Antibiotic Resistance Flashcards
Antibiotic resistance effects
Antibiotic resistance:
Increases mortality
challenges control of infectious diseases
threatens a return to the pre-antibiotic era
increases the costs of health care
jeopardizes health-care gains to society
Enterococci - define
large genus of lactic acid bacteria of the phylum Firmicutes.
gut vancomycin R+ (VREs)
G+ve origin - chickens ?
Acinetobacter - define
Acinetobacter is a genus of Gram-negative bacteria belonging to the wider class of Gammaproteobacteria
gut multiply resistant (can use carbapenems)
G-ve wound infections
hospital acquired infection
MRSA - define
Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium that causes infections in different parts of the body.
MRSA G+ve gut, wounds reserve drug - vancomycin
Mechanisms of antibiotic resistance - list with examples
Drug inactivation
e.g. beta-lactamase
Metabolic by-pass
e.g. vancomycin
D-ala-D-lac
Efflux pump
Overproduction
of target
Intrinsic
impermeability
Altered or new target if resistance shown
Altered or new target e.g. Ribosome Porin PBPs – peptidoglycan synthesis DNA gyrase RNA polymerase Mcr1 & colistin
Paths to Resistance - describe each
Directed at antibiotic itself -
Degrading the drug
Modifying the drug
New or Altered target
antibiotic no longer binds
e.g. PBPs - PBP2a in MRSA
Altered transport
Actively pumping drug out - efflux pump porins no longer influx drug
Metabolic by-pass
metabolic change D-ala-D-lac and vancomycin
Mechanisms of Resistance - types
Natural resistance
Genetic Mechanisms - acquired
Non-Genetic Mechanisms (growth phases)
Describe natural resistance
Drug must reach target - natural barriers, porins, export pump
G+ve peptidoglycan - highly porus - no barrier to diffusion
G-ves outer membrane - barrier resistance advantage
Porins single mutation - multiple resistance
Describe types of genetic mechanisms
Chromosome-mediated Due to spontaneous mutation: in the target molecule in the drug uptake system Mutants are SELECTED ; they are NOT induced
Plasmid-mediated
Common in Gram-negative rods
Transferred via conjugation
Multidrug resistance
Resistance to Beta-Lactams compare gram +ve vs gram -ve
Gram + ve
ß-lactamase (Penicillinase)
Alteration of the transpeptidase enzyme
(PBP)
Gram - ve
ß -Lactamase (Penicillinase)
Alteration of porins
Penicillinase function
Penicillinase destroys active part of penicillin molecule
Augmentin/co-amoxiclav - structure and action
Clavulanic acid + amoxicillin
Binds to and inactivates beta-lactamases
No anti-bacterial activity of its own
Beta-lactam Resistance in Gram –ve bacteria - describe events
1. Porin mutates or new porin type Multi-resistant 2. PBP - mutates or bacteria acquires a new PBP 3. bacteria acquires a beta-lactamase enzyme
PBP =
PBP = Penicillin binding Protein or transpeptidase
Mechanisms by which bacteria become resistant to penicillin - describe all 4
Any of:-
Produce penicillinases / beta lactamases that cleave the beta lactam ring
- penicillin is inactivated
Acquire alternative forms of / or mutations in penicillin binding proteins (PBPs)
- penicillin can’t bind
Acquire alternative forms of / mutations in porins,
- penicillin cannot get into cell
Acquire alternative forms of / mutations in efflux pumps
- penicillins are pumped out faster
Treatment of MRSA
Only effective treatment is vancomycin, a 1.5 kDa glycopeptide
Vancomycin Resistance - describe events and effect
Acquisition of van operon by transposition
Makes D-ala-D-lactate - prevents vancomycin binding
Non-Genetic Mechanism - describe
Inaccessibility to drugs
(e.g., abscess, TB lesion)
Stationary phase/vegetations and biofilms
(non-susceptible to inhibitors of cell wall synthesis)
Disc diffusion test for
Disc diffusion test for antibiotic susceptibility testing of S. pneumoniae
How to prevent/overcome antibiotic resistance
Control use
not in animal feeds
complete course [DOTS for TB]
appropriate prescribing
New or modified drugs few in past 25 years
Combination therapy different targets
overcome mutation rates
Infection control individual - ward - society
Neisseria gonorrhoeae - gonorrhoea
treatmen
Neisseria gonorrhoeae - gonorrhoea
treatment - a single I/M penicillin
↓rates; ↑penicillin R+ ~15%
Then we used new front line drug - Ciprofloxacin
Treatment if cipro R+ N. gonorrhoeae
Switched to single oral dose – cefixime
Now i/m ceftriaxone + 1g Azithromycin
125mg increased to 250mg due to increasing MIC
Carbapenems - define
Carbapenems – broad spectrum antibiotics
of last resort for Gram negative bacteria
e.g. E.coli or Klebsiella (CREs)
