Mid - Respiratory Tract Infections

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Bacterial causes of Community acquired pneumonia

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Most common:
Streptococcus pneumoniae, non-typeable H. influenzae, S. aureus, Streptococcus pyogenes, N. meningitidis, Moraxella catarrhalis, Klebsiella pneumoniae (and other gram negative rods).

May also be caused by:
Mycoplasma
pneumoniae, Chlamydia pneumoniae, Legionella species, influenza virus, respiratory syncytial virus, adenovirus, parainfluenza virus, etc.

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Outpatient Community acquired pneumonia

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Streptococcus pneumoniae
Mycoplasma pneumoniae
Haemophilus infleunzae
Chlamydophila pneumoniae
Respiratory viruses

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Inpatient (non-ICU)

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Streptococcus pneumoniae
Mycoplasma pneumoniae
Haemophilus infleunzae
Chlamydophila pneumoniae
Legionella species
Aspiration
Respiratory viruses

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Inpatient (ICU)

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Streptococcus pneumoniae
Staphylococcus aureus
Legionella species
Gram-negative bacilli
Haemophilus infleunzae

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Streptoccus pneumoniae

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Gram positive diplococci which occurs in pairs or short chains.

Common cause of pneumonia,
especially in the pediatric and elderly populations

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Streptoccus pneumoniae

Virulence factor

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The capsular polysaccharide is the most important virulence factor. In addition, there are protein adhesins that allow binding to epithelial cells in the oropharynx. Secretory IgA protease inhibits function of secretory IgA (which normally binds bacteria to mucin to facilitate clearance from the respiratory tract). Pneumolysin - creates pores in and destroys ciliated epithelial cells and hydrogen peroxide, a reactive 02 intermediate, causes tissue damage. Streptococus pneumoniae also has teichoic acid, peptidoglycan and pneumolysin which activate complement.

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Streptoccus pneumoniae

Clinical presentation

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The organism causes many clinical problems including pneumonia, meningitis, otitis media, sinusitis, bacteremia,
pericarditis, and arthritis.

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Streptoccus pneumoniae

Treatment

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Usually with Beta-lactam
antibiotics including penicillin, amoxicillin. Resistance is now common. Treat with vancomycin, cephalosporins, macrolides, quinolones. resistance is developing for these antibiotics as well

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Mycoplasma pneumoniae

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Walking pneumonia, x-ray appears worse than the patient looks clinically. Mycoplama is the smallest free-living bacteria. It does not have a cell wall, and the cell membrane contains sterols not present in other bacteria.

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Mycoplasma pneumoniae

Epidemiology

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Usually occur in children 5-9 years of age and young adults. does not follow a seasonal pattern.

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Mycoplasma pneumoniae

Treatment

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Because it does not have a cell wall, this organism is resistant to “cell wall” antibiotics such as penicillins, cephalosporins, vancomycin, and others.

Treatment is with erythromycin or tetracycline (or doxycyline children over 9 years old). Prevention is difficult since disease is spread by droplets and close contact and organisms are shed for weeks. Isolation is not feasible. No vaccines are available.

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Mycoplasma pneumoniae

Diagnosis

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M. pneumoniae is a strict aerobe and grows only on special enriched media. grows slowly e.g. 1-6 hours generation time.

Laboratory confirmation is usually by serology or PCR-research based. Bedside tests that suggest the diagnosis of mycoplasma include cold agglutinins (IgM antibodies that bind to the I antigen of the red cells).

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Mycoplasma pneumoniae

Virulence factors

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Mycoplasma has a unique protein, the P1 protein, that acts as an attachment factor and facilitates the attachment to the sialic receptors of the respiratory epithelium and to red cells. Toll–like receptor 2 is also important for binding to respiratory epithelium. Mycoplasma is interesting because it remains extracellular and interacts with the cilia in the respiratory tract causing both the cilia and the epithelial cells to be destroyed which leads to loss of these cells and then interference of normal airway clearance which leads to contamination of the airway with microbes which cause mechanical irritation and then chronic cough.

M pneumoniae also acts as a super antigen stimulating PMNs and macrophages to the site with subsequent release of cytokines including TNF α, IL-1 and IL-6.

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Mycoplasma pneumoniae

Transmission

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Infection is spread by droplets (hence outbreaks occur in close quarters e.g. college, military) and the incubation period is 2-3 weeks with infectious droplets being shed 2-8 days prior to developing symptoms.

