Respiratory Infections Flashcards
Legionella Pneumonia
Gram negative rod (often not detected on gram stain)
Legionnaires’ disease; most common cause of communicy acquired pneumonia; contaminates water, spread by inhalation of aerosolized water from natural water sources, tap water in healthcare facilities, air conditioners, other water based cooling systems
symptoms: very high fever 104ºF, 40ºC history of smoking diarrhea confusion cough (initially only slightly productive) Labs show hyponatremia
diagnosis difficult because of non-specific symptoms.
look for radiographic evidence of pneumonia, high fever, accompanying GI symptoms (diarrhea)
sputum sample unreliable, SHOWS FEW OR NO BACTERIA since unique lipopolysaccharide chains on outer membrane inhibit gram staining.
diagnosis made by testing legionella antigen in urine
Tx:
fluoroquinolones (levofloxacin) or newer macrolides (azithromycin)
Ddx:
mycobacterium Kansasii atypical mycobacterium that can casue similar to M. tuberculosis (acid fast rod similar to L. Pneumonphila in that it’s water contaminant) but it’s usually municipal drinking water systems not nature.
Mycoplasma Pneumoniae
Primary cause of walking pneumonia
symptoms: nagging nonproductive cough, low grade fever, malaise
CXR suggests severe pneumonia even though patient appears relatively well
Mycoplasma species require cholesterol supplementation to grow on artificial media (lack a peptidoglycan cell wall, cell envelope or capsule
Ddx:
strep pneumoniae causes lobar consolidation on CXR, grows on unenriched blood agar, unable to grow in optochin or bile
Kleb Pneumoniae common in debilitated, hospitalized or alcoholics (red currant jelly sputum), grows on any agar but MacConkey agar is best bcz contains bile which inhibits growth of contaminant organism
H. Influenzae requires chocolate agar (heat lyzed blood agar) supplemented with facor X (hematin) and factor V (NAD+) in order to grow
L. pneumophila requires L-cysteine - supplemented agar for growth
Coxiella burnetii causes Q-fever (mild pneumonia-like illness resulting from inhalation of C. Burnetti spores in animal hides.) obligate intracellular parasite needs CELL CULTURE in order to grow
Fungi (coccidioides immitis - san joaquin valley fever) common in southwest US and northern Mexico. Histoplasma capsulatum causes similar illness but typically in Mississippi and Ohio river valleys. both can be cultured on standard bacterial culture media.
Pneumocystis jiroveci is a fungus that cuases severe Pneumonia in HIV+ patients whose CD4 is below 200. ground glass CXR. pneumocytstic jiroveci (PCP) by silver stain during bronchoscopy.
Fungi require ergosterol for growth (drug target)
Asplenic patients prone to infections by
Post-splenectomy infection carries 50% mortality risk
spleen is part of lymphoid system. destruction of RBC, serves are reservoir of RBC, granulocytes and platelets that can be mobilized when needed. Macrophages that line the trabecular meshwork present antigens to B and T cells in splenic white pulp to generate active immune response.
Asplenic patients are prone to infections by encapsulated organisms like S. pneumoniae, H. influenzae, N. meningitidis
spleen serves as site of Ab synthesis and reservoir of phaogyctic cells capable of removing circulating pathogens.
Interstitial Pneumonia with oral thrush and severe lymphopenia during first year of life in baby born to IV drug user indicates what infection? what’s the preventative protocol?
HIV infection. maternal prophylaxis during pregnancy with nucleoside analog zidovudine (ZDV/AZT) - retroviral reverse transcriptase inhibitor, reduces the risk of perinatal transmission by 2/3 in HIV positive women who have not previously received antiretroviral therapy.
immune cells that fight Tuberculosis
Pulmonary tuberculosis infection is controlled by the action of CD4+ TH1 llymphocytes and macrophages. These cells work together to contain M. Tubercuolsis within a caseous granuloma, which offers the macrophages inside an opportunity to kil the remaining organisms if the necrotic area is small enough.
