4. Antibiotics And Antimicrobials Flashcards

1
Q

4 antimicrobials (classification)

A
  • Antibacterial – antibiotics
    • Antifungal
    • Antiviral
    • Antiprotozoal
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2
Q

4 Classification of antibacterial agents

A

– bactericidal or bacteriostatic
– spectrum – ‘broad’ v. ‘narrow’
– target site (mechanism of action)
– chemical structure (antibacterial class)

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3
Q

Define – bactericidal bacteriostatic

A
  • Bacterialcidial = kill bacteria compeltely

* Bacteriostatic = stop bacteria replicating

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4
Q

Define spectrums of antibiotics

A

– spectrum – ‘broad’ v. ‘narrow’
• Treat a broad spectrum of organisms e.g. treat both gram positive and negatitive
• Treat narrow range

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5
Q

6 ideal features of antimicrobial agents

A
  • Selectively toxic
  • Few adverse effects
  • Reach site of infection
  • Oral/IV formulation
      ○ Oral drugs are easier to deliver 

• Long half-life (infrequent dosing)
○ How long drug lasts in body and how often to take drugs

• No interference with other drugs

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6
Q

Selecting the best antibiotic

A

1 empirical therapy → give best broad spectrum antibiotic as you have not yet identified causative organisms

  1. Isolate and identify causative organism
  2. Determine its sensitivity to antibiotics

4 • treat with appropriate narrow antibiotic

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7
Q

4 antibacterial mechanisms of action

A

Interfere with Cell wall synthesis

Interfere with Cell membrane function

Interfere with Protein synthesis – impact bacteria that produce proteins (toxins)

Interfere with Nucleic acid synthesis

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8
Q

Examples of antibacterials that

Interfere with Cell wall synthesis

A

• β-lactams
- bind to enzymes that form cross links between peptidoglycan so prevent cell wall synthesis , gram positive bacteria burst due to high internal osmotic pressure

• Glycopeptides
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9
Q

Examples of antibacterials that

Interfere with Cell membrane function

A
  • Polymixins (e.g. colistin)

* Daptomycin

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10
Q

Examples of antibacterials that

Interfere with Protein synthesis

A
  • Tetracyclines 30s
  • Aminoglycosides 30s

• Macrolides 50s

Antibiotics binds to 30s or 50s ribosomal - subunit causing interference in protein synthesis as mrna is misread or not read

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11
Q

Examples of antibiotics that

Interfere with Nucleic acid synthesis

A

• Quinolones
Bind to dna and enzymes in gram negative causing breaks in dna

* Trimethoprim 
* Rifampicin

Inhibit bacterial cell dna synthesis = death as it inhibits dna gyrase and topoisomerase iv enzymes needed for replication

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12
Q

4 mechanisms of resistance (that bacteria develop)

A
  • Drug inactivating enzymes (inactivate antibioticis)
  • Altered target
  • Altered uptake
  • Biofilm mode of growth
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13
Q

3 types of mechanisms of resistance (that bacteria develop)

A

Intrinisic
Acquired
Adaptive

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14
Q

Intrinsic resistance

A
  • no target or restricted access for drug

Bacteria are just naturally resistance

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15
Q

Acquired resistance

A

Mutates or accquires new genetic material

= most problematic

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16
Q

Adaptative resistance

A

Organism responds to a stress and adapts to its new growth enviroment

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17
Q

Examples of • Drug inactivating enzymes (inactivate antibioticis)

A
  • e.g. β-lactamases, = beta lactamase breaks up beta lactamase ring of penicillin
    • aminoglycoside enzymes
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18
Q

Mechanisms of resistance

-Altered target

A

• target has lowered affinity for antibacterial e.g. resistance to methicillin, macrolides & trimethoprim

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19
Q

Mechanisms of resistance

• Altered uptake

A
  • ↓permeability, so antibiotic can’t easily go into bacteria
    • or ↑efflux, to pump antibiotics out
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20
Q

