Micro - Cell Wall Synthesis Inhibitors

Question 1

Penicillin G, V mech:

Answer 1

Penicillin G (IV/IM); Penicillin V (oral)
Bind penicillin-binding proteins (transpeptidases).
Block transpeptidase cross-linking of peptidoglycan. 
Activate autolytic enzymes

Question 2

Penicillin uses:

Answer 2

Mostly used for gram + organisms (S. pneumo, S. pyogenes, Actinomyces). Also used for N. meningitidis and T. pallidum.
Bactericidal for gram+ cocci, gram+ rods, gram - cocci, and spirochetes
Penicillinase sensitive

Question 3

Penicillin tox:

Answer 3

Hypersensitivity reactions, hemolytic anemia

Question 4

Penicillin resistance:

Answer 4

Penicillinase in bacteria (a type of beta-lactamase) cleaves beta-lactam ring.
Penicillinase can be induced by presence of beta-lactam ring.

Question 5

Ampicillin, Amoxicillin (Aminopenicillins) mech:

Answer 5

Same as penicillin, but wider spectrum: Binds penicillin-binding proteins (transpeptidases)
Block transpeptidase cross-linking of peptidoglycan.
Combine with Clavulanic acid to protect against beta-lactamase

Question 6

Aminopenicillin mnemonic:

Answer 6

AMinoPenicillins are AMPed-up penicillin.

AmOxicillin has greater Oral bioavailability than ampicillin. Food doesn’t interfere with Amox

Question 7

Aminopenicillin uses:

Answer 7

Extended spectrum penicillin - Haemophilus influenzae, E. Coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci, Moraxella catarrhalis, Enterococcus faecalis

Ampicillin/Amoxicillin HELPSS ME kill enterococci

Question 8

Aminopenicillin tox:

Answer 8

Hypersensitivity reactions; rash (1-28 days, not hypersensitivity rxn –> if used for pts with mono)
Pseudomembranous colitis
Superinfections

Question 9

Aminopenicillin MOR:

Answer 9

Penicillinase in bacteria (type of beta-lactamase) cleaves beta-lactam ring.

Question 10

Penicillinase-resistant Penicillins:

Answer 10

Oxacillin, Nafcillin, Dicloxacillin, Methicillin (not used clinically)

Question 11

Penicillinase-resistant Penicillins mech:

Answer 11

Same as penicillin: Binds PBP (transpeptidases). Blocks transpeptidase cross-linking of peptidoglycan. Activates autolytic enzymes.
Narrow spectrum
Penicillinase-resistant because bulky R group blocks access of beta-lactamase to beta-lactam ring

Question 12

Penicillinase-resistant Penicillins uses:

Answer 12

S. aureus (except MRSA; resistant because of altered penicillin-binding protein target site)
“Use naf for staph”

Question 13

Penicillinase-resistant Penicillins tox:

Answer 13

Hypersensitivity rxns, interstitial nephritis (Type IV hypersensitivity)

Question 14

Anti-Pseudomonals:

Answer 14

Ticarcillin, Piperacillin, Carbenicillin

Question 15

Anti-Pseudomonal mech:

Answer 15

Same as penicillin: Binds PBPs (transpeptidases) and blocks transpeptidase cross-linking of peptidoglycan. Activates autolytic enzymes.
Extended Spectrum

Question 16

Anti-Pseudomonal uses:

Answer 16

Pseudomonas spp. and gram - rods (Klebsiella); susceptible to penicillinase; use with beta-lactamase inhibitors

Question 17

Anti-Pseudomonal tox:

Answer 17

Hypersensitivity rxns

Ticarcillin: prolonged bleeding time; excess Na+ in dosage form may be problem for CHF or renal failure

Question 18

Beta-Lactamase Inhibitors:

Answer 18

CAST

Clavulanic Acid, Sulbactam, Tazobactam

Question 19

Beta-Lactamase Inhibitors: uses

Answer 19

Often added to penicillin antibiotics to protect the antibiotic from destruction by beta-lactamase (penicillinase).
Themselves have weak antibacterial activity
Not good inhibitors of inducible beta-lactamases (gram - rods)

Question 20

Penicillins do not penetrate well into:

Answer 20

Eye, prostate, BBB

In meningitis, BBB is disrupted –> penicillins pass into CSF

Question 21

Cephalosporins mech:

Answer 21

Beta-lactam drugs that inhibit cell wall synthesis but are LESS SUSCEPTIBLE to penicillnases.
Bactericidal.

