antimicrobial therapies

Question 1

what is prontosil?

Answer 1

synthetic bacteriostatic antibiotic

sulphonamide antibiotic

Question 2

what is prontosil used to treat?

Answer 2

UTIs, RTIs, bacteraemia, prophylaxis for HIV+ people

Question 3

How do beta-lactams work?

Answer 3

interfere with the synthesis of the peptidoglycan component of the bacterial cells wall

bind to penicillin-binding proteins (PBPs)

PBPs catalyse steps in the synthesis of peptidogylycan

Question 4

examples of beta-lactams?

Answer 4

penicillin, methicillin

Question 5

what are most modern naturally harvested antibiotics produced by?

Answer 5

soil-dwelling fungi, bacteria

Question 6

antimicrobial meaning

Answer 6

chemical that selectively kills/ inhibits microbes

Question 7

antiseptic definition

Answer 7

chemical which kills or inhibits microbes that is usually used topically to prevent infection

Question 8

What is the breakpoint in antibiotics?

Answer 8

clinically-achievable concentration for bacteria to be killed by the antibiotics

i.e. the concentration of antibiotic where a bacterial infection will be eradicated successfully by the antibiotic.

Question 9

What is the minimal inhibitory concentration (MIC)

Answer 9

the lowest conc. of antibiotics required to inhibit growth

Question 10

misconceptions about antibiotics at the start

Answer 10

resistance against more than one class of antibiotics wouldn’t occur at the same time

horizontal gene transfer wouldn’t occur

resistant organisms would be significantly less “fit” (varies)

Question 11

consequences of antibiotic resistance

Answer 11

increased time for effective therapy
requirement for additional approaches, like surgery
use of more expensive (newer drug) therapy
use of more toxic drugs like vancomycin
use of less effective second choice antibiotics

Question 12

gram negative AB resistant bacteria

Answer 12

pseudomonas aeruginosa (cystic fibrosis/burn wound)
E. coli (ESBL) and E. coli, Klebsiella spp
Salmonella spp (MDR)
Acinetobacter baumannii (MDRAB) (wounds, UTI, pneumonia
Neisseria gonorrhoeae

Question 13

gram positive AB resistant bacteria

Answer 13

MRSA/VISA
streptococcus pneumoniae
clostridium difficile (GI)
Enterococcus spp (VRE) (UTI, bacteraemia, infective endocarditis)

TB

Question 14

what is an aminoglycoside

Answer 14

bactericidal antibiotic

Question 15

mechanism of aminoglycosides

Answer 15

target 30S ribosomal subunit, RNA proofreading + can cause damage to cell membrane

Question 16

what’s rifampicin

Answer 16

bactericidal antibiotic (frequent spontaneous resistance)

Question 17

mechanism of rifampicin?

Answer 17

targets RpoB subunit of RNA polymerase

Question 18

what is vancomycin

Answer 18

bactericidal antibiotic which targets Lipid II component of cell wall biosynthesis + wall cross linking via D-ala residues

toxic but used against MRSA etc

Question 19

everything abt linezolid u need to know

Answer 19

bacteriostatic

inhibits protein synthesis by binding to 50s rRNA subunit

only affects gram positive?

Question 20

daptomycin

Answer 20

bactericidal

targets cell membrane

gram positive

toxic

Question 21

4 mechanisms of antibiotic resistance

Answer 21

1- altered active site
2- inactivation of antibiotic
3- decreased drug accumulation
4- altered metabolism

Question 22

how does altered target site mechanism of resistance arise

Answer 22

acquisition of alternative gene/ gene which codes a target-modifying enzyme

Question 23

examples of altered target sites

Answer 23

MRSA encodes an alternative PBP (PBP2) with low affinity for beta-lactams

Streptococcus pneumoniae acquired the erm gene which encodes an enzyme which methylates the antibiotic target site in 50S ribosomal subunit

Question 24

inactivation of antibiotic

Answer 24

enzymatic degradation or alteration, rendering antibiotic ineffective.

Examples: beta-lactamase (bla) and chloramphenicol acetyl-transferase (cat).

ESBL and NDM-1 are examples of broad-spectrum beta-lactamases (can degrade a wide range of beta-lactams, including newest).

Question 25

what's decreased drug accumulation?

Answer 25

reduced permeability of AB into bacterial cell and/or increased efflux of AB out of cell drug does not reach conc required to be effective

Question 26

altered metabolism

Answer 26

increased production of enzyme substrate outcompetes antibiotic inhibitor (e.g. increased production of p-aminobenzoic acid confers resistance to sulphonamides) or bacteria can switch to a diff metabolic pathway, reducing need for PABA

Question 27

what are macrolides

Answer 27

bacteriostatic gram-positive and sometimes gram negative targets 50S ribosomal subunits, stops amino-acyl transfer, and truncation of polypeptides e.g. erythromycin, azithromycin

Question 28

what are quinolones

Answer 28

Synthetic, broad spectrum, bactericidal. Target DNA gyrase in gram neg and topoisomerase IV in gram pos

Question 29

sources of antibiotic resistance genes

Answer 29

plasmids (can carry multiple resistance genes) transposons - integrate into chromosomal DNA + allows gene transfer from plasmid to chromosome and vice versa naked DNA- from dead bacteria released into environment

Question 30

How can AB resistance genes be spread?

Answer 30

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

Question 31

other reasons for resistance/ treatment failure

Answer 31

biofilm intracellular location slow growth spores persisters inappropriate choice for organism poor penetration into target site inappropriate dose inappropriate administration presence of AB resistance within commensal flora (secretion of beta-lactamase)

Question 32

How do hospitals provide strong selective pressure for AB resistance?

Answer 32

large numbers of infected people require high doses of antibiotics- strong selective pressure for emergence/ maintenance of AB resistance

Question 33

examples of hospital acquired infections

Answer 33

MRSA VISA clostridium difficile VRE E. coli (ESBL/NDM-1) P. aeruginosa Acinebacter baumannii Stenotrophomonas maltophilia

Question 34

Risk factors for hospital acquired infection

Answer 34

high number of people crowded wards presence of pathogens broken skin (surgical wounds, IV catheter) indwelling devices (intubation) AB therapy can suppress normal flora transmission by staff

Question 35

how to fix resistance

Answer 35

prescribing strategies reduce use of broad-spectrum antibiotics quicker identification of infections by resistant strains combination therapy knowledge of local strains/resistance patterns

Question 36

overcoming resistance

Answer 36

modify existing modifications e.g. prevent cleavage in beta-lactams or enhance efficacy combine antibiotic + an inhibitor of e.g. beta lactamase