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100 Cards in this Set
- Front
- Back
broad coverage of antibiotics is best during:
|
early stage of the inf's
- narrow, targeted treatment is important to minimize the risk of bacterial R |
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whether static or cidal sometimes depends on:
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dose
|
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ADME =
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time course of a drug
absorption distribution - lipophilicity, prot. binding, CNS penetraition metabolism excretion |
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4 general mech's of R:
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1. cleave the drug
2. alter the drug r's 3. activate special membrane proteins => drug efflux 4. circumvent the blocked pathway by using an alternative pathway |
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treating pneumonia: antimicrobial chosen depends on:
(4) |
1. suspected pathogen
2. likely etiology 3. where pt. developed inf. 4. pattern of signs and symptoms |
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most common causes pneumonia:
(4) |
1. S. penumoniae
2. H. influ 3. SA 4. Klebsiella pneumoniae |
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treating CAP: if ambulatory, give:
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a macrolide
|
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treating CAP: comorbidities within 3 months:
(2) |
1. FQ
2. BL + macrolide |
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treating CAP: if inpatient:
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1. FQ
2. BL + macrolide (same as with comorbidities) |
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treating CAP: in ICU:
(2) |
1. BL
+ EITHER macrolide or FQ |
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treating CAP: if concerned about Pseudomonas, add:
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antiPseudomonas BL
|
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treating CAP: if concerned about CA MRSA, add:
(2) |
1. Vancomycin
or 2. linezolid |
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"nosocomial" penumonias =
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HCAP's
|
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wrt HCAP's, 2 inf's of particular concern:
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1. Pseudomonas
2. MRSA |
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if pneumonia is late-onset or MDR is suspected, use:
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broad-spectrum antibiotics
|
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these 3 species form biofilms on medical equipment, door handles, and computer keys, and cause HCAP:
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1. acinetibacter
2. Kleb pneumonia 3. En. faecium |
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***4 BL/B-lactamase inhibitor combo drugs:***
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1. Augmentin
2. Unasyn 3. Zosyn 4. Timentin |
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Augmentin =
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Clavulanic acid + amoxicillin
|
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Unasyn =
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Sulbactam + ampicillin
|
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Zosyn =
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tazobactam + pipercillin
|
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Timentin =
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Clavulanic acid + ticarcillin
|
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GP's feature =
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THICK peptidoglycan wall,
one membrane |
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GN features:
(2) |
1. OUTER membrane
2. thin peptidoglycan wall |
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when bacteria-static drugs are removed,
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growth resumes
|
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**bacteria-static drugs are NOT given to:**
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imm-comp pts,
since they require an immunologic response to work properly |
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***cidal drugs require ____________________ to work***
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bacterial GROWTH
=> cidal and static drugs are NOT combined |
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MIC =
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lowest conc. that prevents growth
|
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MIC's are specific for:
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BOTH drug AND organism
- a LAB value - can be different in vivo |
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lower MIC =
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better antibiotic
|
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CDK =
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concentration-dependent killing
~~ how certain antib's like AG's and FQ's show inc. in killing as their dose inc's => given at HIGHER doses for SHORTER periods of time |
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TDK =
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time-dependent killing
|
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TDK is seen with:
(2) |
1. BL's
2. vancomycin |
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TDK drugs kill bacteria at:
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the same rate, as long as their conc. is above the MIC
- dosing tries to maximize time above MIC |
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PAE = post-antibiotic effect =
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time required for the antibiotic-treated cultures to return to log growth following removal of antibiotic
|
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PAE allows:
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once-daily dosing
=> dec in toxicity, cost |
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superinfection =
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growth of regularly-stable *pathogenic* organisms
that are normally held in check by normal flora, following antibiotic admin |
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which kind of antibiotics are more likely to kill normal flora?
