   SECTION III  Bacteriology

It appears that M protein and perhaps other streptococ-

cal cell wall antigens have an important role in the patho-
genesis of rheumatic fever. Purified streptococcal cell wall
membranes induce antibodies that react with human cardiac
sarcolemma; the characteristics of the cross-reactive antigens
are not clear. A component of the cell wall of selected M types
induces antibodies that react with cardiac muscle tissue.
Conserved antigenic domains on the class I M protein cross-
react with human cardiac muscle, and the class I M protein
may be a virulence determinant for rheumatic fever.

Toxins and Enzymes

More than 20 extracellular products that are antigenic are
elaborated by S. pyogenes, including the following.

A. Streptokinase (Fibrinolysin)
Streptokinase is produced by many strains of group A
FIGURE 14-2 Group A β-hemolytic streptococci (S. pyogenes) after β-hemolytic streptococci. It transforms the plasminogen of
growth overnight on a 10-cm plate with 5% sheep blood agar. The human plasma into plasmin, an active proteolytic enzyme
small (0.5–1 mm diameter) white colonies are surrounded by diffuse that digests fibrin and other proteins, allowing the bacteria
zones of β-hemolysis 7–10 mm in diameter. (Courtesy of H Reyes.) to escape from blood clots. This process of digestion may
be interfered with by nonspecific serum inhibitors and by a
specific antibody, antistreptokinase. Streptokinase has been
D. Variation given intravenously for treatment of pulmonary emboli, cor-
Variants of the same Streptococcus strain may show different onary artery, and venous thromboses.
colony forms. This is particularly marked among S. pyogenes
strains, giving rise to either matte or glossy colonies. Matte
B. Deoxyribonucleases
colonies consist of organisms that produce much M protein
and generally are virulent. The S. pyogenes in glossy colonies Streptococcal deoxyribonucleases A, B, C, and D degrade
tend to produce little M protein and are often not virulent. DNA (DNases) and similar to streptokinase facilitate the
spread of streptococci in tissue by liquefying pus. The enzy-
matic activity can be measured by the decrease in viscosity of
Antigenic Structure known DNA solutions. Purulent exudates owe their viscos-
ity largely to deoxyribonucleoprotein. Mixtures of streptoki-
A. M Protein
nase and DNases are used in “enzymatic debridement.” They
This substance is a major virulence factor of S. pyogenes. M help to liquefy exudates and facilitate removal of pus and
protein is a filamentous structure anchored to the cell mem- necrotic tissue; antimicrobial drugs thus gain better access,
brane that penetrates and projects from the streptococcal cell and infected surfaces recover more quickly. An antibody to
wall. When M protein is present, the streptococci are virulent, DNAse develops after streptococcal infections (normal limit,
and in the absence of M type-specific antibodies, they are able 100 units), especially after skin infections.
to resist phagocytosis by polymorphonuclear leukocytes by
inhibiting activation of the alternate complement pathway.
C. Hyaluronidase
S. pyogenes that lack M protein are not virulent. Immunity to
infection with group A streptococci is related to the presence Hyaluronidase splits hyaluronic acid, an important com-
of type-specific antibodies to M protein. Because there are ponent of the ground substance of connective tissue. Thus,
more than 150 types of M protein, a person can have repeated hyaluronidase aids in spreading infecting microorganisms
infections with S. pyogenes of different M types. Both groups C (spreading factor). Hyaluronidases are antigenic and spe-
and G streptococci have genes homologous to the genes for M cific for each bacterial or tissue source. After infection with
protein of group A, and M proteins similar to those of group A hyaluronidase-producing organisms, specific antibodies are
have been found on groups C and G streptococci. found in the serum.
The M protein molecule has a rodlike coiled structure
that separates functional domains. The structure allows for D. Pyrogenic Exotoxins (Erythrogenic Toxin)
a large number of sequence changes while maintaining func- Pyrogenic exotoxins are elaborated by S. pyogenes. There
tion, and the M protein immunodeterminants, therefore, can are three antigenically distinct streptococcal pyrogenic
readily change. There are two major structural classes of M exotoxins (Spe): A, B, and C. SpeA has been most widely
protein, classes I and II. studied. It is produced by group A streptococci that carry a

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 CHAPTER 14 The Streptococci, Enterococci, and Related Genera    219

lysogenic phage. The streptococcal pyrogenic exotoxins have spreading infection that involves the tissues and extends
been associated with streptococcal toxic shock syndrome along lymphatic pathways with only minimal local suppu-
and scarlet fever. Most strains of group A streptococci iso- ration. From the lymphatics, the infection can extend to the
lated from patients with streptococcal toxic shock syndrome bloodstream.
either produce Spe A or have the gene that codes for it; in
contrast, only about 15% of group A streptococci isolated 1. Erysipelas—If the portal of entry is the skin, erysipelas
from other patients have the gene. Spe C, also encoded by results. Lesions are raised and characteristically red. There
a phage, may contribute to the syndrome. Spe B, a potent is massive brawny edema and a rapidly advancing, sharply
protease, interferes with phagocytosis. The group A strep- demarcated margin of infection.
tococci associated with toxic shock syndrome are primarily 2. Cellulitis—Streptococcal cellulitis is an acute, rapidly
of M protein types 1 and 3. spreading infection of the skin and subcutaneous tissues.
The pyrogenic exotoxins act as superantigens, which It follows infection associated with mild trauma, burns,
stimulate T cells by binding to the class II major histocom- wounds, or surgical incisions. Pain, tenderness, swelling,
patibility complex in the Vβ region of the T-cell receptor. The and erythema occur. Cellulitis is differentiated from ery-
activated T cells release cytokines that mediate shock and tis- sipelas by two clinical findings: In cellulitis, the lesion is
sue injury. The mechanisms of action appear to be similar to not raised, and the line between the involved and unin-
those caused by staphylococcal toxic shock syndrome toxin-1 volved tissue is indistinct.
and the staphylococcal enterotoxins. 3. Necrotizing fasciitis (streptococcal gangrene)—There
is extensive and very rapidly spreading necrosis of the skin,
E. Hemolysins tissues, and fascia. Bacteria other than S. pyogenes can also
The β-hemolytic group A S. pyogenes elaborates two hemo- cause necrotizing fasciitis. The group A streptococci that
lysins (streptolysins) that not only lyse the membranes of cause necrotizing fasciitis have sometimes been termed
erythrocytes but also damage a variety of other cell types. flesh-eating bacteria.
Streptolysin O is a protein (molecular weight [MW], 60,000) 4. Puerperal fever—If the streptococci enter the uterus after
that is hemolytically active in the reduced state (available– delivery, puerperal fever develops, which is essentially a sep-
SH groups) but rapidly inactivated in the presence of oxygen. ticemia originating in the infected wound (endometritis).
Streptolysin O is responsible for some of the hemolysis seen 5. Bacteremia or sepsis—Infection of traumatic or surgi-
when growth occurs in cuts made deep into the medium cal wounds with streptococci results in bacteremia, which
in blood agar plates. It combines quantitatively with anti- can rapidly be fatal. S. pyogenes bacteremia can also
streptolysin O (ASO), an antibody that appears in humans occur with skin infections, such as cellulitis and rarely
after infection with any streptococci that produce strepto- pharyngitis.
lysin O. This antibody blocks hemolysis by streptolysin O.
This phenomenon forms the basis of a quantitative test for
the antibody. An ASO serum titer in excess of 160–200 units B. Diseases Attributable to Local Infection with
is considered abnormally high and suggests either recent
S. pyogenes and Their By-products
infection with S. pyogenes or persistently high antibody lev-
els caused by an exaggerated immune response to an earlier 1. Streptococcal sore throat—The most common infection
exposure in a hypersensitive person. Streptolysin S is the caused by β-hemolytic S. pyogenes is streptococcal sore
agent responsible for the hemolytic zones around strepto- throat or pharyngitis. S. pyogenes adheres to the pharyn-
coccal colonies growing on the surface of blood agar plates. geal epithelium by means of lipoteichoic acid-covered sur-
It is elaborated in the presence of serum—hence the name face pili and by means of hyaluronic acid in encapsulated
streptolysin S. It is not antigenic. Most isolates of S. pyogenes strains. The glycoprotein fibronectin (MW, 440,000) on
produce both of these hemolysins. Up to 10% produce only epithelial cells probably serves as lipoteichoic acid ligand.
one. In infants and small children, the sore throat occurs as a
subacute nasopharyngitis with a thin serous discharge and
little fever but with a tendency of the infection to extend to
Pathogenesis and Clinical Findings the middle ear and the mastoid. The cervical lymph nodes
are usually enlarged. The illness may persist for weeks. In
A variety of distinct disease processes are associated with older children and adults, the disease is more acute and is
S. pyogenes infections. The infections can be divided into sev- characterized by intense nasopharyngitis, tonsillitis, and
eral categories. intense redness and edema of the mucous membranes,
with purulent exudate; enlarged, tender cervical lymph
A. Diseases Attributable to Invasion by nodes; and (usually) a high fever. Twenty percent of infec-
S. pyogenes, β-Hemolytic Group A Streptococci tions are asymptomatic. A similar clinical picture can
The portal of entry determines the principal clinical pic- occur with infectious mononucleosis, diphtheria, gono-
ture. In each case, however, there is a diffuse and rapidly coccal infection, and adenovirus infection.

