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4.1 Medical Microbiology > Cystic Fibrosis > Flashcards

Cystic Fibrosis Flashcards

1
Q

What kind of disease is CF and what causes it?

A

CF is an autosomal recessive disease
CF is caused by mutations of the the Cystic Fibrosis Transmembrane Conductance Regulator CFTR gene

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2
Q

How common is CF in Ireland and why is this the case?

A

Incidence of about 1 in 1,461 people
With 1 in 19 people being carriers of the condition

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3
Q

How common is CF in Ireland and why is this the case?

A

Incidence of about 1 in 1,461 people
With 1 in 19 people being carriers of the condition

CF is common in Ireland as CFTR gene mutations confer resstance against salmonella typhi which would have provided protection during the great famine, i.e. those with the CFTR mutation were more inclined to have survived the famine

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4
Q

How does CF affect a person?

A

CF affects the lungs, sinuses, pancreas, liver, bones, vas deferens etc etc
Its usually decline in lung function that kills the patient

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5
Q

Explain the pathophysiology of CF as a disease

A

Mutations in the CFTR gene affect mucocilliary transport by causing a depletion of airway surface flluid

The CFTR gene is responsible for normal sodium/chloride and fluid regulation in and out of epithelial cells, mutations in this gene result in a loss of airway surface fluid

CF patients build up a thick layer of mucous which then clogs smaller bronchioles etc

Organisms can become trapped in this mucous

Some organisms can produce proteins such as alginate which are really sticky

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6
Q

What are the main steps in CF as a disease process

A

CF gene mutation

Ion transport abnormailities

Altered airway environment

Inflammation + Infection

Tissue damage

*This cycle of tissue damage will ontinuously repeat

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7
Q

What are the main steps in CF as a disease process

A

CF gene mutation

Ion transport abnormailities

Altered airway environment

Inflammation + Infection

Tissue damage

*This cycle of tissue damage will ontinuously repeat

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8
Q

How exactly does CF affect the lung?

A

Structural damage
Bronchiectasis
Pulmonary insuffuciency
Respiratory failure

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9
Q

List the most commonly isolated organisms from a CF lung
(7)

A

Haemophilus Influenzae (non-capsulated)
Staphylococcus Aureus, MRSA and small colony variants
Pseudomonas Aeruginosa (non mucoid and mucoid)
Burkholderia Cepacia Complex (BCC)
Gram negative non-fermenters
Non-TB-Mycobacterium Species
Scedosporium species

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10
Q

List some gram negative non-fermenters you might isolate from a CF lung
(7)

A

Pseudomonas species (Non-PA)
Alkaligenes species
Chromobacter species
Stenotrophomonas species
Burkholderia gladioli
Pandorea species
Pedunculosis species

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11
Q

Give two examples of non-tb mycobacterium you could isolate from a CF lung

A

Mycobacterium abscessus
Mycobacterium cheloni

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12
Q

Talk about the range of organisms found in a CF lung

A

Huge range of organisms can be found
Haemophilus and staph often found in younger patients
Pseudomonas more in teenagers and up
Burkholderia in older patients
NLFs tend to be opportunistic bacteria -> majority are ubiquitous in nature
Unusual fungal infections can be seen in CF patients such as scedosporium
Infections tend to be polymicrobial

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13
Q

Talk about the range of organisms found in a CF lung

A

Huge range of organisms can be found
Haemophilus and staph often found in younger patients
Pseudomonas more in teenagers and up
Burkholderia in older patients
NLFs tend to be opportunistic bacteria -> majority are ubiquitous in nature
Unusual fungal infections can be seen in CF patients such as scedosporium
Infections tend to be polymicrobial

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14
Q

What are small colony variants?

