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antifungal combination therapy

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https://www.readbyqxmd.com/read/28919893/ripk3-fas-associated-death-domain-axis-regulates-pulmonary-immunopathology-to-cryptococcal-infection-independent-of-necroptosis
#1
Zhenzong Fa, Qun Xie, Wei Fang, Haibing Zhang, Haiwei Zhang, Jintao Xu, Weihua Pan, Jinhua Xu, Michal A Olszewski, Xiaoming Deng, Wanqing Liao
Fas-associated death domain (FADD) and receptor interacting protein kinase 3 (RIPK3) are multifunctional regulators of cell death and immune response. Using a mouse model of cryptococcal infection, the roles of FADD and RIPK3 in anti-cryptococcal defense were investigated. Deletion of RIPK3 alone led to increased inflammatory cytokine production in the Cryptococcus neoformans-infected lungs, but in combination with FADD deletion, it led to a robust Th1-biased response with M1-biased macrophage activation. Rather than being protective, these responses led to paradoxical C...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28911046/animal-models-for-studying-triazole-resistance-in-aspergillus-fumigatus
#2
Russell E Lewis, Paul E Verweij
Infections caused by triazole-resistant Aspergillus fumigatus are associated with a higher probability of treatment failure and mortality. Because clinical experience in managing these infections is still limited, mouse models of invasive aspergillosis fulfill a critical void for studying treatment regimens designed to overcome resistance. The type of immunosuppression, the route of infection, the timing of antifungal administration, and the end points used to assess antifungal activity affect the interpretation of data from these models...
August 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28893786/novel-cell-killing-mechanisms-of-hydroxyurea-and-the-implication-towards-combination-therapy-for-the-treatment-of-fungal-infections
#3
Amanpreet Singh, Ameeta Agarwal, Yong-Jie Xu
We have previously reported that an erg11 mutation affecting ergosterol synthesis and a hem13 mutation in the heme synthesis pathway significantly sensitize the fission yeast Schizosaccahromyces pombe to hydroxyurea (HU) (1, 2). Here we show that treatment with the inhibitors of Erg11 and the heme biosynthesis phenocopies the two mutations in sensitizing wild type cells to HU. Importantly, HU synergistically interacts with the heme biosynthesis inhibitor sampangine and several Erg11 inhibitors, the antifungal azoles, in causing cell lethality...
September 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28884772/afm-combined-to-atr-ftir-reveals-candida-cell-wall-changes-under-caspofungin-treatment
#4
Fabienne Quilès, Isabelle Accoceberry, Célia Couzigou, Grégory Francius, Thierry Noël, Sofiane El-Kirat-Chatel
Fungal pathogens from Candida genus are responsible for severe life-threatening infections and the antifungal arsenal is still limited. Caspofungin, an antifungal drug used for human therapy, acts as a blocking agent of the cell wall synthesis by inhibiting the β-1,3-glucan-synthase encoded by FKS genes. Despite its efficiency, the number of genetic mutants that are resistant to caspofungin is increasing. An important challenge to improve antifungal therapy is to understand cellular phenomenon that are associated with drug resistance...
September 8, 2017: Nanoscale
https://www.readbyqxmd.com/read/28854287/risk-of-superinfection-in-peri-implantitis-after-systemic-broad-spectrum-antibiotics
#5
Fernando Verdugo
Peri-implant disease has developed over the last few years as a complication that is often difficult to resolve. The disease process is mainly attributed to bacterial infection. Proposed combined therapies use broad-spectrum antibiotics to halt its progression. A major associated risk is the undetected development of superinfections that are difficult to eradicate. A group of healthy individuals with advanced peri-implantitis (PI) were referred for evaluation due to severe, rapidly progressive bone loss. Previous nonsurgical and empiric antibiotic therapy had been rendered...
