Resp Part 1-1

Front 1

broad coverage of antibiotics is best during:

Back 1

early stage of the inf's

- narrow, targeted treatment is important to minimize the risk of bacterial R

Front 2

whether static or cidal sometimes depends on:

Back 2

dose

Front 3

ADME =

Back 3

time course of a drug

absorption
distribution - lipophilicity, prot. binding, CNS penetraition
metabolism
excretion

Front 4

4 general mech's of R:

Back 4

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

Front 5

treating pneumonia: antimicrobial chosen depends on:

(4)

Back 5

1. suspected pathogen

2. likely etiology

3. where pt. developed inf.

4. pattern of signs and symptoms

Front 6

most common causes pneumonia:

(4)

Back 6

1. S. penumoniae


2. H. influ
3. SA
4. Klebsiella pneumoniae

Front 7

treating CAP: if ambulatory, give:

Back 7

a macrolide

Front 8

treating CAP: comorbidities within 3 months:

(2)

Back 8

1. FQ

2. BL + macrolide

Front 9

treating CAP: if inpatient:

Back 9

1. FQ

2. BL + macrolide

(same as with comorbidities)

Front 10

treating CAP: in ICU:

(2)

Back 10

1. BL

+

EITHER macrolide or FQ

Front 11

treating CAP: if concerned about Pseudomonas, add:

Back 11

antiPseudomonas BL

Front 12

treating CAP: if concerned about CA MRSA, add:

(2)

Back 12

1. Vancomycin

or

2. linezolid

Front 13

"nosocomial" penumonias =

Back 13

HCAP's

Front 14

wrt HCAP's, 2 inf's of particular concern:

Back 14

1. Pseudomonas

2. MRSA

Front 15

if pneumonia is late-onset or MDR is suspected, use:

Back 15

broad-spectrum antibiotics

Front 16

these 3 species form biofilms on medical equipment, door handles, and computer keys, and cause HCAP:

Back 16

1. acinetibacter

2. Kleb pneumonia

3. En. faecium

Front 17

***4 BL/B-lactamase inhibitor combo drugs:***

Back 17

1. Augmentin

2. Unasyn

3. Zosyn

4. Timentin

Front 18

Augmentin =

Back 18

Clavulanic acid + amoxicillin

Front 19

Unasyn =

Back 19

Sulbactam + ampicillin

Front 20

Zosyn =

Back 20

tazobactam + pipercillin

Front 21

Timentin =

Back 21

Clavulanic acid + ticarcillin

Front 22

GP's feature =

Back 22

THICK peptidoglycan wall,

one membrane

Front 23

GN features:

(2)

Back 23

1. OUTER membrane

2. thin peptidoglycan wall

Front 24

when bacteria-static drugs are removed,

Back 24

growth resumes

Front 25

**bacteria-static drugs are NOT given to:**

Back 25

imm-comp pts,

since they require an immunologic response to work properly

Front 26

***cidal drugs require ____________________ to work***

Back 26

bacterial GROWTH

=> cidal and static drugs are NOT combined

Front 27

MIC =

Back 27

lowest conc. that prevents growth

Front 28

MIC's are specific for:

Back 28

BOTH drug AND organism

- a LAB value - can be different in vivo

Front 29

lower MIC =

Back 29

better antibiotic

Front 30

CDK =

Back 30

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

Front 31

TDK =

Back 31

time-dependent killing

Front 32

TDK is seen with:

(2)

Back 32

1. BL's

2. vancomycin

Front 33

TDK drugs kill bacteria at:

Back 33

the same rate, as long as their conc. is above the MIC

- dosing tries to maximize time above MIC

Front 34

PAE = post-antibiotic effect =

Back 34

time required for the antibiotic-treated cultures to return to log growth following removal of antibiotic

Front 35

PAE allows:

Back 35

once-daily dosing

=> dec in toxicity, cost

Front 36

superinfection =

Back 36

growth of regularly-stable *pathogenic* organisms

that are normally held in check by normal flora,

following antibiotic admin

Front 37

which kind of antibiotics are more likely to kill normal flora?

