The influence of the genotype and respiratory tract microflora on lung function and nutritional status in adult cystic fibrosis patients in long-term follow-up

In recent years, an increase in the number of patients with chronic infection with nonfermenting gram-negative bacteria (NFGNB) in adult patients with cystic fibrosis (CF) has increased. The genotype and phenotype characteristics, NFGNB structure, changes in sensitivity and the development of antibiotic resistance in adult patients have not been adequately studied.

Aim. To determine the impact of genotype severity and Achromobacter xylosoxidans sensitivity to carbapenems on the functional and nutritional status of adult cystic fibrosis patients over a period 2016 – 2021.

Materials. Retrospective analysis of genotypic and microbiological data from 54 adult CF patients and their effects on FEV1 and BMI over a period 2016 – 2021. Sputum cultures were confirmed by MALDI-TOF mass spectrometer. Depending on the severity of the mutation, the patients were divided into 2 groups: group 1 (“severe” genotype) – patients who had 2 mutations of class I – III; group 2 (“soft” genotype) – at least 1 class IV – VI mutation.

Results. The group of patients with “mild” mutations had a higher BMI (kg / m2) than the group with severe mutations for a longer period of follow-up from 2018 – 2021 than in the group with severe mutations: BMI (2016) – 21.14 ± 3.55 / 19.28 ± 3.13 (p = 0.163); BMI (2017) – 21.27 ± 3.43 / 18.31 ± 2.05 (p = 0.123); BMI (2018) – 21.17 ± 4.00 / 18.80 ± 2.12 (p = 0.025); BMI (2019) – 21.01 ± 4.20 / 18.55 ± 2.53 (p = 0.049); BMI (2020) – 20.94 ± 4.12 / 18.41 ± 2.15 (p = 0.050). Age at diagnosis was 20.36 ± 2.18 years for “mild” genotypes and was higher (p = 0.042) than for “severe” genotypes (6.27 ± 1.53 years). All 7 patients who died (100%) were in the “severe” genotype group (23.3%). Functional status assessment showed no differences in FEV1 over 6 years between the “severe” and “mild” genotype groups: FEV1 (2016) – p = 0.51; FEV1 (2017) – p = 0.39; FEV1 (2018) – p = 0.51; FEV1 (2019) – p = 0.35; FEV1 (2020) – p = 0.48. Nonfermenting Gram-negative bacteria accounted for 49.9% of the isolated microorganisms. The group of carbapenem-resistant Achromobacter xylosoxidans lost the FEV1 level faster every year for 6 years (p < 0.05) compared to the group of the sensitive variant.

Conclusion. In general, patients with the “mild” genotype have higher nutritional status and do not differ from patients with the “severe” genotype in terms of FEV1. The survival rate of patients with the “mild” genotype patients survival rate is higher, despite the later diagnosis and start of treatment. Development of carbаpenem resistance in Achromobacter xylosoxidans is associated with an unfavorable prognosis of the functional status decline.

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