A

These are variants of S. areus which originate by mutations in metabolic genes, these resul in auxotrophic bacterial subpopulations

These variants gro slowly and have many atypical characterics

These can be seen in CF lungs as they adapt to conditions within the CF lung

Can be difficult to isolate and identify -> auxotrophic

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15
Q

Talk about mucoid vs non-mucoid pseudomonas

A

Pseudomonas aeruinosa has two forms; mucoid and non-mucoid

P. auriginosa infections in CF patients start of as acute non-mucoid infections but conversion to mucoid PA results in long lasting (often life-long) chronic infection

The conversion from non-mucoid to mucoid affects the lilfe expectancy of a patient drastically -> chronic infections cannot be cleared, life long, no treatment, only immune suppression

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16
Q

Talk about the different microorganisms that can be isolated from CF patients of different age cohorts

A

H influenzae is more common in infancy
S. aureus is more common in younger patients and peaks in teens at about 17
MRSA is more common in young adults peaks at about 20
P. aeruginosa risk worsens with age and peaks at about 40
NLFs such as B cepacia, Stenotrophomons and Achromobacter stay realatively uncommon throughout life

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17
Q

Talk about the prevalence of microorganisms isolaed in CF patients as trends over time

A

The amount of S. aureus weve isolated since the 90s has been increasing
The amount of P. aeruginosa weve isolated since the 90s has been decreasing
MRSA isolations have been increasing
H. influenzae have staed relatively the same
Steno and achromobacter have increased
B. cepacia remained the same

*not entirely reflective as detection methods are a lot better now, less likely to miss an MRSA or an NLF nowadays compared to the 90s etc

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18
Q

Talk about Haemophilus Influenzae involvement in CF

A

A common commensal of the upper respiratory tract
A frequent coloniser of infants and children
Seen in 20% of CF children under 1
Seen in 32% of CF children between 2 and 5
May cause acute exacerbations in chronic conditions
Produces IgA1 proteases and can cause ciliostasis
Can decrease mmucociliary cleanance up to 10 fold in CF patients

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19
Q

What are the main virulence factors of Haemophilus influenzae and how do they affect CF

A

Produces IgA1 proteases which cleave peptide bonds in human IgA

Can cause ciliostasis -> cilia of the airways nolonger move -> prevents mucous from moving

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20
Q

What are the main virulence factors of Haemophilus influenzae and how do they affect CF

A

Produces IgA1 proteases which cleave peptide bonds in human IgA

Can cause ciliostasis -> cilia of the airways nolonger move -> prevents mucous from moving

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21
Q

Talk about Staph aureus involvement in CF

A

S. aureus is often the first isolate
Can be seen in up to 70% of CF isolates
More common in younger patients/teens etc
Concern with empyema (pus build-up) and lung abscesses
Role of slime and teichoic acid which play a role in adherence to respiratory epithelial cells

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22
Q

Talk about the S, aureus biofilm and why it is of concern?

A

S. aureus can produce a multilayered biofilm embedded within a glycocalyx or slime layer, the solid components is primarily composed of teichoic acids

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23
Q

Talk about the MRSA and its incidence in CF

A

Both CA and HA MRSA are seen in CF patients

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24
Q

Talk about Pseudomonas and its role in CF

A

PA is the most prevalent respiratory bacterial pathogen
Higher prevalence in adults
Isolated i about 50% of cf patients
Infection associated with significant morbidity
Mucoid vs non-mucoid
Epidemic strains

