Therapeutic Antimicrobials II Flashcards Preview

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Flashcards in Therapeutic Antimicrobials II Deck (16)
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1

describe the inhibitors of peptidoglycan/cell wall synthesis 

B-lactams

  • includes the groups: penicillin, cephalosporins, monobactams and carbapenems
  • all are active only on growing cells

2

summarize the mechanism of action of B-lactam antibiotics

  • antibiotic binds to bacterial Pencillin Binding Proteins (PBPs)
    • bacterial enzymes normally involved in cross-linking of cell wall
  • transpeptidation blocked
    • normal process in transpeptidation:
      • linkage of terminal glycine of pentaglycine bridge to fourth pentapeptide (D-alanine)
      • hydrolysis of terminal D-alanine generates necessary energy for the process
  • active cell wall synthesis necessary for action
    • metabolically inactive or very slow growing = no or reduced effect respectively
  • activation of bacterial autolytic enzymes/removal of autolysin inhibitor
  • result = bacterial cell lysis

3

describe the inhibitors of nucleic acid synthesis

quinolones & fluoroquinolones

  • analogs of nalidixic acid; quinolone or derived ring
    • inhibitors of topoisomerase IV (gyrase homolog)
      • blocks DNA supercoiling
    • fluoroquinolone = modification of original structure with different side chain substitutions 

4

name the medically important resistant bacteria

  • MRSA
    • Methicillin/Multiple Resistance Staphylococcus aureus
  • VRE
    • Vancomycin Resistant Enterococci
  • KPCs
    • Klebsiella pneumoniae Carbapenemases
  • ESBL producers
    • extended spectrium B-lactamases producers
  • Multidrug resistant (MDR) Mycobacterium tuberculosis

5

describe inherent vs acquired resistance

  • inherent resistance
    • natural absence of tatget for drug to act against
      • mycoplasmas lack cell wall -> resistant to penicillin
      • Enterococci lack folic acid synthesis pathway -> resistant to SMX-TMP
    • structural restriction
      • outer membrane (G-ve) blocks antibiotic access
  • acquired resistance: via genetic diversity
    • transfer of resistance genes (plasmids, conjugation, etc.)
    • random mutation (single > multiple)

6

give example of inherent resistance

7

summarize antibiotic resistance mechanisms

8

describe the mechanism of altered uptake

  • altered uptake prevents intracellular accumulation of antibiotic to therapeutic levels
  • often involves efflux pumps
    • can be antibiotic-induced
    • frequently encoded by mobile genetic elements
  • membrane-located transport proteins
  • present in Gram+ve and -ve
  • can be:
    • specific for one substrate or
    • range of dissimilar classes (multiple antibiotics)

9

describe the mechanism of altered target and give an example 

change in structure of bacterial enzyme/target retains function but make it less able to e.g. bind the antibiotic

  • example: mecA gene
  • possessed by some species of S. aureus and S. pnuemoniae
  • encodes for Penicillin Binding Protein 2a (PBP2a) = a modified transpeptidase
    • significantly lower binding affinity for B-lactam antibiotics
  • impact: bacteria able to continue transpeptidation in presence of the antibiotic

10

describe the mechanism of antibiotic inactivation by secreted enzymes

  • bacterial hydrolytic enzymes that cleave the antibiotic
  • e.g. B-lactamases
  • convert active --> inactive antibiotic
  • constitutive or inducible
  • over 100 B-lactamases indentified
    • TEM B-lactamases (G-ve) are most common
    • range from broad --> specific
  • partial solution: give antibiotic plus a B-lactamase inhibitor (e.g. Clavulanic acid)

11

describe ESBLs

  • extended-spectrium Beta-lactamases (ESBLs): confer resistance to:
    • all B-lactam antibiotics
      • except cephamycines and carbapenems
    • associated with high therapeutic failure and mortality rates of at least 50% 
    • frequently to many other classes of antibiotics, including aminoglycosides and fluoroquinolones
  • main producers are members of Enterobacteriacae, particularly:
    • E. coli
    • Klebsiella species 

12

describe the risk factors for ESBL exposure

13

describe the carbapenemases (CPEs)

  • Carbapenemases - produced by some Enterobacteriaceae
    • specific B-lactamases that target Carbapenem group of antibiotics
      • usually carbapenem antibiotics are relatively unaffected by B-lactamases
  • e.g. MDR and XDR Mycobacterium tuberculosis 
  • impacts include:
    • increased cost in treatment
    • increased duration of treatment and hospital stay (costs $$)
    • need to use drugs with lower selective toxicity increases side effects 

14

describe the Kirby-Bauer sensitivity testing (disk diffusion technique)

Kirby Bauer tells you which antibiotic at which concentrations are effective

15

describe establishing minimum inhibitory concentration (MIC)

16

describe an antibiogram

  • report of susceptibility profiles of isolates from patients across an institution to various antibiotics
  • usually expressed as % susceptible
  • produced and published annually
  • use:
    • guides treatment in advance of individual susceptibility results
    • helps institutions/regions determine & track their susceptibility trends