Pulmonology Flashcards
Streptococcus pneuomoniae Virulence Factors
Encapsulated gram-positive coccus that are oval or lancet-shaped and are arranged in pairs or short chains.
They are alpha hemolytic due to pneumolysin (degrades hemoglobin; creates pores in host cell membranes and suppresses oxididated burst)
Lacks catalase
Virulent strains are covered with polysaccharide capsule (allows survival following phagocytosis; used for vaccine) and have surface protein adhesins that allow binding to oropharynx. They also secrete IgA proteases (avoid binding to mucus) and pneumolysin
Has two types of techoic acid-linked polysaccharides, C polysaccharide (precipitates CRP) and F antigen
Phosphocholine is unique to cell wall of S. pneumoniae and allows the cells bind to PAF receptors, get eaten, and be protected from host immune response.
Most damage to host is done by host defense, not by organism itself. This is augmented by amidase secreted by organism that facilitates shedding of its wall, increasing immune response.
First colonizes the oropharynx and then can spread to the lungs, paranasal sinuses, or middle ear.
Streptococcus pneumoniae Epidemiology
Common colonizer of throat and nasopharynx in healthy people, especially children. More common to see disease in cool months.
Disease is most common in young and elderly, both of which have less protective antibodies against the capsule.
Very often preceded by a viral disease like the flu as well as anything else that inhibits bacterial clearance.
Streptococcus pneumoniae Clinical Diseases
Pneumonia: develops when the bacteria multiply in alveolar spaces following aspiration. Erythrocytes, neutrophils, and macrophages follow organisms into alveolar spaces. Resolution occurs following anticapsular antibody development. Generally preceded by symptoms of a viral respiratory tract infection 1 to 3 days before onset of chills, chest pain, and productive blood tinged cough. Called lobar pneumonia because it normally is aspirated to lower lobes. Mortality is higher with S. pneuomoniae type 3, in elderly, and in those lacking a spleen. Pleural effusions are seen in 25 % of patients
Sinusitis and Otitis Media: normally preceded by a viral infection of the upper respiratory tract. Otitis media is more in children, the sinusitis is not age specific
Meningitis: leading cause of disease in children and adults. Mortality and severe neuro defects are 4 to 20 times higher with S. pneumo as compared to other organisms.
Bacteremia: occurs in 80% of patients with meningitis. Endocarditis may occus. Destruction of valve tissure also common.
Streptococcus pneumoniae Diagnosis and Treatment
Gram stain with quellung reaction (polyvalent anticapsular antibodies are mixed with bacteria then examined, leads to swelling of bacteria)
Pneumococcal C polysaccharide is excreted in urine and can be detected using a commercially prepared immunoassasy
Bile solubility test is also diagnostic (bile kills them) as is optochin (also kills them)
Treat with penicillin, fluoroquionolone, vancomycin combined with ceftriaxone
Also vaccinate susceptible populations with conjugated vaccine
Bacillus anthracis Immunology and Virulence
Gram-positive
large organism arranged as single or paired rods or as long, serpentine chains. Has a polypeptide (poly-D-glutamic acid) capsule which inhibits phagocytosis
Has three toxin protein components on a plasmid pXO1:
1) Protective antigen: forms a pore on the surface of the host cell that is capable of binding up to three EF or LF, leading to endocytosis. It is the most immunogenic of the three
2) edema factor: a calmodulin-dependent adenylate cyclase that increases cAMP resulting in edema
3) lethal factor: zinc-dependent protease that is capable of cleaving MAP kinase leading to cell death.
PA + EF = edema toxin. PA + LF = lethal toxin
Bacillus anthracis Epidemiology and Clinical Disease
Anthrax is a disease primarily of herbivores; we get it through contact with contaminated animals/animal products.
Acquired by inoculation (95%), ingestion, or inhalation (wool sorter’s disease, route of infection for bioterrorism).
Spores are weaponized by breaking them up into small, aerodynamic spores that can more easily reach the lower airways.
