Gram Negative Rods
Related to the respiratory tract
Three medically important gm neg rods are
associated with the diseases of the respiratory tract.
They are Haemophilus influenzae, Bordetella
pertussis and Legionella pneumophia.
H.influenzae and B.pertussis found only in humans.
L.pneumophila found in water sources.
Important cause of Upper respiratory tract infections
like otitis media, sinusitis, conjunctivitis and
Sepsis in children.
Causes pneumonia in adults with obstructive lung
H.ducreyi is an agent causing Chancroid (STD).
H.influenzae used to be a leading cause of meningitis
in children, but the incidence is greatly reduced due
to an effective conjugate vaccine.
H.influenzae is a small. Gm neg rod.
It has a polysaccharide capsule.
Along with pneumococcus and meningococus it is
the third important encapsulated pyogens.
Six serotypes based on their capsular antigen.
Type b causes the most severe, invasive diseases such
as meningitis and sepsis.
Unencapsulated strains usually cause a non-invasive
disease of the upper respiratory tract such as sinusitis
and otitis media.
Growth on chocolate agar with heme (factor X) and NAD (factor V)
for adequate energy production.
Pathogenesis involves the antiphagocytic capsule and endotoxin. No
It produces IgA protease that degrades secretory IgA, facilitating its
attachment to the respiratory tract mucosa. After establishing itself
there, it can now enter the blood stream and spread to the meninges.
Encapsulated type b strains cause 95% of the meningitis caused by
Its route of entry is through inhalation or air borne droplets into the
respiratory tract, causing otitis media, sinusitis or pneumonia.
Infects only humans. No animal reservoir.
For meningitis: Symptoms are typically similar to
pneumococcal and meningococcal species, like fever,
headache, stiff neck along with drowsiness.
Children between 6 months to 6 years are most
susceptible, as they lose maternal IgG and generate
sufficient antibodies against the capsular antigens
They are second only to pneumococcus as the cause of Sinusitis and Otitis media.
Other serious infections include arthritis, cellulitis and sepsis (sepsis especially in
Chocolate agar with X and V- factors sufficient identification.
Other identification to identify capsular antigen such as Quellung reaction, fluorescent
antibody staining, slide agglutination.
Drug of choice for H.influenzae infections is Ceftriaxone as 20-30% strains produce β
Antibiotic treatment should be prompt as infection can be followed by a neurologic
involvement like subdural empyema.
Fatality rate of 90% in meningitis, if untreated.
Upper respiratory tract diseases like otitis media and sinusitis treated with Amoxicillinclavulanate or teimethoprim-sulfamethoxazole.
A more effective conjugated vaccine containing the
type b capsular polysaccharide conjugated to
diphtheroid toxoid or other carrier protein is
available. Depending on the carrier protein can be
given to the age group of 2 and 15 months and is safe.
Rifampin for close contacts of the patients as better
secreted in the saliva than ampicillin.
B.pertussis causes Whooping cough.
They are small, encapsulated gm neg rods.
I) The orgs. attach to the cilia of the epithelial cells of the upper respiratory
tract but do not invade the underlying tissue. This attachment is mediated by
a protein on the pili called ‘filamentous hemagglutinin’. Antibodies against
these hemagglutinins offer protection.
Decreased cilia activity followed by death of the ciliated cells are imp aspects
Highly contagious and spreads through air borne droplets during severe
A pathogen only for humans.
II) Pertussis toxin binds with its B-sub unit and ADP-
ribosylates the Gi protein (the inhibitory unit of G protein
complex), inhibits the inhibitory subunit and with
stimulation of adenylate cyclase and a consequent rise in
cAMP enhance the activity of the dependent protein
The ADP-ribosylation also inhibits the signal transduction
by chemokine receptors. This results in the failure of
lymphocytes to enter the lymphoid tissue such as spleen
and lymph nodes. This causes the striking phenomena of
Leucocytosis in the blood of patients.
III) The orgs also synthesize and export Adenylate
cyclase. This enzyme inhibits the bactericidal activity
of phagocytic cells like neutrophils. Bacterial mutants
lacking cyclase activity are avirulent.
IV) It is a tracheal cytotoxin (a fragment of the
bacterial peptidoglycan) that damages the ciliated
cells and act in concert with the endotoxin to induce
nitric oxide, which kills the ciliated epithelial cells.
Whooping cough is an acute tracheobronchitis that begins with a
mild upper respiratory tract symptoms.
This is followed by severe paroxysmal cough lasting for 1-4 weeks.
The paroxysmal pattern is characterized by a series of hacking cough
accompanied by large amount of mucous. This hacking cough ends
with an inspiratory whoop as air passes through the narrowed glottis.
