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T6 Flashcards

(56 cards)

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1
Q

antimicrobial stewardship

A

select the narrowest spectrum activity
use for the shortest effective duration

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2
Q

mechanisms of antimicrobial resistance

A

reduced antimicrobial concentration at target
inactivation of antimicrobial agent
alterations to bacterial target

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3
Q

reduced antimicrobial concentration: porins

A

protein channels in bacterial walls that allow entry of many drug molecules
mutations or elimination of porins can slow or prohibit antibacterial entry

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4
Q

reduced antimicrobial concentration: efflux

A

bacterial cells have efflux pumps that can actively transport medications out
reduced drug concentration in the cell to an ineffective level

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5
Q

inactivation of antimicrobial agent

A

bacterial cell produces enzyme that are capable of altering or destroying the antimicrobial agent

enzymatic inactivation
beta lactamase
aminoglycoside-modifying enzymes
esterification of macrolides

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6
Q

alterations to bacterial targets

A

mutations in target proteins lead to reduced affinity of the drug for that target

3 causes:
natural mutation of target
enzyme-mediated target modification
bacterial acquisition of a resistant form of the target

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7
Q

AUC

A

area under the curve: measure of total concentration of drug over a period of time

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8
Q

MIC

A

minimum inhibitory concentration: minimum serum concentration needed to inhibit microbial growth

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9
Q

types of antibacterial effects

A

concentration dependent
time dependent

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10
Q

concentration dependent

A

peak drug concentration (Cmax) is predictive of antibiotic efficacy
time over MIC is less relevant
can be dose intermittently due to persisting effects after drug concentration falls below MIC

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11
Q

time dependent

A

time with drug concentration above the MIC is predictive of efficacy
peak concentration (Cmax) has little relevance
antibiotic should be dosed more frequently to ensure that concentration remains above MIC

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12
Q

beta lactam MOA

A

Bind covalently to the Penicillin Binding Protein (PBP) site on bacterial cell walls, Inhibit the last step in bacterial cell wall synthesis – peptidoglycan transpeptidation reaction, Disruption of cross-linking of the cell wall interferes with bacterial growth and the cell dies

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13
Q

beta lactams resistance mechanisms

A

Alterations to the PBP target
-Mutations decrease the affinity of PBPs for the antibiotic
-Ability to express new, low-affinity PBPs, is acquired from resistance strains

Reduced concentration of beta lactam antibiotics at the target site
-Restricted porin permeability
-Efflux pumps

Degradation of the beta lactam antibiotic through beta-lactamase activity

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14
Q

beta lactams

A

penicillins
cephalosporins
carbapenems
monobactams

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15
Q

cell wall synthesis inhibitors

A

beta lactams
glycopeptides
lipopeptides

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16
Q

beta lactamase inhibitors

A

clavulanic acid
sulbactam
tazobactam
avidbactam
relebactam
vaborbactam

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17
Q

penicillin ABXs and spectrum of activity

A
  1. penicillin -> gram +
  2. penicillinase-resistant penicillins -> gram +
  3. aminopenicillins -> mostly gram + and some gram - activity
  4. extended spectrum aminopenicillins -> gram + (MRSA) and gram -
  5. antipseudomonal penicillins -> gram - pseudomonas
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18
Q

pencillins adverse effects

A

injection site reactions with IV/IM
N/V/D w oral

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19
Q

pencillins hypersensitivity reactions

A

skin rash
serum sickness
anaphylaxis
breakdown of beta lactam ring forms penicilloyl, in small number of cases this initiates IgE mediated reaction

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20
Q

all cephalosporins have

A

empiric resistance against enterococcus

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21
Q

cephalosporin classes and spectrum of activity

A
  1. first generation -> gram + and some gram -
  2. second generation -> gram + and better gram -
  3. third generation -> gram - and some gram +
  4. fourth generation -> gram - pseudomonas and some gram +
  5. fifth generation -> gram - and gram + MRSA
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22
Q

cephalosporins adverse effects

A

local irritation w IM or IV
nausea and diarrhea w oral
renal toxicity uncommon

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23
Q

cephalosporins hypersensitivity effects

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A

occur less frequently than penicillin hypersensitivity effects
cross reactivity depend on the beta lactam side chain
-if non severe risk considered low
-if life threatening penicillin allergy, perform skin PCN allergy testing

