scholarly journals Eradication of Pseudomonas aeruginosa in cystic fibrosis patients with inhalation of dry powder tobramycin

2020 ◽  
Vol 14 ◽  
pp. 175346662090527 ◽  
Author(s):  
Anne M. Akkerman-Nijland ◽  
Mina Yousofi ◽  
Bart L. Rottier ◽  
Hester Van der Vaart ◽  
Johannes G. M. Burgerhof ◽  
...  

Background: Pseudomonas aeruginosa ( Pa) is the predominant pulmonary pathogen in patients with cystic fibrosis (CF). Tobramycin nebulization is used for the eradication of Pa infection. Nowadays, tobramycin dry powder inhalation (DPI) is available as well. This study reports the results of eradicating Pa with tobramycin DPI versus nebulization. Methods: Adult CF patients with a Pa isolation between September 2010 and September 2017 from the University Medical Centre Groningen (UMCG), the Netherlands, were included in this retrospective study. Results: In total 27 Pa isolations were recorded. In 13 of these, eradication was attempted with tobramycin, 7 with DPI and 6 with nebulization. DPI eradicated Pa successfully in six isolations (85.7%). Of these, one patient received additional oral ciprofloxacin and one received intravenous ceftazidime. Nebulization eradicated three Pa isolations (50.0%), in two of these, additional oral ciprofloxacin was given. Conclusion: Eradication rates of DPI tobramycin are comparable with those for nebulized tobramycin reported in the literature. This study suggests that DPI tobramycin is an alternative to nebulized tobramycin for eradication of Pa. Trial registration: The Medical Ethics Committee of the UMCG granted a waiver (METC2017-349), as they concluded that this study was not subject to the Medical Research Involving Human Subjects Act. The reviews of this paper are available via the supplemental material section.

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S209-S209
Author(s):  
Melissa S Phuong ◽  
Rafael E Hernandez ◽  
Subash Sad

Abstract Background Chronic bacterial lung infections are the primary cause of morbidity and mortality in cystic fibrosis (CF). The most common CF pathogens, Pseudomonas aeruginosa (P. aeruginosa) or Staphylococcus aureus (S. aureus), are common commensal or environmental organisms that adapt to the CF lung. We sought to investigate whether adaptation from early lung colonizer to chronic pathogen alters the bacterial effects on host inflammation. Methods P. aeruginosa (n = 25) and S. aureus (n = 25) isolates from CF patients with early and chronic infections were acquired from Seattle Children’s CF. Environmental (n = 8) and clinical, non-CF P. aeruginosa (n = 8) isolates were obtained from the University of Ottawa. P. aeruginosa reference strain PA14 and PA14 transposon mutants for T3SS and flagellin were used to observe the relationship between cell death and cytokine production. We infected THP-1-derived macrophages (PMA differentiated) in vitro for 3 hours with various MOIs. We subsequently measured cell death of THP-1-derived macrophages using neutral red assay and cytokine production using ELISAs. Results Infections with PA14 mutants and non-CF P. aeruginosa isolates demonstrated that rapid cell death of THP-1-derived macrophages caused a reduction in cytokine production relative to strains that did not cause as much cell death. At 10 MOI, early P. aeruginosa isolates from CF patients induced more THP-1-derived macrophage cell death compared with chronic isolates (P < 0.0001). Chronic P. aeruginosa isolates induced greater production of TNF, IL-8, and IL-6 (P < 0.01, P < 0.0001, and P < 0.0001, respectively) compared with early strains. No difference in IL-1β production was observed. When controlling for cell death between the two groups by using heat-killed bacteria, the only difference maintained was in TNF production (P < 0.01). Between early and chronic S. aureus isolates, the one difference observed was greater IL-8 production among early isolates (P < 0.01). Conclusion Chronic P. aeruginosa isolates from CF patients induce less cell death but more TNF, IL-8, and IL-6 production compared with early isolates. This suggests that P. aeruginosa producing chronic infections induce inflammatory signals that may contribute to increased morbidity among CF patients. Disclosures All authors: No reported disclosures.


2020 ◽  
Author(s):  
Faria Afzal ◽  
Tony Le Gall ◽  
Tristan Montier ◽  
Mareike Müller

&lt;p&gt;Women with Cystic Fibrosis (CF) have a significantly lower life expectancy compared to men, which is indicated by an earlier impairment of lung function due to chronic colonization of pathogenic bacteria like &lt;em&gt;Pseudomonas aeruginosa&lt;/em&gt; (PA). Reasons for this &amp;#8220;CF gender gap&amp;#8221; until now have not yet been fully clarified and are assumed to be multifactorial.&lt;/p&gt; &lt;p&gt;This study aims to shed light on the contribution of sex hormones to the CF-Gender gap considering microbial endocrinology. Therefor the study investigates whether the sex hormone estradiol, whose blood serum concentrations are significantly fluctuating within the female cycle and during pregnancy, has a regulatory influence on the development of PA biofilms in the context of CF.&lt;/p&gt; &lt;p&gt;For that purpose, biofilms of PA isolates from CF-patients are treated &lt;em&gt;in vitro&lt;/em&gt; with various estradiol concentrations and are examined in a comparative study quantitatively regarding the total biomass, &lt;em&gt;e.g.&lt;/em&gt; via crystal violet staining, and qualitatively, &lt;em&gt;e.g.&lt;/em&gt; via scanning electron microscopy, to characterize the ultrastructure of the biofilm.&lt;/p&gt; &lt;p&gt;We observed that estradiol induces biofilm-forming capacity of CF-PA-isolates with respect to the total biomass and modulates the biofilm structure especially concerning the distribution and clustering of bacteria.&lt;/p&gt; &lt;p&gt;The observed &lt;em&gt;in vitro&lt;/em&gt; correlation between estradiol concentration and extent of biofilm growth provides a possible microbiological explanation for gender differences in CF disease progression.&lt;/p&gt; &lt;p&gt;These insights and further research on possible underlying mechanisms might be relevant in the long-term for new approaches in personalized treatment for female CF patients.&lt;/p&gt; &lt;p&gt;&lt;strong&gt;Acknowledgement&lt;/strong&gt;&lt;/p&gt; &lt;p&gt;This work is supported by a financial grant from Mukoviszidose Institut gGmbH, Bonn, the research and development arm of the German Cystic Fibrosis Association Mukoviszidose e.V., the Christiane Herzog foundation. We further thank the Equal Opportunities Office of the University Siegen as well as the DAAD PPP Frankreich (Project-ID 55976814) for financial support.&lt;/p&gt; &lt;p&gt;&amp;#160;&lt;/p&gt;


2013 ◽  
Vol 16 (7) ◽  
pp. A372 ◽  
Author(s):  
P. Tappenden ◽  
S. Harnan ◽  
L. Uttley ◽  
M. Mildred ◽  
C.J. Taylor ◽  
...  

2016 ◽  
Vol 15 ◽  
pp. S89-S90
Author(s):  
D. Cosgrove ◽  
J.M. Bradley ◽  
K. Lavery ◽  
V. Mills ◽  
V. McClenaghan ◽  
...  

2008 ◽  
Vol 7 (1) ◽  
pp. 30-36 ◽  
Author(s):  
R.W. Brimicombe ◽  
L. Dijkshoorn ◽  
T.J.K. van der Reijden ◽  
I. Kardoes ◽  
T.L. Pitt ◽  
...  

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