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https://www.readbyqxmd.com/read/28808915/cost-effectiveness-of-posaconazole-tablets-for-invasive-fungal-infections-prevention-in-acute-myelogenous-leukemia-or-myelodysplastic-syndrome-patients-in-spain
#1
Rafael Cámara, Irmina Gozalbo, Manuel Jurado, Jaime Sanz, Belén Aragón, Santiago Grau
INTRODUCTION: Posaconazole is superior to fluconazole (FLU) and itraconazole (ITRA) in the prevention of invasive fungal diseases (IFDs) in neutropenic patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). A new tablet formulation of posaconazole with improved pharmacokinetic and pharmacodynamic properties compared to posaconazole oral solution has recently been approved. The objective of this study is to estimate the cost-effectiveness of the newly developed posaconazole tablets versus FLU oral suspension or ITRA oral solution for preventing IFDs in high-risk neutropenic patients with AML or MDS and from the perspective of the Spanish National Health System (NHS)...
August 14, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28807922/are-standard-doses-of-piperacillin-in-piperacillin-tazobactam-regimens-adequate-for-the-management-of-febrile-neutropenia-answers-from-population-pharmacokinetic-modelling-and-monte-carlo-simulations
#2
Fekade Bruck Sime, Uwe Hahn, Morgyn S Warner, Ing Soo Tiong, Michael S Roberts, Jeffrey Lipman, Sandra L Peake, Jason A Roberts
Changes in the pharmacokinetics of piperacillin in febrile neutropenic patients have been reported to result in sub-optimal exposures. This study aimed to develop a population pharmacokinetic model for piperacillin and perform dosing simulation to describe optimal dosing regimens for haematological malignancy patients with febrile neutropenia. Concentration-time data were obtained from previous prospective observational pharmacokinetic and interventional therapeutic drug monitoring studies. Non-parametric population pharmacokinetic analysis and Monte Carlo dosing simulations were performed with Pmetrics® package for R...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28807906/impact-of-type-iii-secretion-effectors-and-of-phenoxyacetamide-inhibitors-of-type-iii-secretion-on-abscess-formation-in-a-mouse-model-of-pseudomonas-aeruginosa-infection
#3
Bryan J Berube, Katherine Murphy, Matthew C Torhan, Nicholas O Bowlin, John D Williams, Terry L Bowlin, Donald T Moir, Alan R Hauser
Pseudomonas aeruginosa is a leading cause of intra-abdominal infections, wound infections, and community-acquired folliculitis, each of which may involve macro- or micro-abscess formation. The rising incidence of multi-drug resistance among P. aeruginosa isolates has increased both the economic burden and the morbidity and mortality associated with P. aeruginosa disease and necessitates a search for novel therapeutics. Previous work from our group detailed novel phenoxyacetamide inhibitors that block type III secretion and injection into host cells in vitro In this study, we used a murine abscess model of P...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28797785/granulocyte-transfusions-a-critical-reappraisal
#4
REVIEW
Caterina Giovanna Valentini, Francesca Farina, Livio Pagano, Luciana Teofili
Granulocyte transfusions (GTs) are seldom used as a life-saving therapy for neutropenic patients with severe infections. Despite several compelling evidences of GT efficacy in retrospective and prospective case series, no study has been successful in demonstrating a definite advantage for recipients in controlled clinical trials. This review will critically revise some aspects emerging from the past experience which might have weakened the evidence of GT benefits. Some specific issues relevant to the efficacy of this therapeutic approach, such as the primary infection, the delivered doses and schedules, and the immunological effects of GTs, will be discussed...
August 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28782216/temporal-changes-in-neutropenic-blood-culture-isolates-and-disease-associations-a-single-centre-series-of-1139-episodes
#5
Nathanael Lucas, Michael Humble, Dalice Sim, Michelle Balm, John Carter, Robert Weinkove
Neutropenic infections are life-threatening and require empiric antibiotic treatment. We examined 1139 blood culture isolates from our institution over a 36-year period from neutropenic patients to examine temporal trends and disease associations. Positive associations were found between viridans streptococci and acute myeloid leukaemia, coagulase negative staphylococci and acute lymphoblastic leukaemia and Pseudomonas aeruginosa and indolent B-cell malignancies.
