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      Pseudomonas infection in antibody deficient patients

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          Abstract

          Pseudomonas aeruginosa (PA) is commonly isolated from the respiratory secretions of antibody deficiency patients, but the significance of this has not been well studied. We have reviewed our adult antibody deficiency cohort of 179 patients and assessed the prevalence and characteristics of PA infection and the effects of early antibiotic eradication treatments. Of the 34 patients with PA, 55.9% (19) underwent successful eradication and were infection-free, 38.2% (13) had intermittent infection, and 5.9% (2) had chronic PA. PA infection was significantly associated with bronchiectasis ( p < 0.0001), with 36.1% (22 out of 61) of patients with bronchiectasis developing a PA infection. Infection status was also significantly associated with chronic sinusitis ( p < 0.0001). Most treated PA exacerbations were symptomatic and with colony counts of ≥1000 cfu/ml. Current eradication protocols used at our center involve early treatment at first positive isolate with ciprofloxacin for 3 weeks and nebulized colomycin for 3 months, and if eradication fails, intravenous ceftazidime and gentamycin or colomycin is administered for 2 weeks. Continued sputum surveillance and early eradication treatments upon positive PA culture may help to limit chronic PA infection in antibody deficiency patients.

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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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              Antibiotic treatment of initial colonization with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis.

              Chronic pulmonary infection with Pseudomonas aeruginosa (PA) develops in most patients with cystic fibrosis (CF) and is associated with a poor prognosis. Much effort has been directed toward treating the chronic infection, but it is almost impossible to eradicate it once established; therefore, prevention is preferable. Since 1989 CF patients at the Danish CF Center in Copenhagen have been treated with an intensive three-step-protocol consisting of colistin inhalations and oral ciprofloxacin at the time of initial PA colonization. This study compares 48 patients treated according to this intensive protocol with 43 historic controls. The study was carried out over 44 months and included 218 patient-years. Only 16% of the treated patients developed chronic PA infection after 3 1/2 years compared with 72% of the control patients (Kaplan Meier estimate, P < 0.005, log rank test). This indicates that aggressive treatment prevented or delayed chronic PA infection in 78% of the patients for 3 1/2 years. Furthermore, aggressive treatment maintained or increased pulmonary function (forced vital capacity and forced expiratory volume in 1 second in percent of predicted values) during the year after inclusion compared with the control group, in which pulmonary function declined (P < 0.01, Mann-Whitney test). Although some of the treated patients eventually developed chronic PA infection, these patients had significantly better pulmonary function at the onset of chronic PA infection compared with control patients (P < 0.001, Mann-Whitney test). When the different steps in the intensive three-step-protocol were analyzed, there was a trend suggesting that 3 months of high-dose treatment with colistin inhalation and oral ciprofloxacin produced the best results in terms of postponement or prevention of chronic PA infection (P < 0.05).
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                Author and article information

                Journal
                1886
                122234
                European Journal of Microbiology and Immunology
                Akadémiai Kiadó
                2062-509X
                2062-8633
                1 December 2014
                16 December 2014
                : 4
                : 4 ( otherID: N2K345420864 )
                : 198-203
                Affiliations
                [ 1 ] Royal London Hospital, Pathology and Pharmacy Building Immunology Department 80 Newark Street, Whitechapel London E1 2ES UK
                [ 2 ] King’s College Hospital Department of Immunological Medicine London UK
                [ 3 ] Barts Health NHS Trust Immunology Department London UK
                Article
                G4V388823R515238
                10.1556/EUJMI-D-14-00026
                7b2648c9-653e-4599-a632-675b45fb92c2
                History
                Categories
                Original Article

                Medicine,Immunology,Health & Social care,Microbiology & Virology,Infectious disease & Microbiology
                immunodeficiency,infection, Pseudomonas ,bronchiectasis

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