SM Flashcards

1
Q

Resist: VRE

A

• VRE (vancomycin resistant enterococcus): mutates terminus to D-ala-D-lactate, Vancomycin normally binds to D-alanyl-D-alanine terminus and blocks linkage to glycopeptide polymers
Vanco: only effective vs gram+

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2
Q

• Coronavirus:

A

• Coronavirus: ssRNA+, encapsulated, replicates in cytoplasm
• Unique: helical virus, SARS, common cold, MERS
○ Acute bronchitis –> acute respiratory distress syndrome
Test via PCR or antibody detection

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3
Q

Resist: MRSA

A

MRSA (methicillin-resistant staph aureus): mutates PBP to PBP2a, now penicillin cannot bind so cross-linking of peptidoglycan continues as normal

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4
Q

MIC interpretation

A

• MIC interpretation: minimum inhibitory concentration (MIC)
• Lowest concentraiton of an antibiotic that prevents visible growth of bacteria after 18-24 hours of incubation
○ Expressed as concentration mg/ML
○ Breakpoint: seperates strains where this is a high likelihood of treatment success vs. those that will likely vail treatment
§ Want to use the drug that is furthest from the breakpoint!
• Serial tube dilution
• Automated microbrowth dilutions or premade cassettes/cards

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5
Q

• Bacillus anthracis

A

• Bacillus anthracis
• Gram + bacillus, “rods in chains”, poly-D-glutamate protein capsule, obligate AEROBE
• Transmission: spores–> inhalation, cutaneous
• Disease:
○ Cutaneous: black eschar with cutaneous inflamed ring
○ Pulmonary anthrax: wool sorters disease, starts with non-specific cough symptoms, can progress to pulmonary hemorrhage (100% mortality), chest x-ray shows widened mediastinum (lymph nodes)
• Virulence/toxins:
○ Edema Factor: acts like adenylate cyclase, increases cAMP, increase edema
○ Lethal Factor: exotoxin, protease that cleaves MAP-kinase, results in tissue necrosis
Tx: Fluoroquinolones, Doxycycline

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6
Q

HPV

A

• HPV: dsDNA, naked
• Strains 1-4: verruca vulgaris (cutaneous common wart)
• Strains 6, 11: Laryngeal papillomatosis (recurrent respiratory papillomatosis),
○ Acquired during vaginal birth
• Strains 6, 11: condyloma cuminata (anogenital warts)
○ Acquired during sex
• Strains 16, 18, 31, 33: anogenital cancers, squamous cell carcinoma
○ Acquired during sex
• HPV vaccine: 6, 11, 16, 18, guardasil
○ Most common STD
• Cancer mechanism: HPV encodes E6 (proteolysis of p53) and E7 (RB targeted)
○ AIDS-defining illnesses: immunosupression increases risk of HPV cancers
○ Post-coital bleeding, think CANCER
Pap smear: screening for cervical cancer (Koilocytes, bi-nucleated risky)

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7
Q

ID of step. spp.

A

Identification of streptococci: grows in strips, patterns of hemolysis differentiate
• Parital lysis, green, Alpha: viridans, pneumoniae
• Total lysis, glow, Beta: pyogenes, agalactiae
No lysis, Gamma: gallolyticus

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8
Q

• Mucormycossis

A

• Mucormycossis
○ R: mucor and rhizopus both cause, opportunistic infections (leukemia, neutropenia, diabetes)
§ Bread mold
§ Transmission: inhalation of spores
○ C: diabetic keto acidosis: most common clinical predisposition
§ Proliferate in blood vessels -> Penetrates the Cribiform plate -> enter brain -> necrotic tissue around eyes and nose “rhinocerebral mucormycoses”
H: Wide-angle branching (90 degress), nonseptate rods

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9
Q

• Malaria

A

• Malaria
○ Transmission of Plasmodium by Anopheles mosquito
○ Clinical manifestation:
§ Falciparum: edothelial cyto-adherence result in capillary bed occlusion –> end organ dysfucntiono
§ Cytokine release: TNF, IFN, IL1, diffuse endothelial activation/inflammation, capillary leak syndrome
§ Anemia
○ Testing: thin-film, thick-film blood smear
§ Rapid test: antigen testing
PCR: send out test, confirms species

