Antimicrobial Therapies

Question 1

Explain aminoglycosides

Answer 1

Gentamicin, streptomycin
Bactecidal. Target protein synthesis 30s ribosomal subunit
So causes lack of proofreading so poor protein production, damage to membrane when inserted

High toxicity so limited use- so increasing use, can cause hearing loss

Question 2

Describe rifampicin

Answer 2

Bactericidal
Targets RpoB subunit of RNA polymerase so stops transcription
Great activity inside host cells such as neutrophils and macrophages
Spontaneous resistance is frequent
Makes secretions go orange or red

Question 3

Describe vancomycin

Answer 3

Targets II lipid component of cell wall biosynthesis as well as cross- linking via D- ala residues
Toxicity limited use so increasing use to MRSA

Give it to the methicillin resistant staphylococcus aureus bacteria

Question 4

Describe Linezolid

Answer 4

Bacteriostatic
Inhibits the initiation of protein synthesis by binding to 50s rRNA subunit
Gram positive spectrum of activity

New
Not affect gram negative as it hasnLPS on the membrane

Question 5

Describe Draptomycin

Answer 5

Bactericidal
Targets bacteria cell membrane
Only Gram positive because it can’t target the LPS in the membrane
Toxic so limits dose and needs to be given IV to patients only

Question 6

Describe Beta lactams

Answer 6

Interfere with synthesis of the peptidoglycan component of the bacterial cell wall
Penicillin Methicillin
Binds to penicillin binding proteins
Inhibits wall biosynthesis and leads to bacterial killing

Question 7

What are some things that the antimicrobials can affect

Answer 7

• inhibition of cell wall synthesis penicillin, cephalosporins, bacltracin, vancomycin
• inhibition of protein synthesis chloramphenicol, erythromycin, tetracyclines, streptomycin
• inhibition of nucleic acid and replication and transcription quinolones, rifampin
• injury to plasma membrane, polymycin B
• inhibition of synthesis of essential metabolites sulfanilamide, trimethoprim

Selective toxicity
Protein synthesis tends to be a bit different so peptidoglycan production and LPS layer of gram negative bacteria

Question 8

Explain macrolides

Answer 8

Erythromycin azithromycin
Gram positive and some gram negative infections targeted by azithomycin
Targets 50s ribosomal subunits preventing amino acrylic transfer and thus truncation of polypeptides

Question 9

Describe quinolones

Answer 9

Synthetic broad spectrum
Target DNA grease in gram negative and topoisomerase IV in gram positive
DNA damage and death of the organism
Gonocococal infections and lung and bloodstream

Question 10

What do we mean by resistance

Answer 10

Above the breakpoint ( clinically- achievable concentration)
The scale goes sensitive intermediate resistant

Minimal inhibitory concentration MIC
Lowest concentration of AB required to inhibit growth
MIC links to the break point

Question 11

Explain antibiotic resistance

Answer 11

Population contains cells with AB resistance due to mutation and acquired. DNA probably with a fitness cost
Presence of selection pressure -resistant mutants out complete
( in absence of selection pressure the resistance strains have no advantage)

Question 12

4 ways antibiotic resistance

Answer 12

Altered target site
Inactivation of antibiotic
Altered metabolism
Decreased drug accumulation

Question 13

What is altered target site?

Answer 13

Alternative gene or a gene that encodes a target modifying enzyme

MRSA - encodes an alternative PBP (PBP2a) with low affinity for beta lactams
Streptococcus pneumoniae -resistance accur via acquisition of erm gene which encodes an enzyme that methylates the AB target site in the 50s ribosomal subunit

Question 14

Explain inactivation of antibiotic

Answer 14

Enzymatic degradation or alteration, rendering antibiotic ineffective
Beta- lactamase( breaks bond in the beta lactam ring of penicillin to disable the molecule, bacteria with this enzyme can resist the effects of penicillin and other beta lactam antibiotics) chloramphenicol acetyl - transferase cat

ESBL and NDML-1 examples of broad spectrum beta - lactamases

Question 15

Explain altered metabolism

Answer 15

Increased production of enzyme substrate can outcompete antibiotic inhibitor
(Increased production of PABA confers resistance to sulfonamides)

Alternatively bacteria switch to other metabolic pathways, reducing the requirement of PAB

Question 16

Explain decreased drug accumulation

Answer 16

Reduce penetration of antibiotic increased influx of antibiotic out of the cell drug does not reach concentration to be affective

Question 17

What are the sources of antibiotic resistance

Answer 17

Plasmids - extra chromosomal circular DNA - often multiple copy
Transposons - integrate into chromosomal DNA, allow transfer from genes to plasmid and to chromosome and vice versa
Naked DNA - dna from dead bacteria released to environment

Question 18

How can DNA be shared

Answer 18

Transformation - uptake of extra cellular DNA
Conjugation - pilus mediated DNA transfer
Transduction- phage mediated DNA transfer

Question 19

What are some none genetic mechanism of resistance

Answer 19

Biofilm - matrix in cased communities of bacteria that are highly drug tolerant
Intracellular location - stay within cells so hard to access
Slow growth - not many processes to replicate so antibiotic can’t inhibit them eg tuberculosis
Spores - resistant to antibiotics, antiseptics and heat
Persister - dormant organisms, not using processes so not inhibited or killed

Question 20

Other reasons for treatment failure

Answer 20

Innaproptpriate choice of organism
Poor penetration of AB into target site
Innapropriate half life
Inappropriate administration (oral vs IV)
Presence of AB resistance within comensal flora eg secretion of beta lactamase

Question 21

Why do hospitals provide a strong selective pressure for antibiotic resistance

Answer 21

Large number of infected people receiving high doses of antibiotics
Strong selective pressure for emergence/ maintenance of AB resistance

Question 22

State 8 HAIs

Answer 22

MRSA 
VISA - vancomycin insensitive S. aureus 
C. Difíciles 
Vancomycin resistant enterococci VRE 
E. Coli - ESBL, NDM-1
P. Aeruginosa 
Afineterbacter baumannii 
Stenotrophomonas maltophilia

Question 23

Risk factors for HAIs

Answer 23

Immunosuppression
Crowded wards
Presence of pathogens
Broken skin
In dwelling devices - intubation
AB therapy supress normal flora - gut health
Transmission by staff - contact with multiple patients

Question 24

Ways to prevent emergence of drug resistant bacteria and nosocomial infections

Answer 24

Prescribing strategies
Reduce use of broad spectrum antibiotics
Quicker ID of infections caused by resistant strains
Combo therapy - 2 or more
Knowledge of local strains/ resistance patterns

Question 25

How to overcome resistance? 2

Answer 25

Modificati of existing medication - prevent cleavage of beta lactams and enhance efficacy
Combination of antibiotic and inhibitor - beta lactamase