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Mycoplasma pneumoniae

Symptoms

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low-grade temperatures (100-102), malaise, headache, dry, non-productive cough that is worse at night and persists for weeks.
Lower tract disease may occur in the form of tracheobronchitis and “atypical pneumonia” or walking pneumonia

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Chlamydophila pneumonias

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Chlamydia is an intracellular parasite because it uses the host energy, ATP, unlike other organisms. It resembles a Gram negative bacteria in that chlamydia has a trilaminar outer membrane that contains LPS even though it is not Gram(-).

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Chlamydia trachomatis pneumonia

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Neonatal pneumonia due to C. trachomatis usually presents between 1-3 months of life (usually 6 weeks). Infants present with a staccato-like cough, rapid respiratory rate, and often do not have fever. On physical examination, wheezing is rarely heard. Diagnostic evaluation reveals hyperinflation and diffuse infiltrates on chest radiograph and a peripheral eosinophilia.

An IgM antibody test for C. trachomatis with a titer of > 1:32 is strongly suggestive of disease. Children with disease consistent with C. trachomatis pneumonia should be started on therapy (erythromycin) while waiting for diagnostic test results. Infection in newborns may be prevented by screening and treating pregnant women.

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Chlamydia pneumoniae (TWAR)

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TWAR may cause pneumonia (up to 28% of school age pneumonias and <10% of adult cases of outpatient pneumonias), bronchitis and sinusitis (5% of cases) and infrequently pharnygitis (<1%).

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Chlamydia pneumoniae (TWAR)

Clinical presentation

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Disease may result after a prolonged incubation period of up to 21 days.
Respiratory disease due to C. pneumonia often has an indolent course beginning with non-specific upper respiratory symptoms such as rhinorrhea or sore throat and progressing to chronic cough that may persist for weeks despite appropriate antibiotic therapy. Patients are usually afebrile. Chest radiographs often show a lobar consolidation but disease may also present as a diffuse interstitial pattern, or with bilateral involvement with pleural effusions and lymphadenopathy. Patients usually have a normal peripheral white blood cell count.

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Chlamydia pneumoniae (TWAR)

Diagnosis

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Usually made with serologic testing using microimmunofluorescence tests to detect C. pneumonia specific antibody. IgM antibody develops within 4 weeks and IgG by 6 weeks. PCR testing of sputum, the pharynx or a pathologic specimen is very sensitive and provides a more prompt result.

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Chlamydia pneumoniae (TWAR)

Treatment

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Standard courses of azithromycin or clarithromycin
is often preferred to erythromycin or doxycycline due to ease of administration and fewer side effects. Either treatment has a clinical efficacy of > 90%. Levofloxacin (a quinolone) works too. Failures do occur and re-treatment may be necessary after a 10-14 day course.

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Chlamydia psittaci

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Many types of birds may carry and transmit this disease through respiratory droplets.

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Chlamydia psittaci

Clinical Presentation

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Atypical pneumonia in that the patient has mild clinical symptoms such as cough, fever, malaise and the chest radiograph appears worse than expected. Non-specific central nervous system findings may also be present such as headache, confusion, cranial nerve palsy (including sensorineural hearing loss), meningitis, and seizures. Hepatitis and pericarditis may be complications of this infection. On physical examination, many patients will have fever, pharyngeal erythema and rales on examination of the lungs. Horder’s spots may appear on the skin. These spots are pink blanching maculopapular lesions. Chest radiographs may show consolidation, a reticular nodular pattern, and/or hilar lymphadenopathy.

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Chlamydia psittaci

Treatment

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tetracycline 500 mg four times a day or doxycycline 100 mg twice a day for 10-21 days. Erythromycin is an alternative but is less efficacious. Most patients respond to therapy within 24 hours of starting medications.

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Legionella

Epidemiology

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Legionella is the cause of 2-6% of community acquired pneumonias. Disease due to legionella occurs sporadically and epidemically. Incidence peaks late summer to fall. People with greatest risk for disease are those with impaired cellular immunity and/or those with compromised pulmonary function e.g. elderly, transplants, neutropenic patients, smokers, alcoholics, etc and those at risk due to occupational exposure e.g. construction- working with moist environments and water systems (cooling towers, hot tubs, showers etc).

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Legionella

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Pleomorphic gram negative bacilli and don’t stain with common reagents and thus need Dieterle’s silver stain. They are fastidious organisms and grow in supplemented media (iron salts, L-cysteine). They are facultative intracellular ubiquitous aquatic saprophyte (live inside amoeba). Thus it is found contaminating sources of water e.g. air conditioning systems and water tanks.

