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0000000Infectious Disease and Life Cycle > ID Unit 1 > Flashcards

ID Unit 1 Flashcards

1
Q

why do we care about ID?

A 
common
diagnosable
communicable
high morbidity and mortality
treatable
newly emerging pathogens

premonitory:
indicative of changes in host and/or environment

can be anticipated (war, famine) and prevented

IDs are going down w/ treatment advancements

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2
Q

3 variables that affect the development of infection and disease

A

microbial variables
host variables
interactions

all contribute to disease and health

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3
Q

Gram staining
innate immune stimulation
antimicrobial susceptibility and resistance

A

Gram Positive:
thick PG layer (accessible)
Teichoic acid
—certain surface antigens

Gram Negative:
thin PG cell wall (PG covered by membrane/porins)
outer membrane with LPS

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4
Q

4 bacterial groups based on stain and shape

A

GPC:
staph (catalase +)
strep (catalase -)

GPR:
Listeria (small)
Clostridium (large)

GNC:
Neisseria
Moraxella

GNR:
E coli (classic lactose fermenter)
Pseudomonas (classic non-lactose fermenter)

Non-staining bacteria:
can be truly neg or actually “positive” for bac that don’t stain
-No cell wall = mycoplasma; chlamydia (GN but too small to stain)
-Intracellular
-Others =
M tuberculosis (Gram+)
Rickettsia, spirochetes (Gram- too small)
Legionella spp. (Gram-)

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5
Q

how to Gram stain

A

heat slide- kill and bind bac

crystal violet (primary stain)

add iodine (mordant that binds the crystal violet to gram + cell wall)

add decolorizer (acetone alcohol to remove stain from gram - cells)

add safranin (counterstain)

~30seconds

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6
Q

Lactose fermenters vs non-lactose fermenters

A

GNRs

Lactose Fermenting GNR:
E coli (INDOLE POSITIVE)
Klebsiella sp.
Enterobacter
(Citrobacter)
(Arizona)
Non-Lactose fermenting GNR:
Pseudomonas aeruginosa (OXIDASE POSITIVE; strict aerobe)
Salmonella
Shigella
all others, etc.
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7
Q

sources of Gram Negative Rods

A

intestine
-appendix, diverticulitis, gallbladder (not pseudomonas)

Urine

  • pos WBC
  • pos symptoms

lung/line
-nosocomial

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8
Q

Gram Negative Cocci

A

few- relatively rare

Neisseria gonorrheae
Nisseria meningitidis
Moraxella catarrhalis
Acinetobacter

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9
Q

Gram Positive Cocci

A 
Pairs/clusters:
Staphylococcus
---Catalase positive!!!!---
Coag positive = Staph aureus
Coag negative = 31, incl
S epidermis
S saprophyticus
S lugdanensis

S lugdanensis
Pairs/chains:
Streptococcus
—Catalase negative!

Pairs:
either

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10
Q

Staph aureus

superficial, deep, disseminated infections

A

GPC

many bugs can be virulent and invasive, or carried asymptomatically

staph clumps (Coag positive!)
pus!

superficial infections:
boils, paronychia, lymphadenitis
cellulitis, impetigo

deep infections:
arthritis
osteomyelitis
pyomyositis
pneumonia (esp nosocomial)

disseminated infections:
bacteremia
-focal source, IV catheter, endocarditis
metastatic abscesses

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11
Q

Coagulase negative staph

A

ask where is the plastic/metal?

generally weak/wimpy unless you have plastic/metal to get a biofilm on

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12
Q

Hemolysis status of streptococci

-alpha, beta, gamma

A

alpha (green)

  • strep pneumoniae
  • Strep Viridans

beta (clear)
-beta is bad (Grade A, B, C, G)

gamma (none)
-usually incl Strep Milleri (pus)

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13
Q

streptococci syndromes

A

one bacteria- many syndromes

Group A strep- Strep Pyogenes
asymptomatic colonization (nares)
pharyngitis
erysipelas
glomerulonephritis
skin, soft tissue
bacteremia, sepsis
Rheumatic Fever
acute endocarditis
pneumonia/empyema
TSS
Necrotizing Fasciitis
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14
Q

Gram positive infections

-bad and less bad bugs

A

Bad bugs: can cause tissue infections (pneumonia, cellulitis)
Staph aureus (incl MRSA)
Strep pneumoniae
Group A strep (S. pyogene)

Less bad bugs:
Coag neg/Staph epidermidis
Strep viridians
Enterococcus

Really wimpy bugs:
P acnes
diphtheroids

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15
Q

Enterococcus

A 
S faecalis
S faecium (esp VRE)
Urine
Abdomen (+/- pathogenic)
endocarditis (subacute)
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16
Q

Gram positive rods

small and large

A 
small:
**Listeria (immunocompromised, pregnant)
diphtheroids
P acnes
actinomyces

Large:
**Clostridium sp.
Bacillus sp.

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17
Q

Anaerobes

sources

A

uncommon in blood cultures- die easily

sources:
oral
lung (aspiration; abscess)
intestine (es B fragilis***)
Female GU tract

commensal microbiota (nl flora) often anaerobes

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18
Q

Syndromes from the 4 bugs

A

GNCs:
meningitis
Neisseria- gonorrhea
Moraxella- pneumonia

GNRs:
E coli- UTI, abdominal problems
NLF- nosocomial

GPCs:
S aureus- cellulitis, endocarditis

GPRs:
Listeria- meningitis
Clostridium- Nec Fasciitis

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19
Q

pneumonia can be caused by

A

*Strep pneumoniae
*Morazella
H influenzae
Mycobacterium tuberculosis
Legionella pneumophila

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20
Q

skin/soft tissue syndromes can be cause day:

A

*Stap aureus
*Group A strep (strep progenes)
*Clostridium perfringens
Group B strep

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21
Q

Enteritis can be caused by

A

*Enterotoxic E coli

Vibrio cholerae

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22
Q

Colitis can be caused by

A

*Clostridium difficile
Shigella
Salmonella
Campylobacter jejune

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23
Q

Endocarditis can be caused by

A

*strep viridans
Staph aureus
S pneumoniae
enterococcus

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24
Q

Meningitis can be caused by

A

*Neisseria meningitidis
*Listeria
S pneumoniae
H influenzae

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25
Q

Intrabdominal syndromes can be caused by

A

*E coli
anaerobes (esp **Bacteriodes fragilis)
Klebsiella
Enterococcus

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26
Q

Sexually transmitted syndromes can be caused by

A

*N gonorrhoeae
Chlamydia trachoma’s
Treponema pallidum

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27
Q

4 (5) signs of inflammation

A

Tumor- swelling
Rubor- redness
Calor- heat
Dolor- pain

loss of function

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28
Q

non-infectious fever causes

A

cancer
lymphomas, RCC, hepatoma lung, sarcoma, myxoma, uterine, liver metastases

chemicals
antibiotics, anti-epileptics, cardiac

collagen/vascular
SLE, RA, vasculitis, Still’s, Gout

Clot
PE, DVT, hematoma, pelvic

Central fever
rare

consider:
hyperthermia, hyperthyroid, cholesterol emboli, pheochromocytoma, sarcoid, factitious, MI

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29
Q

common bugs that can colonize w/ no disease:

A 
Staph aureus (incl MRSA)
Group A strep (strep pyogenes) 
Pneumococcus
Mycobacteria
Fungi (Candida)
Ps aeruginosa

Disease only:
Measles
Ebola Virus

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30
Q

Basic antimicrobial targets

A

Gram positive:
Cell wall synthesis-
beta lactams (PCN, cephalosporins)
Glycopeptides (vancomycin)

Gram Negative:
Cell membrane-
polymyxins
Outer membrane regulates-
Beta lactamases
permeability
efflux
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31
Q

4 questions to ask about a pt w/ a suspected ID

A

Is it an infection? (history, PE, labs)

Where is it? (where is it not?)

What are the bugs likely in this pt? (host, environment, agent)

What are the drugs?

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32
Q

bacteriostatic vs bactericidal drugs

A

Bacteriostatic
would expect to see constant bacterial load
allows time for immune sys to kick in and eventually decrease the bac load
–will not be helpful in neutropenic (immunocompromised) pts

bactericidal
bacterial load should decrease
actively killing bacteria
better- less opportunity for resistance if you have smaller load present

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33
Q

MIC vs MBC

A

minimum inhibitory concentration:
concentration required to stop growth
(all drugs have this)

Minimum bactericidal concentration:
concentration needed to kill 99% of bac
higher than MIC

drug conc’s will decrease until you give another dose and even fall below MBC and MIC lines
-but bac growth still inhibited-
post-antibiotic effect (PAE) of bactericidal drugs
–the half life of these drugs doesn’t necessarily reflect dosing regimen
–if drug has good PAE, you want to minimize the amount of time the drug is above the toxic line- give higher conc of drug less frequently

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34
Q

4 pharmacokinetic stages of drug

A

absorption of drug into body (IV vs oral)

Distribution-
CSF, tissues, bones, etc

Metabolism-
whether drug passes through liver (CP450 interactions that inhibit/activate drug)

Excretion-
hepatic or renal

dosing schedule and duration of tx:
too short- resistance; reoccurrence
too low- resistance
too high- dose-related toxicity

pt compliance

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35
Q

host factors to consider before giving tx

A 
immune system status
very young or very old
hypersensitivities
different susceptibilities
pregnancy
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36
Q

specificity and spectrum of antimicrobial activity
narrow
extended
broad

A 
narrow:
act primarily on GN or GP
Bacitracin
Clindamycin
Metronidazole
Penicillin G, V
Penicillinase- resistant penicillins
Vancomycin
Monobactams
Polymyxins
Daptomycin
Extended:
All can act on GP and some GN
Amino glycosides
Cephalosporins
Extended spectrum penicillins
Fluoroquinolone's
Carbapenems
Macrolide's
Streptogramins
Broad:
bacteriostatic
possibly more superinfections
not useful in immunocompromised pts
Chloramphenicol
Sulfonamides
Tetracycline
Trimethoprim
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37
Q

Cell wall synthesis inhibitors

A

beta lactams:

Penicillins
cephalosporins
carbapenems
monobactams
vancomycin
bacitracin
cycloserine
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38
Q

Penicillins

A

beta lactams (cell wall synthesis inhibitors)

bactericidal

renal excretion

adverse rxns:
anaphylaxis (Type 1)
Rash, etc (type 3)
high dose- convulsions

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39
Q

Penicillin G,V

A 
G = IV/IM (poor oral)
V= good po
spectrum/uses:
All Gram + (cocci and rods)
Gram - cocci
spirochetes
penicillinase sensitive!
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40
Q

Penicillinase-resistant penicillins

A

Methicillin, oxacillin, naficillin

bulky R group to block beta-lactamase access to beta-lactam ring

“use naf for staph” (except MRSA, which has altered PBP’s)

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41
Q

Extended spectrum penicillins

A

Ampicillin, amoxicillin, aminopenicillins (w/ lactase inhibitor)

AMinoPenicillins are AMPed up penicillins
amOxicillin has greater Oral bioavailability than ampicillin

good po

can cause GI upset

spectrum:
penicillinase sensitive!
ampicillin/amoxicillin HELPS kill enterococci
(H influenzae
H pylori
E coli
Listeria monocytogenes
Proteus mirabilis
Salmonella
Shigella
enterococci)

Adverse rxns:
pseudomembranous colitis

MORs:
penicillinase in bacteria (a type of beta-lactamase) cleaves beta-lactam ring

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42
Q

Anti-Pseudomonal penicillins

A

Peperacillin, ticarcillin (w/ lactamase inhibitor)

extended spectrum

clinical use:
Pseudomonas
gram negative rods
penicillinase sensitive!

