Antibacterials Flashcards

(49 cards)

1
Q

how do you select for appropriate antibacterial drug

A
look at toxicity
type of organism
anatomical location (will drug go there?, -cidal or -static?)
host status (age, pregnancy, allergies, renal/hepatic fxn, host defenses)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

MIC

A

minimal inhibitory (static) concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

MBC

A

minimal bactericidal concentration to kill 99.9% of bacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

infections in which -cidal drugs would have an advantage

A

immunocompromised

in immunocompetent: meningitis, endocarditis, deep bone infections, artificial device implants (in these cases, immune system has hard time eradicating the bug b/c hard to get at)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

time dependent killing

A

drugs work most effectively when concentration is above 4x MIC for more than 50% of the time

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

example of time dependent killing drug

A

beta lactams

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

concentration dependent killing

A

want to maximize the peak concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

example of concentration dependent killing

A

aminoglycosides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

concentration x time dependent killing

A

calculated as AUC(over 24 hr)/MIC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

example of concentration x time killing drug

A

quinolones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

properties of beta lactams

A

bactericidal

get maximal activity on growing bacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

MOA of beta lactams

A

covalent binding to PBP-irreversible, competitive

prevents PBP from cross linking cell wall

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what kinds of resistance are there to beta lactams?

A

beta lactamase
altered PBP
beta lactam unable to reach PBP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

how can bacteria that are sensitive to a beta lactam be resistant when in the presence of bacteria that have beta lactamase?

A

bacteria that have beta lactamase release it out of the cell membrane, so the beta lactamase can degrade the beta lactam

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

how many different beta lactamases are there

A

over 400, with different substrates

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

half life of beta lactams

A

short, so dosing intervals are short to keep the drug 4x MIC for more than 50% of the time

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

properties of penicillins

A

well distributed (low penetration into CSF, BUT increases when you have meningitis)

renal elimination-anion transport

short half lives (30 min-3 hr)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what can you do to predict severe penicillin allergies

A

pt history

pre-pen-a skin test

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

penicillins’ side effects

A
allergies
fever (even in normal pts w/o an infection)
diarrhea
enterocolitis
elevated liver enzymes
hemolytic anemia
seizures

ALL antibacterials could cause enterocolitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

MOA of beta lactamase inhibitors

A

beta lactam mimics that bind irreversibly to beta lactamase

21
Q

Examples of beta lactam resistance that is NOT due to beta lactamase

A

penicillin resistant Strep pneumo: actually a change in PBP

MRSA: resistance due to obtaining a new PBP2a

22
Q

properties of cephalosporins

A

distributed well, but only some get to the CSF

most require injection

mechanism same as penicillins

resistance comparable to penicillins

23
Q

what is notable about the 3rd gen cephalosporins

A

effective for many gram neagtives

E coli
Klebsiella
Enterobacter

Works in presence of many gram negative beta lactamases

24
Q

how are cephalosporins metabolized

25
side effects of cephalosporins
allergies nausea, vomiting, diarrhea, enterocolitis hepatocellular damage
26
rationale for developing drugs against extended spectrum beta lactamase containing bacteria
some gram negative species have beta lactamases that inactivate penicillin but also prove resistant against drugs "considered" beta lactamase resistant like the 3rd gen cephalosporins and monobactams
27
what is the treatment of choice for extended spectrum beta lactamse bacteria
carbapenems
28
MOA of quinolones
inhibits DNA gyrase (interferes with DNA replication and repair)
29
properties of quinolones
bactericidal killing predicted by AUC24/MIC
30
side effects of quinolones
``` nausea vomiting, abd pain, enterocolitis dizziness, headache, restlessness, depression rare seizures rashes EKG irregularities, arrhthymias peripheral neuropathy arthropathy, tendon rupture ``` caution: seizure hx, pregnancy, children (may cause cartilage damage)
31
What antibacterials cause C diff enterocolitis?
all of them can
32
antibacterial treatment for c diff enterocolitis
metronidazole (1st choice, esp for mild to moderate) vancomycin (moderate to severe) vancomycin and metronidazole (very severe) fidaxomicin
33
properties of aminoglycosides
bactericidal (the ONLY protein synthesis inhibitors that are) IV, IM, topical post-antibiotic effect--gets into bacteria and there is sustained activity for hours after the aminoglycoside concen. has gone below effective levels (concentration dependent killing) narrow therapeutic window, use only for serious infections
34
MOA of aminoglycosides
taken up into bacteria by an energy-requiring aerobic process binds to several locations on ribosomes: - prevents initiation and induces release of ribosome from mRNA - leads to mRNA misreading
35
uses of aminoglycosides
PRIMARILY gram negative aerobic bacilli (usually used in combo with cell wall inhibitors or quinolones for synergy) poorly effective against anaerobes gram positive requires drug combos (cell wall inhibitors increase the permeability of aminoglycosides)
36
what kind of killing do aminoglycosides exhibit?
concentration dependent
37
side effects of aminoglycosides
narrow therapeutic window nephrotoxicity (usually reversible) ototoxicity (usually irreversible) neuromuscular blockade
38
MOA of tetracyclines
transported into cells | prevents attachment of aminoacyl-tRNA to 30S ribosome subunits
39
how does resistance to tetracycline occur?
drug efflux pumps in bacteria--resistance to 1 tetracycline usually means resistance to all of them
40
uses of tetracyclines
unusual bacteria: rickettsia Lyme disease Chlamydia, mycoplasma, Ureaplasma
41
properties of tetracyclines
bind Ca2+ and inhibits tetracycline absorption
42
Side effects of tetracyclines
GI disturbances, enterocolitis Candida superinfection in colon photosensitization with rash teeth discoloration (avoid in children younger than 8, contraindicated in preg)
43
H pylori treatments
Clarithromycin and amoxicillin and omeprazole Metronidazole and tetracycline and bismuth subsalicylate and proton pump inhibitor
44
MOA of sulfonamides
competitive analog of p-aminobenzoic acid, precursor in folate synthesis
45
sulfonamide use
mostly combined with other antibacterials
46
treating uncomplicated cystitis (UTIs)
1st choice: TMP-SMX others: nitrofurantoin fosfomycin
47
reasons for antibac failure
``` drug choice host factors (abscess, host immune status important for finishing the job with static drugs, foreign bodies are hard to get at) ```
48
quinolone resistance in gram negatives
has gone up concurrently w/ its use
49
drugs used for MRSA
``` hospital acquired: vancomycin linezolid daptomycin tigecycline ``` ``` community: linezolid doxycycline, minocycline clindamycin TMP-SMX ```