Atypical Pneumonia

Atypical Pneumonia

Microbiology and Parasitology

Rachelle P. Mendoza, mD

ATYPICAL PNEUMONIA

 Also called “walking pneumonia”

 Versus typical pneumonia, it is caused by

usual bacteria (streptococcus,

staphylococcus, haemophilus)  Arose during the antibiotic era:

 Not responsive to usual antibiotics (penicillin)

 Could not be attributed by Gram stain or culture to a known bacterial cause Note: Penicillin is the drug of choice for TYPICAL pneumonia

A diseased bronco-alveolar complex (patients with pneumonia) presents with excessive mucous production (crackles) and inflamed airways (wheezing)

Etiologic Agents

 Most common:

 Mycoplasma (most common)  Chlamydia  Legionella  Viruses  Fungi  Parasites Clinical Features

 Two unifying features:

 Non-lobar, patchy, or interstitial pattern on chest radiography

 Failure to identify a causative organism on Gram stain or culture of sputum  Phases:

 Active hyperemia – engorgement of arterial blood vessels

 Red hepatization – neutrophils, fibrin and RBC fill alveoli

 Gray hepatization – fibrin and exudates (empyema)

 Resolution  Clinical outcomes:

 Mild (immunocompetent):

 Recover within 7 days with treatment

 Severe (with comorbidities

/immunocomrpomised):  Requires hospitalization  May lead to complications  Complications:

 CNS infections, such as meningitis, myelitis and encephalitis

 Hemolytic anemia  Severe lung disease

Note: The phases presented above are nice-to-know and are important only in pathology and for board exam purposes.

Atypical Pneumonia Typical Pneumonia

Low grade fevers Dry cough Shortness of breath

Hemoptysis

High fever and chills Productive cough

CHLAMYDIACEAE

 Small, Gram negative, obligate intracellular bacteria

 3 species:

 Chlamydophila pneumoniae  Chlamydophila psittaci  Chlamydia trachomatis  All can cause pneumonia  Cannot synthesize ATP  Cell wall lacks muramic acid

Chlamydophila pneumoniae

 Also known as TWAR (Taiwan acute respiratory agent)

 From the names of the two original isolates – Taiwan (TW-183) and an acute respiratory isolate designated AR-39

 The first known case of infection with C. pneumoniae was a case of sinusitis in Taiwan

 Causes the following:

 Respiratory infections (pharyngitis, bronchitis, pneumonia) - accounts for 5-10% of cases

 Meningoencephalitis  Arthritis

 Myocarditis

 Guillain-Barre syndrome

 A rare disorder that causes you immune system to attack your peripheral nervous system (PNS). This often leads to muscle paralysis (ascending), usually following an infection

 Common CSF findings:

albuminocytologic dissociation  Chronic infection may be a risk factor for

atherosclerosis  Complicated life cycle

 Mode of transmission: respiratory secretions

 Infects smooth muscles, endothelial cells, coronary artery and macrophages

 Epidemiology:

 8% in North America, 7% in Europe, 6% in Latin America and 5% in Asia

 M > F; common in ages 7-40  Reinfection common in elderly  Clinical presentation:

 Incubation: 3-4 weeks  Gradual onset, biphasic  Signs/symptoms:

 Scant sputum  Cough

 Hoarseness  Headache

 Rhonchi and rales  Sinus tenderness

Chlamydia Life Cycle

 Exist in two forms in order to cause a disease

 Elementary body  Infectious due to:

 Environmentally (extacellularly) stable

 Can exist outside the cell but it cannot replicate

 Can attach to a host cell

 Have the required attaching proteins

 Upon attachment, it will be phagocytosed by the cell

 The elementary body will secrete substances that will prevent lysosomal fusion with the phagocyte to form a phagosome

 Elementary body will reorganize and will transform into a reticulate body  Reticulate body

 Larger structure  Can replicate

 Will use the ATP of the host cell to produce proteins necessary for its replication

 Diagnostic form

 One life cycle will take about 48 hours to complete

Note: When the ATP stores of the host is depleted, reticulate bodies will transform back to elementary bodies

