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cystic fibrosis antibiotics

Jordana E Hoppe, Brandie D Wagner, Frank J Accurso, Edith T Zemanick, Scott D Sagel
BACKGROUND: Pulmonary exacerbations (PEx) in children with cystic fibrosis (CF) are frequently treated in the outpatient setting with oral antibiotics. However, little is known about the characteristics of PEx managed on an outpatient basis and the effectiveness of oral antibiotic therapy. We sought to prospectively evaluate clinical and laboratory changes associated with oral antibiotic treatment for PEx. METHODS: Children with CF between 8 and 18 years of age prescribed two weeks of oral antibiotics for a PEx were eligible to enroll...
June 16, 2018: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
Inês N Silva, Filipa D Pessoa, Marcelo J Ramires, Mário R Santos, Jörg D Becker, Vaughn S Cooper, Leonilde M Moreira
Bacteria from the Burkholderia cepacia complex grow in different natural and man-made environments and are feared opportunistic pathogens that cause chronic respiratory infections in cystic fibrosis patients. Previous studies showed that Burkholderia mucoid clinical isolates grown under stress conditions give rise to nonmucoid variants devoid of the exopolysaccharide cepacian. Here, we have determined that a major cause of the nonmucoid morphotype involves nonsynonymous mutations and small indels in the ompR gene encoding a response regulator of a two-component regulatory system...
June 18, 2018: Journal of Bacteriology
A Van Dalem, M Herpol, F Echahidi, C Peeters, I Wybo, E De Wachter, P Vandamme, D Piérard
We tested the in vitro susceptibility of ceftazidime-avibactam and ceftolozane-tazobactam and 13 other antibiotics against 91 Burkholderia cepacia complex (BCC) strains isolated from cystic fibrosis patients since 2012. Highest susceptibility (82%) was found for trimethoprim-sulfamethoxazole. Respectively, 81% and 63% of all BCC strains were susceptible to ceftazidime-avibactam and ceftolozane-tazobactam. For temocillin, ceftazidime, piperacillin-tazobactam and meropenem, at least 50% of the strains were susceptible...
June 18, 2018: Antimicrobial Agents and Chemotherapy
A Young J Park, Joshua Wang, Jordanna Jayne, Lynn Fukushima, Adupa P Rao, David Z D'Argenio, Paul M Beringer
Over the past decade, the prevalence of infections involving Methicillin-resistant Staphylococcus aureus (MRSA) in patients with cystic fibrosis (CF) has increased significantly. Tedizolid (TZD) demonstrates excellent activity against MRSA and a favorable safety profile. The pharmacokinetics of several antibiotics has shown to be altered in CF patients. The purpose of this study was to characterize the pharmacokinetics of tedizolid in this population. Eleven patients with CF were randomized to receive tedizolid phosphate 200 mg PO or IV once daily for 3 doses, with minimum 2-day washout, followed by crossover to the remaining dosage form...
June 18, 2018: Antimicrobial Agents and Chemotherapy
Erika M Zettner, Malcolm A Gleser
Objective Hearing loss is a significant and growing problem as patients with cystic fibrosis (CF) live longer and experience frequent courses of intravenous aminoglycoside antibiotics (hereafter, "IVs"). This study seeks to document that risk in a large adult population with CF, accounting for age and aminoglycoside exposure. Study Design Retrospective case review of patients with CF who had multiple audiograms over years. Setting Tertiary care cystic fibrosis setting. Subject and Methods The first and last audiograms recorded over a 10-year period were compared for 165 adult patients with CF...
June 1, 2018: Otolaryngology—Head and Neck Surgery
Lisa T Hong, Theodore G Liou, Rishi Deka, Jordan B King, Vanessa Stevens, David C Young
BACKGROUND: Several clinical trials have demonstrated the efficacy of continuous infusion (CI) beta-lactam (BL) antibiotics in cystic fibrosis (CF) patients; however, little is known regarding pharmacokinetic changes during treatment of an acute pulmonary exacerbation (APE). Identifying and understanding these changes may assist in optimizing antibiotic dosing during APE treatment. METHODS: This study is a retrospective cohort study of 162 adult CF patients admitted to the University of Utah Hospital between January 1, 2008 and May 15, 2014 for treatment of an APE with both a CI BL and intravenous tobramycin...
