Exploring Gram-Damaging Rods within the Respiratory Tract: Pathogens, Identification, and Implications

Exploring Gram-Damaging Rods within the Respiratory Tract: Pathogens, Identification, and Implications

 

INTRODUCTION

There are 4 medically essential gram-negative rods typi-

cally related to the respiratory tract, particularly, Haemophilus

influenzae, Bordetella pertussis, Legionella pneumophila, and

Acinetobacter baumannii (Desk 19–1). Haemophilus influenzae

and B. pertussis are discovered solely in people, whereas L. pneumophila

is discovered primarily in environmental water sources. Acinetobacter

baumannii is present in environmental water sources but additionally

colonizes the pores and skin and higher respiratory tract.

Extra data relating to the scientific points of

infections brought on by the organisms on this chapter is supplied

in Half IX entitled Infectious Ailments starting on web page 589.

HAEMOPHILUS

Ailments

Haemophilus influenzae was the main explanation for men-

ingitis in younger kids, however using the extremely efficient

“conjugate” vaccine has enormously decreased the incidence of men-

ingitis brought on by this organism. It’s nonetheless an essential trigger

of higher respiratory tract infections (otitis media, sinusitis,

conjunctivitis, and epiglottitis) and sepsis in kids. It additionally

causes pneumonia in adults, significantly in these with persistent

obstructive lung illness. Haemophilus ducreyi, the agent of

chancroid, is mentioned in Chapter 27.

Essential Properties

Haemophilus influenzae is a small, pleomorphic gram-negative

rod (coccobacillary rod) with a polysaccharide capsule

(Determine 19–1). It is without doubt one of the three essential encapsulated

pyogens, together with the pneumococcus and the meningococcus.

Serologic typing is predicated on the antigenicity of the capsular

polysaccharide. Of the six serotypes (a–f), kind b is probably the most

essential. Sort b used to trigger a lot of the extreme, invasive

ailments, akin to meningitis and sepsis, however the widespread use

of the vaccine containing the kind b capsular polysaccharide as

the immunogen has enormously decreased the incidence of invasive

Pathogenesis & Epidemiology

Haemophilus influenzae infects solely people; there isn’t a animal

reservoir. It enters the physique by the inhalation of airborne drop-

lets into the respiratory tract, leading to both asymptomatic

colonization or infections akin to otitis media, sinusitis, or pneu-

monia. The organism produces an IgA protease that degrades

secretory IgA, thus facilitating attachment to the respiratory

mucosa. After turning into established within the higher respiratory

tract, the organism can enter the bloodstream (bacteremia) and

unfold to the meninges. Meningitis is precipitated primarily by the

encapsulated strains, however nonencapsulated strains are steadily

concerned in otitis media, sinusitis, and pneumonia. Word that the

incidence of meningitis brought on by capsular kind b has been enormously

decreased as a result of the vaccine comprises the kind b polysaccharide

because the immunogen. Pathogenesis of H. influenzae entails its

antiphagocytic capsule and endotoxin; no exotoxin is produced.

Most infections happen in kids between the ages of 6 months

and 6 years, with a peak within the age group from 6 months to

1 12 months. This age distribution is attributed to a decline in mater-

nal IgG within the baby coupled with the lack of the kid to

generate adequate antibody towards the polysaccharide capsular

antigen till the age of roughly 2 years.

Medical Findings

Meningitis brought on by H. influenzae can’t be distinguished on

scientific grounds from that brought on by different bacterial pathogens

(e.g., pneumococci or meningococci). The speedy onset of fever,

headache, and stiff neck, together with drowsiness, is typical.

Sinusitis and otitis media trigger ache within the affected space, opaci-

fication of the contaminated sinus, and redness with bulging of the

tympanic membrane. Haemophilus influenzae is second solely to

the pneumococcus as a trigger of those two infections.

