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antifungal combination therapy

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https://www.readbyqxmd.com/read/28724328/smart-tetrazole-based-antibacterial-nanoparticles-as-multifunctional-drug-carriers-for-cancer-combination-therapy
#1
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
#2
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
#3
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 and the echinocandin micafungin, may result in improved outcome in experimental IPA in persistently neutropenic rabbits. Treatment groups included isavuconazole (ISA) at 20 (ISA20), 40 (ISA40), and 60 (ISA60) mg/kg/day, micafungin at 2 mg/kg/day (MFG2), or combinations of (ISA20+MFG2), (ISA40+MFG2), (ISA60+MFG2), and untreated rabbits (UC)...
July 10, 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
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/28680034/high-dose-fluconazole-in-combination-with-amphotericin-b-is-more-efficient-than-monotherapy-in-murine-model-of-cryptococcosis
#7
Julliana Ribeiro Alves Santos, Noelly Queiroz Ribeiro, Rafael Wesley Bastos, Rodrigo Assunção Holanda, Letícia Chagas Silva, Estela Rezende Queiroz, Daniel Assis Santos
Cryptococcus spp., the causative agents of cryptococcosis, are responsible for deaths of hundreds of thousands of people every year worldwide. The drawbacks of available therapeutic options are aggravated by the increased resistance of yeast to the drugs, resulting in inefficient therapy. Also, the antifungal 5FC is not available in many countries. Therefore, a combination of antifungal drugs may be an interesting option, but in vitro and theoretical data point to the possible antagonism between the main antifungals used to treat cryptococcosis, i...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28673609/strong-synergism-of-dexamethasone-in-combination-with-fluconazole-against-resistant-candida-albicans-mediated-by-inhibiting-drug-efflux-and-reducing-virulence
#8
Wenwen Sun, Decai Wang, Cuixiang Yu, Xin Huang, Xiuyun Li, Shujuan Sun
Candida albicans are the most common isolated strains in the clinic and their resistance to fluconazole has beenemergingrapidly.Combinatorial therapy would be is a potentially effective approach against drugresistance. In this study, the combinatorial antifungal effects of dexamethasone and fluconazoleagainst resistant Candida albicans in vitrowere assayed usingminimum inhibitory concentrations, sessile minimum inhibitory concentrations, and time-kill curves. In vivo efficacy of this drug combination was evaluated usingthe Galleria mellonellamodel...
June 30, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28671171/early-onset-de-novo-invasive-pulmonary-aspergillosis-in-an-orthotopic-heart-transplant-recipient
#9
Zaw Min, Manik Veer, Parth Rali, Anil Singh, Nitin Bhanot
Invasive aspergillosis generally occurs during the first 1-6 months after heart transplantation. It has been rarely seen in the first 2 weeks postcardiac transplant. We herein describe a unique case of invasive pulmonary aspergillosis (IPA) diagnosed on day 9 postorthotopic heart transplantation. The known risk factors for IPA in cardiac transplant recipients were not identified in our case. The organ recipients from the same donor did not report Aspergillus infection. Hospital environmental samplings failed to demonstrate Aspergillus spores in the patient's room and his adjacent rooms...
July 2017: Lung India: Official Organ of Indian Chest Society
https://www.readbyqxmd.com/read/28650761/cryptococcal-osteomyelitis-of-the-first-metatarsal-head-in-an-immunocompetent-patient
#10
Jae Hoon Ahn, ChanJoo Park, Choong Woo Lee, Yoon-Chung Kim
Most fungal infections primarily occur in immunocompromised patients. We describe a case of osteomyelitis involving the first metatarsal head due to Cryptococcus neoformans in a previously healthy immunocompetent patient. She was treated with surgical debridement combined with antifungal drug therapy for 6 months. At 5-year follow-up, she remained symptom free with full range of motion of the first metatarsophalangeal joint. Fungal osteomyelitis should be considered as a possible cause in osteolytic lesions in the metatarsal bone...
