Jerina Boelens

Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial

Background Patients with severe asthma are at increased risk of exacerbations and lower respiratory tract infections (LRTI). Severe asthma is heterogeneous, encompassing eosinophilic and non-eosinophilic (mainly neutrophilic) phenotypes. Patients with neutropilic airway diseases may benefit from macrolides. Methods We performed a randomised double-blind placebo-controlled trial in subjects with exacerbation-prone severe asthma. Subjects received low-dose azithromycin (n=55) or placebo (n=54) as add-on treatment to combination therapy of inhaled corticosteroids and long-acting β2 agonists for 6 months. The primary outcome was the rate of severe exacerbations and LRTI requiring treatment with antibiotics during the 26-week treatment phase. Secondary efficacy outcomes included lung function and scores on the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ). Results The rate of primary endpoints (PEPs) during 6 months was not significantly different between the two treatment groups: 0.75 PEPs (95% CI 0.55 to 1.01) per subject in the azithromycin group versus 0.81 PEPs (95% CI 0.61 to 1.09) in the placebo group (p=0.682). In a predefined subgroup analysis according to the inflammatory phenotype, azithromycin was associated with a significantly lower PEP rate than placebo in subjects with non-eosinophilic severe asthma (blood eosinophilia ≤200/µl): 0.44 PEPs (95% CI 0.25 to 0.78) versus 1.03 PEPs (95% CI 0.72 to 1.48) (p=0.013). Azithromycin significantly improved the AQLQ score but there were no significant between-group differences in the ACQ score or lung function. Azithromycin was well tolerated, but was associated with increased oropharyngeal carriage of macrolide-resistant streptococci. Conclusions Azithromycin did not reduce the rate of severe exacerbations and LRTI in patients with severe asthma. However, the significant reduction in the PEP rate in azithromycin-treated patients with non-eosinophilic severe asthma warrants further study. ClinicalTrials.gov number NCT00760838.

Nationwide Surveillance of Azole Resistance in Aspergillus Diseases

ABSTRACT Aspergillus disease affects a broad patient population, from patients with asthma to immunocompromised patients. Azole resistance has been increasingly reported in both clinical and environmental Aspergillus strains. The prevalence and clinical impact of azole resistance in different patient populations are currently unclear. This 1-year prospective multicenter cohort study aimed to provide detailed epidemiological data on Aspergillus resistance among patients with Aspergillus disease in Belgium. Isolates were prospectively collected in 18 hospitals (April 2011 to April 2012) for susceptibility testing. Clinical and treatment data were collected with a questionnaire. The outcome was evaluated to 1 year after a patients inclusion. A total of 220 Aspergillus isolates from 182 patients were included. The underlying conditions included invasive aspergillosis (n = 122 patients), allergic bronchopulmonary aspergillosis (APBA) (n = 39 patients), chronic pulmonary aspergillosis (n = 10 patients), Aspergillus bronchitis (n = 7 patients), and aspergilloma (n = 5 patients). The overall azole resistance prevalence was 5.5% (95% confidence interval [CI] 2.8 to 10.2%) and was 7.0% (4/57; 95% CI, 2.3 to 17.2%) in patients with APBA, bronchitis, aspergilloma, or chronic aspergillosis and 4.6% in patients with invasive aspergillosis (5/108; 95% CI, 1.7 to 10.7%). The 6-week survival in invasive aspergillosis was 52.5%, while susceptibility testing revealed azole resistance in only 2/58 of the deceased patients. The clinical impact of Aspergillus fumigatus resistance was limited in our patient population with Aspergillus diseases.

Healthcare-associated bloodstream infections in a neonatal intensive care unit over a 20-year period (1992-2011) : trends in incidence, pathogens, and mortality