Question 22

Cephalosporins: Organisms not covered

Answer 22

Organisms typically not covered are LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci
Exception: ceftaroline covers MRSA

Question 23

Cephalosporins 1st generation:

Answer 23

Cefazolin, Cephalexin
Gram+ cocci, Proteus mirabilis, E. coli, Klebsiella pneumoniae
1st gen: PEcK

Question 24

Cefazolin: main use

Answer 24

1st gen cephalosporin - used prior to surgery to prevent S. aureus wound infections

Question 25

Cephalosporins 2nd generation:

Answer 25

Cefoxitin, Cefaclor, Cefuroxime, Cefprozil
Gram+ cocci, Haemophilus influenzae, Enterobacter aerogenes, Neisseria spp., Proteus mirabilis, E. coli, Klebsiella pneumoniae, Serratia marcescens
2nd gen: HEN PEcKS

Question 26

Cephalosporins 3rd generation:

Answer 26

Ceftriaxone, Cefotaxime, Ceftazidime, Cefixime

Serious gram - infections resistant to other beta-lactams (Serratia, Pseudomonas, Hib, Neisseria)

Question 27

Ceftriaxone: main uses

Answer 27

meningitis and gonorrhea (single IM), disseminated Lyme dx

Question 28

Ceftazidime: main uses

Answer 28

Pseudomonas

Question 29

Cephalosporins 4th generation:

Answer 29

Cefepime

Increased activity against Pseudomonas and gram+ organisms

Question 30

Cephalosporins 5th generation:

Answer 30

Ceftaroline

Broad gram+ and gram - organism coverage, including MRSA, does not cover Pseudomonas

Question 31

Cephalosporins tox:

Answer 31

Hypersensitivity reactions (no skin tests!), Vitamin K deficiency (kill off vit-K producing bacteria in gut).
Low cross-reactivity with penicillins.
Autoimmune hemolytic anemia.
Increased nephrotoxicity of aminoglycosides.
Alcohol intolerance –> Disulfuram like reaction (buildup of acetaldehyde)

Question 32

Cefaclor tox:

Answer 32

most commonly associated with serum sickness

Question 33

Aztreonam: mech

Answer 33

A monobactam; resistant to beta-lactamases.
Prevents peptidoglycan cross-linking by binding to penicillin-binding protein 3. Synergistic with aminoglycosides. No cross-allergenicity with penicillins.

Question 34

Aztreonam: uses

Answer 34

Gram negative rods only - no activity against gram + or anaerobes. For penicillin-allergic pts and those with renal insufficiency who cannot tolerate aminoglycosides.

Question 35

Aztreonam: tox

Answer 35

Usually nontoxic; occasional GI upset

Question 36

Carbapenems:

Answer 36

Imipenem, meropenem, ertapenem, doripenem

Question 37

Carbapenem mech:

Answer 37

Disrupt bacterial cell wall synthesis. Good permeability with gram - and high affinity for PBP
Beta-lactamase resistant

Question 38

Imipenem: mech

Answer 38

Broad-spectrum, Beta-lactamase-resistant carbapenem. Always administered with Cilastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubules
With imipenem, “the kill is lastin’ with cilastatin.”

Question 39

Carbapenems: uses

Answer 39

Gram+ cocci, gram - rods, and anaerobes.
Wide spectrum, but significant side effects limit use to life-threatening infections or after other drugs have failed.
Meropenem has a decreased risk of seizures and is stable to dehydropeptidase I.

Question 40

Carbapenems: tox

Answer 40

GI distress, skin rash, and CNS toxicity (seizures) at high plasma levels
Allergies: those allergic to penicillin should be considered allergic to carbapenems

Question 41

Vancomycin: mech

Answer 41

IV, except when treating C. Diff (oral)
Inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors.
Bactericidal.

Question 42

Vancomycin: uses

Answer 42

Gram + only - serious, multidrug resistant organisms, including MRSA, enterococci, and C. diff
Penetrates CSF

Question 43

Vancomycin: tox

Answer 43

Well tolerated in general - but NOT trouble free. Nephrotoxicity, Ototoxicity, Thrombophlebitis, diffuse flushing - red man syndrome (can largely prevent by pretreatment with antihistamines and slow infusion rate)

Question 44

Vancomycin: MOR

Answer 44

Occurs in bacteria via amino acid modification of D-ala D-ala to D-ala D-lac.
“Pay back 2 D-alas (dollars) for VANdalizing (vancomycin).”