Exploring the Variety and Significance of Gram-Optimistic Rod Micro organism: From Pathogens to Probiotics

Exploring the Variety and Significance of Gram-Optimistic Rod Micro organism: From Pathogens to Probiotics

 

INTRODUCTION

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-

variable rod.

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

Illness

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.

Essential Properties

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.

Transmission

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

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.

Medical Findings

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.

Laboratory Prognosis

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.

Therapy

Ciprofloxacin is the drug of selection. Doxycycline is an alterna-

tive drug. No resistant strains have been remoted clinically.

Prevention

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

Illness

Bacillus cereus causes meals poisoning.

Transmission

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-

testinal tract.

Pathogenesis

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).

Medical Findings

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.

Laboratory Prognosis

This isn’t normally finished.

Therapy

Solely symptomatic therapy is given.

Prevention

There isn’t a particular technique of prevention. Rice shouldn’t be

saved heat for lengthy intervals.

CLOSTRIDIUM

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

Illness

Clostridium tetani causes tetanus (Determine 17–4).

Transmission

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.

Pathogenesis

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

spinal synapses.

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.

Medical Findings

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.

Laboratory Prognosis

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.”

Therapy

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.

Prevention

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

(DTaP).

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

Illness

Clostridium botulinum causes botulism.

Transmission

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.

Pathogenesis

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.

Medical Findings

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

tar heroin.

Laboratory Prognosis

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 toxin.

Therapy

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.

Prevention

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

the physique.

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.)

Transmission

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).

Pathogenesis

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.

Medical Findings

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.

Laboratory Prognosis

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

not helpful.

Therapy

Penicillin G is the antibiotic of selection. Wounds needs to be

debrided.

Prevention

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.

Transmission

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.

Pathogenesis

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).

Medical Findings

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.

Laboratory Prognosis

This isn’t normally finished. There isn’t a assay for the toxin. Massive

numbers of the organisms could be remoted from uneaten meals.

Therapy

Symptomatic therapy is given; no antimicrobial medicine are

administered.

Prevention

There aren’t any particular preventive measures. Meals needs to be

adequately cooked to kill the organism.

4. Clostridium difficile

Illness

Clostridium difficile causes antibiotic-associated pseudomem-

branous colitis (Determine 17–6). Clostridium difficile is essentially the most

Transmission

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

transmitted.

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.

Pathogenesis

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

intestinal mucosa.

Medical Findings

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.

Laboratory Prognosis

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.

Therapy

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

relapses.

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.

Prevention

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

Illness

Corynebacterium diphtheriae causes diphtheria (Determine 17–7).

Different Corynebacterium species (diphtheroids) are implicated in

opportunistic infections.

Essential Properties

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).

Transmission

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.

Pathogenesis

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.

 

Medical Findings

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

collapse.

(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 Prognosis

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.

Therapy

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.

Prevention

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

organism.

LISTERIA MONOCYTOGENES

Illnesses

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.

Essential Properties

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

enhancement.”

Pathogenesis

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

one other.

Medical Findings

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

or meningitis.

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 Prognosis

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

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

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

stop listeriosis.

GARDNERELLA VAGINALIS

Illness

Gardnerella vaginalis is the primary organism related to

bacterial vaginosis. This illness is the most typical vaginal

an infection of sexually lively girls.

Essential Properties

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.

Pathogenesis

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.

Medical Findings

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.

Laboratory Prognosis

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.)

SELF-ASSESSMENT QUESTIONS

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

synthesis?

(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