Antibiotic Resistance Flashcards
Revision
When does Natural Resistance occur?
Target not present
- Mycoplasma sp have no cell wall
Target not accessible
- e.g. OM Gram-negative prevents vancomycin entry
Developmetnal structure/ state
- e.g. C.difficile spore
- Persistor cells and biofilms more resistant
Metabolsim
- Metronidazile uptake and action require anaerobic conditions
What are Biofilms?
Organisim behaving as part of multi-cellular community.
3D structure.
Contains interfaces.
Spatial heterogeneity.
Permeated by water channels.
Organisms resistant to antimicrobial agents and host defences.
(>90% of microbes exist in communities)
What are Persistor Cells?
Tolerance - not resistance Metabolically inert - very slow growth - Dormant or non-dividing Subpopulation of cells - transient state - Planktonic and biofilm populations - Enriched in biofilms
What is Resistance and how does is occur?
(Drug is on longer active against entire population if cells)
The process of resistance is where there is variation that is selected for and that leads to the evolution of a species.
How does genetic variation occur through genetic variation?
Mutation
- Rapid bacterial growth and multiplication increase the chances of genetic mutations occurring
- Failure in accurate replication of the bacterial DNA
- Leads to new variants of the organism
- Many fail to survive
- Rare stains may be more successful
How does Selective pressure lead to evolution of resistance to antibiotics?
Highest outpatient use of penicillin correlates with highest frequency of resistant bacteria.
Variation -> Selective pressure -> Evolution resistance -> Gene transfer Spread and variation
How does clinical resistance arise and what is the difference between cross resistance and multiple resistance?
(Principles and Definitions)
Clinical resistance.
Resistance can arise by mutation or by gene transfer
- e.g. acquisition of a plasmid
Resistance provides a selective advantage.
Resistance can result from single or multiple steps
Cross resistance vs multiple resistance
- Cross resistance - Single mechanism
(closely related antibiotics)
-Multiple resistance - Multiple mechanisms
(Unrelated antibiotics)
What are the Antimicrobial Drug Resistance Mechanisms?
Altered permeability
- Altered influx (reduced OmpF (Quinoones))
- Active efflux (Energy dependent pump e.g. tetracycline)
Inactivation
- Beta-lactamase (Extended spectrum Beta-lactamase (ESBL)) Chloramphenicol acetyl transeferase.
what are examples of different types of Beta-lactamase (large family and comple classification?
Penicilinase
- include clavulanic acid sensitive and insensitive
Cephalosporinase
- Include clavulanic acid sensitive and insensitive.
Beta-lactamases (Classified as Group 1,2, and 3)
What are different types of Beta-lactamase?
Penicillinase
- resistance to the early penicillins such as amoxicillin
- Largely Gram-positive distribution.
Extended spectrum beta-lactamase (“ESBL”)
- resitance to all the penicillins
- Extends to 3rd generation cephalosporins and monobactams.
Carbapenemase (“CPE”)
- Serine based and metalloenzyme based
- resistance to all the penicillins, all cephalosporins and the carbapenems
- Carbapenens, such as meropenem, were considered “antibiotics of last resort”
What is Metalloenzyme (or metallo b-lactamases)?
New Delhi Metallo Beta-lactamase 1 (NDM-1)
- Carbapenamase
- New Delhi 2008 Klebsiella pneumoniae
- Gram -ves principally E.coli and K.pneumoniae
- By 2010 infections in Uk, USA and Japan plus other organisms e.g. Acinetobacter
- UK cases resistant to b-lactams, fluroquinolones and aminoglycosides
- Last antibiotic treatment polistin
- Old 1949
- Targets outer membrane GM -ves
- IV Dosing difficult
What are the antimicrobial drug resistance mechanisms?
Altered Target Site
- Strep aa change in S12 subunit of 30S
- Eryth ethylation of 25S subunit of 50S
- Penicillin altered/new PBP (staph PBP2)
- Methicilin Resistant S.aureus MRSA
(Flucloxacilin replaced Methicillin. MRSA means resistance to Flucoxaillin).
Altered target Site
- Strep aa change in S12 subunit of 30S
- Eryth methylation of 25S subunit of 50S
- Penecillin altered/ new PBP (staph PBP2)
- Methicillin Resistant S. aureus MRSA
- Vancomycin; cell wall altered Depsipeptide D-alanyl-D-lactate
Replacement of a sensitive pathway
- Acquisition of a resistant enzyme
= Sulfonamides, trimethoprim
What is the 5 year Antimicrobial resistance strategy?
“Modern medical practice relies on the widespread
availability of effective antimicrobials to prevent
and treat infections in humans”
• “Resistance to all antimicrobials, including antivirals
and antifungals, is increasing, but of greatest
concern is the rapid development of bacterial
resistance to antibiotics.
• If the number of hard-to-treat infections continues
to grow, then it will become increasingly difficult to
control infection in a range of routine medical care
settings”
What are the different types of horizontal gene transfer between bacteria?
Bacterial transformation (Natural competence) Bacterial transduction (Bacteriophage) Bacterial conjugation (Sex pili)
What is colistin and what is it’s role?
- Polymxin antibiotic
- Polycationic molecule that interacts with outer membrane of Gram -ve bacteria
- Nephrotoxic given by injection
- Last line of treatment for NDM1 resistant bacteria
- MCR-1 mutation confers resistance
- Gene initially identified on chromosome
- Identified in 20% of raw meat samples tested & 16 patients
- New feature found on conjugative plasmid
- Evidence of spread in Laos and Malaysia