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 220   SECTION III  Bacteriology

S. pyogenes infection of the upper respiratory tract preceded by infection of the skin; rheumatic fever is more
does not usually involve the lungs. Pneumonia, when it commonly preceded by infection of the respiratory tract.
does occur, is rapidly progressive and severe and is most
commonly a sequela to viral infections, such as influenza 1. Acute glomerulonephritis—This sometimes develops
or measles, which seem to greatly enhance the predisposi- 1–5 weeks (mean 7 days) after S. pyogenes skin infection
tion to bacterial superinfection with this and other patho- (pyoderma, impetigo) or pharyngitis. Some strains are
gens, such as S. pneumoniae. particularly nephritogenic, principally with M types 2,
2. Streptococcal pyoderma—Local infection of superficial 42, 49, 56, 57, and 60 (skin). Other nephritogenic M types
layers of skin, especially in children, is called impetigo. It associated with throat infections and glomerulonephritis
consists of superficial vesicles that break down and eroded are 1, 4, 12, and 25. After random streptococcal skin infec-
areas whose denuded surface is covered with pus and later tions, the incidence of nephritis is less than 0.5%.
is encrusted. It spreads by continuity and is highly com- Glomerulonephritis may be initiated by antigen—
municable, especially in hot, humid climates. More wide- antibody complexes on the glomerular basement mem-
spread infection occurs in eczematous or wounded skin or brane. The most important antigens are thought to be
in burns and may progress to cellulitis. Group A strepto- SpeB and a nephritis-associated plasmin receptor. In
coccal skin infections are often attributable to M types 49, acute nephritis, the patient has blood and protein in the
57, and 59–61 and may precede glomerulonephritis (GN) urine, edema, high blood pressure, and urea nitrogen
but do not lead to rheumatic fever. retention; serum complement levels are also low. A few
A clinically identical infection can be caused by patients die, some develop chronic glomerulonephritis
Staphylococcus aureus and sometimes both S. pyogenes with ultimate kidney failure, and the majority recovers
and S. aureus are present. completely.
2. Rheumatic fever—This is the most serious sequela of
C. Invasive Group A Streptococcal Infections, S. pyogenes because it results in damage to heart muscle
Streptococcal Toxic Shock Syndrome, and and valves. Certain strains of group A streptococci con-
Scarlet Fever tain cell membrane antigens that cross-react with human
heart tissue antigens. Sera from patients with rheumatic
Fulminant, invasive S. pyogenes infections with streptococcal
fever contain antibodies to these antigens.
toxic shock syndrome are characterized by shock, bactere-
mia, respiratory failure, and multiorgan failure. Death occurs
The onset of acute rheumatic fever (ARF) is often pre-
in about 30% of patients. The infections tend to occur after
ceded by S. pyogenes pharyngitis 1–5 weeks (mean 19 days)
minor trauma in otherwise healthy persons with several pre-
earlier, although the infection may be mild and may not be
sentations of soft tissue infection. These include necrotizing
detected. In general, however, patients with more severe
fasciitis, myositis, and infections at other soft tissue sites;
streptococcal sore throats have a greater chance of develop-
bacteremia occurs frequently. In some patients, particularly
ing rheumatic fever. Rheumatic fever is not associated with
those infected with group A streptococci of M types 1 or 3,
cutaneous streptococcal infections. In the 1950s, untreated
the disease presents with focal soft tissue infection accom-
streptococcal infections were followed by rheumatic fever in
panied by fever and rapidly progressive shock with multi-
up to 3% of military personnel and 0.3% of civilian children.
organ failure. Erythema and desquamation may occur. The
In the 1980s through 2000 a resurgence of ARF occurred
S. pyogenes of the M types 1 and 3 (and types 12 and 28)
in the United States. M types 1, 3, 5, 6, and 18 were most
that make pyrogenic exotoxin A or B are associated with the
frequently involved. Since that time, the incidence has once
severe infections.
again declined. Rheumatic fever occurs up to 100 times
Pyrogenic exotoxins A–C also cause scarlet fever in
more frequently in tropical countries and is the most impor-
association with S. pyogenes pharyngitis or with skin or soft
tant cause of heart disease in young people in developing
tissue infection. The pharyngitis may be severe. The rash
countries.
appears on the trunk after 24 hours of illness and spreads to
Typical symptoms and signs of rheumatic fever include
involve the extremities. Streptococcal toxic shock syndrome
fever, malaise, a migratory nonsuppurative polyarthri-
and scarlet fever are clinically overlapping diseases.
tis, and evidence of inflammation of all parts of the heart
(endocardium, myocardium, and pericardium). The cardi-
D. Poststreptococcal Diseases (Rheumatic Fever, tis characteristically leads to thickened and deformed valves
Glomerulonephritis) and to small perivascular granulomas in the myocardium
After an acute S. pyogenes infection, there is a latent period (Aschoff bodies) that are finally replaced by scar tissue.
of 1–4 weeks (mean 7 days), after which nephritis or rheu- Patients may develop severe and progressive congestive
matic fever occasionally develops. The latent period suggests heart failure. Sydenham’s chorea is another manifestation
that these poststreptococcal diseases are not attributable to of ARF and is characterized by involuntary, uncoordi-
the direct effect of disseminated bacteria but instead repre- nated movements and associated muscle weakness. It has
sent a hypersensitivity response. Nephritis is more commonly been hypothesized that other types of neurobehavioral

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 CHAPTER 14 The Streptococci, Enterococci, and Related Genera    221

conditions may also follow streptococcal infections. These D. Antigen Detection Tests
are referred to as PANDAS—post-streptococcal autoim- Several commercial kits are available for rapid detection of
mune, neuropsychiatric disorders associated with strepto- group A streptococcal antigen from throat swabs. These
cocci. More research is required to definitely establish a link kits use enzymatic or chemical methods to extract the anti-
to S. pyogenes infections. gen from the swab, then use enzyme immunoassay (EIA) or
Erythrocyte sedimentation rates, serum transaminase agglutination tests to demonstrate the presence of the antigen.
levels, electrocardiograms, and other tests are used to esti- The tests can be completed in minutes to hours after the speci-
mate rheumatic activity. men is obtained. They are 60–90% sensitive, depending on the
Whereas rheumatic fever has a marked tendency to be prevalence of the disease in the population, and 98–99% spe-
reactivated by recurrent streptococcal infections, nephritis cific compared with culture methods. More sensitive assays
does not. The first attack of rheumatic fever usually produces that use DNA probes or nucleic acid amplification techniques
only slight cardiac damage, which, however, increases with are now available and are beginning to replace the earlier anti-
each subsequent attack. It is therefore important to protect gen detection tests, although they remain more costly.
such patients from recurrent S. pyogenes infections by pro-
phylactic penicillin administration. E. Serologic Tests
A rise in the titer of antibodies to many group A streptococ-
Diagnostic Laboratory Tests cal antigens can be estimated. Such antibodies include ASO,
particularly in respiratory disease; anti-DNase B and anti-
A. Specimens
hyaluronidase, particularly in skin infections; antistreptoki-
Specimens to be obtained depend on the nature of the strep- nase; anti-M type-specific antibodies; and others. Of these,
tococcal infection. A throat swab, pus, cerebrospinal fluid the anti-ASO titer is most widely used.
or other sterile body fluid, or blood is obtained for culture.
Serum is obtained for antibody determinations.
Immunity
B. Smears Resistance against streptococcal diseases is M type specific.
Smears from pus often show single cocci or pairs rather than Thus, a host who has recovered from infection by one group
definite chains. Cocci are sometimes Gram-negative because A streptococcal M type is relatively immune to reinfection by
the organisms are no longer viable and have lost their ability the same type but fully susceptible to infection by another M
to retain the blue dye (crystal violet) and be Gram-positive. type. Anti-M type-specific antibodies can be demonstrated
If smears of pus show streptococci but cultures fail to grow, in a test that exploits the fact that streptococci are rapidly
anaerobic organisms must be suspected. Smears of throat killed after phagocytosis. M protein interferes with phago-
swabs are rarely contributory because viridans streptococci cytosis, but in the presence of type-specific antibody to M
are always present and have the same appearance as group A protein, streptococci are killed by human leukocytes.
streptococci on stained smears. Antibody to streptolysin O develops after infection;
it blocks hemolysis by streptolysin O but does not indicate
immunity. High titers (>250 units) indicate recent or repeated
C. Culture
infections and are found more often in rheumatic individuals
Specimens suspected of containing streptococci are cultured than in those with uncomplicated streptococcal infections.
on blood agar plates. If anaerobes are suspected, suitable
anaerobic media must also be inoculated. Incubation in 10%
CO2 often speeds hemolysis. Slicing the inoculum into the Treatment
blood agar has a similar effect because oxygen does not readily All S. pyogenes are uniformly susceptible to penicillin G. Mac-
diffuse through the medium to the deeply embedded organ- rolides, such as erythromycin and clindamycin, have often been
isms, and it is oxygen that inactivates streptolysin O. recommended for penicillin-allergic patients and for patients
Blood cultures will grow hemolytic group A streptococci with necrotizing fasciitis. However, resistance to macrolide
(eg, in sepsis) within hours or a few days. Certain α-hemolytic antibiotics has been increasing in Europe and in the United
streptococci and enterococci may grow slowly, so blood cul- States. Some are resistant to tetracyclines. Antimicrobial drugs
tures in cases of suspected endocarditis may not turn positive have no effect on established glomerulonephritis and rheu-
for a few days. matic fever. In acute streptococcal infections, however, every
The degree and kind of hemolysis (and colonial appear- effort must be made to rapidly eradicate streptococci from the
ance) may help place an organism in a definite group. S. pyogenes patient, eliminate the antigenic stimulus (before day 8), and
can be identified by rapid tests specific for the presence of the thus prevent poststreptococcal disease. Doses of penicillin or
group A-specific antigen and by the PYR test. Streptococci erythromycin that result in effective tissue levels for 10 days
belonging to group A may be presumptively identified by inhi- usually accomplish this. Antimicrobial drugs are also very use-
bition of growth by bacitracin, but this should be used only ful in preventing reinfection with β-hemolytic group A strep-
when more definitive tests are not available. tococci in patients with rheumatic fever.