Despite the severity, orgs restricted to the respiratory tract and blood
cultures are neg.
Pronounced leucocytosis with upto 70% lymphocytes are sen.
The whooping not seen in adults, and cough lasting several weeks(100
day cough) should be evaluated for B.pertussis infection.
Orgs. Isolated from the naso-pharyngeal swab taken
during the paroxysmal stage.
Bordet-Gengou agar with a high % of blood (20-50%) to
inactivate inhibitors in the agar.
Identification of the isolated org. by agglutination with
specific antiserum of by fluorescent antibody staining (can
be used for diagnosis as orgs grow very slowly)
PCR based tests are highly sensitive and specific and must
be used whenever possible.
Detecting antibodies in the serum of a case of prolonged
cough may be diagnostic.
Macrolides such as Erythromycin or Azithromycin
These antibiotics reduce the no. of the orgs. And
decrease the risk of secondary infection, but have
little influence on the course of the disease as the
toxins have already damaged the respiratory mucosa.
Supportive care such as oxygen therapy and suction
of mucous may be necessary.
2 vaccines are available:
A acellular vaccine containing 5 purified proteins from the
org( antigens). The maintoxoid ( antigenic part of the toxin) is the
inactivated pertussis toxin. They are inactivated genetically (first
vaccine to have genetically inactivated toxoid) by introducing 2 amino
acid changes in their protein. This eliminates their ADP-ribosylating
activity but retains their antigenicity. The other antigens are the
filamentous hemagglutinin, pertactin and fimbriae types 2 and 3. The
acellular vaccine has fewer side effects.
Pertussis vaccine given in combination with diphtheria and tetanus
toxoids(DTaP) in 3 doses from 2 months of age (2,4,6 mths of age)
with boosters at 1 and 6 years of age.
A killed vaccine containing killed orgs themselves.
Legionella pneumophila and other legionellae causes pneumonia both
community acquired and hospital acquired in immunocompromised
patients. Famous Legionaire’s disease among people attending the
American legion convention in 1976.
Legionella are gm neg rods that stain faintly with gm stain. They do
however have a gm neg type cell wall.
Legionellae lung biopsy sections stained by Dieterle silver
impregnation stain to visualize orgs. As do not stain with the standard
hematoxylin and eosin (H and E) procedure.
Require a high concentration of iron and cysteine, hence the charcoal
yeast agar, which has been supplemented by these.
L.pneumophila cause 90% of the pneumonia caused by this genus.
Many spp upto 30 are known,L.micdadei and L.bozemanii are two
other species that account for most of the remaining 10%.
The portal of entry is the respiratory tract through air
conditioners and water cooling towers (environmental water
Pathological changes are primarily in the lungs. In severe case,
bacteremia may result accompanied by damage to the vascular
endothelium in multiple organs, especially brain and kidneys.
Major virulent factor is a LPS (endotoxin).
Cell-mediated immunity is the most defense mechanism and
individuals with compromised cell mediated immunity like
cancer, AIDS or transplant patients(on corticosteroids), old
smoker and drinking individual are all predisposed to this
Person to person spread does not occur.
Clinical manifestations vary from mild influenza like to severe
pneumonia accompanied by mental confusion, non bloody diarrhea,
proteinuria, and microscopic hematuria.
Although cough is prominent, mucous is scant and non purulent.
Hyponatremia (serum sodium < or= 130mEq/L) is an imp. Lab finding
that occurs more in Legionellosis than other pneumonia.
Most cases resolve spontaneously in 7-10 days, but can be fatal in
older and immunocompromised individuals.
Legionellosis is an Atypical pneumonia hence has to be distinguished
from other atypical pneumonia like Mycoplasma pneumonia, viral
pneumonia, psittacosis and Q-fever.
Pontiac fever is a mild flu like infection of legionella. It does not result
Sputum gm stain reveal many neutrophils but no orgs.
Grows on charcoal yeast agar supplemented with iron and
Detecting antigens in urine is a rapid way of diagnosis.
It is possible to demonstrate legionella antigens in the
infected lung tissue by fluorescent antibody staining.
Cold agglutinin titer (patients develop auto immune
antibodies that agglutinate human cells at 4 degree
centigrade and not at 37 degrees.)does not rise as in
pneumonia caused by Mycoplasma.
Azithromycin or Erythromycin with or without
Rifampin is treatment of choice.
Fluoroquinolones such as Levofloxacin and
trovafloxacin also drugs of choice.
These drugs effective against Mycoplasma and
Stre.pneumoniae as well.
Penicillins and cephalosporins less effective as orgs
Eliminating aerosols from water sources and in
hospital water sources by using high temp and