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82 Cards in this Set
- Front
- Back
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Antimicrobial drug process is dependent on what triad of things?
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relationship between patient and bug, bug and drug, and patient and drug
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5 patient factors that affect patient drug relationship
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Immune status
Pharmacokinetics Toxicity Organ function Pharmacodynamics |
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4 factors between drug and bug that affect relationship
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Susceptibility
Site of infection Protein binding pH- certain drugs don’t kill in lungs well because of pH |
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patient bug relationship and factors involved (3)
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Immune status- change what organisms are causing the disease
Site of infection Age- neonates vs. adults vs. elderly (different types of bugs) |
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5 steps to selecting an antimicrobial regimen
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Step 1: Establish the need for antimicrobial therapy
Step 2: Attempt to identify the pathogen Step 3: Select empiric antimicrobial therapy Step 4: Monitor therapy for efficacy and toxicity Step 5: Refine antimicrobial therapy for definitive identification of pathogen and infection. |
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establishing whether there is an infection: symptoms to consider (4)
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1) fever- though not always due to infection (can be hemorrhagic stroke, or something else)
2) pain 3) swelling 4) redness |
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clinical signs of infection may be specific for...
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the site or pathogen
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Non specific signs of inflammation (part of infectious process- but can be other things) (3)
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ESR (erythrocyte sedimentation rate)
CRP (C-reactive protein) LFTs (liver function tests, liver transaminases) |
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gram stains are normally performed on what specimens (from where) (4)
usually not sampled from where (idk why) |
Performed on sputum, urine, CSF, and wound specimens (NOT usually on blood).
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do all organisms gram stain?
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Not all organisms gram stain- some are gram variable or reside inside cells
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ways of categorizing pathogens
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gram +/-
an/aerobic |
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gram positive cocci (4)
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Staphylococci, Streptococci, Enterococci, Listeria
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pathogens with unique culture presentations (3)
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Staphylococcus- gram + coccus in clusters
Gram positive cocci in pairs and chains is usually Streptococcus or Enterococcus |
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coagulase negative staph (2)
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staph epidermis
staph saprophyticus |
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coagulase positive staph
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staph aureus
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Lancefield group A- organisms and what they cause
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Strep. pyogenes (strep throat, rheumatic fever)
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Lancefield group B- organisms and where they are found
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Strep. agalactiae found in cervical and vaginal cultures
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Lancefield group D organism and where found
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Streptococcus bovis – found in GI tract
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other 2 bacteria found in GI tract
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Enterococcus faecalis, E. faecium (also VRE)
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Viridans Streptococci - what is it referring to
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catchall term for α-hemolytic strep, producing a green coloration on blood agar plates (hence the name "viridans", from Latin "vĭrĭdis", green), or nonhemolytic. They possess no Lancefield antigens
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primary cause of pneumonia
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Streptococcus pneumoniae –
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6 gram (-) rods; which one has emerging resistance? (the others already have resistance)
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Klebsiella spp- emerging resistance
Enterobacter spp Serratia marcescens Proteus spp Pseudomonas aeruginosa- mortality, a lot of resistance Haemophilus influenzae |
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gram negative cocci (2)
2 diseases caused by this |
Moraxella catarrhalis
Neisseria spp. (n. gonorrhea and n. meningitis) |
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6 species that don't gram stain
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Chlamydia spp.
Mycoplasma pneumoniae Legionella spp. Mycobacteria Rickettsiae Spirochetes |
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gram positive anaerobes usually found where? (2)
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generally of the mouth and upper GI tract- in mouth we have biofilm so bacteria can exist there and in microenvironments (not that much O2) like between teeth, etc.
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4 gram positive anaerobes
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Peptostreptococcus
Peptococcus Propionibacterium acnes Clostridium spp. |
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gram negative anaerobes usually found where?
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generally of the lower GI tract.
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2 gram negative anaerobes
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Bacteroides fragilis- bad. Want to cover for this bacteria.
Prevotella |
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Other tests for Rapid Identification (3) and what they test for
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AFB (acid fast bacilli) test for mycobactera
India ink for cryptococcus Potassium hydroxide for fungal pathogens |
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other tests for identification (may take longer) (3)
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Detection of nonspecific or specific antibodies
Genetic tests- DNA probe hybridization 16s rRNA gene sequencing |
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what organisms would you use serological testing for? (4)
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legionella, treponema pallidum, Chlamydia and Mycoplasma
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timing of serological testing
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Usually two specimens obtained, one during acute phase and one during chronic phase (Ab should be higher in acute phase but present at lower lvl in chronic/convalescent phase showing you have recovered).
