Other lectures (not drugs or bugs) Flashcards
What are Koch’s postulates?
- Organism must be found in all disease cases, not healthy animals
- Organism must be isolated from diseased animals and grown in cultures
- Disease must be reproduced when isolated organism is inoculated into susceptible animals
- Organism must be isolated from experimentally infected animals
What is the infectious cycle of a pathogen?
- Entry/exit of host
- Establishment
- Persistence/Proliferation
- Host damage
What are the two general mechanisms of cellular invasion?
Zipper - ligand binds to receptor, recruits more receptors to bind to ligand, eventually organism is surrounded
Trigger - microbe engages signaling proteins that regulate actin, cytoskeleton engulfs organism
What element is essential for the growth of virtually all bacteria?
Iron (patients with increased iron have increased susceptibility to certain infections)
How many layers is the cell envelope of Gram positive bacteria and what are they?
Two - Cell wall (thick peptidoglycan layer) and cytoplasmic membrane
How many layers is the cell envelope of Gram negative bacteria and what are they?
Three - Outer membrane, cell wall (thin peptidoglycan layer), and cytoplasmic membrane
How many layers is the cell envelope of Acid fast bacteria and what are they?
~2.5 - Cytoplasmic membrane, cell wall (thin peptidoglycan layer), and acyl layer
What PRR recognizes the lipoteichoic acid (LTA) of Gram positive bacteria?
TLR2
What PRR recognizes the lipopolysaccharide (LPS) of Gram negative bacteria?
TLR4
How does Gram staining work?
Add crystal violet stain, decolorize but polysaccharide layer retains stain so Gram positive stay purple.
Counter stain with Safranin so Gram negative look pink.
How does acid fast stain work?
Stain with carbofuschsin, decolorize but waxes retain stain so acid fast bacteria look pink.
Counter stain with methylene blue so everything else besides acid fast bacteria looks blue.
What enzymes are required for peptidoglycan synthesis?
Transglycosylase (links new peptidoglycan monomers)
Transpeptidase (forms peptide cross links between rows and layers of peptidoglycan)
What are the different orientations of flagella on a bacteria?
Monotrichous - single flagella
Lophotrichous - multiple from same spot
Amphitrichous - single flagella on each end
Peritrichous - many in all directions (i.e. E. coli)
If a flagella rotates anticlockwise, what type of movement does it cause?
Forward movement, swimming
If a flagella rotates clockwise, what type of movement does it cause?
Tumbling movement, reorientation
What type of movement do pili/fimbriae cause?
Twitching (grappling hook)
What is the function of pili/fimbriae?
Adhesion to surfaces
Sometimes conjugation
What is the function of glycocalyx capsule or slime layer?
Adhesion (biofilm)
Protects bacteria from phagocytosis
What is the function of endospore?
- Dormant and tough non-reproductive structure that can allow bacteria to survive tough environment
- Can only be destroyed by burning or autoclaving
- Seen in Bacillus and Clostridium
What is the function of a plasmid?
Transfer genetic elements
What PRR recognizes flagella?
TLR5
What is MBC?
Minimum bactericidal concentration - the minimum concentration of antimicrobial to kill the bacteria
What is MIC?
Minimum inhibitory concentration - the minimum concentration of antimicrobial to prevent growth of organism
When is it necessary to have a bactericidal as opposed to bacteriostatic agent?
Endocarditis (need to get rid of biofilm entirely) Neutropenic patient (i.e. due to cancer therapy) Preferred in meningitis (though not proven)
What is the limiting factor in how fast bacteria can grow?
How fast they can replicate their DNA
What are the classifications of bacteria based on oxygen requirement?
Obligate aerobes - need O2
Obligate anaerobes - O2 kills them, get energy via fermentation
Facultative anaerobes - can grow +/- O2 but prefer O2
Microaerophiles - can withstand low levels of O2
Why is oxygen toxic to anaerobes?
Superoxide and hydrogen peroxide are toxic, but anaerobes lack superoxide dismutase and catalase/peroxidase
What are the classifications of bacteria based on temperature?
Mesophiles: best from 30-45 C (includes most pathogenic bacteria)
Thermophiles: 55-75 C (hot springs)
Psychrophiles: temps below 20 C
What are the phases of the bacterial growth curve?
Lag phase: slow growth, get acclimated to environment
Log phase: multiply exponentially
Stationary phase: competition for food and nutrients, growth stops
Decline phase: toxic waste builds up, bugs die
What is the formula for generation time (or doubling time)?
g = t/n
g = generation time t = time interval n = number of generations (number of times population doubles during time interval)
How can you determine how much bacteria was in an original sample?
Pour Plate
Serially dilute original sample and plate.
Each spot is colony forming unit (CFU) derived from 1 bacterium that increased in size by binary fission.
Count number of CFUs on plate of a certain dilution and backtrack.
What are characteristics of a biofilm?
