Bacterial Atypical

(Interstitial) Pneumonia

group [ 51 – 75 ]
 Atypical (or interstitial) pneumonia refers to infection occurring in the interstitial space of
lungs. Cough is characteristically non-productive

Causative agents

Bacterial Viral
Mycoplasma pneumonia influenza viruses
Chlamydiae corona viruses
„ Legionella species Epstein–Barr virus
Coxiella burnetii adenoviruses
Francisella tularensis
Orientia tsutsugamushi
 Mycoplasma pneumonia
 Size: They are very small, 150–350 nm in size [ smallest bacteria ]
 They are filterable by bacterial filters
 They are free living in the environment „ and can grow on artificial cell-free culture
media
 They lack a rigid cell wall, which is replaced by a triple layered cell membrane
containing sterol
 Pleomorphic: They are highly pleomorphic, exist in coccoid, bacillary or filamentous or
even in helical forms (Spiroplasmas)
 Poorly gram stained , reproduced by binary fission and budding , non sporing non
flagellated and gliding motility
 L-form: As mycoplasmas lack cell wall permanently
 They were previously called as pleuropneumonia-like organisms (PPLO) and Eaton’s
agent (after the Monroe Eaton, who first isolated).
 Pathogenesis
Attachment of M. pneumoniae to the respiratory
mucosa is the most important step in pathogenesis, which is mediated
by its membrane bound adhesion proteins (e.g. cytadhesin P1 protein).
Following which, it induces injury to host respiratory tissue.
It is transmitted by air droplets and its incubation period is 2- 4 weeks
Clinical Manifestations
 Upper Respiratory Tract Infections (URTI)

URTI manifests as pharyngitis, tracheobronchitis or rarely as otitis media. It is acute in onset

and is 20 times more common than pneumonia.

Pneumonia
M. pneumoniae causes “atypical” community acquired interstitial pneumonia similar to
pneumonia caused by other agents, such as Chlamydophila pneumoniae, Legionella
pneumophila and viral pneumonia.
™ This is also referred to as Eaton agent pneumonia or primary atypical pneumonia or
walking pneumonia (as symptoms tend to be milder than pneumonia due to other agents)
Pneumonia develops in 3–13% of infected individuals; its onset is usually gradual
™ It is characterized by wheeze or rales, dry cough and peribronchial pneumonia with
thickened bronchial markings and streaks of interstitial infiltration on chest X-ray
Pneumonia usually is mild and self-limited, but can progress into severe disease with acute
respiratory distress syndrome (ARDS).
 Extrapulmonary Manifestations They are rare, occur either as a result of active
Mycoplasma infection (e.g. septic arthritis) or due to postinfectiousautoimmune
phenomena (e.g. Guillain–Barré syndrome). Various manifestations include:
 ™ Neurologic: Meningoencephalitis, encephalitis, Guillain–Barré syndrome and
aseptic meningitis
 ™Dermatologic: Skin rashes including erythema multiforme major (Stevens–Johnson
syndrome)
 ™ Cardiac: Myocarditis, pericarditis
 ™ Rheumatologic: Reactive arthritis
 ™ Hematologic: Anemia and hypercoagulopathy
Laboratory Diagnosis
 SPECIMEN COLLECTION
 Specimen Collection and Transport Ideal specimens are throat swabs, nasopharyngeal
aspirates, bronchial brushing, bronchoalveolar lavages (BAL) and lung biopsies.
 ™ Specimens must be placed immediately into the following transport media to avoid
drying:
 „ Standard Mycoplasma fluid medium containing fetal bovine serum, gelatine and
penicillin „
 Viral transport medium, added with ampicillin and cefotaxime. ™ Transportation
should be immediate. If delay is expected, then specimens should be stored at 4°C for
48 hours and beyond that at –70°C
 Culture
 Specimens are inoculated in culture
media (such as PPLO agar or PPLO
broth) and incubated at 37°C for 5–7
days or sometimes even up to 1–3 weeks.
 ™ In liquid medium (containing PPLO
broth): M. pneumoniae growth is
detected by turbidity and a color change
 ™ In solid medium (containing PPLO
agar): The colonies appear very small
(200–500 μm size), embedded on agar
surface described as fried egg appearance
colonies
 The colonies can be examined by hand
lens or use of special stain such as
Dienes’ staining (nonspecific stain that
imparts color to Mycoplasma colonies on
agar
 Identification
Accurate species identification from colonies is made either by conventional biochemical test or
by automated identification systems such as MALDI-TOF.
 Antigenic Detection
™ Direct immunofluorescence test: Detects Mycoplasma antigens directly in the clinical
specimens ™ Capture ELISA assay is available using monoclonal antibodies against P1 adhesion
antigen.
 Antibody detection
Specific antibody detection tests ;
 Antibodies detected after 1 week of illness and peek at 3-6 weeks
igM antibodies elevated in children with acute infection
In adults igA antibody detection is the method of choice
 Various specific antibodies detection are ;
 Immunofluorescence assays
 Latex agglutination test
 ELISA using protein p1 antigen
 Nonspecific Antibody Detection Tests
Heterophile agglutination tests such as Cold agglutination test and Streptococcus MG tests
were in use in the past; now obsolete as they are neither specific nor sensitive (positive
only in 30–50% of cases)