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10
Q

CMV

A

• CMV: cytomegalovirus, DNA virus, herpes virus family
• Transmission: blood, sex, breast milk, saliva, TORCH
○ Congenital CMV: blueberry muffin rash (petechial rash), hepatosplenomegaly, jaundice, sensorineural deafness, peri-ventricular cranial calcify, ventriculomegaly–> seizures, 85% asymptomatic ; 2nd trimester maternal transmission
§ #1 congenital fetal viral infection: #1 cause sensorineural hearing loss
§ Hydrops fetalis: loss of fetus
○ CMV pneumonia: especially in transplant patients
○ CMV retinitis (pizza pie retinopathy), CMV esophagitis (linear ulcerations), CMV colitis (with ulcerated walls)
§ CD4 count <50
○ CMV mononucleosis: in non-suppressed people, mono-spot test would be negative
• Latency: mononuclear cells (B T macrophages), owl’s eye inclusion bodies in infected cells
• Reactivation: under immunosuppression
• Tx: gancyclovir, phoscarnet (for UL97 gene mutation)

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11
Q

• Streptococcus pyogenes

A

• Streptococcus pyogenes
• Gram + cocci, GAS, bacitracin-sensitive, encapsulated (hyaluronic acid, non-immunogenic), beta-hemolytic
• Diseases:
○ Pharyngitis: strep throat
○ Impetigo: skin, honey-crusted
○ Cellulitis:
○ Erysipelas: well demarcated borders, #1 cause
• Autoimmune mediated disease:
○ Rheumatic Fever: only happens post pharyngitis, auto-immune response to mimicry of M-antigen, resulting in attack of heart tissue/mitral valves, type 2 hypersensitivity rxn
§ Joints polyarthritis, Heart valvular damage, myocarditis, endocarditis, Nodules, Erythema marginatum, Sydenhams Chorea
§ Prevented by penicillin treatment of primary infeection
○ Post-strep glomerular nephritis: coke-colored urine, facial edema, 2 weeks can after pharyngitis or superficial/impetigo, type 3 hypersensitivity rxn (immune complexes deposit into glomerulus)
§ Not prevented by penicillin of primary infection
• Toxin mediated disease:
○ Scarlet Fever: strawberry tongue, pharyngitis, wide-spread rash that spares face
○ Necrotizing fasciitis: invade fascia, spreads rapidly
○ Toxin shock-like syndrome: superantigen
• Toxins
○ SpeA: superantigen TS/SF; SpeB: protease nec. Fasc.; SpeC: super antigen TS/SF
• Virulence:
○ M-protein: interferes with opsonization, antigenic/mimicry in RF
○ Streptolysin O: we generate antibodies to this
○ DNAse
○ Streptokinase: converts plasminogen to plasmin (given to break up clots in people)
• Tx: Penicillin
• Testing: Blood test for Anti-streptolysin O

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12
Q

• Pneumocystosis

A

• Pneumocystosis
○ R:
§ Transmission: respiratory transmission
○ C: Pneumocystis Pneumonia (PCP), healthy and immunocompromised can be infected but compromised only show symptoms
§ AIDS defining illness: CD4 count under 200 (start prophylaxis at this level)
§ X ray: whispy diffuse infiltrate, ground glass appearance (crushed ping pong balls)
H: bronchoaveolar lavage, lung biopsy, methamine silver stain will show disc shaped yeasts

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13
Q

• Lincosamides:

A

• Lincosamides: binds 50S ribosomal subunit–>stops peptide synthesis/protein formation
○ Bacterialstatic
Similar mech to: Macrolides, Clindamycin, Erythromycin, Linezolid, Chloramphenicol

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14
Q

Staphylococcus aureus

A

• Gram + cocci, grows in clusters, coagulase +, catalase +, grows golden on blood agar, beta-hemolytic, ferments mannitol (turns mannitol-salt agar yellow)
• Diseases: colonizes nose
○ Inflammatory:
§ Pneumonia: patchy infiltrate, post-viral secondary superinfection
§ #1 adults Septic arthritis
§ Cellulitis/Impetigo/Carbuncles/Furuncles: erythematous abscess
§ Rapid onset Endocarditis: tricuspid infection (IVDU)
§ #1 osteomyelitis
○ Toxin mediated:
§ Food poisoning: mostly emetic, fast onset, pre-formed toxin, 1-8 hours, meats/creams
§ Scalded skin syndrome: exfoliative toxin, skin peals off
§ Toxic shock syndrome: TSST superantigen, overactivation of T cells cytokine storm, forms in wound packing/tampons
• Virulence:
○ Protein A: component of cell wall, binds FC portion of IgG, prevents opsonization/complement activation
○ TSST-1: mediates toxic shock syndrome, super antigen
○ Exfoliative toxin: mediates scalded skin syndrome
Tx: Naficillin (if methacillin sensative), vancomycin (if MRSA, mutates PBP)