May 2017: Journal of the American Podiatric Medical Association
https://www.readbyqxmd.com/read/28645774/evaluation-of-selected-indian-medicinal-plants-for-antagonistic-potential-against-malassezia-spp-and-the-synergistic-effect-of-embelin-in-combination-with-ketoconazole
#11
Chandran Sivasankar, Subramanian Gayathri, James Prabhanand Bhaskar, Venkat Krishnan, Shunmugiah Karutha Pandian
The genus Malassezia comprises of extremely lipophilic yeasts secreting lipases as a vital factor for survival. They are emerging as opportunistic pathogens in medical microbiology and dermatology by causing recurring and recalcitrant infection. Combinatorial therapy is a constructive way to combat infectious diseases. In that prospect, totally 16 Indian medicinal plants were screened, among which a maximum degree of antimicrobial activity was ascertained in Embelia ribes. Subsequently embelin was identified as the bioactive principle with antagonistic potential by comparative antimicrobial assay and FTIR analysis...
June 20, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28638374/azole-resistance-in-aspergillus-fumigatus-a-consequence-of-antifungal-use-in-agriculture
#12
REVIEW
Sarah Berger, Yassine El Chazli, Ambrin F Babu, Alix T Coste
Agricultural industry uses pesticides to optimize food production for the growing human population. A major issue for crops is fungal phytopathogens, which are treated mainly with azole fungicides. Azoles are also the main medical treatment in the management of Aspergillus diseases caused by ubiquitous fungi, such as Aspergillus fumigatus. However, epidemiological research demonstrated an increasing prevalence of azole-resistant strains in A. fumigatus. The main resistance mechanism is a combination of alterations in the gene cyp51A (TR34/L98H)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28636889/complications-of-hematopoietic-stem-transplantation-fungal-infections
#13
REVIEW
Ali S Omrani, Reem S Almaghrabi
Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are at increased risk of invasive fungal infections, especially during the early neutropenic phase and severe graft-versus-host disease. Mold-active prophylaxis should be limited to the highest risk groups. Empiric antifungal therapy for HSCT with persistent febrile neutropenia is associated with unacceptable response rates, unnecessary antifungal therapy, increased risk of toxicity, and inflated costs. Empiric therapy should not be a substitute for detailed work up to identify the cause of fever in such patients...
June 13, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28621668/blocking-epithelial-to-mesenchymal-transition-in-glioblastoma-with-a-sextet-of-repurposed-drugs-the-eis-regimen
#14
Richard E Kast, Nicolas Skuli, Georg Karpel-Massler, Guido Frosina, Timothy Ryken, Marc-Eric Halatsch
This paper outlines a treatment protocol to run alongside of standard current treatment of glioblastoma- resection, temozolomide and radiation. The epithelial to mesenchymal transition (EMT) inhibiting sextet, EIS Regimen, uses the ancillary attributes of six older medicines to impede EMT during glioblastoma. EMT is an actively motile, therapy-resisting, low proliferation, transient state that is an integral feature of cancers' lethality generally and of glioblastoma specifically. It is believed to be during the EMT state that glioblastoma's centrifugal migration occurs...
June 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28620270/flucytosine-and-amphotericin-b-coadministration-induces-dose-related-renal-injury
#15
Alexandra Folk, Cornel Balta, Hildegard Herman, Alexandra Ivan, Oana Maria Boldura, Lucian Paiusan, Aurel Ardelean, Anca Hermenean
Invasive fungal infections remain an important clinical problem, and despite recent approaches, they bring high morbidity and mortality. Combination therapies are the most effective; however, adverse effects need to be considered. In this study, we aimed to evaluate the nephrotoxicity induced by combined therapy of flucytosine (FL) and amphotericin B (AMF) at 3 different doses administered to mice for 14 days: 300 μg/kg AMF+50 mg/kg FL; 600 μg/kg AMF+100 mg/kg FL; 900 μg/kg AMF+150 mg/kg FL. Antifungal coadministration triggered nuclear translocation of NF-κB and upregulated nuclear factor kappa-light-chain-enhancer of activated B cells subunit p65 (NF-κB p65) messenger RNA mRNA level in dose-dependent manner...
April 2017: Dose-response: a Publication of International Hormesis Society
https://www.readbyqxmd.com/read/28617137/drugs-currently-under-investigation-for-the-treatment-of-invasive-candidiasis
#16
REVIEW
Matthew W McCarthy, Thomas J Walsh
The widespread implementation of immunosuppressants, immunomodulators, hematopoietic stem cell transplantation and solid organ transplantation in clinical practice has led to an expanding population of patients who are at risk for invasive candidiasis, which is the most common form of fungal disease among hospitalized patients in the developed world. The emergence of drug-resistant Candida spp. has added to the morbidity associated with invasive candidiasis and novel therapeutic strategies are urgently needed...
