has great intrinsic antimicrobial resistance limiting the number of effective antibiotics. Thus, other antimicrobial agents such as silver nanoparticles (AgNPs) are considered potential agents to ...help manage and prevent infections. AgNPs can be used in several applications against bacteria resistant to common antibiotics or even multi-resistant bacteria such as
. This study assessed the antimicrobial activity of commercial 10 nm AgNPs on two hospital strains of
resistant to a large number of antibiotics and a reference strain from a culture collection. All strains were susceptible to 5 µg/mL nanoparticles solution. Reference strains INCQS 0230 and P.a.1 were sensitive to AgNPs at concentrations of 1.25 and 0.156 µg/mL, respectively; however, this was not observed for hospital strain P.a.2, which was more resistant to all antibiotics and AgNPs tested. Cytotoxicity evaluation indicated that AgNPs, up to a concentration of 2.5 µg/mL, are very safe for all cell lines tested. At 5.0 µg/mL, AgNPs had a discrete cytotoxic effect on tumor cells HeLa and HepG2. Results showed the potential of using AgNPs as an alternative to conventional antimicrobial agents that are currently used, and a perspective for application of nanosilver with antibiotics to enhance antimicrobial activity.
Before Rosetta, the space missions Giotto and Stardust shaped our view on cometary dust, supported by plentiful data from Earth based observations and interplanetary dust particles collected in the ...Earth’s atmosphere. The Rosetta mission at comet 67P/Churyumov-Gerasimenko was equipped with a multitude of instruments designed to study cometary dust. While an abundant amount of data was presented in several individual papers, many focused on a dedicated measurement or topic. Different instruments, methods, and data sources provide different measurement parameters and potentially introduce different biases. This can be an advantage if the complementary aspect of such a complex data set can be exploited. However, it also poses a challenge in the comparison of results in the first place. The aim of this work therefore is to summarize dust results from Rosetta and before. We establish a simple classification as a common framework for intercomparison. This classification is based on the dust particle structure, porosity, and strength and also on its size. Depending on the instrumentation, these are not direct measurement parameters, but we chose them because they were the most reliable for deriving our model. The proposed classification has proved helpful in the Rosetta dust community, and we offer it here also for a broader context. In this manner, we hope to better identify synergies between different instruments and methods in the future.
Clinical breakpoints have not been established for mold testing. Wild-type (WT) MIC distributions (organisms in a species/drug combination with no detectable acquired resistance mechanisms) were ...defined in order to establish epidemiologic cutoff values (ECVs) for five Aspergillus spp. and itraconazole, posaconazole, and voriconazole. Also, we have expanded prior ECV data for Aspergillus fumigatus. The number of available isolates varied according to the species/triazole combination as follows: 1,684 to 2,815 for A. fumigatus, 323 to 592 for A. flavus, 131 to 143 for A. nidulans, 366 to 520 for A. niger, 330 to 462 for A. terreus, and 45 to 84 for A. versicolor. CLSI broth microdilution MIC data gathered in five independent laboratories in Europe and the United States were aggregated for the analyses. ECVs expressed in μg/ml were as follows (percentages of isolates for which MICs were equal to or less than the ECV are in parentheses): A. fumigatus, itraconazole, 1 (98.8%); posaconazole, 0.5 (99.2%); voriconazole, 1 (97.7%); A. flavus, itraconazole, 1 (99.6%); posaconazole, 0.25 (95%); voriconazole, 1 (98.1%); A. nidulans, itraconazole, 1 (95%); posaconazole, 1 (97.7%); voriconazole, 2 (99.3%); A. niger, itraconazole, 2 (100%); posaconazole, 0.5 (96.9%); voriconazole, 2 (99.4%); A. terreus, itraconazole, 1 (100%); posaconazole, 0.5 (99.7%); voriconazole, 1 (99.1%); A. versicolor, itraconazole, 2 (100%); posaconazole, 1 (not applicable); voriconazole, 2 (97.5%). Although ECVs do not predict therapy outcome as clinical breakpoints do, they may aid in detection of azole resistance (non-WT MIC) due to cyp51A mutations, a resistance mechanism in some Aspergillus spp. These ECVs should be considered for inclusion in the future CLSI M38-A2 document revision.
Members of the species-rich Fusarium solani species complex (FSSC) are responsible for approximately two-thirds all fusarioses of humans and other animals. In addition, many economically important ...phytopathogenic species are nested within this complex. Due to their increasing clinical relevance and because most of the human pathogenic and plant pathogenic FSSC lack Latin binomials, we have extended the multilocus haplotype nomenclatural system introduced in a previous study (D. C. Chang, G. B. Grant, K. O'Donnell, K. A. Wannemuehler, J. Noble-Wang, C. Y. Rao, L. M. Jacobson, C. S. Crowell, R. S. Sneed, F. M. T. Lewis, J. K. Schaffzin, M. A. Kainer, C. A. Genese, E. C. Alfonso, D. B. Jones, A. Srinivasan, S. K. Fridkin, and B. J. Park, JAMA 296:953-963, 2006) to all 34 species within the medically important FSSC clade 3 to facilitate global epidemiological studies. The typing scheme is based on polymorphisms in portions of the following three genes: the internal transcribed spacer region and domains D1 plus D2 of the nuclear large-subunit rRNA, the translation elongation factor 1 alpha gene (EF-1α), and the second largest subunit of RNA polymerase II gene (RPB2). Of the 251 isolates subjected to multilocus DNA sequence typing, 191 sequence types were differentiated, and these were distributed among three strongly supported clades designated 1, 2, and 3. All of the mycosis-associated isolates were restricted to FSSC clade 3, as previously reported (N. Zhang, K. O'Donnell, D. A. Sutton, F. A Nalim, R. C. Summerbell, A. A. Padhye, and D. M. Geiser, J. Clin. Microbiol. 44:2186-2190, 2006), and these represent at least 20 phylogenetically distinct species. Analyses of the combined DNA sequence data by use of two separate phylogenetic methods yielded the most robust hypothesis of evolutionary relationships and genetic diversity within the FSSC to date. The in vitro activities of 10 antifungals tested against 19 isolates representing 18 species that span the breadth of the FSSC phylogeny show that members of this complex are broadly resistant to these drugs.
