Alternatives Flashcards
MRSA
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.
MDR-TB
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
Malaria
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
Fungi
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
HIV
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.
Significant resistance Problems:
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.
Reclaiming the drugs we have:
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
DOTS strategy to fight TB: 5 requirements
Directly observed treatment, short course.
- ) Sustained political and financial commitment
- ) Diagnosis quality ensured sputum-smear microscopy
- ) Standardised short-course anti-TB treatment given under direct and supportive observation
- ) A regular, uninterrupted supply of high quality anti-TB drugs available to all.
- ) Standardised recording and reporting.
Vaccination:
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.
A bigger role for vaccination?
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.
Surgery:
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.
Development of new synthetic antimicrobials
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.
Antimicrobial peptides;
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.
natural substances with Antimicrobial activity
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.
Garlic
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.
Tea Tree Oil
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.
Honey
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
Phage therapy;
These are viruses that infect and kill bacteria.
Already used in food, agriculture and fishery industries
Renewed interest after failure in 20s and 50s.
Genomics
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
Transcriptomics
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
Proteomics
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.
Bioinformatics
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
The omic era:
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
Will the omics deliver?
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.