July 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28593476/synergy-between-azoles-and-1-4-dihydropyridine-derivative-as-an-option-to-control-fungal-infections
#17
Zuzana Ježíková, Tomáš Pagáč, Barbora Pfeiferová, Helena Bujdáková, Stanislava Dižová, Iva Jančíková, Dana Gášková, Petra Olejníková
With emerging fungal infections and developing resistance, there is a need for understanding the mechanisms of resistance as well as its clinical impact while planning the treatment strategies. Several approaches could be taken to overcome the problems arising from the management of fungal diseases. Besides the discovery of novel effective agents, one realistic alternative is to enhance the activity of existing agents. This strategy could be achieved by combining existing antifungal agents with other bioactive substances with known activity profiles (combination therapy)...
June 7, 2017: Antonie Van Leeuwenhoek
https://www.readbyqxmd.com/read/28577122/successful-treatment-of-pulmonary-mucormycosis-caused-by-cunninghamella-bertholletiae-with-high-dose-liposomal-amphotericin-b-10%C3%A2-mg-kg-day-followed-by-a-lobectomy-in-cord-blood-transplant-recipients
#18
Hikari Ota, Hisashi Yamamoto, Muneyoshi Kimura, Hideki Araoka, Takeshi Fujii, Takashi Umeyama, Hideaki Ohno, Yoshitsugu Miyazaki, Daisuke Kaji, Yuki Taya, Aya Nishida, Kazuya Ishiwata, Masanori Tsuji, Shinsuke Takagi, Yuki Asano-Mori, Go Yamamoto, Naoyuki Uchida, Koji Izutsu, Kazuhiro Masuoka, Atsushi Wake, Akiko Yoneyama, Shigeyoshi Makino, Shuichi Taniguchi
Infection caused by Cunninghamella bertholletiae carries one of the highest mortality rates among mucormycosis, and there are no reported cases that survived from the infection in allogeneic hematopoietic stem cell transplantation recipients occurring before neutrophil engraftment. Here, we present two cases of pulmonary mucormycosis caused by C. bertholletiae occurring before neutrophil engraftment after cord blood transplantation. Both were successfully treated with high-dose liposomal amphotericin B (10 mg/kg/day) combined with micafungin, which was then followed by neutrophil recovery, reduction in immunosuppressive agents, and a subsequent lobectomy...
June 2, 2017: Mycopathologia
https://www.readbyqxmd.com/read/28568285/claviform-aspergillus-related-vegetation-in-the-left-ventricle-of-a-patient-with-systemic-lupus-erythematosus
#19
Tetsushi Yamamoto, Shimpei Kasagi, Chiyo Kurimoto, Takamitsu Imanishi, Nobuhide Hayashi, Akio Morinobu, Jun Saegusa
A 38-year-old woman was diagnosed with systemic lupus erythematosus and received immunosuppressive therapy. After 6 months of treatment, workup for low-grade fever yielded elevated enzyme-linked immunosorbent assay titers for Aspergillus antigen in serum and ascites, leading to the diagnosis of disseminated aspergillosis. Transthoracic echocardiography revealed a claviform vegetation attached to the left ventricular anterior septum. Two days after the start of antifungal Amphotericin-B therapy, the patient suffered from several neurologic disorders...
June 1, 2017: Journal of Clinical Ultrasound: JCU
https://www.readbyqxmd.com/read/28556426/retrospective-study-on-the-incidence-and-outcome-of-proven-and-probable-invasive-fungal-infections-in-high-risk-pediatric-onco-hematological-patients
#20
Simone Cesaro, Gloria Tridello, Elio Castagnola, Elisabetta Calore, Francesca Carraro, Ilaria Mariotti, Antonella Colombini, Katia Perruccio, Nunzia Decembrino, Giovanna Russo, Natalia Maximova, Valentina Baretta, Désirée Caselli
BACKGROUND: Invasive fungal infection (IFI) is a cause of morbidity, mortality and increased health costs in children undergoing chemotherapy or hematopoietic stem cell transplant (HSCT). METHODS: Multicenter, retrospective study to assess the incidence, outcome of proven and probable IFI (PP-IFI) in children treated for acute leukemia, non-Hodgkin lymphoma or who underwent HSCT from 2006 to 2012. RESULTS: Over the 7-year period, 127 PP-IFI were diagnosed in 123 patients, median age of 9...
May 27, 2017: European Journal of Haematology
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