Antibiotics I - Med Micro Flashcards

1
Q

The role of Penicillin Binding Proteins and the Cell wall

A

PBPs are needed in order for cross linking and building the peptidoglycan cell wall. Act as transglycosylases and transpeptidases. Cell wal agents act on specific PBPs

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2
Q

transglycosylases

A

PBPs act as these in joining NAG and NAM

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3
Q

transpeptidases

A

PBPs act as these in the cross linking of the peptidoglycan sheets- it will cleave off the final D-ala residue for cross linking to occur

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4
Q

B Lactam Antibiotics AND the Classes

A

Are B Lactam Cell Wall Agents, because they inhibit cell wall synthesis. They consist of Penicillins, Cephalosporins, Carbapenems and Monobactams ( Aztreonam)

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5
Q

Pathways utilized by B lactam antibiotics into the outer membrane of gram negative bacteria

A
  1. a lipid mediated pathway for hydrophobic antibiotics 2. general diffusion porins for hydrophilic antibiotics
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6
Q

What are Penicillins and what do they do?

A

are B lactam based compounds, have a 4 membered B lactam ring and a 5 membered thiazolidine ring its fused to.

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7
Q

Features of the B lactam ring

A
  1. it binds to and inhibits transpeptidases (PBPs), 2. it is a substrate for B lactamases 3. it is a very unstable structure
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8
Q

What are Cephalosporins and what do they do?

A

are described in context of generations, Are structurally similar to penicillins. Have increasing activity to various gram negative bacteria. Higher generations are less susceptible to Beta lactamases

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9
Q

The other Inhibitors of Cell Wall Synthesis

A

Carbapenem and Monobactams

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10
Q

How do the Beta Lactam Antibiotics work?

A

B Lactam Antibiotics are structurally similar to the D-ala-D-ala residue so B lactam antibiotics react/bind to PBP proteins and inactivate them

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11
Q

How does the Bacteria FIGHT back? What’s in its arsenal?

A

B- lactamases, ESBLs (extended spectrum B lactamases), Amp C Beta Lactamases (IDBLs) and the Carbapenemases

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12
Q

What are the B Lactamases and how do they work?

A

Are bacterial enzymes that can inactivate the B Lactam antibiotics by hydrolyzing the B lactam bond and destroying the B Lactam ring. Are a form of resistance to the antibiotics. Can differ in their substrate profile

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13
Q

B Lactamase Production

A

May be constitutive- a constant basal level of the enzyme is produced at all times, not affected by external env’t or inducible - produced after exposure to certain antibiotics in its env’t

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14
Q

Activity of the B lactamase depends on

A

Depends on having a zinc or a serine at the active site to hydrolyze the B lactam ring

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15
Q

Different Classes of B lactamases

A
  1. Narrow Spectrum B Lactamases 2. Extended Spectrum Beta Lactamases (ESBLs) 3. AmpC production (IDBL) 4. Carbapenemase production (CRE)
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16
Q

Two ways to outsmart the Beta Lactamases

A
  1. Build a better drug resistant to the B Lactamases 2. Combine and antibiotic with an Inhibitor that resembles the Antibiotic - B Lactamases will preferentially bind irreversibly to to the Inhibitor ( Antibiotic look alike) and thus, the B Lactamases are out of the system.
17
Q

Extended spectrum Beta Lactamases

A

Are plasmid mediated B lactamases which hydrolyze penicillins, 3rd and 4th generation cephalosporins, and aztreonam.

18
Q

ESBLs are inhibited by and have no activity against

A

Inhibited by B lactamase inhibitors such as clavulanate, tazobactam and subactam and have no activity to the carbapenases (imipenem) or cephamycins (cefoxitin or cefotetan)

19
Q

what are the most effective agents against ESBL producing Enterobacteriacae

A

Carbapenems ( imipenem, ertapenem, meropenem)

20
Q

General Summary on Tests used to detect ESBL producing organisms

A

Are screening and confirmatory tests that are used for isolates of specific organisms, E.Coli, Klebsiella pneumoniae, K. oxytoca and Proteus mirabilis and are based on reduced sensitivity to indicator drugs

21
Q

what are the tests to detect ESBL producers?

A
  1. double disc synergy 2. combination disk method 3. E-test
22
Q

Confirmatory Tests for ESBLs do

A

Indirectly detect the hydrolysis of indicator drugs

23
Q

How does the Double DisK Synergy test work?

A

lll

24
Q

How does the Combination Disk Method work?

A

ll

25
Q

penicillinase resistant penicillin and 2 examples, also what organism is resistant to these kinds of penicillins?

A

are antibiotics not inactivated by penicillinase or B lactamase produced by bacteria. Two examples - Methicillin and oxacillin. MRSA is resistant to these drugs.

26
Q

penicillin and cephalosporins work the same way by

A

inhibiting the cross linking of peptidoglycan by binding to and inactivating the PBPs

27
Q

a patients is allergic to Penicillin

A

give them Cephalosporins

28
Q

1st generation cephalosporins are best at treating

A

gram positive bacteria like Staph/Strep

29
Q

3rd and 4th generation cephalosporins are best at

A

being resistant to the action of many beta Lactamases. Active against most gram negative bacteria including Pseudomonas

30
Q

2nd generation cephalosporins have

A

good activity against Haemophilus influenza

31
Q

An agent that inhibits cell wall synthesis outside of the Beta Lactams

A

Glycopeptides (Vancomyin) - these are effective against Gram positive organisms only, the gram negatives are resistant. Act by binding to D-alanyl D-alanine residues

32
Q

Inhibitors of protein synthesis

A

A.T.M. L.L.C –

Aminoglycosides, Tetracyclines, Macrolids, Lincosamides, Linezolid, Chloramphenicol

33
Q

Carbapenems

A

are a class of B Lactam antibiotics, with a broad spectrum of antimicrobial activity. they are highly resistant to most B lactamases including ESBL’s .

34
Q

what confers methicillin resistance in Staph Aureus

A

In S.aureus, methicillin resistance is conferred by the mecA gene, which encodes PBP2A, which has low affinity for B lactam antibiotics…
With MRSA, Methicillin, oxacilin, nafcillin, and Beta Lactamase inhibitors will not work.

35
Q

pharmacodynamics refers to

A

the effects of the drug on the bacteria

36
Q

pharmacokinetics refers to

A

how the body takes in the drug

37
Q

MIC is what

A

the lowest antibiotic concentration that is inhibitory to 90% of all isolates.

38
Q

Amp C Beta Lactamases

A

“cephalosporinases” these hydrolyze all beta lacatam antibiotics except carbapenems. Amp C gene is in most species except Klebsiella, E.Coli, and Protues.

39
Q

Amp C gene is

A

present in many bacteria it is hardwired, its inducible resistance requires long term extended therapy before Amp c is produced.