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DNA probe/FISH testing used for what organisms (6)
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Chlamydia, Neisseria, coccidoiodes, histoplasma, blastomyces, mycobacterium tb
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rationale behind 16s rRNA gene sequencing (what is it, why can it be used for ID)
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16s ribosomal RNA is a component of the 30s subunit. It is highly conserved between different bacterial species and PCR amplification can be used for identification.
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minimum inhibitor concentration (MIC)
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Lowest concentration of an agent that inhibits the visible growth of an organism in vitro (crude measure)
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MBC (minimum bactericidal concentration)
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The lowest concentration of an agent which results in a 99.9% reduction in colony forming units.
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explain how you would find the MIC/MBC experimentally
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for MIC- increasing conc. of abx in tubes - look at organism growth. the tube that is clear to the naked eye is the MIC
for MBC you would take the tubes from above example and plate them on an agar plate. the first plate/conc. that is completely clean (nothing in broth to grow) is the MBC |
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disk diffusion method- what does it test. how is it done
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Tests susceptibility. Antibiotic containing disks (A-D) are placed on a plate of media containing a “lawn” of organisms. Following a period of incubation, the plate is inspected and zones of inhibition measured
will have info where if disk is > 8mm it is susceptible, etc. |
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broth microdilution- what is it, what's it tell you
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Individual antibiotics are tested in each row (A-H) at doubling concentrations in each well from high (column 1) to low (column 11) with a column containing no antibiotic (column 12) serving as a growth control. The MIC for each antibiotic is the concentration in the first well containing no visual growth
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E test- how does it work, what does it tell you
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E is for ellipses, in the way that the drug diffuses in an elliptical manner from the strip.
An Etest strip is placed on a media plate containing growing organism. After a period of incubation the MIC is detrmined by the point at which the zone of inhibition intersects the test strip. The concentrations at each point are printed on the test strip. |
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breakpoint value
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point at which organism is considered susceptible/resistant
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breakpoint value is based upon (3)
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Drug pharmacokinetics
Distribution of MICs Clinical Efficacy |
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what orgs publish breakpoints
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National Committee for Clinical Laboratory Standards (NCCLS) now called the Clinical and Laboratory Standards Institute (CLSI) publishes breakpoints
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interpreting breakpoints- 3 "breakpoints"
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S
R I (intermediate) |
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determining the true MIC
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The true MIC is rarely determined??
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flaw in MIC- does not take into account what 4 things
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site of infection into account, drug distribution, penetration, protein binding
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MIC50 or MIC90
what are they and what are they used for |
MIC that inhibits 50% or 90% of organisms; used to describe a host of organisms (used to look at resistance rate over time- if MIC90 is creeping up over time)
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3 limitations of MIC
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Do not provide information regarding the rate or extent of killing.
Conducted with a standard inoculum (standard amount/types of bacteria?) Lack of plasma proteins and complement. |
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5 factors that influence potential pathogens
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Patient characteristics
Age Immune status Comorbid conditions- asthma, diabetes… Site of infection |
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as an example of meningitis caused in neonates vs. adults- 4 organisms found in birth canal that cause meningitis in babies
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E. coli, Strep. Agalactiae, Listeria monocytogenes, Klebsiella.
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whereas meningitis in adults typically caused by (2)
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organisms Strep. Pneumoniae and N. meningitidis
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what is an antibiogram? what is it used for?
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Cumulative Antimicrobial Susceptibility Report
Used for selection of empirical regimens. |
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penicillin cross reactivity
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Cross reactivity- penicillins EXCEPTING cephalosporins
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assessing PCN allergies and when to give cephalasporins
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have to distinguish severity of allergic rxn- if rash- minor but don’t give them –cillins anyway but cephalosporins/carbepenems are probably fine. However if severe anaphylactic rxn (type I reaction = hives, angioedema included), would avoid cephalosporins.
