Kays - Exam 1 Flashcards
Gram positive bacteria stain _____
(positive) purple
Gram negative bacteria stain _______
red
difference between bacili and cocci
bacili: rod shape
cocci: little circles
which bacteria are lactose fermenting
CEEK: Citrobacter Enterobacter Escherichia coli Klebsiella
Which drugs/things can MASK a fever
Antipyretics
Corticosteroids
Antimicrobial therapy
an overwhelming infection can mask a fever
Systemic Signs of an infection:
Fever: Temp > _____
38 degrees Celsius/ 100.4 Farenheit
Systemic Signs of an infection:
Increased White blood count (> ________ /mm^3)
> 10,500
Normal WBC?
4,500 - 10,500/mm^3
Systemic Signs of an infection:
Tachy or Brady cardia/pnea
Tachy!!
HR > 90 beats/min
R > 20 breaths/min
Systemic Signs of an infection:
Hypo or hyper tension?
hypo! (SBP < 90 mmHg or an MAP < 70)
Normal WBC Differential:
Mature Neutrophils: _____%
50-70%
Normal WBC Differential:
Immature neutrophils: ____%
0 -5%
Normal WBC Differential:
Eosinophils: ____ %
0-5%
Normal WBC Differential:
Basophils: ____%
0 -2%
Normal WBC Differential:
Lymphocytes: _____%
15-40%
Normal WBC Differential:
Monocytes: _____%
2-8%
Which WBCs are Agranulocytes
Lymphocytes and Monocytes
Which WBCs are Granulocytes
the “Phils”
Neutrophils, Eosinophils, Basophils
Other names for mature neutrophils
PMNs, Polys, Segs
Other names for immature neutrophils
bands
Leukocytosis means ??
increased neutrophils (+/- bands)
Presence of immature forms of neutrophils means what?
aka a left shift = indication of bone marrow response to the infection
Leukocytosis generally means ______ infection
bacteria
Lymphocytosis generally means _________ infection
viral, fungal, or tuberculosis
Monocytosis usually associated with?
tuberclosis or lymphoma
Eosinophillia usually associated with?
ALLERGIC REACTIONS! oar protozoal/parasitic infections
CD4 or CD8?
depleted in HIV infection
CD4
CD4 or CD8?
bind to and directly kill tumor cells
CD8
CD4 or CD8?
help with antibody production and secrete lymphokines
CD4
ESR and CRP when elevated = _______ but not for sure ________
means inflammation; not always meaning infection tho…
Normal ESR value?
0 - 15 mm/hr (males)
0 - 20 mm/hr (females)
Normal CRP value?
0 - 0.5 mg/L
What is PCT
procalcitonin/precursor of calcitonin
Normal value of PCT
< 0.05 ug/L
PCT is more or less specific than ESR or CRP for bacterial infections
MORE! good for finding out if bacterial infection (PCT is not related to viral infections !)
What PCT value is suggestive of sepsis
2 - 10 ug/L
What PCT value means sepsis/systemic bacterial infection
> 10
what PCT value means other condition/localized infection
0.25 - 2 ug/L
Sensitivity or Specificity?
positive result in presence of disease/infection
Sensitivity
Sensitivity or Specificity?
false positive rate
specificity
Sensitivity or Specificity?
negative result in absence of disease/infection
specificity
Sensitivity or Specificity?
False negative rate
sensitivity
to give the drug abacavir – what genetic test must be done
HLA-B5701 = hypersensitivity
Empiric vs directed therapy?
Empiric: BROAD SPECTRUM before pathogen idenitifie
Directed: after pathogen identified/susceptibility results are known; DE-ESCALATE to agent with narrowest effective spectrum of activity
Want to move pts from IV to PO therapy when clinically stable and functioning GI tract annnnd ahve agents with good oral bioavaliability— what are cases where you should NOT
if CNS infection, endocarditis (lil Owen!), and Staph aureus bactermemia
what are the 3 primary reasons for combination antimicrobial therapy?
broad spectrum for polymicrobial infections
synergistic bactericidal activity
prevent emergence of resistance (ex: HIV drug therapy)
disadvantages of combo microbial therapy?
increased cost
greater risk of drug toxicity
superinfection with resistant bacteria
antagonism of drugs to each other
what 3 main things should be used to figure out empiric therapy
- knowledge of the likely pathogen (body site, where infection started (hospital)
- anticipated susceptibility pattern (antiobiogram)
- info from pt history/PE (prior abx use, travel hx/other sick ppl at home)
bactericidal vs bacteriostatic
cidal: KILLS organism….
static: inhibits bacterial replication
what are 3 main ways that an antibiotic can be bactericidal
act on cell wall
act on cell membrane
or act on bacterial DNA
Antimicrobial Tissue Concentrations = mean of ________ and _____ concentrations
extracellular AND intracellular!