Back 37

broad-spectrum

Front 38

3 mech's of MDR:

Back 38

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)

Front 39

4 inhibitors of nucleic acid synthesis:

Back 39

1. Sulfo's

2. TMP's

3. Q's

4. FQ's

Front 40

neither Sulfonamides nor Trimethoprims are used:

Back 40

alone

Front 41

SMZ = sulfamethoxazole

Back 41

sulfamethoxazole

Front 42

bacteria MUST synthesize:

Back 42

folate to grow

Front 43

what do bacteria need to synthesize folic acid?

(3)

Back 43

1. pteridine

2. PABA

3. glutamate

Front 44

how do Sulfonamides inhibit folic acid synthesis?

Back 44

**structural analogs of PABA**

-

Front 45

TMP/SMZ has a *limited toxicity*, b/c:

Back 45

it's got a 50K-fold preference for BACT. DHFR over mammalian DHFR

Front 46

what does TMP/SMZ do?

Back 46

inhibits DHFR

Front 47

what does DHFR do?

Back 47

converts DHF to TetraHF, which is then used as a cofactor for DNA, RNA, and prot synth

Front 48

2 examples of TMP/SMZ:

Back 48

1. Septra

2. Bactrim

Front 49

kernicterus =

Back 49

prot-bound bilirubin in the BG of newborns

Front 50

"selective toxicity" =

Back 50

targeting bacteria-specific pathways/enzymes/factors

Front 51

what kinds of pts are usually folic acid-deficient?

(2)

Back 51

1. alcoholics

2. malnourished

Front 52

during DNA replication, positive supercoils preclude:

Back 52

further replication

Front 53

2 enzymes to solve positive supercoiling:

Back 53

1. gyrA

2. parC

- both make double-strand breaks, relieve supercoil, and reseal

Front 54

inhibition of gyrA and parC by FQ's =>

Back 54

cell death

(in other words, what do FQ's do? inhibit gyrA and parC)

Front 55

use of FQ's is limited by:

Back 55

increasing R

Front 56

FQ's are selectively toxic b/c they:

Back 56

inhibit bact. gyrA at much lower rates than they do the mammalian version

Front 57

2 older agents for the treatment of uncomplicated UTI's:

Back 57

1. Nalidixic acid
(a Q that acts like a FQ)

2. Nitrofurantoin

Front 58

**Nalidixic acid and Nitrofurantoin:**

Back 58

antagonistic,

should NEVER be combined

Front 59

what do BL's do?

Back 59

inhibit cross-linking of peptide chains at the D-Ala-D-Ala

=> no peptidoglycan wall

Front 60

***bacterial PBP's are either:***

(2)

Back 60

1. essential (high-mlclr)

or

2. non-essential

Front 61

***the efficacy of a BL is a function of:***

(2)

Back 61

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)

Front 62

*intrinsic R of bacteria = *

Back 62

its ability to maintain keep PBP's unbound by inhibitors, either through wall or otherwise

Front 63

extrinsic R of bacteria to antibiotics is NOT found in wild-type strains and include:

(4)

Back 63

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

Front 64

how do B-lactamases worK?

Back 64

like PBP's, they bind BL's

=> knock them out of use with rapid hydrolysis

Front 65

B-lactamases can be either:

Back 65

1. chromosomally encoded

or

2. plasmid-encoded

Front 66

"chromosomally encoded" =

Back 66

expression is INDUCED by sensing B-lactam or disruption in recycled cell wall materials

Front 67

in which type of bacteria are B-lactamases more effective, and why?

Back 67

in GN's, b/c they stay in the periplasmic space

- in GP's, they are excreted to the outside world

Front 68

what are ESBL's?

Back 68

extended-spectrum B-lactamases,

expressed by certain types of SA of hospitals,

which hydrolyze previously unhydrolyzable B-lactams

Front 69

Staph. aereus often express B-lactamases, so SA inf's are treated with lactamase-R antibiotics, which are:

(4)

Back 69

1. oxacillin

2. nafcillin

3. 2nd/3rd cephalosporins

4. carbapenems

- but ESBL's are becoming R to even these

Front 70

NDM-1 B-lactamase does NOT form:

Back 70

acyl-enzyme complex with B-lactams

=> VERY wide spectrum

=> hydrolyzes nearly ALL B-lactams

- essentially eliminates the use of BL's for treatment

Front 71

dec. in outer membrane permeability is a function of:

