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Cystic fibrosis (CF) is an autosomal recessive disease of mainly Caucasian populations of European ancestry, which is exacerbated by a continuous cycle of respiratory inflammation and lung infection, which may become chronic, leading to increasing disease severity (
Several bacterial genera and species are particularly associated with increased morbidity and mortality in patients with cystic fibrosis, as detailed in
Whilst
One hundred adult (≥18 years old) CF patients from the Northern Ireland Regional Adult Cystic Fibrosis Centre, Belfast City Hospital, with a diagnosis of CF, were included in this retrospective analysis for the presence of non-
UK Standards for Microbiology Investigations: Investigation of bronchoalveolar lavage, sputum and associated specimens (available at
Complete 16S rDNA sequences of the 10 NAPs, as well as
Whole genomes maps of
A whole genome sequence comparison was performed with
One hundred adult (>18 years old) patients with cystic fibrosis were examined in this study, with a mean age of 24.6 years, median age 24 years, with an age range of 18–76 years. This patient cohort consisted of 50 females and 50 males. Microbiological data was examined from 100 patients from birth to present (31/12/2021), equating to 2455 patient years.
Ten non-
Description of non-
Organism | Occurrence (%) in adult CF patients |
Patient sex | Mean time to first isolation (months) | Median time to first isolation (months) | Time to first isolation (range [months]) | F508del/F508del | F508del/other | other/other |
---|---|---|---|---|---|---|---|---|
|
33 | 60.6% female/39.4% male | 195 | 198 | 23–338 | 45.5 | 48.5 | 6 |
|
18 | 33% female/67% male | 184 | 220 | 11–285 | 50 | 22 | 28 |
|
6 | 33% female/67% male | 171 | 170 | 90–273 | 83 | 17 | |
|
1 | Female | 284 | 100 | ||||
|
1 | Female | 207 | 100 | ||||
|
1 | Female | 195 | 100 | ||||
|
1 | Female | 300 | 100 | ||||
|
1 | Male | 269 | 100 | ||||
|
1 | Female | 160 | 100 | ||||
|
1 | Female | 286 | 100 | ||||
Mean | 183 | 229 |
since birth–equivalent to 2455 patient years.
A microbiological comparison of the non-
Phylogenetic relatedness between the 10 NAPs species and
Whole genomes maps of
Putatively homologous regions were found across the two whole genomes examined, 6,264,404 bp (
Whole genome alignment map of
Cystic fibrosis lung pathology is dominated by the presence of the genus
In this study, we examined the sputum microbiology of 100 adult CF patients from their birth until the present (31 December 2021), which in totality equated to 2455 patient years. Ten species were isolated from this patient cohort during this time period, with three species, i.e.,
The presence of
Previous reports on the involvement of non-
Organism | Description | References |
---|---|---|
|
Isolation of |
( |
Isolation of |
( |
|
Development of a diagnostic PCR assay that targets a heat-shock protein gene ( |
( |
|
In antibiotic susceptibility testing, the activity of ceftazidime was two dilutions greater than the other three cephalosporins against |
( |
|
Isolation of |
( |
|
Isolation of |
||
|
Recovered from oropharyngeal cultures from healthy, non-CF infants in 3 months–6 months age (1/21; 4.8%) and from 6 months to 9 months age group (1/20; 5%). Not isolated from oropharyngeal cultures from 75 CF infants in the first year of life. Not considered pathogenic. Care should be taken to not over interpret the presence of some of these organisms in the oropharyngeal cultures of asymptomatic CF infants | ( |
Misidentification of |
( |
|
Development of a diagnostic PCR assay that targets a heat-shock protein gene ( |
( |
|
Isolation of |
( |
|
Description of |
( |
|
|
Development of a diagnostic PCR assay that targets a heat-shock protein gene ( |
( |
Presence of algT. Whilst |
( |
|
|
Misidentification of |
( |
|
No reports | |
|
Misidentification of |
( |
|
No reports | |
|
Case of metalworking fluids (MWFs)-Hypersensitivity pneumonitis sensitized to |
( |
|
No reports | |
|
No reports | ( |
|
12 |
The isolation of species of low pathogenesis and virulence from the genus
Proposed criteria for evaluating the clinical significance of colonisation of non-
Criteria | Description |
---|---|
1 | Persistent colonisation (intermittent & chronic) as shown by positive repeat sputum cultures for same organism, as defined by the Leeds criteria ( |
2 | High quantitative counts in sputum (108–109 colony forming units/g sputum) |
3 | Reduction in lung function markers (FEV1 & FVC) in absence of known CF microbial pathogens or other clinical reason (e.g., poor adherence to airway clearance) |
4 | Worsening chest radiological imaging in absence of known CF microbial pathogens |
5 | Increase in C-reactive protein (CRP), without other focus of infection or in absence of known CF microbial pathogens |
6 | Clinical improvement and pro rata reduction in NAP organisms after commencement of antibiotic therapy |
7 | Ecological displacement of existing flora with NAP organisms |
8 | Serological response with specific antibody to NAP organisms as determined by counter immunoelectrophoresis (CIE) |
9 | Pathogenic pedigree: Has the NAP organism isolated been associated with NAP-related pathology previously and has known virulence determinants? |
10 | May evolve into phenotypes which are multi- and pan-resistant to antipseudomonal antibiotics, including aminoglycosides, beta-lactams and fluoroquinolones |
FEV1 = forced expiratory volume in the first second.
FVC, forced vital capacity.
NAP, non-aeruginosa
Within the
This study involved examining sputum microbiology from birth to the present (December 2021), of a set of 100 adult CF patients from a single adult CF centre in the UK. Sputum microbiology methods followed UK Standard Operating Procedures in a UK accredited NHS Clinical Microbiology Laboratory which helped to standardise variability in methodology, to potentially account for the comparison of these data with data from other CF centres. Furthermore, the infection control practices at this single centre, as well as infection control-related health literacy of the CF patients may influence the cohort of NAPs isolated and reported in this study. Therefore, it would beneficial to expand this study in the future to include several other CF centres both locally, nationally and internationally.
So why do we not see the dominance of other species of
• • There is a paucity of published information describing the microbiology of non-
• This study describes the diversity of non- • A set of ten clinical and laboratory criteria are proposed to provide key indicators, as to the clinical importance of the non-
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below:
JEM: Conceptualization, formal analysis, methodology, roles/writing—original draft, writing—review and editing. JM: Methodology, writing—review and editing. JR: Writing—review and editing. BM: Conceptualization, formal analysis, methodology, roles/writing—original draft, writing—review and editing.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The Supplementary Material for this article can be found online at: