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Printable Handouts
Navigable Slide Index
- Introduction
- Manifestations of CF
- Improved survival with treatment innovation
- Microbiology is very important
- Pathophysiology
- Periciliary brush and MCC depends on hydration
- Bacterial killing is impaired in CF ASL
- Increasing ASL pH enhances antimicrobial activity
- Anaerobiasis in CF mucus
- Oxygen partial pressure in CF airways
- Anaerobiasis drives mucoidy in P. aeruginosa
- Bacteria epithelia interrelations
- Bacterial infection of CF mucus
- CF sputum
- You only find what you look for
- Sputum processing
- The “culture” microbiota
- Anaerobes detected
- Comparison of viable counts
- Microbe count to TRFLP
- Extended culture vs. molecular identification
- Bacterial families detected in CF airways
- 454 Pyrosequencing
- Clustering
- Taxa occupancy CF
- CF microbiota diversity
- Changes in lung function and diversity
- Airways infection drives inflammation
- Infection and progression of CF lung disease
- Infection
- Current treatment options
- How do we improve survival and QoL?
- CF bugs: the main players
- Staphylococcus aureus
- MRSA
- Survival according to MRSA status
- Treatment of MRSA in CF
- Belfast adults MRSA eradication study
- Natural history of P.a. infection in CF
- P. aeruginosa infection 17 years and less
- Antibiotic strategies for eradicating P. aeruginosa
- Artimino algorithm for AET
- Exacerbations: triggers?
- Exacerbation frequency and clinical outcome
- Why does it matter?
- Other effects of pulmonary exacerbations
- Choosing the antibiotics
- Antibiotic regimens
- Antibiotic treatment options
- Treatment of exacerbations with difficult bacteria
- Therapies which prevent exacerbations
- Macrolides in CF: mechanisms?
- Macrolides
- Should we be cautious?
- Inhaled tobramycin
- Aztreonam lysine in CF
- Actual change in FEV1 % predicted
- Time to need for IV antipseudomonal antibiotics
- Personalised medicine in cystic fibrosis
- FEV1 % predicted absolute change
- Time-to-first pulmonary exacerbation
- Hospitals can be a source of infection
- Conclusions
Topics Covered
- Cystic fibrosis (CF) pathophysiology of infection and inflammation
- Identification of bacteria and other macro-organisms using sequencing techniques in airways of people with CF
- Treatment & prevention of infections and exacerbations
- Challenges of CF care in management of infection with antibiotics
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Elborn, S. (2014, April 2). Infection in the cystic fibrosis lung [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 8, 2024, from https://doi.org/10.69645/CURY2871.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Stuart Elborn has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Microbiology
Transcript
Please wait while the transcript is being prepared...
0:00
My name is Stuart Elborn,
I'm Professor of Respiratory
Medicine at Queen's University,
Belfast, and Director of the
Center for Infection and Immunity.
In this lecture, I'm
going to describe some
of the exciting new discoveries
using second generation sequencing
in identifying bacteria
and other microorganisms
in there airways of people
with cystic fibrosis,
and then go on to discuss some
of the challenges that face us
in cystic fibrosis care relating
to the management of infection
with antibiotics.
0:34
First of all, I'd like to orientate
you around cystic fibrosis.
This is the most common autosomal
recessive disorder affecting
Northwest Europeans that
results in early death.
It's a multi-system disorder because
the genetic condition affects
epithelial cells, and so
all of our hollow organs
are affected in this condition.
The major part of the
morbidity and mortality
is in chronic sinopulmonary disease,
with infection and inflammation
in the airways resulting
from bronchiectasis
and progressive lung injury.
This leads to respiratory failure.
Other organ systems
that are affected
are the hepatobiliary
system, the pancreatic ducts,
the gastrointestinal tract,
reproductive tracts in the vas
deferens, and the endocrine pancreas
is often also affected, probably
as a result of pancreatic scarring
rather than a primary defect,
though there are some
indications that there may also
be some abnormalities
of insulin metabolism.
1:37
Cystic fibrosis as
a critical condition
was reported by a number of
clinicians in the first half
of the 20th century, but it
wasn't until the late 1940s
that Anderson and colleagues
described a number of children
admitted during a heatwave in
New York with severe electrolyte
disturbances and connected
these to the fibrocystic disease
of the pancreas gland.
Over the 1950s, the clinical
condition of cystic fibrosis
was much more clearly
described, the diagnostic test
using the concentration of
chloride and sodium in the sweat
was described.
This sweat test has remained the
pivotal diagnostic investigation
for cystic fibrosis since then,
with a sweat chloride concentration
of greater than 60
million moles per liter
being consistent with a
diagnosis of cystic fibrosis.
On this graph the highlights
of some further interventions
for cystic fibrosis are described.
The red line indicates
the median survival
for people with cystic fibrosis
over the last six or so decades.
As you can see, the median survival
for people with cystic fibrosis
has risen from around five
years in the early '60s to now
being around 40 years.
This progressive improvement
has been due to the organization
of cystic fibrosis care
into specialist clinics,
and the introduction
of key therapies
which have had an impact on the outcome.
First of these was introduction
of pancreatic enzyme replacement
therapy to mitigate the
effects of maldigestion
due to pancreatic enzyme deficiency
because of pancreatic fibrosis
and a reduction in
exocrine function.
Subsequent key interventions
were airway clearance, a range
of antibiotics against
Staphylococcus aureus
and Pseudomonas aeruginosa,
and drugs which improved
mucus clearance such as
DNase and hypertonic saline.
In the last 20 years
or so, antibiotics
have been developed to be used by
the inhaled route, particularly
tobramycin, aztreonam, and colistin.
These have also likely
made a significant impact
on improving survival.
We now are in a new
era in cystic fibrosis
with a drug called
ivacaftor which treats
the basic defect in cystic fibrosis.
It has transformative effect on
key outcome measures such as lung
function and frequency of
pulmonary exacerbations.
Cystic fibrosis centers
throughout the world
now collaborate to improve the
quality of care delivered to people
with cystic fibrosis and to conduct
high quality clinical trials
through the North American
Therapeutic Development Network
and the European Cystic Fibrosis
Society Clinical Trials Network.