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136 Cards in this Set
- Front
- Back
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Exotoxin
Corynebacterium Diptheriae |
gram +
catalase + facultative nonmotile use blood agar reduces tellurite VF: Tox protein carried by Beta phages tx= antitoxin |
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TOX gene
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VF of corynebacterium diptheriae
A-B toxin toxin binds to heparin binding epidermal growth factor toxin is excreted when there is low iron in host cell |
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Pseudomonas aeruginosa
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gram - bacillus
oxidase +, motile, nonfermentative prefers to live in aerobic can live on anything (even 42deg C) found in distilled water opportunistic fruity odor blue-green pigment on cetrimide agar-low iron agar Clinical symptoms: -eye infection (scratches caused by contacts) -swimmers ear (otitis media) -hot tub rash (burn pts. are at HIGH risk) -ecthyma gangrenosum: systemic infection that shows up on skin VF: TONS of them: endotoxin, pyocyanin, degraditive exoenzymes, alginate slime (seen in CF pts) EXOTOXIN A (type 2 secretion): A-B Toxin ADP-rib. on EF2 on dipthamide residue (different receptor then diphtheria) binds to alpha2 macroglobulin receptor LRP1 EXOTOXIN STUY (sty=disrupt airways) type 3 secretion PHOSPHOLIPASE C= helps it spread through tissues heat labile RHAMNOLIPID- surfactant that kills cells and spread through tissues heat stable used to also clean up oil spills |
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Anaerobe
Bacteroides |
gram - bacilli
resistant to bile hydrolyze esculin found in the colon ..Fragilis- most commonly isolated -intraabdominal infections VF= polysac. capsule Drug resistant |
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Anaerobe
Clostridium |
gram + rods
release endospores different species: -Botulism -Tetanus -Perfringes -Difficile |
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C. Botulism
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gram + anaerobe
ingestion of toxin found in foods--> heat resistant spores in cans toxin blocks release of ACh vesicle in the neuromuscular junction 12-36 hrs causes flaccid paralysis (m. weakness) eventually respir. muscles are paralyzed and causes death. tx- antitoxin and not antbiotics bc they are not infected with organism can be seen in infant..but infant colonizes the bacteria..and then produces toxin floppy baby, babies can't cry as loud can occur in wound/lesion contaminated with organism (spores) toxin is absorbed into tissue botox, and m. spasms |
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C. Tetanus
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gram + anaerobe
found in soil and G.I. associated with traumatic wounds produces toxin (A-Btoxin) transmitted via bloodstream or cranial n. nuclei....toxin irreversible finds to nerves prevents inhibitory NT (GABA, glycine) from being released. clinical signs: lock jaw (trismus) m. spasms uncontrollable called opisthotonus (arching of body) 4 types: 1. generalized 2. local 3. cephalic 4. infant- contamination of umbilical cord when it was cut. can't open mouth to feed. TX: antitoxin (but not that helpful bc toxin is irrev. bound to nerve) Penicillin G prevention- VACCINE (toxoid is given) |
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C. perfringes
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produces alpha toxin (lecithinase)
could cause food poisoining which is different from the toxin produced in wounds WOUND DZ is characterized by both destruction of tissue and production of toxin gross black and gangrenous can feel the gangrene gas toxin is carried in bloodstream causing in some people hypotension and fever TX: SURGERICAL REMOVal immediately. Penicillin- bc patient is infected organism NO antitoxin prevention: clean up wound, restoration of oxygenated blood supply so Eh increases and organism will not be able to survive FOOD poisoning toxin enterotoxin causes hypersecretion of jejunum and ileum= diarehhea self limited-->done w.in 1-2 days DX: do gram stain (can see bacillus) |
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C. Difficule
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gram + anaerobic rod
most common cause of nocossmial diarr. when pt is on antibiotics, helps it get in the way of normal flora or not washing hands of healthcare workers 2 toxins: Enterotoxin A and cytoxin B these toxins cause immune response to cause inflammation leading to increase vasc. permeability disruption of intracellular tight junctions causing apoptosis of epith. cells damage only occurs in the colon--> disruption of mucusa--> causing pseudomembrane (due to inflammat. response causing production of mucin and fibrin). and is classified by production of hydrolytic enzymes and toxin symptoms: nonbloody diarr., fever, abdominal pain could progress to pseudomembrane coloitis TX: can use antibiotics Prevention: WASH HANDS DX: toxin in stool culture it |
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Hepatitis
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All are RNA viruses except B
-B uses RNA intermediate but is a DNA virus All naked viruses are transmitted via fecal-oral All enveloped (more delicate) are transmitted via parenteral or sexual-->obligate intracellular (needs to replicate inside cell) Hepatotropic virus- lives in liver A and E are nAkEd capsids- can be transmitted via enteric while envelope would be lost if it went through the GI naked capsids (non envelopes) usually lysis their cells so there is NO carrier state or chronic state |
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coinfection
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dirty blood with Hep B and D
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superimposed
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person has Hep B and then later get Hep D (via a Hep B and Hep D mixture)
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Hepatitis A
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infectious
picoRNAvirus- +ssRNA, naked capsid transmitted via fecal oral mild severity with abrupt onset a good alcohol scrub or soap will not be effective for this survives in GI and bile |
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Hepatitis B
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Serum
could turn into chronic hep. hepaDNAvirus- enveloped DNA but needs RNA intermediate to replicate also needs reverse transcriptase transmitted parenteral or sexually does not cross placenta associated with hepatocellular carcinoma and cirrhosis with effective cellular immunity, this will be resolved but it will still cause a shit load of symptoms such as: -massive damage to cells Has an E antigen in it's core, which still produces Ag even when virus is gone has antigens on enveloped surface called HBsAg which trigger the cell mediated immune response..causing Ab to bind to Ag if CMI is not adequate (alcholics and children) this can become a chronic infection -less cell death--> not as severe symptoms CHRONIC hep _ = are at high risk for fulminant hepatitis if they get infected with Hep D higher risk for cirrhosis and hepatocellular carcinoma |
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Hepatitis C
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Post transfusion
