Keywords
Pharmacology, bioanalysis, anti-infectives, GCLP
Expertise
To successfully treat infectious diseases, we must find
the optimal balance between the pathogen, the host and
the drug to ensure adequate killing of the pathogenic
organism whilst avoiding excessive toxicity.
There is often tremendous variability in response
between people who receive the same dose of drug.
Studies have documented this variability for most
antimicrobials, including those used to treat HIV,
tuberculosis (TB), serious fungal infections, viral hepatitis
and bacterial infections. Nevertheless, treatments still
follow the ‘one dose fits all’ strategy, arguably promoting
widespread resistance in 60 years of treating major
infectious diseases.
There is now a move towards optimising drug dosing
and treatment for individuals or groups of people
(‘
personalised’ medicines). Some of this rests on the
presumption that drug dosing should be either directly
measured (through ‘therapeutic drug monitoring’ (TDM))
or else the adjustment of the dose according to
knowledge about how particular groups of vulnerable
individuals (such as pregnant women, children, ethnic
minorities, patients with underlying disease, high body
mass index, etc) have responded to the drug.
TDM is already routinely undertaken when treating
serious bacterial and fungal infections (aminoglycosides,
glycopeptides, azoles), TB and HIV. The risks of adverse
treatment outcomes increases with drugs which exhibit a
narrow safety margin, widespread variability, and which
are used long-term for chronic infections.
Our bioanalytical researchers have developed a method
using HPLC-mass spectrometry that delivers high-
throughput, highly sensitive and precise measurements
of drugs in plasma and other samples (eg cerebrospinal
fluid, cervical fluid, semen, tissue biopsies and inside
cells). The team focuses on anti-infectives, particularly
HIV and HCV drugs.
Bioanalysis
The University has access to a state-of-the-art
bioanalytical facility which is fully accredited to
Good Clinical Laboratory Practice (GCLP)
standards and able to conduct a variety of drug
analyses for the research community and industry.
Capabilities and facilities
•
Mass spectroscopy, (MALDI, triple-quadrupole,
ion-trap and Q-To-F formats)
•
Advanced gel electrophoresis systems
•
HPLC instrumentation
•
Access to NMR and mass spectrometry facilities.
Relevant centres and groups
•
MRC Centre for Drug Safety Science.
Health & Wellbeing
27
4.3
Improving diagnostics and developing new therapeutics
Also see:
Health & Wellbeing –
6.
Drug safety and personalised
medicine, page 35
Keywords
Antimicrobials, resistance, MRSA, ESBLS, reservoirs
Expertise
Antimicrobial resistance is an important and increasing
problem in both human and veterinary medicine. It is
vital that we determine the reservoirs of antimicrobial
resistant bacteria and resistance determinants. We also
need to understand how these resistant bacteria are
selected and transmitted.
Our multidisciplinary team consists of microbiologists,
molecular biologists, clinicians and quantitative and
qualitative epidemiologists. Their expertise is applied to
study the biological mechanisms of resistance as well
as its social context. We also research the impact that
antimicrobials have on the development of resistance in
animals and the risk that this has for public health.
We have extensive expertise in the ecology and
epidemiology of antimicrobial resistance in a range
of animal populations including wildlife, food and
companion animals. We have studied methicillin resistant
Staphylococcus aureus
(
MRSA) and extended-
spectrum-lactamase (ESBL) producing
E. coli
and
enteric zoonotic bacteria, such as Campylobacter.
These bacteria are of importance in human and
veterinary medicine.
Our expertise is ideal for studies involving different
animal, human or bacterial populations. We have
capabilities to conduct microbiological studies through to
full epidemiological analysis. Our researchers have skills
in: characterising resistance genes and resistant strains;
investigating selection and transmission of
resistance determinants; determining risk in individuals
or populations and testing preventive programmes.
Capabilities and facilities
•
Multi-locus sequence typing
•
Replicon typing of plasmids
•
Characterisation of resistance genes and
resistant strains
•
Molecular epidemiology
•
Testing and evaluating preventative programmes.
4.4
Antimicrobial and anthelmintic resistance
For further information
on all our specialist
centres, facilities and
laboratories
go to page
179
