See Covering the Cover synopsis on page 1225. BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is recommended for treatment of recurrent Clostridium difficile infection (rCDI). We performed a single-center randomized trial to compare the effects of FMT with those of fidaxomicin and vancomycin. METHODS: We studied consecutive adults with rCDI seen at a gastroenterology clinic in Denmark from April 5, 2016 through June 10, 2018. Patients were randomly assigned to a group that received FMT, applied by colonoscopy or nasojejunal tube, after 4-10 days of vancomycin (125 mg 4 times daily; FMTv; n ¼ 24), 10 days of fidaxomicin (200 mg twice daily; n ¼ 24), or 10 days of vancomycin (125 mg 4 times daily; n ¼ 16). Patients who had rCDI after this course of treatment and patients who could not be randomly assigned to groups were offered rescue FMTv. The primary outcome was combined clinical resolution and a negative result from a polymerase chain reaction test for Clostridium difficile (CD) toxin 8 weeks after the allocated treatment. Secondary end points included clinical resolution at week 8. RESULTS: All 64 patients received their assigned treatment. The combination of clinical resolution and negative results from the test for CD were observed in 17 patients given FMTv (71%), 8 patients given fidaxomicin (33%), and 3 patients given vancomycin (19%; P ¼ .009 for FMTv vs fidaxomicin; P ¼ .001 for FMTv vs vancomycin; P ¼ .31 for fidaxomicin vs vancomycin). Clinical resolution was observed in 22 patients given FMTv (92%), 10 patients given fidaxomicin (42%), and 3 patients given vancomycin (19%; P ¼ .0002; P < .0001; P ¼ .13). Results did not differ significantly between patients who received FMTv as their initial therapy and patients who received rescue FMTv. There was 1 serious adverse event that might have been related to FMTv. CONCLUSIONS: In a randomized trial of patients with rCDI, we found the FMTv combination superior to fidaxomicin or vancomycin based on end points of clinical and microbiological resolution or clinical resolution alone. ClinicalTrials.gov, number NCT02743234; EudraCT, j.no 2015-003004-24.

Significant changes in the management of fungaemia have occurred over the last decade with increased use of fluconazole prophylaxis, of empirical treatment and of echinocandins as first-line agents for documented disease. These changes may impact the epidemiology of fungaemia. We present nationwide data for Denmark from 2010 to 2011. A total of 1081 isolates from 1047 episodes were recorded in 995 patients. The numbers of patients, episodes and recovered isolates increased by 13.1%, 14.5% and 14.1%, respectively, from 2010 to 2011. The incidence rate was significantly higher in 2011 (10.05/100 000) than in 2010 (8.82/100 000), but remained constant in the age groups 0-79 years. The incidence rate was highest at the extremes of age and in males. Candida albicans accounted for 52.1% but declined during 2004-11 (p 0.0155). Candida glabrata accounted for 28% and increased during 2004-2011 (p <0.0001). Candida krusei, Candida tropicalis and Candida parapsilosis remained rare (3.3-4.2%). The species distribution changed with increasing age (fewer C. parapsilosis and more C. glabrata) and by study centre. Overall, the susceptibility rates were: amphotericin B 97.3%, anidulafungin 93.8%, fluconazole 66.7%, itraconazole 69.6%, posaconazole 64.2% and voriconazole 85.0%. Acquired echinocandin resistance was molecularly confirmed in three isolates. The use of systemic antifungals doubled over the last decade (2002-2011) (from 717 000 to 1 450 000 defined daily doses/year) of which the vast majority (96.9%) were azoles. The incidence of fungaemia continues to increase in Denmark and is associated with a decreasing proportion being susceptible to fluconazole. Changes in demography, higher incidence in the elderly and higher antifungal consumption can at least in part explain the changes.

New data from the years 2012 to 2015 from the Danish National Fungemia Surveillance are reported, and epidemiological trends are investigated in a 12-year perspective (2004 to 2015). During 2012 to 2015, 1,900 of 1,939 (98%) fungal bloodstream isolates were included. The average incidence was 8.4/100,000 inhabitants, and this appears to represent a stabilizing trend after the increase to 10.1/100,000 in 2011. The incidence was higher in males than females (10.0 versus 6.8) and in patients above 50 years, and those changes were mainly driven by an increasing incidence among 80-to-89-year-old males (65.3/100,000 in 2014 to 2015). The proportion of isolates decreased from 2004 to 2015 (64.4% to 42.4%) in parallel with a doubling of the proportion of isolates (16.5% to 34.6%, < 0.0001). was more common among females (34.0% versus 30.4% in males). Following an increase in 2004 to 2011, the annual drug use stabilized during the last 2 to 3 years of that time period but remained higher than in other Nordic countries. This was particularly true for the fluconazole and itraconazole use in the primary health care sector, which exceeded the combined national levels of use of these compounds in each of the other Nordic countries. Fluconazole susceptibility decreased (68.5%, 65.2%, and 60.6% in 2004 to 2007, 2008 to 2011, and 2012 to 2015, respectively, < 0.0001), and echinocandin resistance emerged in (0%, 0.6%, and 1.7%, respectively, < 0.001). Amphotericin B susceptibility remained high (98.7%). Among 16 (2.7%) echinocandin-resistant isolates (2012 to 2015), 13 harbored FKS mutations and 5 (31%) were multidrug resistant. The epidemiological changes and the increased incidence of intrinsic and acquired resistance emphasize the importance of continued surveillance and of strengthened focus on antifungal stewardship.

The enormous interindividual variation in the plasma concentrations of the atherogenic lipoprotein(a) [Lp(a)] is almost entirely controlled by the apo(a) locus on chromosome 6q26-q27. A variable number of transcribed kringle4 repeats (K4-VNTR) in the gene explains a large fraction of this variation, whereas the rest is presently unexplained. We here have analyzed the effect of the K4-VNTR and of a pentanucleotide repeat polymorphism (TTTTA)n (n = 6-11) in the 5' control region of the apo(a) gene on plasma Lp(a) levels in unrelated healthy Tyroleans (n = 130), Danes (n = 154), and Black South Africans (n = 112). The K4-VNTR had a significant effect on plasma Lp(a) levels in Caucasians and explained 41 and 45% of the variation in Lp(a) plasma concentration in Tyroleans and Danes, respectively.Both, the pentanucleotide repeat (PNR) allele frequencies and their effects on Lp(a) concentrations were heterogeneous among populations. A significant negative correlation between the number of pentanucleotide repeats and the plasma Lp(a) concentration was observed in Tyroleans and Danes. The effect of the 5' PNRP on plasma Lp(a) concentrations was independent from the K4-VNTR and explained from 10 to 14% of the variation in Lp(a) concentrations in Caucasians. No significant effect of the PNRP was present in Black Africans. This suggests allelic association between PNR alleles and sequences affecting Lp(a) levels in Caucasians. Thus, in Caucasians but not in Blacks, concentrations of the atherogenic Lp(a) particle are strongly associated with two repeat polymorphisms in the apo(a) gene. (J. Clin. Invest. 1995. 96:150-157.)

This study emphasizes the importance of infection control measures to limit transmission of VREfm between patients. However, the diversity of the VREfm isolates points to the fact that other important factors may also affect the VREfm increase in Denmark. Finally, WGS is suitable for typing of VREfm and has replaced PFGE for typing of VREfm in Denmark.