Antimicrobial Therapies

Question 1

What’s an antibiotic

Answer 1

An anti microbial agent produced by a microorganism that kills other microorganisms
Soil dwelling fungi are most commonly used

Question 2

Bactericidal meaning

Answer 2

Kills bacteria

Question 3

Bacteriostatic meanjng

Answer 3

Stops bacterial growth

Question 4

Antiseptic meanjng

Answer 4

Chemical that kills or inhibits microbes used topically on skin

Question 5

Beta lactams

Answer 5

Penicillin,methicillin
Bind to PBPs interfere with cell wall synthesis

Question 6

Sulphonamides

Answer 6

Prontosil,trimethoprim,sulfa methoxazole
Bacteriostatic can cause host toxicity
Prontosil treats UTI,RTI
Becoming more common due to AB resistance

Question 7

Aminoglycosides

Answer 7

Gentamycin, steptomycin
Target 30s ribosomes subunits ,damage Cell membrane,rna proofreading

Question 8

Rifampicin

Answer 8

Bactericidal targets RpoB subunit of rna polymerase
Causes red secretions

Question 9

Vancomycin

Answer 9

Bactericidal targets lipid component of cell wall and wall cross linking via d ala residues
Toxic

Question 10

Linezolid

Answer 10

Bacteriostatic inhibits initiation of protein synthesis by binding to 50s rRNA
Gram positive bacteria

Question 11

Daptomycin

Answer 11

Targets bacterial cell membrane
Gram positive bacteria
Bactericidal

Question 12

Macrolides

Answer 12

Target 50s ribsomal subunits preventing amino acyl transfer and thus truncation of polypeptides
Gram positive and negative

Question 13

Quinolones

Answer 13

Synthetic broad spectrum Bactericidal targets dna gyrase in gram negative and topoisomerase in gram positive

Question 14

As the antibiotics Bactericidal

Answer 14

All are apart from linezoid and sulphonamide

Question 15

What is the minimal inhibitory conc

Answer 15

The lowest concentration of antibiotic needed to inhibit growth

Question 16

When is a bacterium considered resistant

Answer 16

If it can grow at or above the minimal inhibitory concentration

Question 17

4 mechanisms through which antibiotic resistance occurs

Answer 17

Altered target site
Inactivation of antibiotic
Altered metabolism
Decreased drug accumulation

Question 18

Altered target site

Answer 18

MRSA encodes alternative PBP with low affinity for beta lactams
Acquisition of erm gene by streptococcus pneumoniae encodes enzyme that methylates AB target site in 50s ribosmal subunit leading to resistance

Question 19

Inactivation of antibiotic

Answer 19

Enzymatic degradation or alteration

Rendering antibiotic ineffective

• e.g. beta-lactamase (bla) and chloraphenicol acetyl-transferase (cat)
  For example ESBL AND NDM-1 are. Betalactamases

Question 20

Altered metabolism

Answer 20

Increased production of enzyme substrate can out-compete antibiotic for target site,

(e.g. increased production of PABA confers resistance to sulfonamides).

Or bacteria can switch to other metabolic pathways, reducing requirement for PABA

Question 21

Decreased drug accumulation

Answer 21

Reduced penetration of AB into bacterial cell

Or increased efflux pumps to keep AB out of cell

Makes it so that drug does not reach concentration required to be effective

Question 22

What are 3 sources of antibiotic resistant genes

Answer 22

• Plasmids- extra-chromosomal circular DNA often carry multiple copies and often carry multiple AB resistant genes so selection for one maintains resistance for all
• Transposons- integrate into chromosomal DNA & allow transfer of genes from plasmid to chromosome and vice versa
• Naked DNA- DNA from dead bacteria released into environment

Question 23

How can bacteria spread their ab resistant genes

Answer 23

1) Transformation- uptake of extracellular DNA

2) Transduction- phage-mediated DNA transfer

3) Conjugation- bacterial sex to share plasmids between them (pilus-mediated DNA transfer)

Question 24

Non genetic mechanisms of resistance

Answer 24

Bio is so slow & persistent BISSP

• Biofilm
• Intracellular location
• Slow growth
• Spores
• Persisters

Question 25

What other reasons are there for ab treatment failure

Answer 25

- **Inappropriate choice for organism** e.g. some ABs kill gram positive but not negative - Poor penetration of AB into target site - **Inappropriate dosage** (half life) - **Inappropriate administration** (oral vs IV) - Presence of AB resistance within commensal flora e.g. secretion of beta-lactamase

Question 26

Hospital acquired infections nosocomal

Answer 26

- **High number of ill people** - **Crowded wards** - **Presence of pathogens** - **Broken skin** e.g. surgical wound or IV catheter - Indwelling devices e.g. intubation where bacteria can come together and form biofilm - **AB therapy may suppress normal gut microbiota** that helps maintain gut health - **Transmission by staff**- contact with multiple patients - How might AB therapy impair commensal flora (microbiota)? **AB therapy removes commensal organisms that helps maintain gut health** and health of whole body Pathogen has **no competition** leading to **overgrowth** **Pathogen produces toxins and damages host**-symptomatic infection Spreads to other patients !https://s3-us-west-2.amazonaws.com/secure.notion-static.com/0886ed10-86db-4f93-bcf5-408afb500cf2/Untitled.png - Give some of the methods we might use to address antibiotic resistance**(6 ways; BE SICK)**? - Reduce use of **broad-spectrum antibiotics** (that can destroy gut microbiota) - **Modification** of **existing medication** to e.g. prevent cleavage (beta lactams) or enhance efficacy e.g. methicillin - **Strategies of prescription**- tighter controls, temporary withdrawal of certain classes to allow prevalence of resistant organisms to drop before reintroduction- restriction of ABs for certain serious infections - **Identify** infections caused by resistant strains quickly - **Combination** **therapy**- using 2 or more AB together + inhibitors - **Knowledge of local strains**/resistance patterns - Fungi- what are the 3 classes of conditions they cause in humans? - Allergy - allergic reactions to fungal products - Mycotoxicoses - ingestion of fungi or their toxic products - Mycoses - superficial, subcutaneous or systemic colonisation, invasion and destruction of human tissue - What do fungi use in their cell membrane instead of cholesterol? Ergosterol - What are the targets for antifungal therapy? !https://s3-us-west-2.amazonaws.com/secure.notion-static.com/b8a01b08-180d-4b75-929d-5797712dc929/Untitled.png

Question 27

How might ab therapy impair commensal flora

Answer 27

**AB therapy removes commensal organisms that helps maintain gut health** and health of whole body Pathogen has **no competition** leading to **overgrowth** **Pathogen produces toxins and damages host**-symptomatic infection Spreads to other patients

Question 28

Fungi

Answer 28

Cause allergy, mycotoxicoses and mycoses

Question 29

Gram negative

Answer 29

**pseudomonas aeruginosa** Cystic fibrosis,burn wound infections,survives in a biotic surfaces **e.coli** GI infect,neonatal meningitis,septicemia,uti **salmonella** Thyphoid,GI infection **acinetobacter baumannii** Wounds,uti,pneumonia **neisseria gonorrhoeae** Gonorrhaea

Question 30

Gram positive

Answer 30

**staphylococcus aureus** Wound and skin infection,pneumonia,septicaemia,endocarditis **streptoccus pneumoniae** Pneumonia,septicemia **clostridium difficile** Diarrhea,colitis **mycobacterium tuberculosis** Tuberculosis

Question 31

What replaces cholesterol in fungi cell wall

Answer 31

Ergosterol