Exploring the Variety and Significance of Gram-Optimistic Rod Micro organism: From Pathogens to Probiotics
There are 5 medically vital genera of gram-positive
rods: Bacillus, Clostridium, Corynebacterium, Listeria, and
Gardnerella. Bacillus and Clostridium kind spores, whereas
Corynebacterium, Listeria, and Gardnerella don’t. Members
of the genus Bacillus are cardio, whereas these of the genus
Clostridium are anaerobic (Desk 17–1).
These gram-positive rods will also be distinguished primarily based
on their look on Gram stain. Bacillus and Clostridium
species are longer and extra deeply staining than Coryne-
bacterium and Listeria species. Corynebacterium species are
club-shaped (i.e., they’re thinner on one finish than the opposite).
Corynebacterium and Listeria species characteristically seem
as V- or L-shaped rods. Gardnerella vaginalis is a brief gram-
Extra data relating to the medical elements of
infections brought on by the organisms on this chapter is offered
in Half IX entitled Infectious Illnesses starting on web page 653.
SPORE-FORMING GRAM-POSITIVE RODS
1. Bacillus anthracis
Bacillus anthracis causes anthrax (Determine 17–1), which is com-
mon in animals however uncommon in people. Human illness happens
in three predominant varieties: cutaneous, pulmonary (inhalation), and
gastrointestinal. In 2001, an outbreak of each inhalation and
cutaneous anthrax occurred in the USA. The outbreak
was brought on by sending spores of the organism by way of the mail.
There have been 18 circumstances, inflicting 5 deaths on this outbreak.
Bacillus anthracis is a big gram-positive rod with sq. ends,
ceaselessly present in chains (Determine 17–2). Its antiphagocytic
capsule consists of D-glutamate. (That is distinctive—capsules
of different micro organism are polysaccharides.) It’s nonmotile, whereas
different members of the genus are motile. Anthrax toxin is encoded
on one plasmid, and the polyglutamate capsule is encoded on a
totally different plasmid.
Spores of the organism persist in soil for years. People are
most frequently contaminated cutaneously on the time of trauma to the
pores and skin, which permits the spores on animal merchandise, akin to
hides, bristles, and wool, to enter. Spores will also be inhaled
into the respiratory tract. Pulmonary (inhalation) anthrax
happens when spores are inhaled into the lungs. Gastrointestinal
anthrax happens when contaminated meat is ingested.
Inhalation anthrax shouldn’t be communicable from individual to
individual, regardless of the severity of the an infection. After being inhaled
into the lung, the organism strikes quickly to the mediasti-
nal lymph nodes, the place it causes hemorrhagic mediastinitis.
As a result of it leaves the lung so quickly, it’s not transmitted by the
respiratory path to others.
Pathogenesis relies totally on the manufacturing of two exo-
toxins, collectively often called anthrax toxin. The 2 exotoxins,
edema issue and deadly issue, every consists of two proteins
in an A–B subunit configuration. The B, or binding, subunit
in every of the 2 exotoxins is protecting antigen. The A, or
lively, subunit has enzymatic exercise.
Edema issue, an exotoxin, is an adenylate cyclase that causes
a rise within the intracellular focus of cyclic adenosine
monophosphate (AMP). This causes an outpouring of fluid from
the cell into the extracellular house, which manifests as edema.
(Notice the similarity of motion to that of cholera toxin.)
Deadly issue is a protease that cleaves the phosphokinase
that prompts the mitogen-activated protein kinase (MAPK)
sign transduction pathway. This pathway controls the expansion
of human cells, and cleavage of the phosphokinase inhibits cell
progress. Protecting antigen varieties pores within the human cell mem-
brane that permits edema issue and deadly issue to enter the
cell. The title protecting antigen refers to the truth that antibody
in opposition to this protein protects in opposition to illness.
The everyday lesion of cutaneous anthrax is a painless ulcer with
a black eschar (crust, scab) (see Determine 17–1). Native edema is
hanging. The lesion is known as a malignant pustule. Untreated
circumstances progress to bacteremia and loss of life.
Pulmonary (inhalation) anthrax, often known as “wool-sorter’s
illness,” begins with nonspecific respiratory tract signs
resembling influenza, particularly a dry cough and substernal
stress. This quickly progresses to hemorrhagic mediastinitis,
bloody pleural effusions, septic shock, and loss of life. Though
the lungs are contaminated, the traditional options and X-ray image
of pneumonia aren’t current. Mediastinal widening seen on
chest X-ray is a vital diagnostic criterion. Hemorrhagic
mediastinitis and hemorrhagic meningitis are extreme life-threat-
ening issues. The signs of gastrointestinal anthrax
embrace vomiting, stomach ache, and bloody diarrhea.