August 30, 2017: International Journal of Periodontics & Restorative Dentistry
https://www.readbyqxmd.com/read/28830348/evaluation-of-trypan-blue-stain-in-a-haemocytometer-for-rapid-detection-of-cerebrospinal-fluid-sterility-in-hiv-patients-with-cryptococcal-meningitis
#6
Richard Kwizera, Andrew Akampurira, Tadeo K Kandole, Kirsten Nielsen, Andrew Kambugu, David B Meya, David R Boulware, Joshua Rhein
BACKGROUND: Quantitative culture is the most common method to determine the fungal burden and sterility of cerebrospinal fluid (CSF) among persons with cryptococcal meningitis. A major drawback of cultures is a long turnaround-time. Recent evidence demonstrates that live and dead Cryptococcus yeasts can be distinguished using trypan blue staining. We hypothesized that trypan blue staining combined with haemocytometer counting may provide a rapid estimation of quantitative culture count and detection of CSF sterility...
August 22, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28827495/the-north-wind-and-the-sun-pediatric-antimicrobial-stewardship-program-combining-restrictive-and-persuasive-approaches-in-hematology-oncology-ward-and-hematopoietic-stem-cell-transplant-unit
#7
Yuho Horikoshi, Tetsuji Kaneko, Yoshihiko Morikawa, Mihoko Isogai, Junichi Suwa, Hiroshi Higuchi, Yuki Yuza, Takayo Shoji, Kenta Ito
OBJECTIVE: The Japanese government's goal for the reduction of antimicrobial consumption is two-thirds of the 2013 rate by 2020. While the antimicrobial stewardship programs (ASP) are essential in health care facilities, ASP data on pediatric hematology-oncology and hematopoietic stem cell transplant (HSCT) patients are limited. Our aim was to evaluate the impact of restrictive and persuasive ASP on immunocompromised children. DESIGN: The ASP for hematology-oncology and HSCT patients at Tokyo Metropolitan Children's Medical Center was assessed...
August 17, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28802855/antifungal-resistance-in-mucorales
#8
E Dannaoui
The order Mucorales, which includes the agents of mucormycosis, comprises a large number of species. These fungi are characterized by high-level resistance to most currently available antifungal drugs. Standardized antifungal susceptibility testing methods are now available, allowing a better understanding of the in vitro activity of antifungal drugs against members of Mucorales. Such tests have made apparent that antifungal susceptibility within this group may be species-specific. Experimental animal models of mucormycosis have also been developed and are of great importance in bridging the gap between in vitro results and clinical trials...
August 9, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28797882/repurposing-antipsychotic-drugs-into-antifungal-agents-synergistic-combinations-of-azoles-and-bromperidol-derivatives-in-the-treatment-of-various-fungal-infections
#9
Selina Y L Holbrook, Atefeh Garzan, Emily K Dennis, Sanjib K Shrestha, Sylvie Garneau-Tsodikova
As the number of hospitalized and immunocompromised patients continues to rise, invasive fungal infections, such as invasive candidiasis and aspergillosis, threaten the life of millions of patients every year. The azole antifungals are currently the most prescribed drugs clinically that display broad-spectrum antifungal activity and excellent oral bioavailability. Yet, the azole antifungals have their own limitations and are unable to meet the challenges associated with increasing fungal infections and the accompanied development of resistance against azoles...
July 19, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28782144/syndrome-of-inappropriate-antidiuretic-hormone-secretion-from-concomitant-use-of-itraconazole-and-vindesine
#10
H Zhou, L Li, Y Zhou, Y Han
WHAT IS KNOWN AND OBJECTIVE: Several studies have reported that itraconazole-induced inhibition of vincristine (VCR) metabolism might result in neurological impairment and syndrome of inappropriate antidiuretic hormone (SIADH). However, there are few reports concerning adverse drug reactions (ADRs) resulting from concomitant use of vindesine (VDS) and itraconazole. Here, we report the first case of adverse drug interactions (ADIs) between itraconazole and VDS in a Chinese child with acute lymphocytic leukaemia (ALL)...
