Cp2, Pharmacology, Antibiotics For Cystic Fibrosis

Front 1

What are the 2 most common infections in cystic fibrosis

Back 1

S. Aureus (64%)and pseudomonas aeruginosa (55%)

Front 2

age related infections in CF

Back 2

70% of pts by time reach adolescence have chronic pseudomonas infection. about 20% have MRSA

Front 3

pseudomonas aeruginosa (gram?)

Back 3

Gram neg bacilli (especially difficult to treat)

Front 4

what special group of agents is useful for pseudomonas

Back 4

B-lactams=the PCN group
1) piperacillin
2) Ticarcillin
Cephalosporins group (also B lactam)
1) ceftazidime
2) Cefepime
Aminoglycoside=tobramycin

Front 5

MOA for PCNs and toxicity

Back 5

cell wall inhibitors
toxicity=hypersensitivity, diarrhea, colitis

Front 6

MOA and toxicity for Cephalosporins

Back 6

MOA=Cell wall inhibitors
toxiticy=hypersensitivity, diarrhea, colitis

Front 7

MOA and toxicity for Aminoglycoside

Back 7

MOA=Protein synthesis inhibitor 30S
toxiticyt=nephrotoxicity and ototoxicity

Front 8

Why are gram neg bacteria so hard to manage?

Back 8

the peptidoglycan is embedded between outer membrane and plasma membrane. Only way to access it is through PORIN=hydrophilic pore.
Drugs that work are hydrophilic and are effective as long as there isn't B-lactamase being produced by bacteria.

Front 9

How do piperacillin, tcarcillin, cefepime adn ceftazidime enter gram - bacteria

Back 9

bind to PBPs and disrupt cell wall integrity

Front 10

Narrow spectrum agents

Back 10

CANNOT traverse porins or membrane sufficiently to work

Front 11

drugs must be 2 things to enter gram neg organisms

Back 11

1) hydrophillic and
2) ionizable
some PCNs,and some cephalosporins are, ALL aminoglycosides are.

Front 12

common IV regimens used to treat P. Aeruginosa

Back 12

1)Tobramycin combined with perpacillin or cefepime
2) carbapenem
tobramycin is the aminoglycoside with greater activity against P. Aeruginosa

Front 13

Aminoglycoside and penicillins combinations should be______

Back 13

staggered, not administered together. there is no clinical evidence for synergy

Front 14

efficacy of tobramycin depends on

Back 14

concentration. Short exposure to high levels correlates with efficacy.Peak=defines efficacy
trough=defines safety.
usually given as singel daily dose

Front 15

B lactam agents and efficacy

Back 15

is related to how LONG you are above MIC. So not associated with the PEAK, more with the TIME

Front 16

how do we get resistance to anti-pseudomonal antibiotics

Back 16

l1)owered permeability (porin deficits, bacteria exresses fewer porins)
2)Altered PBP's and rarely degradation be B-Lactamase
3) anti-pseudomonal aminoglycoside=enzymatic modification of bacteria to deactivate the drug.

Front 17

evolution of CF pseudomonas infections

Back 17

intermittent infections;exacerbation--->Chronic infection

Front 18

Treating intermittent pseudomonas infections

Back 18

1)IV tobramcyin + piperacillin(or ticarcillin)
2) IV tobramycin + cifepime (or ceftaxidime)
3) IV tobramycin + imipenem-cilastatin

Front 19

challenges in treating pseduomonas

Back 19

it creates colonies and biofilm. colonies secrete biofilm "shelter" and they also have a heavy mucous shield

Front 20

one approach to prevent infection of pseudomas

Back 20

aerosol tobramycin
oral azithromcin
aersosol DNA nuclease (Dornase)

Front 21

inhaled/aerosol tobramycin

Back 21

Low toxicity and local efficacy

Front 22

Oral azithromycin

Back 22

anti-inflammatory and broad spectrum antibiotic

Front 23

inhaled DNA nuclease

Back 23

recombinant protein, adjuvant therapy (not acting on bactera, but acts on the environtment to help out other drugs) breaks up mucus=mucolytic
degrades DNA from neutrophils

Front 24

challenges of inhaled/aerosol drugs for CF

Back 24

costs of goods and development (delivery devices are key)
ability to aerosolize the drug (particle size and solubility)
time burden of administration
So, this is why we use systemic drugs more often than aerosolized

Front 25

What are the 3 drugs available in aerozolized form for CF treatment

Back 25

tobramycin, colistin, dornase

Front 26

Why do we give 25X higher than the MIC when giving aerosolized aminoglycosides for CF?

Back 26

because purulent sputum antagonizes aminoglycoside activity. (binds to mucins, DNA and divalent cations)

Front 27

Azithromycinum

Back 27

macrolide class. Inhibits protein translations,. 50S subunit. broad spectrum and atypical organisms., tolerated better than errythromycin.

Front 28

what is the bioavailability of azithromycin

Back 28

for unclear reasons it concentrates in the lungs. Concentrates in sputum! 10-100X plasma level. Direct and indirect anti-inflammatory actions(supresses cytokines). Prevents pseudomonas from making the biofilm. (so tobramycin can do it's job better)

Front 29

inhaled tobramycin and oral azithromycin, and inhaled dornase

Back 29

used to suppress airway destruction. together. fights infection, inflammation and neutrophil DNA "debris"

Front 30

Colistin

Back 30

reserved for late stage problem of multi drug resistant pseudomonas. It is the ONLY option despite it's toxicity. colistin binds to LPS on gram neg outer membrane and disrupts bacterial membrane

Front 31

What drugs are used on Methicillin resistant Staph infections

Back 31

Resistant=use vancomycin

Front 32

treatment of choice for MRSA infection

Back 32

Vancomycin, has no B lactam and not degraded by B-lactamase

Front 33

What if pt doesn't respond to vancomycin. VRSA

Back 33

linezolid (ZYVOX)
protein synthesis inhibitor
is bacteriostatic (NOT CIDAL)

Front 34

What do we use for staph infections that are methicillin sensitive

Back 34

special B-lactams for MSSA.
ticarcillin-clavulanate
piperacillin-taxobactam
Used as combination drugs.
clavulanate is a B-lactamase inhibitor. (It inhibitis B-lactamas so that ticarcillin can do it's job) same with taxobactam

Front 35

Does one use methicillin clinically to treat patients

Back 35

NO, when pts exposed to methicillin pts get interstitial nephritis. (Methicillin resistance is a clinical tool)

Front 36

Why dont we use vancomycin for every staph, whether MRSA or not?

Back 36

because vancomycin is less effective than B-lactams for Methicillin senstive organism. better to treat with appropriate B-lactam

Front 37

**** Most staph is resistant to PCN because------

Back 37

it overproduces b-lactamase**

Front 38

why is MRSA resistant?

Back 38

alters Penicillin binding proteins so PCN cant bind

Front 39

burkholderia cepacia infections

Back 39

are resistant to colistin and often multi or even pan resistant. some combinations of antibiotics (suflamethoxazole-trimethoprim) are effective in vitro but little evidence in clinical efficacy

Front 40

penicillin resitant-methicillin sensitive

Back 40

most staph infections that make B-lactamase are PCN resistent but methicillin sensitive

Front 41

pseudomonas that are not resistant are treated with

Back 41

piperacillin and ticarcillin (bactericidal) if this pt had a co-infection with staph then these 2 drugs do not work. add tazobactam and clavulanate (to inhibit the B-lactamase) Will NOT help against MRSA though.