Smears present giant, gram-positive rods in chains (see Determine
17–2). Spores are normally not seen in smears of exudate as a result of
spores kind when vitamins are inadequate, and vitamins are
plentiful in contaminated tissue. Nonhemolytic colonies kind on
blood agar aerobically. Colonies on blood agar usually have a
attribute flared “comet’s tail” look.
In case of a bioterror assault, speedy analysis could be per-
shaped in particular laboratories utilizing polymerase chain response
(PCR)-based assays. One other speedy diagnostic process is
the direct fluorescent antibody check that detects antigens of the
organism within the lesion. Serologic assessments, akin to an enzyme-linked
immunosorbent assay (ELISA) check for antibodies, require acute
and convalescent serum samples and might solely be used to make
a analysis retrospectively.
Ciprofloxacin is the drug of selection. Doxycycline is an alterna-
tive drug. No resistant strains have been remoted clinically.
Ciprofloxacin or doxycycline was used as prophylaxis in these
uncovered through the outbreak in the USA in 2001. Folks
at excessive threat could be immunized with cell-free vaccine (BioThrax)
containing purified protecting antigen as immunogen. The vac-
cine is weakly immunogenic, and 6 doses of vaccine over an
18-month interval are given. Annual boosters are additionally given to
keep safety. An immune globulin preparation contain-
ing a monoclonal antibody in opposition to protecting antigen (raxi-
bacumab, Anthrasil) is offered for prevention in folks in danger
of inhalational anthrax. Incinerating animals that die of anthrax,
relatively than burying them, will stop the soil from changing into
contaminated with spores.
2. Bacillus cereus
Bacillus cereus causes meals poisoning.
Spores on grains akin to rice survive steaming and speedy frying.
The spores germinate when rice is saved heat for a lot of hours
(e.g., reheated fried rice). The portal of entry is the gastroin-
Bacillus cereus produces two enterotoxins. The mode of motion
of one of many enterotoxins is identical as that of cholera toxin
(i.e., it provides adenosine diphosphate [ADP] ribose, a course of
referred to as ADP-ribosylation, to a G protein, which stimulates ade-
nylate cyclase and results in an elevated focus of cyclic
AMP inside the enterocyte). The mode of motion of the opposite
enterotoxin resembles that of staphylococcal enterotoxin (i.e., it
is a superantigen).
There are two syndromes. (1) One syndrome has a brief incuba-
tion interval (4 hours) and consists primarily of nausea and vom-
iting, just like staphylococcal meals poisoning. (2) The opposite
has a protracted incubation interval (18 hours) and options watery,
nonbloody diarrhea, resembling clostridial gastroenteritis.
This isn’t normally finished.
Solely symptomatic therapy is given.
There isn’t a particular technique of prevention. Rice shouldn’t be
saved heat for lengthy intervals.
There are 4 medically vital species: Clostridium tetani,
Clostridium botulinum, Clostridium perfringens (which causes
both gasoline gangrene or meals poisoning), and Clostridium difficile.
All clostridia are anaerobic, spore-forming, gram-positive rods
(Determine 17–3). Essential options of pathogenesis and preven-
tion are described in Desk 17–3.
1. Clostridium tetani
Clostridium tetani causes tetanus (Determine 17–4).
Spores are widespread in soil. The portal of entry is normally a
wound web site (e.g., the place a nail penetrates the foot), however the spores
will also be launched throughout “skin-popping,” a method used
by drug addicts to inject medicine into the pores and skin. Germination of
spores is favored by necrotic tissue and poor blood provide within the
wound. Neonatal tetanus, by which the organism enters by way of
a contaminated umbilicus or circumcision wound, is a serious
downside in some growing international locations.
Tetanus toxin (tetanospasmin) is an exotoxin produced by veg-
etative cells on the wound web site. This polypeptide toxin is carried
intra-axonally (retrograde) to the central nervous system, the place
it binds to ganglioside receptors and blocks launch of inhibitory
mediators (e.g., glycine and γ-aminobutyric acid [GABA]) at
Tetanus toxin and botulinum toxin (see later) are among the many
most poisonous substances identified. They’re each proteases that cleave
the proteins concerned in mediator launch from the neurons.
Tetanus toxin has one antigenic sort, not like botulinum
toxin, which has eight. There may be due to this fact just one antigenic
sort of tetanus toxoid within the vaccine in opposition to tetanus.