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43
Q

beta lactamase inhibitors

A

CAST

Clavulanic Acid
Sulbactam
Tazobactam

often added to penicillin antibiotics to protect from beta-lactamase (penicillinase) destruction

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44
Q

Cephalosporins general

A

generations 1-5
beta lactic drugs
bactericidal
less susceptible to penicillinases

organisms typically not covered by 1-4th generation cephalosporins are LAME:
Listeria
Atypical (chlamydia, mycoplasma)
MRSA
Enterococci
–exception: ceftaroline (5th gen cephalosporin) covers MRSA

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45
Q

Cephalosporins 1st generation

A

1st gen:
cefazolin, cephalexin

covers:
gram + cocci and
PEcK:
Proteus mirabilis
E coli
Klebsiella pneumoniae 
--Cefazolin prior to surgery to prevent Staph aureus wound infections
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46
Q

Cephalosporins 2nd generation

A

ceFAclor, ceFOXitin, ceFURoxime
(Fake fox fur)

covers:
gram + cocci and HENS PEcK
H influenzae
Enterobacter aerogenes
Neisseria spp
Serrate marcescens
Proteus mirabilis
E coli
Klebsiella pneumoniae
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47
Q

Cephalosporins 3rd generation

A

ceftriaxone, cefotaxime, ceftazidime

treats serious Gram negative infections resistant to other beta lactams

Ceftriaxone:
meningitis, gonorrhea, disseminated Lyme disease

Ceftazidime:
Pseudomonas

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48
Q

Cephalosporins 4th generation

A

Cefepime

treats gram negative organisms with increased activity against Pseudomonas and gram + organisms

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49
Q

Cephalosporins 5th generation

A

Ceftaroline

broad gram positive and gram neg organism coverage, including MRSA

–does not cover Pseudomonas!!

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50
Q

Monobactams

A

Aztreonam

narrow spectrum
aerobic gram negative rods only

for penicillin-allergic pts and those w/ renal insufficiency

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51
Q

Carbapenems

A

Imipenem, Meropenem, Ertapenem, Doripenem

Wide spectrum 
gram + cocci
gram neg rods
anaerobes
(reserve for resistant, life-threatening organisms)
significant side effects (CNS toxicity)

Imipenem is always given w/ Cilastatin (to lower inactivation of drug in renal tubules)
“w/ imipenem, the kill is lastin’ with cilastatin”

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52
Q

Vancomycin

A

bactericidal (except bacteriostatic vs C difficile)

not susceptible to beta-lactamases

covers:
narrow gram positive cocci
serious, multidrug-resistnat organisms incl 
**MRSA, 
S epidermis, 
sensitive Enterococcus species, 
C difficile
well tolerated but NOT trouble free:
Nephrotoxicity
Ototoxicity
Thrombophlebitis
diffuse flushing- red man syndrome
(pretreat w/ antihistamines and slow infusion)

MOR:
“pay back 2 D-ala’s for VANdalizing vancomycin”

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53
Q

Protein synthesis inhibitors

A

target the bacterial ribosome (70s made of 30s + 50s)
-have to be influxed; can be effluxed

“Buy AT 30, CCel at 50”

30s inhibitors:
A= Aminoglycosides (bactericidal)
T- tetracyclines

50s inhibitors:
C= Chloramphenicol, Clindamycin
E= Erythromycin (macrolides)
L= Linezolid (variable)

all are reversible except aminoglycosides (bactericidal)

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54
Q

Aminoglycosides

A

protein synthesis inhibitor

bactericidal
irreversible inhibition of initiation complex via binding 30s subunit
misreading of mRNA
blocks translocation
requires O₂ for uptake (ineffective against anaerobes)

“GNATS caNNOT kill anaerobes in A-MIN(oglycosides)

Gentamicin
Neomycin
Amikacin
Tobramycin
Streptomycin

IV (poor oral)
distribute through total body water

very good against
E coli and pseudomonas
systemic, severe, rapidly progressing infections (severe GNRs)
synergistic w/ beta-lactams 
Neomycin for bowel surgery
therapeutic levels are close to toxicity (where it accumulates)
NNOT:
Nephrotoxicity
Neuromuscular block
Ototoxicity (esp w/ loop diuretics)
Teratogenic
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55
Q

Tetracyclines

A

Protein synthesis inhibitors

Tetracycline
Doxycycline
Minocycline

broad spectrum gram +/-
accumulates intracellularly
good for Rickettsia and Chlamydia, acne

adverse effects:
abnormal bone and tooth development (not <8yo)
superinfections- fungal
photosensitivity
contraindicated in pregnancy
chelates w/ divalent cations (don’t consume milk/iron/antacids)

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56
Q

macrolides

A

protein synthesis inhibitors
via block of translocation (macroSLIDES)

erythromycin
azithromycin
clarithromycin

spectrum:
medium spectrum GP and some GN
atypical pneumonias (mycoplasma, chlamydia, Legionella)
STIs (chlamydia)
B pertussis
adverse rxns:
drug interactions due to inhibition of P450 metabolism
MACRO:
gi Motility issues
Arrhythmia (prolonged QT)
acute Cholestatic hepatitis
Rash
eOsinophilia
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57
Q

chloramphenicol

A

protein synthesis inhibitor

broad spectrum:
treats meningitis
(H influenzae, Neisseria meningitidis, Streptococcus pneumoniae)
treats Rocky Mountain Spotted Fever (Rickettsia rickettsia)

limited use due to high toxicity, but cheap
bone marrow toxicity
anemia (dose dependent)
aplastic anemia (dose independent)
gray baby syndrome (premature infants)
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58
Q

Lincosamides

A

protein synthesis inhibitors

Clindamycin

spectrum:
narrow spectrum gram + cocci (penicillin alternative)
anaerobes ABOVE the diaphragm-
Bactericides spp, C perfringens) in aspiration pneumonia, lung abscesses, oral infections
acne
invasive Group A strep (strep pyogenes)

adverse rxns:
severe diarrhea
pseudomembranous colitis (C diff overgrowth)
fever

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59
Q

streptogramins

A

protein synthesis inhibitor

Quinupristin
Dalfopristin

reserved for life threatening VRE

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60
Q

ozazolidinones

A

protein synthesis inhibitor

Linezolid

gram +, specifically MRSA and VRE

adverse effects:
bone marrow suppression (esp thrombocytopenia)
peripheral neuropathy
serotonin syndrome

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61
Q

important metabolism/hepatic elimination mneumonic

A 
Clindamycin, chloramphenicol
Rifampin
Isoniazid
Metronidazole
Erythromycin
Sulfonamides, streptogramins
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62
Q

Antimetabolites

A

folic acid metabolism and reduction (DNA methylation)

targeted because bac make their own folic acid and humans don’t (but bac can get folic acid from a pustule!! so not helpful there)

MOA:
sulfonamides inhibit dihydropteroate synthase (DHPS)
Trimethoprims inhibit dihydrofolate reductase
— selective toxicity
bacteriostatic w/ delayed onset of action (5-6hrs)
synergistic w/ other drugs in same pathway

Toxicity:
moderately safe
renal damage- crystalluria
hematopoeitc system (anemia)
hypersensitivity rxns
drug interactions (displacement from albumin eg warfarin)
Kernicterus in neonates
GI upset common

earliest antibiotics- lots of resistance; not really used alone anymore

sulfonamides
trimethoprim

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63
Q

sulfonamides

A

antimetabolite- inhibit folate synthesis

sulfamethoxazole SMX
sulfisozazole
sulfadiazine

gram positive
gram negative
Nocardia
Chlamydia
SMX for simle UTI

add trimethoprim in combo w/ sulfonamide for sequential block of folate synthesis
TMP Treats Marrow Poorly- can cause megaloblastic anemia, leukopenia, granulocytopenia)

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64
Q

DNA metabolism inhibitors

A

fluoroquinolone
metronidazole
nitroimidazole

inhibit DNA gyrase and TopoIV
selective toxicity (humans don’t have gyrase)
bactericidal and rapid!!!
many organisms resistant to ahminoglycosides and penicillins are sensitive to fluoroquinolone

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65
Q

fluoroquinolones

A

important drug group!
DNA gyrate inhibitors (induces supercoils)
bactericidal

-floxacin’s (Ciprofloxacin)

spectrum:
gram neg rods of UTIs and GI tracts (incl pseudomonas)
Neisseria
some gram + organisms

do not take w/ antacids! (chelates metals)
"fluoroquinolones hurt attachments to your bones" (cartilage, tendons)
leg cramps/myalgias
GI upset
superinfection
skin rashes
HA, dizziness
contraindicated in pregnancy
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66
Q

metronidazole

A

DNA metabolism inhibitor

  • toxic free radicals that damage bac DNA
  • has to be reduced to be active (good for anaerobic)

bactericidal
anti-protozoal
anti-parasitic

treats anaerobic infection BELOW the diaphragm (vs clindamycin above)- pseudomembranous colitis, severe amebiasis, trichomoniasis

"GET GAP on the Metro w/ Metronidazole!"
treats:
Giardia
Entamoeba
Trichomonas
Gardnerella vaginalis
Anaerobes (bactericides, C diff)
h Pylori (used w/ PPI and clarithromycin for triple therapy)

adverse rxns:
disulfiram-like rxn w/ alcohol (severe flushing, tachy, hypotension)
HA
Metallic taste

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67
Q

nitrofurantoin

A

urinary antiseptic

similar MOA to metronidazole but often only bacteriostatic

uses:
UTIs, esp in pts allergic to sulfa drugs

adverse rxns: moderate
GI upset
hypersensitivity (hemolytic anemia)
neuropathies

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68
Q

quinolone generations

A

2nd generation-
Ciprofloxacin

3rd generation-
Levofloxacin

4th generation-
Moxifloxacin

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69
Q

cell membrane disrupters

A

polymyxins
daptomycin

interact w/ cell membrane

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70
Q

Polymyxin B

A

cell membrane disrupter

used topically due to high toxicity

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71
Q

daptomycin

A

cell membrane disrupter

bactericidal against GRAM POSITIVE (like vancomycin)
-also active against MRSA, VRE, and Linezolid

mild adverse rxns
rare eosinophilic pneumonia
rhabdomyolysis
myopathy

lung surfactant inactivates drug
restricted use

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72
Q

bactericidal vs bacteriostatic agents

A 
bactericidal:
immune compromised, mixed infection, severe infection
penicillins
cephalosporins
vancomycin
ahminoglycosides
fluoroquinolone
rifampin
polymyxins, daptomycin
bacteriostatic:
community setting when pts are immunocompetent
some broad spectrum and can give rise to superinfecitons
sulfonamides
trimethoprim
tetracyclines
macrocodes
clindamycin
chloramphenicol
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73
Q

why antibiotics fail

A

inadequate concentration of Ab at site or decreased activity

site of infection problems (foreign body, pus)

host factors

resistance

superinfection

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74
Q 
staphylococci info:
aerobe status
gram status
shape
morphology
blood agar
chocolate agar
MacConkey agar
catalase
coagulase
clumping factor

virulence factors

A 
aerobic
gram postiive
cocci
clusters and pairs
(staphylo= grape-like
coccus= sphere)
blood agar +
Chocolate agar +
MacConkey agar - 
catalase positive
coagulase positive (often hemolytic and golden)
clumping factor positive (binds to fibrinogen --> fibrin (clumping; protection from phagocytosis)

virulence factors:
cell wall: Protein A!! (binds Fc receptor of IgG’s; prevents Ab-mediated phagocytosis)
also peptidoglycan, teichoic acids, caps, clumping factor!!!, fibronectin, PB2a!!

enzymes: catalase, coagulase, hemolysis, lipase, beta-lactamase
toxins: Enterotoxin A1, Exfoliatin A-B, TSST-1

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75
Q

how does staph’s capsule increase its virulence

A

capsule inhibits phagocytosis- clumps and localizes in clusters- gets bigger than the phagocyte

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76
Q

role of teichoic acids in staph

A

adhesion molecs that stick out of staph to attache to epi layers, particularly nasal/pharyngeal cells

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77
Q

staph cytolytic proteins

A

hemolysins:
alpha, beta, delta gamma hemolysis
cause RBC lysis (all of these cause beta hemolysis)
cause tissue damage

Pantun-Valentine Leucocidin:
WBC lysis
protection from phagocytosis
invasive skin disease
sever invasive disease
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78
Q

staph Exfoliatins

A

Exfoliatin A and B:
2 immunologically distinct toxins w/ identical effects

bind to GM4 glycolipids (infants)

separation at granular cell layer (desmosomes)
-the skin exfoliates but it’s a very superficial layer

Scalded skin syndrome!!

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79
Q

Staph enterotoxins

A

Enterotoxins (enteric):
heat and acid stable proteins
30-40% of Staph aureus strains
PREFORMED toxin in contaminated food causes vomiting and diarrhea when ingested
-mediated by cytokine release! (mast cells)
-most common cause of food poisoning!!)