Different severe infections brought on by this organism embody

septic arthritis, cellulitis, and sepsis, the latter occurring espe-

cially in splenectomized sufferers. Not often, epiglottitis, which may

hinder the airway, happens. A swollen “cherry-red” epiglottis is

seen. This life-threatening illness of younger kids is precipitated

nearly solely by H. influenzae. Pneumonia in aged

adults, particularly these with persistent respiratory illness, may be

brought on by untypeable strains of H. influenzae.

Laboratory Prognosis

Laboratory prognosis depends upon isolation of the organism on

heated-blood (“chocolate”) agar enriched with two progress fac-

tors required for bacterial respiration, particularly, issue X (a heme

compound) and issue V (NAD). The blood utilized in chocolate

agar is heated to inactivate nonspecific inhibitors of H. influenzae

progress.

An organism that grows solely within the presence of each progress

components is presumptively recognized as H. influenzae; different spe-

cies of Haemophilus, akin to Haemophilus parainfluenzae, do

not require each components. Definitive identification may be made

with both biochemical assessments or the capsular swelling (quellung)

response. Extra technique of figuring out encapsulated strains

embody fluorescent antibody staining of the organism and coun-

terimmunoelectrophoresis or latex agglutination assessments, which

detect the capsular polysaccharide.

Remedy

The remedy of alternative for meningitis or different severe systemic

infections brought on by H. influenzae is ceftriaxone. From 20−30%

of H. influenzae kind b isolates produce a β-lactamase that

degrades penicillinase-sensitive β-lactams akin to ampicillin

however not ceftriaxone. It is very important institute antibiotic treat-

ment promptly, as a result of the incidence of neurologic sequelae

(e.g., subdural empyema) is excessive. Untreated H. influenzae

meningitis has a fatality fee of roughly 90%. H. influenzae

higher respiratory tract infections, akin to otitis media and

sinusitis, are handled with both amoxicillin-clavulanate or

trimethoprim-sulfamethoxazole.

Prevention

The vaccine comprises the capsular polysaccharide of H. influenzae

kind b conjugated to diphtheria toxoid or different service protein.

Relying on the service protein, it’s given a while between

the ages of two and 15 months. This vaccine is far more

efficient in younger kids than the unconjugated vaccine and

has decreased the incidence of meningitis brought on by this organ-

ism by roughly 90% in immunized kids. Meningitis

in shut contacts of the affected person may be prevented by rifampin

Rifampin is used as a result of it’s secreted within the saliva to a larger

extent than ampicillin. Rifampin decreases respiratory carriage

of the organism, thereby lowering transmission.

BORDETELLA

Illness

Bordetella pertussis causes whooping cough (pertussis).

Essential Properties

Bordetella pertussis is a small, coccobacillary, encapsulated

gram-negative rod.

Pathogenesis & Epidemiology

Bordetella pertussis, a pathogen just for people, is transmit-

ted by airborne droplets produced in the course of the extreme coughing

episodes. The organisms connect to the ciliated epithelium of the

higher respiratory tract however don’t invade the underlying tissue.

Decreased cilia exercise and subsequent demise of the ciliated

epithelial cells are essential points of pathogenesis.

Pertussis is a extremely contagious illness that happens primarily

in infants and younger kids and has a worldwide distribution.

The variety of circumstances has declined in america as a result of

use of the vaccine is widespread. Nevertheless, outbreaks of pertus-

sis in the course of the years 2005, 2010, and 2012 have led to concern

about waning immunity to the vaccine and to the recommen-

dation that an extra booster immunization be given (see

“Prevention”).

A number of components play a job within the pathogenesis:

(1) Attachment of the organism to the cilia of the epithelial

cells is mediated by a protein on the pili referred to as filamentous hem-

agglutinin. Antibody towards the filamentous hemagglutinin

inhibits attachment and protects towards illness.

(2) Pertussis toxin stimulates adenylate cyclase by catalyzing

the addition of adenosine diphosphate ribose—a course of referred to as

ADP-ribosylation—to the inhibitory subunit of the G protein

complicated (Gi

protein). This ends in extended stimulation of

adenylate cyclase and a consequent rise in cyclic adenosine

monophosphate (AMP) and in cyclic AMP–dependent protein

kinase exercise. This ends in edema of the respiratory mucosa

that contributes to the extreme cough of pertussis. The toxin additionally

has a website that mediates its binding to receptors on the sur-

face of respiratory tract epithelial cells. It’s an A-B subunit

toxin.