August 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28776170/viridans-group-streptococci-bloodstream-infections-in-neutropenic-adult-patients-with-hematologic-malignancy-single-center-experience
#6
J Radocha, P Paterová, A Zavřelová, B Víšek, F Gabalec, H Žemličková, P Žák
Viridans group streptococci bloodstream infections (VGS BSI) remain a significant cause of mortality and morbidity in patients with severe neutropenia. The goal of our study was to evaluate clinical course and microbiological susceptibility of VGS BSI at our center. Retrospective analysis of all microbiologically documented bloodstream infections caused by VGS during the 9-year time period (from January 2006 until December 2014) was carried out. Only patients with severe neutropenia (< 500/μL) were included in the study...
August 3, 2017: Folia Microbiologica
https://www.readbyqxmd.com/read/28775254/adamts-13-regulates-neutrophil-recruitment-in-a-mouse-model-of-invasive-pulmonary-aspergillosis
#7
Astrid Alflen, Steve Prüfer, Katharina Ebner, Sebastian Reuter, Pamela Aranda Lopez, Inge Scharrer, Fumiaki Banno, Michael Stassen, Hansjörg Schild, Kerstin Jurk, Markus Bosmann, Hendrik Beckert, Markus P Radsak
Von Willebrand factor (VWF) is secreted as an acute phase protein during inflammation. ADAMTS-13 regulates the size and prothrombotic activity of VWF by it's specific proteolytic activity. To determine the relevance of this regulatory pathway for the innate inflammatory response by polymorphonuclear neutrophils (PMN), we employed a mouse model of invasive pulmonary aspergillosis (IPA) where PMN functionality is crucial for fungal clearance and survival. IPA was induced by intratracheal application of Aspergillus fumigatus (A...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28774702/candida-and-invasive-mould-diseases-in-non-neutropenic-critically-ill-patients-and-patients-with-haematological-cancer
#8
REVIEW
A L Colombo, J N de Almeida Júnior, Monica A Slavin, Sharon C-A Chen, Tania C Sorrell
Critically ill patients and patients with haematological cancer are HIV-negative populations at high risk of invasive fungal infections. In intensive-care units, candidaemia and intra-abdominal candidiasis predominate, but aspergillosis has emerged as a lethal, under-recognised cause of pneumonia. In patients with haematological malignancies or who have undergone stem-cell transplantations, pulmonary disease due to aspergillus and other mould diseases predominate. In this Series paper, we provide an update on risk assessment, new diagnostic strategies, and therapeutic approaches...
July 31, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28753224/aspergillus-fumigatus-protein-phosphatase-ppza-is-involved-in-iron-assimilation-secondary-metabolite-production-and-virulence
#9
Adriana Oliveira Manfiolli, Patrícia Alves de Castro, Thaila Fernanda Dos Reis, Stephen Dolan, Sean Doyle, Gary Jones, Diego M Riaño Pachón, Mevlüt Ulaş, Luke M Noble, Derek J Mattern, Axel A Brakhage, Vito Valiante, Rafael Silva-Rocha, Ozgur Bayram, Gustavo H Goldman
Metal restriction imposed by mammalian hosts during an infection is a common mechanism of defense to reduce or avoid the pathogen infection. Metals are essential for organism survival due to its involvement in several biological processes. Aspergillus fumigatus causes invasive aspergillosis (IA), a disease that typically manifests in immunocompromised patients. A. fumigatus PpzA, the catalytic subunit of protein phosphatase Z (PPZ), has been recently identified as associated with iron assimilation. A. fumigatus has two high affinity mechanisms of iron acquisition during infection: reductive iron assimilation (RIA) and siderophore-mediated iron uptake...
July 28, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28742113/addition-of-17-allylamino-17-demethoxygeldanamycin-to-a-suboptimal-caspofungin-treatment-regimen-in-neutropenic-rats-with-invasive-pulmonary-aspergillosis-delays-the-time-to-death-but-does-not-enhance-the-overall-therapeutic-efficacy
#10
Jeannine M Refos, Alieke G Vonk, Marian T Ten Kate, Kimberly Eadie, Henri A Verbrugh, Irma A J M Bakker-Woudenberg, Wendy W J van de Sande
Caspofungin (CAS) which is used as salvage therapy in patients with invasive pulmonary aspergillosis (IPA) inhibits the 1,3-β-D-glucan synthesis in Aspergillus fumigatus. Inhibiting 1,3-β-D-glucan synthesis induces a stress response and in an invertebrate model it was demonstrated that inhibiting this response with geldamycin enhanced the therapeutic efficacy of CAS. Since geldamycin itself is toxic to mammalians, the therapeutic efficacy of combining geldamycin with CAS was not studied in rodent models. Therefore in this study we investigated if the geldamycin derivate 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) was able to enhance the therapeutic efficacy of CAS in vitro and in our IPA model in transiently neutropenic rats...
