Alternatives

Question 1

MRSA

Answer 1

Pattern of susceptibility of strains varies, general cross-resistance between Beta-lactam antibiotics.
Once considered noscomial, is now being isolated in community acquired infections. Clearance cantake a long time, and some may never fully be cleared.

Question 2

MDR-TB

Answer 2

Relatively few anti-TB drugs available. M. tuberculosis has a fairly high mutation rate and resistance occurs evenin people who havent been treated before.
MDR-TB strains are resistant to at least isioniazid and rifampicin

Question 3

Malaria

Answer 3

40% of population deemed to be at risk
Caused by the species Plasmodium
Currently no effective vaccine
Number of drugs exist but resistance to many has evolved. MDR-falciparum is widespread in SE Asia and South America and now being reported in Africa
WHO strongly recommend multi-drug therapy including one of the Artemesin family of anti-malrials

Question 4

Fungi

Answer 4

In healthy populations, fungi pose a low risk, but are a significant threat in the immunocompromised.
Not that many antifungals available.
Opportunistic moulds often intrinsically resistant to a number of antifungals.
Acquired resistance is becoming an issue, especially in azole resistant Candida species.
MDR being reported in Candida and Aspergillus

Question 5

HIV

Answer 5

Viral agent of AIDS
Number of therapied available
Usually starting from most tolerable drug downwards.
Resistance being reported in patients who have previously received therapy, and those who havent.
Evolution of resistance in an individual patient is fairly rapid and there is need to sequence the order in which drugs are given.

Question 6

Significant resistance Problems:

Answer 6

Extended beta-lactamase production in Enterobacteriaceae and more recently carbapenemase producing Enterobacteriaceae.
Emergence of Acinetobacter bamaunii as a noscomial infection.
Increasing importance of intrinsically resistant microbes in infection of immunocompromised e.g. Pseudomonas in Cystic fibrosis.
Resistance to the best drugs for certain infections For example, only certain drugs cross the BBB well enough to be first line drugs to meningitis, however resistance is becoming an issue in the major causes of meningitis.

Question 7

Reclaiming the drugs we have:

Answer 7

Stop empiric therapy
Rotation of empiric therapy
Holding some drugs for specific uses
Using drugs currently only used topically for other infections. (colistin)
Further reducing prescription
Stopping over the counter sales

Some of these ideas would potentially increase number of circulating pathogens while people were not being treated until lab tests were performed. Also a disincentive to pharma companies

Question 8

DOTS strategy to fight TB: 5 requirements

Answer 8

Directly observed treatment, short course.

1. ) Sustained political and financial commitment
2. ) Diagnosis quality ensured sputum-smear microscopy
3. ) Standardised short-course anti-TB treatment given under direct and supportive observation
4. ) A regular, uninterrupted supply of high quality anti-TB drugs available to all.
5. ) Standardised recording and reporting.

Question 9

Vaccination:

Answer 9

Currently, vaccination is an important defence against infectious diseases. Particularly when the disease has serious outcomes, where its common, where other treatments are less optimal (or no other treatment).
Vaccination has succesfully eradicated smallpox and polio is nearly gone.

Question 10

A bigger role for vaccination?

Answer 10

Easier said than done
devleopment costs, trials, approval, litigation
Many infections are endogenous
Impact on normal flora may lead to new strains of infection.
Public perception issues.
Some groups cant be vaccinated.

Question 11

Surgery:

Answer 11

Surgery, in some cases has always been used.
Use os surgery for TB has long been an option but recently in days of MDR-TB its having to be carried out more frequently and advocates say it should be done earlier to prevent spread to other lobes of the lung and reduce infectivity.

Question 12

Development of new synthetic antimicrobials

Answer 12

Most new antibiotics are actually variations on existing molecules, often adapted with a specific function in mind, however this increases the risk of cross-resitance.
We need genuinley new classes of drugs which affect microbes in different ways to existing drugs
Other factors should be considered, like development of oral drugs which previously had to be treated in hosopitals. This would reduce the risk of spread of infection if the patient can take the drug at home, and reduce costs on healthcare where professionals previously had to administer the drug. The Dose can also be reveresed if needed through quick vomiting action.

Question 13

Antimicrobial peptides;

Answer 13

12-50 amino acids long with general activity against both bacteria & fungi.
Many are naturally occuring in mammalian host.
Mammalian defensins are a sub-group commonly found in neutrophils (alpha) and some in gut epithelium (beta).
The potential for the development of these into usable antimicrobials is ongoing, some showing promise, particulary as topical fungal agents.