Enterotoxins B and C associated w/ TSS due to focal infection

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80
Q

staph Toxic Shock Toxin

A

TSST-1
superantigen that stimulates cytokines
results in endothelial leakage

Binds to MHC II and TCR outside of antigen binding site to cause overwhelming release of IL-1, IL-2, IFN-γ, and TNF-α –> shock

Toxic shock syndrome:
acute fever,
erythroderma (intense rash)
shock (hypotension, multi-system involvement)

risk factors for TSS:
exposure to TSS-containing staph aureus
organism growth under conditions that promote toxin production
no pre-existing Ab to toxin(s)
genetically predisposed
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81
Q

common staphylococci locations

A

normal flora in most humans

staph aureus:
NOSE
some skin, throat, vagina

coagulase-negative staph:
SKIN
some nose, throat

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82
Q

staph aureus antibiotic resistance

A

altered cell wall permeability

antibiotic-altering enzymes

altered protein targets

altered metabolism

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83
Q

MRSA

A

all staph aureus produce coagulase and nuclease, but MRSA strains carry the mega gene

  • codes for altered PBP2A
  • decreases beta-lactam binding and cell wall inhibition
  • primary mech for methicillin resistance
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84
Q

VISA and VRSA (E-test)

A

Vancomycin inhibits cross-polymerization in peptidoglycan

vancomycin intermediate staph aureus VISA
MIC is 4-8 ug/mL
increased number of PG layers

vancomycin resistant staph aureus VRSA
MIC >=16 ug/nL
van A gene from Enterococcus

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85
Q

MIC creep

A

the phenomenon that has been noted worldwide of slightly increasing vancomycin MIC’s

still within the susceptible range, but assoc w/ tx failures
the higher the MIC, the higher the rate of therapeutic failure

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86
Q

D test

A

positive test looks like a D

shows exposure to erythromycin has induced clindamycin resistance

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87
Q

staph skin infections

A

furunculosis = boils
cellulitis- mild to severe

also lymphadenitis- local lymph node abscess
bet tx- pop and drain; Ab’s are 2ndary

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88
Q

staph and sinusitis

A

staph is uncommon cause of local respiratory spread:
otitis
sinusitis
pneumonia (cystic fibrosis)

generally a single deep focus
-occasionally doesn’t localize well and causes disseminated septicemia

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89
Q

staph effects on bone

A

osteomyelitis w/ hematogenous spread

local bone abscess

staph is most common cause

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90
Q

disseminated staph septicemia

A

does not localize

often assoc w/:
endocarditis or thrombophlebitis

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91
Q

major host defense against staph

A

phagocytosis is major host defense

impeded by:
protein A
Pantun-Valentine Leukocidin
localizing factors (clumping, coagulase factors)

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92
Q

staph and chronic granulomatous disease

A

sex-linked recessive neutrophil defect

most common neutrophil defect

impaired hydrogen peroxide-mediated intracellular killing-
can get chronic infections that just don’t heal

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93
Q

Job’s syndrome

A

leukocyte syndrome - T cell disorder
Hyper IgE
poor neutrophil chemotaxis/cytotaxis
get cold abscesses

FATED: coarse Facies, 
cold (nonin amed) staphylococcal Abscesses, 
retained primary Teeth, 
IgE, 
Dermatologic problems (eczema).
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94
Q

staph toxin diseases

A

scalded skin syndrome: AKA Ritter’s disease
caused by Exotoxin A and B in granular cell layer
blisters are superficial, pts/kids still in pain
you can tx and help kids develop antibody

if you have pre-existing antibody, you’ll get local toxin production (Bullous impetigo)
if you don’t, you’ll get systemic toxin (Ritter’s/Scalded skin/ scarlet fever, depending on age)

Exotoxin destroys keratinocyte attachments in stratum granulosum only (vs toxic epidermal necrolysis, which destroys epidermal-dermal junction).

Characterized by fever and generalized erythematous rash with sloughing of the upper layers of the epidermis G that heals completely. ⊕ Nikolsky sign. Seen in newborns and children, adults with renal insuf chancy.

scarlet fever:
older child
Erythematous, sandpaper-like rash with fever and sore throat
–strawberry tongue in young children

older children have fewer skin receptors, so milder disease

bullous impetigo:
young infants, often in diaper area

localized infections that give you local bulls disease; don’t get systemic disease
—-transplacental antibody protects from systemic disease

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95
Q

staph virulence factors and resultant diseases:
localizing factors
toxins

A

localizing factors:
coagulase
clumping factor
protein A

cause local infection abscesses-
can give bacteremia
disseminated infection, deep localized infection

toxins:
Enterotoxins:
give rise to FOOD POISONING, tss

TSST-1
give rise to TSS, staph scarlet fever

Exfoliatin
give rise to STAPH SCARLET FEVER, SCALDED SKIN SYNDROME

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96
Q

streptococci:
catalase status
hemolytic behavior
immunologic classification

A 
catalase negative (no bubbles) 
hemolytic behavior depends on strain (ex viridans is alpha hemolytic)
immunologic: 
-Lancefield groups A-U
-M and T proteins
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97
Q

lancefield groups of strep

A

lancefield groups = C-carbohydrate of cell wall

Group A = beta hemolysis (s. pyogenes)- throat

Group B= beta or none hemolysis (S agalactiae)- vagina

Group D= alpha hemolysis (E faecalis)- GI

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98
Q

optochin status of strep viridans vs pneumoniae

A

strep pneumoniae- optochin sensitive

strep viridans- optochin resistant

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99
Q 
Group A strep microbiology:
hemolytic status:
catalase:
penicillin:
virulence factors:
M proteins
attachment factors
spreading
toxins
necrotizing factors
A

GAS = strep pyogenes

beta-hemolytic
catalase negative
penicillin susceptible

virulence factors:
many M proteins (antibodies provide type-specific immunity)
attachment factors: pili (adhesion to epi cells), fibrontectin-binding protein
spreading factors!!!: streptokinase, hyaluronidase, DNase
Toxins: pyogenic exotoxins
Necrotizing factors: protease

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100
Q

Group A strep attachments

A

use pili to adhere to different epithelial cells

thinly keratinized squamous epi:
throat (pharyngitis/rheumatic fever)
perineum (anus, vagina)

skin:

superficial: impetigo (nephritis)
invasive: cellulitis, necrotizing fasciitis, TSS

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101
Q

Group A strep M protein

A

M proteins stick out of cell wall- it’s the major virulence factor for S pyogenes
–phagocytes ingest/kill strains w/o M protein

very far variable “A” region gives you 120 different M proteins
–it has a neg charge to repel phagocytes

core of the antibody can’t get to it because you’ve got fibrinogen binding to it; so it can’t be opsonized to be phagocytized

but if you have proper antibody to M protein- strep is eaten/killed by PMNs
–antibody protection is serotype specific

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102
Q

Group A extracellular virulence products and spreading factors

A

Streptomycin O
-hemolytic, cardiotoxic

Streptomycin S
-hemolytic, cytotoxic

Pyrogenic exotoxins A,B,C
-superantigens! cause fever, rash, Strep TSS

spreading factors:
streptokinase
-activates plasminogen, lyses fibrin
hyaluronidase
-dissolves ground sub
DNAase 
-dissolves DNA
proteinase
-proteolytic destruction
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103
Q

eagle effect

A

clindamycin is better tx for severe strep infections, even though it’s not penicillin-resistant

beta-lactams:
bactericidal (only kill actively growing organisms)
fail to kill large inoculum or stationary-phase organisms
may stimulate toxin production and release!

clindamycin:
bacteriostatic
kills (w/ WBCs) all phases
decreases toxin and enzyme production
increases opsonization
improved clinical efficacy
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104
Q

clinical pharyngitis

most common causes?

A

symptoms referable to throat
over 10million acute pharyngitis cases/yr

strep pyogenes- most common cause of bacterial pharyngitis
(M proteins attach to pharyngeal)

BUT 2/3 of sore throats are caused by viruses
-strep much less likely in a pt w/ cough, runny nose, or <3yo- probably shouldn’t culture these pts because you might find strep + as part of normal flora (not sickness)

tender lymph nodes = STREP
close contact = STREP
cough = VIRUS
runny nose = VIRUS
<3yo = VIRUS

also bad culture = bad text results

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105
Q

complications of strep pharyngitis
suppurative
non-suppurative
toxic

A 
suppurative (pus):
otitis media
sinusitis
parapharyngeal abscesses
cervical adenines
pneumonia
non-suppurative:
acute rheumatic fever (only certain M proteins and certain humans)
Post-strep reactive arthritis
PSGN
PANDAS??

toxic:
scarlet fever
TSS

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106
Q

acute rheumatic fever

A

nonsuppurative complication of strep pharyngitis
-onset 3-6 weeks after infection

inflammation of heart valve, skin, joints, CNS

S pyogenes not recovered from site inflammation

best model: autoimmune disease

  • Rheumatic strains: M3 and M18 associated ARF
  • Genetic predisposition: FHx, HLA and B cell alloantigen assoc’s
  • Hypothesis: genetically programmed abnormal immune response to a common infection

common recurrence w/ re-infection
high ASO titers imply greater risk
-can be prevented via therapy of acute infection

JONES criteria

  • polyarthritis
  • endocardidits
  • nodules
  • erythema marginatum
  • Sydenham chorea
107
Q

post streptococcal glomerulonephritis

A

nonsuppurative complication of S pyogenes
-only certain M types (nephritogenic)

onset 2-4 weeks after infection
inflammation of kidney/glomerulus

S pyogenes not recovered from site of inflammation

best model: immune complex disease
-results in low complement levels

108
Q

post streptococcal reactive arthritis

A

small joints as well as big ones and axial

NSAID Unresponsive

evidence of recent strep infection

109
Q

strep serology uses

A

ASO and ADB titers:

will be positive in 15-20% of asymptomatic/normal children

usually not elevated in acute disease

only perform in children where strep is plausible for current illness
-eg rheumatic fever of PSGN

110
Q

skin manifestations of Group A strep
superficial
invasive
toxic

A

superficial:
impetigo

invasive:
perineal
-perianal
-vaginitis (common in prepubertal girls)
myositis
necrotizing fasciitis
cellulitis

toxic:
Scarlet fever
TSS

111
Q

impetigo contagiosa vs cellulitis vs necrotizing fasciitis

A

impetigo:
honey-crusted lesions- usually around mouth
frequent in tropical areas
often assoc w/ acute post-strep nephritis

cellulitis:
only certain strains,
tends to be ~superficial;
spreading factors= hyaluronidase, DNase, streptokinase

Necrotizing fasciitis:
rapidly progressive
classic (but not sensitive_ features:
-blistering, painful, TSS, rash
failure to improve w/ antibiotics
-F/U on presumed cellulitis tx response within hours
imaging not sensitive
-MRI best; not delay surgery if NF suspected
often requires early surgical exploration to assess
may be staph or strep- culture and Ab choice is important
-Vancomycin + Clindamycin + ? Meropenem)

112
Q

classic strep scarlet fever

A

you get scarlet fever if you don’t have antibody

superficial erythroderma (sunburn like skin)
strawberry tongue
conjunctivae not usually involved

113
Q

streptococcal TSS

A

Hypotension or shock + 2 or more:

renal impairment
DIC
liver impairment
ARDS
scarlet fever rash
soft tissue necrosis
114
Q

common cause of perineal infection

A

can be perianal or vulvovaginal infection

Group A strep is most common cause of vaginitis in pre-pubertal girl
different T and emm types

115
Q

Streptococcus agalactiae

general info

A

AKA Group B strep

gram postiive cocci
weakly hemolytic
lipotechoic acid- causes adherence
M,T,R proteins absent
polysaccharide capsule (anti-phagocytic)
-6 serotypes
-antibody against capsules mediates protection; antibody is serotype specific

major site of colonization is female genital tract
-if they’re recently infected and then give birth the baby won’t have time to acquire Ab, so baby gets Group B strep- sepsis, pneumonia, etc (high mortality)

116
Q

Enterococcus

general info

A

colonize normal GI tract

adults: nosocomial infections-
UTI, bacteremia, line sepsis, endocarditis

children: nosocomial bacteria

inherent resistance to cephalosporins, penicillin, ahminoglycosides, tmp/smx, clindamycin

inducible transferable high level vancomycin resistance (VRE)

