Lecture - Cystic Fibrosis Infection Flashcards
1
Q
Cystic fibrosis intro
A
- due to a defective transmembrane conductance regulator
- the most common lethal genertic disorder of caucasians
- 1/2500 caucasians
- less prevalent in other racial groups
- multisystem disease mainly manifested in lungs
- lungs secrete thick mucus - prevents proper function in expelling foreign bodies such as microbes
2
Q
CFTR mutation
A
- caused by point mutations in the gene coding for CFTR
- CFTR regulates chloride movement out of mucus-producing cells
- most common point mutatin is a codon deletion in position 508 of the aa sequence - loss of phenylalanine
- does not allow chloride ion out - leads to a mucus that is deficient, extremely dehydrated and static - not cleared and provides a good microbial habit
3
Q
Microbes commonly infecting people with CG
- bacteria
- fungi
A
- polymicrobial communities that can grow as mixed biofilms
- may be inhaled directly through aerosols but also common oropharyngeal organisms
- bacteria: staph aureaus, h. Influenzae, B. Cenocepacia, Stenotrophomonas maltophilia, Pseudomonas aeruginosa
- Fungi: cryptosporidium sp, aspergillus fumigatus, Candida albicans
4
Q
Changes in bacterial infection patterns with age
A
- initially a mixed
- S aureus most present early on but then drops
- P. Aeruginosa most common in adults
5
Q
Staph aureaus
A
- common commensal
- one of the earliest bacteria detected in infants and children with CF
- peak prevalence between 11-15
- its ability to form biofilms also decrease effectiveness of antibiotic treatment
- antibiotic treatment has been made more difficult by the rise of MRSA in the last 10 yers
6
Q
MRSA
A
- resistance to b-lactam antibiotics and cephalosporins
- conflicting reports on wherther MRSA is associated with a significant decline in lung function
7
Q
Small colony variants of S aureaus
A
- smaller size on agar plates
- less pigmentation
- less hemolysis
- increased intracellular persistence in in bitro studies
- SCV continue to express SigB dependent genes encoding cell surface proteins such as adhesins - important in virulence
- increased ability to adhere to host component, to form biofilms and to invade and persist
8
Q
Treatment for staph aureus
A
- primary prophylaxis
- eradication
- treatment of CF pulmonary exacerbations
- treatment of MRSA
9
Q
- Treatment of staph aureus issues
A
- may lead to a higher infection rate with P. Aeruginosa
- no guidelines or recomendation for MRSA or SCV
- lack of data
- fear of increased MRSA resistance
10
Q
H/ infleunzae
A
- Gram - rod
- also significant resp pathogen in non-CF patients
- common infector early in childhood, decreasing in older. Present in encapsulated and non-encapsulated phenotypes
- prevalence is increasing in children with CF
- non-encapsulated H. Influenza is mostly associated with chronic lung infectin and acute exacerbation
- presence of an adhesive gene and both persistence and long term cross-colonisation are significantly linked
11
Q
Burkholderia cepacia
A
- Bcc comprises 17 specied of catalase +ve, non-lactose fermenting, gfram - bacteria
- opportunistic pathogen
- most common in CF are B. Multivorans and B. Cenocepacia
- not very prevalent but infection by some strains pose an immediate health risk
- ET12 serovars of B cenopcepacia have the most serious health outcome - can be fatal
- resistant to almost all antibiotics
- patient to patient tranmission
12
Q
B.cenopacia pathogenesis
A
- intracellular parasite
- intracellular survival in macrophage is associated with profound changes in metabolic activity and motility
- cytotoxic toward macrophage host cell - killing it
- virulence factors: quorum sensing, iron uptake, LPS, Exopolysaccharide, antimicrobial resistance, flagella
13
Q
Treatment of B. Cenocepacia
A
- resistant to many common antibiotics, including aminoglycosides and polymyxin B
- treatment: ceftazidime, doxycline, piperacillin, meropenem, chloramphrenicol…
14
Q
Stenotrophomonas maltophilia
A
- gram -
- agent of ventilator assisted pneumonia
- MDR, persistent in 20% of cases
- prevalence in CF is 10-15% in lige
- ubiquituous
- patients who acquire S maltophilia usually have more advanced disease and more exaggerated lung function decline
15
Q
Pseudomonas aeroginosa
A
- Gram - bacillus, non lactose fermenting, oxidase positive
- ubiquituous in envt
- adaptable
- highly antibiotic resistant
- prolific biofil former
- acquired by susceptible persons from environment by inhalation
- responsible for most adult CF patient deaths