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25
Talk about mucoid P. auriginosa
PA can change from non-mucoid to mucoid PA forms biofilm -> organism will downregulate their metabolism inside this biofilm Biofilm allows organism to tolerate both the immune response and antimicrobials
26
Talk about epidemic strains of PA
There have been certain transmissable strains of PA such as 'midlands', 'liverpool' and 'australia' These have been associated with CF to CF spread of PA
27
What actually causes tissue damage in CF
Inflammatory response +lots of virulence factors from infection + Cytokines
28
Talk about the evolution of PA infection in CF patients as theey age?
First positive isolate, antibiotic treatment, second isolate clear, infection treated, only an intermittent infection Older patient, third isolate positive, antibiotic treatment, repeated positive isolates, chronic infection, not treated
29
Talk about the evolution of PA infection in CF patients as theey age?
First positive isolate, antibiotic treatment, second isolate clear, infection treated, only an intermittent infection Older patient, third isolate positive, antibiotic treatment, repeated positive isolates, chronic infection, not treated
30
Comment on the microbiome diversity of a CF lung as disease progresses
Usually very diverse early on, usually even find weird NLFs or fungi etc As disease progresses pseudomonas becomes more and more dominant until it takes over
31
How are PA infections classified?
At least 4 cultures in the last 12 months required: >50% positive = chronic infection <= 50% positive = intermittent infection Never positive = free of PA
32
When is a CF patienet most likely to have mucoid PA
In general PA is more common in older people Non mucoid strains are more commonly seen in young people Mucoid strains are more commonly seen in older patients
33
What two organisms have 'transmissible strains' to be concerned about
Pseudomonas and Burkholderia
34
How is pseudomonas infections treated?
In newborns -> avoidance/prevention and antibiotic prophylaxis In young -> treatment of early infections to eradicate pseudomonas In older -> chronic infection -> immune suppression
35
Talk about Burkholderia Cepacia Complex and its role in CF
Ubiqitous -> found in nature -> opportunistic -> non pathogenic in healthy humans Can cause long term colonisation without affecting lung function Can cause chronic infection associated with slowly declining lung function Can cause acute fulminant lung infection leading to death in weeks/months -> necrotising pneumonia/cepacia syndrome Just under 3% of CF patients are infected
36
What are some of the clinical implication of B. cepacia infection?
Deteriorating lung function More pulmonary exacerbations/hospital admissions More IV antibiotics Reduced life expectancy Hospital segregation Social isolation Implications for transplantation
37
Name a Burkholderia epidemic strain
ET12 -> often seen in outbreaks but doesnt always case outbreaks
38
Talk about stenotrophomonas maltophilia in CF
S. maltophilia was initially classed as a pseudomonas but molecular methods allowed for the classing as a steno Found in soil -> mostly community acquired Tends to be transient and recurrent Peakas in teens and young adults
39
What are some of the emerging CF bacteria
Achromobacter xylosoxidans Pandoraea species Inquilinus Limosus Herbaspirillum species Burkholderia gladioli Streptococcus milleri group (SMG)
40
Why should we be concerned with some of the new emerging CF bacteria
These could be potentially transmissible They could be naturally multi-drug resistant -> think of NLFs NLFs could be falely identified as BCC (could take patient of transplant list so we need to be aware of them) Could impact infection control measures
41
Talk about Non Tubercle Mycobacterium Species in CF
NTMs are ubiqituous Risk factors for acquisition are not really understood Increased risk of acquisition if aspergillus isolates found or if on steroid treatment Can be difficult to diagnose and problematic to treat Infection strongly associated with age 2 different types: slow growing and rapid growing
42
What are the two different types of NTBM?
Slow-growing Mycobacterium avium complex (MAC) (including M. avium, M. intraceulare and M. chimaera) Rapid growing M. absessus complex (MABSC)
43
Talk about Aspergillus in CF
Aspergillus causes significant morbidity in CF Wide spectrum of disease Can cause allergic bronchopulmonary aspergillosis
44
Talk about Scedosporium spp in CF
An unusual isolate Lolipop canidia Risk factors for acquisition are not clear Some strains can remain present for years
45
How do we monitor CF patients, sample types etc?
Sampling is done at every hospital visist Sputum is the recommended sample but a cough swab can be carried out if the patient cannot expectorate Induced sputum or BALs can be considered in deterioratig patients Sample should be promptly transported to the lab and any delayed samples should be refrigerated
46
Why are CF samples often difficult to process?
CF samples are often thick and purulent Often ver mucoid Need to be processed prior to streaking etc
47
