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cystic fibrosis antibiotics

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Pseudomonas aeruginosa is the most common Gram-negative bacterium associated with nosocomial and life-threatening chronic infections in cystic fibrosis patients. This pathogen is well-known for its ability to attach to surfaces of indwelling medical devices to form biofilms, which consist of a regular array of extracellular polymers. Tenaciously bound to the surface of devices and inherently resilient to antibiotic treatment, P. aeruginosa poses a serious threat in clinical medicine and contributes to the persistence of chronic infections...
October 19, 2016: Current Drug Targets
Traci M Kazmerski, Daniel J Weiner, Janice Matisko, Diane Schachner, Whitney Lerch, Carol May, Scott H Maurer
INTRODUCTION: Advance care planning (ACP), though recommended, has not been studied in adolescents with cystic fibrosis (CF). This quality improvement project engaged adolescents with advanced CF disease in ACP and assessed patient and CF provider attitudes and preferences regarding ACP discussions and tools. MATERIALS AND METHODS: Patients ≤22 years with advanced CF (FEV1 ≤40% predicted, >2 pulmonary exacerbations requiring IV antibiotics in 1 year, and/or use of home oxygen or non-invasive ventilation) were referred to the pediatric palliative care team (PC)...
October 17, 2016: Pediatric Pulmonology
Arianna Pompilio, Valentina Crocetta, Dipankar Ghosh, Malabika Chakrabarti, Giovanni Gherardi, Luca Agostino Vitali, Ersilia Fiscarelli, Giovanni Di Bonaventura
The present study was carried out to understand the adaptive strategies developed by Stenotrophomonas maltophilia for chronic colonization of the cystic fibrosis (CF) lung. For this purpose, 13 temporally isolated strains from a single CF patient chronically infected over a 10-year period were systematically characterized for growth rate, biofilm formation, motility, mutation frequencies, antibiotic resistance, and pathogenicity. Pulsed-field gel electrophoresis (PFGE) showed over time the presence of two distinct groups, each consisting of two different pulsotypes...
2016: Frontiers in Microbiology
Jianguo Li, Chunyan Hao, Lili Ren, Yan Xiao, Jianwei Wang, Xuemei Qin
The major therapeutic strategy used to treat exacerbated cystic fibrosis (CF) is antibiotic treatment. As this approach easily generates antibiotic-resistant strains of opportunistic bacteria, optimized antibiotic therapies are required to effectively control chronic and recurrent bacterial infections in CF patients. A promising future for the proper use of antibiotics is the management of lung microbiota. However, the impact of antibiotic treatments on CF microbiota and vice versa is not fully understood. This study analyzed 718 sputum samples from 18 previous studies to identify differences between CF and uninfected lung microbiota and to evaluate the effects of antibiotic treatments on exacerbated CF microbiota...
2016: PloS One
Sophie Gohy, Antoine Froidure, Patrick Lebecque
Drug reaction with eosinophilia and systemic symptom (DRESS) syndrome is a rare and severe side-effect, mainly described after intake of anticonvulsants, allopurinol, or antibiotics. It usually begins within 2 months after drug introduction. Symptoms include cutaneous rash, hematologic abnormalities, and internal organ involvement and the diagnosis might be challenging. This case report illustrates for the first time this life-threatening complication in a patient with cystic fibrosis (CF). In this case, withdrawal of the offending drug was sufficient for full recovery...
October 14, 2016: Pediatric Pulmonology
C Van de Kerkhove, P C Goeminne, M Kicinski, T S Nawrot, N Lorent, P Van Bleyenbergh, K De Boeck, L J Dupont
INTRODUCTION: The efficacy of inhaled antibiotics to treat chronic Pseudomonas aeruginosa pulmonary infection in patients with cystic fibrosis (CF) has been well established. Few data are available on the value of continuous alternating inhaled antibiotic therapy (CAIT), a strategy increasingly used in the management of CF. OBJECTIVE: To investigate the effect of CAIT on clinical outcome in adult CF patients treated at the University Hospital Leuven. METHODS: Patients with a documented CF diagnosis who received inhaled antibiotics between March 2010 and January 2015 were retrospectively evaluated...
October 5, 2016: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
Carlo Castellani, Baroukh M Assael
Cystic fibrosis (CF), a monogenic disease caused by mutations in the CFTR gene on chromosome 7, is complex and greatly variable in clinical expression. Airways, pancreas, male genital system, intestine, liver, bone, and kidney are involved. The lack of CFTR or its impaired function causes fat malabsorption and chronic pulmonary infections leading to bronchiectasis and progressive lung damage. Previously considered lethal in infancy and childhood, CF has now attained median survivals of 50 years of age, mainly thanks to the early diagnosis through neonatal screening, recognition of mild forms, and an aggressive therapeutic attitude...