Microbes that are:
- Attached to hydrated surface
- Embedded in polysaccharide slime
- Behave as a community
- Demonstrate antibiotic resistance and resistance to clearance by host immune system
What is the progression of a biofilm?
Single cells come in and attach –> early structure –> mature biofilm –> seeding dispersal
What is the main type of biofilm associated infection?
Indwelling medical device
Why are biofilms resistant to antibiotics?
- Reduce antibiotic penetration
- Cells within a biofilm are very slow growing
- Stress response genes can allow it to resist antibiotic action
Can you culture a biofilm?
No
Definition of asepsis
State of being free of microorganisms
Definition of sterilization
Inactivation or elimination of ALL organisms and their spores
Definition of disinfection
Inactivation or elimination of MOST microorganisms
Definition of sanitization
REDUCES pathogen levels
Definition of germicide
Substance that kills vegetative bacteria and SOME spores
Definition of disinfectant
Kills vegetative bacteria, fungi, viruses but NO spores
Definition of antiseptic
Prevents multiplication of microorganism (bacteriostatic , not bactericidal)
What are methods of physical sterilization?
Autoclave (moisture, heat and pressure)
Hot air sterilization (for materials that would be damaged by moist heat)
Filtration disinfection (for liquids)
Radiation (ionizing via gamma)
What are methods of chemical sterilization?
Ethylene oxide (toxic)
Alcohols
Halogens (basically bleach)
What are implications of biofilms on Infectious Disease?
- Inaccurate MIC/MBC preduction of bacterial populations in situ
- Inaccurate CFU determination from clinical samples
What is the definition of an outbreak?
Incidence of an event / expected rates (endemic)
What is the definition of a pandemic?
A worldwide epidemic
What are the steps of an outbreak investigation?
- Prevent further cases
- Develop a case definition
- Conduct surveillance
- Build epidemic curve
- Summarize data on case patients in a line listing
- Develop and test a hypothesis of what caused outbreak
- Institute and assess efficacy of intervention
What is a case definition?
Defines the disease (clinical symptoms, signs and diagnostic tests) with restrictions on time, person, and place
Definition of sensitivity of case definition
Ability to correctly identify those who have new infection
Definition of specificity of case definition
Ability to correctly identify those who do not have new infections (want this to be high to minimize false positives)
What information can be gained from an epidemic curve?
Whether infection is point source v. ongoing transmission
Incubation period
What should a outbreak hypothesis explain?
Mode of transmission
Source of outbreak
What is a plasmid?
Small, self-replicating extrachromosomal circle of DNA
- Can be transferred from one bacterium to another (conjugative plasmid)
- Can encode antibiotic resistance
What is a transposon?
Jumping genes that cannot replicate independently, but must be inserted into another replicon (plasmid, chromosome, or phage)
- Often encode antibiotic resistance
- Usually inactivates target genes and can cause rearrangements
What is on either end of a transposon?
Inverted repeats
Lytic v. lysogenic bacteriophage
Lytic - immediately lyse and kill cell
Lysogenic - phage DNA incorporated into bacterial chromosome and encode virulence factors (like toxins i.e. diphtheria toxin, Shiga toxin)
What is a pathogenicity island?
Large block of DNA containing multiple virulence genes, located in a region of “house-keeping” genes
i.e. E. coli LEE pathogenicity island
What are the 3 basic mechanisms of genetic exchange in bacteria?
Transformation
Conjugation
Transduction
Definition of bacterial transformation
Naked DNA from one cell taken up by another cell through the cell wall
Definition of bacterial conjugation
Genetic transfer via cell-to-cell contact (bacteria sex)
Definition of bacterial transduction
Transfer of DNA between bacteria by viruses
What is quorum sensing?
Mechanism by which bacteria secrete a low molecular weight compound that signals other bacteria to turn on specific gene expression (this only happens at high bacterial density when signalling compound is at sufficient concentration)
What is the main way that antibiotic resistance factors are spread?
Conjugative plasmids (especially in Gram neg bacteria)
Should you use antibiotics for otitis media with effusion?
No! Could be remnants of previous acute otitis media infection, usually asymptommatic and not bacterial
How can you distinguish between acute otitis media v. otitis media with effusion?
Physical exam.
AOM - bulging tympanic membrane, no light reflex
Otitis media with effusion - air fluid level visible, concave tympanic membrane
What are the three major organisms that cause bacterial acute otitis media?
Moraxella catarrhalis
Strep pneumoniae
Haemophilus influenzae
What is the primary treatment of acute otitis media?
Amoxicillin
“wait and see” is also an option
What is a major complication of acute otitis media?
Mastoiditis (purulent material accumulate in mastoid cavity)
What are the three major organisms that cause bacterial sinusitis?
Moraxella catarrhalis
Strep pneumoniae
Haemophilus influenzae
(same as acute otitis media)
What is the primary treatment of sinusitis?