Tetanus is characterised by sturdy muscle spasms (spastic paral-
ysis, tetany). Particular medical options embrace lockjaw (trismus)
on account of inflexible contraction of the jaw muscle tissue, which prevents the
mouth from opening; a attribute grimace often called risus
sardonicus; and exaggerated reflexes. Opisthotonos, a pro-
nounced arching of the again on account of spasm of the sturdy extensor
muscle tissue of the again, is commonly seen (see Determine 17–4). Respira-
tory failure ensues. A excessive mortality price is related to this
illness. Notice that in tetanus, spastic paralysis (sturdy muscle
contractions) happens, whereas in botulism, flaccid paralysis
(weak or absent muscle contractions) happens.
There isn’t a microbiologic or serologic analysis. Organisms are
hardly ever remoted from the wound web site. Clostridium tetani produces
a terminal spore (i.e., a spore on the finish of the rod). This offers
the organism the attribute look of a “tennis racket.”
Tetanus immune globulin (tetanus antitoxin) is used to neutral-
ize the toxin. The position of antibiotics is unsure. If antibiotics
are used, both metronidazole or penicillin G could be given. An
ample airway should be maintained and respiratory assist
given. Benzodiazepines (e.g., diazepam [Valium]) needs to be
given to stop spasms.
Tetanus is prevented by immunization with tetanus toxoid
(formaldehyde-treated toxin) in childhood and each 10 years
thereafter. Tetanus toxoid is normally given to youngsters in combi-
nation with diphtheria toxoid and the acellular pertussis vaccine
When trauma happens, the wound needs to be cleaned and
debrided, and tetanus toxoid booster needs to be given. If the
wound is grossly contaminated, tetanus immune globulin,
in addition to the toxoid booster, needs to be given and penicillin
administered. Half of the immune globulins needs to be infil-
trated into the wound and the opposite half given intramuscularly
at a web site separate from the tetanus toxoid.
Tetanus immune globulin (tetanus antitoxin) is made in
people to keep away from serum illness reactions that happen when
antitoxin made in horses is used. The administration of each
immune globulins and tetanus toxoid (at totally different websites within the
physique) is an instance of passive–lively immunity.
2. Clostridium botulinum
Clostridium botulinum causes botulism.
Spores, widespread in soil, contaminate greens and meats.
When these meals are canned or vacuum-packed with out
ample sterilization, spores survive and germinate within the
anaerobic setting. Toxin is produced inside the canned
meals and ingested preformed. The very best-risk meals are
(1) alkaline greens akin to inexperienced beans, peppers, and mush-
rooms and (2) smoked fish. The toxin is comparatively heat-labile; it
is inactivated by boiling for a number of minutes. Thus, illness can
be prevented by adequate cooking.
Botulinum toxin is absorbed from the intestine and carried through the
blood to peripheral nerve synapses, the place it blocks launch of
acetylcholine. It’s a protease that cleaves the proteins concerned
in acetylcholine launch. The toxin is a polypeptide encoded by a
lysogenic phage. Together with tetanus toxin, it’s among the many most
poisonous substances identified. There are eight immunologic varieties of
toxin; sorts A, B, and E are the most typical in human ill-
ness. Botox is a industrial preparation of exotoxin A used to
take away wrinkles on the face. Minute quantities of the toxin are
efficient within the therapy of sure spasmodic muscle issues
akin to torticollis, “author’s cramp,” and blepharospasm.
Descending weak point and paralysis of cranial nerves, together with
diplopia, dysphagia, ptosis, and respiratory muscle failure, are
seen. No fever is current. In distinction, Guillain-Barré syndrome
is an ascending paralysis (see Chapter 66).
Two particular medical varieties happen: (1) wound botulism, in
which spores contaminate a wound, germinate, and produce
toxin on the web site and (2) toddler botulism, by which the organ-
isms develop within the intestine and produce the toxin there. Ingestion
of honey containing the organism is implicated in transmis-
sion of toddler botulism. Affected infants develop weak point or
paralysis and might have respiratory assist however normally get better
spontaneously. In the USA, toddler botulism accounts
for about half of the circumstances of botulism, and wound botulism is
related to drug abuse, particularly skin-popping with black
The organism is normally not cultured. Botulinum toxin is
demonstrable in uneaten meals and the affected person’s serum by
mouse safety assessments. Mice are inoculated with a pattern of
the medical specimen and can die except protected by antitoxin.
Enzyme-linked immunoassay (EIA) assessments are additionally used to detect
the toxin, and PCR assessments are used to detect the DNA encoding
The heptavalent antitoxin containing all seven sorts (A to G)
is most popular to the trivalent antitoxin containing sorts A, B,
and E. Respiratory assist is offered as nicely. The antitoxin
is made in horses, and serum illness might happen. A bivalent
antitoxin (sorts A and B) purified from the plasma of people
immunized with botulinum toxoid is offered for the therapy
of toddler botulism.
Correct sterilization of all canned and vacuum-packed meals
is crucial. Meals should be adequately cooked to inactivate the
toxin. Swollen cans should be discarded (clostridial proteolytic
enzymes kind gasoline, which swells cans).