Mechanisms of resistance

• Biofilm mode of growth

A

• Bacteria form biofilm, big tent thing to protect them

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21
Q

4 Genetic mechanisms of resistance

A

Transformation

Transposition

Conjugation

Mutation

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22
Q

Transformation

Genetic mechanisms of resistance

A

• direct uptake of DNA containing resistance genes

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23
Q

Transposition

Genetic mechanisms of resistance

A

• movement of resistance genes from plasmids to genome

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24
Q

Conjugation

Genetic mechanisms of resistance

A

• plasmids containing resistance genes are transferred from other organisms

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25
Mutation Genetic mechanisms of resistance
• base changes or deletions lead to altered targets of antibiotic action
26
3 ways of measuring antibiotic activity
• Disc sensitivity testing Antibiotic sensitivity by Etest Automated antibiotic sensitivity testing
27
• Disc sensitivity testing:
○ Sensitive ○ Intermediate = few bacteria grow ○ Resistant = nothing happens around zone bacteria still grow Look at zones of inhibition to find most effective antibiotic • Know which antibiotic is the most important
28
Antibiotic sensitivity by Etest
• Minimum inhibitory concetration MIC as mg/L ○ Minimum concentration of that antibiotic that inhibits bacterial growth * Strip with different concentrations of antibiotics * Minimum inhibitory concentration is where zone of bacteria stops
29
Automated antibiotic sensitivity testing
• Much faster • Minimum inhibitory concetration MIC as mg/L ○ Minimum concentration of that antibiotic that inhibits bacterial growth
30
Considerations for antibiotic therapy
* when to use antibiotic depends on Severity /cause of infection * Consider patient’s medical history, other drugs and allergy to antibiotics (e.g. allergy to penicillin) * Taking samples (eg swab, blood, urine sample, tissue or bone sample) before start of antibiotic therapy * Broad spectrum antibiotics should be used if there is an urgency and the causative organism has not been identified * Route of administration * Dose of antibiotics * Combination therapy = 2 antibiotics at a time * Longevity of therapy * Prophylaxis = problem with heart valves, heart valves can be very prone to infection
31
Examples of beta lactams | More info on 4'1 slides
* Penicillins * Cephalosporins * Carbapenems * Monobactams
32
Penicillin
• mainly active against streptococci
33
3 types of penicillins
Penicillin Amoxicillin Flucloxacillin
34
Amoxicillin
* also some activity against Gram-negatives | * Broad spectrum
35
Flucloxacillin
• active against staphylococci & streptococci
36
Penicillins: β-lactamase inhibitor combinations
* amoxicillin/clavulanate (all of above +anaerobes + Gram negative bacteria) * piperacillin/tazobactam (as above + Gram negative, including Pseudomonas species
37
Cephalosporins
Broad-spectrum but no anaerobe activity – don't act on anaerobic bacteria (e.g. clostridium) * Cetriaxone has good activity in the CSF * Concern over association with C. difficile major side effect of this drug is c.difficile infection * Ceftazidime + avibactam and ceftolozane + tazobactam used for multidrug resistant Gram negative infections
38
Carbapenems
→ safe if allergic to penicillin ``` • Imipenem • meropenem • ertapenem – very broad spectrum (incl anaerobes) – active against most (not all) Gram negatives – generally safe in penicillin allergy ``` • imipenem + relebactam – serious Gram negative infections (including anaerobes) • meropenem + vaborbactam – complicated Gram negative UTI
39
3 types of glycopeptides
---> interfere with cell wall synthesis Vancomycin Teicoplanin Dalbavancin and telavancin
40
Vancomycin
– active against most Gram positive (not Gram negative) – some enterococci resistant (VRE) – resistance in staphs rare – not absorbed (oral for C. difficile only as it acts locally), normally given intravenously for other infections – therapeutic drug monitoring (TDM) required (narrow therapeutic window)
41
Tetracyclines | Impact bacteria protein synthesis
Tetracycline & doxycycline – similar spectrum, both oral only – broad-spectrum but specific use in penicillin allergy, usually for Gram positive – active in atypical pathogens in pneumonia – active against chlamydia & some protozoa – should not be given to children <12 years = as it affects mineralising tissue
42
Aminoglycosides - impact bacteria protein synthesis
Most common agent is gentamicin = can be quite toxic * Profound activity against Gram negative * Good activity in the blood/urine * Potentially nephrotoxic/ototoxic * Therapeutic drug monitoring (TDM) required * Generally reserved for severe Gram negative sepsis
43
Macrolides - impact bacteria protein synthesis
e.g. erythromycin (& clarithromycin) • Well distributed including intracellular penetration • Alternative to penicillin for mild Gram positive infections • Also active against atypical respiratory pathogens
44
Antifungals