June 13, 2018: Chest
Apparao B Kummarapurugu, Daniel K Afosah, Nehru Viji Sankaranarayanan, Rahaman Navaz Gangji, Shuo Zheng, Thomas P Kennedy, Bruce K Rubin, Judith A Voynow, Umesh R Desai
Cystic fibrosis (CF)1 is a multi-factorial disease in which dysfunction of protease-antiprotease balance plays a key role. The current CF therapy relies on dornase alfa, low dose macrolide antibiotics, hypertonic saline and antibiotics, and does not address the high neutrophil elastase (NE) activity observed in the lung and sputum of CF patients. Our hypothesis is that variants of heparin, which potently inhibit NE but are not anticoagulant, would help restore the protease-antiprotease balance in CF. To realize this concept, we studied molecular principles governing the effectiveness of different heparins, especially 2-O,3-O-desulfated heparin (ODSH), in the presence of sputum components and therapeutic agents...
June 14, 2018: Journal of Biological Chemistry
Sarah Tavernier, Andrea Sass, Michiel De Bruyne, Femke Baeke, Riet De Rycke, Aurélie Crabbé, Ilse Vandecandelaere, Filip Van Nieuwerburgh, Tom Coenye
Background: Streptococcus anginosus, Pseudomonas aeruginosa and Staphylococcus aureus are often co-isolated from the sputum of cystic fibrosis patients. It was recently shown that S. anginosus is protected from the activity of vancomycin when it grows in a multispecies biofilm with P. aeruginosa and S. aureus. Objectives: Elucidating the underlying cause of the reduced susceptibility of S. anginosus to vancomycin when growing in a multispecies biofilm with P. aeruginosa and S...
June 12, 2018: Journal of Antimicrobial Chemotherapy
Luca Freschi, Claire Bertelli, Julie Jeukens, Matthew P Moore, Irena Kukavica-Ibrulj, Jean-Guillaume Emond-Rheault, Jérémie Hamel, Joanne L Fothergill, Nicholas P Tucker, Siobhán McClean, Jens Klockgether, Anthony de Soyza, Fiona S L Brinkman, Roger C Levesque, Craig Winstanley
Pseudomonas aeruginosa is an important opportunistic pathogen, especially in the context of infections of cystic fibrosis (CF). In order to facilitate coordinated study of this pathogen, an international reference panel of P. aeruginosa isolates was assembled. Here we report the genome sequencing and analysis of 33 of these isolates and 7 reference genomes to further characterise this panel. Core genome single nucleotide variant phylogeny demonstrated that the panel strains are widely distributed amongst the P...
June 12, 2018: FEMS Microbiology Letters
Tamara Salloum, Elie Nassour, George F Araj, Edmond Abboud, Sima Tokajian
PURPOSE: Burkholderia cenocepacia is among the most common members of the Burkholderia cepacia complex (Bcc) isolated from patients with cystic fibrosis (CF). The factors triggering the high rates of morbidity and mortality in CF patients are not well elucidated. In this study, we aim to highlight the genome diversity of two clinical isolates of B. cenocepacia through comparative genome analysis. METHODOLOGY: The repertoire of virulence factors and resistance genes compared to reference strains J2315 and K56-2 was elucidated...
June 13, 2018: Journal of Medical Microbiology
Krishna Mohan Gulla, Arvind Balaji, Aparna Mukherjee, Kana Ram Jat, Jhuma Sankar, Rakesh Lodha, Sushil K Kabra
Objective: To study the clinical impact of respiratory viral infection in children with cystic fibrosis (CF). Design: Retrospective cohort study. Setting: Tertiary care referral centre for CF in India. Participants/patients: Children with CF attending a pediatric chest clinic. Methods: Case records of the children with CF who had a pulmonary exacerbation with documented acute respiratory viral infection between October 2013 and December 2014 (Group I) and an equal number of controls (Group II) with pulmonary exacerbation in absence of acute respiratory viral infection were reviewed...