3. Clostridium perfringens
Clostridium perfringens causes two distinct ailments, gasoline gan-
grene and meals poisoning, relying on the route of entry into
Illness: Fuel Gangrene
Fuel gangrene (myonecrosis, necrotizing fasciitis) is one
of the 2 ailments brought on by C. perfringens (Determine 17–5).
Necrotizing fasciitis is commonly referred to as the “flesh-eating” dis-
ease. Along with C. perfringens, Streptococcus pyogenes
and methicillin-resistant Staphylococcus aureus (MRSA) are
vital causes. The medical elements of necrotizing fasciitis
are described in Chapter 77.
Fuel gangrene can be brought on by different histotoxic clostridia such
as Clostridium histolyticum, Clostridium septicum, Clostridium
novyi, and Clostridium sordellii. (C. sordellii additionally causes poisonous
shock syndrome in postpartum and postabortion girls.)
Spores are situated within the soil; vegetative cells are members of the
regular flora of the colon and vagina. Fuel gangrene is associ-
ated with battle wounds, vehicle and bike accidents,
and septic abortions (endometritis).
Organisms develop in traumatized tissue (particularly muscle) and
produce quite a lot of toxins. Crucial is alpha toxin
(lecithinase), which damages cell membranes, together with these
of erythrocytes, leading to hemolysis. Degradative enzymes
produce gasoline in tissues.
Ache, edema, cellulitis, and gangrene (necrosis) happen within the
wound space (see Determine 17–5). If crepitus is palpated within the
affected tissue, it signifies gasoline within the tissue. This gasoline is usually
hydrogen produced by the anaerobic micro organism. Hemolysis and
jaundice are widespread, as are blood-tinged exudates. A foul-
smelling, bloody vaginal discharge can happen in endometritis.
Shock and loss of life can ensue. Mortality charges are excessive.
Smears of tissue and exudate samples present giant gram-positive
rods. Spores aren’t normally seen as a result of they’re shaped
primarily below nutritionally poor situations. The organ-
isms are cultured anaerobically after which recognized by sugar
fermentation reactions and natural acid manufacturing. Clostrid-
ium perfringens colonies exhibit a double zone of hemolysis on
blood agar. The colonies additionally produce a precipitate in egg yolk
agar brought on by the motion of its lecithinase. Serologic assessments are
Penicillin G is the antibiotic of selection. Wounds needs to be
Wounds needs to be cleansed and debrided. Penicillin could also be
given for prophylaxis. There isn’t a vaccine.
Illness: Meals Poisoning
Meals poisoning is the second illness brought on by C. perfringens.
Spores are situated in soil and might contaminate meals. The warmth-
resistant spores survive cooking and germinate. The organisms
develop to giant numbers in reheated meals, particularly meat dishes.
Clostridium perfringens is a member of the traditional flora within the
colon however not within the small bowel, the place the enterotoxin acts to
trigger diarrhea. The mode of motion of the enterotoxin is the
identical as that of the enterotoxin of Staphylococcus aureus (i.e., it
acts as a superantigen).
The illness has an 8- to 16-hour incubation interval and is char-
acterized by watery diarrhea with cramps and little vomiting. It
resolves in 24 hours.
This isn’t normally finished. There isn’t a assay for the toxin. Massive
numbers of the organisms could be remoted from uneaten meals.
Symptomatic therapy is given; no antimicrobial medicine are
There aren’t any particular preventive measures. Meals needs to be
adequately cooked to kill the organism.
4. Clostridium difficile
Clostridium difficile causes antibiotic-associated pseudomem-
branous colitis (Determine 17–6). Clostridium difficile is essentially the most
The organism colonizes the big gut of roughly 3%
of the overall inhabitants and as much as 30% of hospitalized sufferers.
Notice that most individuals aren’t colonized, which explains why
most individuals who take antibiotics don’t get pseudomem-
branous colitis. C. difficile is transmitted by the fecal–oral
route. Both the spores or the bacterial organism itself could be
The vast majority of circumstances happen in hospitalized sufferers, however
about one-third of circumstances are community-acquired. The fingers of
hospital personnel are vital intermediaries.
Antibiotics suppress drug-sensitive members of the traditional
flora of the colon, permitting C. difficile to multiply and produce
giant quantities of exotoxins A and B. Each exotoxin A and exo-
toxin B are glucosyltransferases (i.e., enzymes that glucosylate
[add glucose to] a G protein referred to as Rho GTPase). The primary
impact of those exotoxins is to trigger depolymerization of actin,
leading to a lack of cytoskeletal integrity, apoptosis, and loss of life
of the enterocytes. Exotoxin B is assumed to play the main position
in producing the indicators and signs of human illness.