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broad-spectrum
|
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3 mech's of MDR:
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1. mutation/selection
2. uptake of extracellular DNA from related commensal bact/recombination 3. plasmid-mediated acquisition of R-factors (can have 5 or more R factors on a single plasmid) |
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4 inhibitors of nucleic acid synthesis:
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1. Sulfo's
2. TMP's 3. Q's 4. FQ's |
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neither Sulfonamides nor Trimethoprims are used:
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alone
|
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SMZ = sulfamethoxazole
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sulfamethoxazole
|
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bacteria MUST synthesize:
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folate to grow
|
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what do bacteria need to synthesize folic acid?
(3) |
1. pteridine
2. PABA 3. glutamate |
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how do Sulfonamides inhibit folic acid synthesis?
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**structural analogs of PABA**
- |
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TMP/SMZ has a *limited toxicity*, b/c:
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it's got a 50K-fold preference for BACT. DHFR over mammalian DHFR
|
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what does TMP/SMZ do?
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inhibits DHFR
|
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what does DHFR do?
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converts DHF to TetraHF, which is then used as a cofactor for DNA, RNA, and prot synth
|
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2 examples of TMP/SMZ:
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1. Septra
2. Bactrim |
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kernicterus =
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prot-bound bilirubin in the BG of newborns
|
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"selective toxicity" =
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targeting bacteria-specific pathways/enzymes/factors
|
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what kinds of pts are usually folic acid-deficient?
(2) |
1. alcoholics
2. malnourished |
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during DNA replication, positive supercoils preclude:
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further replication
|
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2 enzymes to solve positive supercoiling:
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1. gyrA
2. parC - both make double-strand breaks, relieve supercoil, and reseal |
|
inhibition of gyrA and parC by FQ's =>
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cell death
(in other words, what do FQ's do? inhibit gyrA and parC) |
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use of FQ's is limited by:
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increasing R
|
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FQ's are selectively toxic b/c they:
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inhibit bact. gyrA at much lower rates than they do the mammalian version
|
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2 older agents for the treatment of uncomplicated UTI's:
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1. Nalidixic acid
(a Q that acts like a FQ) 2. Nitrofurantoin |
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**Nalidixic acid and Nitrofurantoin:**
|
antagonistic,
should NEVER be combined |
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what do BL's do?
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inhibit cross-linking of peptide chains at the D-Ala-D-Ala
=> no peptidoglycan wall |
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***bacterial PBP's are either:***
(2) |
1. essential (high-mlclr)
or 2. non-essential |
|
***the efficacy of a BL is a function of:***
(2) |
1. its affinity for any ONE of the essential PBP's
(an antibiotic that inhibits >1 is even better) 2. its ability to reach PBP's by getting inside GN's periplasm (greater ability to reach periplasm = lower MIC) |
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*intrinsic R of bacteria = *
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its ability to maintain keep PBP's unbound by inhibitors, either through wall or otherwise
|
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extrinsic R of bacteria to antibiotics is NOT found in wild-type strains and include:
(4) |
1. expression of B-lactamases
2. dec. permeability to drugs 3. inc. efflux 4. mut's in essential PBP's that dec. affinity of drug for PBP |
|
how do B-lactamases worK?
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like PBP's, they bind BL's
=> knock them out of use with rapid hydrolysis |
|
B-lactamases can be either:
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1. chromosomally encoded
or 2. plasmid-encoded |
|
"chromosomally encoded" =
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expression is INDUCED by sensing B-lactam or disruption in recycled cell wall materials
|
|
in which type of bacteria are B-lactamases more effective, and why?
|
in GN's, b/c they stay in the periplasmic space
- in GP's, they are excreted to the outside world |
|
what are ESBL's?
