Antimicrobial Therapy Flashcards

1
Q

What was the first example of a sulphonamide antibiotic?

A

Prontosil

Bacteriostatic.

Synthetic

Examples include sulpha-methoxazole. Sometimes used together with Trimethoprim (co-trimoxazole).

Used to treat UTIs, RTIs, bacteraemia and prophylaxis for HIV+ individuals.

Becoming more common due to resistance to other antimicrobials, despite some host toxicity.

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2
Q

What is an antibiotic?

A

An antibiotic is an antimicrobial agent produced by a microorganism that kills or inhibits other microorganisms.

Made by soil fungi or bacteria.

Can be synthethic

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3
Q

What is a antimicrobial?

A

Antimicrobial – chemical that selectively kills or inhibits microbes (bacteria, fungi, viruses).

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4
Q

What is an antiseptic?

A

Antiseptic – chemical that kills or inhibits microbes that is usually used topically to prevent infection.

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5
Q

What antibiotics were found in in the 1940s?

A
gramicidin
Pencillin B
Neomycin
Streptomycin
Cephalosporin
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6
Q

What antibiotics were found in the 1950s?

A
Chloramphenicol
Chlortetracycline
Polymyxin
Erythromycin
Vancomycin
Cirginamycin
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7
Q

Examples of Aminoglycosides? What do they do?

A

E.g. Gentamicin, streptomycin.

Bactericidal.

Target protein synthesis (30S ribosomal subunit), RNA proofreading and cause damage to cell membrane.

Toxicity has limited use, but resistance to other antibiotics has led to increasing use.

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8
Q

Rifampcin?

A

Bactericidal.

Targets RpoB subunit of RNA polymerase.

Spontaneous resistance is frequent.

Makes secretions go orange/red – affects compliance.

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9
Q

Vancomycin?

A

Bactericidal.

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

Toxicity has limited use, but resistance to other antibiotics has led to increasing use e.g. against MRSA

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10
Q

Linezolid?

A

Bacteriostatic.

Inhibits the initiation of protein synthesis by binding to the 50S rRNA subunit.

Gram-positive spectrum of activity.

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11
Q

Daptomycin?

A

Bactericidal.

Targets bacterial cell membrane.

Gram-positive spectrum of activity.

Toxicity limits dose.

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12
Q

What are Beta-lactams?

A

Interfere with the synthesis of the peptidoglycan component of the bacterial cell wall.

Examples include Penicillin and methicillin.

Bind to penicillin-binding proteins.

PBPs catalyse a number of steps in the synthesis of peptidoglycan.

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13
Q

What are Macrolides?

A

E.g. Erythromycin, azithromycin.

Gram-positive and some Gram-negative infections.

Targets 50S ribosomal subunit preventing amino-acyl transfer and thus truncation of polypeptides.

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14
Q

What are Quinolones?

A

Synthetic, broad spectrum, bactericidal.

Target DNA gyrase in Gm-ve and topoisomerase IV in Gm+ve.

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15
Q

Antibiotic resistance occurs via which 4 distinct mechanisms?

A

Altered target site.

Inactivation of antibiotic.

Altered metabolism.

Decreased drug accumulation.

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16
Q

Examples of bacterial altered target site?

A

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.

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17
Q

Examples of bacterial inactivation of antibiotic?

A

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).

18
Q

Examples of bacterial altered metabolism?

A

Increased production of enzyme substrate can out-compete antibiotic inhibitor (e.g. increased production of PABA confers resistance to sulfonamides).

Alternatively, bacteria switch to other metabolic pathways, reducing requirement for PABA.

19
Q

Bacterial decreased drug accumulation examples?

A

Reduced penetration of AB into bacterial cell (permeability) and/or increased efflux of AB out of the cell – drug does not reach concentration required to be effective.

20
Q
Penicillin
Penicillin
tetracycline
Quinolone
Cefotaxime
Spectinomycin 

Resistance mechanisms? What have they acquired due to them?

A

Penicillin : Penicillinases – plasmid transformation

Penicillin : Target site modification – point mutation

tetracycline : Efflux pump – Plasmid-conjugation

Quinolone : target site modification – Plasmid mutation

Cefotaxime : target site modification – Plasmid mutation

Spectinomycin : target site modification – Plasmid mutation

21
Q

What does Pseudomonas aeruginosa do?

A

Gram -

Cystic fibrosis, burn wound infections. Survives on abiotic surfaces.

22
Q

What does E.Coli do?

A

Gram -

GI infect., neonatal meningitis, septicaemia, UTI.

23
Q

What does salmonella do?

A

Gram -

GI infect. , typhoid fever.

24
Q

What does Acinetobacter baumannii do?

A

Gram -

Opportunistic, wounds, UTI, pneumonia (VAP). Survives on abiotic surfaces.

25
Q

What does Neisseria gonorrhoeae?

A

Gram -

Gonorrhoea

26
Q

What does S.Aureus do?

A

Gram +

Wound and skin infect. pneumonia, septicaemia, infective endocarditis.

27
Q

What does Streptococcus pneumoniae do?

A

Gram +

Pneumonia, septicaemia.

28
Q

What does C.diffcle do?

A

Gram +

Pseudomembranous colitis, antibiotic-associated diarrhoea.
Enterococcus

29
Q

What does enterococcus spp do?

A

Gram +

UTI, bacteraemia, infective endocarditis.

30
Q

What does Mycobacterium tuberculosis do?

A

Gram +

Tuberculosis

31
Q

What are three sources of antibiotic resistance genes?

A

Plasmids – extra-chromosomal circular DNA, often multiple copy. Often carry mutliple AB res genes – selection for one maintains resistance to all.

Transposons. Integrate into chromosomal DNA. Allow transfer of genes from plasmid to chromosome and vice versa.

Naked DNA. DNA from dead bacteria released into environment.

32
Q

What three methods can genes be transferred between bacteria?

A

Transformation : uptake of extracellular DNA

Transduction : phase mediated DNA transfer

Conjugation : pilus mediated DNA transfer

33
Q

What non-genetic mechanisms of resistance?

A
Biofilm
Intracellular location
Slow growth
Spores
Persisters
34
Q

Why do hospitals provide strong selective pressures for Antibiotic resistance?

A

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

35
Q

Examples of HAIs?

A

Methicillin-resistant S. aureus (MRSA)

Vancomycin-insensitive S. aureus (VISA)

Clostridium difficle

Vancomycin-resistant enterococci (VRE)
E. coli (ESBL/NDM-1)

P. aeruginosa

Acineterbacter baumannii

Stenotrophomonas maltophilia

36
Q

Risk factors for HAIs?

A

High number of ill people! (immunosuppression)

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

37
Q

What three conditions can fungi cause in humans?

A

Allergy

Mycotoxicoses

Mycoses

38
Q

What is Mycotoxicoses?

A

ingestion of fungi and their toxic products e. g. aflatoxin

39
Q

What is Mycoses?

A

superficial, subcutaneous or systemic colonisation, invasion and destruction of human tissue. See image for their classification in releation to tissue location.

40
Q

How are mycoses classified?

A

By level of tissue affected:

Superficial

Cutaneous

Subcutaneous

or systemically

41
Q

What are the targets for antifungal therapy?

A

Cell membrane - fungi use ergosterol

DNA synthesis - some compounds may be selectively activated by fungi

Cell wall