REALLY likely to turn into chronic hep Flavivirus- enveloped RNA tranmitted parenteral or sexual associated with hepatocellular carcinoma and cirrhosis |
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Hepatitis D
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Delta
turns into chronic hep Defective- Enveloped (circular RNA) transmitted parenterally and sexually death rate is really high abrupt onset and must be COinfected with B no cancer risk bc patient dies too fast |
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Hepatitis E
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Enteric
No possibility of it turning into chronic Calcivirus- naked capsid (RNA) transmitted fecal-oral SEVERE in pregnancy |
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Enveloped Hepatitis
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B, C, D
more delicate- can't go through GI bc it will be lost alcohol makes it noninfectious usually bud through cell--> no lysis is necessary (but some will lyse cell-herpes on skin) the spikes on it causes the immune reaction obligate intracellular- needs to be inside cell to replicate |
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+ strand RNA replication
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it is already in mRNA stage
can immediately attach to ribosome and makes polycistronic proteins these proteins are cleaved to individual proteins (including RNA depend RNA polymerase) RNAdepRNApoly is used to make -ssRNA which is used as a template to make more of the starting product |
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HBV replication
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since it is a partially gapped dsDNA
HBV polymerase has 3 different activities 1. used as DNAdepDNA activity to finish dsDNA 2. used as reverse transcriptase after ssRNA is made using cellular transcriptase= produces half ssRNA and half ssDNA 3. acts as a RNAse and DNAdep DNA to make NEW partial dsDNA |
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HAV replication
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starts as +ssRNA so acts like mRNA
immediately can make proteins (polycistronic proteins) self cleave to get indiv. proteins like RNAdepRNA poly. this polymerase binds to +ssRNA in cell makes - copies which are replicative intermediates these are used with the RNAdepRNA poly to make + strands **but the + strands go back and bind to ribosomes to keep making RNAdepRNA poly and other proteins** all this amplifies production of virus remember cell becomes lysed |
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Negative ssRNA replication (Rabies)
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-ssRNA uses RNAdepRNA poly to become +ssRNA (also called mRNA)
so you can make more proteins using the -ssRNA or more virus from +ssRNA (ALL using RNAdepRNApoly) glycosalated..buds out..no lysis of cell |
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Staphylococcus aureus
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gram + cocci clusters
catalase + oxidase + coagulase + beta hemolysis part of human flora (naris, rectum, vag) resistant to high temp and high salt healthcare, dialysis, DB pt have a high risk of catching it DX: usually clinical, blood (bactremia), swab (epidermal) can cause many different clinical syndromes based on the depth of infection in the tissue most superficial to deep 1. impetigo 2. folliculitis 3. boils (furnicles) 4. abscess (carbuncle) 5. Hidra dentis suppurtiva 6. Erysipelas 7. cellulitis/ Fasclitis (most severe) |
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Impetigo
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most superificial infection caused by staph aureus
looks like small erythema (turns into vessicles) Heals as honey-colored crust |
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Folliculitis
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caused by staph aureus infection (2nd superficial)
rash with pus inside hair follicle |
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Boils (furnicles)
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caused my staph aureus infection (3rd superificial)
large pus containing lesions with yellow center looks like nodules exude purulent material coming out of a single opening |
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abscess (carbuncles)
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caused by staph aureus infection
pus in the deep tissues (subcutaneous tissue) many openings PMNs and PG toxins cause these |
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Hidra dentis suppurative
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infection caused by staph aureus
infection of the apocrine sweat glands causing pus looks like crops of furnicles |
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erysipelas
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reddening of the skin with NO lesions
caused by staph aureus infection when u palpate..causes more pain (2nd to last most deep) |
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cellulitis/ fascilitis
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WORST/DEEPEST staph infection
diffused, but extensive dz introduces bacteria into bloodstream when u palpate..causes more pain |
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risk factors for being infected with staph aureus
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1. defect in leukocyte chemotaxis
- can be congenital (Wiskott-Aldrich syndrome) - or aquired= diabetes 2. defects in opsonization of Ab -opsonization is altering the bacteria so it is easily engulfed by phagocytosis -ex: hypogammaglobinurea, complement defects 3. Defect in intracellular killing/phagocytosis - problems with oxidative burst 4. skin injuries, surgical incisions 5. foreign bodies (catheters) |
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VF of staph aureus
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1. capsule- prevents phagocytosis
2. Peptidoglycan and techoic acids -activate the complement system -enhances chemotaxis on PMNs -causes monocytes to produce IL1 -produces opsonic Ab 3. Protein A -binds to Fc region of G1,2,4 and interfers with: -binding of complement - opsonization and phagocytosis 4. enzymes -help bacteria spread to other tissues (lipases, fibrinogen) -enhance bacterial survival in phagoctye (catalase and carotenoids) -act as an immunlogical disguise (coagulase- turns fibrogen into fibrin --> so now cell wall is protected against phagocytosis) 5. hemolysins: -alpha: lyses PMN and makes pores and eventually ruptures cells -Beta: degrades spingomyeline -gamma + proteins= Panton-Valentine leukocidin (associated with aggressive necrosing skin infections and hemmoragging pnemonia by lysing PMN membranes) 6. Toxins -exfoliatin A and B in scalded skin syndrome -epidemolytic toxins (seen in skin manifestatinons) 7. Superantigens- activate T cells, causing a massive cytokine release and |
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Clinical syndromes caused by staph aureus
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1. skin manifestations
