We analyzed the species distribution of Candida blood isolates (CBIs), prospectively collected between 2004 and 2009 within FUNGINOS, and compared their antifungal susceptibility according to ...clinical breakpoints defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in 2013, and the Clinical and Laboratory Standards Institute (CLSI) in 2008 (old CLSI breakpoints) and 2012 (new CLSI breakpoints). CBIs were tested for susceptiblity to fluconazole, voriconazole and caspofungin by microtitre broth dilution (Sensititre® YeastOne™ test panel). Of 1090 CBIs, 675 (61.9%) were C. albicans, 191 (17.5%) C. glabrata, 64 (5.9%) C. tropicalis, 59 (5.4%) C. parapsilosis, 33 (3%) C. dubliniensis, 22 (2%) C. krusei and 46 (4.2%) rare Candida species. Independently of the breakpoints applied, C. albicans was almost uniformly (>98%) susceptible to all three antifungal agents. In contrast, the proportions of fluconazole- and voriconazole-susceptible C. tropicalis and F-susceptible C. parapsilosis were lower according to EUCAST/new CLSI breakpoints than to the old CLSI breakpoints. For caspofungin, non-susceptibility occurred mainly in C. krusei (63.3%) and C. glabrata (9.4%). Nine isolates (five C. tropicalis, three C. albicans and one C. parapsilosis) were cross-resistant to azoles according to EUCAST breakpoints, compared with three isolates (two C. albicans and one C. tropicalis) according to new and two (2 C. albicans) according to old CLSI breakpoints. Four species (C. albicans, C. glabrata, C. tropicalis and C. parapsilosis) represented >90% of all CBIs. In vitro resistance to fluconazole, voriconazole and caspofungin was rare among C. albicans, but an increase of non-susceptibile isolates was observed among C. tropicalis/C. parapsilosis for the azoles and C. glabrata/C. krusei for caspofungin according to EUCAST and new CLSI breakpoints compared with old CLSI breakpoints.
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BFBNIB, DOBA, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UKNU, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Background
The increasing incidence of candidemia and emergence of drug-resistant Candida species are major concerns worldwide. Long-term surveillance studies are needed.
Methods
The Fungal ...Infection Network of Switzerland (FUNGINOS) conducted a 15-year (2004–2018), nationwide, epidemiological study of candidemia. Hospital-based incidence of candidemia, Candida species distribution, antifungal susceptibility, and consumption were stratified in 3 periods (2004–2008, 2009–2013, 2014–2018). Population-based incidence over the period 2009–2018 derived from the Swiss Antibiotic Resistance Surveillance System (ANRESIS).
Results
A total of 2273 Candida blood isolates were studied. Population and hospital-based annual incidence of candidemia increased from 2.96 to 4.20/100 000 inhabitants (P = .022) and 0.86 to 0.99/10 000 patient-days (P = .124), respectively. The proportion of Candida albicans decreased significantly from 60% to 53% (P = .0023), whereas Candida glabrata increased from 18% to 27% (P < .0001). Other non-albicans Candida species remained stable. Candida glabrata bloodstream infections occurred predominantly in the age group 18–40 and above 65 years. A higher proportional increase of C glabrata was recorded in wards (18% to 29%, P < .0001) versus intensive care units (19% to 24%, P = .22). According to Clinical and Laboratory Standards Institute, nonsusceptibility to fluconazole in C albicans was observed in 1% of isolates, and anidulafungin and micafungin nonsusceptibility was observed in 2% of C albicans and C glabrata. Fluconazole consumption, the most frequently used antifungal, remained stable, whereas use of mold-active triazoles and echinocandins increased significantly in the last decade (P < .0001).
Conclusions
Over the 15-year period, the incidence of candidemia increased. A species shift toward C glabrata was recently observed, concurring with increased consumption of mold-active triazoles.
The incidence of candidemia increased in Switzerland from 2004 to 2018. A species shift toward C glabrata was observed after 2013, now accounting for one fourth of all candidemia, concurring with increased consumption of mold-active triazoles.
•FUNGINOS conducted a nationwide prospective study of candidemia in Switzerland.•Breakthrough candidemia (BTC) occurred in 8% of 567 consecutive candidemias.•BTC was observed in hemato-oncological ...patients with gastrointestinal mucositis.•Prolonged low-dose fluconazole prophylaxis was associated with non-susceptible BTC.•Severity of infection and mortality were not increased in BTC compared to non-BTC.
Breakthrough candidemia (BTC) on fluconazole was associated with non-susceptible Candida spp. and increased mortality. This nationwide FUNGINOS study analyzed clinical and mycological BTC characteristics.
A 3-year prospective study was conducted in 567 consecutive candidemias. Species identification and antifungal susceptibility testing (CLSI) were performed in the FUNGINOS reference laboratory. Data were analyzed according to STROBE criteria.
43/576 (8%) BTC occurred: 37/43 (86%) on fluconazole (28 prophylaxis, median 200 mg/day). 21% BTC vs. 23% non-BTC presented severe sepsis/septic shock. Overall mortality was 34% vs. 32%. BTC was associated with gastrointestinal mucositis (multivariate OR 5.25, 95%CI 2.23–12.40, p < 0.001) and graft-versus-host-disease (6.25, 1.00–38.87, p = 0.05), immunosuppression (2.42, 1.03–5.68, p = 0.043), and parenteral nutrition (2.87, 1.44–5.71, p = 0.003). Non-albicans Candida were isolated in 58% BTC vs. 35% non-BTC (p = 0.005). 63% of 16 BTC occurring after 10-day fluconazole were non-susceptible (Candida glabrata, Candida krusei, Candida norvegensis) vs. 19% of 21 BTC (C. glabrata) following shorter exposure (7.10, 1.60–31.30, p = 0.007). Median fluconazole MIC was 4 mg/l vs. 0.25 mg/l (p < 0.001). Ten-day fluconazole exposure predicted non-susceptible BTC with 73% accuracy.
