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-toknow and are important only in pathology and for board exam purposes. Atypical Pneumonia Low grade fevers Dry cough Shortness of breath Hemoptysis Typical Pneumonia 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

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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

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 Azithromycin prophylaxis

Chlamydophila psittaci
Causes respiratory psittacosis Host: birds, mammals 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
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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: Legionnaires 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. Legionnaires Disease Legionnaires Clinical features Radiographic pneumonia Incubation period Etiologic agents Attack rate Isolation of organism Outcome Pneumonia, cough, fever Yes 2-14 days after exposure Legionella species < 5% Possible Hospitalization common Pontiac Flu-like illness (fever, chills, malaise) without pneumonia No 24-72 hours after exposure Legionella species > 90% Never Hospitalization uncommon

Casefatality/rate: 5-30% Diagnosis

Casefatality/rate: 0%

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 Legionnaires 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
Smallest free-living bacteria 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 m coccoid forms to rods 1 to 2 m 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 IL-1 IL-6

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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

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SUMMARY Organism C. pneumoniae Characteristics Clinical Presentations Incubation:3-4 weeks Gradual onset, biphasic Diagnosis Serology Chest X-Ray: lower lobe infiltrates/consolidation 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 Giemsa-stained smears (conjunctiva/nasopharynx) Serology Chest X-Ray: bilateral interstitial infiltrates with hyperinflation Culture buffered charcoal yeast extract Paired serology Direct fluorescent antibody stain Treatment Doxycycline Macrolides Fluoroquinolones

C. psittaci Small, Gram negative, obligate intracellular organisms Cannon synthesize ATP Lacks muramic acid C. tracomatis Usually among infants (>3 weeks old)

Chlamidiaceae

Incubation: 5-14 days Abrupt onset

Doxycycline Macrolides Fluoroquinolones

Doxycycline Macrolides Fluoroquinolones First line: Levofloxacin, Azithromycin Second line: Cotrimoxazole, tetracycline, ciprofloxacin

Legionella

Mycoplasma

Gram negative, facultative intracellular bacteria Non-capsulated, aerobic with single polar flagellum Requires cysteine and iron Smallest free-living bacteria Strict human pathogen, aerobe, no cell wall Cell membrane contains sterol Pleomorphic Requires cholesterol

Legionnaires: Pneumonia, cough, fever Pontiac: Flu-like illness (fever, chills, malaise) without pneumonia 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!
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