Lenvatinib is a multi-kinase inhibitor approved for patients with radioactive iodine (RAI)–resistant differentiated thyroid cancer (DTC). Before the drug approval from the Italian National Regulatory ...Agency, a compassionate use programme has been run in Italy. This retrospective study aimed to analyse data from the first series of patients treated with lenvatinib in Italy.
The primary aim was to assess the response rate (RR) and progression-free survival (PFS). Secondary end-points include overall survival (OS) and toxicity data.
From November 2014 to September 2016, 94 patients were treated in 16 Italian sites. Seventeen percent of patients had one or more comorbidities, hypertension being the most common (60%). Ninety-eight percent of patients were treated by surgery, followed by RAI in 98% of cases. Sixty-four percent of patients received a previous systemic treatment. Lenvatinib was started at 24 mg in 64 subjects. Partial response and stable disease were observed in 36% and in 41% of subjects, respectively; progression was recorded in 14% of patients. Drug-related side-effects were common; the most common were fatigue (13.6%) and hypertension (11.6%). Overall, median PFS and OS were 10.8 months (95% confidence interval CI, 7.7–12.6) and 23.8 months (95% CI, 19.7–25.0) respectively.
Lenvatinib is active and safe in unselected, RAI-refractory, progressive DTC patients in real-life setting. RR and PFS seem to be less favourable than those observed in the SELECT trial, likely due to a negative selection that included heavily pretreated patients or with poor performance status.
•Patients with metastatic differentiated thyroid cancer (DTC) have poor survival rate.•Lenvatinib improved clinical outcomes in patient with metastatic radioactive iodine-refractory DTC.•Lenvatinib is active and safe, even in a real-life patient population.•Older patients show survival benefit from lenvatinib, without safety concern.
Several members of the order Mucorales (subphylum Mucoromycotina) are important agents of severe human infections. The identification of these fungi by using standard mycologic methods is often ...difficult and time consuming. Frequently, the etiological agent in clinical cases is reported either as a Mucor sp., which is not the most frequent genus of zygomycetes, or only as a member of the MUCORALES: For this reason, the actual spectrum of species of zygomycetes and their incidences in the clinical setting is not well known. The goals of this study were to compare the results of the molecular identification of an important set of clinical isolates, received in a mycological reference center from different regions of the United States, with those obtained by using the traditional morphological methods and to determine the spectrum of species involved. We tested 190 isolates morphologically identified as zygomycetes by using sequencing of the internal transcribed spacer (ITS) region of the ribosomal DNA. Molecular identification revealed that Rhizopus oryzae represented approximately half (44.7%) of these isolates. The remainder was identified as Rhizopus microsporus (22.1%), Mucor circinelloides (9.5%), Mycocladus corymbifer (formerly Absidia corymbifera) (5.3%), Rhizomucor pusillus (3.7%), Cunninghamella bertholletiae (3.2%), Mucor indicus (2.6%), Cunninghamella echinulata (1%), and Apophysomyces elegans (0.5%). The most common anatomic sites for clinically significant zygomycetes, as determined by isolates sent to the Fungus Testing Laboratory for identification and/or susceptibility testing and included in this study, were the sinuses, lungs, and various cutaneous locations, at 25.8%, 26.8%, and 28%, respectively. These sites represented approximately 80% of the isolates evaluated. A high level of correlation (92.6%) between morphological and molecular identifications was found.
Some species in the polyphyletic fungal genus Acremonium are important opportunist pathogens. Determining the actual spectrum of species and their incidence in the clinical setting, however, has long ...been hampered because of the difficulties encountered in phenotypic species-level identification. The goal of this study was to re-identify a large number of clinical isolates morphologically and to confirm the identifications by comparing sequences of the internal transcribed spacer region of the rRNA gene of these isolates to those of type or reference strains of well-known Acremonium species. Of the 119 isolates referred to a United States reference laboratory under the name Acremonium, only 75 were identified morphologically as belonging to that genus. The remainder (44 isolates) were identified as belonging to other morphologically similar genera. The Acremonium clinical isolates were related to species of Hypocreales, Sordariales, and of an incertae sedis family of ascomycetes, Plectosphaerellaceae. A total of 50 of the 75 Acremonium isolates (67%) could be identified by molecular means, the prevalent species being Acremonium kiliense (15 isolates), A. sclerotigenum-A. egyptiacum (11 isolates), A. implicatum (7 isolates), A. persicinum (7 isolates), and A. atrogriseum (4 isolates). One of the most interesting findings of our study was that we identified several species among this large collection of clinical isolates that had not previously been reported from human infections, and we failed to confirm other Acremonium species, such as A. potronii, A. recifei, and A. strictum, that had been considered significant. The most common anatomic sites for Acremonium isolates were the respiratory tract (41.3%), nails (10.7%), and the eye (9.3%). Antifungal susceptibility testing demonstrated high MICs for all agents tested, except for terbinafine. Since numerous isolates could not be identified, we concluded that the list of opportunistic Acremonium species is far from be complete and that a considerable number of additional species will be discovered.
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