Back 71

mutated porins that have constricted channels

Front 72

mut's in essential PBP's are seen most often in:

(4)

Back 72

1. SA

2. SP

3. H. influ

4. N. gonorrhea

Front 73

***pen-R SP contains mutations in:***

Back 73

ALL the essential PBP's

- also R to many other antibiotics

Front 74

pen-R SP is currently treated with:

(3)

Back 74

1. Vancomycin + cefotaxime

2. linezolid

3. Streptogramins

Front 75

Neisseria becomes R to penicillin in 2 ways:

Back 75

1. plasmid-mediated production of B-lactamases

2. chromosomal mutations of endogenous genes (much more common)

Front 76

what determines whether a strain is ceftriaxone-R?

Back 76

the mut's in PBP2

(which is the target of both penicillin AND ceftriaxone)

Front 77

what's the deal with MRSA?

Back 77

have acquired ***NEW PBP, called PBP2a, from Staph fleuretti

=> **PBP2a becomes the ONLY essential PBP**

=> BL's CANNOT be used to treat MRSA

Front 78

MRSA is also cross-resistant to:

Back 78

other antibiotics

Front 79

MRSA is currently treated with:

(3)

Back 79

1. Vancomycin

2. linezolid

3. Streptogramins (Dalfopristin/Quinipristin)

Front 80

CA-MRSA is increasing; a high % of such strains cause:

Back 80

severe necrotizing hemorrhagic pneumonia

Front 81

B-lactamase-R penicillins are used only against:

Back 81

SA,

but NOT MRSA

Front 82

Carbapenem-R Enterobacteriaceae are emerging; Iminepem is hydrolyzed by a:

Back 82

renal dispeptidase, so it's given with a

renal dispeptidase inhibitor, cilistatin

Front 83

mut's in B-lactamases can mitigate both:

Back 83

Augmentin and Unasyn

Front 84

normally, BL tubular secretion is RAPID; one exception =

Back 84

ceftriaxone, whose half life is 8 hours

(compared to 30-120 minutes)

Front 85

the half-life of BL's can be increased by giving:

Back 85

probenizid, which blocks renal secretion, concurrently

Front 86

if a pt has a hyperS rxn to one penicillin, he will:

Back 86

probably have a rxn to another

Front 87

the only BL that doesn't cause a hperS rxn =

Back 87

aztreonam, a monobactam

Front 88

***B-lactams must NEVER be used in pts who:***

Back 88

exhibit anaphylaxic rxns

Front 89

some cephalosporins cause:

Back 89

bleeding disorders

- given Vit K concurrently

Front 90

2 mech's of R to Vancomycin:

Back 90

1. induced directly by Vanco

2. plasmid-mediated

Front 91

bacteria that is most commonly R to Vaoncomycin =

Back 91

E. faecium

Front 92

VISA appears after:

Back 92

prolonged exposure to Vanco

(25 days to 18 weeks)

=> cell wall thickens, trapping the antibiotic in the outer layers

Front 93

VRSA have obtained:

Back 93

VanA,/others by transposon-mediated horizontal transfer

- still rare and susceptible to other antibiotics

Front 94

4 cidal protein synthesis inhibitors:

Back 94

1. AG's

2. Streptogramins

3. metronidazole

4. daptomycin

Front 95

5 bacteria-static protein synthesis inhibitors:

Back 95

1. Tetracyclins

2. Chloramphenicol

3. macrolides

4. clindamycin

5. linezolide

Front 96

AG binding to negative sites of the inner membrane is inhibited by:

Back 96

presence of divalent cations like Ca2+. Mg2+

Front 97

AG's can only reach the cytoplasmic membrane of GP's if:

Back 97

BL's are present

=> often combined

- presence of BL also improves AG's against GN's

Front 98

**uptake of AG's is ___________- dependent

Back 98

oxygen-dependent;

=> AG's are USELESS against strict anaerobes

Front 99

AG's are great for:

Back 99

PAE

=> once-daily dose

Front 100

AG + penicillin treats:

Back 100

E. facium, a GP

- neither is effective against E. faecium by itself => ALWAYS combined to treat enteroccoci inf's