October 5, 2016: Cellular and Molecular Life Sciences: CMLS
J Stuart Elborn, Anne-Lise Vataire, Ayako Fukushima, Samuel Aballea, Amine Khemiri, Curtis Moore, Goran Medic, Michiel E H Hemels
PURPOSE: In Europe, 4 inhaled antibiotics (tobramycin, colistimethate sodium, aztreonam, and levofloxacin) are currently approved for the treatment of chronic Pseudomonas aeruginosa lung infection in patients with cystic fibrosis (CF). Levofloxacin inhalation solution (LIS) is the most recently approved inhaled antibiotic for adult patients with CF. A systematic literature review and Bayesian network meta-analysis (NMA) was conducted to compare the relative short-term (4 weeks) and long-term (24 weeks) outcomes of these inhaled antibiotics versus LIS...
September 28, 2016: Clinical Therapeutics
William T Harris, J Todd Boyd, Gary L McPhail, Alan S Brody, Rhonda D Szczesniak, Leslie L Korbee, Michael L Baker, John P Clancy
RATIONALE: Refractory lung function decline in association with recurrent pulmonary exacerbations is a common, yet poorly explained finding in CF. We reviewed clinically-indicated lung biopsy specimens obtained during a period of persistent decline to investigate histopathologic mechanisms of pulmonary deterioration during adolescence and early adulthood. OBJECTIVES: To determine if peribronchiolar remodeling is prominent in lung biopsy specimens obtained in CF adolescents refractory to conventional therapy...
September 29, 2016: Annals of the American Thoracic Society
Dalila Mil-Homens, Sandra N Pinto, Rute G Matos, Cecília Arraiano, Arsenio M Fialho
Chronic lung disease caused by persistent bacterial infections is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). CF pathogens acquire antibiotic resistance, overcame host defenses and impose uncontrolled inflammation that ultimately may cause permanent damage of lungs' airways. Among the multiple CF-associated pathogens, Burkholderia cenocepacia and other B. cepacia complex (Bcc) bacteria have become prominent contributors of disease progression. Here, we demonstrate that BcaA, a trimeric autotransporter adhesin (TAA) from the epidemic strain B...
September 29, 2016: Cellular Microbiology
M Moreno-Sastre, M Pastor, A Esquisabel, E Sans, M Viñas, D Bachiller, J L Pedraz
In the last decades, the encapsulation of antibiotics into nanoparticulate carriers has gained increasing attention for the treatment of infectious diseases. Sodium colistimethate-loaded solid lipid nanoparticles (Colist-SLNs) and nanostructured lipid carriers (Colist-NLCs) were designed aiming to treat the pulmonary infection associated to cystic fibrosis patients. The nanoparticles were freeze-dried using trehalose as cryoprotectant. The stability of both nanoparticles was analysed over one year according to the International Conference of Harmonisation (ICH) guidelines by determining the minimum inhibitory concentration (MIC) against clinically isolated Pseudomonas aeruginosa strains and by studying their physico-chemical characteristics...
October 14, 2016: Journal of Microencapsulation
Signe M Nielsen, Niels Nørskov-Lauritsen, Thomas Bjarnsholt, Rikke L Meyer
Achromobacter species have attracted attention as emerging pathogens in cystic fibrosis. The clinical significance of Achromobacter infection is not yet fully elucidated; however, their intrinsic resistance to antimicrobials and ability to form biofilms renders them capable of establishing long-term chronic infections. Still, many aspects of Achromobacter biofilm formation remain uncharacterized. In this study, we characterized biofilm formation in clinical isolates of Achromobacter and investigated the effect of challenging the biofilm with antimicrobials and/or enzymes targeting the extracellular matrix...
September 14, 2016: Microorganisms
Thaigarajan Parumasivam, Sharon S Y Leung, Patricia Tang, Citterio Mauro, Warwick Britton, Hak-Kim Chan
The routine of loading multiple capsules for delivery of high-dose antibiotics is time consuming, which may reduce patient adherence to inhaled treatment. To overcome this limitation, an investigation was carried out using four modified versions of the Aerolizer® that accommodate a size 0 capsule for delivery of high payload formulations. In some prototypes, four piercing pins of 0.6 mm each were replaced with a single centrally located 1.2-mm pin and one-third reduced air inlet of the original design. The performance of these inhalers was evaluated using spray-dried antibiotic powders with distinct morphologies: spherical particles with a highly corrugated surface (colistin and tobramycin) and needle-like particles (rifapentine)...