117
Q

strep pneumoniae and strep viridans

A

strep pneumo:
encapsulated pathogen
most common cause of bacterial pneumonia

strep viridans:
many species
non-lancefield typable
nl flora in pharynx
-causes dental caries and endocarditis
118
Q

streptococcus anginosus (millenni)

A

emerging pathogen

usually alpha or non-hemolytic, but may be beta-hemolytic
“butterscotch” odor
normal upper respiratory, intestinal, and vaginal flora

clinical presentation:
brain abscesses
resp infections
-orbital cellulitis (most common cause in kids!!), peritonsillar abscess, penumonia
human bites
less common:
-osteomyelitis, septic arthritis, liver abscess, myositis

usually susceptible to penicillin!
becoming more common in children

119
Q

Enteric bacteria overview

A

bacteria found in the intestine

diarrhea is major cause of global mortality
-cause by Enterobacteriaceae and Vibrionaceae

US- from ingesting contaminated food/drink

extra intestinal disease- pneumonia, sepsis, meningitis, UTI

must overcome host defenses- gastric acidity, intestinal motility, local Ab, nl gut flora

120
Q

4 main causes of enteric infections

A

Salmonella
Shigella
E coli
Yersinia spp

Vibrionaceae, campylobacter, helicobacter are distantly related to enterobacteriaceae

all are gram negative bacilli
Vibrio (curved rods)
Campylobacter (gull-winged or S shaped)
otherwise, look similar

121
Q

antigenic structure of enteric bacteria

A

LPS
in outer membrane of all gram neg bac

H antigens
flagellar protein antigens assoc w/ motel organisms
not all enterics have this

K antigens
capsular polysaccharide
not found in all strains
usually assoc w/ increased virulence
most significant when organism produces extra intestinal infections (eg bacteremias)
122
Q

LPS components of an enteric bacteria

A

Lipid A:
endotoxin
toxic part of LPS
similar but not identical among all gram neg’s

core polysaccharides:
constant region of LPS within a genus

O antigens:
repeating subunits of oligosaccharides of LPS
variable within a genus
helps species identification

123
Q

methods of dx of enteric bacteria infection

A

stool exam
to differentiate non-inflamm, watery diarrhea from inflammatory diarrhea
vol, smell, texture
gram stain, methylene blue stain for fecal leukocytes
wet mount for motility

media and culture conditions

biochemical rxns
-all Enterics are oxides negative, ferment glucose
Vibrios are oxidase positive
API strips for species ID

serological differentiation- usually limited to preliminary grouping

Toxin assays or gene probes
mostly for epidemiology
rapid test kits are now available

124
Q

genetics of enteric bacteria

A

plasmids
many enterics have medically-relevant plasmids
-toxins
-adherence
-invasive factors (Type 3 secretion system)

bacteriophage conversion
genes of a bacteriophage can change the phenotype of the bacterium it lysogenizes

chromosome
very dynamic variability, partly due to transposable elements that carry genes encoding virulence determinants and antibiotic resistances

pathogenicity islands
specific DNA regions found only in chromosomes of pathogenic strains
encode virulence factors (invasion genes, toxins)

125
Q

characteristics and likely cause of watery diarrhea

A

copious watery
no blood or pus
no tissue invasion
Small intestine

likely:
ETEC, EPEC, campylobacter

126
Q

characteristics and likely cause of dysentery

A

scant volume
blood pus or mucus present
tissue invasion
large intestine

likely:
Shigella, EIEC, campylobacter

127
Q

characteristics and likely cause of protracted diarrhea

A

lasting more than 14 days

likely:
EPEC

128
Q

characteristics and likely cause of bloody, watery diarrhea

A

copious vol
some blood, pus
invasion
ileum, colon

likely:
salmonella, campylobacter, Yersiniae

129
Q

characteristics and likely cause of hemorrhagic colitis

A

copious vol
like liquid blood
no leukocytes or invasion
large intestine

likely:
EHEC

130
Q

opportunist enteric pathogens

A

don’t usually cause disease in healthy individuals

usually assoc w/ extrainestinal sites, and in immunocompromised pts

vibrio vulnificus septicemia is 50% fatal in these pts

131
Q

2 basics of pathogenesis in enteric pathogens

A

not mutually exclusive

primarily toxigenic-
Vibrio cholerae, ETEC, EHEC

primarily invasive-
Salmonella

or both mech’s used
Shigella dysenteriae

132
Q

Exotoxin, Enterotoxin, and Endotoxin definitions

A

Exotoxin-
usually a protein secreted out of cell by organism

Enterotoxin-
exotoxin that has specific effects on the intestine

Endotoxin-
LPS- Lipid A + O antigen

133
Q

how the site of enteric infection determines disease outcome

A

generally speaking…

small intestine:
secretory diarrhea

large intestine:
inflammatory diarrhea

Stomach: H pylori

SI: V cholerae, ETEC, Salmonella, Yersinia, Campylobacter

LI: Shigella, EHEC

134
Q

how relatively easy an enteric bacteria is transmitted

A

relative infectivity
main correlation is that organisms that are more sensitive to acid (eg vibrios) have higher infective doses
-these are more likely to be transmitted by food or water

low infective doses
-more likely to be transmitted directly person to person

Shigella- as low as 10-100
Salmonella- anywhere from 100- 10^5
Vibrio, ETEC- 10^8 but may be 10^4 in foods that neutralize stomach acidity

135
Q

non-invasive enteric pathogens

A

Vibrio cholerae

Enterotoxigenic E colic (ETEC)

Enteropathogenic E coli (EPEC)

Enterohemoryhagic E coli (EHEC)

136
Q 
Vibrio cholera 
classification
clinical symptoms
pathogenesis
colonization
toxin production
toxin structure/function
epidemiology
mode of transmission
Tx
A 
cholera-
profuse, watery diarrhea cause by an enterotoxin
prototype for toxigenic diarrheas
no tissue invasion
affects small intestine

classification:
frequently cause by organisms of serotype O1

clinical symptoms:
intubation 2-5 days
abrupt onset of diarrhea, abdominal cramps, some vomiting
no fever
mild to SEVERE watery diarrhea- up to 15-20L/day
severe dehydration, BP drop, vascular collapse
death if untreated

pathogenesis
colonization of small bowel and toxin production
both require factors encoded by different lysogenic phages-
Bacteriophage conversion is important!!

colonization
requires surface-expressed adherence factor TCP pilus, which is also the coat protein of a phage encoding cholera toxin CTX

toxin production
genes encoded as part of phage genome CTX
this phage uses TCP pilus as its receptor

toxin structure and function
prototype A-B type toxin
B subunit binds to cell surface receptors of enterocytes
A subunit then enters cytoplasm, transfers ADP-ribose from NAD to a regulatory G protein
increased Cl- secretion
decreased Na absorption
net secretion of fluid into gut lumen
Cytotonic (does NOT kill the cell)- an intoxicated enterocyte continues secretion until it’s replaced naturally

epidemiology
currently in 7th pandemic, mostly Asia and Africa
endemic on Indian subcontinent
Most US cases imported from endemic areas

mode of transmission:
fecal/oral, generally through contaminated foods
environmental reservoir- aquatic environments

Tx
aimed to restore fluid and electrolyte loss
mild- oral rehydration w/ salt/sugar solns ORS: isotonic Na/K, Cl, citrate or bicarb buffer, and glucose
severe- IV rehydration w/ Ringers lactate + KCl
Antibiotics shorten course, number/vol of stools, and number of Vibrios excreted in stool, and may help reduce carrier state

137
Q

Vibrio parahaemolyticus info

A

non-invasive enteric bacteria

Halophilic (salt loving)
inhabits marine and estuarine environments

causes 3 major syndromes:
gastroenteritis (most common)
wound infections
septicemia

assoc w/ eating raw or undercooked shellfish

disease:
usually acute diarrhea
abdominal cramps
N/V common
occasionally bloody stools- produces hemolysin and is mildly invasive
138
Q

vibrio vulnificus info

A

can cause gastroenteritis
usually from ingestion of contaminated seafood/oysters
proceed to extra intestinal infections in immunocompromised pts, w/ high fatality rates
also infects wounds

139
Q

E Coli

types of diarrhea, epidemiology, and key virulence factors of ETEC, EPEC, and EHEC

A

E coli is nl in human colon and is most abundant facultative anaerobe in feces

ETEC:
traveler’s diarrhea
-worldwide
-heat-labile and heat-stable toxins

EPEC:
watery, persistent diarrhea
-infants < 1 yo
-attaching and effacing (AE)

EHEC
bloody, dysentery diarrhea
-developed
-AE, shiva-like cytotoxin

140
Q 
Enterotoxigenic E coli
general info
symptoms
tx
pathogenesis
A

ETEC

leading cause of traveler’s diarrhea in adults
-important in children’s diarrhea in developing countries

symptoms:
acute onset
watery diarrhea
no blood or pus
rarely have low-grade fever
abdominal cramps
vomiting
can be severe, cholera-like, even in adults

tx:
usually supportive- replace fluids and salt
acute onset, self-limiting nature
Antibiotics (even prophylactic) not usually recommended
Bismuth subsalicylate (pepto-Bismol) helps relieve symptoms and shorten duration

Pathogenesis
toxigenic diarrhea- no tissue invasion
2 types of toxins:
heat labile entereotoxin- same MOA as cholera
heat stable enterotoxin- small peptide toxin that activates guanylate cyclase, raising cGMP levels, leads to increased fluid secretion

must be able to colonize small intestine- express fibril adhesions
adhesion overcomes peristalsis effect

141
Q 
Enteropathogenic E coli
general
symptoms
tx
pathogenesis
A

EPEC

predominantly seen in infants < 1yo
(childcare outbreaks)
occasional adult outbreaks
large inoculate needed

symptoms:
watery stools
no blood or mucus
no tissue invasion
vomiting, low grade fever common
may be prolonged
relapse is common

tx:
restore hydration
usually responds rapidly to antibiotic therapy

pathogenesis
intimately adhere to enterocyte surface
a TYPE 3 SECRETION SYSTEM secretes the translocated-intimin receptor, initiating the characteristic “ATTACHING AND EFFACING LESION”
-microvilli destruction, pedestal formation
probably interferes w/ absorption, leading to diarrhea

142
Q

Invasive enteric pathogens

A

cause structural damage to intestine
usually produce inflammatory diarrhea (frequent, low-vol mucoid or bloody stools), tenesmus, fever, or severe abdominal pain
stools may have leukocytes and gross or occult blood
fecal leukocytes- indicative of colonic damage
M cells play major role in tissue invasion
(antigen-sampling cells that overly the lymphoid follicles of the gut; major initial targets of entry of invasive pathogens)

Shigella spp-- prototypic; dysentery
Salmonella enterica; gastroenteritis (typhoid fever)
Campylobacter
Yersina spp- Yersinosis
Helicobacter pylori
143
Q 
Shigella spp
classification
pathogenesis
clinical symptoms
transmission
reservoir
tx
A

Shigellosis, bacterial dysentery

classification:
based on O antigen grouping:
Group A: S dysenteriae
type 1 causes epidemic dysentery

Group B: S flexneri
most common in developing world (US male homosexuals)
-Groups A and B have haver incidence of dysentery

Group C: S boydii
rare in us; primarily in India

Group D: S sonnei
most prevalent in US
mildest disease, usually watery diarrhea

pathogenesis:
watery diarrhea is Enterotoxins
secretes effector proteins through Type 3 secretory system
entry via M cells, uptake by macrophages
Induce apoptosis and inflammation
invade basal side of epi cells
lyse the vacuole
grow in cyto
spread directly into neighboring cells
inflammatory response increases local spread and severity of symptoms, but ultimately enables pt to clear infection
—only S dysenteriae type 1 make cytotoxic Shiga toxin

clinical symptoms
All shigella can cause dysentery, but severity decreases down the groups
intubation 1-4 days (up to 8 w/ S dysenteriae)
initial fever, malaise, vomiting
followed by watery diarrhea
progress to frank dysentery, freq small stools w/ blood and mucus, cramps, and tenesmus
up to 20 stools/day

LOW infectious dose- 10-100 organisms
very acid resistant, survive stomach

humans only known reservoir- no known animal host

fecal/oral person-to-person transmission w/ four F’s: food, fingers, feces, flies

tx:
supportive, restore fluid balance
milder cases usually self-limiting
Ab tx of severe cases shortens duration of symptoms and shedding of bacteria