2. Bactremia -community or hospital aquired -Risk factors: anything penetrating skin and going to blood, and renal dialysis 3. endocarditis- severe complication of bacteremia - presents as acute septic syndrome -signs: cardiac murmur, septic emboli (Janeway lesions or petechiae) -RF: rheumatic heart dz, hemodialysis, elderly with valve sclerosis 4. Pulmonary infections (breathing or spread through blood) -community or hospital aquired -DEATH rate is high -pnemonia is necrotizing and has rapid progression 5. Scalded skin syndrome (SSSS) is a superficial skin disorder with blistering to generalized scalding -seen in newborns and infants 6. Food poisioning- caused by exotoxin (SEA, B, C,) -induces emetic reflex center -increase peristalsis -foodhandler is source, organism grows in food and then toxin is produced in food (seen in potato salad, canned food, processed meats) -onset of 2-6 hrs after ingestion and is self-limited (goes away) 7. Toxic Shock syndrome (caused by TSST-1) -2 |
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Staph scalded skin syndrome (SSSS)
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-mucosal or skin colonization of toxin (exfoliatin A and B) released locally and spread via blood
-ET-A and ET-B= has proteolytic activity causes what is seen on the skin -remember that MUCOSA is never involved -it localized is skin at level of stratum granulosum on GM4 -GM4 is only seen in young and adults with rare dz two types: 1. generalized- spreads and localizes on skin -it is seen on the skin due to distant release of toxin, therefore u will not see bacteria in the lesion -self limited: goes away in 4-7 d 2. localized (bullus impetigo) -local spread of toxin around a colonized wound -can happen in people with some immunity to toxin (infant with mom's Ab or immunoCOMPETENT adults) -spreading of toxin is limited due to Ab -fluid in blister usually has the bacteria |
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DX staph aureus
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-take culture from site of infection
-susceptibility should be preformed -clinical dx |
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tx staph aureus
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-vancomycin is administered when susceptibility results are unknown
-if bacteria is susceptible to methacillin -use nafcillin or oxacillin |
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Staph. Epidermidis
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gram +
catalase + oxidase + coagulase - susceptible to NOVObiocin non-hemolytic colonizes skin seen in nocosomial pts at sites of foreign bodies makes biofilms that adhere to devices and proliferates preventing antimicrobial penetration and immune system response resistance to antimicrobials due to slime |
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staph. Saprophyticus
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gram +
catalase + oxidase + coagulase - Resistant to NOVObiocin non-hemolytic causes acute UTI VF- urease (bladder tissue invasion) hemagglutinin- binds uroepithelial cells |
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TX for coagulase - Staph
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most are resistant to methicillian
use vancomycin |
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Chlamydiae
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gram -
LPS-weak endotoxin NO PG auxotrophic- uses host AA uses host energy obligate intracellular organisms has 2 forms: 1.elementary body (infects cells and lysis cells) 2. Reticular Body- metabolically active (inside cell-used for replication to make EB) causes: pneumonia (pneumoniae) STD (trichomatis) eye infections (Trachomatis) upper respiratory infection (psittaci) |
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Chlamydiae Trachomatis
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gram -, no PG, obligate intracellular
world's leading cause of blindness (seen in middle east and india) -infects nonciliated cells on mucous membranes -strains A, B, C causes blindness -strains D-K causes infant pneumonia, cervicitis, uretritius (STD), epidimitis (STD), adult conjunctivitis (STD) -strains L1,2,3- lymphogramyloma venerum (LGV) (STD) lesions can spread to lymph node incubation is 1-4wks LGV is the second stage (primary stage of lesion was overlooked bc no pain and healed already) -shows inflammation and spread to lymph nodes -homo men are resovoirs since it is STD MUST TREAT or else: chronic ulcerative (on genitals) or elephantitis Damage: -ocular: causes conjunctivital scarring due to inflammation of eyelids rubbing against eye--> scarring--> blindness -children are usually affected -mucopurulent discharge around eye |
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C. Trachomatis strains D-K
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gram -, obligate intracellular
these specific strains cause: 1. urogenital infections (strain D-K) W: usually asymptomatic -vag discharge -mucopurulent cerviticitis which can cause PID or salpingitis -etopic preg and infertility in men: usually asymptomatic 2. adult inclusion conjunctivitis- mucopurulent discharge 3. neonatal pneumonia usually occurs 2-3 wks after birth -rhinitis, dry cough |
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C. pneumoniae
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Chlamydophilia- causes dz of lungs
gram-, obligate intracellular, auxotrophic, No PG -occurs in adults and causes bronchitis, pneumonia, sinusitis -spread by person to person through respiratory secretions -multiplies within epithelial cells, macrophages, monocytes, lymphocytes -causes usually single lobe of the lungs respiratory infections (atypical pneumonia-walking) -also seen in atheroscolosis bc elementary body infected macrophages which has the plaque inside it |
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C. psittaci
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gram -, obligate intracellular, no PG
causes upper respiratory tract infection (parrot fever) transmitted via inhaling bird feces, urine, or respiratory secretions DX= serological findings, see there has been exposure to birds |
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DX of chlamydiae
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use the purulent discharge and look for existance of gram - diplococci (SHOULD NOT BE PRESENT)
cervix inflammed with secretions test via PCR it is in intracellular serology tests: look for IgM to detect LGV urogenital infections (nucleic acid probe) parrot fever detection culture: needs cell lines, has a high specificity and low sensitivity (good) Antigen detection: ELISA or direct immunoflouresence |
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TX for chlamydiae
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tetracyline, macroslides
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Rickettesia
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gram -
BEAR-arthropod borne obligate intracellular multiply in endothilial cells of small blood vessels produce capillary leakage and vasculitis goes to cytoplasm and nucleus not cultivated on media |
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Ehrichia
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gram -
obligate intracellular part of BEAR -arthropod borne infects monocytes and travels to cytoplasmic vacuole |
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Anaplasm
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gram -
obligate intracellular part of BEAR -arthropod borne infects granulocytes and goes to cytoplasmic vacuole |
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Coxiella
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gram -
obligate intracellular dog ate sheep..licked owner zoonosis that is found in many animals, placenta, mammary glands, and milk infects macrophages and goes to phagolysosomes |
