Hospital acquired infection and antibiotic resistance

Question 1

Antibiotic

Answer 1

an antimicrobial agent produced by a microorganism that kills or inhibits other microorganisms

Question 2

Antimicrobial

Answer 2

chemical that selectively kills or inhibits microbes (bacteria, fungi, viruses)

Question 3

What are antibiotics made from?

Answer 3

Natural, semi-synthetic and synthetic chemicals with antimicrobial activity

Question 4

Bactericidal

Answer 4

kills bacteria

Question 5

Bacteriostatic

Answer 5

stops bacteria growing

Question 6

Antiseptic

Answer 6

chemical that kills or inhibits microbes

Usually used topically to prevent infection

Question 7

After discovery of penicillin, many other antibiotics were identified but

Answer 7

progress has slowed dramatically in recent years

Routine use of penicillin provided selective pressure for acquisition and maintenance of resistance genes

Question 8

Minimal inhibitory concentration (MIC)

Answer 8

lowest concentration of antibiotic required to inhibit growth

Question 9

Misconceptions at the dawn of antibiotic era

Answer 9

Resistance against >1 class of antibiotics at same time wouldn’t occur.
Horizontal gene transfer wouldn’t occur.
Resistant organisms would be significantly less ‘fit’

Question 10

Antibiotic resistance leads to increased mortality, morbidity and cost

Answer 10

Increased time to effective therapy.
Requirement for additional approaches – e.g. surgery.
Use of expensive therapy (newer drugs).
Use of more toxic drugs e.g. vancomycin.
Use of less effective ‘2nd choice’ antibiotics

Question 11

Give 2 examples of Beta Lactams and their mode of action

Answer 11

Penicillin and Methicillin

Interfere with synthesis of peptidoglycan component of bacterial cell wall by binding to penicillin-binding proteins.

Question 12

Name 5 gram negative antibiotic resistant bacteria

Answer 12

Pseudomonas aeruginosa
E. Coli (ESBL) and E. coli, Klebsiella spp (NDM-1) 
Salmonella spp. (MDR)
Acinetobacter baumannii (MDRAB)
Neisseria gonorrhoeae

Question 13

Name 5 gram postive antibiotic resistant bacteria

Answer 13

Staphylococcus aureus (MRSA, VISA)
Streptococcus pneumoniae
Clostridium difficle
Enterococcus spp (VRE)
Mycobacterium tuberculosis (MDRTB, XDRTB)

Question 14

Name 5 antibiotics used therapeutically

Answer 14

Aminoglycosides
Rifampicin
Vancomycin
Linezolid
Daptomycin

Question 15

Aminoglycosides

Answer 15

Bactericidal
Target and corrupt protein synthesis leads to damage in cell membrane
Toxicity limits use

Question 16

Rifampicin

Answer 16

Bactericidal
Targets RpoB subunit of RNA polymerase
Makes secretions (tears) red

Question 17

Vancomycin

Answer 17

Bactericidal.
Targets Lipid II component of cell wall biosynthesis, and wall crosslinking via D-ala residues
Toxicity limits use

Question 18

Linezolid

Answer 18

Bacteriostatic.
Inhibits initiation of protein synthesis by binding to 50S rRNA subunit.
Gram-positive spectrum of activity

Question 19

Daptomycin

Answer 19

Bactericidal.
Targets bacterial cell membrane.
Gram-positive spectrum of activity.
Toxicity limits dose

Question 20

The large number of differences between mammals and bacteria allow antibiotics to be

Answer 20

Selectively toxic

Question 21

4 Mechanisms of antibiotic resistance

Answer 21

Altered target site
Inactivation of antibiotic
Altered metabolism
Decreased drug accumulation

Question 22

Antibiotic resistance: Altered target site

Answer 22

Acquisition of alternative gene or a gene that encodes a target-modifying enzyme

Question 23

Antibiotic resistance: Inactivation of antibiotic

Answer 23

Enzymatic degradation or alteration, rendering antibiotic ineffective

Question 24

Antibiotic resistance: Altered metabolism

Answer 24

Increased production of enzyme substrate can out-compete antibiotic inhibitor

Question 25

Antibiotic resistance: Decreased drug accumulation

Answer 25

Reduced penetration of antibiotic into bacterial cell (permeability) and/or increased efflux of antibiotic out of cell Drug does not reach concentration required to be effective

Question 26

Example of bacteria where multiple resistance mechanisms exist

Answer 26

N. gonorrhoea

Question 27

Macrolides

Answer 27

Prevent protein synthesis | Used for Gram-positive and some Gram-negative infections.

Question 28

what do macrolides target?

Answer 28

Targets 50S ribosomal subunit preventing amino-acyl transfer and thus truncation of polypeptides

Question 29

Quinolones

Answer 29

Synthetic, broad spectrum, bactericidal.

Question 30

What do quinolones target?

Answer 30

Target DNA gyrase in Gm-ve | Target topoisomerase IV in Gm+ve

Question 31

Sources of antibiotic resistance?

Answer 31

Plasmids Transposons Naked DNA

Question 32

How are plasmids sources of antibiotic resistance?

Answer 32

extra-chromosomal circular DNA, often multiple copy. Often carry multiple AB resistant genes: selection for 1 maintains resistance to all

Question 33

How are transposons sources of antibiotic resistance?

Answer 33

Integrate into chromosomal DNA. | Allow transfer of genes from plasmid to chromosome and vice versa

Question 34

How is naked DNA a source of antibiotic resistance?

Answer 34

DNA from dead bacteria released into environment

Question 35

3 modes of spread of antibiotic resistance

Answer 35

Transformation Transduction Conjugation

Question 36

List 5 non-genetic mechanisms of resistance/ treatment failure to antibiotics

Answer 36

``` Biofilm: form large sticky masses Intracellular location: hide inside cells Slow growth Spores Persisters: dormant ```

Question 37

List 5 other reasons for antibiotic treatment failure

Answer 37

Inappropriate choice for organism Poor penetration of AB into target site Inappropriate dose (half-life) Inappropriate administration (oral vs IV) Presence of AB resistance within commensal flora e.g. secretion of beta-lactamase

Question 38

Measuring resistance

Answer 38

Swabs streaked out onto diagnostic agar to identify causative organism. Pathogen streaked over a plate and over-laid with AB-containing test strips or discs. Also could do broth micro-dilution and PCR detection of resistance genes

Question 39

Hospitals provide... for antibiotic resistance

Answer 39

Strong selective pressure as lots of infected people receiving high doses of antibiotics

Question 40

List 7 risk factors for hospital acquired bacterial infections

Answer 40

High No. of ill people (some immunosuppressed) Crowded wards Presence of pathogens Broken skin: surgical wound/IV catheter Indwelling devices: intubation AB therapy may suppress normal flora Transmission by staff: contact with multiple patients

Question 41

In what respect do commensal organisms outcompete pathogens in health?

Answer 41

Adhesion Metabolism Growth So pathogen can't colonise at levels sufficient for infection

Question 42

How are commensal flora effected by antibiotics?

Answer 42

Commensal flora may be impaired

Question 43

List 4 strategies to address resistance

Answer 43

Strict prescribing Reduce use of broad spectrum ABs Combination therapy Quick identification of infection caused by resistant strains

Question 44

Give 2 strategies to overcome resistance

Answer 44

Modification of existing ABs | Combinations of AB + inhibitor