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Flashcards in 33. Cell Envelope Abx Deck (42):
1

what GN bug is usually hospital acquired with intrinsic resistance vs many of our Abx?

pseudomonas

2

principles for prescribing antibiotics? (there are 5)

1. what is the syndrome?
2. Is it a bacterial or viral cause?
3. what bacteria are important?
4. what antibiotics will be effective?
5. choose the most narrow-spectrum effective antibiotic considering allergies, potential toxicities, PK/PD

3

what are the categories of beta-lactam agents?

penicillins, cephalosporins, carbapenems, monobactams

4

synthesis of the peptidoglycan layer?

transglycosylase inserts/links new peptidoglycan monomers

transpeptidase (PBP) forms stabilizing peptide cross links (to create layers of chains/meshlike structure)

constantly remodeled - AUTOLYSINS break linkages to allow for addition of new monomers

5

antimicrobial agents that act on the cell wall are often bactericidal and kill what types of cells?

actively growing cells ONLY

6

antimicrobial agents that act on the cell wall kill in a _____-dependent fashion.

time

7

mechanism of action of penicillins?

B-lactam ring resembles D-ala-D-ala of peptidoglycan monomer and covalently (irreversibly) binds transpeptidase (PBP) so that it can't work, the cell wall is weakened, and the cell die by osmotic lysis. Autolysins continue to work.

8

PCNs mechanisms of resistance?

B-lactamases (hydrolyze B-lactam ring - eg penicillinases, cephalosporinases, carbepenemases, ESBL)

modified PBPs (like PBP2A encoded by MecA gene of MRSA)

9

PCNs PK/PD?

bactericidal, high TI, good tissue penetration

renally excreted (need DAF), short 1/2 life (freq dosing)

10

PCNs adverse effects?

hypersensitivity, acute interstitial nephritis, seizures at high dose

11

Penicillin G?

- IV, short 1/2 life
- resistance (penicillinase) common

- GN cocci only
- GP cocci/anaerobes
- spirochetes

use for Neisseria Meningitides, streptococci, dental abscess/human bites (GP oral anaerobes), syphilis

12

semi-synthetic PCNs?

nafcillin (IV) and dicloxacillin (PO)

bulky R group can't fit into many B-lactamases so increased activity vs S. aureus

still resistance due to altered PBP (PBP2A by MecA in MRSA)

GP only!

used for infections due to methicillin susceptible S. aureus

13

aminopenicillins

ampicillin (IV) & amoxicillin (PO)

slightly better spectrum of activity of PCN because some penetration through GN porins (effective vs. H.flu, E.coli but NOT pseudomonas)

still susceptible to B-lactamases

PCN adverse effects + GI distress, and pts w/mono who are tx w/amoxicillin will get maculopapular rash

use for CA HEENT and URIs (otitis media, epiglottists, sinusitis, pharyngitis, bronchitis), CA UTIs

14

ESBLs

extended-spectrum B-lactamases (mutations that enable them to degrade some Abx designed to resist B-lactamase cleavage)

15

B-lactamases are encoded where?

carried on plasmids, or encoded on chromosome. Txn constitutively OR induced by exposure to B-lactam Abx

16

B-lactamase inhibitors?

Resemble B-lactam Abx but have little or no antimicrobial activity alone – designed to bind to the B-lactamases so that they are hydrolyzed while B-lactam Abx remain intact and able to exert effect

Used in combo w/B-lactam Abx to extend spectrum of Abx to include B-lactamase-producing bacteria

super broad spectrum

use for Polymicrobial infections (skin/ST, intra-abd, odontogenic) or Empiric therapy if the causative agent is unknown (severe infection) *DO NOT USE WHEN NARROW SPECTRUM AGENS WOULD SUFFICE

17

ampicillin-sulbactam and amoxicillin-clavulonic acid

IV - amp-sulbactam
PO - amox-clavulanic acid

overcomes penicillinase resistance of S.aureus (not MRSA), use for B-lactamase producing GNs and anaerobes

18

piperacillin-tazobactam

vs S. aureus (not MRSA)

vs B-lactamase producing GNs (INCL PSEUDOMONAS) and anaerobes

19

cephalosporins mechanism of action and resistance?

B-lactam agents (more resistant to B-lactamases than PCN but resistance still significant)

intrinsic resistance (Pseudomonas, enterococci)
altereed membrane permeability (porins, pseudomonas)
altered PBPs (most afents not effective vs MRSA)
B-lactamases (AmpC and ESBLs)

20

adverse effects of cephalosporins?

minimal, well tolerated

hypersensitivity and cross-reactivity w/PCN allergy

21

cephalosporins spectrum of activity?

most GP but none vs enterococci and only one vs MRSA

increasing GN w/increasing generations

no anaerobic

22

cephalosporins 1st generation?

