Hospital Acquired Infection and Antibiotic Resistance

Question 1

define bacteriostatic

Answer 1

stops bacterial growth

Question 2

define resistance

Answer 2

the ability of an organism to replicate in the presence of a certain concentration of AB

Question 3

define breakpoint

Answer 3

estimate of the reasonable concentration that might be achieved clinically

Question 4

define minimal inhibitory growth

Answer 4

lowest conc of AB required to inhibit growth

Question 5

why has resistance decreased? why was there a high incidence initially?

Answer 5

infection control measure

increased AB usage

Question 6

what were the initial misconceptions of resistance?

Answer 6

can’t be resistant to more than 1 AB
no horizontal gene transfer
resistant organisms would be less fit to cause infection

Question 7

how are infected patient treated?

Answer 7

initially given broad spectrum front line AB till infection identified
treated with specific AB
additional approaches e.g. surgery

Question 8

what are negatives of newer drugs that treatAB resistant bacteria?

Answer 8

more expensive, more side effects/toxic

Question 9

what is selective toxicity?

Answer 9

AB inhibit processes specific to bacteria

Question 10

explain the mechanism for Beta-Lactams and give examples of AB

Answer 10

interfere with peptidoglycan synthesis for cell wall by binding to penicillin binding proteins
e.g. penecillin and methicillin

Question 11

explain the mechanism and limits for aminoglycosides and give examples of AB

Answer 11

bactericidal
target 30s subunit of ribosome to inhibit protein synthesis and proofreading
damage cell wall
toxic but resistance means increasing use
e.g. gentamicin, streptomycin

Question 12

explain the mechanism and limits for rifampicin

Answer 12

bactericidal
targets RpoB subunit of RNA polymerase
affects compliance
spontaneous resistance

Question 13

explain the mechanism and limits for vancomycin

Answer 13

bactericidal
targets lipid II component of cell wall biosynthesis
targets wall cross linking via D-ala residues
toxic but resistance means increasing use

Question 14

explain the mechanism of linezolid

Answer 14

bacteriostatic
inhibits protein synthesis initiation by binding to 50S rRNA subunit
gram +ive activity

Question 15

explain the mechanism and limits of daptomycin

Answer 15

bactericidal
targets cell membrane
gram + activity
toxic limits dose

Question 16

Name the 4 mechanisms for antibiotic resistance

Answer 16

• altered target site
• inactivation of AB
• altered metabolism
• decreased drug accumulation

Question 17

explain altered target site

Answer 17

arise via acquisition of alternative gene or gene that encodes a target modifying enzyme

Question 18

explain inactivation of AB

Answer 18

enzymatic degradation or alteration so ineffective

Question 19

explain altered metabolism

Answer 19

increased production of enzyme substrate so out compete the AB inhibitor
bacteria switch to other metabolic pathways reducing need for target

Question 20

explain decreased drug accumulation

Answer 20

reduced penetration of AB into bacterial cell

increase efflux of AV out of cell so drug concentration not effective

Question 21

what are the sources of antibiotic resistance genes

Answer 21

plasmids - can carry multiple resistance genes
transposons - integrate into chromosomal DNA and transfer genes from plasmid to Chr
DNA - DNA from bacteria released into naked environment

Question 22

explain the mechanism of macrolides and give examples

Answer 22

gram +ive/-ive
targets 50S ribosomal subunit preventing amino-acyl transfer and truncation of polypeptides
e.g. erythromycin, azithromycin

Question 23

explain the mechanism of quinolines

Answer 23

synthetic
broad spectrum
bactericidal
targets DNA gyrase in gram -ive
targets topoisomerase IV in gram +ive

Question 24

list non-genetic mechanism of resistance or treatment failure

Answer 24

biofilm, IC location, slow growth, spores, persisters, inappropriate dose or administration, bad choice of AB

Question 25

why do hospitals provide a strong selective pressure for AB resistance?

Answer 25

large numbers of infected people with high doses of AB creates strong selective pressure for emergence or AB resistance

Question 26

list HAI risk factors

Answer 26

high number of ill people
crowded wards
pathogens present
broken skin - IV, surgery
indwelling devices - intubation
AB therapy suppresses normal microbiota and no competition for resistant 
staff transmission

Question 27

how is drug resistance and nosocomial prevented?

Answer 27

prescribing strategies
reduce broad spectrum AB use
quicker infection identification
combination therapy
knowledge of local strains and resistance patterns

Question 28

how is resistance overcome?

Answer 28

modification of existing meds

combination of AB and inhibitor