Clindamycin was the primary antibiotic to be proven to predis-
pose to pseudomembranous colitis, however many antibiotics are
identified to predispose to this illness. At current, third-generation
cephalosporins are the most typical as a result of they’re so
ceaselessly used. Ampicillin and fluoroquinolones are additionally
generally implicated. Along with antibiotics, most cancers che-
motherapy and proton pump inhibitors predispose to pseu-
domembranous colitis. Clostridium difficile hardly ever invades the
Clostridium difficile causes diarrhea related to pseudo-
membranes (yellow-white plaques) on the colonic mucosa (see
Determine 17–6). (The time period pseudomembrane is outlined in Chapter 7
on web page 38). The diarrhea is normally not bloody, and neutro-
phils are discovered within the stool in about half of the circumstances. Fever and
stomach ache typically happen. The organism hardly ever enters the
bloodstream and barely causes metastatic an infection.
The pseudomembranes are visualized by sigmoidoscopy.
Poisonous megacolon can happen, and surgical resection of the colon
could also be essential. Pseudomembranous colitis could be distin-
guished from the transient diarrhea that happens as a aspect impact
of many oral antibiotics by testing for the presence of the toxin
within the stool. Even with ample therapy, the organism might
not be eradicated from the colon, and recurrences happen at a
price of roughly 15−20%.
In 2005, a brand new, extra virulent pressure of C. difficile emerged.
This hypervirulent pressure causes extra extreme illness, is extra
more likely to trigger recurrences, and responds much less nicely to metroni-
dazole than the earlier pressure. The pressure can be characterised
by resistance to quinolones. It’s thought that the widespread
use of quinolones for diarrheal illness might have chosen for
this new pressure.
The presence of exotoxins within the filtrate of a affected person’s stool speci-
males is the idea of the laboratory analysis. It’s inadequate to
tradition the stool for the presence of C. difficile as a result of folks
could be colonized by the organism and never have illness.
There are two varieties of assessments used to make the laboratory
analysis. One detects the exotoxin itself, and the opposite detects
the genes that encode the exotoxin. To detect the exotoxin itself,
an ELISA check using antibody to the exotoxin is used. To
detect the genes that encode the exotoxin, a PCR assay to deter-
mine the presence of the toxin gene DNA is used. The DNA-
primarily based check has larger sensitivity and specificity than the ELISA
check. Nevertheless, these nucleic acid amplification assessments (NAATs)
needs to be interpreted with warning as a result of an individual might solely
be colonized by C. difficile and be recorded as constructive when, in
reality, C. difficile shouldn’t be the reason for the affected person’s illness.
The causative antibiotic needs to be withdrawn. Oral metronida-
zole or vancomycin needs to be given and fluids changed. Metro-
nidazole is most popular as a result of utilizing vancomycin might choose for
vancomycin-resistant enterococci. Nevertheless, in life-threatening
circumstances, vancomycin needs to be used as a result of it’s more practical
than metronidazole. Vancomycin could be given orally or per
rectum or, in very extreme circumstances, each methods. In life-threatening
circumstances, surgical elimination of the colon could also be required.
In lots of sufferers, therapy doesn’t eradicate the service
state, and recurrent episodes of colitis can happen. Fidaxomicin
(Dificid) is used each within the therapy of pseudomembranous
colitis and in stopping relapses of this illness. It’s efficient
in life-threatening circumstances. Bezlotoxumab, a monoclonal anti-
physique in opposition to exotoxin B of C. difficile, is efficient in stopping
Fecal transplantation is one other attainable therapeutic
method. It entails administering bowel flora from a nor-
mal particular person both by enema or by nasoduodenal tube to
the affected person with pseudomembranous colitis. This method is
TABLE 17–4 Essential Options of Pathogenesis by Corynebacterium diphtheriae and Listeria monocytogenes
Organism Sort of Pathogenesis Typical Illness Predisposing Issue Mode of Prevention
C. diphtheriae Toxigenic Diphtheria Failure to immunize Toxoid vaccine
L. monocytogenes Pyogenic Meningitis; sepsis Neonate; immunosuppression No vaccine; pasteurize milk merchandise
primarily based on the idea of bacterial interference (i.e., to switch
the C. difficile with regular bowel flora). Very excessive treatment charges
are claimed for this system, however aesthetic concerns have
restricted its acceptance.
There aren’t any preventive vaccines or medicine. As a result of antibiotics
are an vital predisposing issue for pseudomembranous
colitis, they need to be prescribed solely when essential. Within the
hospital, strict an infection management procedures, together with rigorous
handwashing, are vital. Probiotics, such because the yeast Sac-
charomyces, could also be helpful to stop pseudomembranous colitis.
