Flashcards in LOs: 25-27 Deck (19)
25 Healthcare-associated infections (HAIs)
Ways in which they occur (5)
Most common infections (4)
Infections that patients acquire during the course of receiving healthcare treatment for other conditions
- Hands of healthcare workers
- Contact w/ contaminated hospital environment
- Poorly cleaned equipment
- Pneumonia (ventilation)
- UTIs (urinary catheter)
- Surgical wound infections
- Bloodstream infections (infected IV lines)
25 Clostridium difficile:
Most common cause of...
Prerequisite to develop infection
Anaerobic spore-forming toxin-producing gram+ rod
Hospital-acquired infectious diarrhea
- Antibiotics alter flora in the gut
- Allows C. difficile to multiply in the gut
- Toxin production by C. difficile leads to diarrhea
- Toxins A & B: enterotoxins, render intestinal epithelial cells nonfunctional & leaky, chemoattractants for neutrophils, provoke inflammation
- Binary toxin: causes cytoskeletal effects
Spectrum from diarrhea to toxic megacolon to death
Culture, microscopy of stool, & sigmoidoscopy
Metronidazole (oral or IV) or oral vancomycin (but NOT IV)
25 Enterococcus faecium:
- Gram+ coccus in pairs & chains
- Facultative anaerobic
Person to person / skin
Bloodstream infection, endocarditis, UTIs
- Alterations in the cell wall leads to ampicillin and vancomycin resistance
- Linezolid and daptomycin against vancomycin resistant Enterococci (VRE)
25 Staphylococcus aureus:
- Gram+ coccus clusters
Wound infections, abscesses and blood stream infections
- Resistant to all beta-lactam antibiotics (except for ceftaroline) in contrast to MSSA
- Coagulase negative
- Colonizes skin
- Causes nosocomial infections w/ IV lines or implanted foreign materials
Gowns & gloves
Gram negative bacillus
- Lower GI tract
- Skin (transiently)
Mucoid, resists phagocytosis
Bloodstream infection, nosocomial pneumonia and urinary tract infection
- All produce SHV-type beta-lactamase
o Resistant to ampicillin
- Some produce ESBL
o Resistant to all beta-lactams except carbapenems
- Some produce K. pneumoniae carbapenemase (KPC) beta-lactamase
o Resistant to all beta-lactams including carbapenems
25 Acinetobacter baumanii:
- Gram negative aerobic rod
- Resistant to dessication
- Genome acquires multiple resistance genes
ICUs & wounded soldiers in Afghanistan
Ventilator associated pneumonia (VAP) (untreatable)
25 Nosocomial Precautions:
- Wash hands
- Mask w/ eye protection or face shield & gown
- Dispose needles
- Transmission by droplet nuclei or dust particles
- Private room, N-95 mask
- Tuberculosis, measles and disseminated varicella (chickenpox; meningitis; shingles in immunocompromised persons)
- Transmission by large-particle (droplet) aerosols
- Private room, surgical mask
- Meningococcus, influenza, pertussis, mumps and rubella
- Transmission from contact
- Private room, gloves, gowns, patient-dedicated stethoscopes
- For MRSA, VRE, C. difficile, any diarrhea, rotavirus, hepatitis A, RSV, lice and scabies
26 Invasive pathogens that only invade epithelium
Speed of symptoms
Respiratory tract - Influenza virus
Urogenital tract - Human papillomavirus 6
- Chlamydia spp.
Skin - Human papillomavirus 1, 2 and 4
GI tract - Shigella spp.
Cause symptoms faster than pathogens that invade and then disseminate
26 Invasive pathogens that invade through the epithelium but stop in subepithelial tissue
Speed of symptoms
GI tract - Salmonella typhi
Urogenital tract - Herpes Simplex virus 1 and 2
- Treponema pallidum
Respiratory Tract - Measles virus
- Varicella zoster virus
- Mycobacterium tuberculosis
Skin - Staphylococcus aureus
Symptoms develop slowly & are more global
26 Invasive pathogens that disseminate through the body after invasion
26 Invasion of Yersinia spp.:
- Mode of entry
- Entry occurs through...
- Transcytosed, released, & spread...
Gram negative rods
Ingestion of contaminated foods/water
Fever, cramps, and diarrhea
- Epithelium of the ileum/colon, penetrates to subepithelium
- Extracellularly by producing Yersinia Outer Proteins (YOPs)
- "Zipper": invasin binds to beta1 integrin, causes host cell membrane to adhere to bacterium & pull it into the cell
- M cells (has beta1 on surface)
- Through lymph to adjacent mesenteric lymph nodes
- Fever from LPS
26 Invasion of Shigella/Salmonella:
- After ingestion, ...
- Genes encode...
- TTSS mediates...
- Results in...
- Expression of genes encoding invasive factors
- A needle (translocon), which moves proteins directly from the cytoplasm out of the Gram- negative bacterial cell (part of a type III secretion system (TTSS))
- Transfer of cytoplasmic proteins to cause membrane ruffling
- Encirclement of the bacterium and engulfment via macropinocytosis
26 Invasion of Shigella vs. Salmonella:
(1) Invasion genes
(2) Enter intestine through...
