Microbiology D

Question 1

what does selective toxicity mean and how is this achieved

Answer 1

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

Antibacterials Selectively toxic by targeting:

• Cell wall
• Protein synthesis
• Process of DNA supercoiling
• Folate metabolism

Question 2

name two bacteria classes that act on the cell wall

Answer 2

1. Beta-lactams

2. Glycopeptides

Question 3

name two bacteria classes that act on the cell wall

Answer 3

1. Beta-lactams:
   - penicillins
   - Penicillin/ beta-lactamase
   inhibitor combinations
   - Cephalosporins
   - Monobactam
   - Carbapenems
2. Glycopeptides

Question 4

name some bacteria classes that are protein synthesis inhibitors

Answer 4

macrolides
aminoglycosides
tetracyclines

quinolones - DNA supercoiling

others - folate metabolism

Question 5

what is a bacterias spectrum activity. what is meant by broad spectrum

Answer 5

The range of bacteria that a given antibiotic is able to kill

Antibiotics effective against a large variety of medically important organisms

Question 6

describe the start smart then focus guidelines for infection treatment

Answer 6

Start smart:

• Do not start antibiotics in the absence of clinical evidence of infection
• Thorough drug allergy history*
• Rapid assessment for Sepsis
• Comply with local guidelines [microguide app
• Document diagnosis and treatment
• Document review and stop date
• Obtain cultures prior to starting treatment

Then focus:
Clinical review, ideally with microbiological results at 48-72 hours:  Document decisions:
		1. Stop
		2. IV to oral switch
		3. change antibiotic
		4. Continue
		5. OPAT (Outpatient Parenteral Antimicrobial Therapy)
Document all decisions

Question 7

how do you Take a thorough allergy history

Answer 7

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- urticarial rash tends to be caused by histamine and so may be IgE mediated)

Question 8

what drug is ok to give after a life threatening reaction to penicillin

Answer 8

Monobactam Aztreonam

Question 9

what drugs are ok to give after a non-life threatening reaction to penicillin

Answer 9

Cephalosporins
Cefuroxime, Ceftriaxone

Monobactam Aztreonam

Carbapenems
Meropenem, Ertapenem

Question 10

name two drugs used for Herpesvirus infections and how they work

Answer 10

Aciclovir
Ganciclovir

Nucleoside analogues: faulty DNA
Aciclovir: HSV and VZV
Ganciclovir: CMV

Question 11

name the drug prescribed for influenza and how does it work

Answer 11

Oseltamivir

can be used for people with influenza or prophylaxis

Inhibitor of Neuraminadase enzyme:
Neuraminadase promotes viral
release and spread from respiratory cells

Question 12

name some of the drugs prescribed for Hepatitis B and C and how do they work

Answer 12

Hepatitis B:
Tenovovir
Peginterferon alfa

Hepatitis C
Peginterferon alfa
Ribavarin

• Tenovovir: analogue of adenosine: a nucleoside reverse transcriptase
  inhibitor
• Peginterferon alfa: naturally
  occurring cytokine with wide variety of antiviral properties
• Ribavarin: Analogue of
  Guanosine: broad antiviral activity, including RNA viruses. Toxic.
  Multiple modes of action

Question 13

name two drugs prescribed for Respiratory syncytial virus and how do they work

Answer 13

Palivizumab
Ribavarin

Palivizumab: Monoclonal antibody
Given as prophylaxis to children at
risk of serious RSV infection

Question 14

name some drugs used in treatment of HIV

Answer 14

Reverse transcriptase inhibitors:
- Nucleoside RTI:
Zidovudine
Tenovovir
- Non-nucleoside RTI:
Efavirenz

Protease inhibitors:
Lopinavir
Ritonavir

Integrase inhibitors:
Raltegravir

Fusion inhibitors:
Enfuviritide

Question 15

describe Highly Active Anti Retroviral Therapy (HAART)

Answer 15

management of HIV

Multiple agents limit development of resistance

Backbone of 2 Nucleoside RTI

Plus one other agent (PI, Non Nucleoside RTI, integrase inhibitor)

Question 16

Define herd immunity, vaccine adjuvant, passive immunotherapy

List the characteristics of a good vaccine.

Distinguish different types of vaccine preparations (live and inactivated) and compare their advantages and disadvantages.

List side effects of vaccine

Identify vaccines on the current UK vaccination schedule

Give examples of patient risk groups that require additional vaccinations

Give examples of post exposure vaccination

Answer 16

.

