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Flashcards in MB6 Antimicrobials 1 Deck (32):
1

Learning Outcomes (for general perusal)

Aim

Introduce core concepts of selective toxicity, ecologic damage, antimicrobial allergy and antiviral agents

Outcomes 

1.  Apply the terms selective toxicity, antimicrobial prophylaxis and broad spectrum antimicrobials appropriately

2.Identify from a list drugs that would be contra-indicated in a patient with type 1 hypersensitivity reaction to a beta-lactam antimicrobial

3.Identify a core list of antiviral agents, their site of action and common usage 

 

a tension here between the drive to conserve antibiotics which often requires restricting prescription and tackling sepsis which requires more antibiotics

2

What will be covered? (for general perusal)

  1. Some language associated with antimicrobial use
  2. 7 categories of antibacterials
  3. A basic approach to using antimicrobials:  ‘Start smart then focus’
  4. Penicillin allergy
  5. Antiviral therapy 

3

1. Some language associated with antimicrobial use

  1. What is selective toxicity?
  2. What can the toxicity of antibiotics be dependant upon?
  3. How can antimicrobials be selectively toxic?

  1. Antimicrobials are intended to be drugs that kill microorganisms but do not harm the host cells

  2. Antibiotics are generally toxic to eukaryotic cells, this can be dependent on dose and duration

  3. By targeting Cell wall, Protein synthesis, Process of DNA supercoiling, Folate metabolism

 

Human Ecosystem:

  100 trillion non human cells

  90 trillion bacteria

  10 trillion fungi

  500 trillion viruses

  8 000 000 genes

4

2. 7 Categories of Antibacterials

Name the 7 Categories 

Cell Wall Active

  1. Beta-Lactams
  2. Glycopeptides

Protein Synthesis Inhibitors

​3. Macrolides

4. Aminoglycosides

5. Tetracyclines

 

6. Quinolones

7. Others

5

Antibacterial Tree

What are the sub groups within the group

Beta lactams

Give examples of drugs

  • Penicillins
    • Benzylpenicillin, Flucloxacillin, Amoxicillin

  • Penicillin/beta-lactamase inhibitor combinations
    • Co-amoxiclav, Piperacillin-tazobactam

  • Cephalosporins
    • Cefuroxime, Ceftriaxone

  • Monobactam
    • Aztreonam

  • Carbapanems
    • Meropenem, Ertapenem

6

Give examples of drugs from the following groups (all except beta lactams)

2. Glycopeptides

3. Macrolides

4. Aminoglycosides

5. Tetracyclines

6.Quinolones

7. Other

2. Vancomycin, Teicoplanin

3. Clarithromycin, Erythromicin

4. Gentamicin

5. Doxycycline

6. Ciprofloxacin, Levofloxacin

7. Metronidazole, Trimethoprim, Nitrofurantoin

7

What does Broad Spectrum mean?

Denoting antibiotics used in human medicine, that are effective against a large variety of medically important organisms

8

Recap: How can bacteria be classified?

  • Gram Positive
    • ​Cocci
      • ​Clusters 

        Staphylococcus aureus

        Staphylococcus epidermidis

      • Chains

        β-haemoyltic Streptococci:

        (Lancefield group A, B, G)

        Streptococcus oralis

        Streptococcus pneumoniae

        Enterococcus faecalis

    • Rods

      Clostridium tetani

      Clostridium difficile

      Clostridium perfringens

      Listeria monocytogenes

      Bacillus species

      Proprionibacterium acnes

      Lactobacillus lacti

  • Gram Negative 
    • ​Cocci

      Neisseria meningitidis

      Neisseria gonorrhoeae

      Haemophilus influenzae

    • Rods
      • ​Enterobactericeae

        Escherichia coli

        Klebsiella pneumoniae

        Proteus mirabilis

        Salmonella enteritidis

      • Non-enterobactericeae

        Bacteroides fragilis

        Pseudomonas aeruginosa

        Campylobacter jejuni

  • Others
    • ​Mycobacterium tuberculosis
    • Legionella pneumophila
    • Chlamydia trachomatis

    • Mycoplasma pneumoniae

    • Treponema pallidum

9

Name the 

  1. Gram positive bacteria
  2. Gram-negative bacteria 
  3. Other bacteria

  1. Staphylococcus aureus

    Staphylococcus epidermidis

    β-haemoyltic Streptococci:

    (Lancefield group A, B, G)