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Streptacoccus pneumoniae
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gram + diplococci (arrow head)
encapsulated (VF) and nonmotile alpha hemolytic-due to hemolysin fastidious needs sheep blood agar needs CO2 catalase - optochin disk will inhibit its growth but not other strains from the same family bile soluble-->cell lyses-->looks clear can use specific antiserum that is specific for that antibody to get Ag-Ab complex -->causes capsular swelling called the quelling rxn in 40% of people we find it in the nasopharnxy flora (normally not present) at greater risk: elderly, smokers, immunocompromise (COPD, DB), alcoholics, aplenia (no spleen- could be structural or functional..its not working like it is suppose) -occur in pt with previous infection like flu -most common caused of pneumonia (community aquired-typical/lobar) -can affect more then one lobe -bacteria goes into aveoli, inflammation occurs in sac -lots of mucus being produced and lots of macrophages, etc -causes consolidation (xray) -productive cough green sputum with red streaks (blood) -abrupt onset, high feve |
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VF for streptococcus pnemoniae
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gram +
catalase - fastidous, encapsulated diplococci 1. capsule- polysaccaride (problems with vaccine for children under 2)okay for others -inhibits phagocytosis -inhibits alternative complement activation bc looks for whats on the surface (PG, etc)..with a capsule it doesnt work well -phagocytes have 3B receptor which bind to bacterial cell normally -with capsule can cover that 3CB that is bound...so phagocytosis is inhibited 2. cell wall components (PG, and techoic acids) -has phosphorylcholine bind to platete activating factor (PAF)...so phagocytosis will occur but PAF will but a shell around this organism and will allow it to enter host aveoli cells -activate alternative complete IL1, TNF 3. surface proteins (adhesion protein that allow it to bind to the dissarchride component of epithelial cells -secretory IgA prevent entrapment in mucus -autolysin- breaksdown peptidoglycan (hydrolase) and usually in cell wall but is inactivated unless (cell death occurs) - cell is too old -introduced to Beta lac |
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DX for streptococcus pnemoniae
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gram +
catalase - fastidous, encapsulated diplococci clincial, radiograph (consolidation of lobar) pt's hx of respir. tract previously take sputum and do gram stain -gram + diplococcus bullet shaped -use to treat pt until the rest of cultures occurs blood cultures urinary Ag test (shed in urine) TX: IV penicillan G -but alot of these strains are resistant, if this is tru treat with vancomycin -therapy:oral if outpt, inpatient could have different therapy |
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vaccines for streptoccous pneumoniae
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gram +
catalase - fastidous, encapsulated diplococci since there is over 90 different strains we have to pick the most important ones..2 different vaccines available: 1. PCV or PneumoVax- polysaccaride vaccine that covers 23 serotypes -give to anyone over age 2 (bc younger then 2 can not react to polysaccaride) 2. PCV7 + CRM197 (pneumococcal conjugate vaccine + nontoxic diphtheria toxin)- covers 7 serotypes -allows kinds to build Ab and must be given in a series (ever 2 mths till 15mths) -can be given to children under 2 |
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encapsulated organisms
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some killers have pretty nice capsules
streptococcus pneumoniae klebsiella pneuomonia haemophilus influenza type b pseudomonas aeruginosa neisseria meningitidis cryptococcus neoformans (yeast) all these prevent phagocytosis the same way as steptococcus pneumonae |
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Mycobacteria
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acid-fast
gram + slow growth resistance to detergents resistance to common antibiotics clumping causes granulomatous infections seen with epithiloid cell aggregates surrounded by macrophages and lymphocytes two organisms that show this: M. tuberculosis M. leprosy |
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Mycobacteria cell wall
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lipoarabinomannan (LAM)
arabinoglatacans mycolic acids more glycolipids and peptidoglycolipids transport proteins and porins on the cell wall are important antigens high G to C ratio |
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Mycobacteria Tuberculosis characteristics
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slow growing (2-8 wks in culture)
non-pigements (or buff color) fac. intracellular organism transmission via inhalation of aerosols (resp. droplets) |
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M. Tubercolosis
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Type IV sensitivity rxn due to T cell response
1. inhale droplet 2. makes its way to aveoli where it infects the macrophages 3. prevents destruction of macrophages via: -blocks phagolyosome fusion by blocking early endosomal autoantigen 1 (EEA1) or -catalyzying the toxic reactive nitrogen intermediates 4. multiply inside phagocyte and then macrophage migrates to lymph node and activate T cells (MHC2 and CD4 T Cells) GRANULOMA FORMATION: 5. dissemination CAN occur to spleen, BM, CNS 6. activation of T cells causes secretion of cytokines (TNF, IL-2, IFN-gamma) 7. INF-gamma activates macrophages and turns them into epithiliod cells and multinucleated giant cells 8. organism continues to divide 9. CD4 T helper cells produce Ab but they are no good in controlling the infection bc bacilli are safe when they are intracellular 9. leads to chronic infection bc organism is still dividing intracellularly inside macrophages and it takes about 3 weeks for T cells to get to site of infection 10. many macrophages die |
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VF of M. Tuberculosis
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1. special entry into macrophages
-Directly: LAM directly binds to macrophages -Indirectly: complement receptors allows it to indirectly bind to macrophages 2. grow intracellularly - invades Ab and complements -inhibits phagolysosome fusion to allow a safe enviroment for more growth 3. intefers with phagocyte killing mechanism - inhibiting phagolysosomes fusion - glycolipids, LAM, and sulfides down regulate cytotoxic mechanisms 4. Slow growers - since the bacilli are slow growing, immune system may not recognize them 5. Waxy cell wall -makes in resistant and impermeable to antimicrobials -resistant from attack by lysosyme 6. **Cord factor** -cell wall component very unique to this organism -causes cell membrane cytotoxicity -inhibits PMN migration -induces granuloma formation |
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TB test
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shows delay type 4 sensitivity
1. inject ppd 2. hardening occurs in dermis 3. wait 48-72 hrs and 3 possible outcomes a. - rxn=barely raised b. intermediate rxn (5-9 mm raised bump) c. + (>10 mm bump) *BCG vaccine will show + test* |
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stages of TB
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person gets infected (primary __)
-since 1st time exposure no Ab made..shows - test and radiograph test is - this has two outcomes: 1. progression to active stage of infection -skin test + -radiograph + -sputum + (do multiple sputum tests) -shows in 10% of infected people -HIV pts show this or 2. latent dormant stage -seen in 90% of infected -skin test + -radiograph + or - from this stage, there are 2 outcomes a. 90% will NOT have the dz or b. secondary (reactivation) occurs -skin test + -radiograph + -sputum + -careful for HIV pts will show this |
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M. TB clinical signs
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-seen in africa
-antimicrobials will not work -pt shoes weight loss -has chronic cough (granuloma formation) -daily fever, night sweats |
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mycobacterium leprae
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-granuloma formation
-slow growing (regen. time 12.5d) -obligate intracellular organism -grows best at low temps a. 27-33 deg. C b. prefers cooler body temps -CANNOT be cultured -transmission via resp. droplets, EXPOSED to infected pts -organism survives and replicates in macrophages 2 forms of this organism that produces Dz 1. Tuberculoid form 2. lepromatous form |
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M. Leprae Tuberculoid form
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-pt shows dry scaly lesions that lack sensation due to thickening of nerve sheath
-HUGE Th1 T cell response producing IL2 and IFN gamma -activate macrophages that engulf bacilli -infected tissures show lymphocytes and granulomas but few bacilli -no caseous necrosis - + ____ skin test |
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M. leprae Lepromatous form
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-lesions that are macular, papillar, or nodular that form through progression of dz
-bacteria survive and multiply in macrophages -weak Th1 T cell response, so bacilli multiply like crazy - see a enormous amt of bacilli in cooler areas of skin and superficial nerves -lesions show large aggregates of macrophages usually filled with masses of acid-fast bacilli -shows - on _____ skin test |
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Enterobacteriaceae (coliform)
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gram - rod
fac. anaerobe contain LPS (VF and has antigenic) ferments glucose (some can produce gas) nonspore formers oxidase - catalase + |
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Common VF for enterobacteriacae
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endotoxin (LPS)
Exotoxin adhesion molecules antiphagocytic capsule antibiotic resistance |
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Eshcerichia coli
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part of the enterobacteriacae:
gram - rod fac. anaerobe contain LPS (VF and has antigenic) ferments glucose and produces gas ferments lactose (on MacConkey agar=hot pink) nonspore formers oxidase - catalase + Host produce Ab to it's antigens: -O: somatic cell wall and is heat stable -H: Flagella -K: capsule can cause 2 types of dz: 1. intestinal: from exogenous sources (diarehea) 2. extranintestinal caused by pts. own normal flora being in areas where it is not suppose to be. (UTI, neonatal menigitis) there are many different strains which have different VF and this is due to plasmids and integrated prophage -some produce exotoxin -some have pilli 6 strains ETEC EHEC EPEC EIEC EAEC DAEC |
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Enterotoxigenic E. coli (ETEC)
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number 1 cause of travelers diar.
ingesting uncooked foods affects the S.I. by adhering to microvilli and secreting its toxins -stays inside the cell -produces 2 exotoxins: 1. LT (labile)- increase cAMP 2. ST (stable toxin)- increase cGMP -both these toxins causes an increase in cAMP which causes increase release of H20 and electrolytes--> WATERY DIARREHEA w/out blood TX: oral rehydration (not with h20) -anti-motility agents (but the diar. helps remove the organism) -Ciprofloxacin |
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Enterohemorrhagic E. coli (EHEC) or STEC
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abdominal cramping and bloody diarrehea w/out fever
affects COLON source is uncooked ground beef -attaches to microvilli and causes a cuplike pedestals to form -imitin secretion causes attachment and attachment/effaces (A//E) lesions -the the organism will secrete shiga like toxin (SLT) only if the lysogenic phage is present SLT (VF): -goes systemically and produces edema -inhibits protein synthesis by affecting the 60S organism produces: -initimin (allows for attachement) -eneteo-hemolysin (bloody diar.) O157:H7 carries locus of enterocyte effacement (LEE) -LEE allows for A/E lesions -LEE - will allow organism to become intracellular -does not ferment sorbitol can also cause hemolytic-uremic syndrome (HUS) -occurs in children <5 and Immuncompromised elderly -causes acute renal failure in children -will see schistocytes in PBS Tx: DO NOT give antimotility or Antibiotics (causes more toxin to be released) -rehydrate -avoid child until 2 neg stool cultures occur -if severe do plasmaphersis bc this is |
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enteropathogenic Escherichia coli (EPEC)
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affects SI
pt has fever, water diarrehea, moderate blood in stool 2nd most common cause of INFANT diar. in developing countries no toxin that causes this organism itself is the problem intimin (allows for attachment) is produced Bundle forming pili (BFP) allows for A/E lesions |
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Enteroinvasive Escherichia coli
(EIEC) |
INVASIVE- travels from cell to cell (transcytosis)
- positive fecal WBC - MUCOID diar. (not watery or bloody)= dysentry -1st watery then mucousy |
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EAEC
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causes traveler's diar. with low grade fever
this organism produces cytotoxin on the surface of epith. cells -clumps together and forms aggregates on mucus biofilm. -enterotoxin is released into cell -effacement of microvilli (esp. in HIV and infants) via: 1. organism produces a toxin that destroys and makes microvilli rounded 2. leading to hemorrag. necrosis |
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DAEC
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causes elongation of microvilli
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EXOTOXIN
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secrete enzymes that act on extracellular matrices
-like collagenase -just a little can kill a person Two types of Toxin: 1. surface active toxins: a. superantigens: activates T cells in an abnormal way -increase cytokines -could lead to toxic shock b. heat stable toxin of E.Coli: activates enzymes of host cell membrane -increase the secretion of cGMP -causes traveler's diar. c. pore forming toxins: damages membranes -could cause lysis of cell -bacteria could use this to get out of cell (dissemination) d. Phospholypases- damages membranes by degrading it e. surfactants- act as detergents -dissolve membran via removing and sequestering lipids 2. Intracellular toxins (toxins want to get into the cell) a. A-B toxin: A=active core (toxic) B: binds to receptors on host cells causing endocytosis b. type 3 effectors: causes inapp. signaling effects -INJECTED into host -some can be type 4 (lack N terminal- seen in pseudomon. aerg.) -not really lethal -not systemic -encoded on pathogenic i |