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extended-spectrum B-lactamases,
expressed by certain types of SA of hospitals, which hydrolyze previously unhydrolyzable B-lactams |
|
Staph. aereus often express B-lactamases, so SA inf's are treated with lactamase-R antibiotics, which are:
(4) |
1. oxacillin
2. nafcillin 3. 2nd/3rd cephalosporins 4. carbapenems - but ESBL's are becoming R to even these |
|
NDM-1 B-lactamase does NOT form:
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acyl-enzyme complex with B-lactams
=> VERY wide spectrum => hydrolyzes nearly ALL B-lactams - essentially eliminates the use of BL's for treatment |
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dec. in outer membrane permeability is a function of:
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mutated porins that have constricted channels
|
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mut's in essential PBP's are seen most often in:
(4) |
1. SA
2. SP 3. H. influ 4. N. gonorrhea |
|
***pen-R SP contains mutations in:***
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ALL the essential PBP's
- also R to many other antibiotics |
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pen-R SP is currently treated with:
(3) |
1. Vancomycin + cefotaxime
2. linezolid 3. Streptogramins |
|
Neisseria becomes R to penicillin in 2 ways:
|
1. plasmid-mediated production of B-lactamases
2. chromosomal mutations of endogenous genes (much more common) |
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what determines whether a strain is ceftriaxone-R?
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the mut's in PBP2
(which is the target of both penicillin AND ceftriaxone) |
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what's the deal with MRSA?
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have acquired ***NEW PBP, called PBP2a, from Staph fleuretti
=> **PBP2a becomes the ONLY essential PBP** => BL's CANNOT be used to treat MRSA |
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MRSA is also cross-resistant to:
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other antibiotics
|
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MRSA is currently treated with:
(3) |
1. Vancomycin
2. linezolid 3. Streptogramins (Dalfopristin/Quinipristin) |
|
CA-MRSA is increasing; a high % of such strains cause:
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severe necrotizing hemorrhagic pneumonia
|
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B-lactamase-R penicillins are used only against:
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SA,
but NOT MRSA |
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Carbapenem-R Enterobacteriaceae are emerging; Iminepem is hydrolyzed by a:
|
renal dispeptidase, so it's given with a
renal dispeptidase inhibitor, cilistatin |
|
mut's in B-lactamases can mitigate both:
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Augmentin and Unasyn
|
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normally, BL tubular secretion is RAPID; one exception =
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ceftriaxone, whose half life is 8 hours
(compared to 30-120 minutes) |
|
the half-life of BL's can be increased by giving:
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probenizid, which blocks renal secretion, concurrently
|
|
if a pt has a hyperS rxn to one penicillin, he will:
|
probably have a rxn to another
|
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the only BL that doesn't cause a hperS rxn =
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aztreonam, a monobactam
|
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***B-lactams must NEVER be used in pts who:***
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exhibit anaphylaxic rxns
|
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some cephalosporins cause:
|
bleeding disorders
- given Vit K concurrently |
|
2 mech's of R to Vancomycin:
|
1. induced directly by Vanco
2. plasmid-mediated |
|
bacteria that is most commonly R to Vaoncomycin =
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E. faecium
|
|
VISA appears after:
|
prolonged exposure to Vanco
(25 days to 18 weeks) => cell wall thickens, trapping the antibiotic in the outer layers |
|
VRSA have obtained:
|
VanA,/others by transposon-mediated horizontal transfer
- still rare and susceptible to other antibiotics |
|
4 cidal protein synthesis inhibitors:
|
1. AG's
2. Streptogramins 3. metronidazole 4. daptomycin |
|
5 bacteria-static protein synthesis inhibitors:
|
1. Tetracyclins
2. Chloramphenicol 3. macrolides 4. clindamycin 5. linezolide |
|
AG binding to negative sites of the inner membrane is inhibited by:
|
presence of divalent cations like Ca2+. Mg2+
|
|
AG's can only reach the cytoplasmic membrane of GP's if:
|
BL's are present
=> often combined - presence of BL also improves AG's against GN's |
|
**uptake of AG's is ___________- dependent
|
oxygen-dependent;
=> AG's are USELESS against strict anaerobes |
|
AG's are great for:
|
PAE
=> once-daily dose |
|
AG + penicillin treats:
|
E. facium, a GP
- neither is effective against E. faecium by itself => ALWAYS combined to treat enteroccoci inf's |