144
Q 
Salmonella enterica 
general
classification
epidemiology
transmission
pathogenesis
clinical symptoms
tx
Immunity
A

Gastroenteritis and Typhoid fever

invasive
enter across intestinal mucosa, can cause both GI and systemic disease
not host adapted (vs shigella)- move easily between environment, animals, and humans- Gastroenteritis
-2nd leading bac cause of gastroenteritis
Typhoid fever- from highly human-host adapted serovars

classification
2500 different servers differentiated by O and H antigen combinations
currently only 2 species recognized- all pathogenic Salmonella belongs to Salmonella enteric subspecies enterica
Enteritidis and Typhimurium are most common serovars affecting humans

Epidemiology, transmission
fecal-oral
typhoid- only transmitted by humans
non-typhoidal salmonellosis is zoonotic- animals are important sources (poultry, eggs, contaminated fresh produce)

pathogenesis
entry via oral route
invasion of M cells, leading to transient bacteremia
uptake by mononuclear phagocytes, where Salmonella multiply

clinical symptoms and tx:

Gastroenteritis
most common
febrile food poisoning presents 24-48hrs after ingestion
N/V, HA, followed by chills, fever, cramps, and watery diarrhea
self-limiting
mostly don’t require Ab tx

Septicemia
prolonged fever, generally w/o diarrhea
dx by multiple positive blood cultures
highly invasive serovars such as Cholerasuis

Typhoid (enteric) fever
S typhi and S paratyphi
inoculum-dependent intubation period days-weeks
constipation or inflammatory diarrhea
then stepwise increase in temp over several days to high fever
untreated, continues 6-8 weeks
colonization of gallbladder can lead to carrier state or intestinal perforation
tx w/ antibiotics

immunity
not good immunity against Salmonella due to different serovars
infection w/ 1 doesn’t usually induce protection against a subsequent infection
Typhoid vaccine w/ purified Vi polysaccharid effective in adults and children >2yo

145
Q

Yersina spp

info

A

Yersinosis
invasive enteric bac

3 human pathogenic app:
Y Pestis
Y enterocolitica
Y pseudotuberculosis

only last 2 are enteric pathogens- causing food borne illness, and zoonotic infections from domestic animals

occasional cause of infections acquired from blood transfusions due to ability to grow at low temp

often assoc w/ eating undercooked pork, dairy products

pathogenesis:
low grade fever
watery diarrhea
some w/ blood
fecal leukocytes
infects terminal ileum
often prod RLQ pain mimicking appendicitis
complications
reactive arthritis (Reiters syndrome) most often w/ HLA-B27 positive pts

Antibiotics not shown to have major impact on outcome, but due to invasiveness and capacity to cause serious illness, infections usually tx w/ antibiotics

146
Q

Campylobacter

A

food-borne gastroenteritis
invasive

most common cause of gastroenteritis in Western world

pathogen and disease
C jejuni and C coli
small, curved, gram neg rods
catalase and oxidase positive
prefer microaerophilic and increased temp for culture- grow best on enriched media w/ antimicrobials that inhibit other intestinal bacteria
low dose inoculum
symptoms
diarrhea
fever
abdominal cramping
half of pts have bloody stools
fetal leukocytes may be present
complications (rare):
Guillain-Barre syndrome- demyelinating degenerative nerve disease, may be due to antibody response against oligosaccharides of O antigen cross reacting w/ sphingolipids on nerve cells
Reiters syndrome (autoimmune reactive arthropathy) frequently occurs w/ HLA-B27 positive pts

pathogenesis
not well understood
3 factors influence disease- invasiveness, enterotoxin production, and cytotoxin production
terminal ileum and proximal colon are sites of invasion
motility and chemotaxis are important factors in colonization of gut

epidemiology and transmission
peak during WARM months
person-person transmission is rare
outbreaks due to contaminated milk or water
sporadic cases assoc w/ young pets w/ diarrhea, improper handling of raw poultry, or eating undercooked poultry
highest in infants; peaks again in young adults males
lowest rates for adults- reflects some immunity
more severe inflammatory diarrhea in industrialized countries vs milder watery diarrhea in developing nations- reflects levels of prior exposure to organism

tx
supportive, fluid replacement
antibiotics in severe cases
Erythromycin or quinolone
Fluroquinolones resistance is emerging due to overuse of related antibiotics in poultry industry
147
Q 
Helicobacter pylori
info
pathogen and disease
pathogenesis
virulence factors
epidemiology and transmission
clinical diagnosis
testing, treatment
A

gastric and duodenal ulcers, gastric cancer

invasive

similar to campylobacter
THE MOST common human bacterial pathogen, infecting more than half the world’s pop

pathogen and disease
primary habitat- human gastric mucosa
colonizes mucus layer of stomach; doesn’t invade epithelium
curved, highly motile, microaerophilic Gram neg rods- strong urease activity
isolated on campy agar w/o antibiotics
H pylori infection causes mucosal inflammation in virtually every pt, w/ epi cell damage and neutrophil infiltration (chronic gastritis, may be asymptomatic)
causes reduction in acid secretion- leads to gastric atrophy, progressing to gastric carcinoma
responsible for nearly all duodenal ulcers and 70% of gastric ulcers

Pathogenesis/virulence factors
high motility- rapid penetration of gastric mucus to reach less acidic environment of gastric epithelium
powerful urease production- creases ammonia to further raise pH
severity of disease correlates w/ strains that have a pathogenicity island encoding potential virulence genes- vacuolating cytotoxin?
autoimmune response postulated- molecular mimicry (like campy)- LPS contains Lewis X and Y blood group antigens

epidemiology and transmission
typically acquired in childhood, is lifelong w/o tx
decreasing in industrialized countries (standard of living)
fecal/oral person-person suggested
prevalence increases w/ overcrowding and low socioeconomic status
genetic disposition for ability to be colonized- some never colonized
predicted to disappear without intervention, but over a century

clinical dx
"gold standard" histo exam of multiple biopsy specimens w/ special stains, followed by culture and isolation of organism
rapid urease tests
breath tests- 13C urea- given w/ meal
ELISA tests for IgG

testing and tx
NIH recommends tx only for pts w/ peptic ulcers (to prevent antibiotic resistance)
successful tx means relief of symptoms and ulcer healing, preventing long-term sequelae
tx- combo of antisecretory agents and antimicrobials- triple therapy recommended
PPI + Bismuth + tetracycline for 14 days
some failures due to antibiotic resistance

148
Q

3 advantages of having an intracellular life

A

nutritional advantages
-avoid competition for space and nutrients
(Facultative vs obligate)

protected site from the antimicrobial actions of immune system
avoid innate and humoral defenses
could lay dormant for decades and emerge in immunosuppressed conditions

protected dissemination around the body
Shigella can spread cell-cell in epi monolayers
Salmonella can disseminate outside of intestine to systemic sites inside phagocytes

149
Q

Zipper vs Trigger mech of entry for intracellular pathogens

A

both: the reorganization of the actin cytoskeleton results in changes at membrane surface, allowing bac uptake

Zipper:
tight interaction between bac cell surface ligands and host cell receptors –> closure of host cell surface around bacterium
ex.
parasite-induced phagocytosis into phagocytes
receptor-mediated phagocytosis of macrophages
coiling phagocytosis

Trigger:
bacterial products induce the cell surface to ruffle, projecting membrane extensions that surround bacteria
products secreted by type 3 secretory systems of Salmonella and Shigella induce this type of uptake

150
Q

challenges inside professional phagocytes for intracellular pathogens

A

professional phagocytes-
modifies internal compartment through acquiring proteins and makers of endosomes- continue maturation and acquire lysosome markers
formation of phagolysosome- main job to kill microbes, degrade molecs, and present antigen to immune sys
-harsh phagocyte environment and slow growth of some intracellular pathogens contribute to chronicity of many infections

antimicrobial defenses of professional phagocytes-
NADPH oxidase-
causes reactive oxygen species production
-some developed ways to prevent assembly of NADPH oxidase complex

inducible NO synthase
produces NO, which targets many intracellular pathogens
-dormancy is a consequence of the continuous NO production

oxygen-independent effector molecs
broad-spectrum antimicrobial peptides
-reduce conc’s of Fe available to intracellular pathogens to levels non-compatible w/ life
-low pH within phagolysosomes

151
Q

mechanisms that intracellular pathogens have devised to adapt to intracellular life

A

escape from vacuole
non-fusogenic organisms
fusogenic orgnaisms
intracellular bacterial of non-professional phagocytes

152
Q

escape method of intracellular pathogens

A

Escape:
Listeria lyses the phagocytic vacuole, escaping into cytosol

in the cytosol, Listeria polymerizes actin to propel itself within cytosol
also allows bac to invade neighboring cells w/o ever going extracellular

advantages:
access to large nutrients, and minimize exposure to antimicrobials in vesicles

host defenses:
cytosolic antimicrobial peptides, and NO synthase can target them
cytotoxic CD8 T cells can lyse infected cells expressing MHC class 1 molecs in assoc w/ microbial peptides
153
Q

non-fusogenic intracellular pathogens

A

contained in membrane-bound compartments that avoid degradation pathway ultimately linked to lysosomal function

advantages:
bac can remain viable inside phagosome
also avoids processing of bac antigens that would lead to immune sys activation via MHC class 2 presentation

host defenses:
many cause long-term infections via formation of granulomas
these lesions develop over months after infection, and consist of activated macrophages and T cells
granulomas contain these infectious agents by maintaining balance between organism growth and antimicrobial host defenses

154
Q

fusogenic organisms and intracellular pathogens

A

Coxiella burnetii- obligate intracellular Gram neg bacterium

only intracellular pathogen to reside within phagolysosome

phagosome matures through endocytic pathway
eventually acquires lysosome properties
pathogen-containing vacuole acidifies
organism is not cytopathic, reaching very high numbers within a single vacuole

155
Q

intracellular bac of non-professional phagocytes

A

non-professional phagocytes like endothelial cells-
limited phagocytic and bactericidal activity
cells w/o lysosomes-
erythrocytes

(Bartonella does this)

156
Q

antibiotic therapy of intracellular pathogens

A

intracellular location causes failure of some antibiotics for some tx of infected hosts

intracellular antibiotic activity depends on:
penetration of euk membrane
sub cellular localization
deleterious interactions w/ the intracellular milieu, incl pH
antibiotic susceptibility of intracellular pathogen

Amino glycosides and macrocodes:
weak bases
concentrated inside lysosomes by pH dependent mech
-preferential localization to lysosomes and partial inactivation by acidic pH– major disadvantage

beta-lactams
-lack of peptidoglycan in cell wall and intracellular lifestyle of chlamydiae may explain poor activity of beta-lactams

157
Q

overview of viral gastroenteritis clinical syndrome

A

signs and symptoms:

acute onset of watery diarrhea (no mucus or blood)
+/- vomiting (often precedes diarrhea)
Nausea
intestinal cramping (from hyper motility)
myalgias, low-grade fever, HA, malaise

158
Q

epidemiology of viral gastroenteritis

A

fast on fast off

short intubation period

prolonged shading in stool (often asymptomatic)- high transmissibility

very stable (can persist on contaminated surfaces)

seasonal

transmission:
person to person fecal-oral
-nosocomial in healthcare, day care, cruise ships
-esp where pts are incontinent- psych, nursing home, etc
food borne
waterborne

159
Q

burden of disease for gastroenteritis

A 
US- think morbidity 
2nd most common cause of illness
1-2 episodes/child/yr
hospitalizations from dehydration
---big burden of disease w/ hospitalizations and healthcare costs

worldwide- think mortality
6-7 episodes/child/yr
deaths from dehydration

160
Q

viral causes of acute gastroenteritis

A

viruses cause >75% of gastroenteritis of known etiology

many different virus families:

  • Caliciviruses (norovirus, saprovirus)
  • Rotavirus
  • Enteric adenoviruses
  • Astroviruses

multiple serotypes of each diarrhea virus

161
Q

pathophysiology of viral gastroenteritis

A

local infection of intestinal epi cells

malabsorption due to virus killing mature enterocytes

local villus ischemia leading to diarrhea
–shortened, blunted villi

viral enterotoxin changing the transepithelial fluid balance

162
Q

diagnosing viral gastroenteritis

A 
specific viral dx is not needed or useful in most situations
useful in:
outbreaks
immune compromised hosts
severe disease

difficult to dx by traditional methods:
difficult to grow in culture
EM difficult to interpret, labor intensive
serology can only tell exposure
viral antigen only available for some viruses

multiplex RT-PCR detection of viral nucleic acid in stool
-overly sensitive, but is tested in correct clinical setting