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15
Q

• Actinomyces

A

• Actinomyces
• Gram + , branched/filamentous rod, OBLIGATE ANAEROBE
• Transmission: normal flora of oral cavity–> jaw trauma/procedures can cause it to spread into wound
• Disease: cervicofacial actinomyces infection
○ Slow course, forms lump then abscess then sinus tracts draining sulfur granules
• Unique: sulfur granules (yellow), sinus tracts
Tx: penicillin G, surgical drainage

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16
Q

• Nocardia

A

• Nocardia
• Gram +, branched/filamentous rod, acid -fast staining (mycolic acid, carboyl-fuchsia staining), catalase +, OBLIGATE AEROBE, urease+
• Transmission: Found in soil
• Primarily effect IMMUNECOMPRIMISED pts, Men&raquo_space;> Women
○ Pulmonary: pneumonia + lung abscess/cavitary lesions
○ CNS: brain abscesses
○ Cutaneous: open wounds exposed to dirt, pyogenic response, indurated lesions
Tx: sulfonamides

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17
Q

• Histoplasmosis

A

• Histoplasmosis
○ R: bird/bat droppings, caves, farmers
§ Geography: midwestern/central USA, mississippi valley
§ Transmission: respiratory system
○ C: systemic, asymptomatic, can cause pnemonia from granuloma formation-> calcify nodules with fibrotic scarring, resembles TB, erythema nodosum on legs
§ Dimorphic: mold in the cold, yeast in the heat
§ Immune compromised disseminated form: hepatosplenomegaly, targets reticulo-endothelial system
○ H: macrophages filled with intracellular oval bodies
§ Stain with KOH prep
§ Much smaller than RBC
Dx: serum rapid antigen test, urine rapid antigen test

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18
Q

Pertussis toxin mechanism

A

Pertussis: AB toxin exists as hexamer, ADP ribosylates a host cell G protein –> increases cAMP levels

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19
Q

• African sleeping sickness

A

• African sleeping sickness
○ African Trypanosomiasis: trypanosoma brucei gambiense (most common) trypanosoma brucei rhodesiense (severe disease)
○ Bite reaction from Tsetse fly: chancre forms 1-3 weeks after bite, leaves no scar
○ 1st stage: hemolymphatic infection
○ 2nd stage: meningoencephalitis
○ Epimastigotes: in fly, transforms into trypomastigote, visualize trypomastigotes in human blood
○ “Antigenic variation” with Variant surface glycoproteins (VSGs) therefore block host immune system from getting at invariant antigens and creates cyclical waves of parasitemia
§ Recycling of VSGs that get recognized by immune system
Testing: Trypomastigotes on blood smear or in CSF

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20
Q

• Escherichia coli

A

• Escherichia coli
• Gram - coccobaccili, lactose fermenter, catalase +, encapsulated, k-antigen on capsule, grows green on EBM agar, fimbrae/pili
• Diseases:
○ #1 UTIs: caused by fimbrae/pili
○ #1 gram negative sepsis: mediated by LPS endotoxin
○ Meningitis in neonates (Requires K antigen)
○ EHEC: undercooked meat, bloody diarrhea, does not ferment sorbitol, can cause HUS
§ Toxin: Shiga-like toxin: inhibits ribosomes at 60S
§ O157:H7 serotype involved in outbreaks
○ ETEC: traveler’s watery diarrhea, transmitted from dirty water, “montezumas revenge”
§ Toxin: heat labile: increased cAMP (like cholera toxin)
§ Toxin: heat stable: increased cGMP
Tx:

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21
Q

Transferrin

A

Transferrin: binds to surface receptor on gonorrhea, iron is removed and internalized

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22
Q

• Human metapneumovirus:

A

• Human metapneumovirus: sRNA-, pneumoviridae
• #2 most common lower resp tract infection in children, less severe than RSV
• Dx: RT-PCR
No Tx, No Vax

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23
Q

• Streptococcus agalactiae

A

• Streptococcus agalactiae
• Gram+ cocci, bacitracin-resistant, hippurate+, beta-hemolytic, CAMP test + (increasing zone of hemolysis when plated with staph aureus), encapsulated, group B strep
• Transmission: mom->baby during vaginal delivery
• Diseases:
○ #1 Meningitis in neonates
○ Sepsis in neonates
○ Pneumonia
• Tx: penicillin for mom before delivery
Prevention: swab mom at 35 wks

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24
Q

• Rotavirus:

A

• Rotavirus: dsRNA, replicates in cytoplasm, naked, segmented (11), type of reovirus
• NSP4 toxin: secretory explosive water diarrhea
○ Increases chloride permeability–> watery diarrhea
○ Winter-time outbreaks
○ Children high risk for infections (#1 cause severe diarrhea in children)
• Tx: live attenuated oral virus vaccine
○ 1st dose: before 3 mo age
Vax side effect: Increases risk of intussusception (telescoping of bowel)

