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https://www.readbyqxmd.com/read/28923871/emergence-of-echinocandin-resistance-due-to-a-point-mutation-in-the-fks1-gene-of-aspergillus-fumigatus-in-a-patient-with-chronic-pulmonary-aspergillosis
#1
Cristina Jiménez-Ortigosa, Caroline Moore, David W Denning, David S Perlin
We have identified the first case of a fks1 hot spot 1 point mutation causing echinocandin resistance in a clinical Aspergillus fumigatus isolate recovered from a chronic pulmonary aspergillosis patient with an aspergilloma who first failed azole and polyene therapy, and then subsequently failed micafungin treatment.
September 18, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28923644/combination-of-echinocandins-and-trimethoprim-sulfamethoxazole-for-the-treatment-of-pneumocystis-jiroveci-pneumonia-after-heart-transplantation
#2
Y-M Lu, Y-T Lee, H-C Chang, H-S Yang, C-Y Chang, C-M Huang, J Wei
BACKGROUND: The echinocandins have shown anti-Pneumocystis jiroveci activity in nonhuman animal models; however, the corresponding human clinical experience has been rarely reported. We report a clinical picture of P jiroveci pneumonia (PJP) and determine the effects of concomitant therapy with echinocandins and trimethoprim (TMP)-sulfamethoxazole (SMZ). METHODS: We investigated a retrospective case series of heart transplantation (HT) recipients with PJP from July 1988 to December 2015...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28922488/isolation-of-rhodotorula-mucilaginosa-from-blood-cultures-in-a-tertiary-care-hospital
#3
Iker Falces-Romero, Emilio Cendejas-Bueno, María Pilar Romero-Gómez, Julio García-Rodríguez
BACKGROUND: Rhodotorula species have traditionally been considered as one of common non-virulent environmental inhabitant. They have emerged as an opportunistic pathogen, particularly in immunocompromised hosts and most infections have been associated with intravenous catheters in these patients. OBJECTIVE: We review the isolates in blood cultures of Rhodotorula mucilaginosa in our Hospital. We describe the demographic and clinical features of the cases and the antifungal susceptibility profiles of the isolates...
September 18, 2017: Mycoses
https://www.readbyqxmd.com/read/28919789/antifungal-resistance-current-trends-and-future-strategies-to-combat
#4
REVIEW
Nathan P Wiederhold
Antifungal resistance represents a major clinical challenge to clinicians responsible for treating invasive fungal infections due to the limited arsenal of systemically available antifungal agents. In addition current drugs may be limited by drug-drug interactions and serious adverse effects/toxicities that prevent their prolonged use or dosage escalation. Fluconazole resistance is of particular concern in non-Candida albicans species due to the increased incidence of infections caused by these species in different geographic locations worldwide and the elevated prevalence of resistance to this commonly used azole in many institutions...
2017: Infection and Drug Resistance
https://www.readbyqxmd.com/read/28911046/animal-models-for-studying-triazole-resistance-in-aspergillus-fumigatus
#5
REVIEW
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/28911043/multidrug-resistant-candida-epidemiology-molecular-mechanisms-and-treatment
#6
REVIEW
Maiken Cavling Arendrup, Thomas F Patterson
Invasive Candida infections remain an important cause of morbidity and mortality, especially in hospitalized and immunocompromised or critically ill patients. A limited number of antifungal agents from only a few drug classes are available to treat patients with these serious infections. Resistance can be either intrinsic or acquired. Resistance mechanisms are not exchanged between Candida; thus, acquired resistance either emerges in response to an antifungal selection pressure in the individual patient or, more rarely, occur due to horizontal transmission of resistant strains between patients...
August 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28911041/culture-independent-molecular-methods-for-detection-of-antifungal-resistance-mechanisms-and-fungal-identification
#7
David S Perlin, Nathan P Wiederhold
Resistance to azoles and echinocandins has emerged as a significant factor affecting the clinical management of patients with invasive fungal infections. Immunosuppressed patients at high risk for invasive fungal infections often have prolonged or repeated exposure to antifungals resulting in either the well-documented selection of naturally occurring, less susceptible fungal species, or the in situ development of specific resistance mechanisms. Nucleic acid-based molecular diagnostics are particularly well suited for the rapid detection of low-abundance fungal pathogens and identification of the infecting pathogen to the genus and species levels, as well as assessment of resistance mechanisms...