Haemophilus Influenzae growth (satellite phenomenon)
Haemophilus species are part of normal flora of Upper resp tract, must differentiate it forom other bacteria through biochemical means. Demonstrate it by showing necessity of X and V factors.
blood loving organism. need factor X(hematin) and V (NAD+) for growth. grow on chocolate agar plate, or around streak of staph aureus due to NAD+.
grow near beta hemolytic S. aureus colonies because they produce factors X and V.
Staph is ß-hemolytic, X factor released and V factor actively secreted by staphylococci into growth medium. both X and V needed by H. influenzae.
Mycoplasma pneumoniae and anemia
mycoplasma pneumoniae is causative agent of walking pneumonia and many cases of tracheobronchitis. has no peptidoglycan cell wall. Only has a phospholipid bilayer cell membrane. Shares antigens with human erythrocytes, and when the body mounts a response against these antigens it also lysis red blood cells leading to anemia. the antibodies causing this RBC destruction are called cold agglutinins becuase they are able to agglutinate RBCs in vitro at low temperatures.
M. pneumoniae can also cause stevens-johnson syndroma nd joint pains among other rare sequelae.
Histoplasma Capsulatum
can survive intracellular within macrophages. It causes a disseminated mycosis in immunocompromized patients. The clinical features include systemic symptoms (fever and weight loss) fiainful oral ulcers, lymphadenopathy, hepatosplenomegaly.
Hyper IgM syndrome
results from inability of B-lymphocytes to undergo isotype switching from IgM to other immunoglobulin isotypes like IgD, IgG, IgE and IgA. Clinically, hyper-IgM syndrome most commonly restuls in lymphoid hyperplasia and recurrent sinopulmonary infectinos. The syndrome results most commonly from a genetic absence of the CD-40 ligand on T-lymphocytes or from a genetic deficiency in the enzymes responsible for the DNA modification that takes place during istoype switching.
Group A strep - S. pyogenes
ß hemolytic, bacitracin sensitive
Group B strep - S. agalactiae in newborns
ß-hemolytic gram positive cocci in chains - bacitraicn resistant
screen prenatally for vaginal and rectal culture at 35-37 weeks gestation. Positive cultures or previous positives, intrapartum antibiotic prophylaxis indicated to prevent neonatal GBS sepsis, pneumonia and meningitis.
Echovirus (picornaviridae family)
single stranded, positive-sense, linear, nonsegmented RNA virus have genome that is independentely active, works as its own mRNA, produces polypeptide coding for several proteins and then cleaves the protein products.
viruses with single-stranded, negative sense, linear RNA
nonsegmented (measles and rabies)
segmented (influenza virus)
S. Pneumoniae polysaccharide vaccine
lancet shaped gram positive diplococci.
80 serotypes with variants of capsular polysaccharide.
types 1-8 repsonsible for 75% of dinfections.
23-valent pneumococcal polysaccharide single dose vaccine is recommended for all adults over age 65 and other patients at high risk of pneumococcal sepsis (HIV, asplenia, COPD, immunosuppressed). 50-90% efficacy.
7-valent conjugated vaccine for kids under 2yo, 90% efficacy.
conjugated vaccine contains polysaccharide antigens that are protein coupled to stimulate the T-cell dependent immune (memory) response.
also vaccine for N. Meningitidis and H. Influenze that are also polysaccharid vaccines.
Aspergillus fumigatus
low virulence fungus does not cause significant infections except in immunocompromized or debilitated patients. Can complicate asthma or CF via a hypersentivity reaction. result is allergic bronchopulmonary aspergillosis or ABPA.
occurs in 5-10% of steroid dependent asthmaics. high serum IgE levels, eosinophilia and IgE plus IgG serum antibodies to Asdpergillus.
causes allergic bronchopulmonary aspergillosis (ABPA) due to aspergillus fumigatus can complicate asthma. ABPA can result in transient recurrent pulmonary infilatrates and eventual proximal bronchiectasis.
Pseudomonas aeruginosa
opportunistic aerobic gram-negative rod that is frequent, sometimes deadly, pulmonary pathogen in patients with CF or neutropenia.
Strongyloidiasis
can cuase pulmonary sympotms: cough, asthma like bronchospasm and hemoptysis. can also produce a transient pneumonia as larvae migrate through the lungs on their way ot the laryngopharynx. In rare cases, chronic lung involvmenet may cause features of obstructive and/or restirctive pulmonary disease.