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25
Resistance: CRE
CRE (Carbapenem-resistant Enterobacteriaceae): efflux of drug OR loss of outer membrane porins
26
• Life cycle of Schistosoma/Bilharzia/snail fever
• Life cycle of Schistosoma/Bilharzia/snail fever • Trematode (flatworm): S. Mansoni: Intestinal, stabbing spike, --> portal hypertension S. Japonicum: Asian intestinal, round --> portal hypertension S. Haematobium: urinary, lancet --> bladder cancer • Cercariae penetrate the skin--> blood vessels of bowel/rectum or bladder, mature into sexual adults and make eggs --> eggs passed from humans into water, eggs hatch and release miracidia--> miracidia penetrate snail tissue and mature into sporocysts --> cercariae released into water Dx: urine eggs
27
• Kirby-Bauer susceptibility testing:
• Kirby-Bauer susceptibility testing: disk diffusion, spread known amount of bacteria evenly on a plate, incubate, organisms grows or dies depending on its MIC and diffusion rate of antibiotic, larger area of killing, greater suspetibility • MIC where growth meets no growth on the E strip Some subjectivity
28
• Blastomycosis
• Blastomycosis ○ R: § Geography: southern, eastern USA, great lakes/ohio river valley § Transmission: inhalation of spores ○ C: patchy alveolar infiltrate on xray, lesions or cavities in lung, acute or chroni pneumonia § Can spread "systemic" in immunocompromised: disseminates to skin and bone (osteomyelitis) § Dimorphic: mold in cold, yeast in heat H: broad based budding, same size as RBC, urine antigen test
29
• Mycobacterium leprae
• Mycobacterium leprae • Thrives in cool temperatures (explaining predilection for extremities), acid-fast staining (mycolic acids) ○ Reservoir: armadillos, Hansen's Disease • Tuberculoid form: Th1 response with cell mediated immunity, able to contain bacteria in macrophages, mild disease, ○ well demarcated, hairless, skin lesion ○ Lepromin skin test: test for immune reaction, positive: demonstrates good cell mediated response, like PPD skin test • Lepromatous form: Th2 mediated- humoral response, prevents containment of bacteria within macrophages, causes humoral response ○ Transmission: unknown, perhaps resp droplets, human-human ○ Neuropathy symmetric with glove stocking pattern ○ Numerous poorly demarcated skin lesions on extensor surfaces of extremities ○ Leonine faces • Tx: ○ Tuberculoid: dapsone, rifamapin 6 months Lepromatous: dapsone, rifampin, clofazimine 2-5 years
30
• Pseudomonas aeruginosa
• Pseudomonas aeruginosa • Gram - bacilli, grape-like odor, catalase +, oxidase +, produces blue/green pigments when plated, obligate aerobe, encapsulated ○ Catalase + : therefore extra susceptible to chronic granulomatous disease • Transmission: environment contaminate • Diseases: ○ Hot-tub folliculitis: puritic papular ○ Ecthyma gangrenosum: Cutaneous necrosis if gets into systemic circualtion ○ #1 Nosocomial Pneumonia ○ #1 Respiratory failure in CF patients: because Cl- channel dysfunctional ○ Nosocomial UTIs/catheter infections ○ Osteomyelitis: IVDU, diabetics ○ Burn patients: feared complication of burn wounds, often fatal ○ Otitis externa • Toxins: Exotoxin A: ADP-ribosylates EF2 Treatment: Piperacillin, fluoroquinolones, aminoglycosides
31
Resistance: ESBL
• ESBL (Extended-spectrum beta-lactamases): produce beta-lactamase in periplasm that chews up the beta-lactams ○ Use combo- beta-lactam/beta-lactamase inhibitor drug combos Carbapenems effective
32
• Rhinovirus:
• Rhinovirus: pico virus family, RNA+, Naked, • Transmission: respiratory system, acid labile (therefore cannot go thru GI tract), transmitted though fomites (yucky hands) ○ Attaches to ICAM-1 on host cells to enter ○ Grows best at 33C (slightly cooler than body), therefore found in upper resp. tract • Translation: use host cell machinery--> polyprotein product, cleavage by viral packaged protease--> processed in cytoplasm MANY different serotypes, therefore tough to make vaccine, common cold!
33
• Herpes zoster vaccine:
• Herpes zoster vaccine: SHINGRX, adjuvanted recombinant vaccine, VZV glycoprotein plus t cell bosting adjuvant (our immune system gets worse when we get old and so shingles pops out when we age) Shingles: reactivation of VZV from dermatomal ganglia
34
• Streptococcus gallolyticus
• Streptococcus gallolyticus • Gram + , alpha or gamma hemolytic, but classified as Group D strep within B-hemolytic streps Blood stream infection associated with colon cancer
