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aerosolized antibiotics

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https://www.readbyqxmd.com/read/27890714/a-randomized-trial-of-the-amikacin-fosfomycin-inhalation-system-for-the-adjunctive-therapy-of-gram-negative-ventilator-associated-pneumonia-iasis-trial
#1
Marin H Kollef, Jean-Damien Ricard, Damien Roux, Bruno Francois, Eleni Ischaki, Zsolt Rozgonyi, Thierry Boulain, Zsolt Ivanyi, Gál János, Denis Garot, Firas Koura, Epaminondas Zakynthinos, George Dimopoulos, Antonio Torres, Wayne Danker, A Bruce Montgomery
BACKGROUND: Clinical failures in ventilator-associated pneumonia (VAP) caused by Gram-negative bacteria are common and associated with substantial morbidity, mortality, and resource utilization. METHODS: We assessed the safety and efficacy of the amikacin fosfomycin inhalation system (AFIS) for the treatment of Gram-negative bacterial VAP in a randomized double-blind, placebo-controlled, parallel group, phase 2 study between May 2013 and March 2016. We compared standard of care in each arm plus 300 mg amikacin/120 mg fosfomycin or placebo (saline), delivered by aerosol twice daily for 10 days (or to extubation if <10 days) via the investigational eFlow Inline System (PARI GmbH, Germany)...
November 24, 2016: Chest
https://www.readbyqxmd.com/read/27809794/alternative-pre-approved-and-novel-therapies-for-the-treatment-of-anthrax
#2
REVIEW
Breanne M Head, Ethan Rubinstein, Adrienne F A Meyers
BACKGROUND: Bacillus anthracis, the causative agent of anthrax, is a spore forming and toxin producing rod-shaped bacterium that is classified as a category A bioterror agent. This pathogenic microbe can be transmitted to both animals and humans. Clinical presentation depends on the route of entry (direct contact, ingestion, injection or aerosolization) with symptoms ranging from isolated skin infections to more severe manifestations such as cardiac or pulmonary shock, meningitis, and death...
November 3, 2016: BMC Infectious Diseases
https://www.readbyqxmd.com/read/27795380/pharmacodynamics-of-aerosolized-fosfomycin-and-amikacin-against-resistant-clinical-isolates-of-pseudomonas-aeruginosa-and-klebsiella-pneumoniae-in-a-hollow-fiber-infection-model-experimental-basis-for-combination-therapy
#3
Fekade Bruck Sime, Adam Johnson, Sarah Whalley, Anahi Santoyo-Castelazo, A Bruce Montgomery, Kathie Ann Walters, Jeffrey Lipman, William W Hope, Jason A Roberts
There has been a resurgence of interest in aerosolization of antibiotics for treatment of patients with severe pneumonia, caused by multi-drug resistant pathogens. A combination formulation of amikacin/fosfomycin is currently undergoing clinical testing although the exposure response-relationships of these drugs have not been fully characterized. The aim of this study was to describe the individual and combined antibacterial effects of simulated epithelial lining fluid exposures of aerosolized amikacin and fosfomycin against resistant clinical isolates of Pseudomonas aeruginosa (MICs 16 mg/L; 64 mg/L) and Klebsiella pneumoniae (MICs 2 mg/L; 64 mg/L) using the dynamic hollow-fiber infection model over 7-days...
October 24, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27776446/inhaled-phage-therapy-a-promising-and-challenging-approach-to-treat-bacterial-respiratory-infections
#4
Elsa Bodier-Montagutelli, Eric Morello, Guillaume l'Hostis, Antoine Guillon, Emilie Dalloneau, Renaud Respaud, Nikita Pallaoro, Hélène Blois, Laurent Vecellio, Jérôme Gabard, Nathalie Heuzé-Vourc'h
Bacterial respiratory tract infections (RTIs) are increasingly difficult to treat due to evolving antibiotic resistance. In this context, bacteriophages (or phages) are part of the foreseen alternatives or combination therapies. Delivering phages through the airways seems more relevant to accumulate these natural antibacterial viruses in proximity to their bacterial host, within the infectious site. Areas covered: This review addresses the potential of phage therapy to treat RTIs and discusses preclinical and clinical results of phages administration in this context...