Pertussis toxin additionally causes a placing lymphocytosis in

the blood of sufferers with pertussis. The toxin inhibits sign

transduction by chemokine receptors, leading to a failure of

lymphocytes to enter lymphoid tissue such because the spleen and

lymph nodes. As a result of the lymphocytes don’t enter lymphoid

tissue, there is a rise of their quantity within the blood (see

the dialogue of chemokines in Chapter 58). The inhibition of

sign transduction by chemokine receptors can be brought on by

ADP-ribosylation of the Gi

protein.

(3) The organisms additionally synthesize and export adenylate

cyclase. This enzyme, when taken up by phagocytic cells (e.g.,

neutrophils), can inhibit their bactericidal exercise. Bacterial

mutants that lack cyclase exercise are avirulent.

(4) Tracheal cytotoxin is a fraction of the bacterial peptido-

glycan that damages ciliated cells of the respiratory tract. Tra-

cheal cytotoxin seems to behave in live performance with endotoxin to

induce nitric oxide, which kills the ciliated epithelial cells.

Medical Findings

Whooping cough is an acute tracheobronchitis that begins with

gentle higher respiratory tract signs adopted by a extreme

paroxysmal cough, which lasts from 1 to 4 weeks. The parox-

ysmal sample is characterised by a collection of hacking coughs,

accompanied by manufacturing of copious quantities of mucus, that

finish with an inspiratory “whoop” as air rushes previous the narrowed

glottis. Regardless of the severity of the signs, the organism is

restricted to the respiratory tract and blood cultures are nega-

tive. A pronounced leukocytosis with as much as 70% lymphocytes is

seen. Though central nervous system anoxia and exhaustion

can happen on account of the extreme coughing, demise is principally due

to pneumonia.

The basic image of whooping cough described above

happens primarily in younger kids. In adults, B. pertussis infec-

tion usually manifests as a paroxysmal cough of various severity

lasting weeks. The attribute whoop is usually absent, main

to issue in recognizing the cough as brought on by this organ-

ism. Within the right scientific setting, adults with a cough lasting

a number of weeks (usually referred to as the 100-day cough) must be evalu-

ated for an infection with B. pertussis.

Laboratory Prognosis

The organism may be remoted from nasopharyngeal swabs taken

in the course of the paroxysmal stage. Bordet-Gengou1

medium used for

this objective comprises a excessive proportion of blood (20–30%) to

inactivate inhibitors within the agar. Identification of the remoted

organism may be made by agglutination with particular antiserum

or by fluorescent antibody staining. Nevertheless, the organism

grows very slowly in tradition, so direct fluorescent antibody

staining of the nasopharyngeal specimens can be utilized for diag-

nosis. Polymerase chain response–primarily based assessments are speedy, particular,

and extremely delicate and must be used if obtainable.

Isolation of the organism in sufferers with a protracted cough

is usually tough. Serologic assessments that detect antibody within the

affected person’s serum can be utilized for prognosis in these sufferers.

Remedy

Azithromycin is the drug of alternative. Word that azithromycin

reduces the variety of organisms within the throat and reduces

the chance of secondary issues however has little impact on the

course of the illness on the “extended cough” stage as a result of the

 

toxins have already broken the respiratory mucosa. Assist-

ive care (e.g., oxygen remedy and suction of mucus) in the course of the

paroxysmal stage is essential, particularly in infants.

Prevention

There are two forms of vaccines: an acellular vaccine containing

purified proteins from the organism and a killed vaccine con-

taining inactivated B. pertussis organisms. The acellular vaccine

comprises 5 antigens purified from the organism. It’s the vac-

cine presently utilized in america. The primary immunogen

on this vaccine is inactivated pertussis toxin (pertussis toxoid).