35
• Cephalosporins:
• Cephalosporins: inhibits trans-peptidase enzyme (penicillin binding protein), therefore no cross linking of peptidoglycans, therefore no stability to cell wall ○ Similar to penicillin ○ Bacterialcidal Time-dependent killing
36
• Fluoroquinolones:
• Fluoroquinolones: disrupts DNA synthesis--> inhibit DNA gyrase and topoisomeraseIV--> inhibits protein synthesis ○ Bacterialcidal ○ Gram - most effective Concentration dependent killing
37
Respiration/Fermentation
• Respiration and fermentation • Respiration: O2 electron acceptor of NO3-, happens between 2 cell membranes/wall, more efficient • Lactose Fermentation: grows pink colonies on MacKonkeys Agar ○ E coli ○ Klebsiella pnemoniae ○ Enterobacteracie ○ Serratia • Maltose fermentation: G. meningitidus yes, G. gorrorehea no • Sorbitol fermentation: NOT EHEC, all other E. coli do Mannitol fermentation: s. aureus, grows golden
38
• Coxiella burnetii
• Coxiella burnetii • Gram +, Obligate intracellular, SPORES • Transmission: spores in dirt, survives animals GI tract and poops out spores, transmitted to humans via aerosolized transmission ○ Reservoir: farm animals • Q fever: pneumonia, headache, fever, HEPATITIS NO RASH
39
• HHV-8:
• HHV-8: dsDNA, herpes virus, • Unique: Kaposi Sarcoma (AIDS/immune suppression) = erythematous on nose, mucous membranes (Gi tract, hard palate), extremities ○ Pathogenesis: angiogenesis by dysregulating VEGF • Infected B cells: primary effusion lymphoma • Transmission: sexual contact/kissing ○ AIDS pts, Elderly Russian men, African folks • Dx: microscopic, leukocytic infiltrate ○ Can be confused with Bartonella hensleae Tx: antiretrovirals for HIV+ pts
40
• Parvovirus B19:
• Parvovirus B19: naked virus, smallest DNA virus, ssDNA • Transmission: respiratory droplet, TORCH • Kids: Slapped-cheek rash/Fifth disease/Erethema infectiosa ○ Rash starts on face and moves downward • Adults: join pain, arthritis, edema • SCD: aplastic anemia, cobweb look In Utero: Hydrops fetalis
41
• Klebsiella pneumoniae
• Klebsiella pneumoniae • Gram -, nosocomial (multi-drug resistance), lactose fermenter, non-motile, encapsulated, urease+ • Diseases: Pneumonia, UTIs ○ Alcoholics, Abscesses, Aspiration § Chest x ray for abscess might look like TB • Unique: current jelly-sputum Tx: Carbapenems
42
• Mycobacterium avium-intracellulare
• Mycobacterium avium-intracellulare • Atypical mycobacterial infection with nontuberculous mycobacteria caused by 2 species of mycos ○ Immunocompromised people more susceptible (AIDS) cystic fibrosis • First presents as persistent cough, also fevers/diarrhea/malabsorption/weight loss, • Common in the environment and infect when inhaled or swallowed Macrolides used as prophylaxis in AIDS pts
43
• Viral replication:
• Viral replication: ss(+)RNA vs ss(-)RNA vs dsDNA vs retrovirus • -RNA: brings along own RNA polymerase, all single stranded, replicates in cytoplasm ○ EXCEPT: orthomyxovirus replicates in nucleus • +RNA: ○ EXCEPT reovirus is double stranded • DNA:
44
• Respiratory syncytial virus:
• Respiratory syncytial virus: ssRNA-, enveloped • #1 Lower respiratory tract illness in children: bronchiolitis, pneumonia, tracheobronchitis, croup • Recurrent wheezing common following severe infection • Dx: antigen detection, RT-PCR • Prevention: monoclonal antibodies for high risk Tx: nebulized hypertonic saline
45
Cytochrome
Cytochrome: bacteria containing cytochrome c = oxidase positive
46
• Francisella tularensis
• Francisella tularensis • Gram - , coccobaccili (radish-like), Tularemia • Transmission: rabbits (meat, direct contact) or through tick vector (dermacentor), CAN BE AEROSOLZIED ○ Tick bite ulcerates to introduce bacteria ○ Goes into macrophages ○ Travels through lymph system to reticular endothelial organs (lymph nodes) ○ Causes caseating necrosis § Swells and make palpable lymphadenopathy of nodes § Can spread systemically to other nodes • Facultative intracellular ○ Therefore recovery depends on cell mediated immunity ○ Helps spread disease through body Tx: aminoglycosides
47
• Risk factors for disease acquisition: echinococcosis
• Risk factors for disease acquisition: echinococcosis • Dog Tape worm, infected with cystic form of tapeworm, humans are intermediate host ○ Often asymptomatic, symptoms result from growth/expansion of cysts, cystic rupture can cause anaphylaxis § Within the cyst is the larvae ○ Dog injects cysts from viscera of sheep, humans accidentally ingest dog feces with eggs inside Ranchers & Shepherds at risk, worldwide
