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POM Flashcards (Y1) > Antimicrobial Therapies > Flashcards

Antimicrobial Therapies Flashcards

1
Q

Define antibiotic

A

Antimicrobial agent produced by a microorganism that kills or inhibits other microorganisms.
Target many different bacterial processes and are SELECTIVELY TOXIC

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2
Q

What are most antibiotics used today produced by?

A

Soil-dwelling fungi or bacteria

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3
Q

Define antimicrobial

A

Chemical that selectively kills or inhibits microbes (bacteria, fungi, viruses)

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4
Q

Define bactericidal

A

Kills bacteria

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5
Q

Define bacteriostatic

A

Stops bacteria growing

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6
Q

Define antiseptic

A

Chemical that kills or inhibits microbes, that is usually used to prevent infection

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7
Q

What was the first example of a sulphonamide antibiotic?

A

Prontosil

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8
Q

What is prontosil used to treat?

A

Urinary tract infections
Respiratory tract infections
Bacteraemia
Prophylaxis for HIV + individuals

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9
Q

What is the mechanism of prontosil?

A

Inhibits dihydropteroate synthase which is critical for synthesis of folate

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10
Q

What are the reasons for why antibiotic resistance may lead to increased mortality, morbidity and cost?

A

Increased time to effective therapy
Requirement for additional approaches e.g - surgery
Use of expensive therapy (newer drugs)
Use of more toxic drugs e.g- vancomycin
Use of less effective ‘second choice’ antibiotics

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11
Q

Give two examples of aminoglycosides

A

Gentamicin

Streptomycin

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12
Q

What is the mechanism of aminoglycosides?

A

Targets 30S ribosomal subunit
Causes damage to cell membrane
Targets protein synthesis and RNA proofreading (aberrant protein production)

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13
Q

What do aminoglycosides treat?

A

Severe infections of abdomen and urinary tract
Bacteraemia
Prophylaxis against endocarditis

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14
Q

Are aminoglycosides bactericidal or bacteriostatic?

A

Bactericidal

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15
Q

What has led to increasing use of aminoglycosides?

A

Resistance to other antibiotics

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16
Q

What is the mechanism of rifampicin?

A

Targets RpoB subunit of RNA polymerase (blocks transcription - bactericidal)

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17
Q

What colour does rifampicin make your secretion go?

A

Orange/red - affects compliance

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18
Q

What is a frequent issue with Rifampicin?

A

Spontaneous resistance

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19
Q

What is the mechanism of vancomycin and is it bactericidal or bacteriostatic?

A

Targets Lipid II component of cell wall biosynthesis, as well as wall cross-linking via D-ala residues
Bactericidal

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20
Q

What has lead to increasing use of vancomycin, despite toxicity?

A

Resistance to other antibiotics, e.g MRSA

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21
Q

What is the mechanism of linezolid?

A

Inhibits the initiation of protein synthesis by binding to 50S rRNA subunit (bacteriostatic)

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22
Q

What spectrum of activity does linezolid have?

A

Gram positive spectrum of activity

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23
Q

What limits the dose of daptomycin?

A

Toxicity (has to be delivered intravenously)

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24
Q

What is the mechanism of daptomycin?