NON–SPORE-FORMING GRAM-POSITIVE RODS
There are three vital pathogens on this group:
Corynebacterium diphtheriae, Listeria monocytogenes, and
Gardnerella vaginalis. Essential options of pathogenesis
and prevention of C. diphtheriae and L. monocytogenes are
described in Desk 17–4.
Corynebacterium diphtheriae causes diphtheria (Determine 17–7).
Different Corynebacterium species (diphtheroids) are implicated in
Corynebacteria are gram-positive rods that seem club-shaped
(wider at one finish) and are organized in palisades or in V- or
L-shaped formations (Determine 17–8). The rods have a beaded
look. The beads include granules of extremely polymerized
polyphosphate—a storage mechanism for high-energy phos-
phate bonds. The granules stain metachromatically (i.e., a dye
that stains the remainder of the cell blue will stain the granules crimson).
People are the one pure host of C. diphtheriae. Each toxi-
genic and nontoxigenic organisms reside within the higher respi-
ratory tract and are transmitted by airborne droplets. The
organism may infect the pores and skin on the web site of a preexisting pores and skin
lesion. This happens primarily within the tropics however can happen world-
broad in indigent individuals with poor pores and skin hygiene.
Though exotoxin manufacturing is crucial for pathogenesis, inva-
siveness can be essential as a result of the organism should first estab-
lish and keep itself within the throat. Diphtheria toxin inhibits
protein synthesis by ADP-ribosylation of elongation factor-2
(EF-2). The toxin impacts all eukaryotic cells no matter tissue
sort however has no impact on the analogous consider prokaryotic cells.
The toxin is a single polypeptide with two useful
domains. The binding (B) area mediates binding of the toxin
to glycoprotein receptors on the cell membrane. The lively (A)
area possesses enzymatic exercise that cleaves nicotinamide
from nicotinamide adenine dinucleotide (NAD) and transfers
the remaining ADP-ribose to EF-2, thereby inactivating it.
Different organisms whose exotoxins act by ADP-ribosylation are
described in Tables 7–10 and seven–11.
The DNA that codes for diphtheria toxin is a part of the DNA
of a temperate bacteriophage referred to as beta phage. In the course of the
lysogenic part of viral progress, the DNA of this virus integrates
into the bacterial chromosome and the toxin is synthesized.
Corynebacterium diphtheriae cells that aren’t lysogenized by
this phage don’t produce exotoxin and are nonpathogenic.
The host response to C. diphtheriae consists of the next:
(1) A neighborhood irritation within the throat, with a fibrinous exu-
date that varieties the powerful, adherent, grey pseudomembrane
attribute of the illness.
(2) Antibody that may neutralize exotoxin exercise by block-
ing the interplay of the binding area with the receptors,
thereby stopping entry into the cell. The immune standing of a
individual could be assessed by Schick’s check. The check is carried out by
intradermal injection of 0.1 mL of purified standardized toxin.
Though diphtheria is uncommon in the USA, physicians ought to
pay attention to its most distinguished signal, the thick, grey, adherent
pseudomembrane over the tonsils and throat (see Determine 17–7).
(The time period pseudomembrane is outlined in Chapter 7 on web page 38.)
The opposite elements are nonspecific: fever, sore throat, and cervical
adenopathy. There are three distinguished issues:
(1) Extension of the membrane into the larynx and trachea,
inflicting airway obstruction.
(2) Myocarditis accompanied by arrhythmias and circulatory
(3) Nerve weak point or paralysis, particularly of the cranial
nerves. Paralysis of the muscle tissue of the taste bud and pharynx
can result in regurgitation of fluids by way of the nostril. Peripheral
neuritis affecting the muscle tissue of the extremities additionally happens.
Cutaneous diphtheria causes ulcerating pores and skin lesions coated
by a grey membrane. These lesions are sometimes indolent and sometimes
don’t invade surrounding tissue. Systemic signs hardly ever
happen. In the USA, cutaneous diphtheria happens pri-
marily within the indigent.
Laboratory analysis entails each isolating the organism and
demonstrating toxin manufacturing. It needs to be emphasised that
the choice to deal with with antitoxin is a medical one and can’t
look ahead to the laboratory outcomes. A throat swab needs to be cultured
on Loeffler’s medium, a tellurite plate, and a blood agar plate.
The tellurite plate comprises a tellurium salt that’s lowered to
elemental tellurium inside the organism. The everyday gray-black
colour of tellurium within the colony is a telltale diagnostic criterion.
If C. diphtheriae is recovered from the cultures, both animal
inoculation or an antibody-based gel diffusion precipitin check
is carried out to doc toxin manufacturing. A PCR assay for
the presence of the toxin gene within the organism remoted from the
affected person will also be used.
