Primary antifungal prophylaxis with micafungin in patients with haematological malignancies: real-life data from a retrospective single-centre observational study.

Mould-active antifungal prophylaxis is increasingly used in patients at risk for invasive fungal disease. Between June 2011 and June 2012, one hundred patients with various haematological malignancies at risk for invasive fungal disease received primary antifungal prophylaxis with intravenous micafungin at a daily dosage of 50 mg during neutropenia. The median number of days on micafungin prophylaxis was 14 (range, 6-48 d).

Incidence of Cyp51 A key mutations in Aspergillus fumigatus-a study on primary clinical samples of immunocompromised patients in the period of 1995-2013.

As the incidence of azole resistance in Aspergillus fumigatus is rising and the diagnosis of invasive aspergillosis (IA) in immunocompromised patients is rarely based on positive culture yield, we screened our Aspergillus DNA sample collection for the occurrence of azole resistance mediating cyp51 A key mutations. Using two established, a modified and a novel polymerase chain reaction (PCR) assays followed by DNA sequence analysis to detect the most frequent mutations in the A. fumigatus cyp51 A gene conferring azole resistance (TR34 (tandem repeat), L98H and M220 alterations).

Platelet immunology in fungal infections.

Up to date, perception of platelets has changed from key players in coagulation to multitaskers within the immune network, connecting its most diverse elements and crucially shaping their interplay with invading pathogens such as fungi. In addition, antimicrobial effector molecules and mechanisms in platelets enable a direct inhibitory effect on fungi, thus completing their immune capacity. To precisely assess the impact of platelets on the course of invasive fungal infections is complicated by some critical parameters.

Assessing micafungin/triazole combinations for the treatment of invasive scedosporiosis due to Scedosporium apiospermum and Scedosporium boydii.

Objectives: Scedosporium infections are associated with high therapeutic failure rates. Combination therapy may be an alternative approach to improve outcome. The in vitro and in vivo efficacy of micafungin plus posaconazole or plus voriconazole was investigated herein.

Laboratory diagnosis of mucormycosis: current status and future perspectives.

Fungal infections caused by members of the Mucorales order are rapidly progressing and fatal. The importance of mucormycosis has grown in recent years as the number of patients with predisposing factors has increased dramatically. Clinical symptoms are elusive and conventional techniques are often insensitive and unspecific; in particular, cultures are often negative even though direct microscopy is positive.

Bronchoalveolar lavage lateral-flow device test for invasive pulmonary aspergillosis in solid organ transplant patients: a semiprospective multicenter study.

Background: Invasive pulmonary aspergillosis (IPA) remains an important cause of morbidity and mortality among patients undergoing solid organ transplantation (SOT). Because of the crude mortality of 80% to 90% in the absence of adequate treatment, timely diagnosis and early intervention with antifungal drugs are key factors in the successful treatment of IPA. Diagnosis, however, remains difficult.

Computed tomography guided percutaneous lung biopsies and suspected fungal infections in pediatric cancer patients.

Background: The spectrum of potential fungal pathogens known to cause invasive pulmonary infections has grown as a result of intensified immunosuppressive therapy and the emergence of antifungal resistance.

Procedure: In a retrospective single center study, we investigated computed tomography guided percutaneous lung biopsies in 16 childhood patients with suspected fungal infections. Microbiological analysis consisted of microscopic examination, culture, and a broad-range fungal polymerase chain reaction for detection of either Aspergillus or Mucorales species.

In vitro antifungal susceptibility of Candida glabrata to caspofungin and the presence of FKS mutations correlate with treatment response in an immunocompromised murine model of invasive infection.

It has been argued that the in vitro activity of caspofungin (CSP) is not a good predictor of the outcome of echinocandin treatment in vivo. We evaluated the in vitro activity of CSP and the presence of FKS mutations in the hot spot 1 (HS1) region of the FKS1 and FKS2 genes in 17 Candida glabrata strains with a wide range of MICs. The efficacy of CSP against systemic infections from each of the 17 strains was evaluated in a murine model.

Risk assessment of transfusion-associated babesiosis in Tyrol: appraisal by seroepidemiology and polymerase chain reaction.

Background: After malaria, babesiosis is the second most common transfusion-transmitted parasitic disease in the United States. In Europe, one reported transfusion case, concerning Babesia microti, occurred in Germany.

Study Design And Methods: Due to the fact that Babesia spp.

Breakpoints for antifungal agents: an update from EUCAST focussing on echinocandins against Candida spp. and triazoles against Aspergillus spp.

Candida and Aspergillus infections have emerged as significant pathogens in recent decades. During this same time, broad spectrum triazole and echinocandin antifungal agents have been developed and increasingly used. One consequence of widespread use is leading to the emergence of mutants with acquired resistance mutations.

Why is biopsy of suspected fungal lung lesions necessary?