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Retroviridae
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7 types but only 2 that causes infections
1. deltaretrovirus (HTLV) 2. Lentiviruses (HIV) -all are diploid +ssRNA -enveloped with nucleoprotein inside that carries the RNA genome -carry their own reverse transcriptase, integrase, -they are immature until cleaved by protease -spikes (gp120 and gp41) on envelope helps fuse with host cell |
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Deltaretroviruses
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Made up of 2 lineages:
1. HTLV 1 a. adult T cell luekemia b. HAM/TSP (wkness in lower extremities) 2. HTLV 2 which is ASSOCIATED with hairy T cell leukemia |
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HTLV 1
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-seen mostly in South America and part of sub saharin Africa
Transmitted through cell to cell contact -BREAST FEEDING is #1 concern -blood, intercoarse Prevent: AVOID breastfeeding!!!, condoms, avoid sharing needles causes a. adult T cell luekemia -infection of T cells will allow HTLV into host genome -causing malignant T lymophocytes in peripheral blood -these cells have highly INDENTED or LOBULATED nuclei b. HAM/TSP (wkness in lower extremities) -occurs in many dzs that affect lungs, joints, eye, or skin - associated with chronic progessive myelopathy -also associated with tropical spastic paraparesis which is damage to spinal cord causing weakness in legs |
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HTLV 2
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Deltaretrovirus
which is ASSOCIATED with hairy T cell leukemia |
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HTLV 1 mechanism
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since it affects other cells via cell to cell contact--> leads to INTEGRAStion of viral DNA into Host DNA
1. when there is an immune response TAX is expressed 2. causes increased T lymphocyte cell replication and therefore more viral replication -increasing viral mRNA and number of growth proteins like: (IL2, IL15, Egr 1 and 2) by activating NF-Kb, Creb, AP-1 while inhibiting cell cycling regulators like (DNA repair, apoptosis) *there will be an immune response to the expression of TAX--> CD8 cells will remove them--> but a few will survive after many yrs (~40) there will be MUTATION in the cell line -leading to the expression of Tax for AUTO-PROLIFERATION will no longer be needed -they will be able to dodge the immune system -PROGRESSION of T CELL LEUKEMIA will occur |
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HTLV 1 DX and TX
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in lab: CD4 and CD25 "flower cells" (lobulated nuclei)
-could also test for antibodies in pt's serum using ELISA method or -test for monoclonal integration of _____ in T lymphocytes TX: -combo therapy with CHOP (antimalignant therapy) -Bone marrow transplant |
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Lentiviruses
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1. HIV 1
2. HIV 2- longer incubation and lower death rates -seen in the sub-saharan africa -both are nonlytic and cause AIDs |
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Replication of retroviruses
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1. the spikes on the envelope attach to host cell membrane
2. allows for FUSION of the two cells and allows virus into cell so it can UNCOAT 3. in the CYTOPLASM the ssRNA is converted to DNA strand by Reverse transcriptase and this is brought into the NUCLEUS 4. Viral DNA is INTEGRATED into host genome (pro-virus) 5. amplification by normal means to create proteins 6. ENVELOPE proteins are translated in RER *all genes for the envelope are located on the env portion of the viral genome *all viral enzymes are on the pol region *structural proteins are encoded on the GAG region -these type of viruses are organized with LTRs flanking their genome and the order of genes are: Gag, Pol, and Env -LTRs can act as promoters or enhancers -the same TF human genome uses can be used for viral DNA= EXPRESSION IS CONTROLLED BY IMMUNE ACTIVATION |
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Replication of HIV
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- Virus is aquired
-on it's envelope the virus expresses gp120 and gp41 1. gp120 binds to CD4+ receptors on host T lymphocytes causes a conformational change in gp120 2. gp120 is pulled apart from virus by CCR5 located on the host cell -this exposes gp41 3. gp41 levers the virus but eventually bending so virus can come into contact with cell and virus causing FUSION 4. after inside host cell, acidification occurs to uncoat caspid 5. RT acts on the ssRNA to create DNA in cytsol and then is transferred to the nucleus 6. inside nucleus, DNA meets us with INTEGRASE and is integrated into host DNA genome 7. synthesis of virus takes place mostly in cytosol -Env proteins (env. and spikes) are made in RER -self assembly occurs from outside to inside (matrix, capsid, then nuclear capsid) -we want nascant viruses with all the goods so it can be activated by cleavage using protease -nonenveloped viruses will congragate around the golgi (where spike proteins are) gag (structural proteins) are made 1st then po |
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HIV 1
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-seen everywhere in the world
-North America and Europe are affected by the B clade transmission: SEXUAL, parenteral, vertical to baby (1:4 if not tx) -seen more in HOMO sex -USE CONDOM and avoid breast feeding -causes AIDS clinical presentation: 1. Primary infection (3-4mths) -fast replication is occuring until CD8 respond -RNA decreases due to SEQUESTRATION and some being REMOVED by VIRUS -pt. seems to have MONONUCLEOSIS (FEVER, malaise, HA, maculopapular rash) 2. Secondary Infection (avg. 10 yrs if no TX) -virus accumlates due to more mutations bc of poor proof reading -asymptomatic -cellular immunity declines but viral load and Ab remain constant -CD4 cells drop in number -progession to next phase depends of pts VIRAL LOAD (12,000=slow progression 60,000= fast progression) AIDS= symptomatic or end stage -CD4 cell count is < 200 -pts get "SIGNATURE INFECTION" which is due to OPPORTUNISTIC organisms (ex: Candida albican, penumocystis jirovecii, mycobacterium avium, Kaposi's sarcoma, etc) -CD4 cells |
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DX and TX of HIV
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1. screening with ELISA searching for Ab against the virus
-2 positive results are needed to be positive 2., Western blot in search of viral protein -neg=total absence of band -pos= presence of at least 2 (p24 (one of the 1st bands to appear and usually is the strongest) ,gp41,gp120, or gp160) TX: 1. attachement/fusion - Enfuvirtide-->gp41 -Maraviroc--> CCR5 anatgonist NRTI: -Zidovudine (AZT) -Lamivudine (3TC) -Emtricitabine (FTC) NNRTI -Efavirenz Integrase Inhibitor -Raltegravir Protease Inhibitor - Idinavir -Ritonavir -nelfinavir |
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Herpes Virus
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attacks WBC but does not cause immunodef.