48
• Leishmaniasis
• Leishmaniasis ○ Visceral: Kala-azar, parasties in macrophages of reticuloendothelial system § Shows up like lymphoma, hepatosplenomegaly, amastigotes in macrophages in bone marrow § L. donavi, brazil, africa, indian ○ Cutaneous: skin, more common, world wide § Old world: limited to skin, self limited, scar § New world: L. braziliensis, L. mexicana, L. panamensis more difficult to treat, spread to mucosa (worry about this!) ○ Transmission: sand fly injects promastigote into human, transforms to amastigote in macrophages § Human to human, with sand fly in between, zoonotic Testing: skin biopsy/culture
49
Oxidase
Oxidase: oxidase test detects cytochrome c, measures ability of bacteria to oxidize and change color of NNdeimehtylppenlendiamine
50
• Life cycle of Plasmodium spp.
``` • Life cycle of Plasmodium spp. • Injected from mosquito as sporozoite--> infect hepatic macrophages, transform from schizont and asexual replication and release merozoites--> merozoite infects RBC--> mature into trophozoite (differences based on spp.) form either--> gametocytes (small proportion) to mosquito (sexual phase) OR schizont to merozoites to new RBC • Timelines: ○ 1 day: P. knowlesi, monkey reservoir ○ 2 days: p. vivax, p. ovale ○ 3 days: p. malariae Erratic: p. falciparum (kinda 48 hours) ```
51
Pili
• Pili/fimbrae: long thin filamentous, all over surface of cell, composed of pilin, mediate adherence to host tissues, pili bind to receptors that consist of sugar resides on glycolipids/glycoproteins in the host cell, therefore ay types of pili, determines tissues specificity of many bacterial pathogens • Sex pili: important in bacterial conjugation Changing expression of pili: phase varition or antigenic variation
52
• Glycopepetides:
• Glycopepetides: binds to d-ala-d-ala and blocks transpeptidase activity ○ Ex: vancomycin Bacterialcidal
53
Antiretroviral therapy targets:
Antiretroviral therapy targets: two nucleoside analogues plus integrase inhibitor or protease inhibitor
54
Concentration- versus time-dependent killing
• Concentration: work best when concentration is very high relative to the MIC, ○ cmax/mic ○ High-dose or extended interval dosing ○ There is a time frame when cmax/mic is very high, but also a "post-antibiotic effect" interval where drug concertation decrease to levels below the MIC and there is persistent suppression of growth § The high the drug concentration the longer the duration of the PAE and the smaller the residual bacterial population when the next dose is given • Time: "Time above the MIC" hours time/mic, want more than 40-50% of time usually Alternative dosing to maximize time/MIC
55
• Candidiasis
• Candidiasis ○ R: normal flora ○ C: § Baby: severe diaper rash § Oral: immunocompromised or steroids, can scrape off white mucosa § Esophagitis: AIDS defining illness, white psudomembranese, CD4 count 100 § Vaginal candidiasis: diabetics, antibiotics, birth control □ Does not change pH of secretions (4 pH) § Endocarditis: tricuspid valve, IVDU § Systemic: dimorphic, yeast form with pseudohypi in cold (20C), germ tubes in heat (37C) ○ H: catalase + (individuals with chronic granulomatous disease esp. suseptible) KOH prep
56
TSST-1
TSST-1: exotoxin, toxic shock syndrome, staph aureus, super antigen
57
• Chagas disease
• Chagas disease ○ American Trypanosomiasis: T. cruzi, zoonotic, many animal hosts tough to eradicate, WESTERN HEMISPHERE ○ Transmission: kissing bug/reduviid bug, blood meal and deposits feces into the bite/eye § Inoculated as trypomastigote which circulates, can get taken up by another bug and complete life cycle in vector □ Affinity for cardiac muscle and smooth muscle of GI tract ○ Disease: chagoma: inflammatory lesion at site of entry (Romana sign: swollen eye) ○ Disease: cardiomyopathy, pseudocyst filled with amastigotes within cardiac tissue ○ Disease: megacolon, megaesophagus, loss of muscle tone Testing: Blood smear for trypanosomes, Serology, heart histology
58
Ebola virus vaccine:
Ebola virus vaccine: vaccine in development, it works, moAB
59
• Antifungal agent mechanism of action