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 222   SECTION III  Bacteriology

Epidemiology, Prevention, and Control Concept Checks

Although humans can be asymptomatic nasopharyngeal or • Streptococci are a large group of Gram-positive organisms
perineal carriers of S. pyogenes, the organism should be con- that are catalase negative and tend to grow in pairs and
sidered significant if it is detected by culture or other means. long chains.
The ultimate source of group A streptococci is a person har- • No one system accurately classifies all streptococci, and
boring these organisms. The individual may have a clinical or the taxonomy continues to evolve. Major classifications
subclinical infection or may be a carrier distributing strepto- include the type of hemolysis (α, β, or no hemolysis) condi-
cocci directly to other persons via droplets from the respira- tions for growth, and capacity to cause disease.
tory tract or skin. The nasal discharges of a person harboring • Streptococci will grow well on 5% sheep blood agar and
S. pyogenes are the most dangerous source for spread of these other media that support the growth of Gram-positive
organisms. cocci.
Many other streptococci (eg, viridans streptococci and • S. pyogenes (group A β-hemolytic streptococcus) is the
enterococci) are members of the normal microbiota of the most virulent pathogen in the Streptococcus family. It elabo-
human body. They produce disease only when established rates numerous proteins, hemolysins, enzymes, and toxins
in parts of the body where they do not normally occur (eg, responsible for the broad range of suppurative (eg, cellulitis)
heart valves). To prevent such accidents, particularly in the and immunologic diseases (poststreptococcal GN, RF)
course of surgical procedures on the respiratory, gastrointes- associated with this organism.
tinal, and urinary tracts that result in temporary bacteremia,
antimicrobial agents are often administered prophylactically
to persons with known heart valve deformity and to those STREPTOCOCCUS AGALACTIAE
with prosthetic valves or joints. Guidelines published by the
American Heart Association and other professional societies These are the group B streptococci. They typically are
have clarified some of these recommendations (see Wilson β-hemolytic and produce zones of hemolysis that are only
et al, 2007). slightly larger than the colonies (1–2 mm in diameter). The
Control procedures are directed mainly at the human source: group B streptococci hydrolyze sodium hippurate and give
a positive response in the so-called CAMP (Christie, Atkins,
1. Detection and early antimicrobial therapy of respiratory Munch-Peterson) test.
and skin infections with group A streptococci. Prompt Group B streptococci are part of the normal vaginal flora
eradication of streptococci from early infections can and lower gastrointestinal tract in 5–30% of women. Group
effectively prevent the development of poststreptococcal B streptococcal infection during the first month of life may
disease. This requires maintenance of adequate penicillin present as fulminant sepsis, meningitis, or respiratory dis-
levels in tissues for 10 days (eg, benzathine penicillin G tress syndrome. Substantial reductions in the incidence of
given once intramuscularly). Erythromycin is an alterna- early-onset neonatal group B streptococcal infections have
tive drug, although many S. pyogenes are now resistant. been observed after the 1996 recommendations for screening
2. Antistreptococcal chemoprophylaxis in persons who have pregnant women at 35–37 weeks of pregnancy. This is done
suffered an attack of rheumatic fever. This involves giving by using either broth-enriched culture or molecular methods
one injection of benzathine penicillin G intramuscularly on rectal and vaginal swabs obtained at the time of screening.
every 3–4 weeks or daily oral penicillin or oral sulfon- Intravenous ampicillin given to mothers who are colonized
amide. The first attack of rheumatic fever infrequently with group B streptococci and are in labor prevents coloni-
causes major heart damage; however, such persons are par- zation of their infants and subsequent group B streptococ-
ticularly susceptible to reinfections with streptococci that cal disease. Group B streptococcal infections are increasing
precipitate relapses of rheumatic activity and give rise to among nonpregnant adults. Two expanding populations,
cardiac damage. Chemoprophylaxis in such individuals, namely elderly adults and immunocompromised hosts, are
especially children, must be continued for years. Chemo- most at risk for invasive disease. Predisposing factors include
prophylaxis is not used in glomerulonephritis because of diabetes mellitus, cancer, advanced age, liver cirrhosis, cor-
the small number of nephritogenic types of streptococci. ticosteroid therapy, HIV, and other immunocompromised
An exception may be family groups with a high rate of states. Bacteremia, skin and soft tissue infections, respiratory
poststreptococcal nephritis. infections, and genitourinary infections in descending order
3. Eradication of S. pyogenes from carriers. This is especially of frequency are the major clinical manifestations.
important when carriers are in areas such as obstetric
delivery rooms, operating rooms, classrooms, or nurseries.
Unfortunately, it is often difficult to eradicate β-hemolytic GROUPS C AND G
streptococci from permanent carriers, and individuals may These streptococci occur sometimes in the nasopharynx and
occasionally have to be shifted away from “sensitive” areas may cause pharyngitis, sinusitis, bacteremia, or endocardi-
for some time. tis. They often look like group A S. pyogenes on blood agar

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 CHAPTER 14 The Streptococci, Enterococci, and Related Genera    223

medium and are β-hemolytic. They are identified by reac- GROUPS E, F, G, H, AND
tions with specific antisera for groups C or G. Groups C and
G streptococci have hemolysins and may have M proteins
K–U STREPTOCOCCI
analogous to those of group A S. pyogenes. Poststreptococ- These streptococci occur primarily in animals. One of the
cal sequelae of acute glomerulonephritis (AGN) and RF have multiple species of group G streptococci, Streptococcus canis,
been rarely reported. can cause skin infections of dogs but uncommonly infects
humans; other species of group G streptococci infect humans.

