Antibiotic Resistance

Question 1

Antibiotic resistance effects

Answer 1

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

Question 2

Enterococci - define

Answer 2

large genus of lactic acid bacteria of the phylum Firmicutes.

gut vancomycin R+ (VREs)
G+ve origin - chickens ?

Question 3

Acinetobacter - define

Answer 3

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

Question 4

MRSA - define

Answer 4

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

Question 5

Mechanisms of antibiotic resistance - list with examples

Answer 5

Drug inactivation
e.g. beta-lactamase

Metabolic by-pass
e.g. vancomycin
D-ala-D-lac

Efflux pump

Overproduction
of target

Intrinsic
impermeability

Question 6

Altered or new target if resistance shown

Answer 6

Altered or new target
e.g. 
Ribosome
Porin
PBPs – 
peptidoglycan synthesis
DNA gyrase
RNA polymerase
Mcr1 & colistin

Question 7

Paths to Resistance - describe each

Answer 7

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

Question 8

Mechanisms of Resistance - types

Answer 8

Natural resistance

Genetic Mechanisms - acquired

Non-Genetic Mechanisms (growth phases)

Question 9

Describe natural resistance

Answer 9

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

Question 10

Describe types of genetic mechanisms

Answer 10

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

Question 11

Resistance to Beta-Lactams compare gram +ve vs gram -ve

Answer 11

Gram + ve

ß-lactamase (Penicillinase)

Alteration of the transpeptidase enzyme
(PBP)

Gram - ve

ß -Lactamase (Penicillinase)

Alteration of porins

Question 12

Penicillinase function

Answer 12

Penicillinase destroys active part of penicillin molecule

Question 13

Augmentin/co-amoxiclav - structure and action

Answer 13

Clavulanic acid + amoxicillin

Binds to and inactivates beta-lactamases
No anti-bacterial activity of its own

Question 14

Beta-lactam Resistance in Gram –ve bacteria - describe events

Answer 14

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

Question 15

PBP =

Answer 15

PBP =
	Penicillin 
	binding 
	Protein or
transpeptidase

Question 16

Mechanisms by which bacteria become resistant to penicillin - describe all 4

Answer 16

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

Question 17

Treatment of MRSA

Answer 17

Only effective treatment is vancomycin, a 1.5 kDa glycopeptide

Question 18

Vancomycin Resistance - describe events and effect

Answer 18

Acquisition of van operon by transposition

          Makes D-ala-D-lactate   - prevents vancomycin binding

Question 19

Non-Genetic Mechanism - describe

Answer 19

Inaccessibility to drugs
(e.g., abscess, TB lesion)

Stationary phase/vegetations and biofilms
(non-susceptible to inhibitors of cell wall synthesis)

Question 20

Disc diffusion test for

Answer 20

Disc diffusion test for antibiotic susceptibility testing of S. pneumoniae

Question 21

How to prevent/overcome antibiotic resistance

Answer 21

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

Question 22

Neisseria gonorrhoeae - gonorrhoea

treatmen

Answer 22

Neisseria gonorrhoeae - gonorrhoea
treatment - a single I/M penicillin
↓rates; ↑penicillin R+ ~15%

Then we used new front line drug - Ciprofloxacin

Question 23

Treatment if cipro R+ N. gonorrhoeae

Answer 23

Switched to single oral dose – cefixime
Now i/m ceftriaxone + 1g Azithromycin
125mg increased to 250mg due to increasing MIC

Question 24

Carbapenems - define

Answer 24

Carbapenems – broad spectrum antibiotics
of last resort for Gram negative bacteria
e.g. E.coli or Klebsiella (CREs)