Achromobacter xylosoxidansairway infection is associated with lung disease severity in children with cystic fibrosis

Abstract

BackgroundDespite the increasing prevalence of Achromobacter xylosoxidans (A. xylosoxidans) lung infection in patients with cystic fibrosis (CF), its clinical pathogenicity remains controversial. The objective of this study was to evaluate the effects of this emerging bacterium on lung disease severity in CF children.MethodsThis case-control retrospective study took place in two French paediatric CF centres. Forty-five cases infected by A. xylosoxidans were matched for age, sex, CFTR genotypes and pancreatic status, to 45 never infected controls. Clinical data were retrieved from clinical records over the 2 years before and after A. xylosoxidans initial infection.ResultsAt infection onset, lung function was lower in the cases compared to controls (p=0.006). Over the 2 years prior A. xylosoxidans acquisition, compared to controls, cases had more frequent pulmonary exacerbations (p=0.02), hospitalisations (p=0.05), as well as intravenous (p=0.03) and oral (p=0.001) antibiotic courses. In the 2 years following A. xylosoxidans infection, the cases remained more severe with more frequent pulmonary exacerbations (p=0.0001), hospitalisations (p=0.0001), as well as intravenous (p=0.0001) and oral antibiotic courses (p=0.0001). Lung function decline tended to be faster in the cases (−5.5%/year) compared to controls (−0.5%/year).ConclusionsThis case-control study demonstrates that A. xylosoxidans occurs more frequently in the patients with the worse lung disease. Further studies assessing the pathogenicity of this emerging pathogen and international treatment recommendations are warranted.

Achromobacter xylosoxidans Purulent Bronchitis in a Previously Healthy Child: An Unexpected Consequence of COVID-19 Infection

“…The prevalence of lung colonization in patients with CF nowadays ranges from approximately 10% to 18%, suggesting an increasing trend, in comparison to earlier reports [1,[8][9][10]. According to a recent case-control retrospective study conducted in two major French pediatric CF centers, the acquisition of A. xylosoxidans was associated with accelerated lung function decline, leading to recurrent pulmonary exacerbations and hospitalizations of the affected children.…”

“…Due to its adaptability to survive in diverse environments, it was isolated in supposedly sterile hospital equipment such as respirators, humidifiers, ultrasound gels, etc. In a similar way to Pseudomonas aeruginosa, the bacterium possesses a denitrification system, enabling its survival and biofilm synthesis in hypoxic and anoxic airways of CF patients [1][2][3][4][5][6][7]. Other adaptive mechanisms leading to bacterium's deleterious pathogenicity include hypermutability, microevolution, and subsequent ability to withstand fluctuating environmental conditions in CF lungs [6].…”

“…However, the link between the presence of A. xylosoxidans and the decline of pulmonary function was difficult to establish, as children with positive isolates had worse lung function to start with. The hypothesis was that children with severe forms of CF were more prone to A. xylosoxidans infection, which further aggravated the disease course through cytokine production and chronic pulmonary inflammation [1].…”

“…This emerging pathogen is becoming increasingly detected in respiratory specimens of adults and children with underlying lung conditions and/or immunodeficiency disorders, cystic fibrosis (CF) being the most commonly associated disease [1][2][3][4][5][6][7]. Recent data in pediatric CF patients show a strong correlation between A. xylosoxidans acquisition and faster lung function decline, more frequent hospitalizations, and the need for antibiotic courses [1]. The bacterium was first described in 1971 but it still remains underdiagnosed, unabling its early eradication.…”

In Vitro Activity of 22 Antibiotics against Achromobacter Isolates from People with Cystic Fibrosis. Are There New Therapeutic Options?

“…This opportunistic pathogen has been associated with acute pulmonary exacerbations, chronic infections and higher concentrations of TNF-α in sputum samples. Achromobacter infection occurs most commonly in CF patients with advanced lung disease and is associated with a poor clinical course [2][3][4][5][6][7]. Achromobacter species are well-armed for colonisation and persistence in the CF lung, as they harbour a large panel of adaptive strategies (biofilm formation, antibiotic resistance, hypermutation, secretion and quorum sensing systems) [8].…”