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Legionella

Pathogenesis

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Inhaled and multiplies within macrophages and monocytes in the alveoli (intracellular). Flagellae and pili allow attachment to respiratory epithelium and macrophages
Once it binds to the complement receptor on alveolar macrophages and gets into the cell by endocytosis. Trafficking within the cell is due to dot (defective organelle trafficking) and icm (intracellular multiplication) genes which allow the organism to evade phagosome-lysosome fusion.
The bacilli proliferate in the lungs and produce proteolytic enzymes, phosphatase, lipase, and nuclease which kill the cell when the vacuole is lysed. This causes multifocal microabscess formation.

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Legionnaires’disease

Clinical presentation

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Symptomatic infection due to legionella may present as two different syndromes -- pneumonia or influenza like illness. Legionnaires’ disease is severe pneumonia due to legionella. Incubation period is up to 10 days and then symptoms manifest themselves abruptly with high fevers (105), rigors, cough (non-productive), headache etc. The pneumonia is usually multilobar with areas of microabscesses. As the disease progresses it spreads from lobe to lobe. Extrapulmonary manifestations include diarrhea, abdominal pain, nausea, mental confusion or delirum. Laboratory evaluation reveals high white cell counts (10-20,000) with a left shift in the majority of cases. Liver and renal functions may also be affected. Overall mortality is 15-20% depending on the immune function of the host. Death is usually due to respiratory or renal failure and/or shock.

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Legionella

Diagnosis

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Direct fluorescent antibody test (DFA). Legionella can be cultured on special media, buffered charcoal-yeast extract agar.

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Pontiac Fever

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Due to L. pneumophila causes a self-limited febrile illness like the flu (fevers, chills, myalgia, headaches etc.). Symptoms last 2-5 days and resolve spontaneously. It is called Pontiac fever after the town, Pontiac, Michigan, in which workers developed these symptoms in 1968

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Bordetella pertussis

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Organism responsible for pertussis or whooping cough -- an acute respiratory infection marked by episodic spasmodic coughing in the paroxysmal phase. It causes significant clinical disease such as bronchopneumonia especially in young children (<6 months).

Bordetella organisms are small, aerobic, fastidious, gram negative cocobacilli. It requires special media (including blood, charcoal and starch- also called Bordet-Gengou agar

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Bordetella pertussis

Transmission

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Spread primarily by respiratory droplets. The organism colonizes and rapidly multiplies in the mucus membrane of the respiratory tract. Bacteremia does not occur. Disease is caused by the toxins that cause local tissue damage.
B. Pertussis attaches to the ciliated epithelial cells in the respiratory tract. This is facilitated by the action of the pertussis toxin and filamentous hemagglutinin.

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Bordetella pertussis

Toxins

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Pertussis contains many toxins: pertussis toxin, adenylate cyclase toxin, heat labile toxin.
Pertussis toxin- ↑ CAMP, ↑ secretions (paroxysmal stage)
Adenylate cyclase and hemolysin toxin - Inhibit WBC chemotaxis, phagocytosis, and killing
Heat-labile toxin - Local tissue destruction
Tracheal cytotoxin - Destroys ciliated cells, IL-1 (fever), NO (kills epithelial cells)
Lipid A and Lipid X - -Activate alternative complement, cytokine release

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Bordetella pertussis

Clinical presentation

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Aerosolized droplets infect the host and after a 7-10 day
incubation period:
First Stage: Catarrhal stage - This stage resembles the common cold with rhinnorhea (runny nose), sneezing, malaise, anorexia, and low-grade fever.
Second Stage: Paroxysmal Stage: This stage occurs 1-2 weeks after symptoms have begun. During this stage, the patient characteristically coughs and “whoops” – that is a series of coughs followed by an inspiratory whoop. Vomiting after these coughing spasms is a common occurrence. Lymphocytosis is noted at this time.
Third Stage: Convalescent Stage - After 2-4 weeks, the cough is subsiding however other complications occur such as pneumonia (often due to other organisms that colonize the airway e.g. Streptococcus pneumoniae), seizures, and encephalopathy.

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Bordetella pertussis

Treatment

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Although B. pertussis is susceptible to erythromycin, antibiotics do not alter the course of the infection but may decrease the communicability. Thus treatment is usually supportive. Chemoprophylaxis is recommended for household contacts without regard to immune status or age.

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Legionella

Treatment

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Macrolide or levofloxacin