163
Q

tx and prevention of viral gastroenteritis

A

rehydration and electrolyte correction
-oral rehydration
Na, K, bicarb, glucose

-IV fluids if severe

no antibiotics!! can prolong host’s transmissibility time

prevention:
hygiene (hand washing, food prep)
sanitation (toilets, diapers, water supply)
environmental cleaning
isolation of pts
vaccines (rotavirus available)
164
Q

serotypes of caliciviruses

A

many human serotypes

G2.4 Sydney is currently most important in US outbreaks

variants arise by mutation or recombination

165
Q

Norovirus virology

A

small round ssRNA virus
cup shaped indentations

naked, non-enveloped

viral-encoded protease cleaves viral polyproteins

  • necessary for viral replication
  • potential drug target

difficult to grow in culture

166
Q

clinical characteristics and epidemiology of Norovirus

A

1/3 asymptomatic but still contagious/shedding virus

N/V, watery diarrhea, cramping
malaise, HA, myalgia, low-grade fever

occasionally dehydration, esp in:
young children
elderly
immunocompromised

quickest on, quickest off

incubation: 15hrs-2 days
duration: 1-2 days

most common cause of diarrheal outbreaks in adults
-2nd most common in young children

has replaced rotavirus as #1 in areas where rotavirus vaccine is in use

sources:
person-person (fecal oral)
contaminated surfaces
food borne (esp shellfish)
waterborne

seasonality:
year round, but winter predominance

shedding: 10 million/mL
infectious dose: 10-100 viruses

common cause of outbreaks on cruise ships, hospitals, and nursing homes

167
Q

Norovirus immunology, dx and x

A

immunity is short lived
~6 months
due to strain diversity and antigenic shift

some lucky hosts are innately resistant

  • FUT2 gene required for virus to bind to intestinal cells
  • FUT2 -/- are resistant

dx:
antigen tests newly viable, but RT-PCR is more sensitive

tx:
currently- only rehydration
effective vaccines would have to cover many serotypes

168
Q

virology and classification of rotavirus

A

rota= wheel

11 double stranded RNA genome segments
-each segment encodes one viral protein VP

non-enveloped, but 3 protein shells:
outer capsid layer
-acid stability; VP7 with VP4 spikes

inner capsid layer
VP6

innermost core:
VP2

classification:
serotypes depend on VP7 and VP4 on outer capsid layer
12 major genotypes
Groups based on immunologic assay to the inner capsid layer
–Group A: frequent human infection; most important human group

169
Q

Rotavirus reassortment, replication, and pathogenesis

A

reassortment:
allows introduction of segments from animal rotavirus into human rotavirus, causing epidemics

replication:
uncoated virus enters ER, then pinched out into intestine to get its outer shell
-NSP4, a secreted non-structural protein

pathogenesis:
affects small intestine
replicates in villus epi cells
mononuclear inflammation
villus shortening, stunting
Mech causing diarrhea is unclear 
high viral titers shed in stool, esp in NICU
170
Q

rotavirus enterotoxin

A

NSP4

destabilizes membranes, leading to cell death

mobilizes intracellular Ca- activating signal transduction pathway to transport from ER

Cl secretion and water follows

? activation of enteric NS

171
Q

clinical manifestations and epidemiology of Rotavirus

A

up to 50% of infections are asymptomatic

symptomatic:
abrupt onset fever and vomiting, followed by diarrhea
-stools are explosive, watery, non bloody
-frequently leads to dehydration in children

symptoms last 4-8 days, self-limited

incubation period: 1-3 days

peak viral shedding on day 3, can be prolonged >3 weeks

epidemiology:
common in infants and young children
fecal-oral transmission
remain on infected surfaces

seasonality:
predominant fall/WINTER/spring
year round in tropics

high risk groups:
immunocompromised, malnourished, elderly

172
Q

rotavirus burden of disease

A

Rotavirus is the single most important cause of severe infantile gastroenteritis worldwide!!!!! peak 3 mo-2yo

–can lead to life-threatening dehydration in infants
poor skin turgor
sunken eyes
mucus membranes dry

treatable by oral/IV rehydration

preventable by available rotavirus vaccines

173
Q

dx and tx and immunology of Rotavirus

A

Dx:
antigen detection ELISA in stool
Rotazyme, “diaper dipstick”
PCR

tx:
no effective antiviral therapy available
rehydration and electrolyte correction- paramount
probiotics may decrease freq and duration

immunology:
evidence of IgM, IgG, and IgA
cellular immune response
repeated infections may occur (2nd generally milder)
symptomatic infection is less common in pts <6mo (protective IgA breast feeding)
chronic infection in cellular immune deficiencies, transplant pts

174
Q

Current Rotavirus vaccines

A

RotaTeq (RV5): Pentavalent live bovine

Rotarix (RV1): Monovalent live human

US children hospitalized for rotavirus has decreased by 85%

175
Q

enteric adenoviruses

A

non-enveloped, icosahedral double stranded DNA virus

most commonly cause URI, pharyngitis, conjunctivitis (Pink eye), pneumonia, hemorrhagic cystitis

Serotypes 40,41!! cause gastroenteritis

2-22% of pediatric gastroenteritis
peak incidence 2yo
no seasonality
incubation 3-10 days
fecal-oral transmission

often asymptomatic
watery diarrhea, then vomiting lasting 5-12 days!!
-less dehydration than rotavirus
low grade fever
re-infections can occur
can cause persistent, severe infection in immunocompromised hosts

dx
EM
antigen immunoassays
PCR
difficult to grow in culture

tx:
no antiviral available
rehydration
no vaccine available

176
Q

astroviruses

A

virology:
small non-enveloped single stranded RNA virus
star shaped capsomers
can be grown in viral culture
Trypsin necessary to activate infectivity in gut
7 serotypes identified

epidemiology
2-8% of diarrheal disease in children
excreted for prolonged periods in immunocompromised
person-person and food borne spread
outbreaks in daycares, nursing homes, cafeterias, and nursing homes

177
Q

STDs in the US

A

chlamydia- most common notifiable disease in US >1.5 million

gonorrhea- 2nd most

syphillis- 20% increase over 2014 for primary and secondary

all of these have increased

178
Q

Neisseriaceae species

A

Neisseria gonorrheoeae

Neisseria meningitidis

Moraxella catarrhalis

morphology-
all gram neg diplococci
individual cocci are kidney-shaped

179
Q

specificity vs sensitivity

A

specificity = negativity in health

  • accounting for false positives
  • testing 100 healthy pts, how many of them will have have a negative test?

sensitivity= positivity in disease

  • accounting for false negatives
  • testin 100 dz pts, how many would have a positive test?

Gold standard- best test that tells you pts have that infection an vice versa

180
Q

culture tests of bac infections
advantages
where to collect in M and F

A

advantages:
low cost
suitable for variety
antimicrobial susceptibility can be performed

indicated in pts who have exposure Hx, significant gonococcal infection, complaints, or clinical findings

men: urethra, pharynx, retum
women: cervix, pharynx, rectum, vagina, Bartholin’s or Skene’s glands

181
Q

Neisseria gonorrhea histo

A

in infection- should be GN diplococci INSIDE PMNs

seeing them outside you’d be suspicious for normal flora

but if you took oral culture and did gram stain- you might get positive culture of commensal diplococci after teeth cleaning

182
Q

non-culture tests for bac infections

A

amplified tests- NAATS
-PCR

non amplified tests
-DNA probe

gram stain smear

doesn’t tell you if bug is alive, it tells you the bug is present
doesn’t tell you bug’s resistance either

183
Q

rapid diagnosis of Neisseria gonorrhoeae

A

Gram stain
-GN diplococci in neutrophils

sensitivity good for M, bad for F (still have infection and won’t test positive)
specificity good for both

caveat-
gram stain not sufficient to detect asymptomatic, endocervical, pharyngeal, or rectal infections

184
Q

growth characteristics of Neisseriaceae

A

strictly aerobic- but have to give organism increased CO₂ (not a regular incubator)- both N gonorrhoeae and N meningitidis; can use a jar w/ lit candle to the side

can use nitrate as e- acceptor when grown under anaerobic conditions

complex growth requirements

GOLD STANDARD- 3 steps if you find GN diplococci to dx Neisseria Gonorrhoeae

oxidase positive
(colonies turn black)

2 kinds of media:
chocolate agar- blood agar that’s been heated to release heme and other things
—Neisseria grows on chocolate agar but not regular blood agar; but also grows the normal flora
Thayer-Martin chocolate agar has antibiotics- kills of nl flora and allows Neisseria to grow

look for sugar fermentation of Neisseria;

185
Q

criteria for clinical dx of Neisseria gonorrhoeae

A

suggestive:
mucopurulent endocervical or urethral exudate
sexual exposure

presumptive: (one)
growth or non-culture lab test

definitive: (both)
Isolation of Neisseria gonorrhoeae from sites of exposure by future and demonstration of appropriate growth characteristics
confirmation of isolates by biochem, enzymatic, serologic, or nucleic acid testing

-Adults
NAATs preferred for sexual assault regardless of penetration

  • Children
  • culture is preferred for intra boys or all extra genital specimens
  • NAATS can be used as alternative for vaginal/urine from girls
186
Q

Neisseria gonorrhoeae epidemiology

A

obligate human pathogen

high degree of infectivity

many asymptomatic carriers (F»M)

almost exclusively transmitted by sexual contact

eye infection in neonates born from infected mothers (preventable)

sexual abuse is most frequent cause of gonococcal infection in preadolescents

not uniform across the US
spiked during WW2 and the sexual revolution, but it’s starting to increase now because of vancomycin resistance

187
Q

Gonorrhea direct and distal infections

A

direct-
mucosal and glandular structures (urethritis, pharyngitis, cervicitis, proctitis, etc)

distal-
bacteremia (dermatitis, arthritis, endocarditis, meningitis, perihepatitis, etc)
very uncommon, but more likely the longer this is in the pt

188
Q

Gonorrhea in Male

A

incubation 2-5 days

urithritis: pain/burning during urination
purulent discharge

assoc w/ PMN influx and shedding of epithelial cells

dysuria

most common complication of acute epididymitis

189
Q

Gonorrhea in F

A

primary site of infection: cervix, urethra

symptomatic disease within 10 days: cervicitis, urethritis
vaginal discharge, dysuria

~50% F asymptomatic

sending infection in up to 45%

PID, fallopian tube scarring, infertility, ectopic pregnancy

disseminated infection:
up to 3%
swelling and pain in joints
rash
gonococcal conjunctivitis frequently serum resistant

can cause neonatal conjunctivitis
-exposed during passage through infected birth canal
eyelids become puffy, red, tender
discharge
can cause corneal perforation and destruction of deeper eyes structures
antibiotic drops routine used

190
Q

virulence factors of Neisseria gonorrhoeae

A

pili
initiate binding to epi cells
undergo antigenic variation and phase variation
-within a single person you can see different types of pili– which aids in their resistance

Opa proteins
opaque appearance of colonies
important for intimate attachment
undergo antigenic variation and phase generation

antigenic variation:
single cell can give rise to structurally and anti genetically different daughter cells while still retaining biological function
up to a million different pili variants
—cured pts can be re-infected despite a strong antibody response
–this is a big reason why we can’t conquer gonorrhea yet

191
Q

what is the last line of defense for treating gonorrhea

A

third generation cephalosporins-
ceftriaxone or cefimine
AND
azithromycin or doxycycline

(fluoroquinolone no longer recommended in US- widespread resistance)

pts treated for gonorrhea should also be treated for chlamydia trachoma’s

all known sexual partners should be treated

prophylaxis:
instillation of 1% silver nitrate
1% tetracycline or 0.5% erythromycin into eyes at birth

192
Q

chlamydia basic

A

obligate intracellular pathogen
gram negative cocci
–cannot make own ATP

human pathogens:
C trachoma’s
C psittaci
C pneumoniae

highly infectious, but rarely kill their host

among most prevalent pathogens in world

193
Q

chlamydia growth characteristics

A

obligate intracellular bacteria

C trachoma’s and C pneumonia are obligate human pathogens

C psittaci infects animals- birds

multiply in specialized endosome
depending on host cell for ATP and nutrients

spread to other cells by extracellular route

very simple organism- elementary bodies
see inclusion bodies on Giemsa stain, Lugol stain, immunofluorescence staining,