Chlamydophila psittaci

 Mode of transmission: respiratory secretions via aerosol or direct contact  Birds known to cause ornithosis: cockatiels,

parrots, parakeets, macaws, chickens, ducks, turkeys, pigeons and sparrows  Epidemiology:

 9-25 cases/year in US

 Anyone exposed to birds is at risk  Clinical presentation:  Incubation: 5-14 days  Abrupt onset  Signs/symptoms:  Non-productive cough  Chest pain

 Fever (Tmax 40) – most common

 Erythematous, blanching,

maculopapular rash (horder spots)  Splenomegaly

 Hepatitis (most common),

meningitis, DIC, reactive arthritis

Chlamydia trachomatis

 Most common cause of STD worldwide  Mode of transmission: passage thru infected

birth canal  Causes:  Neonatal conjunctivitis  Nasopharyngitis  Otitis media  Pneumonitis  Epidemiology:  5-22% of pregnant women  30-50% of neonates

 15-25% present with clinical

conjunctivitis and/or

nasopharyngitis

 11-20% of infants develop symptomatic pneumonia before age of 8 weeks

 Clinical presentation:

 Usually among infants > 3 weeks old  Signs and symptoms

 Nasal obstruction and discharge  Cough (staccato)

 Tachypnea  Afebrile

 Scattered crackles with good breath sounds

 Conjunctivitis and otitis media

Diagnosis

 C. pneumoniae  Serology

 Chest X-Ray: lower lobe

infiltrates/consolidation  C. psittaci (CDC criteria)

 Isolation of the organism by culture (McCoy cell culture)

 Clinical illness with a 4-fold rise in antibodies

 Detection of an IgM titer of 16 or greater

 Chest X-Ray: lower lobe consolidation, pleural effusuion

 C. trachomatis

 Giemsa-stained smears

(conjunctiva/nasopharynx)  Serology

 Chest X-Ray: bilateral interstitial infiltrates with hyperinflation

Treatment

 Doxycycline  Drug of choice

 Not for children (<9 years old) and pregnant women

 Growth retardation  Macrolides

 Fluroquinolones

Prevention

 Avoid handling birds

 Treat birds with freed with

chlortetracycline

 Screen and treat pregnant patients and their partners

Legionella pneumophila

 Gram negative, facultative intracellular bacteria

 Non-encapsulated, aerobic with a single polar flagellum

 Requires cysteine and iron  Found naturally in water system  Natural host: protozoans

 Humans are dead-end, accidental host  Transmitted by: inhalation of mist/vapor

from a water system  Causes:

 Legionnaire’s disease  Pontiac fever

Risk Factors

 Exposure to whirpool spas  Immunosuppression  Cigarette smoking  Renal or hepatic failure  Diabetes

 Systemic malignancy

 Other factors: old age (>50), cancer and alcohol intake

Pathogenesis

 Once the Legionella is phagocytosed, the phagosome vacuole is surrounded by vesicles coming from the rER

 Protects the bacteria from lysosome fusion

 Lysosomes will surround the vacuole, releasing protein materials into the vacuole for the use of the Legionella

Virulence Factors  Beta-lactamases  Exotoxins:  Hemolysins  Cytotoxin  Deoxyribonuclease  Ribonuclease  Protease  Endotoxin  Flagella

Pontiac Fever vs. Legionnaire’s Disease Legionnaire’s Pontiac

Clinical

features cough, fever Pneumonia,

Flu-like illness (fever, chills, malaise) without pneumonia Radiographic pneumonia Yes No Incubation

period 2-14 days after exposure after exposure 24-72 hours Etiologic agents Legionella species Legionella species Attack rate < 5% > 90% Isolation of

organism Possible Never

Outcome Hospitalization _common Hospitalization _uncommon

Case-fatality/rate: 5-30% Case-fatality/rate: 0% Diagnosis

 Culture – buffered charcoal yeast extract  Most sensitive and specific

 Paired serology

 Direct fluorescent antibody stain

Treatment  First line:  Levofloxacin  Azithromycin  Second line:  Cotrimazole  Tetracycline  Ciprofloxacin

