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ID Review > B&B Beta Lactams > Flashcards

B&B Beta Lactams Flashcards

1
Q

Penicillin consists

A 
Beta Lactam Ring
Thiazolidine Ring (only found in penicillin)
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2
Q

Carbapenems, Aztreonam, Cephalosporins

A

Beta Lactam Antibiotics
Have similar MOA to penicillin
Bind transpeptidases (penicillin-binding proteins)
Prevents peptidoglycan crosslinking
Autolysis
Usually bacteriocidal
Potentially susceptible to beta lactamase enzymes (because contain beta lactamase ring)

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3
Q

Carbapenems

A

Imipenem, Meropenem, Ertapenem, Doripenem

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4
Q

Carbapenems are

A

Beta-lactams (not penicillins b/c not attached to thiazoladine ring)
Resistant to cleavage by most beta-lactamase

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5
Q

Extended Spectrum Beta Lactamase (ESBL)

A 
Plasmid-mediated bacterial enzymes
Confer resistance to most beta-lactam antibiotics:
-Penicillin
-Cephalosporins
-Aztreonam
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6
Q

Where are extended spectrum beta lactamase (ESBL) enzymes found?

A

Gram-negative bacteria

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7
Q

Gram-negative bacteria

A 
Pseudomonas
Klebsiella
E. Coli
Enterobacter
Salmonella
Serratia
Shigella
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8
Q

Carbapenems

A

Impenem, Meropenem, Etrapenem, Doripenem

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9
Q

What is the drug of choice for ESBL bacteria?

A 
Carbapenems
Broad spectrum:
-Gram (+)
-Gram (-) including pseudomonas, enterobacter
-Anaerobes including B. fragilis
Used in hospitalized patients
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10
Q

First commercially available Carbapenem

A 
Imipenem
Metabolized in kidneys
-Loss of antibacterial effect
-Nephrotoxic metabolites
Proximal tubule enzyme: dehydropeptidase I
Given with cilastatin (enzyme inhibitor)
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11
Q

Carbapenem S/E

A

N/V/D

Skin rash

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12
Q

Carbapenem S/E with high doses or renal failure

A

Neurotoxicity

  • Seizures due to inhibition of GABA receptors
  • Lower risk with Meropenem
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13
Q

Aztreonam

A

Monobactum: Beta-lactum ring not fused to another ring

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14
Q

Aztreonam MOA

A 
Binds only to penicillin-binding protein 3 (PBP-3)
-Found in gram (-) bacteria
-Prevents cross-linking of peptidoglycan
-Bactericidal
Limited susceptibility to beta-lactamase
-Some resistance in ESBL bacteria
Only active against gram (-) bacteria
-Does not bind PBP of gram (+) bacteria
-No activity against gram (+) or anaerobes
-Active against pseudomonas
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15
Q

Aztreonam is administered

A

IV (hospitalized patients)

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16
Q

Aztreonam is synergistic with

A

aminoglycosides

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17
Q

Does Aztreonam cross-react with penicillin allergies?

A

No. Can be used safely with penicillin allergy.

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18
Q

Cephalosporin

A

Similar structure to penicillin but not attached to thiazolidine

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19
Q

Cephalosporins are divided into

A

1st through 4th generations

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20
Q

1st generation Cephalosporins

A

Mostly gram positive coverage

21
Q

Successive generations of Cephalosporins

A

Gradually increased gram (-) coverage

22
Q

1st Generation Cephalosporins

A

Cefazolin, Cephalexin

23
Q

1st Generation Cephalosporins (Cefazolin and Cephalexin) were developed to treat

A

S. Aureus resistance to penicillin

24
Q

1st Generation Cephalosporins (Cefazolin and Cephalexin) covers

A

Many gram (+) including S. Aureus (but not MRSA

  • Stable against. S. Aureus beta lactamase
  • Does not cover enterococcus or listeria
  • Susceptible to gram (-) beta lactamases
25
Q

Main uses of 1st Generation Cephalosporins

A 
Surgical wound (skin) infections
Cefazolin give pre-op for prevention
26
Q

2nd Generation Cephalosporins

A

Cefuroxime, Cefutoxin, Cefotetan

  • Developed to treat amoxicillin-resistant infections
  • Increased affinity for gram (-) PBPs
  • More resistant to beta lactamase
  • Increased gram (-)
  • Increased anaerobic coverage (B. fragilis)
27
Q

