Cell-Wall Antibiotics

Question 1

All cell-wall synthesis inhibitors are?

Answer 1

Bactericidal

Question 2

Where is the weakest bond in a Beta-LACTAM?

Answer 2

Between the Nitrogen and Carbonyl Group (site of Beta-Lactamases)

Question 3

Mechanism of action of ALL LACTAMS

Answer 3

1. Bind PBPs 2. Inhibit transpeptidation 3. Inhibit cross-linking (final step in cell-wall synthesis)

Question 4

Mechanism of resistance to ALL LACTAMS

Answer 4

1. Beta-Lactamases
2. Structural change in PBPs
3. Change in porin structure (only Gram -)

Question 5

How is MRSA resistant?

Answer 5

Structural change in PBPs (D.O.C. = Vancomycin)

Question 6

How is Pseudomonas resistant?

Answer 6

Change in porin structure

Question 7

Narrow Spectrum, Beta-Lactamase Sensitive

Answer 7

Penicillin G (IV) and Penicillin V (oral)

Good for Treponema pallidum (spirochete)

Question 8

Very Narrow Spectrum, Beta-Lactamase Resistant

Answer 8

Nafcillin, Methicillin, Oxacillin

Question 9

Treat what with Nafcillin, Methicillin, or Oxacillin?

Answer 9

Sort of a trick question…MSSA is NEVER treated with Methicillin (use Nafcillin instead)

Methicillin is only good, in the lab, for determining if a strain is sensitive (MSSA) or resistant (MRSA)

Question 10

Broad spectrum, Aminopenicillins, Beta-Lactamase Sensitive

Answer 10

Ampicillin (IV) and Amoxicillin (Oral)

Question 11

Extended spectrum, Antipseudomonal, Beta-Lectamase Sensitive

Answer 11

Ticarcillin, Piperacillin, Azlocillin, Carbenicillin

(increased activity againt gram - rods, including Pseudomonas)

Question 12

Clavulanic acid, Sulbactam, and Tazobactam

Answer 12

“Suicide Inhibitors”

Used in combination with Penicillins. Beta-Lactamase metabolizes them to a product that inhibits itself (i.e., Beta-Lactamase Inhibitors)

Clavulanic = Oral

Sulbactam = IV

Question 13

How are Nafcillin and Oxacillin eliminated?

Answer 13

In bile (all other drugs are eliminated via tubular secretion)

Question 14

Side effects of Penicillins

Answer 14

1. Hypersensitivity
2. GI distress (killing exogenous flora in the gut)

*Jarisch-Herxheimer reaction in treatment of syphilis

Question 15

Mechanism of action/resistance of Cephalosporins

Answer 15

Identical to penicillins

(Bind PBPs, Inhibit Transpeptidation, Inhibit Cross-Linking)

[Beta-Lactamases, Change in PBPs, Change in Porin Structure]

Question 16

Organisms not covered by cephalosporins

Answer 16

“LAME”

Listeria, Atypicals (e.g., chlamydia, mycoplasma, urea),

MRSA, and Enterococci

Treat L with amoxicillin, A with macrolides, M with vancomycin, and E with amoxicillin

Question 17

Ampicillin and Amoxicillin are used to treat what?

Answer 17

H.E.E.L.P.S.S

H. Influenza, E. Coli, Enterobacter, Listeria, Proteus, Salmonella, Shigella

Borrelia burgdorferi (Lyme disease)

NOTE: giving ampicillin/amoxicillin to someone with mono will result in a generalized rash (patient is not allergic, it is a consequence of the EBV interaction)

Question 18

First generation cephalosporins

Answer 18

Cefazolin and Cephalexin (+ anything with “ph”)

Question 19

What is Cefazolin used for?

Answer 19

PEcK

Proteus, E. Coli, Klebsiella

COMMON USE in SURGICAL PROPHYLAXIS (long duration of action)

Question 20

What is Ticarcillin used for?