June 9, 2018: Journal of Tropical Pediatrics
Nicole Mayer-Hamblett, George Retsch-Bogart, Margaret Kloster, Frank Accurso, Margaret Rosenfeld, Gary Albers, Philip Black, Perry Brown, AnneMarie Cairns, Stephanie D Davis, Gavin R Graff, Gwendolyn S Kerby, David Orenstein, Rachael Buckingham, Bonnie W Ramsey
RATIONALE: New isolation of Pseudomonas aeruginosa (Pa) is generally treated with inhaled antipseudomonal antibiotics such as tobramycin inhalation solution (TIS). A therapeutic approach complementing traditional antimicrobial therapy by reducing the risk of pulmonary exacerbation (PEx) and inflammation may ultimately prolong time to Pa recurrence. OBJECTIVES: To test the hypothesis that the addition of azithromycin to TIS in children with CF and early Pa decreases the risk of PEx and prolongs time to Pa recurrence...
June 11, 2018: American Journal of Respiratory and Critical Care Medicine
Andrea Hahn, Matthew L Bendall, Keylie M Gibson, Hollis Chaney, Iman Sami, Geovanny F Perez, Anastassios C Koumbourlis, Timothy A McCaffrey, Robert J Freishtat, Keith A Crandall
Cystic fibrosis (CF) is an autosomal recessive disease associated with recurrent lung infections that can lead to morbidity and mortality. The impact of antibiotics for treatment of acute pulmonary exacerbations on the CF airway microbiome remains unclear with prior studies giving conflicting results and being limited by their use of 16S ribosomal RNA sequencing. Our primary objective was to validate the use of true single molecular sequencing (tSMS) and PathoScope in the analysis of the CF airway microbiome...
2018: Frontiers in Microbiology
The-Thien Tran, Celine Vidaillac, Hong Yu, Valerie F L Yong, Dan Roizman, Ravishankar Chandrasekaran, Albert Y H Lim, Teck Boon Low, Gan Liang Tan, John A Abisheganaden, Mariko Siyue Koh, Jeanette Teo, Sanjay H Chotirmall, Kunn Hadinoto
Non-cystic fibrosis bronchiectasis (NCFB) characterized by permanent bronchial dilatation and recurrent infections has been clinically managed by long-term intermittent inhaled antibiotic therapy among other treatments. Herein we investigated dry powder inhaler (DPI) formulation of ciprofloxacin (CIP) nanoplex with mannitol/lactose as the excipient for NCFB therapy. The DPI of CIP nanoplex was evaluated against DPI of native CIP in terms of their (1) dissolution characteristics in artificial sputum medium, (2) ex vivo mucus permeability in sputum from NCFB and healthy individuals, (3) antibacterial efficacy in the presence of sputum against clinical Pseudomonas aeruginosa strains (planktonic and biofilm), and (4) cytotoxicity towards human lung epithelial cells...
June 7, 2018: International Journal of Pharmaceutics
James D Finklea, Rita Hollaway, Karen Lowe, Francesca Lee, Jade Le, Raksha Jain
Ceftolozane/tazobactam is a combination intravenous antibiotic with potentially important activity against drug-resistant Gram-negative organisms. Ceftolozane/tazobactam's in vitro activity was evaluated in 30 samples collected from 23 adult cystic fibrosis patients with extended and pan-resistant Pseudomonas aeruginosa in 2015. Testing results demonstrated that 30% of the isolates were susceptible,13% were intermediate, and 57% were resistant. This suggests that ceftolozane/tazobactam may be a useful antibiotic in carefully selected, multidrug-resistant Pseudomonas isolates...