October 25, 2016: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/27745954/intranasal-delivery-of-a-protein-subunit-vaccine-using-a-tobacco-mosaic-virus-platform-protects-against-pneumonic-plague
#5
Paul M Arnaboldi, Mariya Sambir, Christina D'Arco, Lauren A Peters, Jos F M L Seegers, Lloyd Mayer, Alison A McCormick, Raymond J Dattwyler
Yersinia pestis, one of history's deadliest pathogens, has killed millions over the course of human history. It has attributes that make it an ideal choice to produce mass casualties and is a prime candidate for use as a biological weapon. When aerosolized, Y. pestis causes pneumonic plague, a pneumonia that is 100% lethal if not promptly treated with effective antibiotics. Currently, there is no FDA approved plague vaccine. The current lead vaccine candidate, a parenterally administered protein subunit vaccine comprised of the Y...
November 11, 2016: Vaccine
https://www.readbyqxmd.com/read/27716468/potential-microbial-hazards-from-graywater-reuse-and-associated-matrices-a-review
#6
Maya Benami, Osnat Gillor, Amit Gross
Millions of decentralized graywater-reuse systems are operating worldwide. This water is directly accessible to household inhabitants, raising environmental and public health concerns. Graywater may contain a variety of harmful organisms, the types and numbers of which vary with source-type, storage time, and background levels of infection in the community source. In this review, we find that most studies indicate high amounts of microbial pathogens in raw graywater and therefore treatment and disinfection are recommended to lower possible health risks...
September 28, 2016: Water Research
https://www.readbyqxmd.com/read/27708777/cough-impact-beliefs-and-expectations-from-a-national-survey
#7
Roberto W Dal Negro, Massimiliano Mazzolini, Paola Turco, Alessandro Zanasi
BACKGROUND: Cough is one of the most common discomforts affecting general population, which can disrupt subjects' quality of life due to its physical, social, and psychological effects. Aim of the study was to investigate the impact of cough and related beliefs of general population. METHODS: A cross-sectional telephone survey was carried out by means of a specific, validated questionnaire on a representative sample of Italian general population. All the interviews were carried out according to the Computer Assisted Telephone Interview (CATI) methodology by expert, professional interviewers...
2016: Multidisciplinary Respiratory Medicine
https://www.readbyqxmd.com/read/27680980/pre-emptive-antibiotic-therapy-to-reduce-ventilator-associated-pneumonia-thinking-outside-the-box
#8
Donald E Craven, Jana Hudcova, Yuxiu Lei, Kathleen A Craven, Ahsan Waqas
Mechanically ventilated, intubated patients are at increased risk for tracheal colonization with bacterial pathogens that may progress to heavy bacterial colonization, ventilator-associated tracheobronchitis (VAT), and/or ventilator-associated pneumonia (VAP). Previous studies report that 10 to 30 % of patients with VAT progress to VAP, resulting in increased morbidity and significant acute and chronic healthcare costs. Several natural history studies, randomized, controlled trials, and a meta-analysis have reported antibiotic treatment for VAT can reduce VAP, ventilator days, length of intensive care unit (ICU) stay, and patient morbidity and mortality...
September 29, 2016: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/27679516/the-delivery-of-high-dose-dry-powder-antibiotics-by-a-low-cost-generic-inhaler
#9
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
https://www.readbyqxmd.com/read/27678160/what-if-there-were-no-new-antibiotics-a-look-at-alternatives
#10
Jordi Rello, Eleonora Bunsow, Antonio Perez
Bacterial resistance to antibiotics is increasing worldwide, due to the emergence of multidrug-resistant strains. With this panorama, there is a serious danger that we may be entering the 'post-antibiotic era'. Areas covered: We assess why so few new classes of antibiotics have been developed in the past years and discuss a variety of treatments that may be able to replace antimicrobials: monoclonal antibodies, bacteriophages, stem cells and anti-virulence agents such as liposomes. Expert commentary: There are a series of economic, scientific-research and regulatory reasons for the scarcity of new antimicrobials...