Legionella pneumophila
commonly contaminates natural bodies of water, municipal water, humidification systems and air conditionsing and water based cooling systems. inhaled in aerosolized water and establishes infection by the pulmmonary route. requires special enrigched media for growth (L-cysteine) and agar used is buffered charcoal yeast extract agar.
rhinovirus
ss+ RNA virus, naked virus can cause infection.
other nonenveolped RNA viruses include enteroviruses (poliovirus, coxsackievirus, echovirus, hepatitis A virus)
reovirusis (rotavirus) and
Norwalk virus
Influenza A virus type
orthomyxovirus that contains SS- RNA. to replicate in horst cell, RNA0dependent RNA polymerase with the intact virion must also gain entry
Respiratory syncytial virus (RSV)
paramyxovirus containing SS- RNA. needs an RNA-depenent RNA polymeraase within the intact virion.
HIV virus
retrovirus that contains SS+ RNA packaged with reverse transcriptase, an RNA-dependent DNA polymerase
Rotavirus
reovirus containing double stranded RNA
naked RNA is therefore incapbable of inducing viral protein synthesis in a host cell and is noninfectious. need a viral RNA polyemaser in intact virion.
Histoplasma capsulatum
dimorphic fungus located intracellularly within macrophages. Affects the lugns and reticuloendothelial system. It is present in bird and bat droppings, and is endemic to the mississippi and ohio river basins.
dimorphic fungus found as mold in soil. patients report history of exploring caves exposure to bats or clearning bird cages or coops.
fungus ingested by macrophages and seen as small intracellular oval bodies. similar immune reaction to M. tuberculosis. cell response with foration of ranuloma. fungus targets histiocytes and the reticuloendothelial system, can cuase lymphaednopathy and hepatosplenomegaly.
sympotms: cough, fever, pleuritic chest pain and pumonary infiltrates. People with underlying lung idsease can develop chronic pulmonary histoplasmsiss, a condition that resembles tuberculosis (cough malaise, weight loss and cativation in the upper lung lobes_. Disseminteaed disease in immunocompromised.
Th2 immune mechanism behind extrinsic allergic asthma. Which chemokines are secreted? what do they do?
Th2 cells secrete IL4 and IL13 which together promote B-lymphocytes class switching for IgE synthesis. They also secrete IL-5 which activates eosinophils and promotes IgA synthesis. An excess of these Th2 produced lymphokines may contribute to pathogenesis of extrinsic allergic asthma.
IL-1 is secreted by macrophages to stimulate helper T cells.
IL3 from helper T cells recruits bone marrow stem cells.
IFN-gamma from helper T cells functions mainly to activate macrophages.
TGF-ß is growth factor involved in tissue regeneration and repair.
Th1 cells secrete IFN-gamma, IL2 and others to stimulate cell mediated repsonse (CD8 T cells) and type IV delayed hypersensitivy reactions.
Th2 cells mediate an abnormal Type 1 hypersensitivity reaction and associated chronic eosinophilic bronchitis.
MRSA carriage site
Anterior nares. 25-30% are carriers with nasal colonization with SA. anterior nares most common site for both MRSA and MSSA
green discoloration of pus or sputum from bacterial infections is due to..
Myeloperoxidase (MPO) from neutrophil azurophilic granules. MPO is a heme-containing pgimented molecuel.
Chronic Granulomatous Disease due to staphylococcal pneumonia. what stains with nitroblue tetrazolium in neutrophils?
X-linked disorder resulting from a deficiency of NADPH oxidase. Deficiency of this enzyme leads to an inability of neutrophils to form the oxidative burst to kill organisms in their phagolysosomes. Organisms that produce catalase are ineffectively killed by these defective neutrophils while organisms that do not produce catalase can still be killed due to accumulation of bacterial hydrogen peroxide within the phaogosome.
Bacterial Pneumonia secondary to influenza A infection
Patients over 65yo are prone to developing secondary bacterial pneumonia after influenza infection. In order, the pathogens most often responsible for secondary bacterial pneumonia:
streptococcus pneumoniae
staphylococcus aureus
haemophilus influenzae
symptoms of INfluenza A: abrupt onset fever, headache, myalgia, malaise
symptoms of secondary bacterial pneumonia: recurrent fever, dyspnea and productive cought with CXR showing consoldidation.