24
Q

monobactam (aztreonam) spectrum of activity

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A

gram - pseudomonas
no gram + or anaerobic activity

25
monobactam (aztreonam) adverse effects
skin rash hepatotoxicity
26
monobactam (aztreonam) hypersensitivity
lack of allergic cross reactivity w other beta lactam ABXs safe in pt w hx of PCN anaphylaxis
27
carbapenem clinical uses
reserved for multi drug resistant pathogens ESBL (extended spectrum beta lactamases) producing organisms
28
carbapenem spectrum of activity
ertAPEnam = weakest acinobacter pseudomonas enterococcus imipenem and meropenem = broad spectrum gram +, gram - psuedomonas and anaerobes
29
carbapenem adverse effects
nausea and vomiting seizures rarely
30
carbapenem hypersensitivity
Most patients who are allergic to other β-lactam antibiotics can safely receive carbapenems those with severe immediate-type reactions should consider an initial carbapenem challenge
31
glycopeptide (vancomycin) MOA
Bind covalently to D-alanyl-D-alanine binding site of peptidoglycan Inhibits cross-linking of cell wall units which interferes with bacterial growth and the cell die
32
glycopeptide (vancomycin) resistance
Alteration of D-alanyl-D-alanine target to D-alanyl-D-lactate or D-alanyl D-serine Impaired ability of antibiotic to bind to target and loss of activity
33
glycopeptide (vancomycin) clinical uses and spectrum of activity
oral - C. diff only IV - severe infections (meningitis, endocarditis, osteomyelitis) gram + MRSA
34
glycopeptide (vancomycin) adverse effects
ototoxicity - caused by excess serum concentration, may be irreversible acute kidney injury - reduce freq. of infusion red man syndrome - infusion reaction caused by histamine release, no more than 1 gram/hr
35
glycopeptide (vancomycin) monitoring
serum concentration to be drawn at steady state 30 minutes prior to 4th dose vancomycin removed via hemodialysis
36
lipopeptide (daptomycin) MOA
Binds to the inner bacterial membrane and induces depolarization and loss of membrane potential which results in cell death
37
lipopeptide (daptomycin) resistance
Poorly defined, seem to be related to changes in the cell wall that impede daptomycin binding
38
lipopeptide (daptomycin) spectrum
NOT to be used in respiratory infections gram + (MRSA and VRE)
39
lipopeptide (daptomycin) adverse effects
myopathy and rhabdomyolysis
40
protein synthesis inhibitors
Tetracyclines Macrolides Lincosamides Oxazolidinones
41
tetracyclines MOA
Tetracyclines bind reversibly to the 30S bacterial ribosomal subunit Prevent tRNA binding thereby inhibiting protein synthesis
42
tetracyclines resistance
Reduced antimicrobial concentration at target -Decreased influx of tetracyclines -Expression of an efflux pathway -Ribosomal protection protein displaces tetracyclines from their targets Inactivation of antimicrobial agent -Destructases induce enzymatic modification of Tetracyclines
43
tetracyclines spectrum
gram + MRSA some gram - atypicals
44
tetracyclines adverse effects
GI irritation (impaired absorption when ingested w dairy and antacids) Photosensitivity permanent brown discoloration of teeth (avoid in pregnancy and peds through 8 years old)
45
macrolides MOA
Macrolides reversibly bind the 50S bacterial ribosomal subunit Induces a conformational change that terminates protein synthesis and causes the dissociation of the tRNA
46
macrolides resistance
Reduced antimicrobial concentration at target -Drug efflux by active pump mechanism Inactivation of antimicrobial agent -Hydrolysis of drug via esterases produced by Enterobacter species Alterations to bacterial target -Mutations to the 50S subunit -Modification of ribosomal target by methylase enzymes leading to reduced drug bindin
47
macrolides spectrum
gram + atypicals fidamixocin - not well absorbed; only effective for C. diff
48
macrolides adverse effects
cardiac toxicity - QT prolongation and ventricular tachycardia ototoxicity and tinnitus
49
lincosamide ABX (clindamycin) MOA
Target 50S bacterial ribosomal subunit Similar MOA and target to Macrolide antibiotics
50
lincosamide ABX (clindamycin) resistance
Inactivation of antimicrobial agent -Enzymatic inactivation of clindamycin Alterations to bacterial target -Mutations to the 50S subunit -Modification of ribosomal target by methylase enzymes leading to reduced drug binding
51
lincosamide ABX (clindamycin) spectrum
gram + and anaerobes
52
lincosamide ABX (clindamycin) adverse effects
diarrhea w high risk of C diff superinfection skin rash
53
oxazolidinone MOA
Binds to the P site of the 50S bacterial ribosomal subunit Prevents formation of a larger ribosomal subunit that plays a role in initiation of protein synthesis
54
oxazolidinone resistance
Unique mechanism of action allows for greater activity against resistant bacteria Alterations to bacterial target -Point mutations in the 23S rRNA -Methyltransferase that induces ribosomal modification
55
oxazolidinone spectrum of activity
gram + (MRSA and VRE)
56
oxazolidinone adverse effects
Myelosuppression (Thrombocytopenia) Neuropathy, optic neuritis, and lactic acidosis risk with prolonged use (>6 weeks)
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