September 27, 2016: AAPS Journal
William H DePas, Ruth Starwalt-Lee, Lindsey Van Sambeek, Sripriya Ravindra Kumar, Viviana Gradinaru, Dianne K Newman
: Physiological resistance to antibiotics confounds the treatment of many chronic bacterial infections, motivating researchers to identify novel therapeutic approaches. To do this effectively, an understanding of how microbes survive in vivo is needed. Though much can be inferred from bulk approaches to characterizing complex environments, essential information can be lost if spatial organization is not preserved. Here, we introduce a tissue-clearing technique, termed MiPACT, designed to retain and visualize bacteria with associated proteins and nucleic acids in situ on various spatial scales...
September 27, 2016: MBio
Hoon Cho, Xiaoqin Huang, Yu Lan Piao, Da Eun Kim, So Yeon Lee, Eun Jeong Yoon, So Hee Park, Kyoung Lee, Chul Ho Jang, Chang-Guo Zhan
Administration of an efficient alginate lyase (AlgL) or AlgL mutant may be a promising therapeutic strategy for treatment of cystic fibrosis patients with Pseudomonas aeruginosa infections. Nevertheless, the catalytic activity of wild-type AlgL is not sufficiently high. It is highly desired to design and discover an AlgL mutant with significantly improved catalytic efficiency against alginate substrates. For the purpose of identifying an AlgL mutant with significantly improved catalytic activity, in this study, we first constructed and validated a structural model of AlgL interacting with substrate, providing a better understanding of the interactions between AlgL and its substrate...
September 27, 2016: Proteins
A C Fluit, M D Jansen, T Bosch, W T M Jansen, L Schouls, M J Jonker, C H E Boel
The distinct epidemiology of original hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) and early community-associated MRSA is largely unexplained. S. aureus carries either 5 or 6 rRNA operon copies. Evidence is provided for a scenario in which MRSA has adapted to the hospital environment by rRNA operon loss (6 to 5 copies) due to antibiotic pressure. Early CA-MRSA in contrast results from wild-type MSSA that acquired mecA without loss of a rRNA operon. Of the HA-MRSA isolates (n=77) 67...
September 26, 2016: Antimicrobial Agents and Chemotherapy
Floriana Cappiello, Antonio Di Grazia, Segev-Zarko Li-Av, Silvia Scali, Loretta Ferrera, Luis Galietta, Alessandro Pini, Yechiel Shai, Y Peter Di, Maria Luisa Mangoni
Pseudomonas aeruginosa is the major microorganism colonizing the respiratory epithelium in cystic fibrosis (CF) sufferers. The widespread usage of available antibiotics has drastically reduced their efficacy, and antimicrobial peptides (AMPs) are a promising alternative. Among them, the frog-skin derived AMPs i.e. Esc(1-21) and its diastereomer Esc(1-21)-1c have recently shown potent activity against free-living and sessile forms of P. aeruginosa. Importantly, this pathogen also escapes antibiotics treatment by invading airway epithelial cells...
September 26, 2016: Antimicrobial Agents and Chemotherapy
Laia Fernández-Barat, Oana Ciofu, Kasper N Kragh, Tania Pressler, Ulla Johansen, Anna Motos, Antoni Torres, Niels Hoiby
BACKGROUND: The influence of suppressive therapy on the different P. aeruginosa phenotypes harbored in the lungs of cystic fibrosis (CF) patients remains unclear. Our aim was to investigate the phenotypic changes (mucoidy, hypermutability, antibiotic resistance, transcriptomic profiles and biofilm) in P. aeruginosa populations before and after a 2-week course of suppressive antimicrobial therapy in chronically infected CF patients in Denmark. MATERIAL AND METHODS: Prospective observational clinical study...
September 16, 2016: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
Chao Wang, John R McPherson, Lian-Hui Zhang, Steve Rozen, Kanaga Sabapathy
Pseudomonas aeruginosa is an opportunistic pathogen which infects cystic fibrosis and cancer patients with compromised immune systems. LasR is a master regulator which controls the virulence of P. aeruginosa in response to bacterial cell-density and host signals. During infection, lasR is frequently mutated, conferring P. aeruginosa a growth advantage in hosts and enhances resistance to widely used antibiotics. However, the mechanistic basis of lasR mutation is not well understood. We have tested here the hypothesis that transcription strength is a contributory determinant of lasR mutagenesis...
October 2016: DNA Repair
Lindsay J Marshall, Wilson Oguejiofor, Robert Price, Jagdeep Shur
The airways of most people with cystic fibrosis are colonized with biofilms of the Gram-negative, opportunistic pathogen Pseudomonas aeruginosa. Delivery of antibiotics directly to the lung in the form of dry powder aerosols offers the potential to achieve high local concentrations directly to the biofilms. Unfortunately, current aerosolised antibiotic regimes are unable to efficiently eradicate these biofilms from the airways. We investigated the ability of the innate antimicrobial, lactoferrin, to enhance the activity of two aminoglycoside antibiotics (tobramycin and gentamicin) against biofilms of P...
September 11, 2016: International Journal of Pharmaceutics
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