    Streptococcus oralis

    Streptococcus pneumoniae

    Enterococcus faecalis

    Clostridium tetani

    Clostridium difficile

    Clostridium perfringens

    Listeria monocytogenes

    Bacillus species

    Proprionibacterium acnes

    Lactobacillus lacti

  2. Neisseria meningitidis

    Neisseria gonorrhoeae

    Haemophilus influenzae

    Escherichia coli

    Klebsiella pneumoniae

    Proteus mirabilis

    Salmonella enteritidis

    Bacteroides fragilis

    Pseudomonas aeruginosa

    Campylobacter jejuni

  3. Legionella  pneumophila

    Chlamydia trachomatis

    Mycoplasma pneumoniae

    Treponema pallidum

    1. Mycobacterium tuberculosis

10

Narrow vs. Wide Spectrum

For general persual

In GREEN: usually effective or >60% susceptible

In AMBER: clinical trails lacking or 30-60% susceptible

In RED: not clinically effective or <30% susceptible

11

Narrow vs. Wide Spectrum

  1. Name a narrow spectrum antibacterial drug
  2. From what group is it from?
  3. What is it usually effective in (or 60% susceptible)
  4. What are clinical trails lacking for use in?
  5. What is it NOT clinically effective in?

  1. Flucloxacillin
  2. Beta-lactams, Penicillins
  3. Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Clostridium tetani, Clostridium perfringens

  4. Streptococcus oralis

  5. All others 

12

Narrow Vs. Wide Spectrum

  1. Name a wide spectrum antibacterial drug
  2. From what group is it from?
  3. For which bacteria is it NOT effective?
  4. For which are clinical trials ongoing?
  5. For which bacteria is it effective?

  1. Meropenem
  2. Beta-lactem, Carbapanem
  3. Legionella  pneumophila

    Chlamydia trachomatis

    Mycoplasma pneumoniae

  4. Enterococcus faecalis, Mycobacterium tuberculosis

  5. All others

13

3. A basic approach to using antimicrobials

 ‘Start smart then focus’

  1. What is a huge cause of mortilty?
  2. What is the issue with infection and diagnosis?
  3. What are the principles of antimicrobial use?

  1. Sepsis
  2. There is not a single definitive  clinical or laboratory marker of infection. Temperature and laboratory tests cause more harm than good if the diagnostic process is not followed. Focus on patient and the symptoms and signs at the inflamed organ site

  3. Do not start antibiotics in the absence of clinical evidence of infection. Thorough drug allergy history required.

14

Penicillin Allergy

  1. Why is it so prevalent?
  2. What is the prevalence?
  3. What is the pathological process and symptoms involved?

  1. 10% of patients report allergy to penicillin: nausea, diarrhoea, thrush, rash, headache, fever, collapse, wheeze, swelling of face, mouth or tongue

  2. Probably <1% have had a type one hypersensitivity reaction 

  3. •IgE mediated with mast cell degranulation of histamine

    •Immediate onset

    •collapse, wheeze, swelling of face, mouth or tongue, rash of urticarial (nettle-sting) appearance

15

Penicillin Allergy

What is the effect of so many people reporting penicillin allergies?

Fewer choices

Less efficacious choices

More toxic choices

Specific patient group problems: pregnancy, renal failure

16

What does a thorough drug history entail?

  • What drug
  • When did you take it (i.e. What age were you)
  • How long after taking the drug did the adverse reaction start (type 1, IgE reactions tend to be immediate)
  • Describe the reaction (paying attention to the appearance of rash)

17

Penicillin Reactions

  1. What is a life-threatening reaction?
  2. What CANNOT be given?
  3. What can be given in a reaction that wasn't life-threatening?

  1. IgE Mediated type one hypersensitivity reaction
  2. NO Beta-lactams, except Aztreonam (from Monobactam group)

  3. Avoid penicillins,  all other beta lactams are fine

    1. Penicillin / beta-lactamase inhibitor combinations, Cephalosporins, Monobactam, Carbapanems

18

Outline the 'Start Smart then Focus' approach to antimicrobial use?

  • Do not start antibiotics in the absence of clinical evidence of infection
  • Thorough drug allergy history
  • Rapid assessment for Sepsis 
  • Comply with local guidelines

  • Document diagnosis and treatment

  • Document review and stop date

  • Obtain cultures prior to starting treatment

 

19

'Start Smart then Focus' approach to antimicrobial use

  1. When should a clinical review take place?
  2. What decisions can be made?

  1. with microbiological results at 48-72 hours
  2. 1. Stop

      2. IV to oral switch

      3. change antibiotic

      4. Continue

      5. OPAT (Outpatient Parenteral Antimicrobial Therapy)

    Document all decisions

20

Antimicrobial prophylaxis

  1. What is prophylaxis?
  2. Why is this uncertain?
  3. When is this common practice?

  1. the prevention of disease

  2. Breaks (or bends) the cardinal rule of infection: no antibiotic unless there is clinical evidence of infection

  3. Surgery: excellent evidence of reduced post operative infection rates when prophylaxis is given

    A single dose at start of anaesthesia is generally enough 

21

5. Antiviral Therapy

  1. What does viral infection involve?
  2. Describe the pathological process.

  1. Obligate intracellular parasites. 
  2. Receptors on host cells at the site of entry to the body (eg respiratory epithelium)

    Viruses uncoat (remove their protein coat) then start utilising host cell metabolism

    Replicate viral nucleic acid, make new protein coat, release from the host cell

    Spread and infect new cells

22

5. Antiviral Therapies

Recap: How are viruses classified?

