Microbiology 3- Hospital acquired infection and antibiotic resistance

Question 1

Identify bacteria which are multi drug resistant, classifying them by gram- (6) or gram + (5)

Answer 1

Gram-negative:
Pseudomonas aeruginosa
E. Coli (ESBL)
Klebsiella spp (NDM-1)
Salmonella spp. (MDR)
Acinetobacter baumannii (MDRAB)
Neisseria gonorrhoeae

Gram positive:
Staphylococcus aureus (MRSA, VISA)
Streptococcus pneumoniae
Clostridium difficle
Enterococcus spp (VRE)
Mycobacterium tuberculosis (MDRTB, XDRTB)

Question 2

List reasons for high rate of hospital acquired infections (6)

Answer 2

High density of suceptiable people

Presence of pathogens

Staff vectors

Open wounds

Inserted medical devices

disruption of normal flora due to antibitotic prophylaxis/ttherapy

Question 3

Describe the action of Beta-Lactams and give two examples of AB that use this action

Answer 3

Interfere with synthesis of the PEPTIDOGLYCAN component of the bacterial cell wall

Binds to Penicillin Binding Proteins (PBP) - they catalyse a number of steps in peptidoglycan synthesis

The beta-lactam ring is similar in structure to a precursor of peptidoglycan - interferes with the biosynthetic pathway of peptidoglycan

Examples: Penicillin and methicillin

NOTE: MRSA has a different PBP (PBP2a) which doesn’t bind with high affinity to beta-lactams

Question 4

Describe the action of tertacyline

Answer 4

Inhibits PROTEIN SYNTHESIS

Binds to the 16S component of the 30S ribosomal subunit thus preventing charged aminoacyl tRNAs from binding to the mRNA/ribosome complex

Prevents elongation of the polypeptide

Question 5

Describe the action of Chloramphenicol

Answer 5

Inhibits protein synthesis.
Binds to 50S ribosomal subunit and blocks peptidyl transfer step.
Often used topically due to toxicity. However, increasing AB resistance is renewing interest in Chloramphenicol as a systemic therapeutic.

Question 6

Describe the action of Quinolones

Answer 6

Bactericidal - broad spectrum

Targets DNA gyrase (in Gram NEGATIVE) and topoisomerase (in Gram POSITIVE)

DNA gyrase and topoisomerase is responsible for unravelling DNA

Question 7

Describe the action Sulphonamides

Answer 7

Used to treat UTI, Reproductive Tract Infection (RTI) and bacteraemia

Interferes with the folate pathway

Question 8

Describe the action of Aminoglycosides and give two examples

Answer 8

Bactericidal

Affect PROTEIN SYNTHESIS

Affects RNA PROOFREADING which leads to misfolded proteins

Some of these proteins are incorporated into the membrane and allow leakage so the cells rupture.

Has toxicity issues

EXAMPLES: Gentamycin, Streptomycin

Question 9

Describe the action of Macrolides

Answer 9

Gram POSITIVE infections

Targets 50S ribosomal subunit preventing aminoacyl transfer

Causes truncation of polypeptides

EXAMPLE: Erythromycin

Question 10

What are the 4 mechanisms of antibiotic resistance

Answer 10

Altered target site.
Inactivation of antibiotic.
Altered metabolism.
Decreased drug accumulation.

Question 11

Describe how altered target site can cause AB resistance

Answer 11

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

Methicillin-resistant Staphylococcus aureus (MRSA) encodes an alternative PBP (PBP2a) with low affinity for beta-lactams.

Streptococcus pneumoniae resistance to erythromycin occurs via the acquisition of the erm gene, which encodes an enzyme that methylates the AB target site in the 50S ribosomal subunit.

Question 12

Describe how inactivation of antibiotic can cause AB resistance

Answer 12

Enzymatic degradation or alteration, rendering antibiotic ineffective.

Examples include 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 13

Describe how Altered metabolism can cause AB resistance

Answer 13

Re-engineer the metabolic pathways so you bypass the step that the antibiotic interferes with.

Increased production of enzyme substrate can be used to outcompete antibiotic inhibitor

EXAMPLE: increased production of PABA confers resistance to sulphonamides

Question 14

Describe how Decreased drug accumulationm can cause AB resistance

Answer 14

Reduced permeability of AB into bacterial cell

Increase EFFLUX of AB out of cell

Drug does not reach sufficient concentration to be effective

Question 15

Summarise some of the main approaches to prevent drug resistant bacteria

Answer 15

Better prescribing practises

Infection control

Combination therapy

Narrow vs broad spectrum antibiotics