OBJECTIVE To analyze trends in the incidence and pathogen distribution of healthcare-associated bloodstream infections (HABSIs) over a 20-year period (1992-2011). DESIGN Historical cohort study. SETTING Thirty-two-bed neonatal intensive care unit (NICU) in a tertiary referral hospital. PATIENTS Neonates with HABSIs defined according to the criteria of the National Institute of Child Health and Development (NICHD). METHODS A hospital-based ongoing surveillance program was used to identify HABSI cases in neonates. A distinction between definite or possible HABSI was made according to the NICHD criteria. Incidence, incidence densities (HABSIs per 1,000 hospital-days and HABSIs per 1,000 total parenteral nutrition-days), and case fatality rate were calculated. Logistic regression analysis was used to find time trends. Four periods of 5 years were considered when executing variance analysis. RESULTS In total, 682 episodes of HABSIs occurred on 9,934 admissions (6.9%). The median total incidence density rate was 3.1 (interquartile range, 2.2-3.9). A significant increasing time trend in incidence density was observed for the period 1995-2011 (P < .003). A significant decrease in the case fatality rate was found in the last 5-year period (P < .001). No neonate died following possible HABSIs, whereas the case fatality rate among neonates with definite HABSIs was 9.7%. Most HABSIs were caused by coagulase-negative staphylococci (n = 414 [60.7%]). A significant increase in Staphylococcus aureus HABSI was observed in the last 10-year period (P < .001). CONCLUSIONS An increase in incidence density rate occurred, while the case fatality rate dropped. Better perinatal care could be responsible for the latter. A decrease in days before infection and a high incidence of coagulase-negative Staphylococcus HABSIs indicate the need for vigorous application of evidence-based prevention initiatives, in particular for catheter care.

Edwardsiella tarda sepsis in a live-stranded sperm whale (Physeter macrocephalus).

Whale strandings remain poorly understood, although bacterial infections have been suggested to contribute. We isolated Edwardsiella tarda from the blood of a stranded sperm whale. The pathogen was identified with MALDI-TOF MS, confirmed by 16S rRNA gene sequencing and quantified in blood by qPCR. We report the first case of sepsis in a sperm whale. The zoonotic potential of E. tarda and the possible role of bacterial infections in the enigmatic strandings of cetaceans are discussed.

Steroid effects on ZAP-70 and SYK in relation to apoptosis in poor prognosis chronic lymphocytic leukemia

There is resurgent interest in glucocorticoids (GCs) in the treatment of poor prognosis chronic lymphocytic leukemia (CLL). Little is known however on how GCs induce apoptosis in CLL. Methylprednisolone (MP) induces apoptosis in ZAP-70 positive CLL more readily than in ZAP-70 negative CLL, which is in contrast to the effects of radiation and chemotherapy. The increased GC sensitivity of ZAP-70+ CLL was studied in relation to the expression status of ZAP-70 and the related signal transducing tyrosine kinase SYK. Both ZAP-70 and SYK were downregulated by GC treatment. Moreover, SYK was dephosphorylated by the phosphatase PTP1B of which the expression and translation levels were induced by GCs. Inhibition of PTP1B successfully restored ZAP-70 expression and SYK phosphorylation but did not interfere with GC-induced apoptosis. Therefore, the downregulation of ZAP-70 and P-SYK per se during treatment with GCs is not sufficient to induce apoptosis, and different mechanisms must therefore be responsible for the increased steroid sensitivity of ZAP-70+ CLL.

Assessment of faecal microbial transfer in irritable bowel syndrome with severe bloating

We read with interest the work by Halmos et al 1 in which they describe the effects of dietary FODMAP (Fermentable Oligo-, Di- and Mono- saccharides And Polyols) restriction in patients with IBS on the intestinal microbiota. They showed that low FODMAP intake was associated with reduced total bacterial and lower relative abundance of butyrate-producing Clostridium cluster XIVa, changes that are generally considered unfavourable.2 Therefore, they discourage long-term dietary FODMAP restriction, a suggestion also supported by the recent work of McIntosh and colleagues who noticed unfavourable changes in both microbiota and metabolome of patients with IBS who were on a low FODMAP diet.3 Although low FODMAP intake reduces GI symptoms in almost 75% of patients with IBS, the effects of this diet on the intestinal microbiota might be disadvantageous in the long run. Combining these observations with the important role for the intestinal microbiota in IBS pathogenesis,4 we report here faecal microbiota transplantation (FMT) as an alternative to FODMAP restriction in patients with IBS. We applied FMT in 12 refractory IBS patients (Rome III criteria) with intermittent diarrhoea and severe bloating, …

Microbial etiology and antimicrobial resistance in healthcare-associated versus community-acquired and hospital-acquired bloodstream infection in a tertiary care hospital

Infections that occur in patients with significant exposure to the nosocomial environment while they reside in the community are currently classified separately as healthcare-associated infections. In this retrospective study, conducted at Ghent University Hospital between January 1, 2009, and May 31, 2011, we compared microbial characteristics of healthcare-associated bloodstream infection (HCAB) with that of community-acquired bloodstream infection (CAB) and hospital-acquired bloodstream infection (HAB). Three hundred eighty-six pathogens isolated from patients with HCAB were compared with 141 and 605 pathogens identified in patients with CAB and HAB, respectively. HCAB was associated with a distinct pathogen profile and with an antimicrobial susceptibility pattern different from that of other categories of bloodstream infection. We conclude that the concept of HCAB provides guidance in the choice of empirical antibiotic therapy but should be translated according to local epidemiology.