Question 14

natural substances with Antimicrobial activity

Answer 14

A number of natural products have antimicrobial properties.
The mechanism in many is not always clear, but the possibility of developing new antimicrobials from naature is ongoing.
Aloe vera is a latex compound which has activity against S. aureus. Laurus nobilis is an essential oil of the Terpenoids class which has activity against some bacteria and fungi.

Question 15

Garlic

Answer 15

One of the best characterised natural antimicrobials.
Contains the chemical Allicin, Alliumin and other sulphur compounds. Evidence has been found for activity vs Neisseria gonorrhoeae, Staph aureus and fungi.
Properties much higher in freshly squeezed garlic- many other preparations have little or no activity.
Not yet avilable in truly clinical form but som IV studies in mice have been successful.

Question 16

Tea Tree Oil

Answer 16

In vitro killing of MRSA has been reported. however in vivo studies have been poor with nasal carriage not being reduced by TTO. In another in vitro study, otitis externa isolates were found to be largely sensitive to TTO. Studies have shown effect against oral microbes, though not currently viable for market as a mouthwash due to unpleasant taste.
Studies also supported as use as a handwash, however TTO can cause contact dermatitis so issues over current form.

Question 17

Honey

Answer 17

Shown to have antimicrobial properties, in part, linked to osmolarity. Can be used in wound dressings where it has been shown to speed the healing process of ulcerous wounds through a mixture of both debridement and antimicrobial activity.
Honey has been shown to reduce attachment of some GI pathogens to gastric cell lines in vitro
Some honey shown to have traces of chloramphenicol and tetracycline

Question 18

Phage therapy;

Answer 18

These are viruses that infect and kill bacteria.
Already used in food, agriculture and fishery industries
Renewed interest after failure in 20s and 50s.

Question 19

Genomics

Answer 19

What genes are present in a genome?
Can then go on to look at whether or not there are similarities between bacterial genomes
Genome sequencing- the whole genomes of a number of pathogenic bacteria are now available

Question 20

Transcriptomics

Answer 20

Studying RNA- is the present gene actually being transcribed?
Transcription can be constitutive or induced, and techniques such as microarray analysis can help decipher what is happening in bacterial cultures at a given time.
But just because a gene is being transcribed doesnt mean its doing something

Question 21

Proteomics

Answer 21

Total protein, or fractions of proteins are extracted from biomass. The proteins in the samples are separated by using two of their physical characteristics.
1st technique separates based on isolecectric focusing point. 2nd is separates them based on molecular weight. Identities can then be determined.

Question 22

Bioinformatics

Answer 22

Advances in computer based assistance for the analysis of genes and proteins is the most important aspect. Without computer software, many of the techniques that have become common place wouldn’t be possible. internet very important in terms of fields of research

Question 23

The omic era:

Answer 23

Still in relative infancy.
No major steps just yet
Possibly in danger of data overload as one or two microarray experiments can produce data which can take many months to analyse, then need to tie up the transcriptomic and proteomic results which takes even longer. Data must also been confrimed by some sort of biological study

Question 24

Will the omics deliver?

Answer 24

Already some impatience, genomic analysis of major pathogens hasnt resulted in flood of potential therapeutic targets. for therapy.
Number of companies already converted back to traditional methods such as compound screening.

Question 25

What’s in it for the pharma companies?

Answer 25

Most major drug companies have scaled back on work looking for antibacterials.
Why?:

Upfront cost of around 500 mil
efforts to reduce prescriptions from US an EU
Pressure to keep retail price low
Regulatory approval- to get FDA approved, the drugs must be better than existing drugs on market. Drugs also require more stringent testing these days.

Question 26

Prevention: Breaking the cycle

Answer 26

Resevoir –> Transmitter –> Host –> shedding

Quarantine: long history in infectious diseases, from leper communes in days gone, and the more recent SARS outbreak.

Question 27

Isolation:

Answer 27

Quarantine is hospital setting
Can range from use of side rooms through to use of isolation tents.
Can be used to protect the public from an infected individual, or vice versa

Question 28

Bed nets;

Answer 28

Simple, but correct use of bed nets can reduce risk of being bitten by various insects.
Can greatly impact spread of diseases, especially malaria.

Question 29

maintainng good health

Answer 29

More healthy you are, better at fighting infections
boosting vitamins through fruit and veg can boost immune function.
Regular health checks

Question 30

Infection control in hospitals

Answer 30

surveillance schemes
staff training and compliance
patient/visitor compliance
assessment of specific risks
barrier nursing
isolation
Reducing movement of patients between hospitals
Hand-washing protocols
Appropriate use of protective equioment

Question 31

Infection control in community

Answer 31

Surveillance schemes
training staff to recognise risks in the communities
Information to help public play their role
Rapid hospitilastion where possible
Use of vaccination prophylactics in outbreak settings
Industry compliance