Cutaneous anthrax: starts with a painless papule at inoculation site that progresses to eschar. Massive edema may develop, mortality is 20% if untreated
Gastrointestinal anthrax: Nearly 100% fatal, symptoms depend on if it gets upper GI tract or lower
Inhalation anthrax: can be associated with prolonged latant period. Initial symptoms are nonspecific (flu-like). Second stage shows lots of edema, enlargement of mediastinal lymph nodes, respiratory failure, sepsis. Almost all cases proceed to shock and death within three days unless it is treated.
Bacillus anthracis Diagnosis and Treatment
One of few orgnanisms that can be seen when peripheral blood is Gram stained. They form long, thin strands that are nonmotile
It is difficult to tell apart from Bacillus cereus, but can do so by seeing if they colonies are hemolytic (cerues) or not (anthracis)
Capsule is not normally produced in culture
Forms “Medusa head” colonies (Uworld hits this a lot)
Treat with penicillin, doxycycline, or ciprofloxacin, not with sulfonamides or cephalosporins.
Vaccinate susceptible animals and burn the animals that die of anthrax, also vaccinate people that are likely to encounter the organism
Bacillus cereus
opportunistic pathogens that have relatively low capacities for virulence.
GI: Has two enterotoxins, one is heat stable and causes the emetic form of the disease (normally caused by eating contaminated rice; an intoxication), the other is heat-labile (similar action as V. cholerae) and causes the diarrheal form of disease (an actual infection, contaminated meat, vegetables or sauces). Treat symptoms
Ocular: three toxins implicated (necrotic toxin, cereolysin, phospholipase C) leads to rapid destruction of the eye. Normally follows a traumatic eye injury leading to soil in eye. Treat with vancomycin, clindamycin, ciprofloxacin, gentamicin
Don’t use penicillins and cephalosporins
Other: can cause IV catheter and CNS shunt infections. May be associated with ingestion of tea in immunocompromised.
It appears that the virulence pXO1 plasmid can be transferred from anthracis to cereus
Ubiquitous organisms found in soil, often found as insignificant contaminate in lab samples
Corynebacterium diptheriae Immunology and Virulence
Coryneform (“club shaped”) bacteria that is an irregularly staining, pleomorphic rod. Metachromatic granules have been pbserved following staining with methylene blue. Species is subdivided into four biotypes: belfanti, intermedius, gravis and mitis. The last two are associated with disease
Diptheria toxin: exotoxin produced at site of infection. It is introduced into orgnaism by a lysogenic bacteriophage (B-phage). Example of the classic A-B toxin. Receptor (heparin-binding epidermal growth factor receptor) binding and endocytosis are on B, catalytic component is on A. A inactivates elongation factor 2, halting host protein synthesis.
Found in poor areas where crowding and lack of vaccination is prevalent. Maintained in the population by asymptomatic carriage in the oropharynx. Humans are only known reservoir.
Corynebacterium diptheriae Clinical Disease
Respiratory Diphtheria: Onset is sudden iwth malaise, sore throat, exudative pharyngitis, and a low-grade fever. Exudate evolves into a pseudomembrane. This is eventually expectorated. This leads to myocarditis and neurotoxicity.
Cutaneous Diphtheria: Acquired through skin contact with infected persons. Leads to a papule that develops into a chronic, nonhealing ulcer.
Diagnosis is made clinically. ID is based on presence of cysteinase and absence of pyrazinamidase. All diphtheriae is tested for production of exotoxin via the Elek test.
Treat with diphtheria antitoxin, then with penicillin or erythromycin to eliminate the organism. Patients fail to develop protective antibodies following a natural infection.
Nocardia General Information
Strict aerobic rods that form branched filamentous form in tissues and culture. They resemble molds, and at one time Nocardia was thought to be a fungus. They are Gram positive, but most Gram stain poorly and appear to be gram-negative.
Similar cell wall to mycobacteria (tuberculostearic acid), but length of mycolic acids is shorter in Nocardia than in mycobacteria.
Described as “weakly acid-fast” which is used to distinguish from Actinomyces
Cord factor is an important virulence factor that facilitates intracellular survival.
Upon culture, presence of aerial hyphae and acid-fastness is unique to Nocardia
Nocardia Virulence, Immunity, and Clinical Disease
Protects itself from phagocytic killing by secreting catalase and superoxide dismutase. It can also use cord factor to prevent fusion of the phagosome-lysosome, prevent acidification of phagosome, and avoid acid phosphatase by using it as a carbon source.