October 6, 2016: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/27668749/identification-of-genome-wide-mutations-in-ciprofloxacin-resistant-f-tularensis-lvs-using-whole-genome-tiling-arrays-and-next-generation-sequencing
#11
Crystal J Jaing, Kevin S McLoughlin, James B Thissen, Adam Zemla, Shea N Gardner, Lisa M Vergez, Feliza Bourguet, Shalini Mabery, Viacheslav Y Fofanov, Heather Koshinsky, Paul J Jackson
Francisella tularensis is classified as a Class A bioterrorism agent by the U.S. government due to its high virulence and the ease with which it can be spread as an aerosol. It is a facultative intracellular pathogen and the causative agent of tularemia. Ciprofloxacin (Cipro) is a broad spectrum antibiotic effective against Gram-positive and Gram-negative bacteria. Increased Cipro resistance in pathogenic microbes is of serious concern when considering options for medical treatment of bacterial infections. Identification of genes and loci that are associated with Ciprofloxacin resistance will help advance the understanding of resistance mechanisms and may, in the future, provide better treatment options for patients...
2016: PloS One
https://www.readbyqxmd.com/read/27639659/formulation-and-characterization-of-nanocluster-ceftazidime-for-the-treatment-of-acute-pulmonary-melioidosis
#12
Sara I Ruiz, Nashwa El-Gendy, Larry E Bowen, Cory Berkland, Mark M Bailey
Melioidosis is an infectious disease caused by Burkholderia pseudomallei. The disease is responsible for a high proportion of human pneumonia and fatal bacteremia in the endemic areas of the world and is highly resistant to most commonly available antibiotics. Studies have shown that prophylactic antibiotic treatment, when administered 24 h following bacterial challenge, can prevent infection in a murine model. Prophylactic treatment against this disease using a pulmonary antibiotic formulation has not previously been examined, but may reduce the number of treatments required, allow for the delivery of higher doses, eliminate the need for intravenous administration, and help to minimize systemic side effects...
November 2016: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27628783/investigation-of-the-enhanced-antimicrobial-activity-of-combination-dry-powder-inhaler-formulations-of-lactoferrin
#13
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
https://www.readbyqxmd.com/read/27572404/molecular-epidemiology-of-mutations-in-antimicrobial-resistance-loci-of-pseudomonas-aeruginosa-isolates-from-cystic-fibrosis-airways
#14
Leonie Greipel, Sebastian Fischer, Jens Klockgether, Marie Dorda, Samira Mielke, Lutz Wiehlmann, Nina Cramer, Burkhard Tümmler
The chronic airway infections with Pseudomonas aeruginosa in people with cystic fibrosis (CF) are treated with aerosolized antibiotics, oral fluoroquinolones and/or intravenous combination therapy with aminoglycosides and β-lactam antibiotics. An international strain collection of 361 P. aeruginosa isolates from 258 CF patients seen at 30 CF clinics was examined for mutations in 17 antimicrobial susceptibility and resistance loci that had been identified as hot spots of mutation by genome sequencing of serial isolates from a single CF clinic...
August 29, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27558619/cross-species-prediction-of-human-survival-probabilities-for-accelerated-anthrax-vaccine-absorbed-ava-regimens-and-the-potential-for-vaccine-and-antibiotic-dose-sparing
#15
G V Stark, G S Sivko, M VanRaden, J Schiffer, K L Taylor, J A Hewitt, C P Quinn, E O Nuzum
Anthrax vaccine adsorbed (AVA, BioThrax) was recently approved by the Food and Drug Administration (FDA) for a post-exposure prophylaxis (PEP) indication in adults 18-65years of age. The schedule is three doses administered subcutaneous (SC) at 2-week intervals (0, 2, and 4weeks), in conjunction with a 60-day course of antimicrobials. The Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) developed an animal model to support assessment of a shortened antimicrobial PEP duration following Bacillus anthracis exposure...