GROUP D STREPTOCOCCI
Concept Checks
The group D streptococci have undergone recent taxonomic
changes. There are eight species in this group, many of which • Streptococci that have Lancefield antigens other than group
do not cause infections in humans. The S. bovis group is of A are a diverse group of organisms that include other pyo-
most importance to human disease and is further classified genic streptococci (groups B, C, and G), streptococci that
into biotypes (old classification), which are important epi- occur primarily in animals (E, H, and K–U), the S. bovis
demiologically, and more recently into four DNA clusters. group (group D), and small colony variant members of the
Animal species in the bovis group have been assigned to the S. anginosus group (primarily group F).
species Streptococcus equinus (DNA cluster I). Biotype I (in • S. agalactiae (group B streptococci) are important patho-
DNA cluster II) isolates ferment mannitol and are now desig- gens among pregnant women and their neonates. Rectal
nated as S. gallolyticus subspecies gallolyticus. This organism and vaginal screening at 35–37 weeks of pregnancy and
causes human endocarditis and is frequently epidemiologi- treatment of colonized moms during labor with penicillin
cally associated with colon carcinoma. DNA cluster II also has significantly reduced the incidence of early-onset neo-
includes S. gallolyticus subspecies pasteurianus (formerly natal group B streptococcal infections.
S. bovis biotype II.2) and S. gallolyticus subspecies macedonius. • Groups C and G streptococci cause infections similar to
S. bovis biotype II.1 is now in DNA cluster III and has the those of group A streptococci, including rare reports of
species name Streptococcus infantarius, which includes two poststreptococcal sequelae such as AGN and RF.
subspecies (subsp. infantarius and subsp. coli). Biotype II • The S. bovis group (group D non-enterococci) has under-
bacteremias are often associated with biliary sources and less gone significant taxonomic reclassification. These organ-
frequently with endocarditis. Finally, DNA cluster IV has isms are PYR negative and bile esculin positive but do not
one species, Streptococcus alactolyticus. Because of the con- grow in 6.5% NaCl. They are associated with bacteremia
fusing taxonomy and the failure of most automated or kit and endocarditis in patients with significant biliary tract
systems to discriminate to the subspecies level, most diag- disease or colon pathology, including carcinoma.
nostic microbiology laboratories will likely continue to refer • Members of the S. anginosus group (include S. intermedius
to these organisms as either the S. bovis group or group D and S. constellatus) may be β-hemolytic, can possess Lance-
non-enterococci. All group D streptococci are nonhemolytic field antigens A, C, F, and G; tend to be small colony vari-
and PYR negative. They grow in the presence of bile and ants (<0.5 mm); and are associated with brain, lung, and
hydrolyze esculin (bile esculin positive) but do not grow in liver abscesses.
6.5% NaCl. They are part of the normal enteric microbiota of
humans and animals.

VIRIDANS STREPTOCOCCI
STREPTOCOCCUS ANGINOSUS GROUP
The many species of the viridans streptococci are classified
Other species names in the S. anginosus group are S. constellatus into groups and include the S. mitis group, S. anginosus group
and S. intermedius. These streptococci are part of the normal (see above), S. mutans group, Streptococcus salivarius group,
microbiota of the throat, colon, and urogenital tract. They and S. bovis group (see above). Typically they are α-hemolytic,
may be β-, α-, or nonhemolytic. S. anginosus group includes but they may also be nonhemolytic. As discussed earlier,
β-hemolytic streptococci that form minute colonies (<0.5 mm members of the S. anginosus group can be β-hemolytic.
in diameter) and react with groups A, C, or G antisera and Their growth is not inhibited by optochin, and colonies are
all β-hemolytic group F streptococci. Those that are group A not soluble in bile (deoxycholate). The viridans streptococci
are PYR negative. S. anginosus are Voges-Proskauer test posi- are the most prevalent members of the normal microbiota of
tive. They may be classified as viridans streptococci. These the upper respiratory tract and are important for the healthy
organisms are frequently associated with serious infections state of the mucous membranes there. They may reach the
such as brain, lung, and liver abscesses. They can be easily bloodstream as a result of trauma and are a principal cause of
detected in the laboratory by their characteristic butter- endocarditis on abnormal heart valves. Some viridans strep-
scotch or caramel odor. tococci (eg, S. mutans) synthesize large polysaccharides, such

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 224   SECTION III  Bacteriology

as dextrans or levans, from sucrose and contribute impor- be nonhemolytic. MALDI-TOF MS has been shown to reli-
tantly to the genesis of dental caries. ably differentiate them from streptococci and other catalase
In the course of bacteremia, viridans streptococci or negative Gram-positive cocci. NVS are part of the normal
enterococci and rarely pneumococci, may settle on nor- microbiota and occasionally cause bacteremia or endocardi-
mal or previously deformed heart valves, producing acute tis and can be found in brain abscesses and other infections.
endocarditis. Rapid destruction of the valves frequently Clinically, they are very similar to the viridans streptococci.
leads to fatal cardiac failure in days or weeks unless sur-
gery can be performed to place a prosthetic valve during
antimicrobial treatment or following therapy. More fre- PEPTOSTREPTOCOCCUS
quently, the viridans streptococci are associated with a AND RELATED GENERA
subacute course.
Subacute endocarditis often involves abnormal valves These streptococci grow only under anaerobic or microaero-
(congenital deformities and rheumatic or atherosclerotic philic conditions and variably produce hemolysins. They are
lesions). Although any organism reaching the bloodstream part of the normal microbiota of the mouth, upper respiratory
may establish itself on thrombotic lesions that develop on tract, bowel, and female genital tract. They often participate
endothelium injured as a result of circulatory stresses, sub- with many other bacterial species in mixed anaerobic infec-
acute endocarditis is most frequently caused by members tions (see Chapter 21). Such infections may occur in wounds,
of the normal microbiota of the respiratory or intestinal in the breast, in postpartum endometritis, after rupture of an
tract that have accidentally reached the blood. After dental abdominal viscus, in the brain, or in chronic suppuration of
extraction, at least 30% of patients have viridans strepto- the lung. The pus usually has a foul odor.
coccal bacteremia. These streptococci, ordinarily the most
prevalent members of the upper respiratory microbiota, are
also the most frequent cause of subacute bacterial endocar- STREPTOCOCCUS PNEUMONIAE
ditis. The group D streptococci (enterococci and S. bovis)
also are common causes of subacute endocarditis. About S. pneumoniae (pneumococci) is a member of the S. mitis
5–10% of cases are caused by enterococci originating in group (see Table 14-1) and are indistinguishable from them
the gut or urinary tract. The lesion is slowly progressive, on the basis of 16SrRNA. Pneumococci are Gram-positive
and a certain amount of healing accompanies the active diplococci, often lancet shaped or arranged in chains, pos-
inflammation; vegetations consist of fibrin, platelets, blood sessing a capsule of polysaccharide that permits typing
cells, and bacteria adherent to the valve leaflets. The clini- with specific antisera. Pneumococci are readily lysed by
cal course is gradual, but the disease is invariably fatal in surface-active agents, which probably remove or inactivate
untreated cases. The typical clinical picture includes fever, the inhibitors of cell wall autolysins. Pneumococci are nor-
anemia, weakness, a heart murmur, embolic phenomena, an mal inhabitants of the upper respiratory tract of 5–40% of
enlarged spleen, and renal lesions. humans and can cause pneumonia, sinusitis, otitis, bronchi-
α-Hemolytic streptococci and enterococci vary in their tis, bacteremia, meningitis, peritonitis, and other infectious
susceptibility to antimicrobial agents. Particularly in bacte- processes.
rial endocarditis, antibiotic susceptibility tests are useful to
determine which drugs may be used for optimal therapy.
Aminoglycosides often enhance the rate of bactericidal
Morphology and Identification
action of penicillin on streptococci, particularly enterococci. A. Typical Organisms
The typical Gram-positive, lancet-shaped diplococci
(Figure 14-3) are often seen in specimens of young cultures.
NUTRITIONALLY VARIANT In sputum or pus, single cocci or chains are also seen. With
STREPTOCOCCI age, the organisms rapidly become Gram-negative and tend
to lyse spontaneously. Autolysis of pneumococci is greatly
The nutritionally variant streptococci (NVS) are now clas- enhanced by surface-active agents. Lysis of pneumococci
sified in the genus Abiotrophia (Abiotrophia defectiva is occurs in a few minutes when ox bile (10%) or sodium deoxy-
the sole species) and the genus Granulicatella (two species cholate (2%) is added to a broth culture or suspension of
Granulicatella adiacens and Granulicatella elegans). They organisms at neutral pH. Viridans streptococci do not lyse
have also been known as “nutritionally deficient strepto- and are thus easily differentiated from pneumococci. On
cocci” and “pyridoxal-dependent streptococci.” They require solid media, the growth of pneumococci is inhibited around
pyridoxal or cysteine for growth on blood agar and may grow a disk of optochin; viridans streptococci are not inhibited by
as satellite colonies around colonies of staphylococci and optochin (Figure 14-4).
other bacteria that produce pyridoxal. Routinely supplement- Other identifying points include almost uniform viru-
ing blood agar medium with pyridoxal allows recovery of lence for mice when injected intraperitoneally and the “cap-
these organisms. They are usually α-hemolytic but may also sule swelling test,” or quellung reaction (see below).

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 CHAPTER 14 The Streptococci, Enterococci, and Related Genera    225

that is found in the cell wall of all S. pneumoniae can be

detected in the urine and cerebrospinal fluid (CSF) as useful
diagnostic tests for pneumococcal infections.