(3) Intracellular site
(1) Invasion genes: plasmid-encoded
(2) Enter intestine through M cells
(3) Intracellular site: cytoplasm
(1) Invasion genes: chromosomal
(2) Enter intestine through M cells & enterocytes
(3) Intracellular site: endosome
26 Host Consequences of Invasion
- May help clear/limit infection
- Contributes to disease symptoms (e.g. fever)
- Causes high levels of fecal leucocytes
Virulence Factors (5)
- Gram-negative rods
- Facultative anaerobes
- Do not ferment lactose, do not make H2S, and are nonmotile
- Resistance to gastric acid
Humans (can be asymptomatic carriers)
- Fecal-oral (ingestion of contaminated food/water)
- Extremely virulent
- LPS (endotoxin)
- Ipa proteins (mediate invasion)
- Mxi-Spa proteins (translocon) needle of TTSS
- IcsA and IcsB (involved in intercellular spread of Shigella)
- Shiga toxin (S. dysenteriae)
- Microscopic exam for fecal leucocyctes
- Culture: MacConkey agar (clear colonies b/c lactose negative)
- Antibiotics reduce severity & duration
- Replenish fluids & electrolytes
- Live attenuated vaccines in developing countries & for military use
- Good hygiene
a. After ingestion, Shigella produces...which assemble into...After Shigella adheres, ...
b. ... proteins assemble...affects...triggers...
c. Once inside the M cell, ...
d. The bacteria kill...and then enter...
e. Using Ipas, Shigella induces...Once intracellular, the bacteria...& move through...
f. If the Shigella cell reaches the basolateral surface of the colonocyte, ...which involves...IcsB...Advantage...
g. Shigella interactions with macrophages promotes...
h. Colonic inflammation causes...
i. GI symptoms of shigellosis vary from...disease of the ...
j. Death can occur from...
a. After ingestion, Shigella start producing Ipa proteins and Mxi-Spa proteins. The Mxi-Spa proteins assemble into a TTSS (translocon) needle. After Shigella adhere to colonic M cells, they begin secreting Ipa proteins by the TTSS.
b. The Ipa proteins assemble as a complex on the M cell. This affects signal transduction pathways in the M cell, triggering membrane ruffling and entrance of the bacteria via macropinocytosis.
c. Once inside the M cell, the Shigella cell (still in an endosome) is transcytosed and picked up by underlying macrophages.
d. The bacteria kill the initial macrophage(s) and then enter other macrophages or the basal surface of colonocytes (and perhaps small intestinal enterocytes).
e. Using Ipas, Shigella induces membrane ruffling to promote its uptake into colonocytes. Once intracellular, the bacteria escapes from the endosome into the cytoplasm of the colonocyte. These cytoplasmic bacteria start multiplying and move through the cytoplasm. This movement is mediated by the host cell cytoskeletion, due to IcsA affects on actin polymerization.
f. If the Shigella cell reaches the basolateral surface of the colonocyte, it can enter other colonic epithelial cells without ever becoming extracellular. This involves localization of the Shigella cell in a protrusion, which becomes localized in a double-membrane enclosed vesicle in the colonic epithelial cell. IcsB helps the Shigella escape from this vesicle into the cytoplasm of the colonic enterocyte. Advantage: No exposure to the immune system (at least for awhile).
g. Shigella interactions with macrophages promotes inflammation; PMNs are attracted and migrate into the colonic epithelium, disrupting its integrity).
h. The above colonic inflammation (along with shiga toxin, if S. dysenteriae involved) cause GI symptoms and fever.
i. GI Symptoms of shigellosis vary from mild diarrhea (no blood) to dysentery (low volume, bloody stool). Shigellosis is usually considered a disease of the colon; it may also involve the ileum? S. sonnei infections usually mildest; S. dysenteriae and S. flexneri more severe.
j. Death can occur from fluid/electrolyte imbalances.
27 Molecular Mimicry
- Results in...
- Production of microbial antigens or binding of host antigens so host cannot recognize as foreign
- Results in inadequate immune response to pathogen
Production of Antigens
- Induces cross-reactivity with host tissues
- Results in pathologic immune response attacking self-antigens on host tissues
27 Neisseria meningitidis:
Virulence Factors (6)
Types: Colonization, Growth, & Features
- Neisseria meningitidis
- Neisseria gonorrhoeae
- Commensal Neisseria
Carrier state risk factors (3)
Disease risk factors (3)
Clinical Diagnosis (4)
Lab Diagnosis (2)
- Gram- diplococci
- *Capsule: carbohydrate, avoid immune response, multiple serotypes
- Outer membrane proteins: attachment, antigenic variation
- Pili: attachment, antigenic variation
- LOS: inflammatory, vascular leak
- IgA-Protease: inhibits opsonization
- Complement-binding proteins: prevents complement
- Respiratory tract, Thayer-Martin/Martin Lewis, carbohydrate capsule, acid from maltose
- Genital tract, Thayer-Martin/Martin Lewis, pili & opa for attachment, no acid from maltose
- Oral & GI tract, not Thayer-Martin/Martin Lewis, no capsule, pili, or disease
- Nasopharynx (carrier state)
- Young adults
- Geographic regions
- Crowded social settings
- Recent colonizaiton
- New strain
- Immune deficiency: *asplenic, complement
- Attach via pili & outer membrane proteins
- Avoid mucosal defense w/ IgA protease
- Invade epithelial cells & vascular space
- Multiple, releae LOS
- Circulate to skin (meningitis) & skin (purpura)
- Meningitis (fever, headache, stiff neck)
- Rash: petechiae or purpura
- Fulminant: death
- Culture blood & CSF (gram- diplococci, oxidase-positive, acid from glucose & maltose)
- Serotype for capsule & Opa
- Reduce contact
- Vaccinate (prob: no capsular vaccine to serotype B)