Clinical Implications of Azole Resistance in Aspergillus fumigatus, the Netherlands, 2007-2009

Contains fulltext : 95722.pdf (publisher's version ) (Open Access)The prevalence and spread of azole resistance in clinical Aspergillus fumigatus isolates in the Netherlands are currently unknown. Therefore, we performed a prospective nationwide multicenter surveillance study to determine the effects of resistance on patient management strategies and public health. From June 2007 through January 2009, all clinical Aspergillus spp. isolates were screened for itraconazole resistance. In total, 2,062 isolates from 1,385 patients were screened; the prevalence of itraconazole resistance in A. fumigatus in our patient cohort was 5.3% (range 0.8%-9.5%). Patients with a hematologic or oncologic disease were more likely to harbor an azole-resistant isolate than were other patient groups (p<0.05). Most patients (64.0%) from whom a resistant isolate was identified were azole naive, and the case-fatality rate of patients with azole-resistant invasive aspergillosis was 88.0%. Our study found that multiazole resistance in A. fumigatus is widespread in the Netherlands and is associated with a high death rate for patients with invasive aspergillosis

Anerkennung von Bürgerschaftlichem Engagement - Eine Analyse am Beispiel der Stadt Stuttgart

Bürgerschaftliches Engagement ist eine tragende Säule in unserer Gesellschaft. Bürgerinnen und Bürger, die sich aktiv in das Gemeinwesen einbringen und demokratische und soziale Strukturen mit Leben erfüllen, sind das Fundament unserer Gesellschaft. Wir leben alle von denjenigen, die sich über das gewöhnliche Maß hinaus in das gesellschaftliche Leben einbringen. Um dieses Fundament nicht zu beschädigen, bedarf es öffentlicher und politischer Anerkennung sowie intensiver Förderung und Unterstützung. Zur Engagementkultur gehört auch immer eine Anerkennungskultur. Es muss immer wieder darauf hingewiesen werden, dass nicht nur die bezahlte Erwerbsarbeit viel wert ist, sondern dass vor allem das unbezahlte Bürgerschaftliche Engagement Anerkennung verdient. Daher handelt diese Arbeit von der Anerkennungskultur von Bürgerschaftlichem Engagement am Beispiel der Stadt Stuttgart

Influence of photoperiod and sex on locomotor behavior of meadow voles (Microtus pennsylvanicus) in an automated light-dark 'anxiety' test

This study examined the influence of photoperiod on affective behavior (anxiety) of adult male and female meadow voles (Microtus pennsylvanicus), maintained in either a long or short day photoperiod, when tested in an automated (VersaMax) light-dark test. The light-dark test is based on an innate aversion of rodents to novel, brightly illuminated spaces and has been used with laboratory raised species, such as mice, to assess anxiety and/or fear related behaviors. Male and female meadow voles, housed either in a long day (LD: 16h light) or short day (SD: 8h light) photoperiod, were tested in the light-dark apparatus for 30 min on 3 consecutive days. All animals spent significantly (p<0.001) less time in the brightly lit chamber (900 lux) than in the dark chamber. LD voles, especially females, spent significantly less time in the brightly lit area than did SD voles. Both horizontal and vertical movements occurred less frequently per unit time in the dark area relative to the light, but only in the LD voles. LD female voles were the least active group in the dark area on the first test day but the most active group in the light area, despite spending the least amount of time in this area on the second and third test days. The present results show that LD voles exhibit more anxiety related behaviors in this test situation than do SD voles. LD females avoided the brightly lit area the most, particularly when the apparatus was novel. Thus, both photoperiod and sex influence situation-based anxiety in this species. These findings suggest that meadow voles are an excellent animal model in which to examine the role of gonadal hormones, and their modulation of defence related neural systems, in the induction of anxiety.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83869/1/influence_of_photoperiod_and_sex.pd

Efficacy of serology driven “test and treat strategy” for eradication of H. pylori in patients with rheumatic disease in the Netherlands

The treatment of choice of H. pylori infections is a 7-day triple-therapy with a proton pump inhibitor (PPI) plus amoxicillin and either clarithromycin or metronidazole, depending on local antibiotic resistance rates. The data on efficacy of eradication therapy in a group of rheumatology patients on long-term NSAID therapy are reported here. This study was part of a nationwide, multicenter RCT that took place in 2000–2002 in the Netherlands. Patients who tested positive for H. pylori IgG antibodies were included and randomly assigned to either eradication PPI-triple therapy or placebo. After completion, follow-up at 3 months was done by endoscopy and biopsies were sent for culture and histology. In the eradication group 13% (20/152, 95% CI 9–20%) and in the placebo group 79% (123/155, 95% CI 72–85%) of the patients were H. pylori positive by histology or culture. H. pylori was successfully eradicated in 91% of the patients who were fully compliant to therapy, compared to 50% of those who were not (difference of 41%; 95% CI 18–63%). Resistance percentages found in isolates of the placebo group were: 4% to clarithromycin, 19% to metronidazole, 1% to amoxicillin and 2% to tetracycline