• Azoles (active against yeasts +/- molds – inhibit cell-membrane synthesis – fluconazole used to treat Candida • Itra/vori/posaconazole also active against Aspergillus • Polyenes (nystatin and amphotericin) – inhibit cell membrane function – nystatin for topical treatment of Candida – amphotericin for IV treatment of systemic fungal infections (e.g. Aspergillus) Fungal infections = very severe in immunocompromised patients
45
Metronidazole – antibacterial and antiprotozoal agents
• Active against anaerobic bacteria • Also active against protozoa: – Amoebae (dysentery & systemic) – Giardia (diarrhoea) – Trichomonas (vaginitis)
46
Antivirals
• Aciclovir – when phosphorylated inhibits viral DNA polymerase = inhibit DNA viruses – Herpes simplex – genital herpes, encephalitis – Varicella zoster – chicken pox & shingles • Oseltamivir (‘Tamiflu’) – inhibits viral neuraminidase = stops virus from leaving the cell – influenza A & B • Specialist agents for HIV, HBV, HCV, CMV
47
Process of antibiotic resistance
→ through natural selection 1. Genetic mechanisms confer drug resistance due to mutations and genetic variation 2. Antibiotics kill non-resistant bacteria 3. Drug resistant bacteria selected and reproduce due to competitive advantage (less competition for food and space etc) 4. Drug resistance gene transmitted through (exposure naïve) population
48
3 levels of antibiotic resistance
MDR (multi-drug resistant) XDR (extensively drug resistant) PDR (pan-drug resistant)
49
MDR (multi-drug resistant)
Non-susceptibility to at least one agent in three or more antimicrobial categories
50
XDR (extensively drug resistant)
• Non-susceptibility to at least one agent in all but two or fewer antimicrobial categories
51
PDR (pan-drug resistant)
* Non-susceptibility to all agents in all antimicrobial categories * Smallest populations of bacteria
52
Relationship between antimicrobial use and resistance
As prescribing and use increases so does resistance
53
3 forms of Evidence that anti-bacterials cause resistance
Laboratory evidence Ecological studies Individual level data
54
Laboratory evidence
* Provides biological plausibility | * Colonies growing on agar plates – see antibiotics working
55
Ecological studies
* Relates levels of antibacterial use in a population with levels of resistance * Patterns of resistance and prescribing
56
Individual level data
• Relates prior antibacterial use in an individual with the subsequent presence of bacterial resistance (detected by culture or molecular means)
57
Pharmaceutical companies and antiniotics
* Get a lot of money for making medications for chronic conditions * Not much money to be made in antibiotics * Hard to make antibiotics from scratch as we don't have enough understanding
58
Define antimicrobial stewardship
Commitment to always use antibiotics appropriately and safe Only when they are needed Choose right antibiotics and administer them in the right way
59
Why do GP staff prescribe antibiotics – inappropriately
• Relief of symptoms ○ They think the antibiotics might work, better than just leaving the infection • Worry about complications/more serious illness ○ Worried that leaving it untreated may lead to something more serious • Patient pressure ○ what the patient wants, we want to be liked by patients
60
IDSA defintion of antimicrobial | Stewardship
Coordinated interventions designed to improve and measure the appropriate use of antimicrobials by promoting the selection of the optimal antimicrobial drug regimen, dose, duration of therapy, and route of administration. Antimicrobial stewards seek to achieve optimal clinical outcomes related to antimicrobial use, minimize toxicity and other adverse events, reduce the costs of health care for infections, and limit the selection for antimicrobial resistant strains
61
Symptom benefit from antibiotics
---> if antibiotics are given appropriately, duration of infection can be reduced • The antibitoics do relieve symptoms but patients need to understand if the antibiotics will actually be benefical for them NNT – number needed to treat • NNT for an adverse effect is always lower than the NNT for one additional benefit to patient • If you take na antibiotic and give it to patient= you are more likely to harm them than improve them if the antibiotic is given inappropriately
62
3 Elements of antimicrobial stewardship programme
• MDT Surveillance Interventions
63
• MDT
Effective collaboration across multidisciplinary team in implementing antimicrobial stewardship
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• Surveillance
– Process measures • Antibacterial use (quantity, type, appropriateness) • Benchmarking within and between organisations – Outcome measures • Patient • Emergence of resistant organisms
65
• Interventions
– Persuasive = people, opinions, advice – Restrictive = rules and regulations – Structural = • Computerised records, Rapid lab tests, Expert systems,Quality monitoring
66
Cellulitis - cause
Infection of deep dermis Streptococcus pyogenes Staphylococcus aureus
67
How does phagocytotic cell recognise pathogen
Prp recognise pamps
68
Cellutis supportive treatment
Nsaid Pain relief Elevation and immobilisation of leg Saline dressings
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Antibiotics for cellulitis
Vancomyosin flucloxacilin Doxycilin
70
Dysuria
Difficulty, pain , discomfort passing urine