August 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28894103/the-candida-albicans-transcription-factor-cas5-couples-stress-responses-drug-resistance-and-cell-cycle-regulation
#8
Jinglin L Xie, Longguang Qin, Zhengqiang Miao, Ben T Grys, Jacinto De La Cruz Diaz, Kenneth Ting, Jonathan R Krieger, Jiefei Tong, Kaeling Tan, Michelle D Leach, Troy Ketela, Michael F Moran, Damian J Krysan, Charles Boone, Brenda J Andrews, Anna Selmecki, Koon Ho Wong, Nicole Robbins, Leah E Cowen
The capacity to coordinate environmental sensing with initiation of cellular responses underpins microbial survival and is crucial for virulence and stress responses in microbial pathogens. Here we define circuitry that enables the fungal pathogen Candida albicans to couple cell cycle dynamics with responses to cell wall stress induced by echinocandins, a front-line class of antifungal drugs. We discover that the C. albicans transcription factor Cas5 is crucial for proper cell cycle dynamics and responses to echinocandins, which inhibit β-1,3-glucan synthesis...
September 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28890395/the-antifungal-arsenal-alternative-drugs-and-future-targets
#9
Nathan P Wiederhold
Clinically available antifungals for the treatment of invasive fungal infections primarily target either ergosterol in the fungal cell membrane or 1,3-β-D-glucan in the fungal cell wall. These classes include the polyene amphotericin B, the triazoles, and the echinocandins. Although newer antifungals and improved formulations of others have advanced our ability to treat patients with invasive mycoses, these drugs are often limited by toxicities, drug interactions, and the need for intravenous administration...
September 7, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28882013/antimicrobial-management-in-nosocomial-peritonitis-microbiota-drug-and-time
#10
REVIEW
A Montero, P Salgado Aranda, F Gilsanz, E Maseda
Complicated intra-abdominal infection requires surgical treatment and broad-spectrum empiric antibiotic treatment used early. The rapid spread of multidrug-resistant bacteria has become a serious threat, especially in critical care units. The excessive use of carbapenems has led to carbapenemase-producing Enterobacteriaceae, leaving tigecycline and colistin as therapeutical options. The new antimicrobials, ceftazidime-avibactam and ceftolozane-tazobactam open new horizons in the treatment of multi-drug resistant Enterobacteriaceae...
September 2017: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
https://www.readbyqxmd.com/read/28882010/invasive-candidiasis-in-the-neutropenic-patient
#11
REVIEW
J Fortún, F Gioia
There are major differences in the epidemiology and prognosis of invasive candidiasis and candidemia in the neutropenic patient; however, a recent study performed in Spanish hospitals (Candipop) confirmed that mortality at 1 month is 30%, which is similar to that observed in the general population. Although Candida albicans is the most frequently isolated species, C. tropicalis, C. glabrata, and C. krusei are more prevalent than in non-neutropenic patients. The benefit of neutrophil transfusion is unclear, and catheter withdrawal must be tailored and based on confirmation of the diagnosis...
September 2017: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
https://www.readbyqxmd.com/read/28840541/drugs-in-clinical-development-for-fungal-infections
#12
Maria F Gonzalez-Lara, Jose Sifuentes-Osornio, Luis Ostrosky-Zeichner
Despite increasing rates of invasive fungal infections being reported globally, only a single antifungal drug has been approved during the last decade. Resistance, toxicity, drug interactions and restricted routes of administration remain unresolved issues. This review focuses on new antifungal compounds which are currently in various clinical phases of development. We discuss two azoles with a tetrazole moiety that allows selective activity against the fungal CYP: VT-1161 for Candida infections and VT-1129 for cryptococcal meningoencephalitis...
August 24, 2017: Drugs
https://www.readbyqxmd.com/read/28831086/potential-use-of-maldi-tof-mass-spectrometry-for-rapid-detection-of-antifungal-resistance-in-the-human-pathogen-candida-glabrata
#13
Antonietta Vella, Elena De Carolis, Enrica Mello, David S Perlin, Dominique Sanglard, Maurizio Sanguinetti, Brunella Posteraro
The echinocandins are relatively new antifungal drugs that represent, together with the older azoles, the recommended and/or preferred agents to treat candidaemia and other forms of invasive candidiasis in human patients. If "time is of the essence" to reduce the mortality for these infections, the administration of appropriate antifungal therapy could be accelerated by the timely reporting of laboratory test results. In this study, we attempted to validate a MALDI-ToF mass spectrometry-based assay for the antifungal susceptibility testing (AFST) of the potentially multidrug-resistant pathogen Candida glabrata against anidulafungin and fluconazole...
August 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28827419/antifungal-activity-of-scy-078-and-standard-antifungal-agents-against-178-clinical-isolates-of-resistant-and-susceptible-candida-species
#14
Wiley A Schell, A M Jones, Katyna Borroto-Esoda, Barbara D Alexander
SCY-078 in vitro activity was determined for 178 isolates of resistant and susceptible C. albicans, C. dubliniensis, C. glabrata, C. krusei, C. lusitaniae, and C. parapsilosis, including 44 Candida isolates having known genotypic (FKS1 or FKS2 mutations), phenotypic or clinical resistance to echinocandins. Results were compared to those for anidulafungin, caspofungin, micafungin, fluconazole and voriconazole. SCY-078 was shown to have excellent activity against both wild-type isolates and echinocandin- and azole-resistant isolates of Candida species...