In general how are sputa samples processed?
Evaluate specimen -> describe appearance Add mucolyse and homogenise Gram stain (not always done) Culture Prepare smear for acid fast bacilli
48
In general how are NTB mycobacterium investigations carried out on sputa for CF patients
Done through either direct detection of nucleic acid or be preparing a smear for staining Staining requires a decontamination step -> both liquid culture and solid media are put up -> e.g. MGIT (BacT for Myco)
49
What are some standard culture media put up for sputa for CF patients?
Blood Chocolate MacConkey Burkholderia Cepacia selective agar Chromagar plates like SAID or pseudomonas ID Fungi plate like Sabouraud agar
50
Talk about te use of Burkholderia cepacia selective agar
A plate made selective by polymixin and gentamicin Will grow more than just B. cepacia e.g. resistant P aeruginosa and resistant NLFs such as achromobacter Plates get extended incubation if query NTBM Any query B cepacias have to undergo confirmatory ID by molecular methods Think of it like an extended MacConkey plate
51
What is the standad agar used for fungi for CF patients?
sabaroud Dextrose agar
52
What are the most common fungi in CF specimens
Aspergillus species Scedosporium species
53
Why is the Staph aureus ID chromagar extra important in CF patients?
This plate has improved recovery of Small colony varients compared to MSA alpha-glucosidase-producing colonies
54
In reality in the lab how are straight forward pathogens ID'd?
Standard ID on MALDI TOF Susceptibility testing on VITEK Doesnt work for a lot of the NLF GNBs though
55
What should you do if query a non fermentative GNB?
Must be confirmed by molecular ID methods
56
Why does AST often fail to predict treatment outcomes in CF?
This is because CF airwa infections tend to be polymicrobial and chronic This leads to bacterial diversification and adaptation
57
Why does AST often fail on chronic CF infections?
Our AST methods are based on recommendations for the treatment of organisms causing acute infection and pharmacokinetics/pharmocodynamics (PK/PD) models using blood levels of antibiotics Do not address the particular challenges of treatment in the CF respiratory tract Our AST methods arent designed to test organisms of chronic infection
58
What AST is currently carried out for CF patients?
Susceptibiltiy testing on P. aeruginosa isolates associated with early an intermittent colonisation only (no chronic) -> EUCAST Manual susceptibility testing on P. aeruginosa especially mucoid Manual susceptibility for all organisms on Burkholderia Cepacia Selective agar -> no breakpoints available for BC
59
Why are CF ASTs often disregarded?
AST is often poorly predictive of clinical outcome especialy in the management of P. aeruginosa Omissions dont really adversely affect short term clinical outcome There is a lack of correlation between conventional susceptibility test results and the actual therapeutic success especially in chronic infections
60
Why is it thought that AST for chronic PA infections is so unreliable?
Cells within biofilm can e either planktoni or sessile Sessile cells are dormant cells while planktonic cells are active
61
Why is it usually not possible to do AST when you have a pseudo?
Pseudos tend o take over plates especially mucoid pseudos This makes it difficullt to do any AST
62
What organisms have to be confirmed with molecular IDs and why
BCC, any gram negs such as stenos or any strange pseudos Phenotypic methods are just nnot reliable for these
63
What organisms have to be confirmed with molecular IDs and why
BCC, any gram negs such as stenos or any strange pseudos Phenotypic methods are just nnot reliable for these
64
Why are molecular methods for pseudomonas becoming increasingly common?
Molecular methods allow us to detect pseudomonas before traaditional culture can This can be important in preventing chronic infection - patient will be molecular positive before they will have a positive culture, this allows us to treat the infection early on to prevent it from ever becoming chronic - better for the long term treatment of the patient
65
Why are molecular methods for pseudomonas becoming increasingly common?
Molecular methods allow us to detect pseudomonas before traaditional culture can This can be important in preventing chronic infection - patient will be molecular positive before they will have a positive culture, this allows us to treat the infection early on to prevent it from ever becoming chronic - better for the long term treatment of the patient
66
Compare the use of molecular detection vs traditional cutlure for the detection of pseudomonas
Based of a crumlin hospital study: - culture was 82% sensitive while PCR was 93% - 80 specimens were PCR positive but culture negative, 26 of which were P. aueriginosa => PC has the potential to detect P. aeruginosa earlier than culture - no epidemic strains were found in this cohort
67
How much earlier can PCR detect P. aeruginosa compared to traditional culture?
According to a Belfast study it can detect up to 4-17 months earlier
68
What is the most commonly looked at gene for BCC identification and why is this?