The recognition of antifungal resistance is necessary for the choice of the appropriate treatment in patients with invasive fungal disease. In this case report, the need for a computed tomography-guided percutaneous lung biopsy of a suspected fungal lesion in a patient treated for acute leukemia is demonstrated. Detection of Amphothericin-B resistant Aspergillus flavus infection has prompted the switch in antifungal therapy, followed by full resolution of symptoms, completion of chemotherapy and remission since then.

EUCAST technical note on Candida and micafungin, anidulafungin and fluconazole.

The European Committee on Antimicrobial Susceptibility Testing Subcommittee on Antifungal Susceptibility Testing has determined breakpoints for micafungin and revised breakpoints for anidulafungin and fluconazole for Candida spp. This Technical Note is based on the corresponding rationale documents (http://www.eucast.

Platelets as immune cells in infectious diseases.

Platelets have been shown to cover a broad range of functions. Besides their role in hemostasis, they have immunological functions and thus participate in the interaction between pathogens and host defense. Platelets have a broad repertoire of receptor molecules that enable them to sense invading pathogens and infection-induced inflammation.

Hypoxia promotes danger-mediated inflammation via receptor for advanced glycation end products in cystic fibrosis.

Rationale: Hypoxia regulates the inflammatory-antiinflammatory balance by the receptor for advanced glycation end products (RAGE), a versatile sensor of damage-associated molecular patterns. The multiligand nature of RAGE places this receptor in the midst of chronic inflammatory diseases.

Objectives: To characterize the impact of the hypoxia-RAGE pathway on pathogenic airway inflammation preventing effective pathogen clearance in cystic fibrosis (CF) and elucidate the potential role of this danger signal in pathogenesis and therapy of lung inflammation.

Immune reconstitution syndrome-like entity in lung transplant recipients with invasive aspergillosis.

Background: Incidence, characteristics, and risk-factors for invasive aspergillosis (IA)-associated immune reconstitution syndrome (IRS) in lung transplant recipients are not known.

Methods: Patients comprised 68 lung transplant recipients with proven/probable IA followed for 12 months. IRS was defined based on previously proposed criteria.

Determination of isavuconazole susceptibility of Aspergillus and Candida species by the EUCAST method.

Isavuconazole is a novel expanded-spectrum triazole, which has recently been approved by the FDA as an orphan drug to treat invasive aspergillosis and is currently being studied in phase III clinical trials for invasive candidiasis. The susceptibility of relatively few clinical isolates has been reported. In this study, the isavuconazole susceptibilities of 1,237 Aspergillus and 2,010 Candida geographically diverse clinical isolates were determined by EUCAST methodology at four European mycology laboratories, producing the largest multicenter data set thus far for this compound.

Rep-PCR and RAPD-PCR fingerprinting of Aspergillus terreus.

We compared two PCR methods for molecular typing the medically important filamentous fungus Aspergillus terreus. In a set of 46 strains investigated we found 19 and 12 different fingerprinting types obtained by random amplified polymorphic DNA PCR (RAPD) and semi-automated repetitive element PCR (rep-PCR), respectively.

Virulence and thrombocyte affectation of two Aspergillus terreus isolates differing in amphotericin B susceptibility.

Aspergillus terreus-induced invasive infections exhibit high lethality, partly due to the intrinsic resistance for amphotericin B (AmB). We compared the virulence and pathogenesis of an AmB-resistant isolate of A. terreus (ATR) with that of a rare variant showing enhanced sensitivity for AMB (ATS).

Clinical-scale generation of multi-specific anti-fungal T cells targeting Candida, Aspergillus and mucormycetes.

Background Aims: Invasive fungal infections, in particular, infections caused by Candida, Aspergillus and mucormycetes, are a major cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation. Adoptive transfer of donor-derived anti-fungal T cells shows promise to restore immunity and to offer a cure. Because T cells recognize only specific epitopes, the low rate of patients in which the causal fungal pathogen can be identified and the considerable number of patients with co-infection with several genera or species of fungi significantly limit the application of adoptive immunotherapy.

Risk factors and outcomes in lung transplant recipients with nodular invasive pulmonary aspergillosis.

Background: Whether nodular lesions have specific risk-factors or influence outcomes in lung transplant recipients with invasive aspergillosis, is not fully known.

Methods: The study population consisted of 64 consecutive lung transplant recipients with proven or probable invasive aspergillosis. Nodules, with or without halo/air crescent-sign were considered nodular presentations.

The Mediterranean red alga Asparagopsis taxiformis has antifungal activity against Aspergillus species.

The red algae Asparagopsis taxiformis collected from the Straits of Messina (Italy) were screened for antifungal activity against Aspergillus species. EUCAST methodology was applied and extracts showed antifungal activity against A. fumigatus, A.

Minireview: host defence in invasive aspergillosis.

Aspergillus is a saprophytic fungus, which mainly becomes pathogenic in immunosuppressed hosts. A failure of host defences results in a diverse set of illnesses, ranging from chronic colonisation, aspergilloma, invasive disease and hypersensitivity. A key concept in immune responses to Aspergillus species is that host susceptibility determines the morphological form, antigenic structure and physical location of the fungus.