Implementation of a multidisciplinary infectious diseases team in a tertiary hospital within an Antimicrobial Stewardship Program

Abstract Background: In January 2011, as part of an antimicrobial stewardship program the Antimicrobial Management Team (AMT) at the Ghent University Hospital initiated a multidisciplinary Infectious Diseases Team (MIT) consisting of infectious diseases physicians, clinical microbiologists, and clinical pharmacists. The aim of this study is to describe the type and acceptance rate of recommendations provided by the MIT. Method: Prospective, observational study in a tertiary care, university teaching hospital with 1062 beds in non-consecutive hospitalized adult patients, excluding intensive care units and paediatrics. Results: The MIT communicated 432 recommendations in 87 days observed. Of the 293 patients for whom a recommendation was made, the median age was 57 years (range: 16–91 years) and 169 (57·7%) were male. Skin or soft tissue infections (14%), respiratory tract infections (13%), infections without known focus (11%), abdominal infections (11%), and bone infections (8%) were most common. Recommendations were made to perform additional clinical investigation(s) [N = 137 (27%)], to adjust the dose of an antimicrobial drug [N = 42 (8%)], to stop an antimicrobial drug [N = 104 (21%)], to switch from a parenteral to an oral drug [N = 39 (8%)] or to initiate an antimicrobial drug [N = 178 (36%)], with an acceptance rate of 73·0%, 83·3%, 81·7%, 76·9%, and 84·0%, respectively. Conclusions: The MIT formulated about five recommendations a day primarily focusing on pharmacotherapy, but also on clinical investigations. In both fields, a high acceptance rate was observed.

Surveillance of Endoscopes: Comparison of Different Sampling Techniques

OBJECTIVE To compare different techniques of endoscope sampling to assess residual bacterial contamination. DESIGN Diagnostic study. SETTING The endoscopy unit of an 1,100-bed university hospital performing ~13,000 endoscopic procedures annually. METHODS In total, 4 sampling techniques, combining flushing fluid with or without a commercial endoscope brush, were compared in an endoscope model. Based on these results, sterile physiological saline flushing with or without PULL THRU brush was selected for evaluation on 40 flexible endoscopes by adenosine triphosphate (ATP) measurement and bacterial culture. Acceptance criteria from the French National guideline (<25 colony-forming units [CFU] per endoscope and absence of indicator microorganisms) were used as part of the evaluation. RESULTS On biofilm-coated PTFE tubes, physiological saline in combination with a PULL THRU brush generated higher mean ATP values (2,579 relative light units [RLU]) compared with saline alone (1,436 RLU; P=.047). In the endoscope samples, culture yield using saline plus the PULL THRU (mean, 43 CFU; range, 1–400 CFU) was significantly higher than that of saline alone (mean, 17 CFU; range, 0–500 CFU; P<.001). In samples obtained using the saline+PULL THRU brush method, ATP values of samples classified as unacceptable were significantly higher than those of samples classified as acceptable (P=.001). CONCLUSION Physiological saline flushing combined with PULL THRU brush to sample endoscopes generated higher ATP values and increased the yield of microbial surveillance culture. Consequently, the acceptance rate of endoscopes based on a defined CFU limit was significantly lower when the saline+PULL THRU method was used instead of saline alone. Infect Control Hosp Epidemiol 2017;38:1062–1069

ER stress in diffuse large B cell lymphoma: GRP94 is a possible biomarker in germinal center versus activated B-cell type

The process of B-cell development is characterized by the activation of the unfolded protein response. Under certain circumstances, the unfolded protein response can be manipulated in a cell death-inducing way. Therefore, tackling the unfolded protein response might be an attractive strategy in the treatment of diffuse large B-cell lymphomas. Our research showed more basal unfolded protein response activity and differences in the inducibility of ER stress in activated B-cell versus germinal center cell lines. Moreover, the diffuse large B cell lymphoma patient data revealed that the glucose-regulated protein 94 is new potential discriminator for diffuse large B cell lymphoma.