Outcomes of BTC and non-BTC were similar. Fluconazole non-susceptible BTC occurred in three out of four cases after prolonged low-dose prophylaxis. This implies reassessment of prophylaxis duration and rapid de-escalation of empirical therapy in BTC after short fluconazole exposure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Summary Objectives Human studies on the role of mannose-binding lectin (MBL) in patients with invasive candidiasis have yielded conflicting results. We investigated the influence of MBL and other ...lectin pathway proteins on Candida colonization and intra-abdominal candidiasis (IAC) in a cohort of high-risk patients. Methods Prospective observational cohort study of 89 high-risk intensive-care unit (ICU) patients. Levels of lectin pathway proteins at study entry and six MBL2 single-nucleotide polymorphisms were analyzed by sandwich-type immunoassays and genotyping, respectively, and correlated with development of heavy Candida colonization (corrected colonization index (CCI) ≥0.4) and occurrence of IAC during a 4-week period. Results Within 4 weeks after inclusion a CCI ≥0.4 and IAC was observed in 47% and 38% of patients respectively. Neither serum levels of MBL, ficolin-1, -2, -3, MASP-2 or collectin liver 1 nor MBL2 genotypes were associated with a CCI ≥0.4. Similarly, none of the analyzed proteins was found to be associated with IAC with the exception of lower MBL levels (HR 0.74, p = 0.02) at study entry. However, there was no association of MBL deficiency (<0.5 μg/ml), MBL2 haplo- or genotypes with IAC. Conclusion Lectin pathway protein levels and MBL2 genotype investigated in this study were not associated with heavy Candida colonization or IAC in a cohort of high-risk ICU patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The prevalence of symptomatic CD in Switzerland is thought to be 1 in 1,000 inhabitants. As in other countries, oligo- and asymptomatic CD is being diagnosed with increasing frequency in all age ...groups.
To assess the prevalence of asymptomatic CD in adolescents in eastern Switzerland.
Between September 1999 and July 2000 total serum IgA titres, anti-endomysium IgA (EMA) titres and anti-human tissue transglutaminase IgA (hTTG) titres were measured in the serum of healthy 11- to 18-year-old Swiss lower and upper secondary school students.
Of the 1,450 students (871 f = 60.1%, CI 95%) tested, 11 (10 f) had elevated levels of both EMA and TTG. The diagnosis of CD was confirmed in eight of these students by mucosal jejunal morphology (Marsh III); one exhibited normal histology. Two of the 11 students refused to undergo mucosal biopsy. None of the students, however, had symptoms suggestive of CD, nor were they stunted or underweight, and none of them had family members with known CD. All of the eight students with enteropathy went on a glutenfree diet and felt subjectively better than on a normal diet. Of the remaining students, 38 (2.6%) had family members with known CD. None of those with the relevant family history had elevated EMA or TTG levels.
Asymptomatic CD is common. It occurs in 1 in 132 (0.75%) Swiss adolescents. The absence of subjectively recognisable symptoms suggestive of family history or other risk factors makes it difficult to diagnose this type of CD.
In a recent article, Hussain et al. evaluated a commercial latex agglutination test (LA), the MRSA-Screen (Denka Seiken Co., Niigata, Japan), for rapid detection of penicillin-binding protein 2a ...(PBP2a) in mecA-positive and mecA-negative coagulase-negative staphylococci (CNS). The sensitivity and specificity were 100 and 99.5%, respectively, although the MRSA-Screen was initially developed for rapid detection of PBP2a in methicillin-resistant Staphylococcus aureus (MRSA). However, this was a retrospective study with selected CNS strains. Furthermore, they used oxacillin-induced colonies for the LA since without induction only 72 (57.6%) of 125 mecA-positive CNS gave a positive result and additionally required an extended reaction time, i.e., 3 to 15 min, for agglutination.
Background: Public health authorities want to evaluate their sexually transmitted disease (STD) surveillance systems to promote the most effective use of health resources. Goal: The goal of this ...study was to estimate the sensitivity of national laboratory reports of Chlamydia trachomatis in Switzerland (the proportion of cases detected by national laboratory reports). Study Design: A cross sectional prevalence study was conducted by the Swiss Sentinel Surveillance Network of Gynecologists in 1998. Two groups of women aged less than 35 years were included in the study: those having a first consultation for pregnancy and those having a routine check-up. Results: A total of 1589 women were tested for C trachomatis. The prevalence among pregnant women (n = 817) was 1.3%, and that among sexually active women (n = 772) was 2.8%. Using the prevalences observed among check-up women, we estimate that there were at least 24,400 C trachomatis infections in Switzerland among women aged 20 to 34 years in 1998 (95% CI: 14,300-34,300). The number of labo-ratory reports of C trachomatis in this age group was 1150 in 1998. Conclusion: Our study suggests that the sensitivity of national laboratory reports of C trachomatis in 1998 was less than 5% for women aged 20 to 34 years.
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