194
Q

chlamydia pathogenicity

A 
highly infectious
attachment factors (adhesions)
inhibit phagolysosome fusion
heat-labile toxin
may cause latent infections
195
Q

epidemiology and transmission of chlamydia

A

short survival outside of host

infections recently linked to atherosclerosis, arthritis, heart disease, and Alzheimer’s

trachomatis- direct person-person contact
psittaci- aerosols from infected birds
pneumoniae- aerosols from infected humans

196
Q

clinical manifestations of C trachoma’s and N gonorrhoeae

A

adults males:
urethritis
leading to other complications

adult F:
acute urethral syndrome, cervicitis
leading to other complications

incidence is much higher in F; likely due to asymptomatic presentation
not uniform across US

197
Q

diagnose C trachomatis

A

culture,
antigen detection or DNA hybridization
PCR
serology

198
Q

urogenital tract infections caused by C trachomatis

A

sexually transmitted

many asymptomatic carriers (75% of women; 50% men)

urethritis in men

urethritis, cervicitis, and salpingitis in women

purulent urethral discharge will contain PMNs but no chlamydia! on gram stain

199
Q

inclusion conjunctivitis caused by C trachomatis

A

occurs in both infants and adults

most common cause of neonatal conjunctivitis in US

mucopurulent conjunctivitis
7-12 days after delivery

may disseminate and cause pneumonia

200
Q

prevent/tx neonatal chalmidia infections

A

antibiotics to infected pregnant women:
Erythromycin or Amoxicillin for 7-14 days

neonatal ocular prophylaxis doesn’t prevent perinatal transmission

tx of infants w/ chlamydial conjunctivitis and/or pneumonia
-Erythromycin for 10-14 days

201
Q

Lymphogranuloma venereum caused by C trachomatis

A

STI

caused by serovariants L1-L3

infection begins as small ulcer and disseminates to inguinal lymph nodes

possible complications:
peritonitis in F
ulcerative colitis in M

most prevalent in Africa and S America

202
Q

prevention and tx of STD chlamydia trachomatis

A

use condoms or diaphragm

CDC recommendations:
Azithromycin single dose
Doxycycline- 7 days

all sexual partners should be tx

203
Q

spirochetes (syphilis?) growth characteristics

A

reproduce by transverse vision

pathogenic treponema cannot be cultured in vitro- difficult to study

T palladium remains motile 3-6 days

Leptospira grows aerobically
-uses long chain fatty acids as E source and urea as N source

204
Q

diseases caused by treponema

A 
ssp pallidum:
Syphilis
systemic
STI
worldwide
sexually active; and congenital newborns
ssp pertunue:
Yaws
localized
nonvenereal transmitted
tropics
all ages
ssp endemicum:
Bejel
localized
nonvenereal transmitted
desert
all ages
205
Q

syphilis

A

4 defined stages

1 and 2-
infection is transmissible by blood
lesions are highly infectious

latent and 3-
infection is NOT transmissible by blood
lesions are caused by immune mediated destruction of tissues

30% of pts w/ untreated syphilis develop clinical tertiary syphilis
–25% of these pts go on to die

206
Q

syphilis pathogenesis

A

starts w/ lesion
spreads to different organ
antibody/inflammatory response causes a lot of destruction in tissue

incubation 3 weeks
primary syphilis 2-6 weeks
asymptomatic period 2-24 weeks

secondary syphilis 2-6 weeks
latent syphilis
asymptomatic for 3-30 years
tertiary syphilis

25% of t. pallidum heal spontaneously if it’s local

systemic- skin lesions (rash), mucus membranes, lymph nodes, CNS

30% of untreated pts develop tertiary syphilis and 25% die

207
Q

primary syphilis

A

primary lesion or “chancre” develops at the site of inoculation

chancre:
progresses from macule to papule to ulcer
-typically painless, indurated, and has clean base
-highly infectious
-heals spontaneously within 3-6 weeks
-multiple lesions can occur

regional lymphadenopathy:
classically rubbery, painless, bilateral

serologic tests for syphilis may not be positive during early primary syphilis

208
Q

suspicious for haemophilus ducreyi

A

it’s a gram neg bacillus

chancroid ulcers- but typically multiple PAINFUL (vs non painful syphilis) ulcers

209
Q

secondary syphilis

A

2ndary lesions occur several weeks after primary chancre
may persist for weeks-months

primary and secondary stages may overlap

mucocutanous lesions most common

clinical manifestations:
rash 75-100%
lymphadenopathy
malaise
mucous patches
condylomata lata
alopecia
liver and kidney involvement can occur
splenomegaly occasionally present

serologic tests are highest in titer during 2ndary stage!!

210
Q

latent syphilis

A

host suppresses infection, but no lesions are clinically apparent

only evidence is a positive serologic test!!

may occur between 1 and 2ndary stages, between 2ndary relapses, and after 2ndary

categories:
early latent < 1 yr duration
late latent >= 1 yr

211
Q

tertiary late syphilis

A

approx 30% of untreated pts progress to tertiary 1-20 yrs

rare because of widespread availability and use of antibiotics

manifestations:
Gummatous lesions
Cardiovascular syphilis

212
Q

Neurosyphilis

A

occurs when T pallidum invades CNS

may occur at any stage of syphilis
can be asymotpmatic

clinical manifestations:
syphilitic meningitis, meningovascular syphilis, and ocular involvement

neuro involvement can occur decades after infection, and is rarely seen
–general paresis, TABES DORSALIS, and ocular involvement

213
Q

congenital syphilis

A

infection in utero w/ Treponema pallidum

wide spectrum
only severe cases clinically apparent at birth

infant/young child <2yo
hepatosplenomegaly, rash, condyloma lata (wart like genital lesions), snuffles, jaundice, pseudo paralysis, anemia, edema (nephrotic syndrome and/or malnutrition)

older child:
stigmata (interstitial keratitis, nerve deafness, anterior bowing of shins, frontal bossing, mulberry molars, HUTCHINSON TEETH, saddle nose, rhagades, Clutton joints

214
Q

immunology of syphilis

A

humoral (antibody) response
not very protective
extremely useful for dx

cell mediated (T cell) response
very important in immunity to reinfection and protection against tertiary syphilis
probably responsible for some of the damage seen in tertiary syphilis (eg gummas)
215
Q

testing for sypilis

A

rapid plasma reagin RPR card
(non-treponemal based test)

Fluorescent Treponemal Antibody FTA test
(treponemal based test to detect whether pt has antibodies against T pallidum)

lots of reasons a false positive may happen

216
Q

elimination goals and elimination strategies for syphilis

A

goals:
enhancement of public health services and interventions

prioritization of evidence-based, culturally competent interventions

accountable services and interventions

strategies:
improve surveillance and outbreak response
improve clinical and partner services
mobilization of affected communities
training and staff development
research and development
217
Q

prevention and tx strategies of syphilis

A

use of condoms

prompt and adequate tx

parenteral penicillin G- NO clinical resistance

alternatively, doxycycline or tetracycline

F/U on sources of infections and contacts

NOTE- azithromycin resistance has now been found, mainly in organisms from homosexual men

218
Q

Jarisch Herxheimer Reaction

A

rxn that develops 2-24 hrs after Penicillin tx in pts infected w/ Spirochetes (syphilis, Lyme disease)
most common in pts w/ 2ndary syphilis 90%
rare in late syphilis

symptoms:
fever
chills
HA
N
general joint aches
general muscle aches
tachycardia

pts w/ general paresis or a high CSF cell count are likely to develop serious disorders- seizures or strokes

reduction of penicillin dose does NOT decrease likelihood of occurrence

may indicate coexistent syphilis in pts treated for other conditions w/ antibiotics active against syphilis

This rxn should be explained to the pt before tx

219
Q

basic strategy of a herpes viral infection

A

primary/initial/acute infection when exposed
–>

during infection- lytic replication
making virus particles
--disease
--or transmit- called shedding
significant infectious particles released
nuclear and cytoplasmic inclusions
cytomegalic cells and syncytia formation

viral will undergo latency
virus isn’t producing particles
-this is why herpes viruses stay with you for life
genome persists in nucleus of specific cells,

reactivation of latent infection is source of majority of disease

220
Q

3 subfamilies of herpesvirales

A

Herpesviridae divided into 3 broad subfamilies = clinical syndromes

alpha herpes virus
think neurons

beta
myeloid lineage cells

gamma
B cells/ myeloid and transform cells- think atypical cells

221
Q

shared properties of all herpesviruses and what determines a specific infection

A

morphology- they all look the same
big linear dsDNA genomes (some unique long and unique short segments UL US)
have both lytic and latent phases of replication

specific glycoproteins will determine what cell that virus can get into

222
Q

Alphaherpesvirinae

A

Herpes Simplex Virus-1 HSV1
HSV2
Varicella-Zoster Virus VZV

grow RAPIDLY and lyse infected cells (12-24 hrs)

establish latent infections in NEURONS of Peripheral NS, primarily SENSORY nerve ganglia

223
Q

Betaherpesvirinae

A

Human Cytomegalovirus CMV
Human Herpes Virus-6 HHV6 (HHV7)

grow very slowly (80-120 hrs) and infect wide variety of cell types

est latent infections in cells of MYELOID lineage and endothelial cells

224
Q

Gammaherpesvirinae

A

Epstein-Barr virus EBV
Kaposi’s Sarcoma-associated Herpesvirus KSV or KSHV

grow very slowly (80-120 hrs) and infect a wide variety of cell types

est latency in B CELLS, ENDOTHELIAL CELLS, capable of TRANSFORMING these cells

eBv- think “B” cells
Kaposi’s- think purplish lesions

225
Q

basics of virology

A

virus receptors= immune response target

replication = targets for treatment

virus entry

packing of viral DNA = helps w/ diagnostics

226
Q

process of herpesvirus lytic replication cycle

A 
Attachment and entry-
dump capsid (linear dsDNA into nucleus)

forms an episome (circle)

3 gene expression events-
immediate early, early, and late

capsid is transported through ER, Golgi, then exported

227
Q

significance of viral glycoproteins

A

mediate cellular tropism- causes attachment to cell membrane and determines what virus can get into which cell

targets of the adaptive immune response!!
(T and B cells recognize these and attack)

exposure to a virus via close contact allows attachment/entry:

oral or genital mucosa, abraded skin
body fluids (HSV1,2, CMV, HHV6, EBV, and KSHV)

blood transfusions or organ transplant (BMT, SOT) (CMV!!!, HHV6, EBV, KSHV)

respiratory secretions (VZV only)

228
Q

three temporarily regulated gene group expressions determining lytic and/or latent outcome of virus

A

1- Immediate early IE
sets up environment conducive for viral replication

2- Early E
encode replication enzymes (viral DNA polymerase initiates replication- each virus has a different DNA polymerase)

3- Late
encode structural proteins for assembly to get out

uses genome replication rolling circle replication to lop off new genomes; can make a lot quickly
capsidation process inside the nucleus, then rolling DNA
-not 100% perfect, so you get intracellular inclusions which help make the dx

229
Q

significance of thymidine kinase TK

A

HSV-1 and HHV-8 make TK (alpha and gamma)

CMV doesn’t make TK (beta)

acyclovir is dependent on a TK to be activated-
these are prodrugs that need to be phosphorylated to shut off virus replication (does not happen in normal human cell)
–cannot tx CMV w/ acyclovir
–use broad spectrum Ganciclovir for beta herpesvirus

Ganciclovir-
uses a different initial phosphorylation event
works in beta viruses
–side effects and worry of CMV resistance causes us to avoid using it regularly
but still some cases of resistance, so you’d use cidofovir or foscarnet that just use cellular kinases to activate, but they have lots of side effects

230
Q

Herpes Virus inclusion bodies

A

Intranuclear:

acidophilic: Cowdry Type A (HSV, VZV)
basophilic: “owl eyes”- CMV

Intranuclear and intracytoplasmic:
HHV6, CMV

231
Q

host response to Herpesvirus infection

A

host response determines extent of disease

innate immune responses:
important for controlling acute/lytic infections
IFN/cytokine production
NK cell activities

adaptive immune responses:
important in acute but also preventing latency
neutralizing antibodies
CD4+ and CD8+ T cell functions

