(545) Respiratory microbiological surveillance in patients with CF (pwCF)- analysis of respiratory samples pre and post Kaftrio in a large adult UK CF Centre

Background: Pathogen surveillance remains crucial but has become more challenging in the era of highly effective modulator therapy (HEMT), with many pwCF noting a considerable reduction or even absence of sputum on Kaftrio. This challenge has been exacerbated by reduced face to face (F2F) contact with patients due to variable Covid-19 government restrictions on travel and social interaction- or ‘lockdowns’- from March 20, relying on pwCF returning high quality samples by post. For those with pre-established bronchiectasis it is likely chronic infections and risk of new acquisition of infections remain on Kaftrio, although registry data does suggest reduced prevalence of respiratory microorganisms on Ivacaftor[1]. We aimed to examine the impact of Kaftrio on both frequency of respiratory pathogen surveillance and microorganism growth in our large adult UK CF centre.

Methods: A retrospective analysis of pathology results from respiratory samples received from March 19-Dec 21 was completed for all patients commenced on Kaftrio at our large adult UK CF centre.

Results: Respiratory samples from 216 pwCF who had commenced Kaftrio were analyzed. The median start date of Kaftrio was Oct 10th 2020.

Prior to Kaftrio the average number of respiratory samples /month was 108. This reduced by 55% to an average of 48 /month when the first 50 pwCF commenced on Kaftrio and reduced to 20 /month (82% reduction from pre Kaftrio) when 100 pwCF had commenced Kaftrio.

The number of positive samples/month decreased from Jan 20, correlating with the introduction of Kaftrio and the reduction of respiratory samples received (Figure 1).

The proportion of cough swabs and sputum samples remained similar from March 19-Dec 21 (6 month average found 19% of samples were cough swabs and 80% sputum for both March–June 19 and July–Dec 21).

We found no significant changes in the proportion of samples positive for non-Pseudomonas spp. gram negative organisms, Burkholderia spp., gram positive organisms (predominantly S.aureus) isolated over the time period. There was a reduction by over 50% of Fungi and Candida spp., and a slight trend towards an increase in Pseudomonas spp. (mainly P.aeruginosa).

40% of those pwCF who had 1 respiratory sample post Kaftrio, and 20% of those who had 2 or more samples post Kaftrio showed a change in organism growth post Kaftrio. In nearly 50% of these cases the organism changed from a gram negative to a gram positive organism (P.aeruginosa to S.aureus in 69% of cases).

Conclusions: The introduction of Kaftrio and its impact on sputum production has reduced surveillance of our patients’ respiratory microbiology. This has been exacerbated by the impact of reduced F2F contact with patients due to the Covid-19 pandemic. The trends show a reduction in the isolation of fungi and yeasts and a slight increase in isolating Pseudomonas spp.. In those who we have seen a change in organism growth many have gone from gram negative to gram positive organisms. These data highlight the challenges of monitoring for new positive cultures and changes in microbiology cultures post HEMT.

Acknowledgements:

References: [1] Bessonova L, Volkova N, Higgins M, Bentsson L, Tian S, Simard C, Kinstan M, Sawicki G, Sewall A, Nyangoma S, Elbert A, Marshall B, Bilton D. Data from the US and UK cystic fibrosis registries support disease modification by CFTR modulation with ivacaftor. Thorax 2018; 73:731–740.