B. Quellung Reaction
When pneumococci of a certain type are mixed with spe-
cific antipolysaccharide serum of the same type—or with
polyvalent antiserum—on a microscope slide, the capsule
swells markedly, and the organisms agglutinate by cross-
linking of the antibodies (see Figure 14-4C). This reac-
tion is useful for rapid identification and for typing of the
organisms, either in sputum or in cultures. The polyva-
lent antiserum, which contains antibody to all of the types
(“omniserum”), is a good reagent for rapid microscopic
determination of whether or not pneumococci are present
in fresh sputum. This test is rarely used because of the high
reagent costs and the expertise required in assay perfor-
mance and interpretation.
FIGURE 14-3 S. pneumoniae in sputum are seen as lancet-
shaped Gram-positive diplococci. Degenerating nuclei of Pathogenesis
polymorphonuclear cells are the large darker irregular red shapes
A. Types of Pneumococci
(arrow). Mucus and amorphous debris are present in the background.
Original magnification ×1000. In adults, types 1–8 are responsible for about 75% of cases
of pneumococcal pneumonia and for more than half of all
fatalities in pneumococcal bacteremia; in children, types 6,
B. Culture
14, 19, and 23 are frequent causes.
Pneumococci form small round colonies, at first dome-
shaped and later developing a central depression with an
B. Production of Disease
elevated rim. Other colonies may appear glistening because
of capsular polysaccharide production. Pneumococci are Pneumococci produce disease through their ability to multi-
α-hemolytic on blood agar. Growth is enhanced by 5–10% ply in the tissues. The virulence of the organism is a function
CO2. of its capsule, which prevents or delays ingestion by phago-
cytes. A serum that contains antibodies against the type-
specific polysaccharide protects against infection. If such a
C. Growth Characteristics
serum is absorbed with the type-specific polysaccharide, it
Most energy is obtained from fermentation of glucose; this loses its protective power. Animals or humans immunized
is accompanied by the rapid production of lactic acid, which with a given type of pneumococcal polysaccharide are sub-
limits growth. Neutralization of broth cultures with alkali at sequently immune to that type of pneumococcus and pos-
intervals results in massive growth. sess precipitating and opsonizing antibodies for that type of
polysaccharide.
D. Variation
Pneumococcal isolates that produce large amounts of cap- C. Loss of Natural Resistance
sules appear as large mucoid colonies. Capsule production is Because 40–70% of humans are at some time carriers of viru-
not essential for growth on agar medium, and capsular pro- lent pneumococci, the normal respiratory mucosa must pos-
duction is therefore lost after a small number of subcultures. sess great natural resistance to the pneumococcus. Among
The pneumococci will, however, again produce capsules and the factors that probably lower this resistance and thus pre-
have enhanced virulence if injected into mice. dispose to pneumococcal infection are the following:

1. Viral and other respiratory tract infections that damage sur-

Antigenic Structure
face cells; abnormal accumulations of mucus (eg, allergy),
A. Component Structures which protect pneumococci from phagocytosis; bronchial
The pneumococcal cell wall has peptidoglycan and teichoic obstruction (eg, atelectasis); and respiratory tract injury
acid, similar to other streptococci. The capsular polysaccha- caused by irritants disturbing its mucociliary function.
ride is covalently bound to the peptidoglycan and to the cell 2. Alcohol or drug intoxication, which depresses phagocytic
wall polysaccharide. The capsular polysaccharide is immu- activity, depresses the cough reflex, and facilitates aspira-
nologically distinct for each of the 91 types. C-polysaccharide tion of foreign material.

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 226   SECTION III  Bacteriology

A B

C
FIGURE 14-4 A: Optochin inhibition and bile solubility of S. pneumoniae. The S. pneumoniae were grown overnight on 5% sheep blood
agar. The optochin (ethyl hydrocupreine HCl) or P disk was placed when the plate was inoculated. The pneumococci are α-hemolytic with
greening of the agar around the colonies. The zone of inhibition around the P disk is larger than 14 mm, indicating that the organisms are
pneumococci rather than viridans streptococci. A drop of desoxycholate (“bile”) solution was placed on the overnight growth just to the right
of the P disk area (arrow); after about 20 minutes at room temperature, the colonies of pneumococci were solubilized (bile soluble). B: The
growth of viridans streptococci appears similar to the growth of pneumococci, but growth of the viridans streptococci is not inhibited by
optochin. C: S. pneumoniae quellung reaction: a small amount of growth is mixed with saline, antisera against the capsule polysaccharide, and
methylene blue stain. After incubation at room temperature for 1 hour, the reaction is observed under the microscope. The organisms are
outlined in light blue. A positive reaction shows clumping because of cross-linking of the antibodies and pneumococci. The halo effect around
the pneumococci is apparent capsular swelling. A negative control would show no clumping or capsular swelling. (Courtesy of H. Reyes.)

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 CHAPTER 14 The Streptococci, Enterococci, and Related Genera    227

3. Abnormal circulatory dynamics (eg, pulmonary conges- B. Capsule Swelling Tests

tion and heart failure). Fresh emulsified sputum mixed with antiserum causes cap-
4. Other mechanisms, such as malnutrition, general debility, sule swelling (the quellung reaction) for identification of
sickle cell anemia, hyposplenism, nephrosis, or comple- pneumococci.
ment deficiency.
C. Culture
Pathology The culture is created by inoculating sputum to blood agar
Pneumococcal infection causes an outpouring of fibrinous and incubating the plate in CO2 at 37°C. A blood culture is
edema fluid into the alveoli followed by red blood cells and leuko- also usually obtained.
cytes, which results in consolidation of portions of the lung. Many
pneumococci are found throughout this exudate, and they may D. Nucleic Acid Amplification Tests
reach the bloodstream via the lymphatic drainage of the lungs. Several manufacturers have included S. pneumoniae on pan-
The alveolar walls remain normally intact during the infection. els for identification of positive blood culture bottles and sev-
Later, mononuclear cells actively phagocytose the debris, and this eral of these assays are FDA cleared. Also, in development
liquid phase is gradually reabsorbed. The pneumococci are taken are panel tests for meningitis and separate molecular panels
up by phagocytes and digested intracellularly. for direct detection of S. pneumoniae in respiratory samples
obtained from specimens in patients suspected of having
community acquired or health care-associated pneumonia.
Clinical Findings
The onset of pneumococcal pneumonia is usually sudden, with E. Immunity
fever, chills, and sharp pleural pain. The sputum is similar to
Immunity to infection with pneumococci is type specific
the alveolar exudate, being characteristically bloody or rusty
and depends both on antibodies to capsular polysaccharide
colored. Early in the disease, when the fever is high, bacteremia
and on intact phagocytic function. Vaccines can induce pro-
is present in 10–20% of cases. With antimicrobial therapy, the
duction of antibodies to capsular polysaccharides (see later
illness is usually terminated promptly; if drugs are given early,
discussion).
the development of consolidation is interrupted.
Pneumococcal pneumonia must be differentiated from
pulmonary infarction, atelectasis, neoplasm, congestive Treatment
heart failure, and pneumonia caused by many other bacteria. Over the last several decades, pneumococci have become
Empyema (pus in the pleural space) is a significant complica- increasingly more resistant to a broad range of antimicrobial
tion and requires aspiration and drainage. agents. Penicillin G can no longer be considered the empiric
From the respiratory tract, pneumococci may reach agent of choice. Around 15% of pneumococci from nonmen-
other sites. The sinuses and middle ear are most frequently ingeal sources are penicillin resistant (minimum inhibi-
involved. Infection sometimes extends from the mastoid to tory concentration [MIC] ≥ 8 µg/mL). High-dose penicillin
the meninges. Bacteremia from pneumonia has a triad of G appears to be effective in treating pneumonia caused by
severe complications: meningitis, endocarditis, and septic pneumococci with MICs to penicillin below 8 µg/mL (resis-
arthritis. With the early use of chemotherapy, acute pneumo- tant breakpoint) but would not be effective in treatment of
coccal endocarditis and arthritis have become rare. meningitis caused by the same strains. Some penicillin-resis-
tant strains are resistant to cefotaxime. Resistance to tetra-
Diagnostic Laboratory Tests cycline, erythromycin, and fluoroquinolones also occurs.
Pneumococci remain susceptible to vancomycin. Because
Blood is drawn for culture; CSF and sputum are collected for
resistance profiles are not predictable, routine susceptibility
demonstration of pneumococci by smear and culture. CSF
testing using a method that can determine MIC values for
and urine can be used to detect pneumococcal C-polysaccha-
isolates from sterile sites should be performed for all pneu-
ride by rapid immunochromatographic membrane assays.
mococcal infections.
Serum antibody tests are impractical. All specimens should
be sent to the microbiology laboratory as soon as possible
after collection because pneumococci tend to autolyse and Epidemiology, Prevention, and Control
delay will significantly impact recovery by culture. Sputum Pneumococcal pneumonia accounts for about 60% of all bac-
may be examined in several ways. terial pneumonias. In the development of illness, predispos-
ing factors (see earlier discussion) are more important than
A. Stained Smears exposure to the infectious agent, and a healthy carrier is more
A Gram-stained film of rusty-red sputum shows typical important in disseminating pneumococci than a sick patient.
organisms, many polymorphonuclear neutrophils, and many It is possible to immunize individuals with type-specific
red blood cells. polysaccharides. Such vaccines can probably provide 90%