Question 17

Define herd immunity

Answer 17

Concept of herd immunity – level of immunity at which an infectious agent can no longer continuously circulate (R becomes <1)

Question 18

what’s the difference between dead or live vaccines

Answer 18

All vaccines should contain at least one of the protective antigens of the microbe.

Dead vaccines generally less effective than live

Live:

• microbes with artificially reduced virulence (‘attenuated’)
• microbes with naturally reduced virulence for humans

Dead:

• Inactivated virus
• subcellular fragments/ Sub-unit vaccines
• Toxoids
• Genetically engineered recombinant vaccines.

Question 19

list some Pros and Cons of Live Attenuated Vaccines

Answer 19

Advantages:

• Good immunogens
• Induce long-lived, appropriate immunity
• Tend to produce mucosal immunity
• May offer alternative routes (e.g. oral)

Disadvantages:

• Labile: Cold chain vital for live vaccines
• Potentially unstable genetically (possible reversion to virulence)
• Not possible to produce in all cases - trial and error
• Contamination possible (e.g SV40 virus) in poliovirus vaccine
• Inappropriate/accidental vaccination to at risk groups (immunosuppressed and pregnant) may pose risk

Question 20

list some Pros and Cons of Live Attenuated Vaccines

Answer 20

Advantages:

• Good immunogens
• Induce long-lived, appropriate immunity
• Tend to produce mucosal immunity
• May offer alternative routes (e.g. oral)

Disadvantages:

• Labile: Cold chain vital for live vaccines
• Potentially unstable genetically (possible reversion to virulence)
• Not possible to produce in all cases - trial and error
• Contamination possible (e.g SV40 virus) in poliovirus vaccine
• Inappropriate/accidental vaccination to at risk groups (immunosuppressed and pregnant) may pose risk

Question 21

list some Pros and Cons of Inactivated Vaccines

Answer 21

Inactivated whole virus- Poliovirus, Rabies, inactivated HAV

Advantages:

• Stable
• Little or no risk (if properly inactivated)

Disadvantages:

• Not possible for all viruses; denaturation may lead to loss of antigenicity and adverse affects, e.g. measles, RSV.
• Not as effective at preventing infection as live viruses (mucosal immunity - IgA).
• May only protect for a short period protect

Question 22

describe Sub-Cellular (Sub-Unit Vaccines)

Answer 22

Subcellular fractions can be used as vaccines if protective immunity is directed against a particular part of an organism

Question 23

list the Pros and Cons of Sub-unit Vaccines

Answer 23

Advantages:
Selected virus proteins or peptides used so:
- Completely safe, except for rare adverse reactions.
- Specific Antibody and T cell reactions can be selected.
- Can be made using recombinant DNA techniques

Disadvantages:

• Tend to be the least effective.
• (Relatively) poor antigenicity (especially short peptides)
• Vaccine delivery (carriers/adjuvants needed)

Question 24

describe Toxoid Vaccines

Answer 24

• Bacterial toxins – proteins realised by bacteria which induce inflammatory responses
• Toxoids: inactivated toxins (usually by formaldehyde) so no longer toxic, but still induce protective antibody
• Two toxoids: diphtheria and tetanus- among the most successful and widely used of all vaccines.
• In combination with killed Bordetella pertussis, they constitute the triple vaccine, DTP (diphtheria, tetanus, pertussis).
• Pertussis acts as an ‘adjuvant’ as well as a specific vaccine.

Question 25

describe some proven concerns with vaccine safety

Answer 25

Live attenuated vaccines: - Insufficient attenuation - Reversion to wild type - Administration to immunodeficient patient & Persistent infection - Contamination by other viruses - Fetal damage. Non-living vaccines: - Contamination by toxins or chemicals - Allergic reactions - Autoimmunity. Genetically engineered vaccines: ??Possible inclusion of oncogenes - hasn't been proven

Question 26

list some at risk groups for vaccines

Answer 26

- Immunodeficiency - HIV positive - Asthma - Chronic Lung Disease - Congenital Heart Disease - Definite hypersensitivity- Severe or Generalised Reaction to Preceding Dose - Down’s Syndrome - Avoid live vaccines in pregnancy - Small For Dates infants - Premature infants

Question 27

Give examples of post exposure vaccination

Answer 27

Examples: MMR in measles exposures, HBV vaccination in HBV exposure

Question 28

describe the use of passive immunisation with immunoglobulin

Answer 28

to prevent infection after exposure (e.g. rabies, tetanus) to minimise its severity (varicella, measles in immunodeficient children). Primary treatment (e.g diphtheria)