  • DNA Viruses
    • Herpesviruses: 

      Herpes simplex v. (HSV)

      Varicella zoster  v.(VZV)

      Epstein-Barr  v.(EBV)

      Cytomegalovirus v. (CMV)

    • Papillomavirus
    • Parovirus B19
    • Smallpox Virus
  • RNA Viruses
    • ​Rotavirus
    • Picornavirus
      • Enterovirus
      • Rhinovirus
      • Poliovirus
      • Hepatovirus

    • ​​​Norovirus
    • Rubella virus
    • Hepatitis C virus
    • Influenza viruses
    • Paromyxoviruses
      • Respiratory Syncytial virus
      • Measles virus
      • Mumps virus
    • Rabies virus; Ebola virus
  • Reverse Transcribing Viruses
    • ​DNA: Hepatitis B virus
    • RNA: Retroviruses including HIV
       

23

Which Viruses can be treated with Antiviral agents?

  • Herpesviruses: HSV, HZV, EBV, CMV
  • HCV
  • Influenza Viruses: RSV
  • Ebola Virus
  • HBV
  • Retroviruses including HIV

24

What is the core list of antiviral agents?

Herpesvirus infections - Aciclovir, Ganciclovir

Influenza - Oseltamivir

Viral Hepatitis - Tenovovir, Peginterferonalfa, Ribavarin

Respiratory Syncytial Virus - Palivizumab, Ribavarin

HIV Infection

  • Reverse transcriptase inhibitors
    • Nucleoside RTI - Zidovudine, Tenovovir
    • Non-nucleoside RTI - Efavirenz

  • Protease inhibitors - Lopinavir, Ritonavir

  • Integrase inhibitors - Raltegravir

  • Fusion Inhibitors - Enfuviritide

 

25

Antiviral Agents

  1. Name the agents used for Herpesvirus infections
  2. What do nucleoside analogues target?
  3. What does aciclovir target?
  4. What does Ganciclovir target?

  1. Aciclovir, Ganciclovir

  2. faulty DNA

  3. HSV and VZV

  4. CMV

26

Antiviral Agents

  1. Name the agent used for influenza
  2. How does it act?

  1. Oseltamivir
  2. Inhibitor of Neuraminadase enzyme: Neuraminadase promotes viral release and spread from respiratory cells

27

Antiviral Agents

  1. What agents are used for Hepatitis B
    1. How do they act?
  2. What agents are used for Hepatits C
    1. How do they act?

  1. Tenovovir - analogue of adenosine: a nucleoside reverse transcriptase inhibitor

    Peginterferon alfa - naturally occurring cytokine with wide variety of antiviral properties

  2. Peginterferon alfa -  as above

    Ribavarin - analogue of Guanosine: broad antiviral activity, including RNA viruses. Toxic. Multiple modes of action

28

Antiviral Agents

  1. What is used to treat Respiratory Syncytial Virus?
    1. How do they act?

  1. Palivizumab - Monoclonal antibody Given as prophylaxis to children at risk of serious RSV infection

    Ribavarin - Analogue of Guanosine: broad antiviral activity, including RNA viruses. Toxic. Multiple modes of action

29

Antiviral Agents

Outline the antiviral agents that are used to treat HIV infection

HIV Infection

Reverse transcriptase inhibitors

  • Nucleoside RTI - ZidovudineTenovovir
  • Non-nucleoside RTI - Efavirenz

Protease inhibitorsLopinavirRitonavir

Integrase inhibitorsRaltegravir

Fusion InhibitorsEnfuviritide

30

Antiviral Agents (HIV Therapies)

  1. How does fusion inhibition act?
  2. What is reverse transcriptase?
  3. What is integrase enzyme?
  4. How does HIV protease act?

  1. Inhibits HIV virus fusion to host cell
  2. Viral enzyme, transcribes viral RNA to DNA
  3. integrates ‘Viral’ DNA into host genome
  4. New virus needs to be tidied up by HIV Protease 

31

What is Highly Active Anti Retroviral Therapy (HAART)?

What drugs does it involve?

Multiple agents limit development of resistance

  •   Backbone of 2 Nucleoside RTIs
  •  Plus one other agent (PI, Non Nucleoside RTI,   integrase inhibitor)

32

Next antimicrobial lecture (for general perusal)