Pooling isolates to address the diversity in antimicrobial susceptibility of Pseudomonas aeruginosa in cystic fibrosis.

IMPORTANCE: People with cystic fibrosis (pwCF) often suffer from chronic lung infections with Pseudomonas aeruginosa. While antibiotics are still commonly used to treat P. aeruginosa infections, there is a high discordance between in vitro and in vivo antibiotic efficacy, which contributes to suboptimal antibiotic therapy. In the present study, we found that isolates from the same sputum sample had highly diverse antibiotic resistance profiles [based on the minimal inhibitory concentration (MIC)], which may explain the reported discrepancy between in vitro and in vivo antibiotic efficacy. Through systematic analysis, we report that pooling nine isolates per sputum sample significantly decreased intrasample diversity in MIC and influenced clinical interpretation of antibiotic susceptibility tests compared to single isolate testing. Hence, pooling of isolates may offer a solution to obtain a consistent MIC test result and could lead to optimizing antibiotic therapy in pwCF and other infectious diseases where diversity in antibiotic resistance is observed.

Factors associated with clinical progression to severe COVID-19 in people with cystic fibrosis: A global observational study.

BACKGROUND: This international study aimed to characterise the impact of acute SARS-CoV-2 infection in people with cystic fibrosis and investigate factors associated with severe outcomes. Methods Data from 22 countries prior to 13th December 2020 and the introduction of vaccines were included. It was de-identified and included patient demographics, clinical characteristics, treatments, outcomes and sequalae following SARS-CoV-2 infection. Multivariable logistic regression was used to investigate factors associated with clinical progression to severe COVID-19, using the primary outcome of hospitalisation with supplemental oxygen. RESULTS: SARS-CoV-2 was reported in 1555 people with CF, 1452 were included in the analysis. One third were aged <18 years, and 9.4% were solid-organ transplant recipients. 74.5% were symptomatic and 22% were admitted to hospital. In the non-transplanted cohort, 39.5% of patients with ppFEV1<40% were hospitalised with oxygen verses 3.2% with ppFEV >70%: a 17-fold increase in odds. Worse outcomes were independently associated with older age, non-white race, underweight body mass index, and CF-related diabetes. Prescription of highly effective CFTR modulator therapies was associated with a significantly reduced odds of being hospitalised with oxygen (AOR 0.43 95%CI 0.31-0.60 p<0.001). Transplanted patients were hospitalised with supplemental oxygen therapy (21.9%) more often than non-transplanted (8.8%) and was independently associated with the primary outcome (Adjusted OR 2.45 95%CI 1.27-4.71 p=0.007). CONCLUSIONS: This is the first study to show that there is a protective effect from the use of CFTR modulator therapy and that people with CF from an ethnic minority are at more risk of severe infection with SARS-CoV-2.