The toxoid within the vaccine is pertussis toxin that has been inacti-

vated genetically by introducing two amino acid adjustments, which

eliminates its ADP-ribosylating exercise however retains its antige-

nicity. It’s the first vaccine to include a genetically inactivated

toxoid. The opposite pertussis antigens within the vaccine are filamen-

tous hemagglutinin, pertactin, and fimbriae varieties 2 and three. The

acellular vaccine has fewer uncomfortable side effects than the killed vaccine

however has a shorter length of immunity.

The pertussis vaccine is normally given mixed with diph-

theria and tetanus toxoids (DTaP) in three doses starting

at 2 months of age. A booster at 12 to fifteen months of age and

one other on the time of coming into faculty are beneficial.

As a result of outbreaks of pertussis have occurred amongst teenag-

ers, a booster for these between 10 and 18 years previous is recom-

mended. This vaccine, referred to as Boostrix, comprises diphtheria and

tetanus toxoids additionally. One other vaccine referred to as Adacel additionally con-

tains diphtheria and tetanus toxoids. A pertussis booster dose is

beneficial for adults as effectively. To guard newborns, pregnant

girls ought to obtain pertussis vaccine. Antipertussis IgG will

go the placenta and shield the new child.

The killed vaccine is now not utilized in america

as a result of it’s suspected of inflicting numerous uncomfortable side effects, together with

postvaccine encephalopathy at a fee of about one case per million

doses administered. The killed vaccine is in use in lots of nations

aside from america.

Azithromycin is beneficial in prevention of illness in uncovered,

unimmunized people. It must also be given to immunized

kids youthful than 4 years who’ve been uncovered as a result of

vaccine-induced immunity will not be utterly protecting.

LEGIONELLA

Illness

Legionella pneumophila (and different legionellae) causes pneu-

monia, each locally and in hospitalized immuno-

compromised sufferers. The genus is called after the well-known

outbreak of pneumonia amongst folks attending the American

Legion conference in Philadelphia in 1976 (Legionnaires’

illness).

Essential Properties

Legionellae are gram-negative rods that stain faintly with the

customary Gram stain. They do, nevertheless, have a gram-negative

kind of cell wall, and growing the time of the safranin counter-

stain enhances visibility. Legionellae in lung biopsy sections do

not stain by the usual hematoxylin-and-eosin (H&E) pro-

cedure; due to this fact, particular strategies, such because the Dieterle silver

impregnation stain, are used to visualise the organisms.

Throughout the 1976 outbreak, preliminary makes an attempt to develop the

organisms on bizarre tradition media failed. It is because the

organism requires a excessive focus of iron and cysteine.

Tradition media supplemented with these vitamins will help

progress.

Legionella pneumophila causes roughly 90% of pneu-

monia attributed to legionellae. There are 16 serogroups of

L. pneumophila, with most circumstances brought on by serogroup 1 organisms.

There are about 30 different Legionella species that trigger pneumo-

nia, however a lot of the remaining 10% of circumstances are brought on by two

species, Legionella micdadei and Legionella bozemanii.

Pathogenesis & Epidemiology

Legionellae are related mainly with environmental water

sources akin to air conditioners and water-cooling towers.

Outbreaks of pneumonia in hospitals have been attributed to

the presence of the organism in water faucets, sinks, and show-

ers. Legionellae can replicate to massive numbers in free-living

amebas in these water sources. The amebas additionally improve the

survival of legionellae. Beneath opposed environmental condi-

tions, the amebas encyst, making certain each their very own survival and

the survival of the intracellular legionellae as effectively.

The portal of entry is the respiratory tract, and pathologic

adjustments happen primarily within the lung. Nevertheless, in extreme circumstances,

bacteremia happens, accompanied by injury to the vascular

endothelium in a number of organs, particularly the mind and kid-

neys. The most important virulence issue of the organism is lipopolysac-

charide (endotoxin). No exotoxins are produced.

