Selma Tobudic

The clinical outcomes and safety of dalbavancin as primary and sequential treatment of gram-positive bacteremia with infective endocarditis were evaluated retrospectively. The clinical success rate was high (92.6%), but in 24 of 27 patients dalbavancin was used only after clearance of bacteria from the bloodstream.

Candida albicans are the most common fungi associated with biofilm-related infections. Biofilms are defined as microbial communities encased in a matrix of extracellular polymeric substances. The most important feature of biofilm growth is the high resistance to antimicrobial agents that can be up to 1000-fold greater than that of planktonic cells. This review discusses the factors affecting antifungal resistance as well as activity of mono- and combination therapy of different antifungal classes and antifungal activity in vitro and in vivo against C. albicans biofilms.

OBJECTIVES: The aim of the present study was to evaluate the in vitro activity and synergism of the combinations of amphotericin B/caspofungin and amphotericin B/posaconazole against Candida albicans, grown either as planktonic cells or in biofilms. METHODS: Ten C. albicans bloodstream isolates used in this study were collected from intensive care patients admitted to the Vienna University Hospital between 2006 and 2007. Chequerboard tests were employed to determine the efficacy of the antifungal combinations amphotericin B/caspofungin and amphotericin B/posaconazole against both planktonic cells and biofilms. C. albicans biofilms were prepared using the static microtitre plate model. The activity of antifungal combination therapy was determined by visual reading for planktonic cells and using the XTT assay for biofilms. RESULTS: For Candida biofilms the median MIC was 4 mg/L for amphotericin B and caspofungin, and >256 mg/L for posaconazole. The combination amphotericin B/posaconazole yielded synergism [fractional inhibitory concentration index (FICI) <0.26], whereas amphotericin B/caspofungin yielded indifferent interaction only (FICI 0.75-1.25) against all isolates when grown in biofilms. Under planktonic conditions, synergism was demonstrable for the combination amphotericin B/caspofungin against 4 of the 10 isolates, whereas the combination of caspofungin/posaconazole was indifferent against all tested isolates. CONCLUSIONS: We showed that MICs for planktonic and biofilm forms of C. albicans were much lower when treated with an antifungal combination than when treated with single agents. The combination of amphotericin B/posaconazole yielded synergism against Candida biofilms, whereas amphotericin B/caspofungin yielded indifferent interaction.

BACKGROUND: Allogeneic hematopoietic stem cell transplant (HSCT) recipients experience an increased risk for invasive fungal diseases (IFDs). METHODS: This retrospective cohort study at the Medical University of Vienna aspired to assess the incidence, characteristics and the outcome of IFDs as well as the associated risk factors in a setting where only 43 % of patients were given systemic antifungal prophylaxis during aplasia. IFDs were classified as probable or proven according to the EORTC/MSG consensus group. All adult patients (n = 242) receiving an allogeneic HSCT at the University Hospital of Vienna from January 2009 to December 2013 were enrolled. RESULTS: The primary outcome of this study was the one-year incidence for IFDs after HSCT, which was 10.3 % (25/242). Overall 28 patients experienced an IFD - 20 probable and 8 proven - with invasive aspergillosis being the predominant IFD (n = 18), followed by invasive candidiasis (n = 7) and pneumocystis pneumonia (n = 3). Patients with an IFD were more likely to be admitted to an intensive care unit (64 % versus 12 %, p < 0.0001) and had a significantly higher mortality in the first year after HSCT (48 % versus 25 %, p = 0.02). Multivariate regression analysis revealed that intensified immunosuppressive therapy (high-dose cortisone and basiliximab or etanercept) because of severe graft-versus-host disease (adjusted odds ratio (AOR) 3.6, p = 0.01) and transplant-associated microangiopathy (AOR 3.7, p = 0.04) were associated with an increased risk for IFD, while antifungal prophylaxis given during aplasia and post-engraftment was associated with a decreased risk (AOR 0.3, p = 0.02). CONCLUSIONS: We documented a one-year incidence for IFDs of 10.3 % and no selection of rare pathogens at a centre with moderate use of antifungal prophylaxis. Intensified immunosuppressive therapy and transplant-associated microangiopathy were significant risk factors for IFDs.