Enveloped viruses and ether
Loss of infectivity after ether exposure is characteristic of enveloped viruses because ether and other organic solvents dissolve the lipid bilayer that makes up the outer viral envelope.
mycoplasma sp. treatment with antibiotics that attack peptidoglycan cell wall
not affected by agents that attack peptidoglycan cell wall like penicillin, cephalosporins, carbapenems, and vancomycin. Lack peptidoglycan cell walls. Mycoplasma infections can be treated with anti-ribosomal agents like tetracycline and erythromycin.
blood supply to the bronchi and bronchioles
from left and right bronchial arteries from the descending aorta. the venous (deoxy) returns to LV along with oxygenated blood from pulmonary arteries/veins to reduce the pO2 from 104 to 100mmHg.
V/Q from apex to base of lung
Ventilation and perfusion both increase from apex to base, but perfusion increases more due to gravity. V/Q decreases from apex to base or increases from base to apex.
Blood flow decreases from base to apex.
Blastomyces dermatitides
dimorphic fungus that can cause pulmonary infections in immunocompetent people.
Travel to Great Lakes, Mississippi and Ohio River basins
in mold form, soil, organic matter, dogs, horses.
in lungs, transforms to yeast form.
characterized by granuloma formation.
can cause pulmonary disease in immunocompetent host. can lead to disseminated mycosis (fever, pulmonary symptoms, skin and bone involvement)
sputum with KOH is diagnostic. revelas round yeast with thick doubly refractive walls.
each yest has single broad based bud, itraconazole is treatment.
Haemophillus influenzae type b vaccine Hib vaccine
why conjugate to tetanus or diphteia toxoid?
consists of polyribose ribitol phosphate capsular polysaccharide conjugated with either tetanus or diptheria toxoid. Protein conjugation causes T-cell mediated immune repsonse leading to immunoglobulin class switching and geneartion of memory B-lymphocytes. This response would not ocur with pure polysaccharide immunization. Used in infants and young kids who are able to mount a T-cell mediate repsonse but not a B cell mediated one.
Streptococcus pneumoniae
most common cause of community-acquired pneumonia in immunocompetent patients (including HIV+ individuals with high CD4+ counts)
opportunistic infections with immunocompromized individuals:
Pneumocystis jiroveci. Tuberculosis is slower onset.
lung abcess containing peptostreptococcus and fusobaceterium
normal oral flora. seizure patients may aspirate oropharyngeal ocontents causing lung abscess. also alcoholism, prolonged anesthesia, severe neurologic diseases
bacterial pneumonia too: usually nosocomial: s. aureus, e.coli, k. pneumoniae, s. pneumoniae type 3.
infective endocarditis: staphylococcus and sterptococcus species and ecoli and fungi
Chronic Granulomatous Disease
X-linked disorder resulting in deficiency of NADPH oxidase, the enzyme responsible for formation of ROS in neutrophil phagolysosomes. Neutrophils affected by this disorder are unable to kill catalase producing organisms (staphylococcus, serratia, E. coli, etc.) but they remain effective in killing non-catalase producing organisms.
nitroblue tetrrazolium testing tests for NADPH oxidase
normally NADPH oxidase produces ROSs and ROS are converted to H2O2 in the phaoglysosome by superoxide dismutase. H2O2 serves as primary antibac agent in phaogosome. kills both catalase positive and catalase negative species because it overhwelms bacterial systems.
Cold Agglutinins
test positive for mycoplasma pneumoniae (respiratory infections)
also EBV and hematologic malgnancy
these are antibodies specific for mycoplasma pneumoniae antigens that happen to be homologous to antigens on human erythrocytes that only cause agglutination or clumping or red blood cells at low temperatures
responsible for transient anemia in many patients with M. pneumoniae infections.