2017: PloS One
https://www.readbyqxmd.com/read/28734773/epico-4-0-total-quality-in-the-management-of-invasive-candidiasis-in-critically-ill-patients-by-analysing-the-integrated-process
#11
Rafael Zaragoza, Ricard Ferrer, Pedro Llinares, Emilio Maseda, Alejandro Rodríguez, Santiago Grau, Guillermo Quindós
BACKGROUND: A high quality integrated process in the clinical setting of non-neutropenic critically ill patients at risk for invasive candidiasis is a necessary tool to improve the management of these patients. AIMS: To identify the key points on invasive candidiasis in order to develop a set of recommendations with a high level of consensus required for the creation of a total quality integrated process for the management of non-neutropenic critically ill patients at risk of invasive candidiasis...
July 2017: Revista Iberoamericana de Micología
https://www.readbyqxmd.com/read/28716109/clinical-characteristics-and-outcomes-of-pseudomonas-aeruginosa-bacteremia-in-febrile-neutropenic-children-and-adolescents-with-the-impact-of-antibiotic-resistance-a-retrospective-study
#12
Hyo Sup Kim, Bo Kyoung Park, Seong Koo Kim, Seung Beom Han, Jae Wook Lee, Dong-Gun Lee, Nack-Gyun Chung, Bin Cho, Dae Chul Jeong, Jin Han Kang
BACKGROUND: Although the proportion of Pseudomonas aeruginosa infections has reduced after the introduction of antibiotics with anti-pseudomonal effects, P. aeruginosa bacteremia still causes high mortality in immunocompromised patients. This study determined the clinical characteristics and outcomes of P. aeruginosa bacteremia and the antibiotic susceptibilities of strains isolated from febrile neutropenic patients. METHODS: Thirty-one febrile neutropenic children and adolescents with underlying hematologic/oncologic disorders diagnosed with P...
July 17, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28699245/effects-of-intranasally-dosed-posaconazole-on-fungal-load-and-biomarkers-in-aspergillus-fumigatus-infected-immunocompromised-mice
#13
Genki Kimura, Takahiro Nakaoki, Yuki Nishimoto, Yuto Suzuki, Garth Rapeport, Pete Strong, Kazuhiro Ito, Yasuo Kizawa
Although anti-fungal triazoles are dosed orally or systemically for Aspergillus fumigatus infection, systemic adverse events and limited exposure of the lung cavity would make a topical treatment for the lung an attractive option. In this study, we examined the effects of intranasally dosed posaconazole on survival rates and biomarkers in A. fumigatus (itraconazole susceptible: ATCC13073 [Af]; or resistant: NCPF7100 [AfR]) infected, temporarily neutropenic A/J mice. Once daily treatment produced a dose-dependent improvement of survival of Af-infected mice (ED50 : 0...
July 11, 2017: Mycoses
https://www.readbyqxmd.com/read/28696047/a-randomized-trial-of-the-effectiveness-of-the-neutropenic-diet-versus-food-safety-guidelines-on-infection-rate-in-pediatric-oncology-patients
#14
Karen M Moody, Rebecca A Baker, Ruth O Santizo, Inan Olmez, Jeanie M Spies, Amanda Buthmann, Linda Granowetter, Robin Y Dulman, Kanyalakshmi Ayyanar, Jonathan B Gill, Aaron E Carroll
BACKGROUND: The neutropenic diet (ND) is prescribed to avoid introduction of bacteria into a host's gastrointestinal tract and reduce infection. Due to a lack of evidence to support the ND, there continues to be debate among pediatric oncologists regarding its usefulness. This prospective randomized controlled trial evaluated the difference in neutropenic infection rates in pediatric oncology patients randomized to Food and Drug Administration approved food safety guidelines (FSGs) versus the ND plus FSGs during one cycle of chemotherapy...
