Cell Wall Synthesis Antibiotics

Question 1

Beta-lactam

1. ) Mechanism
2. ) Cidal or static?
3. ) Adverse effects

Answer 1

1. ) Penicillin mimics D-Ala-D-Ala and irreversibly binds to transpeptidase-> inactivates enzyme-> no peptidoglycan cross-linking occurs-> cell lyses
2. ) Bactericidal
3. ) Non-toxic at grams/days dose. Side effects: Allergic reactions

ex: penicillin G-> acid labile; Beta-lactamase sensitive

Question 2

Beta-lactam: Amoxicillin

1. ) Mechanism and usage
2. ) Affected organisms
3. ) Adverse effects

Answer 2

1. ) Extened spectrum penicillins; Usage: UTIs, sinusitis, otitis, LRI
2. ) Acid stable. Greater acivitiy against Gram negative b/c of ability to penetrate outer membrane.
3. ) Adverse reactions

Question 3

Beta-lactam: Oxacillin, cloxacillin, dicloxacillin

1. ) Description
2. ) Affected organisms

Answer 3

1. ) anti-staphylococcal penicillins; Acid stable; Beta-lactamase resistant
2. ) Beta-lactamase producing strains of staph; Not suitable for enterocci, anaerobic bacteria, and gram negative rods/cocci

Question 4

Cephalosporins

1. ) Mechanism of action
2. ) Affected organism
3. ) Adverse effects

Answer 4

1.) Broad spectrum, ↑ resistance to β-lactamase
2.) Good against MRSA especially
1st gen – don’t penetrate CNS
2nd gen- no allergic cross-reactivity w/ penicillin
3rd gen - Ceftazidime + Beta-lactamase inhibitor(avibactam) =Avycaz
4th gen – penetrate CNS
3.) Hypersensitivity reactions- anaphylaxis; nephritis, granulocytopenia and hemolytic anemia; Candida superinfection

Question 5

Ceftolozane

1. ) Usage
2. ) class

Answer 5

1. ) Tx of gram negative bacteria that have become resistant to other drugs, **Pseudomonas infections; Complicated UTI’s; Complicated intra-abdominal infections
2. ) 5th Generation Cephalosporin
   * Ceftolozane/tazobactam = Zerabaxa

Question 6

Monobactams: Azetreonam

1. ) Mechanism of action
2. ) Affected organisms
3. ) Adverse reactions

Answer 6

1. ) Resistant to beta-lactamases
2. ) Active against Gram negative rods; does not bind transpeptidases of Gram postive or anerobic bacteria
3. ) No major toxicities and no cross reactivity w/ penicillin

Question 7

Carbapenems: Imipenem

1. ) Mechanism of action
2. ) Affected organism
3. ) Adverse effects

Answer 7

1. )Broad spectrum; given w/ Cilastatin – inhibitor of renal dehydropeptidase to increase half-life; imipenem is inactivated by dehydropeptisases in renal tubules
2. ) Mixed infections-+/-
3. ) GI issues, skin rashes, seizures if renal insuff.; cross-sensitivity in pts w/ penicillin allergies

Question 8

Beta-lactamase inhibitors: Clavulanic acid

1. ) Mechanism of action
2. ) Cidal/static & affected organisms
3. ) Adverse effects

Answer 8

1. )Binds to bacterial β-lactamases covalently, inactivates them irreversibly; use w/ beta-lactam antibiotics to extend 1/2 lives
2. ) Neither- no Abx activity
3. ) N/A

Question 9

Betalactamase inhibitor: Avibactam

1. ) Description
2. ) Differentiates this drug from others of its class

Answer 9

1. ) Broader spectrum beta-lactamases inhibitor -> works on class A and C enzymes and some D enzymes
2. ) The inhibitor does not contain a beta-lactam core

Question 10

Vancomycin

1. ) Mechanism of action
2. ) Affected organism
3. ) Side effects

Answer 10

1. ) Drug binds to D-Ala-D-Ala nascent peptide pentapeptide -> binding interferes w/ transglycosylation & transpeptidation rxn -> weakend peptidoglycan layer makes cell susceptible to lysis
2. )Bacteriocidal; Gram positive – good for MRSA
3. ) Minor, phlebitis @ injection site, chills, fever, rare ototoxicity and nephrotoxicity

Question 11

Daptomycin

1. ) Mechanism of action
2. ) Affected organisms

Answer 11

1. ) Bacterial cell membrane pore former -> K+ loss w/o cell rupture + no toxin release
2. ) Gram positive skin/soft tissue infections; MRSA

Question 12

Polymyxins

1. ) Mechanism of action
2. ) Affected organisms

Answer 12

1. ) Lipopeptides that bind outer membrane of Gram neg bacteria -> permeability of both inner and outer membrane (perforations, not pores)
2. ) Gram negatives

Question 13

Fosfomycin

1. ) Mechanism of action
2. ) Utility

Answer 13

1. )Inhibits 1st committed step in cell wall synthesis (blocks NAG-UDP -> NAM-UDP) via binding covalently to active site cysteine of MurA enzyme
2. ) Active against Gram +/-; Syngergistic when combined w/ other antibiotics; Uncomplicated UTIs

Question 14

Bacitracin

1. ) Mechanism of action
2. ) Utility
3. ) Adverse effects

Answer 14

1. )Inhibits 2nd step: inhibits lipid phosphatase -> dephosphorylates lipid carrier of peptidoglycan subunit -> can’t flip NAM out
2. ) Gram positive
3. ) Only used topically b/c nephrotoxic; allergic reactions

Question 15

D-cycloserine

1. ) Mechanism of action
2. ) Utility
3. ) Adverse effects

Answer 15

1. ) Competitively inhibits alanine racemase and D-alanine ligase
2. ) Used in combination with other antibiotics to treat TB
3. ) 2nd line drugs: Dose related CNS toxicities