August 21, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28827418/effects-of-echinocandins-in-combination-with-nikkomycin-z-against-invasive-candida-albicans-bloodstream-isolates-and-the-fks-mutants
#15
Yuk-Yam Cheung, Mamie Hui
The in vitro and in vivo effects of nikkomycin Z combined with an echinocandin (anidulafungin or micafungin) against two Candida albicans isolates and their lab-derived echinocandin-resistant fks mutants with FKS1 S645Y and FKS1 S645P were evaluated. Synergistic effects were observed in all tested strains (FICI < 0.5). Enhanced survival were observed in an immunocompromised murine model (log-rank test, P < 0.02). Our study demonstrated the therapeutic potential of nikkomycin Z-echinocandin combinations in managing echinocandin resistance...
August 21, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28826987/in-vitro-potency-and-fungicidal-activity-of-cd101-a-novel-echinocandin-against-recent-clinical-isolates-of-candida-spp
#16
Danielle Hall, Robert Bonifas, Lauretta Stapert, Mary Thwaites, Dean L Shinabarger, Chris M Pillar
Candida infections vary in severity and manifestation. Common infections include invasive bloodstream infections among hospitalized/immunocompromised patients and vulvovaginal candidiasis among women. Echinocandins and azoles are commonly utilized to treat Candida infections, although echinocandin use has been restricted to indications amenable to once-daily IV administration. CD101, a novel echinocandin with a long plasma half-life and enhanced stability, is in development for once-weekly IV administration for the treatment of candidemia and invasive candidiasis...
July 21, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28809155/microbe-profile-candida-albicans-a-shape-changing-opportunistic-pathogenic-fungus-of-humans
#17
Neil A R Gow, Bhawna Yadav
(a) Morphotypes of Candida albicans (blue sector, vegetative forms; pink sector, forms related to mating or changes in ploidy). Cell types shown include: budding yeast cells; elongated conjoined yeasts forming pseudohyphae; parallel-sided hyphae; chlamydospores formed from suspensor cells; enlarged goliath cells formed under zinc deprivation (unpublished study, image from Duncan Wilson); intestinal gut form cells (image from Suzanne Noble); mating competence defined by white-grey-opaque cell transitions (images from Guanghua Huang); elongated chemotactic shmoo-mating projections leading to tetraploid zygote formation (images from David Soll and Karla Daniels); trimera formed by unequal chromosome segregation under antifungal exposure (image from Judith Berman)...
August 15, 2017: Microbiology
https://www.readbyqxmd.com/read/28797491/candidemia-in-the-intensive-care-unit
#18
REVIEW
Oleg Epelbaum, Rachel Chasan
Candidemia presents several challenges to the intensive care unit (ICU) community. Recognition and treatment of this infection is frequently delayed, with dramatic clinical deterioration and death often preceding the detection of Candida in blood cultures. Identification of individual patients at the highest risk for developing candidemia remains an imperfect science; the role of antifungal therapy before culture diagnosis is yet to be fully defined in the ICU. The absence of well-established molecular techniques for early detection of candidemia hinders efforts to reduce the heavy clinical and economic impact of this infection...
September 2017: Clinics in Chest Medicine
https://www.readbyqxmd.com/read/28797484/overview-of-treatment-approaches-for-fungal-infections
#19
REVIEW
Eva M Carmona, Andrew H Limper
Invasive fungal diseases cause high morbidity and mortality in an immunocompromised host. Antifungals are the drugs of choice and can be divided into 4 main groups: polyenes, azoles, echinocandins, and pyrimidine analogues. Each class has its specific mechanism of action, spectrum of activity, and pharmacokinetic and side effects. It is important to understand the precise use of the established and new antifungal agents to successfully manage these complex infections in an already tenuous and frail host. This article discusses the main characteristics, clinical uses, and secondary effects of the main antifungals used in clinical practice...
September 2017: Clinics in Chest Medicine
https://www.readbyqxmd.com/read/28782390/treatment-of-pneumocystis-jirovecii-pneumonia-in-hiv-infected-patients-a-review
#20
Yu-Shan Huang, Jen-Jia Yang, Nan-Yao Lee, Guan-Jhou Chen, Wen-Chien Ko, Hsin-Yun Sun, Chien-Ching Hung
Pneumocystis pneumonia is a potentially life-threatening pulmonary infection that occurs in immunocompromised individuals and HIV-infected patients with a low CD4 cell count. Trimethoprim-sulfamethoxazole has been used as the first-line agent for treatment, but mutations within dihydropteroate synthase gene render potential resistance to sulfamide. Despite advances of combination antiretroviral therapy (cART), Pneumocystis pneumonia continues to occur in HIV-infected patients with late presentation for cART or virological and immunological failure after receiving cART...
September 2017: Expert Review of Anti-infective Therapy
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