The standard candidate for Legionnaires’ illness is an older

man who smokes and consumes substantial quantities of alcohol.

Sufferers with acquired immunodeficiency syndrome (AIDS),

most cancers, or transplants (particularly renal transplants) or sufferers

being handled with corticosteroids are predisposed to Legionella

pneumonia, which signifies that cell-mediated immunity

is an important protection mechanism. Regardless of airborne

transmission of the organism, person-to-person unfold does

not happen, as proven by the failure of secondary circumstances to happen in

shut contacts of sufferers.

Medical Findings

The scientific image can differ from a light influenzalike sickness

to a extreme pneumonia accompanied by psychological confusion,

nonbloody diarrhea, proteinuria, and microscopic hematuria.

Though cough is a outstanding symptom, sputum is steadily

scanty and nonpurulent. Hyponatremia (serum sodium ≤130

mEq/L) is a vital laboratory discovering that happens extra

usually in Legionella pneumonia than in pneumonia brought on by

different micro organism. Most circumstances resolve spontaneously in 7 to 10 days,

however in older or immunocompromised sufferers, the an infection can

be deadly.

Legionellosis is an atypical pneumonia2

and should be dis-

tinguished from different related pneumonias akin to Mycoplasma

pneumonia, viral pneumonia, psittacosis, and Q fever.

Pontiac fever is a light, flulike type of Legionella an infection

that doesn’t lead to pneumonia. The title “Pontiac” is

derived from town in Michigan that was the positioning of an out-

break in 1968.

Laboratory Prognosis

Sputum Gram stains reveal many neutrophils however no micro organism.

The organism fails to develop on bizarre media in a tradition of

sputum or blood, however it can develop on charcoal-yeast agar, a spe-

cial medium supplemented with iron and cysteine. Prognosis

normally depends upon a big improve in antibody titer in

convalescent-phase serum by the oblique immunofluorescence

assay. Detection of L. pneumophila antigens within the urine is a

speedy means of creating a prognosis. The urinary antigen check is

obtainable just for serogroup 1 organisms. If tissue is out there, it

is feasible to display Legionella antigens in contaminated lung

tissue through the use of fluorescent antibody staining. The cold-agglu-

tinin titer doesn’t rise in Legionella pneumonia, in distinction to

pneumonia brought on by Mycoplasma.

Remedy

Azithromycin or erythromycin (with or with out rifampin) is

the remedy of alternative. Sure fluoroquinolones, akin to levo-

floxacin and trovafloxacin, are additionally medicine of alternative. These medicine

are efficient not solely towards L. pneumophila but additionally towards

Mycoplasma pneumoniae and Streptococcus pneumoniae. The

organism steadily produces β-lactamase, and so penicillins

and cephalosporins are much less efficient.

Prevention

Prevention entails lowering cigarette and alcohol consump-

tion, eliminating aerosols from water sources, and lowering the

incidence of Legionella in hospital water provides through the use of excessive

temperatures and hyperchlorination. There is no such thing as a vaccine.

ACINETOBACTER

Acinetobacter species are small coccobacillary gram-negative

rods discovered generally in soil and water, however additionally they colonize

the pores and skin and higher respiratory tract. They’re opportunistic

pathogens that readily colonize sufferers with compromised

host defenses. Acinetobacter baumannii, the species normally

concerned in human an infection, causes illness mainly in a hospital

setting normally related to respiratory remedy tools

(ventilator-associated pneumonia) and indwelling catheters.

Pneumonia and urinary tract infections are probably the most frequent

2

A pneumonia is atypical when its causative agent can’t be remoted on ordi-

nary laboratory media or when its scientific image doesn’t resemble that of

typical pneumococcal pneumonia.

manifestations. Laboratory prognosis is made by culturing the

organism.

Acinetobacter baumannii is remarkably antibiotic resistant,

and a few isolates are immune to all identified antibiotics. Imipe-

nem is the drug of alternative for infections brought on by prone

strains. Colistin is beneficial in carbapenem-resistant strains. There

isn’t any vaccine. Earlier genus names for this organism embody

Herellea and Mima.