Who to test for Legionnaire’s Disease

 Patients who have failed outpatient antibiotic therapy

 Patients with severe pneumonia in particular those requiring intensive care  Immunocompromised host with pneumonia  Patients with pneumonia in the setting of a

legionellosis outbreak  Patients with a travel history

 Patients suspected of healthcare-associated pneumonia

Mycoplasma pneumoniae

 Strict human pathogen, aerobe, no cell wall

 Cell membrane contains sterol, containing “spikes” and a terminal structure (P1 adhesin) for adhesion

 Pleomorphic shapes varying from 0.2 to 0.3 μm coccoid forms to rods 1 to 2 μm long  Requires cholesterol for culture

 For the synthesis of cell membrane  Generation time: 1 to 16 hours (binary

fission)

 Major antigenic determinants:

 Membrane glycolipids and proteins

Pathogenesis

 Incubation: 2-3 weeks

 Transmitted by: close contact/droplet  Adhesion to respiratory epithelium

 P1 adhesin interacts with sialated glycoprotein receptors at the base of cilia on the epithelial cell surface and on erythrocytes

 Ciliostasis occurs

 Destruction of cilia and epithelial cells  Stimulation of inflammatory cells to

migrate to the site of infection and release cytokines (superantigen):

 Tumor necrosis factor α  IL-1

Clinical Presentation

 Asymptomatic carriage  Tracheobronchitis

 Low-grade fever, malaise, headache and a dry, non-productive cough

 Acute pharyngitis

 Pneumonia (patchy bronchopneumonia seen on chest radiographs) – most common atypical pneumonia in young adults

Secondary complications

 Neurologic abnormalities (e.g.,

meningoencephalitis, paralysis, myelitis)  Pericarditis

 Haemolytic anemia  Arthritis

 Mucocutaneous lesions

Diagnosis

 Positive cold agglutinins (autoantibody to RBC)

 Culture – mulberry shaped colonies on sterol-containing agar (10 days)

 PCR/Nucleic acid probes

Treatment

 Erythromycin

 Tetracycline (particularly doxucycline)  Fluroquinolone

SUMMARY

Organism Characteristics Clinical Presentations Diagnosis Treatment

Chlamidiaceae

C. pneumoniae

 Small, Gram negative, obligate intracellular organisms

 Cannon synthesize ATP

 Lacks muramic acid

 Incubation:3-4 weeks

 Gradual onset, biphasic

 Serology

 Chest X-Ray: lower lobe infiltrates/consolidation  Doxycycline  Macrolides  Fluoroquinolones C. psittaci  Incubation: 5-14 days  Abrupt onset

 Isolation of the organism by culture (McCoy cell culture)

 Clinical illness with a 4-fold rise in antibodies

 Detection of an IgM titer of 16 or greater

 Chest X-Ray: lower lobe consolidation, pleural effusuion  Doxycycline  Macrolides  Fluoroquinolones C. tracomatis

 Usually among infants (>3 weeks old)

 Giemsa-stained smears (conjunctiva/nasopharynx)

 Serology

 Chest X-Ray: bilateral interstitial infiltrates with hyperinflation

 Doxycycline

 Macrolides

 Fluoroquinolones

Legionella

 Gram negative, facultative intracellular bacteria

 Non-capsulated, aerobic with single polar flagellum

 Requires cysteine and iron

 Legionnaire’s: Pneumonia, cough, fever

 Pontiac: Flu-like illness (fever, chills, malaise) without pneumonia

 Culture – buffered charcoal yeast extract

 Paired serology

 Direct fluorescent antibody stain

 First line: Levofloxacin, Azithromycin

 Second line: Cotrimoxazole, tetracycline, ciprofloxacin

Mycoplasma

 Smallest free-living bacteria

 Strict human pathogen, aerobe, no cell wall

 Cell membrane contains sterol  Pleomorphic  Requires cholesterol  Asymptomatic carriage  Tracheobronchitis  Acute pharyngitis  Pneumonia  Culture

 Positive cold agglutinins

 PCR/Nucleic acid probes

 Erythromycin

 Tetracycline

 fluoroquinolones

END

Not all recordings are included in this transcription due to the fact that Doc Mendoza speaks too fast, haha, but the important ones are included in this transcription. Good luck and God bless 2016!