Factors Associated with Worse Lung Function in Cystic Fibrosis Patients with Persistent Staphylococcus aureus

被引：57

作者：

Junge, Sibylle ^{[1
]}

Göerlich, Dennis ^{[2
]}

den Reijer, Martijn ^{[3
]}

Wiedemann, Baerbel ^{[4
]}

Tuemmler, Burkhard ^{[5
]}

Ellemunter, Helmut ^{[6
]}

Duebbers, Angelika ^{[7
]}

Kuester, Peter ^{[8
]}

Ballmann, Manfred ^{[9
]}

Koerner-Rettberg, Cordula ^{[9
]}

Grosse-Onnebrink, Joerg ^{[10
]}

Heuer, Eberhardt ^{[11
]}

Sextro, Wolfgang ^{[11
]}

Mainz, Jochen G. ^{[12
]}

Hammermann, Jutta ^{[13
]}

Riethmueller, Joachim ^{[14
]}

Graepler-Mainka, Ute ^{[14
]}

Staab, Doris ^{[15
]}

Wollschlaeger, Bettina ^{[16
]}

Szczepanski, Ruediger ^{[17
]}

Schuster, Antje ^{[18
]}

Tegtmeyer, Friedrich-Karl ^{[19
]}

Sutharsan, Sivagurunathan ^{[20
]}

Wald, Alexandra ^{[21
]}

Nofer, Jerzy-Roch ^{[22
]}

van Wamel, Willem ^{[3
]}

Becker, Karsten ^{[23
]}

Peters, Georg ^{[23
]}

Kahl, Barbara C. ^{[23
]}

机构：

[1] Clin Paediat Pulmonol Allergol & Neonatol, Hannover, Germany

[2] Univ Hosp Munster, Inst Biostat & Clin Res, Munster, Germany

[3] Erasmus MC, Dept Med Microbiol & Infect Dis, Rotterdam, Netherlands

[4] Tech Univ Dresden, Inst Med Informat & Biometr, Dresden, Germany

[5] Hannover Med Sch, Clin Paediat Pulmonol Allergol & Neonatol, Clin Res Grp, Hannover, Germany

[6] Med Univ Innsbruck, Dept Child & Adolescent Hlth, CF Ctr Innsbruck, Innsbruck, Austria

[7] Univ Hosp Munster, Dept Paediat, Munster, Germany

[8] Clemenshosp Munster, Dept Paediat, Munster, Germany

[9] Ruhr Univ, Paediat Clin, St Josef Hosp, Bochum, Germany

[10] Univ Hosp Essen, Dept Paediat, Essen, Germany

[11] Kinderarztl Ambulanz, Hamburg, Germany

[12] Jena Univ Hosp, Dept Paediat, CF Ctr, Jena, Germany

[13] Univ Clin Dresden, Dept Paediat, Dresden, Germany

[14] Univ Clin Tubingen, Dept Pediat, Tubingen, Germany

[15] Charite Univ Med Berlin, Dept Paediat Pulmonol & Immunol, Campus Virchow Klinikum, Berlin, Germany

[16] Univ Hosp Halle, Halle, Germany

[17] Childrens Hosp Osnabruck, Osnabruck, Germany

[18] Univ Dusseldorf, Dept Paediat, Dusseldorf, Germany

[19] Pk Schonefeld Clin, Kassel, Germany

[20] Ruhrlandklin, Essen, Germany

[21] Univ Clin Leipzig, Leipzig, Germany

[22] Univ Hosp Munster, Ctr Lab Med, Munster, Germany

[23] Univ Hosp Munster, Inst Med Microbiol, Munster, Germany

来源：

PLOS ONE | 2016年 / 11卷 / 11期

关键词：

SMALL-COLONY VARIANTS; C-REACTIVE PROTEIN; PSEUDOMONAS-AERUGINOSA; NASAL CARRIAGE; STENOTROPHOMONAS-MALTOPHILIA; FEV1; DECLINE; RISK-FACTORS; INFECTION; CHILDREN; EXACERBATIONS;