-linear dsDNA -enveloped -tegumented: proteins btwn the envelop and nuclear capsid -some have an excess of 200 ORF (open reading frame) in contrast to HIV that has about 15 ORF 3 subfamilies: 1. alpha____virinae (HHV 1/2, 3) 2. Beta____virinae (HHV 5 [CMV], 6/7) 3. Gamma___virinae (HHV 4, 8) oncogenic -establish latency |
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Betaherpesvirinae (HHV 5)
human cytomegalovirus (HCMV) |
-found worldwide and most people get infected with this
-asypmtomatic in pts esp children -self limited=goes away -can show up as mononucleosis in immunocompetent teenagers and young adults -severe if aquired in utero a. transplacental (crosses placenta) b. perinatal via genital secretions c. postnatal via saliva, genital secretions, fomites, blood transfusion, solid organ transplants -can be reactived in immunocompromised pts and this is a source of the severe version -virus can infect a bunch of organs and glands and endothilial cells and MACROPHAGES Pathogenisis: depends on when and how much of virus enters the bloodstream (viremia) a. low viremia= tissue damage caused by HOST IMMUNE RESPONSE against virus b. High viremia= tissue damage caused by DIRECT VIRAL CYTOTOXICITY and host immune response DX: -PCR = presence of virus -serology= current vs. remote infection TX: since self limiting tx is for immunocompromised pts - Ganciclovir * mutations in UL97 and UL54 genes induce antiviral resistance |
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Betaherpesvirinae (HHV 6 and 7)
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-responsible for roseola infantum or known as the SIXTH DZ
-affects children < 2 -symptoms of high fever with rash on trunk and neck -tranmission could be from saliva -found worldwide -proliferate in CD4 lymphocytes and can infect B lymphocytes and monocytes./macrophages (resivoir for latent viruses) -lasts for a week and resolves -reactivations of latent version (usually with HCMV) in immunocompromised pt lead to: a. bone marrow suppression b. encephalitis c. pneumonitis d. acute graft vs. host dz e. worsens HIV infection Pathogenisis: -increase CD4 expression and NK cells -decreased CD3= decrease TCR signaling -increased cytokine relase= lymphoproliferation -CD4 cell activation in HIV pts (bad) DX: clinical, serology, PCR |
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Gammaherpevirinae (HHV 4)
Epstein-Barr virus (EBV) |
responsible for:
1. INFECTIOUS MONONUCLEOSIS 2. Burkitt's lymphoma 3. nasopharyngeal carcinoma 4. Hodgkin's Dz -seen worldwide in adults a. 90-95% of adults have this -transmitted via oropharnygeal secretions pathogenisis: -infects orophary. epith. cells and B LYMPHOCYTES *viral replication is maintained by sporadic lytic activation -B lymphocyts (memory) cause viral dissemination and PERSISTENCE -is associated with expression of latent genes and genes taht PROMOTE cell activation and PROLIFERATION -proliferation of B lymoBLASTs which disseminate cause T LYMPHOCYTE response (CTL) and increased number of ATYPICAL CD8 lymphocytes --> characteristic of INfectious MONOnucleosis symptoms of Infectious mono.: -enlargement and tenderness of cervical lymph node -PHARYNGITIS -fever, HA, malaise Primary ___ infection in children is usually asymptomatic Complications of virus: -could cause hepatitis -morbilliform skin rashes after taking ampicillin -splenic rupture -airway obstruction -Guillain-Barre syndrome |
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Gammaherpevirinae (HHV 8)
Kaposi's sarcoma associated with herpes virus |
- unevenly seen around the world
Transmission: -during childhood via mother -during adult via sex Pathogensis: -induces proliferative pathways ex: virokynes, v-cylins -angiogenisis and apoptosis inhibited symptoms: -firm, blue-brownish plaques on skin -nodules present and likely to ulcerate and bleed on lower extemities DX: serelogy, PCR TX: indirect (many cases ass. with AIDS) -use HAART or ART |
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Healthcare aquired infection (HCA)
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-do not come from hospitals
- can be endogenous and exogenous -MRSA |
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endogenous sourcee
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pts. own body, own flora
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exogenous source
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from other patients
workers equipment |
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Hospital aquired infection (HAI)
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-can get it from exogenous or endogenous source
-seen at least 48hrs after being admitted or w/in 48 hrs of leaving -common causes: a. crowding b. immunocompromised pts c. invasive procedures d. lack of adequate prevention control -fall into 4 categories due to breeching the natural barriers 1. UTI 2. surgical infections 3. pneumonia 4. bloodstream infections -often resistant to at least 1 antibiotic -most lethal is pneumonia and bactermia |
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ways to control infections
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1. exclude the source
-sterlize, disinfect..etc=aseptic techniques -screening staff -screening blood products 2. block transmission -cleaning -using approp. isolation -HANDWASHING -vector control 3. survillance of trends and dealing with outbreaks 4.identify causative organisms -use antibiograms -typing -molecular technq like pulsed field gel electroph. (PFGE) a. allows us to see if pts are carrying the same strain parhogen b. MLST- also determines "relatedness" of subtypes |
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Staph aureus
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causes all types of HAI infections
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Strep. Pneumoniae
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HAI infection caused: respiratory
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Enterococcus faecium and faecalis
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HAI infection caused:
-surgical -bacteremia -UTI |
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Pseudo. aeruginosa
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HAI infection caused:
-respiratory -surgical |
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E. coli
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HAI infection caused:
-MAJOR cause of UTI -anything else |
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klebsiella pneumoniae
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HAI infection caused:
ALL |
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candida
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HAI infection caused:
-UTI (minor) -bacteremia |
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UTI
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caused by:
e.coli proteus mirabilis enterococcus staph candida |
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Surgical infections
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caused by:
staph enterococcus E. Coli Pseudomonas Enterobacter |
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Respiratory infections
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caused by:
P. aeruginosa k. penuomoniae E. coli S. pneumoniae H. influenza |
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Bacteremia
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caused by:
staph entercoccus candida gram - |
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GI infections
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caused by:
clostridium difficule |
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negative pressure
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usually done for SOURCEs of infection
air can come in bugs can't leave TB patients |
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positive pressure
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used for patients at risk
immunocompromised patients -neutropenic -chemo pts air leaves when door is opened |
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droplet precaution
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1. large droplet fall to the floor
need mask and eye protection for 3ft pt must wear mask when leaving the room can group patients together witht the same dz 2. aerosols:stay in the air -pt has their own room -use - pressure with HEPA filter -MASK is required -use for TB, measles, small pox, SARS |