Amoxicillin/clavulanate
What is a major complication of sinusitis?
Orbital cellulitis - proptotic, muscle stranding and swelling
What is the major organism that causes pharyngitis?
Group A beta hemolytic strep (Strep pyogenes)
What is the primary treatment for pharyngitis from Group A Strep (Strep pyogenes)?
Penicillin! resistance remains low
What are major complications of Strep pharyngitis?
Acute rheumatic fever
Glomerulonephritis
What are major pathogens that cause typical bacterial pneumonia?
Strep pneumoniae
H. influenzae
Staph aureus
Group A strep (Strep pyogenes)
What are major pathogens that cause atypical pneumoniae?
VIRUSES (#1!)
Mycoplasma pneumoniae
Chlamydophila pneumoniae
Legionella pneumoniae
How can you differentiate from typical v. atypical pneumoniae?
Typical - usually lobar, pulmonary symptoms (pleuritic chest pain, purulent cough)
Atypical - usually diffuse, extrapulmonary symptoms (fatigue, sore throat, nonproductive cough)
What is the primary treatment for atypical pneumonia?
Macrolides (azithro)
What can precede the development of severe pneumonia due to S. aureus?
Influenza infection
What are major pathogens that can cause severe pneumonia?
Strep pneumoniae
H. influenza
Mycoplasma
If very severe, worry about Legionella, S. aureus (MRSA)
What is the treatment for a low risk outpatient pneumonia patient?
Azithromycin (macrolide)
What is the treatment for a high risk outpatient or low risk inpatient pneumonia (assume they had antibiotic in past 3 months)?
Fluoroquinolone
What is the treatment for a very high risk ICU pneumonia patient?
Broad beta lactam + azithro/fluoroquinolone
In what group of patients should you treat asymptomatic bacteriuria?
Pregnant women since its associated with premature and low birthweight babies
What factors will make a UTI complicated as opposed to uncomplicated?
History of childhood UTIs Immunocompromised Preadolescent or postmenopausal Pregnant Underlying metabolic disorder (diabetes) Urologic abnormalities (catheters, stones, etc.)
What is most common organism that causes UTIs?
E. coli
How does cystitis commonly present?
LUTS (lower urinary tract symptoms like burning)
Frequency of urination and urgency of urination
What is the first line of treatment for UTIs?
Nitrofurantoin
Fosfomycin
TMP-SMX
How does acute pyelonephritis commonly present?
Flank pain
Shaking chills (rigor)
Fall in blood pressure
Nausea and vomiting
What is treatment for Acute pyelonephritis?
Usually fluoroquinolone like ciprofloxacin
If more serious/local fluoroquinolone resistance >10%, can give initial IV dose of ceftriaxone
Why are pediatric UTIs particularly dangerous?
Sometimes associated with veiscoureteral reflux, can pool in the bladder
Can cause renal scarring
What are common causes of acute gastroenteritis?
Preformed toxins such as:
- Staph aureus enterotoxins
- Clostridium perfingens enterotoxin
What is clinical presentation of acute gastroenteritis?
Abrupt onset of severe nausea, vomiting, diarrhea
Lasts less than 24 hours
What is the clinical presentation of acute non-inflammatory diarrhea?
Watery diarrhea without blood or mucus
What is the most important treatment in diarrheal disease management?
Rehydration therapy!
What are common causes of acute non-inflammatory diarrhea?
ETEC, EAEC, EPEC
Vibrio cholera
Campylobacter, Salmonella, Shigella
What are key components of oral rehydration solution?
Sodium and glucose
Increases absorption via sodium/glucose transporter and repletes volume
What is clinical presentation of acute inflammatory diarrhea?
Fever, chills, malaise, abdominal pain and diarrhea
Stools may contain mucus or blood
Dysentery is severe form of this
What is clinical presentation of dysentery?
Severe form of acute inflammatory diarrhea
Frequent small bowel movements with blood/mucus, urge to defecate, painful defecation (tenesmus)
What are common causes of acute inflammatory diarrhea?
C. diff (especially in hospitalized patients or those recently on antimicrobials)
Campylobacter, Salmonella, Yersinia, EAEC
Shigella can cause dysentery
What lab finding indicates acute inflammatory diarrhea?
Fecal leukocytes
What is treatment for C. diff?
Metronidazole
Vancomycin if severe
Fidaxomycin for relapses
What is treatment for V. cholerae?
Oral rehydration primarily
Can give tetracycline to shorten diarrhea time
What is treatment Shigella?
Check resistances, usually okay with cipro
What is treatment for acute inflammatory diarrhea PRIOR to getting culture?
DO NOT give antibiotics if you see bloody diarrhea or suspect salmonella
- Could be EHEC, would increase risk of HUS
- Could be salmonella, wouldn’t have effect on duration
Otherwise usually okay with cipro
