"Pathogen Eradication" and "Emerging Pathogens": Difficult Definitions in Cystic Fibrosis.

Infection is a common complication of cystic fibrosis (CF) airway disease. Current treatment approaches include early intervention with the intent to eradicate pathogens in the hope of delaying the development of chronic infection and the chronic use of aerosolized antibiotics to suppress infection. The use of molecules that help restore CFTR (cystic fibrosis transmembrane conductance regulator) function, modulate pulmonary inflammation, or improve pulmonary clearance may also influence the microbial communities in the airways. As the pipeline of these new entities continues to expand, it is important to define when key pathogens are eradicated from the lungs of CF patients and, equally important, when new pathogens might emerge as a result of these novel therapies

In vitro activity of seven hospital biocides against Mycobacterium abscessus: Implications for patients with cystic fibrosis

Background: Mycobacterium abscessus pulmonary infection has recently emerged as a significant pathogen in patients with cystic fibrosis (CF) and is associated with significant morbidity and accelerated pulmonary decline. There is a paucity of data describing the activity of hospital biocides against this organism. Methods: M. abscessus isolates (n = 13) were recovered from CF and non-CF respiratory specimens. Seven commonly employed hospital biocides with generic ingredients as follows: acetone, propan-2-ol, diethylene glycol, 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one, chlorine dioxide, 4% chlorhexidine, alcohol, and disodium carbonate, compound with hydrogen peroxide, 10% sodium hypochlorite were assayed for their biocidal activity against M. abscessus. Fresh cultures of M. abscessus were exposed to biocide in liquid medium as per manufacturers' instruction and were immediately plated following the completion of the contact period. The mean concentration of M. abscessus plated was 9.82 × 106 colony-forming units (range: 1.63 × 105–1.12 × 108). In addition, the remaining bacteria/biocide solution was enriched nonselectively in Mueller Hinton broth (37°C/1 week) and then plated. Results: All M. abscessus isolates survived in alkyl dimethyl benzyl ammonium chloride, 5-chloro-2-methyl-2H-isothiazol-3-one (EC No. 247-500-7) and 2-methyl-2H-isothiazol-3-one, 4% Chlorhexidine™, O-phenylphenol and Sodium Lauryl Sulfate™ and disodium carbonate, compound with hydrogen peroxide. One out of 13 M. abscessus cultures was killed by Chlorine Dioxide™ and one by Sodium Dichloroisocyanurate™, representing a 5-log kill. Two isolates were killed by Alcohol™ again representing a 5 log kill. Following enrichment, O-phenylphenol and Sodium Lauryl Sulfate™ showed the greatest biocidal activity with 11/13 isolates, whereas 2/13 cultures were killed by sodium dichloroisocyanurate™. All other biocide/culture combinations yielded growth. Conclusion: These data indicate that M. abscessus may persist after exposure to several common hospital biocides. Further work is urgently needed to define unequivocal biocide contact treatments to prevent cross-infection with this mycobacterial species in this patient population and thus ensure effective infection control and prevention

Infection dynamics of <i>Aspergillus fumigatus</i> in adults with cystic fibrosis (CF)

ObjectiveAspergillus fumigatus (A. fumigatus) has emerged as a significant pathogen in patients with cystic fibrosis (CF) and currently is within the top five isolated organisms reported in several international CF patient registries. A. fumigatus has been attributed to disease progression, although its role remains controversial. There is a paucity of reports on its infection dynamics, it was the aim of this study to examine time to first laboratory reports of A. fumigatus acquisition and to correlate this with patient gender and cystic fibrosis transmembrane conductance regulator (CFTR) mutation type.MethodsOne hundred adult (≥ 18 years) CF patients were examined (50 females, 50 males; mean age 24.6 years ± 6.25 (SD), median age 24 years; maximum age 76 years). CFTR mutation groups consisted (i) F508del/F508del homozygous (n = 45), (ii) F508del/other heterozygous (n = 45) and (iii) others (n = 10). CFTR mutation type, patient gender, presence/absence of A. fumigatus and time (months) to first isolation of A. fumigatus were examined.ResultsMicrobiological data was examined from 100 patients from birth to present (31/12/2021), equating to 2455 patient years. A. fumigatus was isolated from 66/100 (66%) adult CF patients; (i) F508del/F508del homozygous (82%; 37/45), (ii) F508del/other heterozygous (56%; 25/45) and (iii) others (40%; 4/10). Within the F508del/other heterozygous group, 14 mutations were noted on the second allele, with R560T and R117H collectively accounting for 36% of the second mutations. Four unique allele/allele mutations were noted in the Other Mutations category. There was a trend to a higher A. fumigatus acquisition in F508del/F508del homozygous patients than with F508del/other patients (p = 0.0529). Of the 66 patients who were positive for A. fumigatus, 35(53%) were male and 31(47%) were female. The median and mean time to first isolation of A. fumigatus in all A. fumigatus-positive patients was 119.5 months and 128 months, respectively, shortest time was 12 months, longest time 288 months. There was a statistical significance in time-to-first isolation in relation to CFTR mutation group (p = 0.0272), whereby F508del homozygous individuals had their first isolation of A. fumigatus at 116.8 ± 7.9 months (mean ± standard error of the mean (SEM)) and F508del heterozygous patients had their first isolate of A. fumigatus at 150.4 months ± 13.7 months (mean ± SEM), approximately 2.75 years after their F508del homozygous peers. There was no significant difference (p = 0.12) in time to first acquisiton between males and females, whereby males had their first A. fumigatus isolate at 118 ± 9.4 months, whereas females had their first A. fumigatus isolate at 140 ± 10.8 months. The highest rate of first A. fumigatus isolation was from 4 years until 16 years and by the age of 16 years, approximately 85% of A. fumigatus-positive patients had recorded their first A. fumigatus isolate.ConclusionTo minimise the risk of first acquisition of A. fumigatus, it is important that infection prevention educational messaging is delivered in the paediatric clinic, to enhance health literacy around A. fumigatus acquisition.<br/

Cystic fibrosis: Infection prevention &amp; control recommendations for universities, colleges and institutes of further and higher education - A practical guide

Background: The avoidance of cross-infection remains of critical importance to prevent the transmission of cystic fibrosis (CF)-related microbial pathogens to persons/people with cystic fibrosis (PwCF). To date, there has been a paucity of infection prevention and control (IPC) guidance relating to infection risk at higher educational institutions. With improvements in treatments, more PwCF are now attending universities/colleges and educational institutions now seek CF-specific guidance on IPC from clinical CF teams/centres. Methods: Real world infection-related questions from university students, educators, university support staff and the CF multidisciplinary team were received and collated from various stakeholders, including individual consultations and focus group sessions with two local universities. Subsequently, evidence-based recommendations were compiled from existing peer-reviewed literature and from cystic fibrosis organisations. Glossaries were constructed relating to clinical, microbiological and educational/pedagogical terminology to aid with the understanding amongst these stakeholder groups. Results: This review addresses CF-related IPC recommendations across five areas of university/college life, including (i) on campus estate, (ii) teaching (lectures/tutorials/small study group work/group assignments), (iii) laboratory practicals, (iv) field trips/study visits/work placements and (v) residential accommodation and lists practical recommendations to help prevent the transmission of infections to PwCF students. Conclusions: It is important that the educational institutional environment is safe permitting the PwCF student to enjoy their educational experience and journey through higher education, culminating in achievement of their educational goals, employment and independent living. The guidance presented in this review is intended to equip educational establishments in creating their own bespoke and robust IPC policies relating to PwCF students