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228   SECTION III  Bacteriology

protection against bacteremic pneumonia. A polysaccha- and bile soluble. Furthermore, enterococci are PYR positive,
ride vaccine containing 23 types (PPSV23) is licensed in the grow in the presence of bile, hydrolyze esculin (bile-esculin
United States. A pneumococcal conjugate vaccine contains positive), and in contrast to non-enterococcal group D strep-
capsular polysaccharides conjugated to diphtheria CRM197 tococci, enterococci grow well in 6.5% NaCl. Enterococci
protein. The current conjugate vaccine is a 13-valent one grow well at a wide temperature range between 10°C and
(PCV13, Prevnar 13, Wyeth Pharmaceuticals). PCV13 con- 45°C, streptococci generally grow at a much narrower tem-
tains the polysaccharide conjugates of the serotypes found in perature range. In the laboratory, enterococci can be read-
the PCV7 vaccine (4, 6B, 9V, 14, 18C, 19F, 23 F) plus serotypes ily identified using commercially available semiautomated or
1, 3, 5, 6A, 7F, and 19A. It is recommended for all children as a automated bacterial identification systems; organism identi-
four-dose series at 2, 4, 6, and 12–15 months of age. Children fication based on biochemical properties can be cumbersome
younger than 24 months of age who began their vaccination and time consuming. Alternatively, enterococci can be iden-
with PCV-7 and who have received one or more doses can tified by MALDI-TOF mass spectrometry or by molecular
complete the series with PCV-13. Older children and those test methods (eg, PCR).
with underlying medical conditions who were fully vacci-
nated with PCV-7 should receive a single dose of PCV-13.
Adults 19 years of age or older with immunocompromis- Pathogenesis and Pathology
ing conditions should receive both PPSV23 and PCV13. The To date, the pathogenesis of enterococcal infections is poorly
schedule for vaccine administration depends upon the tim- understood; however, several potential virulence factors have
ing and type of prior vaccination. The reader is referred to the been identified. Most enterococcal infections appear to arise
latest recommendations published by the Centers for Disease from the endogenous flora via translocation from their major
Control and Prevention for current guidelines and schedules colonization site (GI tract). In general, virulence is mediated
(http://www.cdc.gov/vaccines/schedules/downloads/adult/ by two major properties, including (intrinsic) antimicrobial
adult-combined-schedule.pdf). In 2014, in addition to the exist- resistance of enterococci as well as their ability to adhere to
ing recommendation to receive PPSV23, persons more than cells and tissues and form biofilms. Several potential viru-
65 years of age should now also receive one dose of PCV13. See lence factors have been identified and may play a role in the
above-mentioned guidelines for complete information. pathogenesis of enterococcal infections. These virulence fac-
tors include surface adhesion proteins, membrane glycolip-
ids, secreted toxins (eg, cytolysin and hemolysin), secreted
ENTEROCOCCI proteases (eg, gelatinase), and extracellular superoxide. How-
ever, none of these virulence factors has yet been established
Enterococci are Gram-positive, catalase-negative, faculta- as a major contributor and/or cause for enterococcal infec-
tively anaerobic bacteria that are usually oval-shaped and are tions in humans.
arranged in pairs or short chains; occasionally, single organ-
isms can be seen as well. The enterococci possess the group D
group-specific substance and were therefore previously clas- Clinical Findings
sified as group D streptococci. Because the group D cell wall- Enterococci are commensal bacteria and part of the normal
specific antigen is a teichoic acid, it is not an antigenically enteric microbiota. E. faecalis and E. faecium are the most
good marker; enterococci are usually identified by character- commonly isolated enterococcal species causing infections
istics other than immunologic reactions with group-specific in humans. Other, less frequently encountered enterococci
antisera. There are at least 47 species of enterococci, but less include Enterococcus gallinarum, Enterococcus casseliflavus,
than one-third of these are associated with disease in humans, and E. raffinosus. Historically, E. faecalis has been recognized
with Enterococcus faecalis and Enterococcus faecium being as the most commonly isolated species causing 85–90% of
the two species most commonly isolated from clinical speci- enterococcal infections; E. faecium causes 5–10%. However,
mens. Enterococci are part of the normal enteric microbiota. in recent years these percentages have been changing, recog-
nizing a rise in infections due to E. faecium, particularly as
a cause of blood stream infections. In hospitalized patients,
Morphology and Identification the most common sites of infection are the urinary tract,
Enterococcus species grow readily on nonselective media, such burn and surgical wounds, biliary tract, and blood. Urinary
as sheep-blood agar and chocolate agar. Enterococci are usu- tract infections (UTIs) are by far the most common form of
ally nonhemolytic, but are occasionally α-hemolytic, or rarely enterococcal infections, and are frequently associated with
β-hemolytic. While enterococci can sometimes resemble indwelling catheters, instrumentation, or structural abnor-
S. pneumoniae on Gram-stains, prepared directly from clinical malities of the genitourinary tract. Intraabdominal and pelvic
specimens, the organisms can be readily differentiated on the infections are also frequently caused by enterococci. How-
basis of various simple biochemical tests. Enterococcus species ever, these infections are often polymicrobial, as are UTIs and
are resistant to optochin and colonies do not dissolve when wound infections. In such cases, it may be difficult to define
exposed to bile, whereas S. pneumoniae is optochin-susceptible the exact pathogenic role of the enterococci in the infection.
 CHAPTER 14 The Streptococci, Enterococci, and Related Genera    229

Bacteremia and endocarditis are also common forms of B. Resistance to Aminoglycosides