Smears of the throat swab needs to be stained with each Gram
stain and methylene blue. Though the analysis of diphtheria
can’t be made by examination of the smear, the discovering of
many tapered, pleomorphic gram-positive rods could be sugges-
tive. The methylene blue stain is superb for revealing the typi-
cal metachromatic granules.
The therapy of selection is antitoxin, which needs to be given
instantly on the idea of medical impression as a result of there
is a delay in laboratory diagnostic procedures. The toxin binds
quickly and irreversibly to cells and, as soon as sure, can’t be neu-
tralized by antitoxin. The operate of antitoxin is due to this fact to
neutralize unbound toxin within the blood. As a result of the antiserum
is made in horses, the affected person should be examined for hypersensitiv-
ity, and medicines for the therapy of anaphylaxis should be
accessible. Serum illness (see Chapter 65) might happen after
administration of antiserum made in horses.
Therapy with penicillin G or erythromycin can be recom-
mended, however neither is an alternative choice to antitoxin. Antibiotics
inhibit progress of the organism, scale back toxin manufacturing, and
lower the incidence of continual carriers.
Diphtheria may be very uncommon in the USA as a result of youngsters
are immunized with diphtheria toxoid (normally given as a
mixture of diphtheria toxoid, tetanus toxoid, and acellular
pertussis vaccine, typically abbreviated as DTaP). Diphtheria toxoid
is ready by treating the exotoxin with formaldehyde. This
therapy inactivates the poisonous impact however leaves the antigenicity
intact. Immunization consists of three doses given at 2, 4, and
6 months of age, with boosters at 1 and 6 years of age. As a result of
immunity wanes, a booster each 10 years is really useful.
Immunization doesn’t stop nasopharyngeal carriage of the
Listeria monocytogenes causes meningitis and sepsis in new-
borns, pregnant girls, and immunosuppressed adults. It additionally
causes outbreaks of febrile gastroenteritis. It’s a main explanation for
concern for the meals business.
Listeria monocytogenes is a small gram-positive rod organized
in V- or L-shaped formations just like corynebacteria. The
organism displays an uncommon tumbling motion that distin-
guishes it from the corynebacteria, that are nonmotile. Colo-
nies on a blood agar plate produce a slender zone of β-hemolysis
that resembles the hemolysis of some streptococci.
Listeria grows nicely at chilly temperatures, so storage of con-
taminated meals within the fridge can improve the chance of gas-
troenteritis. This paradoxical progress within the chilly is known as “chilly
Listeria infections happen primarily in two medical settings: (1) in
the fetus or in a new child because of transmission throughout the
placenta or throughout supply and (2) in pregnant girls and
immunosuppressed adults, particularly renal transplant sufferers.
(Notice that pregnant girls have lowered cell-mediated immu-
nity through the third trimester.)
The organism is distributed worldwide in animals, vegetation,
and soil. From these reservoirs, it’s transmitted to people
primarily by ingestion of unpasteurized milk merchandise, under-
cooked meat, and uncooked greens. Contact with home farm
animals and their feces can be an vital supply. Within the
United States, listeriosis is primarily a foodborne illness associ-
ated with consuming unpasteurized cheese and delicatessen meats.
Following ingestion, the micro organism seem within the colon after which
can colonize the feminine genital tract. From this location, they
can infect the fetus if membranes rupture or infect the neonate
throughout passage by way of the delivery canal.
The pathogenesis of Listeria is dependent upon the organism’s capability
to invade and survive inside cells. Invasion of cells is mediated
by internalin made by Listeria and E-cadherin on the floor of
human cells. The power of Listeria to move the placenta, enter the
meninges, and invade the gastrointestinal tract is dependent upon the
interplay of internalin and E-cadherin on these tissues.
Upon getting into the cell, the organism produces listeriolysin,
which permits it to flee from the phagosome into the cytoplasm,
thereby escaping destruction within the phagosome. As a result of Listeria
preferentially grows intracellularly, cell-mediated immunity is a
extra vital host protection than humoral immunity. Suppres-
sion of cell-mediated immunity predisposes to Listeria infections.
Listeria monocytogenes can transfer from cell to cell by means
of actin rockets—filaments of actin polymerize—and propel
the micro organism by way of the membrane of 1 human cell and into
An infection throughout being pregnant may cause abortion, untimely
supply, or sepsis through the peripartum interval. Newborns
contaminated on the time of supply can have acute meningitis 1 to
4 weeks later. The micro organism attain the meninges through the blood-
stream (bacteremia). The contaminated mom is both asymp-
tomatic or has an influenzalike sickness. Listeria monocytogenes
infections in immunocompromised adults could be both sepsis
Gastroenteritis brought on by L. monocytogenes is characterised
by watery diarrhea, fever, headache, myalgias, and stomach
cramps however little vomiting. Outbreaks are normally brought on by
contaminated dairy merchandise, however undercooked meats akin to
hen and scorching canine and ready-to-eat meals akin to coleslaw
have additionally been concerned.