The agent is exogenous (as opposed to actinomyces) orgnanism is not a part of the normal human flora, but is present in soil rich with organic matter
Bronchopulmonary disease in immunocompromised patients (especialy T-cells) with a high predilection for hematogenous spread to the CNS or skin. Develops after initial colonization of the upper respiratory tract by inhalation and then aspiration into lower airways. Causes cough, dyspnea, fever, and cavitation and spread to pleura are common.
Cutaneous Infections: Can be primary infections or spread from bronchopulmonary infections. Mycetoma has draining tracts with granules normally caused by N. brasiliensis. Lymphocutaneous infections mimic Sporothrix schenckii infections.
A third of all patients with Nocardia have dissemination to the brain that can form single or multiple brain abscesses
Can detect easily by microscopy, use acid fast test to distinguish from actinomyces. It is possible to grow the organism on BCYE agar.
Treat with antibiotics combined with surgical intervention. Trimethoprim-sulfamethoxazole is often used to treat local infections.
Prognosis is poor for immunocompromised patients with desseminated disease.
Actinomyces
Facultatively anaerobic or strictly anaerobi gram-positive rods that are not acid-fast. They develop delicate filamentous forms or hyphae and resemble fungi.
Produce chronic, slowly developing infections
Normally colonize the upper respiratory, GI, and female genital tracts but are not normally present on skin. They have a low virulence potential and cause diseaes only when the normal mucosal barriers are disrupted by trauma, surgery or infection.
Actinomycosis: characterized by development of chronic granulomatous lesions that become suppurative and form abscesses connected by sinus tracts. Macroscopically looks like “grains of sand”
Disease is endogenous (no person to person spread or outside inoculation)
Cervicofacial actinomycosis: most common infection. May occur as acute, pyogenic infection that can lead to draining sinus tracts along the jaw.
Can lead to a solitary brain abscess in CNS
Tough to confirm in lab because of cross contamination
Treat with penicillin and surgical debridement
Mycobacterium Tuberculosis
An intracellular pathogen that is able to establish lifelong infection. Infection begins in alveoli with phagocytosis by alveolar macrophages. M. tuberculosis prevents fusion of phagosome with lysosomes.
Upon infection, macrophages secrete IL-12 and TNF-alpha, driving a TH1 response and leading to increased macrophage killing. If this goes overboard it can lead to tissue necrosis. The organism does not directly damage host cells.
Alveolar macrophages, epitheliod cells, and Langhans giant cells with intracellular mycobacteria form a central core of a necrotic mass that is surrounded by a dense wall of CD4, CD8, and NK T cells and macrophages (granuloma). Organism can stay dormant for long periods of time in granulomas surrounded by fribrous material.
Humans are only natural reservoir
Initial focus is in middle or lower lung fields.
Tuberculosis
Disease can be insidious at onset. Patients have nonspecific complaints of weight loss, cough, night sweats, malaise, and bloody sputum.
Diagnosis is made by radiographic evidence, positive skin test and lab detection of mycobacteria through microscopy or in cultures.
Mycobacterium avium Complex
Can cause disease in immunocompetetent patients. Disease in HIV-infected patietns is primarily caused by M. avium.
Disease is often seen in middle-aged or older men with underlying pulmonary disease, which leads to a cavitary disease that resembles TB on chest X-ray.
Lady Windermere syndrome: Second form of MAC infection is observed in elderly female nonsmokers who may chronically suppress their cough reflex. They have lingular or middle lobe infiltrates. This is associated with significant morbitity and mortality.
Third form of disease is formation of a solitary pulmonary nodule
AIDS has made infection with MAC the most common mycobacterial infection in the US. In this case, the disease is disseminated with no organ spared.
Rapidly Growing Mycobacteria
low virulence potential,stain irregularly with traditional mycobacterial stains, and are more susceptible to conventional antibiotics.
Associated with disease occurring after bacteria are introduced into the deep subcutaneous tissues by trauma or iatrogenic infections.
