Pseudomonas aeruginosa in Chronic Obstructive Pulmonary Disease

Murphy, Timothy F.; Brauer, Aimee L.; Eschberger, Karen; Lobbins, Phyllis; Grove, Lori; Cai, Xueya; Sethi, Sanjay

doi:10.1164/rccm.200709-1413oc

Cited by 257 publications

(111 citation statements)

References 47 publications

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“…Despite the potential for saliva admixture, collection of sputum represents the only practical approach for repeated airway sampling of COPD patients, particularly during exacerbations, when bronchoscopy may be unsafe. Important microbial insights, including several from this cohort, have been gleaned from analysis of sputum in many studies of COPD (2,3,8,43).…”

Section: Discussionmentioning

confidence: 99%

“…The sputum samples analyzed were collected from 12 subjects enrolled in a longitudinal study of bacterial infection in COPD described extensively in previous publications (2,3,13). To briefly summarize, the parent study has been conducted at the Buffalo Veterans Affairs Hospital and approved by the VA Western New York Institutional Review Board since 1994.…”

Section: Methodsmentioning

confidence: 99%

“…Culture-based evaluations have implicated bacteria in ϳ50% of exacerbations (1). While acquisition of new strains of Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Pseudomonas aeruginosa is associated with exacerbations (2,3), these represent relatively few species compared to the overall diversity of airway microbiota recently described in COPD (4)(5)(6)(7).…”

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Airway Microbiome Dynamics in Exacerbations of Chronic Obstructive Pulmonary Disease

et al. 2014

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Specific bacterial species are implicated in the pathogenesis of exacerbations of chronic obstructive pulmonary disease (COPD).However, recent studies of clinically stable COPD patients have demonstrated a greater diversity of airway microbiota, whose role in acute exacerbations is unclear. In this study, temporal changes in the airway microbiome before, at the onset of, and after an acute exacerbation were examined in 60 sputum samples collected from subjects enrolled in a longitudinal study of bacterial infection in COPD. Microbiome composition and predicted functions were examined using 16S rRNA-based culture-independent profiling methods. Shifts in the abundance (>2-fold, P < 0.05) of many taxa at exacerbation and after treatment were observed. Microbiota members that were increased at exacerbation were primarily of the Proteobacteria phylum, including nontypical COPD pathogens. Changes in the bacterial composition after treatment for an exacerbation differed significantly among the therapy regimens clinically prescribed (antibiotics only, oral corticosteroids only, or both). Treatment with antibiotics alone primarily decreased the abundance of Proteobacteria, with the prolonged suppression of some microbiota members being observed. In contrast, treatment with corticosteroids alone led to enrichment for Proteobacteria and members of other phyla. Predicted metagenomes of particular microbiota members involved in these compositional shifts indicated exacerbation-associated loss of functions involved in the synthesis of antimicrobial and anti-inflammatory products, alongside enrichment in functions related to pathogen-elicited inflammation. These trends reversed upon clinical recovery. Further larger studies will be necessary to determine whether specific compositional or functional changes detected in the airway microbiome could be useful indicators of exacerbation development or outcome.A cute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a major source of morbidity, characterized by worsening of respiratory symptoms from the baseline normal variation that require new treatment (http://www.goldcopd.org/). Culture-based evaluations have implicated bacteria in ϳ50% of exacerbations (1). While acquisition of new strains of Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Pseudomonas aeruginosa is associated with exacerbations (2, 3), these represent relatively few species compared to the overall diversity of airway microbiota recently described in COPD (4-7).Detection of bacteria in most prior studies was limited by the use of culture-based methods (8, 9). Application of more sensitive molecular tools has consistently shown a greater diversity of airway microbiota in COPD, despite differences in specimens and platforms across studies (4-7, 10). With increasing appreciation of the fact that the microbial microenvironment can modify the behavior of primary pathogens (11,12), this invites speculation that other microbiota members may contribute to the pathogenesis o...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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Airway Microbiome Dynamics in Exacerbations of Chronic Obstructive Pulmonary Disease

et al. 2014

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“…A plausible explanation is that PA requires a more serious involvement of the respiratory epithelium and local respiratory defenses to colonize inferior airways [26,27,28]. In advanced COPD, acquisition of different strains of PA and posterior clearance even without antibiotic treatment is frequent [29], and PA isolates obtained from respiratory samples of COPD patients show lower motility and cytotoxicity compared with strains isolated by culturing of blood samples [30], suggesting lesions of the airway epithelium rather than virulence of the PA itself. One of the most important points of criticism in studies dealing with PA and COPD is the inclusion of patients with bronchiectasis.…”

Section: Discussionmentioning

confidence: 99%

Pseudomonas aeruginosa and Mortality after Hospital Admission for Chronic Obstructive Pulmonary Disease