 Molecular Methods
 ™ PCR targeting M. pneumoniae specific 16S rRNA gene and P1 adhesion gene is
available
 Multipex pcr
 Real – time pcr
 Biofire filmarray

 Macrolides are drug of choice (oral azithromycin, 500 mg on day 1, then 250 mg on
days 2 to 5) ‰ Alternative drugs are as follows: Doxycycline , Respiratory
fluoroquinolones such as levofloxacin, moxifloxacin and gemifloxacin (not
ciprofloxacin)
Chlamydiae Pnemonia
 There are three Chlamydia species
 C. pneumoniae, C. psittaci, C. trachomatis; all capable
of causing atypical (interstitial) pneumonia
Psittacosis (Chlamydophila psittaci )
 C. psittaci is a pathogen of parrots and other psittacine birds causing psittacosis.
 ™ Reservoirs: Pet birds (parrots, parakeets, macaws, and cockatiels) and poultry (turkeys
and ducks) act as natural reservoir of infection and are involved in transmission of
infection to humans ™
 Mode of transmission: inhalation of aerosols from avian nasal discharges and from
infectious avian fecal or feather dust ™
 Clinical manifestations: Incubation period ranges from 5–19 days. It can present as—(1)
Respiratory manifestation (most common form), varies from a mild influenza-like
syndrome to an interstitial pneumonia, (2) rarely septicemia and typhoid-like syndrome
 Treatment: Tetracycline is the drug of choice, given 250 mg four times a day for at least 3
weeks to avoid relapse. Erythromycin (500 mg four times a day, per oral) is given
alternatively.
Chlamydophila pneumoniae
 C. pneumoniae is an exclusively human pathogen. strain – TWAR strain [Taiwan acute
respiratory strain] It is transmitted from person to person by inhalational route. It causes
various manifestations.
 ™ Atypical pneumonia: C. pneumoniae is a common cause of atypical (interstitial)
pneumonia accounting for 10% of cases of community-acquired pneumonia
 ™ Upper respiratory tract involvement is frequent, such as pharyngitis and sinusitis
 ™ Atherosclerosis: There is a strong evidence of association between C. pneumoniae and
atherosclerosis of coronary and other arteries ™
 Asthma and COPD: C. pneumoniae may cause exacerbations of bronchial asthma and
COPD (chronic obstructive pulmonary disease)
 ™ Treatment: Tetracycline or erythromycin (500 mg four times a day) is recommended
for 10–14 days.
Chlamydia trachomatis (Infant Pneumonia)

 C. trachomatis serotypes D to K can cause infant pneumonia. ™ It is an interstitial

pneumonia that develops within 3 weeks to 3 months of birth ™ Infection spreads from
conjunctiva to pharynx via the nasolacrimal duct ™ Infection via the eustachian tube may
cause otitis media
 ™ Treatment: Erythromycin is given orally at a dosage of 50 mg/kg per day in four divided
doses, for 2 weeks.
 Legionellosis
 Legionellae are fastidious, pleomorphic gram-negative, short rods, associated with
interstitial pneumonia, known as—Legionnaires’ disease