July 11, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28694231/repurposing-ivacaftor-for-treatment-of-staphylococcus-aureus-infections
#15
Ritesh Thakare, Alok Kumar Singh, Swetarka Das, N Vasudevan, Gorakhnath R Jachak, D Srinivas Reddy, Arunava Dasgupta, Sidharth Chopra
Drug repurposing of non-antimicrobials is a novel method to augment a seriously depleted drug pipeline for targeting drug-resistant pathogens. This article highlights the potent antimicrobial activity of Ivacaftor against Staphylococcus aureus, including vancomycin- and other multidrug-resistant strains. The potent activity of Ivacaftor in vivo is also demonstrated in a murine neutropenic thigh infection model. Taken together, these results support the potential of Ivacaftor as an antimicrobial agent for the treatment of staphylococcal infections...
July 7, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28692817/complications-of-hematopoietic-stem-transplantation-bacterial-infections
#16
REVIEW
Ali S Omrani, Reem S Almaghrabi
Bacterial infections remain a common complication of hematopoietic stem cell transplantation (HSCT), especially in the pre-engraftment phase. The risk of bacterial infections is mainly related to neutropenia, mucositis, and the presence of vascular lines. Most parts of the world have witnessed a shift in epidemiology toward Gram-negative bacteria; a large proportion of which are resistant to fluoroquinolones, extended-spectrum beta-lactams, carbapenems, and in some units even colistin. Meticulous infection control practices are essential for prevention of bacterial infections in HSCT...
July 3, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28672417/-infections-as-a-cause-of-unexplained-fever
#17
Bernd Salzberger, Gabriele Birkenfeld, Michael Iberer, Florian Hitzenbichler
Fever of unexplained (or unknown) origin (FUO) remains a relevant clinical problem even with modern diagnostic methods. In addition to the classical definition, new categories of FUO describe different clinical situations: nosocomial FUO, FUO in neutropenic/immundeficient patients and FUO in patients with HIV-infection. The new categories are defined by much shorter duration of fever, i. e. mostly three days. Each category of FUO shows a different spectrum of infectious diseases. Often, subacute bacterial endocarditis is very difficult to verify...
July 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28669678/virulence-and-antifungal-therapy-of-murine-disseminated-infection-by-rhodotorula-mucilaginosa
#18
Pamela Thomson, Loida López-Fernández, Josep Guarro, Javier Capilla
Rhodotorula infections have emerged in recent years causing mainly fungemia associated to high mortality. We have evaluated the in vitro activity of nine antifungal drugs against four clinical strains of Rhodotorula mucilaginosa, being amphotericin B, voriconazole and posaconazole the most active compounds. The experimental virulence of this fungus and the efficacy of the three mentioned drugs were evaluated in disseminated infections in neutropenic mice. Infection resulted in a high fungal load in all the organs studied without evident particular tropism...
June 16, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28668427/typical-mr-imaging-findings-of-perianal-infections-in-patients-with-hematologic-malignancies
#19
Nuray Haliloglu, Basak Gulpinar, Esra Ozkavukcu, Ayse Erden
OBJECTIVE: We aimed to investigate the MR imaging findings of patients with hematologic malignancies who have symptoms suggesting perianal infection and to demonstrate the importance of imaging. SUBJECTS AND METHODS: The study included 36 patients with hematologic malignancies who underwent anorectal MR imaging in our department between September 2011-May 2016. Two radiologists experienced in abdominal radiology viewed the MR images in consensus. Abscesses, fistulous or sinus tracts, signal alterations and contrast enhancement in keeping with an inflammation and edema in the perianal region were recorded...
August 2017: European Journal of Radiology
https://www.readbyqxmd.com/read/28662943/discovery-of-novel-antimycobacterial-drug-therapy-in-biofilm-of-pathogenic-nontuberculous-mycobacterial-keratitis
#20
Thet Tun Aung, Wei Hong Jeff Chor, Joey Kuok Hoong Yam, Michael Givskov, Liang Yang, Roger W Beuerman
PURPOSE: The potential of slow-growing mycobacteria to form biofilms in human tissues contributes to the problem of establishing an effective treatment strategy. The purpose of this study was to examine new antibiotic strategies to enhance current treatment options for these infections. METHODS: Sensitivities of Mycobacterium fortuitum ATCC 49404 and Mycobacterium chelonae ATCC 35752 were evaluated for different antimicrobials singly and in combination using broth microdilution and FICI (Fractional Inhibitory Concentration Index) synergy screening...
June 26, 2017: Ocular Surface
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