recA gene polymorphisms enable both differentiation of BCC from other closely related bacteria Identification of different genomovars
69
Talk about the use of PCR for sputa samples
BD MAX system used for multiplex PCR detection of: - Pseudomonas aeruginosa - Burkholderia cepacia - Achromobacter xylosoxidans - Stenotrophomonas maltophilia
70
Talk about the use of PCR for CF samples
BD MAX system used for multiplex PCR detection of: - Pseudomonas aeruginosa - Burkholderia cepacia - Achromobacter xylosoxidans - Stenotrophomonas maltophilia
71
What four GN NF organisms can be detected by multiplex PCR on the BD max that interest CF patients
- Pseudomonas aeruginosa - Burkholderia cepacia - Achromobacter xylosoxidans - Stenotrophomonas maltophilia
72
Why is the BDMax platform for Gram negative Non-lactose fermenters ID a promising plateform?
A lot of labs already have the BDMax system in place It is n automated system Can identify organisms that traditional cutlure usually struggles with
73
Why is molecular ID needed for BCC?
Maldi cant speciate BCC ID needed to distinguish species within BCC
74
Talk about the use of targets for the ID of BCC
Cannot use an individual target to ID BCC Multi-target approach required for relible ID
75
Talk about the use of targets for the ID of BCC
Cannot use an individual target to ID BCC Multi-target approach required for relible ID
76
What are the four main targets for BCC?
hisA rpsU recA 16s rRNA
77
Talk about the use of PCR for P. aeruginosa
P. aeruginosa requires species specific PCR targets
78
What are the PCR targets for P aeruginosa?
16s rRNA gyrB ecfX oprL
79
Other than P. aeriginosa and BCC, what two organisms require molecular ID?
Stenotrophomonas Achromobacter spp
80
Talk about the Molecuar ID of NTB Mycobacterium
Line probe assays are used Molecular ID needed to differentiate between the NTB Myco species e.g. MAC versus M. abscessus i.e. molecular methods needed to speciate NTB Mycos
81
How does a line probe assay work
Strip of nitrocellulose with probes all along it Take organism, extract DNA, amplify up Add DNA to strip Targets match to specific nucleotides of the organism Look for colour change along card
82
How does a line probe assay work
Strip of nitrocellulose with probes all along it Take organism, extract DNA, amplify up Add DNA to strip Targets match to specific nucleotides of the organism Look for colour change along card
83
What is the main advantage and disadvantage of using line probe assays to speciate NTB Myco?
It is not a closed system -> risk of infection -> a lot of steps -> not straight forward Good performance, successfully identifies 92% of MAC and 100% of M. abscessus
84
What is the main advantage and disadvantage of using line probe assays to speciate NTB Myco?
It is not a closed system -> risk of infection -> a lot of steps -> not straight forward Good performance, successfully identifies 92% of MAC and 100% of M. abscessus
85
Where has BCC caused significant outbreaks?
Toronto and Canada
86
Where has BCC caused significant outbreaks?
Toronto and Canada
87
What are the two main markers found in epidemic strains of BCC
BCESM -> Burkholderia cepacia Epidemic Strain Marker cbLA -> cable-like pili
88
What are the two main markers found in epidemic strains of BCC
BCESM -> Burkholderia cepacia Epidemic Strain Marker cbLA -> cable-like pili
89
Why is there concern around the ET-12 strain of BCC?
ET-12 Burkholderia cenocepacia IIA has both BCESM and cbIA markers ET-12 has been the causative strain of outbreaksa -> not all but some There have also been epidemic BCC strains which have neither markers
90
Why is there concern around the ET-12 strain of BCC?
ET-12 Burkholderia cenocepacia IIA has both BCESM and cbIA markers ET-12 has been the causative strain of outbreaksa -> not all but some There have also been epidemic BCC strains which have neither markers
91
Where is the BCC reference lab?
Collindale UK Tallaght
92
Talk about epidemic P. aeruginosa strains
These are transmissible strains in paediatric and adult CF centres They tend to be non-motile, non-pigmented and multi-resistant Correct ID important in infection control and therapeutics Molecular ID and typing is the gold standard
93
Howhas molecula ID of atypical P. aeruginosa changed over years?
Used to use gel electrophoresis -> enzyme cuts DNA into fragments, separated out etc -> this only allowed us to group 'similar pseudo strains' not definitivel ID strains
94
Howhas molecula ID of atypical P. aeruginosa changed over years?
Used to use gel electrophoresis -> enzyme cuts DNA into fragments, separated out etc -> this only allowed us to group 'similar pseudo strains' not definitivel ID strains
95
Why are there often many abnormal strains of Pseudo identified when studies done on CF pateitns
Unusual strains tend to be ubiquituous, dont tend to be found in healthy people but can be found in CF patients
96
Why are we concerned with Myco. abscessus?
Its exact transmission route is yet to be estblished We dont know how it is being spread

4.1 Medical Microbiology (30 decks)

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