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

Paul Briaud,Catherine Mainguy,Laura Camus,Marie Boyadjian,Sylvère Bastien,François Vandenesch,Anne Doléans-Jordheim,Karen Moreau,Philippe Reix

doi:10.3389/fcimb.2020.00266

Abstract

Staphylococcus aureus (SA) is the major colonizer of the lungs of cystic fibrosis (CF) patients during childhood and adolescence. As patients age, the prevalence of SA decreases and Pseudomonas aeruginosa (PA) becomes the major pathogen infecting adult lungs. Nonetheless, SA remains significant and patients harboring both SA and PA are frequently found in the worldwide cohort. The overall impact of co-infection remains controversial. Furthermore, co-infecting isolates may compete or coexist. The aim of this study was to analyse if co-infection and the coexistence of SA and PA could lead to worse clinical outcomes. The clinical and bacteriological data of 212 Lyon CF patients were collected retrospectively, and patients were ranked into three groups, SA only (n = 112), PA only (n = 48) or SA plus PA (n = 52). In addition, SA and PA isolates from co-infected patients were tested in vitro to define their interaction profile. Sixty five percent (n = 34) of SA/PA pairs coexist. Using univariate and multivariate analysis, we confirm that SA patients have a less severe clinical condition than others, and PA induces a poor outcome independently of the presence of SA. Regarding co-infection, no significant difference in clinical outcomes was observed between patients with coexisting pairs and patients with competitive pairs. However, when compared to SA mono-infected patients, patients with coexisting pair presented higher frequency and length of hospitalizations and more exacerbations. We suggest that coexistence between SA and PA may be an important step in the natural history of lung bacterial colonization within CF patients.

Highlights

Cystic fibrosis (CF) is the most common genetic disease among the Caucasian population that affects multiple organs and causes various complications associated with patient death, such as cystic fibrosis liver disease (Debray et al, 2017) (CFLD) and cystic fibrosis related diabetes (Brennan and Beynon, 2015) (CFRD).Coexistence of S. aureus and P. aeruginosa in CFthe first cause of morbidity and mortality in CF remains the progressive decrease in pulmonary function, leading to an obstructive syndrome (Davis, 2006)
Of the 655 CF patients monitored in Lyon hospitals, we selected patients with at least three respiratory specimens with Staphylococcus aureus (SA) and/or Pseudomonas aeruginosa (PA) during the study period
The lungs of CF patients are colonized by multiple bacteria and several studies were conducted to decipher the impact of these colonisations on clinical outcomes

Summary

Introduction

The first cause of morbidity and mortality in CF remains the progressive decrease in pulmonary function, leading to an obstructive syndrome (Davis, 2006). This decline is generally due to the continuous inflammation provoked by polymicrobial infections (Davis, 2006). Despite the implication of SA in a worse clinical status, PA, which becomes the dominant pathogen of the respiratory tract in adulthood (Zolin et al, 2019) (up to 60% of patients > 18 years), traditionally remains the most feared pathogen due to its strong association with most severe clinical outcomes, such as more aggravated inflammation, an increase in the number of exacerbations and a decrease in forced expiratory volume in one second (FEV1) (Kerem et al, 1990; Nixon et al, 2001; Hubert et al, 2013; Ahlgren et al, 2015)

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