A critical review of definitions used to describe Pseudomonas aeruginosa microbiological status in patients with cystic fibrosis for application in clinical trials

Abstract

Background: Definition of Pseudomonas aeruginosa (Pa) microbiological status is essential for patients' inclusion in clinical trials. The aim of this study was to agree on the definitions of Pa infection status for initial infection, eradication and chronic infection to be used in clinical trials and to propose additional future study areas. Methods: An exhaustive literature search was performed. The clinimetric properties of different definitions of Pa microbiological status were evaluated. Results: Historical studies have mostly used culture-based definitions, although some have also involved complementary anti-Pa antibodies. Clinimetric analysis showed great variability in the definitions used, leading to differences in reliability, validity, responsiveness to treatment and correlation with outcome measures. Use of serology for initial Pa infection and successful Pa eradication introduced a greater level of complexity as antibody tests are not standardised. Moreover, the chronology of the immune response to Pa antigenic determinants was not completely clear. Chronic Pa infection was characterized by high levels of antibodies and good concordance between culture results and serology. Conclusions: Microbiological monitoring, regular sampling from the airways and standardization of culture methods remain essential requisites for microbiological definitions. Despite limitations, serology should be incorporated in the definitions of initial infection and eradication used in clinical trials to better classify patients at enrolment, mainly in non-expectorating children. This requires standardization of serological testing.

High-Throughput Immunochemical Method to Assess the 2-Heptyl-4-quinolone Quorum Sensing Molecule as a Potential Biomarker of Pseudomonas aeruginosa Infections

“…The data obtained showed that it might be possible to distinguish between isolates obtained from chronic or acute infection, thus adding valuable clinical information that has been never reported, based on the production of QS alkylquinolones. As an example, clear knowledge of the P. aeruginosa microbiological status is essential in order to make decisions 45 on whether a patient could be included in a clinical trial. Early diagnosis of pulmonary P. aeruginosa is a key issue since infection by this bacterium is associated with poor outcomes in CF.…”

Pf4 Phage Variant Infection Reduces Virulence-Associated Traits in Pseudomonas aeruginosa

“… Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes acute and chronic infections in immunocompromised hosts, including patients with cystic fibrosis (CF), burns, or cancers ( 1 – 3 ). P. aeruginosa is one of the most prevalent bacterial pathogens in the lungs of CF patients associated with poor clinical outcomes due to their problematic eradication ( 4 , 5 ). This pathogen exhibits high intrinsic and acquired antibiotic resistance and is classified by the World Health Organization (February 2017) as “critical” (carbapenem resistant).…”

Impact of Coexistence Phenotype Between Staphylococcus aureus and Pseudomonas aeruginosa Isolates on Clinical Outcomes Among Cystic Fibrosis Patients

“…Furthermore, these criteria may lack sensitivity and are not always considered by clinicians (Hoo et al, 2018). Alternatively, PA serology appears to be a sensitive criterion for classifying PA infection, especially in non-expectorating children, but is not always available (Taccetti et al, 2019). In order to clearly study the impact of SA and/or PA infection, we focused on stabilized infections.…”