D O I：

10.1371/journal.pone.0166220

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Background Staphylococcus aureus is an important pathogen in cystic fibrosis (CF). However, it is not clear which factors are associated with worse lung function in patients with persistent S. aureus airway cultures. Our main hypothesis was that patients with high S. aureus density in their respiratory specimens would more likely experience worsening of their lung disease than patients with low bacterial loads. Methods Therefore, we conducted an observational prospective longitudinal multi-center study and assessed the association between lung function and S. aureus bacterial density in respiratory samples, co-infection with other CF-pathogens, nasal S. aureus carriage, clinical that no competing interests exist. status, antibiotic therapy, IL-6- and IgG-levels against S. aureus virulence factors. Results 195 patients from 17 centers were followed; each patient had an average of 7 visits. Data were analyzed using descriptive statistics and generalized linear mixed models. Our main hypothesis was only supported for patients providing throat specimens indicating that patients with higher density experienced a steeper lung function decline (p<0.001). Patients with exacerbations (n = 60), S. aureus small-colony variants (SCVs, n = 84) and co-infection with Stenotrophomonas maltophilia (n = 44) had worse lung function (p = 0.0068; p = 0.0011; p = 0.0103). Patients with SCVs were older (p = 0.0066) and more often treated with trimethoprim/sulfamethoxazole (p = 0.0078). IL-6 levels positively correlated with decreased lung function (p<0.001), S. aureus density in sputa (p = 0.0016), SCVs (p = 0.0209), exacerbations (p = 0.0041) and co-infections with S. maltophilia (p = 0.0195) or A. fumigatus (p = 0.0496). Conclusions In CF-patients with chronic S. aureus cultures, independent risk factors for worse lung function are high bacterial density in throat cultures, exacerbations, elevated IL-6 levels, presence of S. aureus SCVs and co-infection with S. maltophilia.

引用

页数：18

共 50 条

[1] Staphylococcus aureus Small-Colony Variants Are Independently Associated With Worse Lung Disease in Children With Cystic Fibrosis
Wolter, Daniel J.
Emerson, Julia C.
McNamara, Sharon
Buccat, Anne M.
Qin, Xuan
Cochrane, Elizabeth
Houston, Laura S.
Rogers, Geraint B.
Marsh, Peter
Prehar, Karandeep
Pope, Christopher E.
Blackledge, Marcella
Deziel, Eric
Bruce, Kenneth D.
Ramsey, Bonnie W.
Gibson, Ronald L.
Burns, Jane L.
Hoffman, Lucas R.
CLINICAL INFECTIOUS DISEASES, 2013, 57 (03) : 384 - 391
[2] Adaptation of Staphylococcus aureus to the cystic fibrosis lung
Goerke, Christiane
Wolz, Christiane
INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY, 2010, 300 (08) : 520 - 525
[3] Staphylococcus Aureus Small-Colony Variants Are Independently Associated With Worse Lung Disease In A Cohort Of Children With Cystic Fibrosis
Hoffman, L.
Wolter, D.
Emerson, J.
McNamara, S.
Buccat, A.
Qin, X.
Cochrane, E.
Houston, L.
Rogers, G.
Marsh, P.
Prehar, K.
Pope, C.
Blackledge, M.
Deziel, E.
Bruce, K.
Ramsey, B.
Gibson, R. L.
Burns, J. L.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2013, 187
[4] Presence of methicillin resistant Staphylococcus aureus in respiratory cultures from cystic fibrosis patients is associated with lower lung function
Ren, Clement L.
Morgan, Wayne J.
Konstan, Michael W.
Schechter, Michael S.
Wagener, Jeffrey S.
Fisher, Kathryn A.
Regelmann, Warren E.
PEDIATRIC PULMONOLOGY, 2007, 42 (06) : 513 - 518
[5] Variation in lung function is associated with worse clinical outcomes in cystic fibrosis
Heinzmann-Filho, Joao Paulo
Pinto, Leonardo Araujo
Cauduro Marostica, Paulo Jose
Fagundes Donadio, Marcio Vinicius
JORNAL BRASILEIRO DE PNEUMOLOGIA, 2015, 41 (06) : 509 - 515
[6] Risk factors for persistent methicillin-resistant Staphylococcus aureus infection in cystic fibrosis
Jennings, Mark T.
Dasenbrook, Elliot C.
Lechtzin, Noah
Boyle, Michael P.
Merlo, Christian A.
JOURNAL OF CYSTIC FIBROSIS, 2017, 16 (06) : 681 - 686
[7] Staphylococcus aureus in Early Cystic Fibrosis Lung Disease
Wong, John K.
Ranganathan, Sarath C.
Hart, Emily
PEDIATRIC PULMONOLOGY, 2013, 48 (12) : 1151 - 1159
[8] Genomic Staphylococcus aureus adaptation to the cystic fibrosis lung
Hirschhausen, N.
Neumann, C.
Goesmann, A.
Peters, G.
Kahl, B.
INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY, 2011, 301 : 51 - 51
[9] Persistent infection with small colony variant strains of Staphylococcus aureus in patients with cystic fibrosis
Kahl, B
Herrmann, M
Everding, AS
Koch, HG
Becker, K
Harms, E
Proctor, RA
Peters, G
JOURNAL OF INFECTIOUS DISEASES, 1998, 177 (04): : 1023 - 1029
[10] Staphylococcus aureus and cystic fibrosis
Mimica, Marcelo J.
JOURNAL OF CYSTIC FIBROSIS, 2012, 11 (01) : 71 - 71

← 1 2 3 4 5 →