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      Gram negative infections in cystic fibrosis: a review of preventative and treatment options

      1 , 2 , 2 , 3

      Expert Opinion on Orphan Drugs

      Informa UK Limited

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          The changing microbial epidemiology in cystic fibrosis.

           John J LiPuma (2010)
          Infection of the airways remains the primary cause of morbidity and mortality in persons with cystic fibrosis (CF). This review describes salient features of the epidemiologies of microbial species that are involved in respiratory tract infection in CF. The apparently expanding spectrum of species causing infection in CF and recent changes in the incidences and prevalences of infection due to specific bacterial, fungal, and viral species are described. The challenges inherent in tracking and interpreting rates of infection in this patient population are discussed.
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            Evaluation of a new definition for chronic Pseudomonas aeruginosa infection in cystic fibrosis patients.

            Patients were defined each successive month as either 'chronic' when more than 50% of the preceding 12 months were PA culture positive, 'intermittent' when < or =50% of the preceding 12 months were PA culture positive, 'free of PA', with no growth of PA for the previous 12 months, having previously been PA culture positive, or 'never infected', when PA had never been cultured. Cross-sectional analysis of 146 children attending the Leeds Regional Cystic Fibrosis Centre was performed to assess relationship between the new definition and clinical scores and investigations. The response variable was regressed on age and sex and the residuals analysed using the Kruskal-Wallis test. The 'chronic' group (18% of patients) had significantly worse Shwachman-Kulczycki (SK) and Northern chest X-ray scores, and % predicted FEV(1) values than the 'free' (28%) or 'never' (20%) categories (P<0.004). The 'intermittent' group (34%) had a significantly higher SK score than the 'chronic' group (P<0.0001), and a significantly lower % predicted FEV(1) value than the 'free' or 'never' groups (P<0.0003). 'Chronic' patients were significantly associated with a positive, and 'never' patients with a negative, PA antibody result (P<0.001). The validity and importance of identifying these four subgroups is demonstrated. Previous definitions may over-estimate the prevalence of chronic infection.
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              Longitudinal development of mucoid Pseudomonas aeruginosa infection and lung disease progression in children with cystic fibrosis.

              Although Pseudomonas aeruginosa is the most common virulent respiratory pathogen in cystic fibrosis (CF), the longitudinal development of P aeruginosa infection and its effect on antibody responses and lung disease progression in children with CF remain unclear. To prospectively examine the epidemiology of P aeruginosa infection and its impact on CF pulmonary morbidity. We prospectively evaluated 56 CF patients at 2 CF centers in Madison and Milwaukee, Wis, from birth up to age 16 years between April 15, 1985, and April 15, 2004, with diagnoses made through the Wisconsin CF Neonatal Screening Project. Timing of nonmucoid P aeruginosa and mucoid P aeruginosa acquisition was assessed by first positive result. Longitudinal development from no P aeruginosa to nonmucoid P aeruginosa and from nonmucoid P aeruginosa to mucoid P aeruginosa was examined. Outcome measurements included antibody titers, respiratory symptoms, quantitative chest radiography, and pulmonary function tests. Sixteen patients (29%) acquired nonmucoid P aeruginosa in the first 6 months of life. The age-specific prevalence of mucoid P aeruginosa increased markedly from age 4 to 16 years. Nonmucoid and mucoid P aeruginosa were acquired at median ages of 1.0 and 13.0 years, respectively. In contrast with the short transition time from no P aeruginosa to nonmucoid P aeruginosa, the transition time from nonmucoid to mucoid P aeruginosa was relatively long (median, 10.9 years) and could be slightly extended by brief/low anti-P aeruginosa antibiotic treatment. Antibody titers increased with both transitions, but the deterioration in cough scores, chest radiograph scores, and pulmonary function correlated best with transition from nonmucoid to mucoid P aeruginosa. Early prevention and detection of nonmucoid and mucoid P aeruginosa are critical because of early acquisition and prevalence. There is a window of opportunity for suppression and possible eradication (by aggressive anti-P aeruginosa treatment) of initial nonmucoid P aeruginosa. Mucoid P aeruginosa plays a much greater role in CF lung disease progression than nonmucoid P aeruginosa. Antibody titers, cough scores, and chest radiographs are early signs of nonmucoid P aeruginosa and especially mucoid P aeruginosa stages.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                Expert Opinion on Orphan Drugs
                Expert Opinion on Orphan Drugs
                Informa UK Limited
                2167-8707
                January 02 2020
                January 29 2020
                January 02 2020
                : 8
                : 1
                : 11-26
                Affiliations
                [1 ] Centre for Medical Education, Queen’s University Belfast, Belfast, UK
                [2 ] Northern Ireland Regional Adult CF Centre, Belfast Health and Social Care Trust, Belfast, UK
                [3 ] Centre for Experimental Medicine, Queen's University Belfast, Belfast, UK
                Article
                10.1080/21678707.2020.1713748
                © 2020

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