• Antifungal agent mechanism of action • Amphotericin B: polyene: binds ergosterol, disrupts fungal cell membrane (like penicillin but make if FUNgi), significant toxicity • Azoles: inhibit ergosterol synthesis, broad spectrum, safer • Allylamines: terbinafine: inhibits squalene epoxidase (eralier step in the sterol synthesis) • Echinocandins: inhibit cell wall glucan synthesis, impairs cell wall stress tolerance ○ First choice empiric anti fungal in hospital, IV Fungal cell wall: ergosterol vs. Mammalian cell wall: cholesterol
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Gram-positive v. Gram-negative:
Gram-positive v. Gram-negative: gram+ takes up crystal violet stain in cell wall based on high peptidoglycan content
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• Staphylococcus saprophyticus
• Staphylococcus saprophyticus • Gram + cocci, novobiocin-resistant, catalase +, urease +, coagulase - Diseases: UTIs, especially young sexually active women
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• Viridans streptococci
• Viridans streptococci • Gram +, optochin-resistant, alpha-hemolytic, bile-insoluble/resistant, NOT encapsulated • Diseases: dental caries ○ Subacute endocarditis of damaged heart valves (most commonly mitral valve) § Pathogenesis: adhere to fibrin platelet aggregates by producing dextrans that make the bugs stick Tx: Macrolides, Cephtriaxone
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• Listeria
• Listeria • Gram + baccili, Beta-hemolytic, survives at cold temperatures • Transmission: soft cheese/milks, pregnant mom->baby • Unique: flagella outside cell tumbling motility, inside cells use actin rockets and propel from one cell to another without leaving (Immune evasion) • Unique: pregnant women more susceptible, DON’T EAT SOFT CHEESE, can be passed to baby or early preg. Terminate • Unique: babies and old people especially susceptible • Baby: 3rd common cause neonate meningitis Tx: Ampicillin
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• Influenza A and B viruses
• Influenza A and B viruses: orthomyxovirus, RNA-, enveloped • Unique: replicates inside the nucleus, segmented (therefore antigenic shift/drift) ○ Antigenic drift: point mutations in genome, slighlty altered (new flu shot needed), responsible for seasonal flu ○ Antigenic shift: RNA shared between different species (H and N reassortment), responsible for pandemics § A: pandemic/epidemic, drift and shift § B: endemic outbreaks, drift ○ Hemagglutinin (HA): glycoprotein on surface of influenza viruses, binds to sialic acids on upper resp. tract., causes RBCs to clump together in test tubes § HA antigens: H1, H2, H3, etc. determines cell tropism (cells that can be infected by virus) ○ M2 protein: needed to create proper pH for viral encoding § Amantadine/rimantadine inhibit M2, old treatments for FluA ○ Neuroaminidase (NA): cleaves sialic acid to release newly formed virions from infected cell § NA inhibitors: oseltamivir/anamivir ○ Transmission: resp. droplets, dec-feb § Give Vax in october □ Live attenuated nasal spray □ Injectable: killed version ○ Pneumonia: major complication, staph aureus common culprit ○ Aspirin: contraindicated in children with viral illnesses: REYES SYNDROME: fatty liver/liver failure/encephalitis § Uncouples ETC in hepatic mitochondria • RT-Ascending paralysis from Guillain-Barre Syndrome associated with vax • Dx: rapid antigen test, RT-PCR
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• Mycobacterium tuberculosis
• Mycobacterium tuberculosis • Mycobacterium, acid-fast stained because of mycolic acids (carboyl fuschia stain), cultures very slowly, requires Lowenstein-Jensen media, obligate AEROBE, cell wall also has • Transmission: respiratory droplets, human to human, once infected lives in macrophages • Virulence: ○ Cord factor: glycolipid, serpentine shape, CRITICAL FOR Pathogenicity, sticky cell wall, once penetrates macrophages and induces TNFa, granuloma forms and remains walled off inside ○ Sulfatides: prevent phagolysosome fusion, creates incompetent secondary lysosomes/phagosomes in macrophages and allows TB to persist inside • Primary infection: infects lungs in middle lung lobes and involves hilar lymph node ○ Ghon complex: hilar lymphadenopathy + peripheral granulomatous lesion in middle/lower lung lobe ○ Tubercules: caseating granuloma, langerhans giant cells (activated macrophages) make walled off scarred area filled with necrotic macrophages ○ Symptoms: prolonged fever, most causes resolve by fibrosis and becomes latent infection, mostly children effected § Will have positive PPD, type 4 hypersensitivity test □ can be positive in active infection, latent, or BCG vaccines • Disease paths after primary infection: 1. Healed latent infection: resolve by fibrosis 2. Miliary TB: multi-organ failure, can seed multiple organs, lethal possible 3. Reactivation of latent infection: 5-10% of people, immune suppression downregulates TNFa allowing the TB to escape the walled off granuloma and reactivate i. Therefore: when starting patients on TNFa inhibitors, screen for TB first ii. Reactivation: upper lobes, 1. cough, 2. night sweats, 3. hemoptysis 1) TNFa: promotes wasting, produced in response to cord factor 2) Pott's disease: spinal column, damages vertebral bodies 3) CNS invovlement: cavitary lesion with tuberculoma • Tx: rifampin, isoniazid, pyrazinamide, ethambutol Prophylaxis: Rifampin, isoniazid (9 months!)
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• Therapeutic drug monitoring:
• Therapeutic drug monitoring: most commonly for vancomycin and tobromycin, want to avoid toxicity • Especially important in obesity and renal impairment • Trough monitoring • Substantial interpatient variability exists in serum concentration on standard drugs • Small diff between therapeutic and toxic doses You need an accurate asasy to measure this
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Capsules
Capsules: made of water, aids in avoiding the immune system/opsonization/complement activation
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• Coccidiodomycosis
• Coccidiodomycosis ○ R: § Geography: southwestern USA § Transmission: inhalation of spores in dust, increased risk during dust storms/earthquakes ○ C: cough, fever, arthralgia, some radiographics may show cavities or nodeules some will be unremarkable, erythema nodosum on shins (robust immune response so only in healthy people) § Immunecompromised: disseminate to bone, skin, lung, meningitus § Dimorphic: mold in cold, spheriol of endospores in bodies -> ruptures and releases, larger than RBCs H: KOH stain/culture, serology IgM vs cocci
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Catalase
Catalase: reduces H2O2 into H2O and O2
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Siderophore
Siderophores: remove iron from host molecules and take up into bacterial cells
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Superoxide dismutase
Superoxide dismutase: degrades superoxide to hydrogen peroxide
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Toxic Shock Syndrome mechanism
toxic shock syndrome: superantigen, sticks APC MHCII and CD4+ T cell together, constitutive activation, cytokine release, tissue damage
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• Proteus mirabilis
``` • Proteus mirabilis • Gram - rod, flagellates, swarming-motility, fishy-odor, urease + (responsible for forming of struvite stones!) • Diseases: ○ UTIs ○ Kidney stones: stag horn calculi Tx: sulfonamides ```
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• Wolbachia
• Wolbachia • Gram - Endosymbiont, most significant in oncocerca volvulus (transmit by black fly), the increased river blindness is associated with increased wolbachia present, generates much inflame response when the filariae die and release wolbaccie ○ Present in W. bancrofti, B. Malayi, O. volvulus ○ NOT PRESENT IN LOA LOA Tx: doxycycline kills off wolbachia without killing the microfilariae, but reduces blindness
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• Streptococcus pneumoniae
• Streptococcus pneumoniae • Gram + lancet-diplo cocci, optochin sensitive, encapsulated, alpha-hemolytic, bile-soluble (cannot grow in bile) • Diseases: #1 ○ M-eningitus ○ O-titis media ○ P-nemonia: community-acquired, rust colored sputum, lower lobe ○ S-inusitis: • Virulence: ○ polysacc capsule ○ IgA protease • Unique: SCD pts particularly suseptible • Tx: Macrolide, Cephtriaxone • Prevention: ○ Adult vax: 23 valent, IgM, T-cell independent response Children vax: 7 valent, IgG, conjugated polysac to a protein to make more robust immune response with IgG
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• Norovirus:
• Norovirus: ssRNA+, naked, one long polyprotein that is cleaved by viral proteases, replicates in cytoplasm • Calicivirus family • Outbreaks/Transmissions: cruises, close contact of humans, young children/schools/daycares, shellfish Diarrheal illness: viral gastroenteritis, explosive watery diarrhea
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Peptidoglycan
Peptidoglycan: protein made up of alternating NAG/NAM