May 12, 2018: Diagnostic Microbiology and Infectious Disease
Francesca Buttini, Anna Giulia Balducci, Gaia Colombo, Fabio Sonvico, Serena Montanari, Giovanna Pisi, Alessandra Rossi, Paolo Colombo, Ruggero Bettini
The purpose of this work was to study a new dry powder inhaler (DPI) of tobramycin capable to simplify the dose administration maneuvers to maximize the cystic fibrosis patient care in antibiotic inhalation therapy. For the purpose, tobramycin/sodium stearate powder (TobraPS) having a high drug content, was produced by spray drying, characterized and the aerodynamic behavior was investigated in vitro using different RS01 DPI inhalers. The aerosols produced with 28, 56 or 112 mg of tobramycin in TobraPS powder using capsules size #3, #2 or #0 showed that there was quasi linear relationship between the amount loaded and the FPD...
June 5, 2018: International Journal of Pharmaceutics
Sergey Zaichik, Christian Steinbring, Claudia Menzel, Ludwig Knabl, Dorothea Orth-Höller, Helmut Ellemunter, Katharina Niedermayr, Andreas Bernkop-Schnürch
The aim of this study was to develop a self-emulsifying drug delivery system (SEDDS) containing the fluoroquinolone antibiotic ciprofloxacin (CIP) exhibiting highly mucus permeating properties and antimicrobial activity in in vitro models. Various SEDDS formulations were developed and evaluated regarding droplet size, polydispersity index, zeta potential and formulation stability. Furthermore, SEDDS permeating properties were investigated in porcine intestinal mucus, as well as in cystic fibrosis (CF) sputum freshly collected from CF patients using Transwell® setup and single particle tracking (SPT), respectively...
June 5, 2018: International Journal of Pharmaceutics
Philip Zachariah, Chanelle Ryan, Sruti Nadimpalli, Gina Coscia, Michelle Kolb, Hannah Smith, Marc Foca, Lisa Saiman, Paul J Planet
BACKGROUND: The clinical utility of culture-independent testing of pediatric bronchoalveolar lavage (BAL) specimens is unknown. Additionally, the variability of the pediatric pulmonary microbiome with patient characteristics is not well understood. METHODS: Study subjects were ≤22 years old and underwent BAL from May 2013 - July 2015 as part of clinical care. DNA extracted from BAL specimens was used for 16S rRNA gene-based (16S-based) microbiome analysis, and results compared to routine cultures from the same samples...
June 7, 2018: Annals of the American Thoracic Society
Jessica K Wong, Lara C Chambers, Elizabeth J Elsmo, Tiffany L Jenkins, Elizabeth W Howerth, Susan Sánchez, Kaori Sakamoto
Isolates of the Burkholderia cepacia complex (BCC) are known as plant and human pathogens. We describe herein BCC infections as the cause of subcutaneous abscesses and purulent cellulitis in 5 cats. All cats were presented with an open wound, and 4 received standard wound care and empiric antibiotic therapy. Despite treatment, clinical signs worsened in 4 cats. Isolates of the BCC were obtained from all 5 cases. Two cats were submitted for postmortem examination. Subcutaneous abscesses with draining fistulas were observed...
June 1, 2018: Journal of Veterinary Diagnostic Investigation
Peter H Gilligan, Damian G Downey, J Stuart Elborn, Patrick A Flume, Sebastian Funk, Deirdre Gilpin, Timothy J Kidd, John McCaughan, B Cherie Millar, Philip G Murphy, Jacqueline C Rendall, Michael M Tunney, John E Moore
Infection is a common complication of cystic fibrosis (CF) airways disease. Current treatment approaches include early intervention with the intent to eradicate pathogens in the hope of delaying development of chronic infection and chronic use of aerosolized antibiotics to suppress infection. The use of molecules that help restore CFTR function, modulate pulmonary inflammation, or improve pulmonary clearance, may also influence the microbial communities in the airways. As the pipeline of these new entities continues to expand, it is important to define when key pathogens are eradicated from the lungs of CF patients and equally important, when new pathogens might emerge as a result of these novel therapies...
June 6, 2018: Journal of Clinical Microbiology
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