enterococcal infections, and are frequently associated with Therapy with combinations of a cell wall-active antibiotic (a
metastatic abscesses and high mortality rates. Infections of penicillin or vancomycin) plus an aminoglycoside (streptomy-
the respiratory tract (eg, pneumonia, otitis, and sinusitis) cin or gentamicin) is essential for severe enterococcal infec-
and/or the central nervous system (eg, meningitis) have been tions, such as endocarditis. Although enterococci have intrinsic
described, but occur rarely. Two forms of enterococcal men- low-level resistance to aminoglycosides (MICs < 500 µg/mL),
ingitis have been described: spontaneous and postoperative they have synergistic susceptibility when treated with a cell
meningitis. Spontaneous meningitis is typically a commu- wall-active antibiotic plus an aminoglycoside. However,
nity-associated infection in patients with severe comorbidities some enterococci have high-level resistance to aminoglyco-
(eg, diabetes, chronic renal failure, and immunosuppression), sides (MICs > 500 µg/mL) and are not susceptible to the syn-
whereas postoperative meningitis is a hospital-acquired infec- ergism. This high-level aminoglycoside resistance is due to
tion (eg, associated with ventricular shunt devices, CNS elec- enterococcal aminoglycoside-modifying enzymes. The genes
trodes). Neonatal infections due to enterococci have also been that code for most of these enzymes are usually on conjuga-
described. Enterococci are part of the normal adult vaginal tive plasmids or transposons. The enzymes have differential
microbiota, and can therefore be acquired by neonates during activity against the aminoglycosides. Resistance to gentami-
vaginal delivery. Neonatal enterococcal infections are typi- cin predicts resistance to the other aminoglycosides except
cally late-onset sepsis, pneumonia, but other infections such streptomycin. (Susceptibility to gentamicin does not predict
as UTIs, surgical site infections, and meningitis have also susceptibility to other aminoglycosides.) Resistance to strep-
been described. tomycin does not predict resistance to other aminoglycosides.
The result is that only streptomycin or gentamicin (or both or
Treatment and Antibiotic Resistance neither) is likely to show synergistic activity with a cell wall-
active antibiotic against enterococci. Enterococci from severe
Treatment of enterococcal infection can be challenging to clini-
infections should have susceptibility tests for high-level ami-
cians due to the fact that enterococci are frequently resistant to
noglycoside resistance (MICs > 500 µg/mL for gentamicin
various antibiotics. Traditionally, therapy for systemic entero-
and >1000 µg/mL for streptomycin in broth media) to predict
coccal infections consists of the combination of a cell-wall
therapeutic efficacy.
active antibiotic (eg, ampicillin or vancomycin) with an amino-
glycoside. However, some cell-wall active antibiotics (eg, oxacil-
lin and cephalosporins) have no activity against enterococci. In C. Vancomycin Resistance
addition, enterococci have developed resistance against some of The glycopeptide vancomycin is the primary alternative drug
the commonly used cell-wall active antibiotics (eg, vancomy- to the beta-lactam/aminoglycoside combination (eg, penicil-
cin). While newer antibiotics have been developed, including lin plus gentamicin or streptomycin) for treating enterococcal
linezolid, quinupristin–dalfopristin, daptomycin, enterococci infections. In the United States, enterococci that are resistant
quickly developed resistance to some of these newer antibiot- to vancomycin have increased in frequency. These entero-
ics as well. E. faecium is usually much more resistant to anti- cocci are not synergistically susceptible to vancomycin plus
biotics when compared to E. faecalis. Antimicrobial resistance an aminoglycoside. Vancomycin resistance has been most
is classified as either intrinsic or acquired; intrinsic resistance common in E. faecium, but vancomycin-resistant strains of
is related to inherent or natural chromosomally encoded resis- E. faecalis also occur.
tance patterns, many of which are present in all or most of the There are multiple vancomycin resistance genotypes
enterococci. and phenotypes. The VanA phenotype is manifested by
inducible high-level resistance to vancomycin and teicoplanin.
A. Intrinsic Resistance VanB phenotypes are inducibly resistant to vancomycin but
Enterococci are intrinsically resistant to cephalosporins, pen- susceptible to teicoplanin. VanC strains have intermediate to
icillinase-resistant penicillins, and monobactams. They have moderate resistance to vancomycin. VanC is constitutive in
intrinsic low-level resistance to many aminoglycosides, are of the less commonly isolated species, E. gallinarum (VanC-1)
intermediate susceptibility or resistant to fluoroquinolones, and E. casseliflavus (VanC-2/VanC-3). The VanD phenotype
and are less susceptible than streptococci (10- to 1000-fold) is manifested by moderate resistance to vancomycin and low-
to penicillin and ampicillin. Enterococci are inhibited by level resistance or susceptibility to teicoplanin. The VanE
β-lactams (eg, ampicillin) but generally are not killed by them. phenotype is classified as low-level resistance to vancomycin
High-level resistance to penicillin and ampicillin is most and susceptibility to teicoplanin. VanG and VanL isolates
often due to altered penicillin-binding proteins; β-lactamase (usually E. faecalis) have low-level resistance to vancomycin
producing strains have been rarely identified. In addition, few and are susceptible to teicoplanin.
enterococci (ie, E. casseliflavus and E. gallinarum) are consid- Teicoplanin is a glycopeptide with many similarities to
ered to be intrinsically resistant to vancomycin. This is a low- vancomycin. It is available for patients in Europe but not in
level, constitutive resistance which is chromosomally encodes the United States. It has importance in investigation of the
by the VanC gene. vancomycin resistance phenotype of enterococci.

Riedel_CH14_p215-p234.indd 229 04/04/19 2:00 PM

 230   SECTION III  Bacteriology

ORF1 ORF2 vanR vanS vanH vanA vanX vanY vanZ

IRL IRR
Histidine
Response Dehydro- Dipepti- DD-Carboxy-
Transposase Resolvase protein Ligase Unknown
regulator genase dase peptidase
kinase

Transposition Regulation Required for glycopeptide Accessory proteins

resistance

FIGURE 14-5 Schematic map of transposon Tn1546 from E. faecium that codes for vancomycin resistance. IRL and IRR indicate the left and
right inverted repeats of the transposon, respectively. (Adapted and reproduced with permission from Arthur M, Courvalin P: Genetics and
mechanisms of glycopeptide resistance in enterococci. Antimicrob Agents Chemother 1993;37:1563.)

Vancomycin and teicoplanin interfere with cell wall Epidemiology, Prevention, and Control
synthesis in Gram-positive bacteria by interacting with the
E. faecalis and E. faecium are the two most common entero-
d-alanyl-d-alanine (d-Ala-d-Ala) group of the pentapep-
coccal species causing infections in humans. In general, and
tide chains of peptidoglycan precursors. The best-studied
based on their intrinsic properties, enterococci are capable of
vancomycin resistance determinant is the VanA operon. It
surviving under harsh environmental conditions, and have
is a system of genes packaged in a self-transferable plas-
adapted to various ecological niches. In humans, they are
mid containing a transposon closely related to Tn1546
predominantly inhabitants of the intestinal microbiota, and
(Figure 14-5). There are two open reading frames that code
are considered an important opportunistic pathogen. Con-
for transposase and resolvase; the remaining seven genes
sidering the high numbers of enterococci present in feces,
code for vancomycin resistance and accessory proteins. The
combined with their ability to survive harsh environmen-
vanR and vanS genes are a two-component regulatory sys-
tal conditions, enterococci may also serve as indicators for
tem sensitive to the presence of vancomycin or teicoplanin
fecal contamination and hygienic quality (eg, for food and
in the environment. vanH, vanA, and vanX are required for
water). The enterococci are among the most frequent causes
vancomycin resistance. vanH and vanA encode for proteins
of health care-associated infections, particularly in intensive
that manufacture the depsipeptide (d-Ala-d-lactate) rather
care units, and are selected for by therapy with cephalo-
than the normal peptide (d-Ala-d-Ala). The depsipeptide,
sporins and other antibiotics to which they are resistant. In
when linked to UDP-muramyl-tripeptide, forms a penta-
addition, enterococci can be transmitted from one patient to
peptide precursor that vancomycin and teicoplanin will
another patient primarily by the hands of hospital personnel,
not bind to. vanX encodes a dipeptidase that depletes the
some of whom may even carry the organisms in their gastro-
environment of the normal d-Ala-d-Ala dipeptide. vanY
intestinal tracts. The organisms can survive on the hands,
and vanZ are not essential for vancomycin resistance. vanY
gloves, and gowns of health care workers for extended peri-
encodes a carboxypeptidase that cleaves the terminal d-Ala
ods of time, representing probably the most common source
from the pentapeptide, depleting the environment of any
of transmission of vancomycin-resistant enterococci in
functional pentapeptide that may have been manufactured
health care settings. Enterococci occasionally are transmit-
by the normal cell wall building process. vanZ’s function
ted on medical devices. The Society for Healthcare Epidemi-
is unclear.
ology of America has published comprehensive guidelines to
Similar to vanA, vanB, and vanD code for d-Ala-d-Lac,
prevent such transmission of enterococci. However, preven-
but vanC and vanE code for d-Ala-d-Ser.
tion and control of enterococcal infections in the health care
Because enterococci that are resistant to vancomycin
setting continues to present major challenges; careful and
frequently carry plasmids that confer resistance to ampicillin
restrictive use of antibiotics and implementation of appro-
and the aminoglycosides, newer agents such as daptomycin,
priate infection-control practices remain to be the corner-
linezolid, quinupristin–dalfopristin, and tigecycline (among
stones to reduce the risk of colonization and/or infection
others) are used for treatment of vancomycin-resistant
with enterococci.
enterococci (VRE) infections (see Chapter 28).

