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Longitudinal development of initial, chronic and mucoid Pseudomonas aeruginosa infection in young children with cystic fibrosis.

ABSTRACT: BACKGROUND:While the emergence of chronic and mucoid Pseudomonas aeruginosa (Pa) infection are both associated with poorer outcomes among CF patients, their relationship is poorly understood. We examined the longitudinal relationship of incident, chronic and mucoid Pa in a contemporary, young CF cohort in the current era of Pa eradication therapy. METHODS:This retrospective cohort was comprised of patients in the U.S. CF Foundation Patient Registry born 2006-2015, diagnosed before age 2, and with at least 3 respiratory cultures annually. Incidence and age-specific prevalence of Pa infection stages (initial and chronic [? 3Pa+cultures in prior year]) and of mucoid Pa were summarized. Transition times and the interaction between Pa stage and acquisition of mucoid Pa were examined via Cox models. RESULTS:Among the 5592 CF patients in the cohort followed to a mean age of 5.5years, 64% (n=3580) acquired Pa. Of those, 13% (n=455) developed chronic Pa and 17% (n=594) cultured mucoid Pa. Among those with mucoid Pa, 36% (211/594) had it on their first recorded Pa+culture, while mucoid Pa emerged at or after entering the chronic stage in 12% (73/594). Mucoidy was associated with significantly increased risk of transition to chronic Pa infection (HR=2.59, 95% CI 2.11, 3.19). CONCLUSIONS:Two-thirds of early-diagnosed young children with CF acquired Pa during a median 5.6years of follow up, among whom 13% developed chronic Pa and 17% acquired mucoid Pa. Contrary to our hypothesis, 87% of young children who developed mucoid Pa did so before becoming chronically infected.

SUBMITTER: Heltshe SL

PROVIDER: S-EPMC5924440 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Longitudinal development of initial, chronic and mucoid Pseudomonas aeruginosa infection in young children with cystic fibrosis.

Heltshe S L SL Khan U U Beckett V V Baines A A Emerson J J Sanders D B DB Gibson R L RL Morgan W W Rosenfeld M M

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 20171028 3

<h4>Background</h4>While the emergence of chronic and mucoid Pseudomonas aeruginosa (Pa) infection are both associated with poorer outcomes among CF patients, their relationship is poorly understood. We examined the longitudinal relationship of incident, chronic and mucoid Pa in a contemporary, young CF cohort in the current era of Pa eradication therapy.<h4>Methods</h4>This retrospective cohort was comprised of patients in the U.S. CF Foundation Patient Registry born 2006-2015, diagnosed before ...[more]

PMID: 29110966

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Project description:Individuals with cystic fibrosis (CF) suffer from frequent and recurring microbial airway infections. The Gram-negative bacterium Pseudomonas aeruginosa is one of the most common organisms isolated from CF patient airways. P. aeruginosa establishes chronic infections that persist throughout a patient's lifetime and is a major cause of morbidity and mortality. Throughout the course of infection, P. aeruginosa must evolve and adapt from an initial state of early, transient colonization to chronic colonization of the airways. Here, we examined isolates of P. aeruginosa from children under the age of 3 years old with CF to determine genetic adaptations the bacterium undergoes during this early stage of colonization and infection. These isolates were collected when early aggressive antimicrobial therapy was not the standard of care and therefore highlight strain evolution under limited antibiotic pressure. Examination of specific phenotypic adaptations, such as lipid A palmitoylation, antibiotic resistance, and loss of quorum sensing, did not reveal a clear genetic basis for such changes. Additionally, we demonstrate that the geography of patient origin, within the United States or among other countries, does not appear to significantly influence genetic adaptation. In summary, our results support the long-standing model that patients acquire individual isolates of P. aeruginosa that subsequently become hyperadapted to the patient-specific airway environment. This study provides a multipatient genomic analysis of isolates from young CF patients in the United States and contributes data regarding early colonization and adaptation to the growing body of research about P. aeruginosa evolution in the context of CF airway disease. IMPORTANCE Chronic lung infection with Pseudomonas aeruginosa is of major concern for patients with cystic fibrosis (CF). During infection, P. aeruginosa undergoes genomic and functional adaptation to the hyperinflammatory CF airway, resulting in worsening lung function and pulmonary decline. All studies that describe these adaptations use P. aeruginosa obtained from older children or adults during late chronic lung infection; however, children with CF can be infected with P. aeruginosa as early as 3 months of age. Therefore, it is unclear when these genomic and functional adaptations occur over the course of CF lung infection, as access to P. aeruginosa isolates in children during early infection is limited. Here, we present a unique cohort of CF patients who were identified as being infected with P. aeruginosa at an early age prior to aggressive antibiotic therapy. Furthermore, we performed genomic and functional characterization of these isolates to address whether chronic CF P. aeruginosa phenotypes are present during early infection.

Dataset Information

Longitudinal development of initial, chronic and mucoid Pseudomonas aeruginosa infection in young children with cystic fibrosis.

Publications

Longitudinal development of initial, chronic and mucoid Pseudomonas aeruginosa infection in young children with cystic fibrosis.

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