If allergic to cephalosporins then don’t give any other cephalosporins |
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patient factors that affect abx choice (7)
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allergies
renal fxn hepatic fxn? site of infection concomitant drug therapy Underlying conditions (Chronic illness, pregnancy) PKPD |
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CCG
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(140-age)*IBW / Scr *72
*0.85 if female |
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how to calc IBW for male vs female
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Males: 50 + 2.3 x (inches over 5’)
Females 45.5 + 2.3 x (inches over 5’) |
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Childs Pugh classification- applied to what 2 drugs for hepatic impairment
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caspofungin
tigecycline |
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child pugh- grade a,b,c what do they mean
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Grade A Well compensated (mild)
Grade B Functional compromise (moderate) Grade C Decompensated disease (severe) |
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2 disease states where site of infection will affect what abx to choose
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TB meningitis, prostatitis
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2 examples where abx choice will differ depending on underlying condition
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Sulfonamides not used in last trimester of pregnancy- can cause kinecterus?
Empiric therapy for cellulitis in pt with or without DM (DM tends to make it more severe so therapy slightly diff) |
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5 PK factors important for abx dosing/choice
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Cmax, half-life, AUC
Tissue penetration, protein binding |
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pharmacodynamics definition for abx (2)
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Relationship between drug concentration and rate and extent of microbial killing
Pharmacokinetics (AUC, Cmax) in relationship with MIC of pathogen |
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for abx, most PD deals with...(2)
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concentration/activity relationships and postantibiotic effect
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conc. dependent bactericidal activity- definition
goal of dosing regiment to optimize this type of killing |
The rate and/or extent of bactericidal activity increase with increasing antimicrobial concentrations.
The goal of a dosing regimen is to optimize the peak:MIC |
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5 abx with conc. dependent killing
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Aminoglycosides (gentamicin and tobramycin)
Fluoroquinolones (ciprofloxacin and ofloxacin) Metronidazole Amphotericin B Daptomycin |
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daptomycin dose dep toxiciy
how to avoid |
Dose dependent toxicity (CK elevation leading to rhabdo) with short half life; give a bigger dose once daily which avoids accumulation and AE
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goal of time dependent bactericidal activity therapy
definition (2) |
The rate and extent of killing do not increase with increasing antibiotic concentrations.
Bactericidal activity is increased by increasing the length of exposure. The goal of dosing regimens is to optimize the time concentrations remain above the MIC (t>MIC) |
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efficacy of time dep bactericidal activity are mainly dependent on what parameter?
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Efficacy of agents with this characteristic are mainly dependent trough concentration (peak not correlated with outcomes)
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time dep bactericidal activity- efficacy vs. MIC
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Optimum bactericidal activity should be observed as t > MIC approaches 100%. However, as t > MIC for as little as 50% of dosing interval may be effective.
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time dep bactericidal activity influenced by...(3)
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1) Host immune status
2) Microorganism 3) Synergy |
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2 types of regimens that can be used to optimize time above MIC
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Continuous infusion and extended infusion dosing regimens can be used to optimize the t > MIC (the time drug conc. is greater than MIC)
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abx that exhibit conc. independent killing (5)
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Beta-lactams (penicillins and cephalosporins)
Glycopeptides (vancomycin)- we measure trough because it is time dependent Clindamycin Macrolides (erythromycin) Fluconazole |
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what is AUC?
takes into account...(2) |
Quantification of overall drug exposure
takes into account peak and trough (it’s the whole area) |
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AUC:MIC ratio can be correlated with what?
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AUC:MIC may be correlated with bacterial killing properties of concentration-dependent and non-concentration-dependent killers ( i guess cuz it takes into acct peak and trough??)
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Concentration-effect curves need to be evaluated keeping what in mind? why?
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keeping the pharmacokinetics of the drug in mind.
have to make sure things like toxicity and intervals of dosing, etc. are maximized/optimized |
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effects after drug removal (2)
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Post-antibiotic effect (PAE)- e.g. when drugs inhibit protein synthesis- takes a while for organism to recover after drug is taken away- in vitro
Sub-inhibitory effect- seen in vivo |
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PAE definition
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Persistent suppression of bacterial growth following a brief exposure to an antimicrobial.
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technical PAE definition
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Experimentally, PAE is defined as the difference in time required for a control culture and test culture to increase one log CFU/ml following drug removal.
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PAE may be the result of... (2)
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non-lethal cell damage
persistence of the antimicrobial at the binding site |
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4 things that affect PAE
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Microorganism
Antimicrobial Length of antimicrobial exposure ( increased exposure, increased PAE) Antimicrobial concentration ( increased concentration, increased PAE) |
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drugs with long PAEs and conc. DEPENDENT dosing should be administered how? why?
3 examples of drugs |
Agents which exhibit concentration-dependent killing and have long PAEs (i.e., aminoglycosides, amphotericin B, and fluoroquinolones) should be administered as large infrequent doses to maximize their pharmacodynamic properties
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