Term
| What are the 4 major mechanisms of antibiotic resistance? |
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Definition
1) Enzymatic inactivation (Beta-lactamase)
2) Synthesis of substitute proteins (PBPs)
3) Alteration of Permeability (Porins)
4) Efflux pumps (Quinolone resistance in Pseudomonas spp.) |
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Term
| How is Beta-Lactamase-mediated antibiotic resistance achieved? |
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Definition
1) Many pathogens make Beta-lactamase (penicillinase in S. aureus), which hydrolyzes the beta-lactam ring of many antibiotics.
2) Hydrolyzed rings cannot bind PBPs (happens with Extended Specrum Beta-Lactamases (ESBLs) for 3rd and 4th generation Cephalosporins as well!) |
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Term
| Provide 4 examples of how Altered Targets can confer antibiotic resistance. |
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Definition
1) PBPs in beta-lactam resistance
2) Mutant peptidoglycan precursors in Vanocmycin-resistance (VRE).
3) DNA gyrase alterations in Quinolone resistance.
4) Ribosome alterations in Macrolide resistance |
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Term
| How does quinolone resistance develop (3 ways)? |
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Definition
1) Mutation of DNA gyrase prevents binding of quinolones.
2) Mutation in OprD Porin prevents Quinolones from entering Pseudomonas aeruginosa
3) Efflux pumps in Pseudomonas spp (remember, Levofloxacin and Ciprofoxacin treat Pseudomonas) |
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Term
| Which bacteria have exhibited PBP resistance? |
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Definition
Gram-positives: S. aureus, E. faecium and S. pneumoniae.
PBPs can't bind beta-lactams, and antibiotics fail |
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Term
| Which organism exhibits porin-mediated antibiotic resistance? |
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Definition
Pseudomonas aeruginosa.
Quinolones enter P. aeruginosa through OprD porin, and porin alterations that prevent this are selected for through antibiotic pressure. |
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Term
| What are two bacterial species that exhibit Efflux-pump mediated resistance? |
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Definition
1) Gram positive cocci with Macrolide resistance
2) Quinolone resistance in Pseudomonas spp. |
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Term
| How might Biofilms contribute to antibiotic resistance? |
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Definition
| Prevent drug access to pathogens living within them |
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Term
| How does antimicrobial resistance occur in E. coli? |
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Definition
1) Causes cystitis, pyelonephritis and bacteremia as nosocomal infections.
2) Simple beta-lactamase-mediated resistance to amoxicillin and often resistant to TMP/SMZ.
3) ESBLs are increasing |
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Term
| How does antimicrobial resistance occur in Enterococci? |
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Definition
1) 3rd most common nosocomal infection in adults causing intrabdominal infections, UTIs and bacteremia
2) Naturally resistant- only susceptible to Ampicillin and Vancomycin, with ampicillin resistance becoming increasingly common |
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Term
| How does antimicrobial resistance occur in S. aureus? |
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Definition
#1 nosocomal pathogen causing skin, wound infection, bacteremia and hospital-acquired pneumonia
1) Community Aquired MRSA often susceptible to TMP/SMZ
2) Vancomycin most often used, but VRE transposon contributes to Staph resistance.
** MAJOR PROBLEM IN HEALTHY CHILDREN** |
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Term
| What is "Glycopeptide Resistance" in S. aureus? |
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Definition
- Reduced sensitivity to Vancomycin
- Some evidence of VRE-transposon in isolates for PA. |
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Term
| How does antimicrobial resistance occur in Streptococcus pneumoniae? What are the major risk factors? |
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Definition
- Frequent cause of bacteremia and CA-pneumonia, accounting for 30-50% of acute otitis media and bacterial sinusitis
1) Altered PBP leading to multiply-resistant strains
2) Most at risk are age < 2 years, daycare and recent treatment with antibiotic. |
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Term
| How does antimicrobial resistance occur in Group A streptococci? |
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Definition
1) Common cause of pharyngitis and skin infection in children
2) Macrolide resistance in GAS involving ribosomal methylation (target modification) and Macrolide efflux pump |
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Term
| What is the clinical importance of the NDM-1 carbapenemase gene? |
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Definition
Multiple resistance genes and mobility!
- discovered in isolates of K. pneumoniae
- Metallo-beta-lactamase/carbapenemase located on large resistance containing genetic element coding for multiple classes of resistance.
- Shown to be transferable to to multiple GNR species raising worry about "pan-resistance." |
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Term
| Why might a mutation in the 23s ribosome be of clinical importance in selecting antibiotic treatment? |
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Definition
| This is the target of Macrolides (Azithromycin and Clarithromycin) |
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Term
| How does macrolide resistance develop (2 ways) |
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Definition
1) Altered target when 23s ribosome is mutated.
2) Efflux pump in gram + cocci such as Strep, Enterococci and Staph. |
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Term
| What are the unique genetics of Healthy Children suffering from MRSA, as compared to HA-MRSA? |
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Definition
| 10 SCCMec IV and Panton-Valentine Leukocidin (easier to treat) |
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Term
| What is the different between VISA, HVISA and VRSA glycopeptide resistance in S. aureus? |
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Definition
VISA= Thicken cell wall (D-ala:D-ala) prevents vancomycin binding.
HVISA= Thickened cell wall but variable
VRSA- Plasmid transfer from enterococci (get VRE) |
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Term
| How has resistance to Acinetobacter emerged? |
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Definition
| Dissemination of carbapenemase enzymes. |
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