Gram (-)

A

H. influenza, Enterobacter, Proteus

E. Coli, Klebsiella, Serratia, N. gonorrhea

28
Q

Cefuroxime (oral)

A

2nd generation Cephalosporin

  • Otitis media (S. pneumonia, H. flu)
  • UTI in kids (E. coli, no fluoroquinolones)
29
Q

Cefoxitin/Cefotetan (IV)

A

2nd generation Cephalosporin
PID (covers Neisseria, also give doxycycline for chlamydia)
Pre-op in kids with appendicitis
-E. Coli
-Covers gram negatives and some anaerobes
-Usually given with metronizadole

30
Q

3rd Generation Cephalosporins

A

Ceftriaxone
Cefotaxime
Ceftazidime

31
Q

3rd Generation Cephalosporins have

A

Broad gram (-) coverage

  • more resistance to beta lactamase enzymes
  • more gram (-) PBP affinity
32
Q

Ceftriaxone, Cefotaxime

A

3rd Generation Cephalosporins

Do not cover pseudomonas well

33
Q

Ceftazidime

A

3rd Generation Cephalosporins
Covers pseudomonas
-Used in hospitalized patients with gram (-) infections
-Sepsis/pneumonia

34
Q

3rd Generation Cephalosporins (Ceftriaxone, Cefotaxime, Ceftazidime): Most achieve good

A

CSF penetration (meningitis)

35
Q

Ceftriaxone

A 
3rd Generation Cephalosporin
Commonly used in N. gonorrhea
Commonly used in meningitis
-Active against S. pneumonia, N. meningitis
-Good CSF penetration
36
Q

4th Generation Cephalosporin

A 
Cefepime
Broad spectrum (>3rd generation drugs)
-MSSA
-Many gram (+)'s
-Many gram (-)'s including pseudomonas
Resistant to some ESBL
Hospitalized patients with gram (-) infections
37
Q

Sensitivity to beta-lactamase is based on

A

side chain

38
Q

Most sensitive to beta-lactamase

A

Penicillins

Exception: Antistaphylococcal penicillins can resist staph penicillinase

39
Q

Which Cephalosporin Generation is most resistant to beta-lactamase?

A

4th Generation

40
Q

Aztreonam is very resistant to beta-lactamase but

A

is resistant to gram (-) only

41
Q

Most resistant to beta-lactamase

A

Carbapenems most resistant to beta-lactamase so drug of choice in setting of ESBL bacteria

42
Q

What resistance mechanisms do bacteria use against Cephalosporins?

A

Modified penicillin binding proteins (PBPs)
Altered cell permeability
Beta lactamase

43
Q

Cephalosporins Adverse Effects

A

Same hypersensitivity reactions as penicillin

44
Q

Cephalosporins have some allergic cross-reactivity with

A

Penicillin

45
Q

Cephalosporins Adverse Reactions: Vitamin K Deficiency

A

Vitamin K1 from diet
Vitamin K2 from GI bacteria
Antibiotics reduce bacterial vitamin K production
Result: Increased INR and potential bleeding
Problem for patients on Warfarin
May be caused by any antibiotic

46
Q

What is a cause of bleeding that is unique to Cephalosporins?

A

Hypoprothrombinemia (reduced clotting factor levels)
Cefotetan and Cefazolin have NMTT side chains that inhibit epoxide reductase (similar to Warfarin)
-decrease in hepatic synthesis of clotting factors
-may prolong PT/INR
-Reversible with Vitamin K
-mostly reported in malnourished patients

47
Q

Cephalosporins can cause nephrotoxicity when combined with

A

aminoglycosides (well known cause of nephrotoxicity)

48
Q

What can occur when alcohol is consumed with Cephalosporin?

A

Disulfuram reaction
Alcohol consumption with cephalosporins
Warmth, flushing, sweating
Inhibition of acetaldehyde dehydrogenase
Accumulation of acetaldehyde occurs with certain side chain structures
Only occurs with Cefoperazone, Cefamandole, and Cefotetan

49
Q

Ethanol Metabolism

A

Ethanol is metabolized to acetaldehyde by alcohol dehydrogenase
Acetaldehyde is metabolized to acetate by aldehyde dehydrogenase
Cephalosporins inhibit aldehyde dehydrogenase
Increased levels of acetaldehyde makes alcoholics sick and not want to drink

ID Review (23 decks)

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