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Flashcards in Pharm Antimicrobial DSA Deck (54)
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1

Aminopenicillins

i) Ampicillin (PO, IV, IM)
ii) Amoxicillin (PO)

2

Third Generation Cephalosporins

i) Ceftriaxone [Rocephin] (IV, IM)
ii) Ceftazidime [Fortaz] (IV, IM)

3

Fourth generation cephalosporins

cefepime

4

Carbapenems

b) Meropenem
c) Ertapenem

5

B-lactamase Inhibitors

a) Ampicillin-sulbactam
b) Amoxicillin-clavulanic acid
c) Piperacillin-tazobactam

6

Glycopeptides

Vancomycin

7

Fluoroquinolones

Levofloxacin

8

Aminoglycosides

Gentamicin

9

Tetracyclines/Glycylcyclines

Doxycycline

10

Macrolides/Ketolides

Azithromycin

11

Lincosamides

Clindamycin

12

Oxazolidinones

Linezolid

13

to assess whether antimicrobials are warranted:

i) Is an antimicrobial indicated based on clinical findings?
ii) Have appropriate cultures been obtained?
iii) What is the likely causative organism?
iv) What must be done to prevent secondary exposure?
v) Is there clinical evidence or established guidelines that have determined antimicrobial therapy provides a clinical benefit?

14

Once the pathogen is known, one must always continue to question whether management is appropriate and optimized:

i) Would a narrower spectrum antimicrobial be more appropriate compared to the empiric regimen?
ii) Is one agent or a combination of agents necessary?
iii) Has the dose, route of administration, and duration of therapy been optimized?
iv) Have the most appropriate tests been completed (e.g., susceptibility)?
v) Are adjunctive measures also applicable (e.g., surgery to remove necrotic tissue)?

15

Prophylactic Therapy

i) Goal: prevent infection or prevent dangerous disease in those already infected.
ii) Examples: based on CD4 counts, antimicrobials are initiated in HIV infection (immunocompromised patient) to prevent opportunistic disease; post-exposure prophylaxis is provided to those who have been in contact with a patient with meningococcal meningitis.

16

Preemptive Therapy

i) Goal: provide early, targeted antimicrobial therapy in high-risk patients who are currently asymptomatic but have become infected.
ii) Example: cytomegalovirus (CMV) treatment after stem cell and solid organ transplants.

17

Empiric Therapy

i) Goal: provide antimicrobial therapy to a symptomatic patient without initial identification of infecting organism. Must consider knowledge of which microorganisms are most likely to cause specific infection/symptoms found in patient.
ii) Example: prescribing antimicrobials for community-acquired pneumonia (CAP) based on knowledge of most likely infecting pathogen.

18

Definitive Therapy

i) Goal: infecting organism now known, antibiotics should be streamlined based on susceptibility and duration should be limited to appropriate length.
ii) Example: Staphylococcus aureus bacteremia treated empirically with vancomycin but susceptible to nafcillin, antimicrobials appropriately changed to most narrow spectrum antibiotic.

19

Post-Treatment Suppressive Therapy

i) Goal: continue lower dose, antimicrobial therapy when infection has not been completely eradicated and immunological or anatomical defect still present which lead to original infection.
ii) Example: orthopedic implant that has become infected but cannot be removed.

20

Most valuable, time tested method for immediate identification of bacteria

gram stain

21

Minimum inhibitory concentration (MIC):

lowest concentration of drug required to inhibit growth.

22

Kinds of lab interpretations

(a) Susceptible (S): isolates are inhibited by usually achievable concentrations of antimicrobial when dose recommended to treat site of infection is used.
(b) Intermediate (I): antimicrobial MIC approaches usually attainable blood and tissue levels, and for which response rates may be lower than for susceptible isolates.
(c) Resistant (R): isolates are not inhibited by the usually achievable concentrations of antimicrobial, and/or MICs or zone diameters fall in the range where specific resistance mechanisms are likely, and clinical efficacy of the agent has not been reliably shown.

23

Dilution tests

(1) Antibiotics used in broth medium in serially diluted concentrations.
(2) After 18-24 hours of incubation, growth of organism is measured.
(3) MIC determined based on the lowest concentration of drug that inhibits visible growth.
(4) Can use automated system: broth dilution & measure optical density to assess bacterial growth.

24

Disk diffusion

(1) Antibiotic containing disks on agar.
(2) Measure size of clear zone after 18-24 hours of incubation.
(3) Standardized zone sizes for bacterial species to distinguish between susceptible and resistant.
(4) Only qualitative “susceptible” or “resistant”, no MIC value measured.

25

Gradient diffusion

(1) Test strip with varying antibiotic concentrations placed on agar which shows clear elliptical zones to determine MIC.

26

Antibacterial Spectrum

a) Narrow-spectrum: act on a single or a limited group of microorganisms
b) Extended-spectrum: active against gram-positive bacteria but also significant number of gram-negative
c) Broad-spectrum: act on a wide variety of bacterial species, including both gram-positive and -negative

27

Bacteriostatic vs. Bactericidal Drugs

a) Bacteriostatic: arrests growth and replication of bacteria (limits spread of infection).
i) In general, bacterial protein synthesis inhibitors.

b) Bactericidal: kills bacteria.
i) Concentration-dependent killing: rate & extent of killing increase with increasing concentrations
(1) Examples: aminoglycosides and fluoroquinolones

ii) Time-dependent killing: activity continues as long as serum concentration is above minimum bactericidal concentration
(1) Examples: B-lactams and vancomycin

28

Antibacterial Targets:

i) Cell wall synthesis
ii) Cell membrane synthesis
iii) Protein synthesis (30S and 50S ribosomal subunits)
iv) Nucleic acid metabolism
v) Function of topoisomerases
vi) Folate synthesis

29

Bacterial Resistance

Two factors associated with development of antimicrobial resistance:
i) Evolution
ii) Clinical/environmental practices

Resistance Mechanisms
i) Reduced entry of antibiotic into pathogen
ii) Enhanced export of antibiotic by efflux pumps
iii) Release of microbial enzymes which destroy antibiotic
iv) Alteration of microbial proteins that transform prodrugs to the effective moieties
v) Alteration of target proteins
vi) Development of alternative pathways to those inhibited by antibiotics

30

Beta-Lactams

Compounds containing a four-membered lactam ring: penicillins, cephalosporins, monobactams, carbapenems, and B-lactamase inhibitors. These agents share features of chemistry, mechanism of action, pharmacology, and immunologic characteristics.