Hib - Haemophilus influenzae type b vaccine
contains bacterial capsular polysaccharide conjugated with diphtheria toxoid
can do this with streptococcus pneumoniae, neisseria meningitidis and Hib.
converts antigens from T-cell independent to T-cell dependent antigens.
approved carriers: mutant nontoxic diphteria toxin, neisseria meningitidis outer membrane protein complex and tetanus toxoid.
basis of streptomycin resistant M. tuberculosis
aminoglycoside can only be administered parenterally, works by inhibiting the bacterial 30S ribosomal subunit (preventing bac protein synthesis.)
mutations of genes that encode ribosomal proteins are responsible for aminoglycoside resistance because they modify the ribosomal binding sites for these drugs.
aminoglycoside streptomycin inhibits protein synthesis by inactivating the 30S (small) ribosomal subunit
decreased activity of bacterial catalase-peroxidase is one mechanism of mycobacterial resistance to isoniazid
structural alteration of enzymes involved in RNA synthesis (DNA-dependent RNA polymerase) is the mechanism through which organisms become resistant to rifampin.
Bacteria that are able to be transformed and become virulent
streptococcus pneumoniae
H. Influenza
neisseria gonorrhoeae and meningitidis
Methacholine challenge
highly sensitive but not specific measure of bronchial hyperreactivity in patients suspected of having asthma. A negative methacholine challenge test can help exclude (not rule out) asthma.
CXR, blood eosoniophil count, serum IgE level, skin reactivity to various allergens are less sensitive. Normal findings on these tests can’t exclude diagnosis.
Azoles
inhibit synthesis of ergosterol by the fungal cytochrome P450 enzymes. Also suppress the human P450 enzymes, resulting in many drug-drug interactions.
MOA: inhibit demethylation of lanosterol into ergosterol in fungal cells.
they increase serum concentratinos of drugs metabolized by liver P450 enzymes. many drugs can reach toxicity in presence of azoles.
avoid with warfarin, cyclosporine, tacrolimus, phenytoin, isoniazid, rifampin, oral hypoglycemics and many others.
cytochrome oxidase inducers (rifampin, phenytoin, carb, penobarb, increase azole metabolism and lower [azole] in blood.
amphotericin B puts holes in fungal cell memrbane.
Griseofulvin - binds fungal MT’s inhibiting mitosis
caspofungin and other echinocandins block glucan syntehsis to break down the polysaccharide component of the fungal cell wal.
Flucytosine inhibits both DNA and RNA in fungal cells. used with Amphotericin B. mostly impt in cryptococcal meningitis.
Coccidioides immitis infection
can be asymptomatic or can cause pulmonary disease ranging from flu-like illness to chronic pneumonia. Causes disseminated disease in immunocompromized patietns. Spherules containing endospores are found in tissue samples.
common in people in desert areas of US and mexico.
silver stain with thick walled spherules packed with endospores. also culture on Sabouraud’s agar and serology.
Polyribsoyl-ribitol-phosphate (PRP) and epiglottitis connection.
Hib vaccine composed of this, it’s acomponent of the Hib capsule conjugated with diptheria or tetanus toxoid. Immune activation with Ab production and memory B lymphocyte induction against PRP provides lasting immunity agasint Hib in children as yojng as 2 months. Epiglottitis is almost exclusively caused by Haemophilus influenzae type b.
Aspergillus fumigatus
mold that is widely present in organic matter. Forms septate hyphae that branch at 45º angles (V-brnaching). Spores are inhaled with air and are cleared by mucus and ciliated epithlelium of the respiratory tract. Individuals with suppressed immune defenses can get a number of diseases.
Colonizing aspergillosis - in old lung cavities from tb, emphysema, sarcoid. grows in cavity in fungus ball, aspergilloma. can be asympatomatic or cause hemoptysis. CXR shows radiopague that shifts when patient changes position.
Hypersenstivity reactions to aspergillus occur in patients with astham, allergic bronchopulmonary aspergillosis (ABPA): wheezing fever and migratory pulmonary infilatrates
invasive aspergillosis - in immunosuppressed and neutropenic patients characterized by primary lung involvement with symptoms of cough, hemoptysis, pleuritic chest pain, fever. Necrotizing pneumonia and granuloma formation also occur. Lung biopsy shows hyphae in lung tissue. extrapulmonary invovement also common.
