Search

Infections due to the Aspergillus species constitute an important challenge for human health. Invasive aspergillosis represents a life-threatening disease, mostly in patients with immune defects. Drugs used for fungal infections comprise amphotericin B, triazoles, and echinocandins. However, in the last decade, an increased emergence of azole-resistant Aspergillus strains has been reported, principally belonging to Aspergillus fumigatus species. Therefore, both the early diagnosis of aspergillosis and its epidemiological surveillance are very important to establish the correct antifungal therapy and to ensure a successful patient outcome. In this paper, a literature review is performed to analyze the prevalence of Aspergillus antifungal resistance in European countries. Amphotericin B resistance is observed in 2.6% and 10.8% of Aspergillus fumigatus isolates in Denmark and Greece, respectively. A prevalence of 84% of amphotericin B-resistant Aspergillus flavus isolates is reported in France, followed by 49.4%, 35.1%, 21.7%, and 20% in Spain, Portugal, Greece, and amphotericin B resistance of Aspergillus niger isolates is observed in Greece and Belgium with a prevalence of 75% and 12.8%, respectively. The prevalence of triazole resistance of Aspergillus fumigatus isolates, the most studied mold obtained from the included studies, is 0.3% in Austria, 1% in Greece, 1.2% in Switzerland, 2.1% in France, 3.9% in Portugal, 4.9% in Italy, 5.3% in Germany, 6.1% in Denmark, 7.4% in Spain, 8.3% in Belgium, 11% in the Netherlands, and 13.2% in the United Kingdom. The mechanism of resistance is mainly driven by the TR 34 /L98H mutation. In Europe, no in vivo resistance is reported for echinocandins. Future studies are needed to implement the knowledge on the spread of drug-resistant Aspergillus spp. with the aim of defining optimal treatment strategies.

Cefiderocol is a new siderophore cephalosporin that is effective against multidrug-resistant Gram-negative bacteria, including carbapenem-resistant strains. The aim of this study was to evaluate the activity of this new antimicrobial agent against a collection of pathogens using broth microdilution assays and to analyze the possible mechanism of cefiderocol resistance in two resistant Klebsiella pneumoniae isolates. One hundred and ten isolates were tested, comprising 67 Enterobacterales , two Acinetobacter baumannii , one Achromobacter xylosoxidans , 33 Pseudomonas aeruginosa and seven Stenotrophomonas maltophilia. Cefiderocol showed good in vitro activity, with an MIC < 2 μg/mL, and was able to inhibit 94% of the tested isolates. We observed a resistance rate of 6%. The resistant isolates consisted of six Klebsiella pneumoniae and one Escherichia coli , leading to a resistance rate of 10.4% among the Enterobacterales. Whole-genome sequencing analysis was performed on two cefiderocol-resistant Klebsiella pneumoniae isolates to investigate the possible mutations responsible for the observed resistance. Both strains belonged to ST383 and harbored different resistant and virulence genes. The analysis of genes involved in iron uptake and transport showed the presence of different mutations located in fhu A, fep A, iut A, cir A, sit C, apb C, fep G, fep C, fet B, yic I, yic J, and yic L. Furthermore, for the first time, to the best of our knowledge, we described two Klebsiella pneumoniae isolates that synthesize a truncated fecA protein due to the transition from G to A, leading to a premature stop codon in the amino acid position 569, and a TonB protein carrying a 4-amino acid insertion (PKPK) after Lysine 103. In conclusion, our data show that cefiderocol is an effective drug against multidrug-resistant Gram-negative bacteria. However, the higher resistance rate observed in Enterobacterales underlines the need for active surveillance to limit the spread of these pathogens and to avoid the risks associated with the emergence of resistance to new drugs.

Europe has faced a massive spread of the varicella-zoster virus through the years. Since the introduction of an effective vaccine, complications and severe forms of chickenpox have been restricted. Nevertheless, among the population, some categories need specific care, such as pregnant women, who present one of the most fragile conditions facing this infection, both for the mother and the fetus. In this review, we highlight how the varicella-zoster virus can be dangerous during pregnancy, underlining the problem of treatment and vaccination, and collect information about the European epidemiology among this particular category of women.

Psoriasis and inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are interlinked. In fact, the prevalence of IBD is higher in patients with psoriasis, with a risk of ulcerative colitis of 1.6-times higher than in the general population. Analogously, patients with psoriasis have a greater risk of developing IBD. Furthermore, they share some clinical features and pathogenic mechanisms. Both are chronic inflammatory diseases with a relapsing-remitting condition that persists for the patient's whole life and exhibit increased permeability of the mucosal barrier of skin and gut, allowing an increased interaction of pathogens with inflammatory receptors of the immune cells. A key element in the pathogenesis of these diseases is represented by the microbiota; in particular, the gut microbiota is an important driver of CD pathogenesis, while in psoriasis changes in gut and skin microbiota have been described without a defined pathogenic function. Furthermore, genetic predispositions or environmental factors contribute to disease manifestation, with a central role attributed to the immune responses and, in particular, to a dysregulated role played by T helper 17 cells both in psoriasis and IBD. The purpose of this review was to summarize present information about the links between psoriasis, inflammatory bowel disease, in particular Crohn's disease, and changes in gut and/or skin microbiome.

Saprochaete capitata is an arthroconidial yeast, found principally in the environment, even if it belongs also to the normal microbial flora that colonize human subjects. This yeast is increasingly associated with invasive infections in hematological patients, in particular in those affected by acute leukemia. An important risk factor that predisposes to this infection is the profound neutropenia present in such immunocompromised patients. Saprochaete spp. were found resistant to both echinocandins and fluconazole so the treatment is often difficult. Here, we report two cases of sepsis in two patients with acute leukemia. All of them had fatal events, due to the worsening of their clinical condition. An early diagnosis and appropriate management of these pathogens is important in consideration of the poor prognosis associated to these fungal invasive infections.

HIV-1 diversity is increasing in European countries due to immigration flows, as well as travels and human mobility, leading to the circulation of both new viral subtypes and new recombinant forms, with important implications for public health. We analyzed 710 HIV-1 sequences comprising protease and reverse-transcriptase (PR/RT) coding regions, sampled from 2011 to 2017, from naive patients in Spedali Civili Hospital, Brescia, Italy. Subtyping was performed by using a combination of different tools; the phylogenetic analysis with a structured coalescence model and Makarov Chain Monte Carlo was used on the datasets, to determine clusters and evolution. We detected 304 (43%) patients infected with HIV-1 non-B variants, of which only 293 sequences were available, with four pure subtypes and five recombinant forms; subtype F1 (17%) and CRF02&#95;AG (51.1%) were most common. Twenty-five transmission clusters were identified, three of which included >10 patients, belonging to subtype CRF02&#95;AG and subtype F. Most cases of alleged transmission were between heterosexual couples. Probably due to strong migratory flows, we have identified different subtypes with particular patterns of recombination or, as in the case of the subtype G (18/293, 6.1%), to a complete lack of relationship between the sequenced strains, revealing that they are all singletons. Continued HIV molecular surveillance is most important to analyze the dynamics of the boost of transmission clusters in order to implement public health interventions aimed at controlling the HIV epidemic., Competing Interests: The authors declare no conflicts of interest.