Gram Positive vs Gram negative Cell wall comparison:
has lots of peptidoglycan
Positive
Gram Positive vs Gram negative Cell wall comparison:
has porins
negative
Gram Positive vs Gram negative Cell wall comparison:
has lipopolysaccharide outer membrane (LPS/endotoxi)
negative
Gram Positive vs Gram negative Cell wall comparison:
has beta lactamases on the outside of the cell/towards environinment
gram positive
Gram Positive vs Gram negative Cell wall comparison:
has beta lactamases in periplasmic space
negative
what are PBPs?
pencillin binding proteins:
aka enzymes vital for cell wall synthesis, cell shape, and structural integrity
what is the most important PBP and why
transpeptidase:
it catalyzes final cross link between sugar and peptide in peptidoglycan molecule
3 types of genetic exchange that leads to resistance
conjugation
transduction
transformation
what is conjugation (genetic exchange shit)
direct contact or mating via sex pilli **most common
what is transduction (genetic exchange shit)
genes transferred via bacteriophages (viruses) between bacteria
what is transformation (genetic exchange shit)
uptake of “free floating” DNA from the environment then gets integrated into the hosts DNA
Plasmids or transposons:
transferred from organism to organism
self replicating
extrachromosomal DNA
plasmid
3 main mechanisms of bacterial resistance
enzymatic inactivation
alteration of target site
altered permeability of bacterial cell
what are examples of abx resistance via enzymatic inacivation
beta lactamases
aminoglycoside modifying enzyme
what are examples of abx resistance via alteration target site
PBPs
cell wall precursors
ribosomes
DNA gyrase/topoisomerase
what are examples of abx resistance via altered permeability of bacterial cell
efflux pumps
porin changes
what are beta lactamases/how do they work
they inactivate beta lactam abxs
work by hydrolzying/splitting amide bond = inactivate drug
what gene in beta lactamases are we to know
AmpC
what does ESBL stand for
Extended spectrum beta lactamases
which bacteria typically contain AmpC
SPICE
serratia, pseudomonas, indole-positive proteus, citrobacter, enterobacter
what drugs are beta lactamase inhibitors
tazobactam
clavulanic acid
sulbactam —- resistance to the SPICE organisms has happened!!
avibactam = lactamase inhibited in SPICE by this drug does happen tho
how is AmpC induced?
the gene is normally repressed, when a beta lactam is present the gene gets DEPRESSED which cause beta lactamase production
when inducer is removed then the gene gets repressed again
what abxs are strong inducers of AmpC
Penicillin G
Ampicillin
1st gen cephalosporings
Cefoxitin
*Clavulanic acid = potent induce of AmpC beta lactamases
SPICE are typically constitutively making beta lactamases….
avoid using what abx because of developed resistance?
avoid 3rd gen cephalosporins
ESBLs seen most frequently in what bacteria
Klebsiella pneumoniae
and
E.Coli
ESBLs are _____ mediated and tend to hydrolyze _______ and ______
plasmid mediated;
hydrolyze PCNs and cephalosporins
what drug may be useful for the CTX-M enzyme of ESBLs
tazobactam
what is normally the treatment of choice for ESBLs
carbapenems
what are the 3 most important carbapenemases
KPC (klebsiella pneumoniae carbapenemase)
Oxa-type (seen in acinetobacter)
NDM (new delhi metallo beta lactamases)
T or F: CRE can last in the body for only 6 months
falseeee
carbampenemase resistant enzymes can last in the body for 12 months!! aka bacteria can get spread allllll over
NDM-1 is resistant to all antibiotics except what?