December 12, 2016: Vaccine
https://www.readbyqxmd.com/read/27531420/pulmonary-pharmacokinetics-of-levofloxacin-in-rats-after-aerosolization-of-immediate-release-chitosan-or-sustained-release-plga-microspheres
#16
Marisa C Gaspar, Nicolas Grégoire, João J S Sousa, Alberto A C C Pais, Isabelle Lamarche, Patrice Gobin, Jean-Christophe Olivier, Sandrine Marchand, William Couet
A comparative pharmacokinetic study was conducted in rats after intratracheal aerosolization of levofloxacin, as a solution, as immediate-release chitosan microspheres or as sustained-release PLGA microspheres. A pharmacokinetic model was constructed to model levofloxacin concentrations both in plasma and in the lung epithelial lining fluid (ELF). The plasma and ELF experimental concentration profiles versus time were similar for the intravenous and intratracheal levofloxacin solutions and for the intratracheal levofloxacin-loaded chitosan microsphere dry powder, indicating that levofloxacin diffused almost instantaneously through the broncho-alveolar barrier and that the chitosan microspheres released levofloxacin very rapidly, as anticipated from in vitro release studies...
October 10, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27527086/the-stringent-response-factors-ppx1-and-ppk2-play-an-important-role-in-mycobacterium-tuberculosis-metabolism-biofilm-formation-and-sensitivity-to-isoniazid-in-vivo
#17
Yu-Min Chuang, Noton K Dutta, Chien-Fu Hung, T-C Wu, Harvey Rubin, Petros C Karakousis
Mycobacterium tuberculosis (Mtb) remains a global health threat largely due to the lengthy duration of curative antibiotic treatment, contributing to medical nonadherence and the emergence of drug resistance. This prolonged therapy is likely due to the presence of Mtb persisters, which exhibit antibiotic tolerance. Inorganic polyphosphate (poly(P)) is a key regulatory molecule in the Mtb stringent response mediating antibiotic tolerance. The polyphosphate kinase PPK1 is responsible for poly(P) synthesis in Mtb, while the exopolyphosphatases PPX1 and PPX2, and the GTP synthase PPK2 are responsible for poly(P) hydrolysis...
August 15, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27451375/adjunctive-aerosolized-antibiotics-to-treat-ventilator-associated-pneumonia-a-clinical-conundrum-continues
#18
EDITORIAL
G Christopher Wood
No abstract text is available yet for this article.
August 2016: Respiratory Care
https://www.readbyqxmd.com/read/27431222/efficacy-projection-of-obiltoxaximab-for-treatment-of-inhalational-anthrax-across-a-range-of-disease-severity
#19
Brent J Yamamoto, Annette M Shadiack, Sarah Carpenter, Daniel Sanford, Lisa N Henning, Edward O'Connor, Nestor Gonzales, John Mondick, Jonathan French, Gregory V Stark, Alan C Fisher, Leslie S Casey, Natalya V Serbina
Inhalational anthrax has high mortality even with antibiotic treatment, and antitoxins are now recommended as an adjunct to standard antimicrobial regimens. The efficacy of obiltoxaximab, a monoclonal antibody against anthrax protective antigen (PA), was examined in multiple studies conducted in two animal models of inhalational anthrax. A single intravenous bolus of 1 to 32 mg/kg of body weight obiltoxaximab or placebo was administered to New Zealand White rabbits (two studies) and cynomolgus macaques (4 studies) at disease onset (significant body temperature increase or detection of serum PA) following lethal challenge with aerosolized Bacillus anthracis spores...
October 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27431219/obiltoxaximab-prevents-disseminated-bacillus-anthracis-infection-and-improves-survival-during-pre-and-postexposure-prophylaxis-in-animal-models-of-inhalational-anthrax
#20
Brent J Yamamoto, Annette M Shadiack, Sarah Carpenter, Daniel Sanford, Lisa N Henning, Nestor Gonzales, Edward O'Connor, Leslie S Casey, Natalya V Serbina
The Centers for Disease Control and Prevention recommend adjunctive antitoxins when systemic anthrax is suspected. Obiltoxaximab, a monoclonal antibody against protective antigen (PA), is approved for treatment of inhalational anthrax in combination with antibiotics and for prophylaxis when alternative therapies are not available. The impact of toxin neutralization with obiltoxaximab during pre- and postexposure prophylaxis was explored, and efficacy results that supported the prophylaxis indication are presented here...
October 2016: Antimicrobial Agents and Chemotherapy
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