A

Bactericidal - targets bacterial cell membrane

25
What is the spectrum activity of daptomycin?
Gram-positive spectrum
26
Give 2 examples of beta-lactams
Penicillin | Methicillin
27
What is the mechanism of beta-lactams?
Interfere with the synthesis of the peptidoglycan component of the bacterial cell wall (bind to penicillin-binding proteins) Bactericidal
28
Give 2 processes that are unique to bacterial cells
Production of peptidoglycan | Maintenance of LPS layer of gram negative bacteria
29
Give 2 examples of macrolides
Erythromycin | Azithromycin (can be used for gonococcal infections)
30
What spectrum of infections do macrolides target?
Gram-positive | Some Gram-negative infections
31
Describe the mechanism of macrolides
Targets 50S ribosomal subunit preventing amino-acyl transfer | Thus truncation of polypeptides
32
What are quinolones?
Synthetic, broad spectrum, bactericidal antibiotics
33
What do quinolones target?
``` DNA gyrase (Gram -) Topoisomerase IV (Gram +) ```
34
What are quinolones used to treat?
Lower respiratory tract infection, blood infections, UTIs (e.g gonococcal) and skin infections
35
What is meant by resistance?
If a bacterium can grow at or above the breakpoint concentration (minimal inhibitory concentration of antibiotic)
36
Why might there be more of a resistance to penicillin in hospitals than the community?
Routine use of penicillin in hospitals provides a selection pressure For the acquisition and maintenance of resistance genes
37
What are the 4 distinct mechanisms by which antibiotic resistance can occur?
Altered target site Inactivation of antibiotic Altered mechanism (bypass processes inhibited by AB) Decreased drug accumulation
38
Give 2 examples in which a target site can be altered
MRSA encodes alternative PBP with low affinity for beta lactams Acquisition of erm gene by streptococcus pneumoniae encodes an enzyme that methylates AB target site in 50S ribosomal subunit
39
How does inactivation of antibiotic occur?
Enzymatic degradation or alteration, rending antibiotic ineffective. E.g beta-lactamases (bla) and chloramphenicol acetyl-transferase (cat)
40
What is one of the greatest threats to antibiotic use at the moment?
Bacteria that encode broad-spectrum beta-lactamases | Such as ESBL and NDM-1 which can degrade a wide range of beta-lactams
41
How does the altered metabolism pathway occur within antibiotic resistance?
Increased production of enzyme substrate can out-compete antibiotic for target site, e.g increased PABA production - resistance to sulphonamides Bacteria can switch to other metabolic pathways, reducing requirement for PABA
42
How does decreased drug accumulation occur?
Reduced penetration of AB into bacterial cell Or increased efflux pumps to keep AB out of cell Makes it so that AB doesn’t reach concentration in cell to be effective
43
What gram negative bacteria is associated with cystic fibrosis, burn wound infections and survives on abiotic surfaces?
Pseudomonas aeruginosa
44
What gram negative bacteria is associated with GI infection, neonatal meningitis, septicaemia and UTI?
E.coli
45
What gram negative bacteria is associated with GI infection and typhoid fever?
Salmonella spp.
46
What gram negative bacteria is associated with opportunistic infections, wounds, UTI, pneumonia and survives on abiotic surfaces?
Acinetobacter baumannii
47
What gram positive bacteria is associated with wound and skin infections, pneumonia, scepticaemia and infective endocarditis?
Staphylococcus aureus
48
What gram positive bacteria is associated with pseudomembranous colitis and antibiotic-associated diarrhoea?
Clostridium difficile
49
What gram positive bacteria is associated with UTI, bacteraemia and infective endocarditis?
Enterococcus spp
50
What are the 3 sources of antibiotic resistant genes and how do they work?
Plasmids - extra-chromosomal circular DNA, often carry multiple AB resistant genes and selection for one maintains resistance for all Transposons - integrate into chromosomal DNA and allow transfer of genes from plasmid to chromosome and vice versa Naked DNA - DNA from dead bacteria released into the environment
51
Describe the 3 ways that bacteria can spread their AB resistant genes.
Transformation - uptake of extracellular DNA Transduction (phage-mediated) - viruses infect bacteria and take up some of their DNA and then go on to infect other bacteria, passing on the DNA Conjugation - bacterial sex to share plasmids between them
52
Give some of the non-genetic mechanisms of resistance/treatment failure.
Biofilm - matrix encased communities of bacteria that are highly drug tolerant will minimise penetrative effect of antibiotics Intracellular location - harder for antibiotics to get to bacteria Slow growth - hard for antibiotics to inhibit replication processes if they do not occur as much Spores - resistant to heat, antibiotics, antiseptics; spore coat is impermeable to antibiotics, preventing access to target organelles Persisters - dormant bacteria that are not carrying out the processes that antibiotics inhibit
53
What are three solutions to reducing antibiotic resistance?
Phage antibiotic combination therapy Modifications of existing antibiotics (prevent cleavage) Combination of inhibitor and antibiotic
54
In what sectors are antibiotics used more?
Critical care | Wards
55
What are some of the risk factors for HAI?
``` High number of ill people Crowded wards Presence of pathogens Broken skin - surgical wound/IV catheter Indwelling devices - intubation AB therapy - may suppress normal flora Transmission by staff - contact with multiple patients ```
56
How might AB therapy impair commensal flora?
AB therapy removes commensal organisms Pathogen has no competition leading to overgrowth Pathogen produces toxins and damages host-symptomatic infection Spreads to other patients
57
Give some of the methods we might use to address resistance
Prescribing strategies - tighter controls, temporary withdrawal of certain classes and restrictions of ABs for certain serious infections Reduced use of broad spectrum antibiotics Quicker identification of infections caused by resistant strains Combination therapies Clinicians should have knowledge of local strains and resistance patterns
58
What 3 broad classes of conditions are caused by fungi?
Allergy - allergic reactions to fungal products, e.g ABPA Mycotoxicoses - ingestion of fungi and their toxic products, e.g aflatoxin Mycoses - superficial, subcutaneous or systemic colonisation, invasion and destruction of human tissue.
59
What do fungi cell membranes contain instead of cholesterol?
Ergosterol Also have a cell wall

POM Flashcards (Y1) (28 decks)

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