Colistin
best way to treat CRE bugs?
is serine carbapenemase: ceftazidime + avibactam
if the NDM-1/metallo-b lactamase = use aztreonam
what 4 things can predispose someone to an infection
FLORA: alteration to normal flora of host
BARRIERS: disruption to barriers (skin, cilia, pH changes)
AGE
IMMUNOSUPPRESION: due to malnutrition, underlying disease, hormones (pregnancy or corticosteroids), drugs (cytotoxic agents)
what does MIC stand for and its definition
minimum inhibitory concentration
lowest concentration of abx that prevents VISIBLE growth
what does MBC stand for and its definition
minimum bactericidal concentration: lowest concentration resulting > 99.9% decrease in initial inoculum
what is an Etest
epsilometer test: abx on entire strip with a continuous gradient of the drug:
an eliptical shape will form – “largest death area” = where most drug is…
MIC found where the inhibition ellipse intersects with the strip
what is agar dilution
agar with two fold dilutions of abx in it;
bacteria inoculated on to them;
MIC will be agar plate with the lowest concentration and no growth of an organism
what is broth dilution
two fold dilutions of abx in liquid broth;
MIC will be lowest concentration of the drug that prevents visible growth
T or F: broth in broth dilution method has no protein in it
true (note because there is protein in the body tho and like drug protein binding shit)
Definition: susceptible (for breakpoints)
isolated bacteria is inhibited by usually achievable concentrations when normal dosing regimens are used
Definition: S-DD (susceptible dose dependent)
susceptibility is dependent on the dosing regimen used (need higher doses!!)
Definition: intermediate (for breakpoints)
we guessin’
treatment MAY be successful when max doses are used or if drug is concentrated at the site of infection
MIC approaches achievable blood or tissue concentrations
How are MIC breakpoints (aka interpretive criteria) established
clinical pharmacology of the drug
clinical/bacteriologic response from human studies
Tolerance in susceptibility tests is defined as ??
MBC >/= to 32 x MIC
rarely identified clinically bc MBCs not routinely determined
what is the inoculum effect
a laboratory phenomenon that is described as a significant increase in the minimal inhibitory concentration of an antibiotic when the number of organisms inoculated is increased
what is MIC(50) and how do you find it
abx concentration that inhibits 50% of bacteria tested
ex: if you have 100 samples — put them in MIC order and find the MIC value that inhibits at least 50% of bacteria?
what is MIC(90) and how do you find it
abx concentration that inhibits 90% of bacteria tested
ex: if you have 100 samples — put them in MIC order and find the MIC value that inhibits at least 90% of bacteria?
what is Geometric mean MIC and how do you find it…
the antilog of the mean of the log MICs……. wut is math
what is modal MIC and how do you find it
simply the most frequent MIC
definition of synergy:
activity of antimicrobial combo is greater than that expected from additive activity of the individual agents
definition of antagonism: (synergy testing)
activity of an antimicrobial combo is less than that expected from the additive activity of the individual agents
Definitions additivity or indifference: (synergy testing)
neither synergy or antagonism
two different tests for testing synergy
checkboard test (grid of using two diff abx in broth, less growth/more clear plates = synergy..)
and
time kill curves (showing effect of drugs alone vs together vs control)
what does PAE stand for and what is the definition
post antibiotic effect
after abx removed, there is still some inhibitory effects on the bacterial growth still
PAE is a phenomenon in in vivo or in vitro
vitro!!
not vivo!! the body has WBCs and stuff to also have extra effects after abx
antibiotic stewardship wants rapid diagnostic testing to increase why
they want to detect resistant bugs faster
what are some molecular diagnostic techniques for rapid diagnostic
PCR PNA-FISH LAMP MALDI-TOF Verigene/BioFire
aminoglycoside modifying enzyme mechanisms? (3 total)
acetylation
nucleotidylation
phosphorylation
aminoglycoside modifying enzyme:
they modify the structure by transferring an indicated chemical group to a ___________
this will impair ______ and/or _______
to a specific side chain
impair cellular uptake/binding to ribosome
There is a bifunctional enzyme that modifies aminoglycosides:
mainly seen in what bacteria?
the enzyme leads to high level resistance to ______ but not _______
mainly seen in ENTEROCOCCI
resistance to gentamicin
not resistant to streptomycin tho
Resistance mechanisms:
what are examples of Altered target sites - PBPs
1 - S. Pneumoniae resistant to PCN and Cephalosporins
2 - Staphylococci is resistant to Methicillin via mecA gene
Methicillin resistance is seen in what abx because of what gene?
staphylococci are resistant because of mecA gene
the mecA gene encodes for production of a new PBP that is called ______
PBP2A or PBP2’
how does vancyomyocin normally work as an antibiotic?
inhibits cell wall synthesis –
does this by binding to D-alanine-D-alanine terminus of pentapeptide (a peptidoglycan precursor)
what bacteria is known to have vancomyocin resistance through the VanA gene
S. Aureus = VRSA
how does the VanA gene cause resistance
causes the D-Ala-D-Ala part becomes D-Ala-D-Lac and vancomyocin can’t bind to the D-Ala-D-lac part
Altered ribosomal targets lead to resistance in what antibiotics
macrolides, azalides, aminoglycosides, tetracyclines, clindamycin
Altered DNA gyrase/topoisomerases lead to resistance to the drug class(es) of _______?
and this resistance is seen in what bugs most?
fluoroquinolones
seen in S. Pneumoniae and gram negative
what are some drugs that have had reported chromosomal/plasmid mediated resistance with efflux pumps occur?
