Antimicrobial Therapies

Question 1

What is an antibiotic?

Answer 1

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

Question 2

What is bactericidal?

Answer 2

Kills bacteria

Question 3

What is bacteriostatic?

Answer 3

Stops bacteria growing but doesn’t kill them

Question 4

What is prontosil?

Answer 4

First sulphonamide antibiotic
Eg. sulfamethoxazole. Sometimes used with trimethoprim
Used to treat UTIs, RTIs, bacteraemia and prophylaxis for a HIV+ patient
Only acts on gram positive bacteria

Question 5

What is antiseptic?

Answer 5

Chemical that kills or inhibits microbes

Question 6

What is antimicrobial?

Answer 6

Chemicals that selectively kill or inhibit microbes

Question 7

What are aminoglycosides?

Answer 7

E.g. Gentamicin, Streptomycin
Bactericidal
Target protein synthesis (30S ribosomal subunit) and affect RNA proofreading and cause damage to cell membrane

Question 8

What is rifampicin?

Answer 8

Bactericidal
Targets RpoB subunit of RNA polymerase
Makes secretions go orange/red- affects compliance

Question 9

What is vancomycin?

Answer 9

Bactericidal

Targets lipid II component of cell wall synthesis as well as crosslinking via D- ala residues

Question 10

What is linezolid?

Answer 10

Bacteriastatic
Inhibits initiation of protein synthesis by binding to 50S RNA subunit
Affects gram positive bacteria

Question 11

What is daptomycin?

Answer 11

Bactericidal
Targets bacteria cell membrane
Targets gram positive bacteria

Question 12

What are beta lactams?

Answer 12

E.g. penicillin, methicillin
Inhibits bacterial cell wall peptidoglycan formation
Binds transpeptidases (penicillin binding proteins -PBPs)
PBPs catalyse a number of steps in the synthesis of peptidoglycans

Question 13

What are macrolides?

Answer 13

E.g. erythromycin, azithromycin
Affect gram positive and some gram negative infections
Target 50S ribosomal subunit preventing amino-acyl transfer and translocation of polypeptides

Question 14

What are quinolones?

Answer 14

Synthetic and bactericidal

Target DNA gyrase in gram negative bacteria and topoisomerase IV in gram positive bacteria

Question 15

What is the minimal inhibitory concentration?

Answer 15

The lowest concentration of antibiotic required to inhibit growth

Question 16

How does antimicrobial resistance develop?

Answer 16

Selection pressures: resistant mutants outcompete other strains

Question 17

Through what mechanisms does antibiotic resistance occur by?

Answer 17

1. Altered target site: methicillin- resistant staphylococcus aureus encodes an alternate penicillin binding protein with low affinity for beta lactams
2. Inactivation of antibiotic- Beta lactamase destroys beta lactam ring
3. Altered drug metabolism- increased production of PABA- resistant to sulfonamides
4. Decreased drug accumulation- antibiotic efflux pump

Question 18

How do bacteria alter their metabolism to resist effects of antibiotics?

Answer 18

Increased production of enzyme substrate can out-compete antibiotic inhibitor
Alternatively bacteria switch to other metabolic pathways reducing requirement for PABA

Question 19

How do resistant bacteria decrease drug accumulation?

Answer 19

Reduced penetration of antibacterials into bacteria cell and/or increased efflux of antibiotic out of cell

Question 20

What are the major gram negative antibiotic resistant bacterial pathogens?

Answer 20

Pseudomonas aeruginosa
E.coli (ESBL)
E.coli Klebsiella spp. (NDM-1) 
Salmonella Spp (MDR)
Acinetobacter Bacmannia 
Neisseria gonorrhoeae

Question 21

What are major gram positive antibiotic resistant bacterial pathogens?

Answer 21

Staphylococcus aureus (MRSA, VISA)
Streptococcus pneumoniae
Clostridium difficile
Enterococcus Spp
Mycobacterium Tuberculosis

Question 22

What are sources of antibiotic resistant genes?

Answer 22

Plasmids: extrachromosomal circular DNA, often multiple copies. Often carry multiple antibiotic resistant genes-selection for one maintains resistance to all

Transposons: integrate into chromosomal DNA and allow transfer of genes from plasmid to chromosome and vice versa

Naked DNA: DNA from dead bacteria released into environment

Question 23

What are 3 mechanisms for spread of antibiotic resistance genes?

Answer 23

Transformation- uptake of intracellular DNA
Conjugation- pilus mediated DNA transfer
Transduction- phage mediated DNA transfer

Question 24

What are non-genetic mechanisms of resistance?

Answer 24

Biofilm- communities of bacteria that are highly drug tolerant
Intracellular location- doesn’t change location so makes it hard for antibodies to access them
Slow growth- if bacteria doesn’t use many processes to replicate then it’s hard for antibiotics to inhibit them
Spores- extremely resistant to heat, antiseptics and antibiotics
Persisters: organisms not using any processes that are inhibited by antibiotics

Question 25

What are other reasons of treatment faliure?

Answer 25

Inappropriate choice for organism Poor penetration of antibiotic into target site Inappropriate dose Inappropriate administration Presence of antibiotic resistance with commensal flora

Question 26

Why is antibiotic resistance common in hospitals?

Answer 26

Large number of infected people receiving high doses of antibiotics- strong selection pressure

Question 27

What are risks for hospital acquired infections?

Answer 27

``` High number of ill people Crowded wards Presence of pathogen Broken skin Indwelling devices AB therapy may suppress normal flora Transmission by staff ```

Question 28

What harm can come about when antibiotic therapy impares commensal flora?

Answer 28

Commensal organisms can outcompete pathogen for adhesion, metabolism and growth Pathogen cannot colonise at levels sufficient for infection After AB therapy pathogen has no competition which can lead to overgrowth The pathogen produces toxins which damage the host and becomes a symptomatic infection

Question 29

How can we prevent the emergence of drug resistant bacteria?

Answer 29

Prescribing strategies- tighter controls Reduce use of broad spectrum antibiotics Quicker identification of infection caused by resistant strain Knowledge of local strains/ resistance patterns Modification of existing medications Combination of antibiotic and inhibitor

Question 30

What are 3 broad classes of conditions that fungi cause in humans?

Answer 30

Allergy- allergic reaction to fungal products Mycotoxicosis- ingestion of fungi and their toxic products Mycoses- superficial, subcutaneous or systemic colonisation and invasion and destruction of human tissue

Question 31

What are the targets for antifungal therapy?

Answer 31

Cell membrane- fungi use ergosterol instead of cholesterol DNA synthesis- some compounds may be selectively activated by fungi, arresting DNA synthesis Cell Wall- unlike mammalian cells, fungi have a cell wall