Almagro¹,

Salvadó²,

García-Vidal³

et al. 2011

Respiration

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Background:Pseudomonas aeruginosa (PA) is isolated in advanced stages of chronic obstructive pulmonary disease (COPD). Objectives: The aim of our study was to determine whether PA isolation during hospitalization for COPD exacerbation was associated with a poorer prognosis after discharge. Methods: We prospectively studied all patients with COPD exacerbation admitted between June 2003 and September 2004. A sputum culture was obtained at admission. Comorbidity, functional dependence, hospitalizations during the previous year, dyspnea, quality of life and other variables previously associated with mortality in COPD were studied. Spirometry and a 6-min walking test were performed 1 month after discharge. Mortality was evaluated 3 years after discharge. Results: A total of 181 patients were included in the study. Of these, 29 (16%) had PA in the sputum. The mean age was 72 years, and mean basal postbronchodilator forced expiratory volume in 1 s was 45.2% predicted (SD 14.4). The mean point value on the BODE index was 5.1 (SD 2.5). At 3 years, 17 of 29 patients (58.6%) in the PA group had died, compared to 53 of the 152 non-PA patients [34.9%; p < 0.004; hazard ratio (HR) 2.23, 95% confidence interval (CI) 1.29–3.86]. In the multivariate analysis, PA remained statistically related to posthospital mortality (p = 0.02; HR 2.2, 95% CI 1.2–4.2) after adjustment for age (p < 0.02; HR 1.04, 95% CI 1.007–1.07), BODE index (p < 0.02; HR 1.15, 95% CI 1.02–1.3) and comorbidity (p < 0.02; HR 1.24, 95% CI 1.03–1.5). Conclusions: PA isolation in sputum in patients hospitalized for acute exacerbation of COPD is a prognostic marker of 3-year mortality. Poor prognosis is independent of other significant predictors of mortality such as BODE index, age and comorbidity, as measured by the Charlson index.

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“…Pneumonia caused by Gram-negative bacteria, in particular, Pseudomonas aerugi-nosa, shows increased incidence in immunocompromised individuals (10)(11)(12)(13). Recently, a retrospective study failed to show that macrolide treatment of P. aeruginosa airway infections during the first 48 h reduced mortality rates (14).…”

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confidence: 99%

The Nonantibiotic Macrolide EM703 Improves Survival in a Model of Quinolone-Treated Pseudomonas aeruginosa Airway Infection

Kasetty

Bhongir

Papareddy

et al. 2017

Antimicrob Agents Chemother

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Macrolide antibiotics are used as anti-inflammatory agents, e.g., for prevention of exacerbations in chronic obstructive pulmonary disease and cystic fibrosis. Several studies have shown improved outcomes after the addition of macrolides to ␤-lactam antibiotics for treatment of severe community-acquired pneumonia. However, a beneficial effect of macrolides in treating Gram-negative bacterial airway infections, e.g., those caused by Pseudomonas aeruginosa, remains to be shown. Macrolide antibiotics have significant side effects, in particular, motility-stimulating activity in the gastrointestinal tract and promotion of bacterial resistance. In this study, EM703, a modified macrolide lacking antibiotic and motility-stimulating activities but with retained anti-inflammatory properties, was used as an adjunct treatment for experimental P. aeruginosa lung infection, in combination with a conventional antibiotic. Airway infections in BALB/cJRj mice were induced by nasal instillation of P. aeruginosa; this was followed by treatment with the quinolone levofloxacin in the absence or presence of EM703. Survival, inflammatory responses, and cellular influx to the airways were monitored. Both pretreatment and simultaneous administration of EM703 dramatically improved survival in levofloxacin-treated mice with P. aeruginosa airway infections. In addition, EM703 reduced the levels of proinflammatory cytokines, increased the numbers of leukocytes in bronchoalveolar lavage fluid, and reduced the numbers of neutrophils present in lung tissue. In summary, the findings of this study show that the immunomodulatory properties of the modified macrolide EM703 can be important when treating Gram-negative pneumonia, as exemplified by P. aeruginosa infection in this study.KEYWORDS macrolide, EM703, host defense, anti-inflammatory, Pseudomonas aeruginosa M acrolide antibiotics (for example, erythromycin, azithromycin, and clarithromycin) have caught interest for use in the treatment of chronic airway inflammation (1). Reduction of pulmonary exacerbations has been demonstrated in cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) (2, 3). Macrolides display broad biological responses, including bacteriostatic activity, stimulation of gastrointestinal motility, and anti-inflammatory properties (4-6). Each of these effects could be advantageous, depending on the clinical context; however, promotion of drug-resistant bacteria and diarrhea limit the clinical use of macrolides as anti-inflammatory agents.In severe community-acquired pneumonia, which is often caused by the Grampositive coccus Streptococcus pneumoniae, meta-analyses have shown that the addition of a macrolide antibiotic to a ␤-lactam has beneficial effects, reducing mortality rates (7-9). Pneumonia caused by Gram-negative bacteria, in particular, Pseudomonas aerugi-

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Pseudomonas aeruginosa in Chronic Obstructive Pulmonary Disease

Cited by 257 publications

References 47 publications

Airway Microbiome Dynamics in Exacerbations of Chronic Obstructive Pulmonary Disease

Airway Microbiome Dynamics in Exacerbations of Chronic Obstructive Pulmonary Disease

<b><i>Pseudomonas aeruginosa</i></b> and Mortality after Hospital Admission for Chronic Obstructive Pulmonary Disease

The Nonantibiotic Macrolide EM703 Improves Survival in a Model of Quinolone-Treated Pseudomonas aeruginosa Airway Infection

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