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steriliant
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-destroys ALL viable organisms via
1. heat= steam is preferred bc it doesn't take as long -usually kills everything 2. irradiation- mantains protein structure -usually kills everything 3. Filtration- used in liquids -use in pyogen free products like: a. air b. liquid c. IV fluids -not good at killing viruses 4. chemicals- can do the whole room -Ethane Oxide: TOXIC -formaldehyde/glutaraldehyde: CARCINOGENIC -plasma gas:H202 kills FREE RADICALs and breaks down into O2 and water -better bc airing out time is not as long |
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Disinfectant
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-destroys MOST (not all) viable organisms
*does not kill spores 1. High level: BLEACH (can't kill if there is a high spore load) 2. Intermediate: lodophor, alcohol, phenolics -kills mycobacteria, viruses, and fungi -ALCOHOL does not kill SPORES or NONEVELOPED viruses 3. Low Levels: quaternary ammonium compouds -kills vegatative bacteria -surfaces that come into contact with skin |
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Antiseptic
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-dissinfects LIVE tissue
-ALCOHOL -BETADINE: can kill mycobacteria -chlorohexidine -cant kill spores |
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surfactant
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DOES NOT kill microbes
but allows their REMOVAL to be easier soaps detergents |
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pulsed field gel electroph. (PFGE)
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-take bacterial chromosome
-use restriction enzymes -run it in gel..should get large pieces of DNA -helps identify bug -acts like a fingerprint |
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MIC
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lowest concentration of drug to inhibit growth
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MAB
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lowest concentration of drug to kill organism
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tolerance
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occurs when the antibacterial's action becomes STATIC (inhibiting growth) from CIDAL (killing)
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Resistance
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when organism is not inhibited or killed by biologically achieved levels of antibiotics
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Innate resistance
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due to lack of target or structural defense prohibiting reaching the target
ex: organism itself is an antibiotic producer -has machinary to make these antibiotics (mold) so it cant be killed by its own antibiotics -vancomycin can't kill gram - bc they dont have a cell wall |
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aquired resistance
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organism obtains this type of resistance wither by:
-point mutations -gaining a gene via: a. conjugation b. transformation (direct uptake) c. transduction (plasmid) this change can be advantageous (organism will outcompete others allowing change to be maintained) or disadvantageous -compensation: change that occured causes decrease fitness but then another change occured that restored the fitness or even improved it this could lead to the resistance change to be permnant some organism could become drug addicts |
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selective pressure
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a particular change in genetic that becomes beneficial to organism
the organism with the change will outcompete others w.out change and will be able to replicate more |
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methods antibacterial resistance can occur
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1. mediated through transport
2. mediated by modifications or replacement of target 3. modification of the drug *these methods work bc they keep drug concentrations below the MIC |
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resistance occuring via transport
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access of antibiotics can be affected by:
1. efflux- more of it leaves the cell -these pumps require energy -most are H antiporters -ABC pumps need energy 2. reduced influx (decreased amount entering cell) -decreased permeability -more efficient -downside is it can block other things as well -Pseudomonas aeruginosa and acinebacter baumannii have NOTORIOUS imper. cell wall 3. sequestration of the drug |
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resistance occuring via modification or replacement of target
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-increased amt of targets = higher MIC to where the drug has no effect. this can be caused by:
a. mutation in the promoter region, gene duplication, or altered expression ex: vancomycin resistance - modification so drug has NO effect of target ex: FQ resistant campylobacter have altered their DNA gyrase so it can no longer be effected by drug and allows faster replication to occur -usualy change to target came via a mutation rather then a REPlACEMENT (due to aquiring a gene) |
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examples of resistance occuring via modification or replacement of target
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1. due to point mutations (more common) alteration of target
a. linezoid b. FQ c. XDR TB 2. aquired genes: a. MRSA b. Vancomycin resistance 3. Penicillian resistance in Strep 4. addition of functional groups after translation which prevent antibiotic binding -usually aquired -involves an entire enzyme a. MLSB |
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linezoid drug resistance
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due to point mutation
protein synthesis inhibitor blocks formation of 70s DOES A SINGLE POINT MUTATION ON THE 23S ON RDNA TO PREVENT BINDING DEGREE IS BASED ON THE NUMBER OF COPIES AFFECTED |
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FQ drug resistance
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targets DNA gyrase
IN STREP THERE IS POINT MUTATIONS w/in gyrA parC/parE level or resistance is due to number of mutations (increased mutations = increased resistance) |
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XDR TB
extensively drug resistance TB |
resistance to more than rifampin and INH
due to single point mutation in genes that target: -katG/inhA=isoniazid -rproB for rifampin -gyrA for quinolines |
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MRSA
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aquired gene causes this resistance
resistance to nifcillin and oxacillin and methicillin due to alternate PBP that is encoded by MecA (a mobile element) |
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Vancomycin resistanvce
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-caused by altering target from D-ala-D-ala to either a:
-terminal serine or lactate -MOST LIKELY CAME BY BACTERIA PRODUCING LACTATE OR SERINE AA -probably caused by STAPH AUREUS OR ENTEROCOCCUS FAECALIS |
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Beta lactams
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-ring structure found in antibiotics
a. penicillan b. cephlasporin -these organism have beta lactamases that break down the ring of the beta lactam important in gram + in a. staph aureus and n. gonorehea acquires resistant via: 1. target replacement: a. PBP2a doesnt bind to drug efficiently -mecA in MRSA and MRSE b. mosaic PBPs do not bind drug effienctly -s. pneumoniae 2. altered drug a. point mutationin PBP5 reduces binding -E. faecium 3. Degradation a. various of these type of drugs -many species |
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antifungal and antiparasitic
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aquire drug resistance in all methods except alteration of drug
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antiviral
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via point mutation
due to having no machinary to aquire resistance alters drug target |