SELF-ASSESSMENT QUESTIONS

1. Your affected person is a 75-year-old man who has smoked cigarettes

(two packs a day for greater than 50 years) and consumed alcoholic

drinks (a six pack of beer every day) for many of his grownup life. He

now has the indicators and signs of pneumonia. Gram stain of

the sputum reveals neutrophils however no micro organism. Colonies seem

on buffered charcoal yeast (BYCE) agar however not on blood agar.

Which one of many following micro organism is probably to be the trigger

of his pneumonia?

(A) Bordetella pertussis

(B) Haemophilus influenzae

(C) Klebsiella pneumoniae

(D) Legionella pneumophila

(E) Pseudomonas aeruginosa

2. Relating to the affected person in Query 1, which one of many following is

the most effective antibiotic to deal with the an infection?

(A) Azithromycin

(B) Ceftriaxone

(C) Gentamicin

(D) Metronidazole

(E) Piperacillin/tazobactam

3. Your affected person is a 6-year-old boy who’s complaining that his ear

hurts. His mom says this started yesterday and that he has a fever

of 103°F. On bodily examination, you see a perforated eardrum that’s

exuding a small quantity of pus. Utilizing a swab, you get hold of a sam-

ple of the pus and do a Gram stain and tradition. The Gram stain

reveals small coccobacillary rods. There is no such thing as a progress on a blood

agar plate, however a chocolate agar plate supplemented with X and

V components grows small grey colonies. Which one of many following

micro organism is the probably explanation for his otitis media?

(A) Bordetella pertussis

(B) Haemophilus influenzae

(C) Klebsiella pneumoniae

(D) Legionella pneumophila

(E) Pseudomonas aeruginosa

4. It’s time to play “What’s my title?” I’m a small gram-negative

rod that causes an essential respiratory tract illness. I produce

an exotoxin that ADP-ribosylates a G protein. One exceptional

function of my illness is a superb improve in lymphocytes. I don’t

trigger illness generally in america now due to the

widespread use of the vaccine that induces antibodies towards 5

of my proteins, one in every of which is the exotoxin. The id of the

thriller organism is usually possible which one of many following?

(A) Bordetella pertussis

(B) Haemophilus influenzae

(C) Klebsiella pneumoniae

(D) Legionella pneumophila

(E) Pseudomonas aeruginosa

5. Your affected person is a 75-year-old lady with a 110-pack-year historical past

of cigarette smoking who now has a fever of 39°C and a cough

productive of yellowish sputum. Gram stain of the sputum exhibits

small gram-negative rods. There is no such thing as a progress on blood agar, however

colonies do develop on chocolate agar supplemented with hemin

and NAD. Which one of many following micro organism is the probably

explanation for her pneumonia?

(A) Bordetella pertussis

(B) Haemophilus influenzae

(C) Klebsiella pneumoniae

(D) Legionella pneumophila

(E) Pseudomonas aeruginosa

6. Your affected person is a 5-year-old boy with a excessive fever and indicators of

respiratory tract obstruction. Visualization of the epiglottis exhibits

irritation characterised by marked swelling and “cherry-red”

look. Which one of many following is the most effective antibiotic to

deal with the an infection?

(A) Ampicillin

(B) Ceftriaxone

(C) Doxycycline

(D) Gentamicin

(E) Metronidazole

ANSWERS

(1) (D)

(2) (A)

(3) (B)

(4) (A)

(5) (B)

(6) (B)

SUMMARIES OF ORGANISMS

Transient summaries of the organisms described on this chapter

start on web page 653. Please seek the advice of these summaries for a speedy

evaluation of the important materials.

PRACTICE QUESTIONS: USMLE &

COURSE EXAMINATIONS

Questions on the subjects mentioned on this chapter may be discovered

within the Medical Bacteriology part of Half XIII: USMLE

(Nationwide Board) Observe Questions beginning on web page 715. Additionally

see Half XIV: USMLE (Nationwide Board) Observe Examination