Answer 20

Increased activity against gram (-) rods, including Pseudomonas

Usually combined with Tazobactam

Question 21

Second generation cephalosporins

Answer 21

Cefoxitin, Cefotetan, Cefaclor, and Cefuroxime

HENS PEcK

H. Influenza, Enterobacter, Neisseria, Serratia, Proteus, E. Coli, Klebsiella

Pneumonic = Fur, Fox, Tea

Question 22

Third Generation Cephalosporins

Answer 22

Ceftriaxone (IM), Cefotaxime (parenteral), Cefidinir and Cefixime (oral),Ceftazidime

Question 23

Use of Ceftriaxone & Ceftazidime

Answer 23

Third generation cephalosporins:

Empiric management of MENINGITIS and SEPSIS

Note: Both Ceftazidime and Cefepime (4th generation) are useful against pseudomonas

*Ceftriaxone is used commonly in “real life” and will often NOT be the correct answer on tests (look for the drug that doesn’t cover everything, just specifically what the question asks for)

Question 24

Cefepime

Answer 24

Fourth Generation Cephalosporin:

Even wider spectrum, resistant to most beta-lactamases, enters CNS

IV

Question 25

Probenecid

Answer 25

Blocks active tubular secretion of penicillins and cephalosporins (i.e., prolongs their effects)

Question 26

Side effects of cephalosporins

Answer 26

1. Hypersensitivity: assume complete cross-allergenicity b/w individual cephalosporins and partial cross-allergenicity with penicillins (5%) 2. Positive Coombs test, but hemolysis is rare 3. Disulfiram-like effects (i.e., hangover) \*Most authorities recommend avoiding cephalosporins in patients allergic to penicillins

Question 27

Allergic to penicillin and infected with gram (+) organism

Answer 27

Consider macrolides

Question 28

Allergic to penicillin, infected with gram (-) organism

Answer 28

Consider **aztreonam**

Question 29

Mechanism of action for Imipenem, Meropenem, and Ertapenem (broad class = **Carbapenems**)

Answer 29

Same as penicillins and cephalosporins BUT resistant to Beta-Lactamases \*Imipenem is given w/ cilastatin (renal dehydropeptidase inhibitor) which inhibits metabolism to a nephrotoxic metabolite \*All drugs under renal elimination (decrease dose in renal dysfunction)

Question 30

What are **Carbapenems** commonly used for?

Answer 30

Empiric use in severe life-threatening nosocomial infections Gram (+) cocci, Gram (-) rods [including pseudomonas], and anaerobes NOT USEFUL AGAINST MRSA

Question 31

Side effects of "-penem's"

Answer 31

1. GI stress 2. Drug fever (partial cross-allergencity with penicillins) 3. **CNS effects**, including seizures in OD or renal dysfunction

Question 32

**Aztreonam**

Answer 32

Same MOA as penicillins and cephalosporins (binds PBP3) Resistant to Beta-Lactamases Monobactam IV drug active against gram (-) rods _NO CROSS-ALLERGENICITY_ W/ PENICILLINS OR CEPHALOSPORINS

Question 33

MOA for **Vancomycin**

Answer 33

NOT A LACTAM... 1. Binds at D-ala-D-ala muramyl pentapeptide 2. Sterically hinders transglycosylation rxns involved in elongation 3. Indirectly prevents transpeptidation \*DOES NOT interfere with PBPs

Question 34

Spectrum for **Vancomycin**

Answer 34

**MRSA** Enterococci Orally for C. Difficile (after metronidazole)

Question 35

Resistance to **Vancomycin**

Answer 35

1. VRSA and VRE 2. Change in muramyl pentapeptide target: D-ala-D-ala replaced w/ D-ala-D-lac

Question 36

Pharmacokinetics of **Vancomycin**

Answer 36

1. Used IV (orally for colitis b/c it is not absorbed) 2. Enters most tissues (e.g., bone), but not CNS 3. Eliminated by renal filtration

Question 37

Side effects of **Vancomycin**

Answer 37

**N.O.T. Red** 1. "**Red** man syndrome" (histamine release) 2. **O**totoxicity (permanent) 3. **N**ephrotoxicity (mild, but additive with other drugs) 4. **T**hrombophlebitis

Question 38

If a patient suffers from "red man syndrome," what are the nexts steps you need to take?

Answer 38

1. Give anti-histamines and discontinue vancomycin 2. After symptoms cease, deliver vancomycin at a lower dose * This is not considered an allergy and treatment can continue*

Question 39

Cell Wall Inhibitors that are effective against Pseudomonas

Answer 39

Cefepime and Ceftazidimine Aztreonam Carbapenems Ticarcillin, Piperacillin, Carbenicillin

Question 40

In general, what happens when you move from 1st generation cephalosporins to 4th generation?

Answer 40

Sacrifice gram (+) coverage for increased gram (-) coverage