Efficacy of Two Triple Eradication Regimens in Children with Helicobacter pylori Infection

Triple therapy with bismuth subsalicylate, amoxicillin, metronidazole (BAM) or with omeprazole, amoxicillin, clarithromycin (OAC) has been commonly used for the eradication of Helicobacter pylori infection. We compared the efficacy of these triple therapies in children with H. pylori infection. We retrospectively analyzed results in 233 children with H. pylori infection and treated with OAC (n=141) or BAM (n=92). Overall eradication rates of triple therapy with OAC and BAM were 74% and 85%, respectively, which showed no statistical difference. Our study showed that the triple therapy with BAM was more effective for the first-line eradication of H. pylori infection in Korean children, but has no statistical difference with OAC regimen

Pharmacological validation of individual animal locomotion, temperature and behavioural analysis in group-housed rats using a novel automated home cage analysis system: A comparison with the modified Irwin test

Background: The ActualHCA™ system continuously monitors the activity, temperature and behavior of group-housed rats without invasive surgery. The system was validated to detect the contrasting effects of sedative and stimulant test agents (chlorpromazine, clonidine and amphetamine), and compared with the modified Irwin test (mIT) with rectal temperature measurements. Methods: Six male Han Wistar rats per group were used to assess each test agent and vehicle controls in separate ActualHCA™ recordings and mIT. The mIT was undertaken at 15, 30 mins, 1, 2, 4 and 24 h post-dose. ActualHCA™ recorded continuously for 24 h post-dose under 3 experimental conditions: dosed during light phase, dark phase, and light phase with a scheduled cage change at the time of peak effects determined by mIT.Results: ActualHCA™ detected an increase stimulated activity from the cage change at 1-2 h post-dose which was obliterated by chlorpromazine and clonidine. Amphetamine increased activity up to 4 h post-dose in all conditions. Temperature from ActualHCA™ was affected by all test agents in all conditions. The mIT showed effects on all 3 test agents up to 4 h post-dose, with maximal effects at 1-2 h post-dose. The maximal effects on temperature from ActualHCA™ differed from mIT. Delayed effects on activity were detected by ActualHCA™, but not on mIT.Conclusions: Continuous monitoring has the advantage of capturing effects over time that may be missed with manual tests using pre-determined time points. This automated behavioural system does not replace the need for conventional methods but could be implemented simultaneously to improve our understanding of behavioural pharmacology

Analysis of antimicrobial susceptibility and virulence factors in Helicobacter pylori clinical isolates

BACKGROUND: In this study, we evaluated the prevalence of primary resistance of Brazilian H. pylori isolates to metronidazole, clarithromycin, amoxicillin, tetracycline, and furazolidone. In addition, the vacA, iceA, cagA and cagE genotypes of strains isolated from Brazilian patients were determined and associated with clinical data in an effort to correlate these four virulence markers and antibiotic resistance. METHODS: H. pylori was cultured in 155 H. pylori-positive patients and MICs for metronidazole, clarithromycin, amoxicillin, tetracycline, and furazolidone were determined by the agar dilution method. Genomic DNA was extracted, and allelic variants of vacA, iceA, cagA and cagE were identified by the polymerase chain reaction. RESULTS: There was a strong association between the vacA s1/cagA -positive genotype and peptic ulcer disease (OR = 5.42, 95% CI 2.6–11.3, p = 0.0006). Additionally, infection by more virulent strains may protect against GERD, since logistic regression showed a negative association between the more virulent strain, vacA s1/cagA-positive genotype and GERD (OR = 0.26, 95% CI 0.08–0.8, p = 0.03). Resistance to metronidazole was detected in 75 patients (55%), to amoxicillin in 54 individuals (38%), to clarithromycin in 23 patients (16%), to tetracycline in 13 patients (9%), and to furazolidone in 19 individuals (13%). No significant correlation between pathogenicity and resistance or susceptibility was detected when MIC values for each antibiotic were compared with different vacA, iceA, cagA and cagE genotypes. CONCLUSION: The analysis of virulence genes revealed a specific association between H. pylori strains and clinical outcome, furthermore, no significant association was detected among pathogenicity and resistance or susceptibility