August 6, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28771470/chromoblastomycosis-in-india-review-of-169-cases
#11
REVIEW
Reshu Agarwal, Gagandeep Singh, Arnab Ghosh, Kaushal Kumar Verma, Mragnayani Pandey, Immaculata Xess
Chromoblastomycosis (CBM) is a chronic, progressive, cutaneous and subcutaneous fungal infection following the traumatic implantation of certain dematiaceous fungi. The disease has worldwide prevalence with predominant cases reported from humid tropical and subtropical regions of America, Asia, and Africa. Diagnosis is often delayed or misdirected either due to poor degree of clinical suspicions or clinical simulation of dermatological conditions. The infection is not uncommon in India and several case reports from the sub-Himalayan belt and western and eastern coasts of India have been published; however, very few have reviewed the cases...
August 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28766033/antifungal-mechanism-of-the-combination-of-cinnamomum-verum-and-pelargonium-graveolens-essential-oils-with-fluconazole-against-pathogenic-candida-strains
#12
Rym Essid, Majdi Hammami, Dorra Gharbi, Ines Karkouch, Thouraya Ben Hamouda, Salem Elkahoui, Ferid Limam, Olfa Tabbene
The present study aimed to investigate the anti-Candida activity of ten essential oils (EOs) and to evaluate their potential synergism with conventional drugs. The effect on secreted aspartic protease (SAP) activity and the mechanism of action were also explored. The antifungal properties of essential oils were investigated using standard micro-broth dilution assay. Only Cinnamomum verum, Thymus capitatus, Syzygium aromaticum, and Pelargonium graveolens exhibited a broad spectrum of activity against a variety of pathogenic Candida strains...
August 1, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28762125/progress-in-definition-prevention-and-treatment-of-fungal-infections-in-cystic-fibrosis
#13
REVIEW
Carsten Schwarz, Dominik Hartl, Olaf Eickmeier, Andreas Hector, Christian Benden, Isabelle Durieu, Amparo Sole, Silvia Gartner, Carlos E Milla, Peter James Barry
Cystic fibrosis (CF) is a chronic lethal multi-system condition; however, most of the morbidity and mortality is dependent on the status of the respiratory system. Progressive respiratory decline is mediated by chronic infection and inflammation, punctuated by important acute events known as pulmonary exacerbations which can lead to accelerated decline. The main bacterial species causing infections include Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae and Achromobacter xylosoxidans. In addition to bacteria, fungi are detected in a significant number of patients...
July 31, 2017: Mycopathologia
https://www.readbyqxmd.com/read/28739646/koh-mount-as-an-aid-in-the-management-of-infectious-keratitis-at-secondary-eye-care-centre
#14
Varsha M Rathi, Monica Thakur, Savitri Sharma, Rohit Khanna, Prashant Garg
AIMS: To report the clinical outcome of infectious keratitis managed after doing 10% KOH mount of corneal smears and reporting done by an ophthalmologist in the secondary eye care centre in South India. METHODS: 103 consecutive cases of microbial keratitis were studied. Inclusion criteria were presence of corneal infiltrate on slit lamp biomicroscopy. An ophthalmologist carried out microbiological evaluation of 10% KOH mount of corneal scrapings. No cultures were done at secondary centres...
July 24, 2017: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/28724328/smart-tetrazole-based-antibacterial-nanoparticles-as-multifunctional-drug-carriers-for-cancer-combination-therapy
#15
Elham Zakerzadeh, Roya Salehi, Mehrdad Mahkam
Due to multidrug resistance of cancer tissues and immune-suppression of cancerous patients during chemotherapy in one hand and the use of tetrazole derivatives in medicine because of its anticancer, antifungal and antiviral properties, on the other, we were encouraged to design novel smart antibacterial nanocomposites-based polymer of tetrazole as dual anticancer drug delivery systems. The structures of nanocomposites characterized by FTIR, (1)H NMR, FESEM-EDX and TGA analyses and antibacterial activity of smart carriers were evaluated by determination of minimum inhibitory concentration (MIC) values against some bacteria and fungi...
July 20, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28702763/pharmacokinetics-of-antifungal-drugs-practical-implications-for-optimized-treatment-of-patients
#16
REVIEW
Romuald Bellmann, Piotr Smuszkiewicz
INTRODUCTION: Because of the high mortality of invasive fungal infections (IFIs), appropriate exposure to antifungals appears to be crucial for therapeutic efficacy and safety. MATERIALS AND METHODS: This review summarises published pharmacokinetic data on systemically administered antifungals focusing on co-morbidities, target-site penetration, and combination antifungal therapy. CONCLUSIONS AND DISCUSSION: Amphotericin B is eliminated unchanged via urine and faeces...