Laboratory analysis is made primarily by Gram stain and
tradition. The looks of gram-positive rods resembling
diphtheroids and the formation of small, grey colonies with a
slender zone of β-hemolysis on a blood agar plate recommend the
presence of Listeria. The isolation of Listeria is confirmed by the
presence of motile organisms, which differentiate them from
the nonmotile corynebacteria. Identification of the organism as
L. monocytogenes is made by sugar fermentation assessments.
Therapy of invasive illness, akin to meningitis and sepsis,
consists of ampicillin with or with out gentamicin. Trimethoprim-
sulfamethoxazole will also be used. Resistant strains are uncommon.
Listeria gastroenteritis usually doesn’t require therapy.
Prevention is troublesome as a result of there is no such thing as a immunization. Restrict-
ing the publicity of pregnant girls and immunosuppressed
sufferers to potential sources akin to cattle, unpas-
teurized milk merchandise, and uncooked greens is really useful.
Trimethoprim-sulfamethoxazole given to immunocompro-
mised sufferers to stop Pneumocystis pneumonia may
Gardnerella vaginalis is the primary organism related to
bacterial vaginosis. This illness is the most typical vaginal
an infection of sexually lively girls.
Gardnerella vaginalis is a small, facultative gram-variable rod.
The time period “gram-variable” refers back to the remark that some
organisms are purple whereas others are pink in a Gram-stained
specimen. Structurally, it has a gram-positive cell wall, however the
wall is skinny and older organisms are likely to lose the purple colour.
The pathogenesis of bacterial vaginosis is unsure. Gardnerella
vaginalis is commonly present in affiliation with anaerobes akin to
Mobiluncus and Prevotella and non-anaerobes akin to Myco-
plasma hominis and Ureaplasma urealyticum. Collectively they
trigger the signs of bacterial vaginosis.
Bacterial vaginosis shouldn’t be regarded as transmitted by sexual
exercise. Slightly, it’s thought of to be a dysbiosis by which the
Lactobacillus which can be discovered as regular flora within the vagina are
changed by these different organisms.
Bacterial vaginosis is characterised by a malodorous, white or
gray-colored vaginal discharge. The discharge has a character-
istic “fishy” odor. Inflammatory adjustments are usually absent,
which is why it’s referred to as a “vaginosis” relatively than a “vaginitis.”
Delicate itching might happen. Ladies with bacterial vaginosis have
a better incidence of preterm deliveries, and consequently, a
greater incidence of morbidity and mortality happens of their
new child youngsters.
Clue cells, that are vaginal epithelial cells coated with bac-
teria, are an vital laboratory discovering seen in a microscopic
examination of the vaginal discharge (Determine 17-9). As well as,
the “whiff ” check, which consists of treating the vaginal discharge
with 10% KOH and smelling a pungent, “fishy” odor, is commonly
constructive. Nevertheless, trichomoniasis, which might additionally trigger a posi-
tive whiff check, should be dominated out earlier than a analysis of bacterial
vaginosis could be made. A pH of larger than 4.5 of the vaginal
discharge helps the analysis of bacterial vaginosis.
Therapy and Prevention
The drug of selection is metronidazole. Therapy of sexual part-
ners shouldn’t be really useful as it’s not thought of to be transmis-
sible. There isn’t a vaccine.
FIGURE 17–9 Clue cells in bacterial vaginosis. Notice that the
decrease epithelial cell is a “clue cell” as a result of its floor is roofed
with micro organism. The higher epithelial cell shouldn’t be a “clue cell” as a result of its
floor has few micro organism. (Reproduced with permission from Usatine RP et al.
The Colour Atlas of Household Medication, New York, NY: McGraw-Hill; 2009. Courtesy of E.J.
Mayeaux, Jr., MD.)
1. Which one of many following is a club-shaped, gram-positive rod
that causes illness by producing an exotoxin that kills cells by
inhibiting elongation factor-2, ensuing within the inhibition of protein
(A) Bacillus anthracis
(B) Bacillus cereus
(C) Clostridium perfringens
(D) Corynebacterium diphtheriae
(E) Listeria monocytogenes
2. Which one of many following is a big gram-positive rod that
causes necrosis of tissue by producing an exotoxin that degrades
lecithin, ensuing within the lysis of cell membranes?
(A) Bacillus anthracis
(B) Bacillus cereus
(C) Clostridium perfringens
(D) Corynebacterium diphtheriae
(E) Listeria monocytogenes