Antimicrobial Resistance Flashcards
Describe the difference between intrinsic and acquired antibiotic resistance and list ways a bacterium may acquire antibiotic resistance.
Intrinsic occurs “just because” of the natural properties of the bacteria (e.g. mycoplasma resistant to B-lactams because they don’t have a cell wall)
Acquired (genetic mutation or by acquisition):
- transformation, transduction, conjugation
Tolerance (are susceptible in vitro, but resist in vivo)
- Biofilm
- Metabolic bypass
- Anaerobic growth
- Stationary phase (non-dividing cells are sometimes not susceptible to drug)
Describe the broad categories of antibiotic resistance
Change the drug (β-lactamases)
Change the target (DNA gyrase mutations)
Prevent the two from meeting (porin mutation or inc efflux)
Describe how porins and efflux pumps can mediate antibiotic resistance and for which types of drugs and for which types of bacteria they are important.
Porin: G-, conduit for hydrophilic ABX; alter # or structure
Efflux: G+/-, get rid of substrate, some are specific for 1 drug, some for multi
Describe the structure and building of peptidoglycan as it relates to the mechanisms of activity of beta-lactams and vancomycin and how changes in peptidoglycan synthesis may result in resistance to these agents.
Precursor: 2 sugars, peptides, ends in 2xD-Alanine
Join sugars, transpeptidase (PBP) cross-links the two chains, and one D-Alanine is cleaved off
Describe how beta-lactams work and how bacteria can become resistant to beta-lactams.
They IRREVERSIBLY bind the PBPs (transpeptidases). They become resistant by:
- modifying the drug: beta-lactamases
- modifying the target: altered PBPs
Describe the spectrum of activity and list bacteria that may house “narrow-spectrum” beta-lactamases.
(Most of the bad beta-lactamases are GNR) Narrow spectrum = penicillinase - S. Aureus: bla (plasmid) - E-Coli: TEM-1 - Klebs pneum: SHV-1 (chromosome)
ALL 3 cleave PCN, Amp, & Amox
Define an ESBL, know which bacteria may express them, and what class of beta-lactam antibiotics may still be used against organisms housing an ESBL
Extended Spectrum BLs
Cleave all PCN and all Cephalosporins
Found in Klebsiella & E. Coli
Inhibited by Beta Lactamase inhibitors
Describe the regulation of ampC expression, know which bacteria house ampC in their chromosome, and know what class of beta-lactams may be used against organisms that have ampC.
Same spectrum as ESBL (when induced)
Inducible (with Amp and Cefazolin) or constitutive
When induced, resistant to Amp & Cefazolin
When constitutive, resistant to ALL PCN & CEPHALOSPORINS
Found in: Enterobacter, Pseudomonas
Treat w/ carbapenam
Describe KPC and NDM-1 and know which bacteria may house these resistance determinants.
Carbapenamase, resist to ALL Beta Lactams (including Carbapenam)
Found in Klebsiella & E. Coli
Describe the different ways that PBPs may be altered that lead to beta-lactam resistance and which bacteria may house altered PBPs.
Staph: mecA-PBP2a (MRSA)
- Cassette encodes for a transpeptidase can cross link w/o inhib by B-lactams
Strep pneumo: “mosaic” PBP
- Creates a mosaic PBP from pieces of DNA (likely from viridians strep)
Enterococ faec: PBP5
- Mutation or over-expression of PBP5 (low affinity PBP)
Describe the organisms and mechanisms associated with vancomycin resistance.
Enterococcus: VanA gene encode enzyme that changes terminal peptide: d-ala-d-ala –> d-ala-D-LAC (Vanc won’t recognize)
Staph Aureus (VISA): “hanging tails” of peptidoglycan in cell wall bind up the incoming Vanc –> doesn’t stop it at step 2
Gram (-) bugs are INTRINSICALLY resistant since Vanc can’t fit through porin
Distinguish the mechanisms of antibiotic resistance between Enterococcus faecium and Enterococus faecalis.
Faecium: RESISTS AMP because it alters PBP (also commonly VRE)
Faecalis: susceptible to Amp
Don’t need to know…
- Enterococcus faecium: mutations or over-expression of the PBP5 gene (low affinity PBP).
- E. faecalis: RARE, β-lactamase (narrow-spectrum), which can be inhibited by β-lactam inhibitors
Describe how quinolones work and how resistance to these agents develops.
Trap gyrase (Gram neg) or Topoisomerase IV (Gram pos) in a drug-enzyme-DNA complex –> DNA strand breaks
Resistance: Random pt mutations accumulate in QRDR region of GyrA/ParC –> fluoro resistance
Moxi hits Topo more than gyrase
Cipro hits gyrase more than topi
Levo is in the middle
If a sensitivity test shows R to one quin, it must have some mutation (it’s already halfway there to higher level resistance). So, don’t use fluoro!
Describe how macrolides work and how resistance to these agents develops.
Macrolides work by targeting the 23S rRNA of 50S ribosomal subunit; prevents chain elongation
msr gene is an efflux pump
erm gene dimethylates 23S rRNA, which also inhibits clindamycin
- can be i or c
- also inhibits clindamycin
Occurs in strep pneumonia & staph
Describe the mechanism of erm-mediated resistance and its relation to clindamycin resistance and understand how to interpret results from the D-test.
If bug has the erm gene, Erythromycin can induce resistance. This will also cause resistance to Clinda. However, when you do a sensitivity test, results will show Erythro = R and clinda = S if it’s erm or msr! So, you need a D test.
If it’s msr, you’ll only see a big ring around clinda (small amount near erythro)
If it’s erm, you’ll see a big ring around clinda, but part of it will be pushed in (looks like D). This means it’s erm.
If it’s erm, don’t give the pt clinda. Although it’s sensitive, that erm gene can easily become constitutive, then you’re screwed.