July 12, 2017: Infection
https://www.readbyqxmd.com/read/28696236/combination-therapy-with-isavuconazole-and-micafungin-for-treatment-of-experimental-invasive-pulmonary-aspergillosis
#17
Vidmantas Petraitis, Ruta Petraitiene, Matthew W McCarthy, Laura L Kovanda, Myo H Zaw, Kaiser Hussain, Naima Shaikh, Bo Bo W Maung, Navjot K Sekhon, William W Hope, Thomas J Walsh
Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity and mortality in immunocompromised patients. We hypothesized that simultaneous inhibition of biosynthesis of ergosterol in the fungal cell membrane and (1→3)-β-d-glucan in the cell wall, respectively, by the antifungal triazole isavuconazole (ISA) and the echinocandin micafungin (MFG) may result in improved outcomes in experimental IPA in persistently neutropenic rabbits. Treatments included ISA at 20 mg/kg of body weight/day (ISA20), 40 mg/kg/day (ISA40), and 60 mg/kg/day (ISA60); MFG at 2 mg/kg/day (MFG2); combinations of ISA20 and MFG2, ISA40 and MFG2, and ISA60 and MFG2; and no treatment (untreated controls [UC])...
September 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28694566/antifungal-resistance-metabolic-routes-as-drug-targets-and-new-antifungal-agents-an-overview-about-endemic-dimorphic-fungi
#18
REVIEW
Juliana Alves Parente-Rocha, Alexandre Melo Bailão, André Correa Amaral, Carlos Pelleschi Taborda, Juliano Domiraci Paccez, Clayton Luiz Borges, Maristela Pereira
Diseases caused by fungi can occur in healthy people, but immunocompromised patients are the major risk group for invasive fungal infections. Cases of fungal resistance and the difficulty of treatment make fungal infections a public health problem. This review explores mechanisms used by fungi to promote fungal resistance, such as the mutation or overexpression of drug targets, efflux and degradation systems, and pleiotropic drug responses. Alternative novel drug targets have been investigated; these include metabolic routes used by fungi during infection, such as trehalose and amino acid metabolism and mitochondrial proteins...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28688551/pediatric-invasive-fungal-rhinosinusitis-an-investigation-of-17-patients
#19
Daniel Vinh, Michael Yim, Ankhi Dutta, John K Jones, Wei Zhang, Matthew Sitton
PURPOSE: To investigate outcomes of pediatric patients at a single institution with invasive fungal rhinosinusitis (IFRS) and to determine variables that impact overall survival. METHODS: All pediatric patients at a large tertiary children's hospital diagnosed with IFRS confirmed by surgical pathology from 2009 to 2015 were retrospectively reviewed. Demographics, underlying diseases, symptoms, antifungal therapy, absolute neutrophil count (ANC), surgical management,and outcomes were analyzed...
August 2017: International Journal of Pediatric Otorhinolaryngology
https://www.readbyqxmd.com/read/28685145/oral-candida-in-patients-with-fixed-orthodontic-appliance-in-vitro-combination-therapy
#20
Wisam Alhamadi, Rafal J Al-Saigh, Nebras N Al-Dabagh, Hussam W Al-Humadi
BACKGROUND: Fixed orthodontic appliance (FOA) increases the cariogenic microorganisms of mouth including candida. The aim was to evaluate the pharmacodynamic effects of some antibacterial drugs in combination with most applicable antifungal agents on candida isolated from patients with FOA. METHODS: Three antifungal agents (amphotericin B (AMB), ketoconazole (KET), and itraconazole (ITZ)) and three antibacterial drugs (ciprofloxacin (CIP), doxycycline (DOX), and metronidazole (MET)) with serial concentrations have been used and microdilution broth method has been done for single and combination therapy, then fungal growth was assessed spectrophotometrically, and the combinations were evaluated by bliss independent analysis...
2017: BioMed Research International
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