Herpesvirus countermeasures the host responses during an acute infection

  • blocks interferons, dendritic cell maturation, complement activation, and NK function
  • mimetics and decoy receptors, interfere w/ antigen presentation
232
Q

Alpha-Herpes viruses latency for HSV1 and HSV2

A

latency-
est latency in nerve nucleus
doesn’t kill but hurts nerve;
commonly reactivates back to where it came from (rarely, travels to brain and causes encephalitis)

HSV-1
latency- trigeminal ganglion
commonly assoc w/ oral herpes

HSV-2
latency- lumbar sacral ganglion
commonly assoc w/ genital herpes

233
Q

Alpha-Herpes viruses pathogenesis for HSV1 and HSV2

A

HSV pathogenesis:

HSV invades through breaks in integument

initially get a papule
(infect cells at/above basal layer and lyse)

vesicle
(lysis of many cells w/ cytokines and inflammation–> fluid production)

pustule
(subsequent leukocyte response)

scab
(dried pustule)

–only when it scabs over that you’re no longer infectious

234
Q

HSV characteristics- HSV1 vs 2

A

2 types of HSV:

type 1- above the belt
type 2- below the belt
–distinction is decreasing

share only 50% genetic relatedness

usually typed w/ monoclonal antibodies

labile (enveloped)- spreads by close contact

235
Q

oral HSV

A

usually Type 1 HSV
>90% are seroposeivie by 50yo
-acquired in childhood (after maternal Ab clears) and another peak after puberty

most have minor illness
20% have systemic/viremic symptoms

classic canker sore reactivation
typically self-limited

herpetic GINGIOVOSTOMATITIS-
diffuse inflammation of gums (bad primary infection or immunosuppressed)
unusual presentation of HSV1
-responds to antiviral therapy

older pts- severe pharyngitis

you get type 2 on the mouth from oral-genital contact

236
Q

4 common causes of severe exudative pharyngitis

A

HSV
adenovirus
streptococcus
EBV (infectious mono)

237
Q

reactivation of HSV

A

prodrome of sensory symptoms (hours)

shortened court compared to 1st episode

rarely is systemic

fever and sun exposure are recognized triggers

antiviral tx is NOT standard of care

minimal illness w/ reactivation indicates pre-existing immunological memory
CD8 T cell are important for controlling the viruses

238
Q

2 important complications of HSV-1 in the normal host

A

Herpetic keratitis (purulent, inflammatory eyes)

HSV encephalitis (necrosis, hemorrhage, edema of brain)
fever, HA
focal CNS findings (deficit, seizure)
encephalopathy/AMS
-CSF:
mononuclear cells/ HSV DNA
-Imaging
MRI
give High Dose Acyclovir
239
Q

genital HSV

A

HSV-2 > HSV-1 3:2

most pts have minor illness the first episode of HSV-2
20% have significant symptoms

illness peaks 7-10 days
heals next 1-2 weeks

1-1.5 days shortened by EARLY antiviral therapy

recurrent:
shortened version of 1st episode
mean 3-4 recurrences/yr; declines over time
psychosocial significance
antiviral therapy decreases morbidity minimal, but effective w/ prophylaxis

240
Q

complications of genital HSV

A 
usually w/ first episode:
urethritis
meningitis (HSV2)
yeast (candida) superinfection (vaginitis)
perianal/perirectal disease

shedding:
similar to oral
major source of spread (asymptomatic)

-during a flair up, contact is typically painful so you avoid sex during then anyway

241
Q

HSV in the immunocompromised pt

A

severe local disease- oral or genital

neonatal HSV- often severe/fatal

important role for antiviral therapy!

most severe in pts w/ defective T cell immunity (incl newborns and transplant pts)
–high index of suspicion:
chronic ulcer, crusted lesion, or mouth sores

242
Q

alpha herpes viruses- Varicella zoster virus

A

Varicella

Zoster- reactivation

Chickenpox- primary

243
Q

herpesvirus latency for VZV

A

spreads by droplets from varicella (chickenpox) or by formites (spread via touch) from a case of herpes zoster

virus infection via conjunctiva and upper resp tract
replication in primary lymph nodes- primary viremia

replicates in liver and spleen

goes to sensory ganglia (typically dorsal root ganglia from skin- remains there for life) and undergoes latency- secondary viremia

can reactivate in infected skin- rash
(rarely, can infect NS)

244
Q

VZV clinical features

A

kid- mild
“crops of vesicles at varying ages”- some vesicles, papule, and ulcerated/crusted over– CLASSIC for varicella/chiceknpox (vs smallpox- all the same stage)

mild symptoms for 3-5 days

infectious just prior to onset
until scabbing

peak incidence at grade school age

245
Q

Dx and prevention of varicella

A

mainly clinical Dx-
PCR

prevention:
childhood immunization
any susceptible adult immunized, ESP MED PERSONNEL

246
Q

complications of Varicella

A

bacterial superinfection 2%

adult infection- often severe

infection in immunocompromised children

encephalitis

congenital

247
Q

herpes zoster

A

reactivation of VZV

typically unilateral
(bilateral- less likely zoster)
reactivation of a single dorsal root ganglia nerve cell explains the dermatomal pattern characteristic of herpes Zoster

prodrome: abnormal sensation/pain in determatomal distribution (~3-7 days)
(pain precedes rash)
dermatomal vesicular rash
variable pain (increases w/ age)
post-herpetic neuralgia (weeks-yrs)
therapy within 3-4 days- Acyclovir
–increases w/ age because CD8 T cell response decreases w/ age

248
Q

complications of herpes zoster

A

immediate pain/rash (increase w/ age)

secondary infection
eye involvement
motor deficit
encephalitis
post-herpetic neuralgia!!!
-severe in immunocompromised
249
Q

pathogenesis of Herpes Zoster

A

VZV-specific T-Cell Mediated Immunity (VZV-CMI) declines w/ age (or immune suppression)

reactivation in sensory ganglia occurs intermittently; normally surpassed or lessened by VZV-CMI

if VZV-CMI is below threshold, VZV will propagate, cause ganglionitis (pain), and descend in nerve to cause a dermatomal rash (w/ pain)

250
Q

preventing Herpes Zoster

A

a vaccine, like the varicella vaccine, only more potent
-recommended for all immune competent pts >60yo

prevents cases and pain of HZ

prevents 67% of POST-HERPETIC NEURALGIA

251
Q

CMV latency

A

cytomegalovirus CMV

CD34+ bone marrow progenitors
circulating monocytes
endothelial cells
tissue-renewing stem cells?

inflammatory stimuli can reactivate the virus w/o disease
-pretty frequent, esp in hospital

prophylactic therapy for pts at risk for CMV infection (transplant pts and donor/recipient serologic status)

252
Q

childhood CMV

A 
perinatal-
from maternal shedding of + mother
--birth canal
--milk
--10% of exposed infants are infected

outcome if infected:
mild, “virus”-like illness (term baby)
prolonged CMV shedding

maternal antibody via placenta protects infants for several months from severe herpesvirus infection

toddler:
infected by playmates
-urine, saliva, prolonged shedding
illness is mild

adolescence:
CMV shed in saliva and genital secretions
-sexual transmission is common
“CMV mononucleosis syndrome”

253
Q

dx CMV

A

IgM anti-CMV antibody
–implies you had a recent infection

PCR tissue

or see tissue intranuclear inclusions

254
Q

severe CMV

A

in an immune compromised host

severe end organ disease + viremia: wide tropism

risk factors:
degree of immune suppression
age (premature infant, elderly)
donor has latent CMV and recipient doesn’t

disseminated CMV:
tx:
Ganciclovir (NOT acyclovir)
resistant virus- Foscarnet
prevention:
screen organ donors
screen blood products/tx blood
use prophylactic antivirals
check pts regularly for viremia
early tx before symptoms
255
Q

congenital CMV infection

A

a lot of kids are exposed, but 90% don’t develop disease- reflects maternal immune status

symptomatic disease: 10%
jaundice, enlarged liver/spleen, microcephaly, low plts)
10-20% mortality; others w/ sequelae

asymptomatic disease: 90%

256
Q

HHV6 and HHV7

A

beta herpesvirus (along w/ CMV)

Roseola (6th disease)- HHV6 and 7

HHV6 antibody in newborns declines until 5mo, then approaches 100% by 2yo

  • -in saliva of adults and children
  • -genital tracts of women at term
  • -spread occurs early (once maternal Ab is gone) from caretakers and playmates

HHV7 antibody rises more slowly through 4yo and from teens to 30yo

257
Q

pathogenesis of Roseola

A

infects cells at back of throat (tonsillar tissue)- 6mo to 2yo

HHV6/7 infects B and T cells and becomes latent in similar cells or precursors

both viruses cause a persistent lytic infection in salivary glands

258
Q

clinical manifestation of Roseola

A

high fever 3-7 days (>104)

  • looks good otherwise!!
  • may have minor symptoms
  • -relatively common cause of febrile seizure and rash

Rash appears as fever ends abruptly!!
-may occur w/o fever

maculopapular rash starts on trunk –> face, neck, extremities; 1-2 days

dx: clinical, esp tempo of events!!
tx: for immune compromised host, tx w/ same antivirals effective against CMV

259
Q

complications of HHV6/7

A

febrile seizures

in immune compromised:
bone marrow suppression
colitis
encephalitis
hepatitis
pneumonitis
organ rejfection
260
Q

Epstein Barr Virus

A

gamma herpesvirus
“infectious mononucleosis”

acute infection:
viral capsid antigen VCA
early antigen EA
–typically develop antibodies to VCA and EA

latent infection:
infects native B cells for latency- for life!
encodes 9 latency-associated proteins
—ex helps maintain viral genome and turn on latent genes
Epstein-Barr nuclear antigen EBNA
–having EBNA means you’ve probably had EBV for a while and not an acute infection

261
Q

EBV pathophysiology

A

found everywhere- 97% adults have antibody

childhood- like any other minor illness; unexplained fever

adolescnece- infectious mononucleosis

patho:
EBV enters mucosal cells in pharynx
B cells infected; travel throughout body
-lymph nodes, spleen, tonsils, liver
T cells destroy infected B cells--> symptoms!!

associated w/ malignancies, but no evidence they’re direct causes

  • -first human virus to be assoc w/ cancer
  • -tumors contain EBV genome and express characteristic EBV gene sets
  • -most tumors appear to have cofactors
262
Q

mononucleosis syndrome

A

fever, malaise, fatigue
adenopathy
pharyngitis
hepatosplenomegaly
atypical lymphocytes (activated T cells killing B cells)
Heterophil antibodies (antibodies to other animal antigens; infected B cells are making weird antibodies)

dx is clinical
heterophile ("likes foreign") antibody
-"monospot" is rapid test
atypical lymphocytes (abnl cyto)
specific EBV serology
263
Q

Kaposi Sarcoma Herpes Virus KSHV

A

HHV8
gammaherpesvirus

purplish violatious vascular lesions
endemic from Africa that can affect non-immune compromised pts
can cause oropharyngeal problems down to lungs; variety of mucosal surfaces

results from HIV immune dysfunction
HHV8 is latent in B cells
periodically shed asymptomatically in saliva

main significance:
as a cause of sentinel malignancy (Kaposi sarcoma) at the beginning of the HIV epidemic

discovered because 50% of untreated (MSM) HIV pts developed rare tumor
-considered an STI

Tx:
lowering immune suppression
operationally most successful by treating HIV
Chemotherapy

264
Q

Vaccines for viruses

A 
Rotavirus
-segmented dsRNA genomes
-use genetic reassortment to produce vaccine
RotaTeq (live-attenuated)
Rotarix (live-attenuated) 
-vaccinate ASAP in child

HPV
-doesn’t grow well in tissue culture
Gardacil and Cervarix (recombinant DNA expression of L1 proteins–> VLPs; these are subunit particles; not live attenuated)
-vaccinate 11-12 yo’s before becoming sexually active

Varicella/Zoster
high risk contraindication for most live-attenuated viruses (incl VZV): immunosuppression/ leukemia
low risk contraindication: pregnancy (DON’T GIVE LIVE ATTENUATED ANYTHING TO A PREGNANT WOMAN)
Varicella- kids
Zoster- adults

0000000Infectious Disease and Life Cycle (5 decks)

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