 Classification ™
 Out of several species infecting man, L. pneumophila is the most important species,
associated with 80–90% of human infections. It consists of 15 serogroups. Majority of
cases are associated with serogroup 1 followed by 4 and 6 ™
 Other species are rarely associated with human infection particularly in
immunocompromised state, such as L. micdadei (Pittsburgh pneumonia agent), L.
wadsworthii and L. longbeachae.
 ™ Transmission:
 Multiple routes have been proposed „
 Aspiration (predominant mode): It occurs either via oropharyngeal colonization or
directly via drinking of contaminated water
 „ Aerosols from contaminated air conditioners, nebulizers, and humidifiers
 „ Direct instillation into the lungs during respiratory tract manipulations
 „ There is no man-to-man transmission.
 ™ Predisposing factors for Legionella infections include:
 „ Smoking, alcoholism or chronic lung disease
 Advanced age
 „ Immunosuppression-transplantation,
 HIV infection, steroid therapy „
 Prior hospitalization „ Patients with nasogastric tubes or those undergoing surgery with
general anesthesia promotes aspiration
 Pathogenesis
 Following entry, legionellae
reach the lungs where they
are engulfed by alveolar
macrophages by a
mechanism called as coiling
phagocytosis. They invade
and grow within the alveolar
macrophages by inhibiting
phagosome-lysosome fusion.
Being intracellular organism,
cellular immunity is
responsible for the recovery
 Clinical Manifestations
 Pontiac Fever
it is an acute, flu-like illness characterized by malaise, fever, and headache. Incubation
period is about 24–48 hours. It is self-limiting, never develops into pneumonia.
 Legionnaires’ Disease (Pneumonia)
It is an interstitial atypical pneumonia with incubation period about 2–10 days. ™ It is
characterized by non-productive cough (with or without blood tinged), dyspnea, chest pain,
high fever and diarrhea ™ Chest X-ray shows pulmonary infiltrates ™ Legionella is among the
leading causes of pneumonia both in the community and hospital settings
 Extrapulmonary Legionellosis
Usually it results from blood-borne dissemination from the lung. ™ The most common
extrapulmonary site is heart (myocarditis, pericarditis and prosthetic valve endocarditis) ™
Other manifestations include sinusitis, peritonitis, pyelonephritis, skin and soft tissue infection
Laboratory Diagnosis
 ™ Direct microscopy: „
 Gram stain reveals numerous neutrophils but no organisms (as legionellae are poorly
stained, often missed or sometimes appear as faint pleomorphic gram-negative rods or
coccobacilli) „ Silver impregnation and Giemsa stains can be used „ Direct
immunofluorescence test using monoclonal or polyclonal sera is more specific but
sensitivity is poor than culture. It is more useful in advanced stage of disease „ Acid-fast
staining: L. micdadei is weakly acid fast
 ™ Culture:
 Culture is highly sensitive (80–90%) and
specific (100%) and provides definite
diagnosis „ Buffered charcoal, yeast extract
(BCYE) agar: Legionellae are highly
fastidious and grow on complex media, such
as BCYE agar after 3–5 days of incubation
at 37°C in 5% CO2
 „ Identification: Species identification of
Legionella from colonies is made either by
conventional biochemical tests or by
automated identification systems such as
MALDI-TOF.
 ™ Antibody detection:
 Primarily, serology is used for epidemiologic purpose (sero-prevalence estimation)
 „ Indirect immunofluorescent antibody test and enzyme immunoassays are available
 Antibodies usually appear late after 12 weeks; a single titer of 1:256 gives presumptive
evidence of Legionnaires’ disease
 „ Cross-reactivity has been observed with other Legionella species.
 ™ Urinary antigen test: Enzyme immunoassays are available to detect L. pneumophila
serogroup 1 specific soluble antigens in urine. Advantages include as follows:
 It is rapid, cheaper, easy to perform
 It is highly sensitive (70 to 90%), and specific (95– 100%)
 Antigen in urine is detectable shortly after the onset of symptoms and disappears over 10
months
 The test is not affected by prior antibiotic administration
 Molecular methods: BioFire FilmArray; automated multiplex PCR is available. Its
respiratory panel can simultaneously detect 22 pathogens including L. peumophila.

 TREATMENT
 Macrolides (especially azithromycin) and the respiratory quinolones (e.g. levofloxacin) are
now the antibiotics of choice.
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