FT-IR Spectroscopy to Discriminate Old from New Pseudomonas aeruginosa Infections in People with Cystic Fibrosis

Chronic Pseudomonas aeruginosa colonisation leads to lung deterioration and poor prognosis in people with cystic fibrosis (pwCF). Early and aggressive therapies can achieve P. aeruginosa eradication, which may recur later. Therefore, determining whether it has resisted therapy or has been newly acquired may guide subsequent treatment(s). This information is crucial also for patients treated with CFTR modulators representing P. aeruginosa after prolonged negativity and to confirm chronic infections. We evaluated the ability of Fourier-transform infrared (FT-IR) spectroscopy to determine intra-patient isoclonality for 103 P. aeruginosa strains isolated from 36 pwCF. Two were chronically and two intermittently colonised; twelve were on modulators with a past P. aeruginosa colonisation; and twenty received eradication therapy, ten of whom were also treated with modulators. FT-IR data were validated by Whole Genome Sequencing (WGS) identification of Sequence Type. FT-IR identified persistence of P. aeruginosa in 24 patients, with a WGS-confirmed positive predictive value of 100% and diagnostic accuracy of 94%. The eradication therapy success rate was 45%, and the time to P. aeruginosa reappearance was similar in both patients with failed eradication treatment and those who initially cleared the infection but later acquired a new strain. Nine patients in modulators showed persistent infections. FT-IR can rapidly determine the clonality of P. aeruginosa isolates, allowing discrimination of recurring versus new infections both in patients with established colonisations and those subjected to eradication therapy representing P aeruginosa. By overcoming the time-based criteria used to define new infections and by providing the actual success rate of eradication therapies, FT-IR can effectively contribute to the development of efficient therapeutic strategies.