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      Determinants of bacteriological outcomes in exacerbations of chronic obstructive pulmonary disease

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          Abstract

          Purpose

          Changes in sputum microbiology following antibiotic treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD), including patterns of bacteriological relapse and superinfection are not well understood. Sputum microbiology at exacerbation is not routinely performed, but pathogen presence and species are determinants of outcomes. Therefore, we determined whether baseline clinical factors could predict the presence of bacterial pathogens at exacerbation. Bacterial eradication at end of treatment (EOT) is associated with clinical resolution of exacerbation. We determined the clinical, microbiological and therapeutic factors that were associated with bacteriological eradication in AECOPD at EOT and in the following 8 weeks.

          Methods

          Sputum bacteriological outcomes (i.e., eradication, persistence, superinfection, reinfection) from AECOPD patients ( N = 1352) who were randomized to receive moxifloxacin or amoxicillin/clavulanate in the MAESTRAL study were compared. Independent predictors of bacterial presence in sputum at exacerbation and determinants for bacteriological eradication were analyzed by logistic regression and receiver operating characteristic (ROC) analyses.

          Results

          Significantly greater bacteriological eradication with moxifloxacin was mainly driven by superior Haemophilus influenzae eradication ( P = 0.002, EOT). Baseline clinical factors were a weak predictor of the presence of pathogens in sputum (AUC ROC = 0.593). On multivariate analysis, poorer bacterial eradication was associated with antibiotic resistance ( P = 0.0001), systemic steroid use ( P = 0.0024) and presence of P. aeruginosa ( P = 0.0282).

          Conclusions

          Since clinical prediction of bacterial presence in sputum at AECOPD is poor, sputum microbiological analysis should be considered for guiding antibiotic therapy in moderate-to-severe AECOPD, particularly in those who received concomitant systemic corticosteroids or are at risk for infection with antibiotic-resistant bacteria.

          Electronic supplementary material

          The online version of this article (doi:10.1007/s15010-015-0833-3) contains supplementary material, which is available to authorized users.

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          Most cited references23

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          Persistent colonization by Haemophilus influenzae in chronic obstructive pulmonary disease.

          Nontypeable Haemophilus influenzae colonizes the respiratory tract of adults with chronic obstructive pulmonary disease (COPD) and causes intermittent exacerbations. Isolates of H. influenzae collected monthly in a prospective study were subjected to molecular typing. During a 7-year study spanning 345 patient-months of observation, 122 episodes of negative cultures lasting 1 month or more, and that were preceded and followed by isolation of an apparently identical strain of H. influenzae, were found. Seventeen such episodes of negative cultures, lasting 6 months or more and spanning 203 patient-months, were studied in detail to test the hypothesis that these periods of negative cultures represented continuous colonization by the same strain of H. influenzae. Molecular typing by three independent methods established that the strains preceding and following the episodes of negative cultures were indeed identical. Strain-specific H. influenzae DNA was detected in some of the sputum samples that had yielded negative cultures. These results indicate that some patients with COPD are persistently colonized with H. influenzae and that sputum cultures underestimate the frequency of colonization of the respiratory tract by H. influenzae in COPD. This observation has a significant impact on understanding bacterial colonization in COPD.
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            Time course of recovery of health status following an infective exacerbation of chronic bronchitis.

            The magnitude and time course of effect of an acute exacerbation of chronic bronchitis (AECB) on health status are not known. Data from the GLOBE study, a randomised double blind trial of antibiotic therapy, were used to investigate these effects. 438 patients with AECB received either gemifloxacin 320 mg once daily for 5 days (214 patients) or clarithromycin 500 mg twice daily for 7 days (224 patients) and were followed up for 26 weeks. St George's Respiratory Questionnaire (SGRQ) scores were obtained at baseline and after 4, 12, and 26 weeks. At presentation during an exacerbation SGRQ scores were worse (Total score difference 5.4 units, 95% CI 1.9 to 8.8, p=0.002) in patients who had a subsequent exacerbation during follow up. The greatest improvement in SGRQ score occurred within the first 4 weeks (mean 8.9 units, 95% CI 6.5 to 11.5, p<0.0001). Subsequently, scores improved more rapidly in patients with no further exacerbations. At 26 weeks the difference between the two groups was 9.6 units (95% CI 5.7 to 13.4, p<0.0001). In patients with no further exacerbations the SGRQ score improved between 4 and 12 weeks by a further 4.1 units (95% CI 2.2 to 5.9, p<0.0001). A single infective AECB has a sustained effect on health status. The recovery period is long even in patients who have no further exacerbations. A second episode within 6 months limits recovery markedly. Treatments that reduce exacerbation frequency could have a significant impact on health status.
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              Relationship between bacterial flora in sputum and functional impairment in patients with acute exacerbations of COPD. Study Group of Bacterial Infection in COPD.

              To investigate the possible relationship between functional respiratory impairment measured by FEV1 and isolation of diverse pathogens in the sputum of patients with exacerbations of COPD. Multicenter, cross-sectional, epidemiologic study. Pneumology units in six secondary or tertiary hospitals in Spain. Ninety-one patients with acute exacerbation of COPD were included. A quantitative sputum culture was performed, and bacterial growth was considered significant only when the germ was isolated at concentrations > 10(6) cfu (> 10(5) for Streptococcus pneumoniae) in samples with 25 leukocytes per low magnification field (x 100). Germs isolated were the following: Haemophilus influenzae (20 cases; 22%), Pseudomonas aeruginosa (14 cases; 15%), S. pneumoniae (9 cases; 10%), Moraxella catarrhalis (8 cases; 9%), other gram-negative bacteria (7 cases; 7%), and non-potentially pathogenic microorganisms (non-PPMs; 33 cases; 36%). P. aeruginosa and H. influenzae were isolated more frequently among the patients with FEV1 50% (p 50% was low, with a predominance of non-PPMs. Low FEV1 and active tobacco smoking are data that should be considered when establishing an empiric antibiotic treatment for exacerbated COPD.
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                Author and article information

                Contributors
                +1 716 862 7875 , ssethi@buffalo.edu
                Journal
                Infection
                Infection
                Infection
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0300-8126
                1439-0973
                14 September 2015
                14 September 2015
                2016
                : 44
                : 65-76
                Affiliations
                [ ]Division of Pulmonary, Critical Care and Sleep Medicine, University at Buffalo, State University of New York, Buffalo, NY USA
                [ ]VA Medical Research, 151, 3495 Bailey Avenue, Buffalo, NY 14215 USA
                [ ]South Texas Veterans Health Care System, University of Texas Health Science Center at San Antonio, San Antonio, TX USA
                [ ]Pneumology Department, Hospital Universitari Vall d’Hebron, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain
                [ ]Bayer HealthCare, Loos, France
                [ ]Bayer HealthCare Pharmaceuticals, Whippany, NJ USA
                [ ]Bayer Inc., Toronto, ON Canada
                [ ]Host Defence Unit, Royal Brompton Hospital, London, UK
                Article
                833
                10.1007/s15010-015-0833-3
                4735236
                26370552
                bfe6b106-5093-421b-83c4-05362fc41ea7
                © The Author(s) 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 21 April 2015
                : 14 August 2015
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100000801, Bayer Healthcare;
                Categories
                Original Paper
                Custom metadata
                © Springer-Verlag Berlin Heidelberg 2016

                Infectious disease & Microbiology
                bacteriological outcomes,beta-lactams,exacerbation of chronic obstructive pulmonary disease,fluoroquinolones,risk factors,systemic corticosteroids

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