Macrolizes/Azalides
Carbapenems
what bug has had reported efflux pump resistance to macrolides/azalides
S.Pneumoniae
what bug has had reported efflux pump resistance to carbapenems
P.Aerugonisa
For efflux pump resistance:
for P.Aerugonisa that has resistance to Carabapenems:
which carabapenem drug is best to use? (because it does not get effluxed out…)
IMIPENEM is best!! (definitely not pumped out as much as meropenem)
P.Aeruginosa has multidrug efflux pumps… which drug(s) were bolded/in every single multidrug efflux pump…
Ciprofloxain/Levofloxain
Porins will typically allow a drug to go through it when the drug is (small or large?) (more or less negative)(hydrophobic or hydrophillic?)
go through when small, less negative charges(aka it prefers zwitterionic charge); hydrophillic
Mutations in porins seen most commonly in what bugs?
Enterobacteriaceae bois and P.Aeruginosa
what resistance mechanisms are most common for beta lactam drugs
hydrolysis (aka beta lactamase);
altered target site;
efflux
resistance mechanisms for aminoglycosides?
aminoglycoside modifying enzymes…..
altered target site…
efflux
what resistance mechanisms are most common for glycopeptides (aka vancomyocin)
altered cell wall precursors (D-Ala-D-Lac)
Intrinsic Resistance:
what bug has intrinsic resistance to beta lactams?
mycoplasma
Intrinsic Resistance:
what bug has intrinsic resistance to vancomyocin?
gram negative (because they got no peptidoglycan)
Intrinsic Resistance:
what bug has intrinsic resistance to cephalosporins
enterococci
Intrinsic Resistance:
what bug has intrinsic resistance to aminoglycosides
anaerobes
P.Aeruginosa: Common resistance mechanisms?
ESBLs
Efflux Pump
Reduced outer membrane permeability
K.Pneumoniae Common resistance mechanisms?
Carbapnemases
E.Coli: Common resistance mechanisms?
ESBL
S. Aureus: Common resistance mechanisms?
Methicillin Resistance - mecA gene
Vanc resistance
Enterococci: Common resistance mechanisms?
vancomyocin resistance via altered cell wall precursors
what PK/PD parameter do aminoglycosides use?
peak/mic
what PK/PD parameter do Beta lactams use?
Time above MIC
what PK/PD parameter does Daptomyocin use?
AUC(0-24)/MIC or Peak/MIC
what PK/PD parameter do Fluoroquinolones use?
AUC(0-24)/MIC
what PK/PD parameter does vancomycoin use?
AUC(0-24)/MIC
which abx are time dependent
beat lactams
vancomyocin
what abx are concentration dependent
aminoglycosides
daptomyocin
fluoroquinolones
For beta lactam abx: what are the goal %’s for time above MIC for GRAM NEGATIVES:
carabapenems: > _____%
PCNs: > ____%
cephalosporins: > ____ %
40%
50%
60%
For beta lactam abx: what are the goal %’s for time above MIC for GRAM POSITIVES?
> 40%
Goal AUC/MIC ratio for Fluoroquinolones?
> 100 for Gram negative bugs
> 30 for Gram Positive (maybe > 100…?)
Goal Peak/MIC ratio for aminoglycosides
8 - 10
Goal AUC/MIC ratio for vancomyocin
400 - 600
High risk for nephrotoxicity with vancomyocin when AUC is in the range of _________
600 - 700 or higher of course!
what are all the lactose fermenting bacteria
CEEK + VAP
citrobacter, enterobacter, e.col, kleibsella
+
vibrio cholerae, pasturella multicoda, aeromonas hydrophilia
what bacteria are known as “atypical bacteria”? (the cell walls are difficult to stain— or maybe mycoplasma aka no cell wall)
chlamydophila pneumoniae
chlamydia trachomatis
legionella pneumophilia
mycoplasma pneumoniae
what bacteria is gram variable bacilli
gardenerella vaginalis