Cefazolin (IV q8h), cephalexin (PO)

excellent tx penetration

penetrate outer membrane of many GN bacilli

used for surgical prophylaxis, skin/soft tissue infections (limited/resistance due to MRSA so dicloxacillin often used instead)

23

2nd generation cephalosporins?

cefoxitin (IV)
cefotetan (PO)

increased GN activity

GOOD ANAEROBIC ACTIVITY - AN EXCEPTION

used for prophylaxis for intraabdominal surgery

24

3rd generation cephalosporins

ceftriaxone (IV, q24h) for CA pneumonia, meningitis, serious infections, and HA UTIs

ceftazidime (IV) for pseudomonas

excellent GN activity

excreted through biliary tract (no DAF needed unless liver failure)

25

4th generation cephalosporins

cefepime (IV)

highly resistant to B-lactamases

vs PSEUDOMONAS

use for serious or resistant infections

26

5th generation cephalosporins?

ceftaroline (IV)

overcomes MRSA resistance (binds to PBP2A) but susceptible to ESBLs

only ceph w/MRSA activity

not good vs Pseudomonas (similar to 3rd generation)

27

cephalosporin PLUS b-lactamase inhibitors?

ceftolozane/tazobactam
ceftazidime/avibactam

overcomes resistance to some B-lactamases (incl common ESBLs)

extend activity of cephalosporins

use for GN, incl pseudomonas

useful for resistant infections, UTI and intraabdominal infections

28

carbapenems?

imipenem (given w/cilastatin), meropenem, ertapenem (qd)

resistant to B-lactamases, but emergence of carbapenemases (incl KPC and metallo-B-lactamases) and multiple agents (islands), challenging to treat

bactericidal

IV, needs DAF

same adverse effects as PCN (cross-reactivity w/PCN allergy)

good vs GP (but ertapenem has no enterococci activity)

good vs GN incl pseudomonas and ESBL producers (but ertapenem has no activity vs pseudomonas or acinobacter)

good vs anaerobes

use EMPIRICALLY FOR SERIOUS INFECTION TREATMENT OR RESISTANT INFECTIONS

29

what % of reported PCN allergies are true allergies?

10-15

30

monobactams

aztreonam IV (needs DAF)

little hypersensitivty, but little potency, so use for pts w/TRUE PCN allergy

use for ALL GNs (incl pseudomonas and anaerobes) but NO GPs

31

Glycopeptides mechanism of action and resistance?

action: binds to terminal D-ala-D-ala so inibits transglycosylase and transpeptidase

resistance thanks to alteration of binding site (vanA changes to D-ala-D-lac, also vanB, vanC, vanD, and vanE genes)
OR thanks to thickened cell wall (decreased penetration: VISA = vancomycin intermediate susceptible staph aureus = GISA)

32

Glycopeptides PK/PD

vancomycin

bactericidal, IV (oral doesn't penetrate GI tract so use for C.diff)

renally excreted (needs DAF)

33

glycopeptides adverse effects, spectrum, and uses?

vancomycin

adverse effects: red man syndrome, nephrotoxicity (avoid other nephrotoxic agents), dose dependent ototoxicity (so MONITOR LEVELS)

spectrum of activity: GP only (incl MRSA) - GP anaerobes like c.diff

use: inferior to B-lactams, use for severe GP infectoins or when there are allergies to PCN OR oral for c.diff

34

cyclic lipopeptides?

daptomycin (IV, qd)

lipophilic tail inserts into cell membrane, K+ efflux, cell death without lysis

failures re: increased MIC to both vanc and daptomycin (thanks to thickened cell wall)

bactericidal

inhibited by pulmonary surfactant (don't use for pneumonia)

concentration dependent

adverse: GI distress, headache, eosinophillic pneymonia, elevated CPK/rhabdomyolysis w/BID dosing (monitor and avoid statins)

GP only (incl MRSA and VRE)

use for complicated GP infections (skin/st; bacteremia; endocarditis)

35

polymixins?

polymixin B and colistin

binds to LPS and disrupts outer membrane

IV only or topical

NEPHROTOXICITY, neurotoxicity, bronchospasm if inhaled

GN only (not proteus, serratia, or burkholderia)

use for serious resistant GN infections (when no other choice)

36

bacitracin

topical, GP only

37

fosfomycin

oral powder, GP and GN, use for UTI only

38

oral cell envelope Abx?

amoxicillin, dicloxicillin, cephalexin

39

GP ONLY cell envelope Abx?

nafcillin, vancomycin, daptomycin, bacitracin

40

GN only cell envelope Abx?

aztreonam, polymixins

41

adverse events:
PCN?
vancomycin?
daptomycin?

PCN: hypersensitivity
Vancomycin: red man, nephro (oto) toxicity
daptomycin: rhabdomyolysis, eosinophilic pna

42

cell envelope Abx vs MRSA?

ceftaroline, vancomycin, daptomycin