D. Trimethoprim–Sulfamethoxazole Resistance OTHER CATALASE-NEGATIVE

Enterococci often show susceptibility to trimethoprim– GRAM-POSITIVE COCCI
sulfamethoxazole by in vitro testing, but the drugs are not
effective in treating infections. This discrepancy is because There are nonstreptococcal Gram-positive cocci or coc-
enterococci are able to utilize exogenous folates available in cobacilli that are causing disease with increasing frequency
vivo and thus escape inhibition by the drugs. (Table 14-2). These organisms have many growth and

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 CHAPTER 14 The Streptococci, Enterococci, and Related Genera    231

TABLE 14-2 Most Frequently Encountered Non-streptococcal Catalase-Negative Gram-Positive Cocci and
Coccobacilli
Vancomycin
Genusa Catalase Gram-Stain Susceptibility Comments

Abiotrophia b
Negative Cocci in pairs, short Susceptible Normal microbiota of oral cavity; isolated
(nutritionally variant chains from cases of endocarditis
streptococcus)

Aerococcus Negative to Cocci in tetrads and Susceptible Environmental organisms occasionally

weakly clusters isolated from blood, urine, or sterile
positive sites

E. faecalis, E. faecium (and Negative Cocci in pairs, short Some are resistant, Abdominal abscess, urinary tract
other enterococci) chains, or occur as mostly E. faecium infection, endocarditis
single organisms

Gemella Negative Cocci in pairs, tetrads, Susceptible Decolorize easily and may look Gram-
clusters, and short negative; grow slowly (48 hours);
chains part of normal human microbiota;
occasionally isolated from blood and
sterile sites

Granulicatellab Negative Cocci in chains, clusters Susceptible Normal microbiota of oral cavity; isolated
(nutritionally variant from cases of endocarditis
streptococcus)

Leuconostoc Negative Cocci in pairs and chains; Resistant Environmental organisms; look
coccobacilli, rods like enterococci on blood agar;
isolated from a wide variety of
infections

Pediococcus Negative Cocci in pairs, tetrads, Resistant Present in food products and human
and clusters stools; occasionally isolated from
blood and abscesses

Lactobacillus Negative Coccobacilli, rods in pairs Resistant (90%) Aerotolerant anaerobes generally
and chains classified as bacilli; normal vaginal
flora; occasionally found in deep-
seated infections
a
Other genera in which isolates from humans are rare or uncommon include Dolosicoccus, Dolosigranulum, Facklamia, Globicatella, Helcococcus, Ignavigranum, Lactococcus,
Tetragenococcus, Vagococcus, and Weissella.
b
Require pyridoxal for growth.

morphologic characteristics similar to viridans streptococci. They tracts, but they can be associated with serious infec-
may be α-hemolytic or nonhemolytic. Most of them are catalase tions, such as bacteremia and endocarditis under certain
negative; others may be weakly catalase positive. Pediococcus and conditions.
Leuconostoc are the genera whose members are vancomycin • S. pneumoniae is α-hemolytic; optochin susceptible; and
resistant. Lactobacilli are anaerobes that can be aerotolerant and virulent largely because of its polysaccharide capsule,
α-hemolytic, sometimes forming coccobacillary forms similar to which inhibits phagocytosis.
the viridans streptococci. Most lactobacilli (80–90%) are vanco- • S. pneumoniae is the major cause of community-acquired
mycin resistant. Other organisms that occasionally cause disease pneumonia but can also disseminate via the bloodstream
and should be differentiated from streptococci and enterococci to the central nervous system. Invasive disease is prevent-
include Lactococcus, Aerococcus, and Gemella, genera that gener- able through vaccination using either the 23-valent poly-
ally are vancomycin susceptible. Rothia mucilaginosa was pre- saccharide vaccine (adults) or the 13-valent conjugate
viously considered a Staphylococcus, but it is catalase negative; vaccine (children). Drug resistance has become a problem
colonies show a distinct adherence to agar. in certain geographic regions.
• Enterococci are remarkable for the varieties of resistance
determinants they have evolved that include β-lactam
CHAPTER SUMMARY agents, glycopeptides, and aminoglycosides, among oth-
ers. Newer agents such as linezolid and tedizolid are used
• Viridans streptococci and enterococci are part of the nor- for treatment of VRE infections. These organisms play a
mal microbiota of the human oral and gastrointestinal prominent role in health care-associated infections.

Riedel_CH14_p215-p234.indd 231 04/04/19 2:00 PM

 232   SECTION III  Bacteriology

REVIEW QUESTIONS (C) For all children ages 2–23 months plus selected older
children and adults with immunocompromising
1. A 48-year-old alcoholic man is admitted to a hospital because conditions
of stupor. He is unkempt and homeless and lives in an encamp- (D) For children ages 24–72 months
ment with other homeless people, who called the authorities (E) For all age groups older than age 2 months
when he could not be easily aroused. His temperature is 38.5°C, 6. An 8-year-old boy develops a severe sore throat. On examina-
and his blood pressure 125/80 mm Hg. He moans when attempts tion, a grayish-white exudate is seen on the tonsils and pharynx.
are made to arouse him. He has positive Kernig and Brudzinski The differential diagnosis includes group A streptococcal infec-
signs, suggesting meningeal irritation. Physical examination and tion, Epstein-Barr virus infection, severe adenovirus infection,
chest radiography show evidence of left lower lobe lung con- and diphtheria. (Neisseria gonorrhoeae pharyngitis would also
solidation. An endotracheal aspirate yields rust-colored sputum. be included, but the patient has not been sexually abused.) The
Examination of a Gram-stained sputum smear shows numerous cause of the boy’s pharyngitis is most likely
polymorphonuclear cells and numerous Gram-positive lancet-
(A) A catalase-negative Gram-positive coccus that grows in
shaped diplococci. On lumbar puncture, the cerebrospinal fluid
chains
is cloudy and has a white blood cell count of 570/µL with 95%
(B) A single-stranded positive-sense RNA virus
polymorphonuclear cells; Gram-stain shows numerous Gram-
(C) A catalase-positive Gram-positive coccus that grows in
positive diplococci. Based on this information, the likely diag-
clusters
nosis is
(D) A catalase-negative Gram-positive bacillus
(A) Pneumonia and meningitis caused by S. aureus (E) A double-stranded RNA virus
(B) Pneumonia and meningitis caused by S. pyogenes
7. A primary mechanism responsible for the pathogenesis of the
(C) Pneumonia and meningitis caused by S. pneumoniae
boy’s disease (Question 6) is
(D) Pneumonia and meningitis caused by E. faecalis
(E) Pneumonia and meningitis caused by Neisseria (A) A net increase in intracellular cyclic adenosine
meningitidis monophosphate
(B) Action of M protein
2. The patient in Question 1 is started on antibiotic therapy to
(C) Action of IgA1 protease
cover many possible microorganisms. Subsequently, culture
(D) Action of enterotoxin A
of sputum and cerebrospinal fluid yields Gram-positive diplo-
(E) Inactivation of elongation factor 2
cocci with a minimum inhibitory concentration to penicillin
G of greater than 2 µg/mL. The drug of choice for this patient 8. A 40-year-old woman develops severe headache and fever. Her
until further susceptibility testing can be done is neurologic examination findings are normal. A brain scan shows
a ring-enhancing lesion of the left hemisphere. During surgery,
(A) Penicillin G
a brain abscess is found. Culture of the abscess fluid grows an
(B) Nafcillin
anaerobic Gram-negative bacillus (Fusobacterium nucleatum)
(C) Trimethoprim–sulfamethoxazole
and a catalase-negative Gram-positive coccus that on Gram-
(D) Gentamicin
stain is in pairs and chains. The organism is β-hemolytic and
(E) Vancomycin
forms very small colonies (<0.5 mm in diameter). One person
3. This infection (Question 1) might have been prevented by thought it smelled like butterscotch. It agglutinates with group F
(A) Prophylactic intramuscular benzathine penicillin every antisera. The organism most likely is
3 weeks (A) S. pyogenes (group A)
(B) A 23-valent capsular polysaccharide vaccine (B) E. faecalis (group D)
(C) A vaccine against serogroups A, C, Y, and W135 capsular (C) S. agalactiae (group B)
polysaccharide (D) S. anginosus group
(D) A vaccine of polyribosylribitol capsular polysaccharide (E) S. aureus
covalently linked to a protein
9. Important methods for classifying and speciating streptococci
(E) Oral penicillin twice daily
are
4. The pathogenesis of the organism causing the infection
(A) Agglutination using antisera against the cell wall group-
(Question 1) includes which of the following?
specific substance
(A) Invasion of cells lining the alveoli and entry into the (B) Biochemical testing
pulmonary venule circulation (C) Hemolytic properties (α-, β-, nonhemolytic)
(B) Resistance to phagocytosis mediated by M proteins (D) Capsular swelling (quellung) reaction
(C) Migration to mediastinal lymph nodes where hemorrhage (E) All of the above
occurs
10. An 8-year-old girl develops Sydenham’s chorea (“St. Vitus
(D) Lysis of the phagocytic vacuole and release into the
dance”) with rapid uncoordinated facial tics and involuntary
circulation
purposeless movements of her extremities, strongly sugges-
(E) Inhibition of phagocytosis by a polysaccharide capsule
tive of acute rheumatic fever. She has no other major mani-
5. A 13-valent capsular polysaccharide protein conjugate vaccine festations of rheumatic fever (carditis, arthritis, subcutaneous
for the pathogen in Question 1 is recommended nodules, skin rash). The patient’s throat culture is negative for
(A) For children up to age 18 years and for selected adults S. pyogenes (group A streptococci). However, she, her brother,
(B) Only on exposure to a patient with disease caused by the
organism

Riedel_CH14_p215-p234.indd 232 04/04/19 2:00 PM

 CHAPTER 14 The Streptococci, Enterococci, and Related Genera    233

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