No association of complement mannose-binding lectin deficiency with cardiovascular disease in patients with Systemic Lupus Erythematosus.

Cardiovascular (CV) morbidity is the major cause of death in patients with Systemic Lupus Erythematosus (SLE). Previous studies on mannose-binding lectin (MBL) gene polymorphisms in SLE patients suggest that low levels of complement MBL are associated with cardiovascular disease (CVD). However, as large studies on MBL deficiency based on resulting MBL plasma concentrations are lacking, the aim of our study was to analyze the association of MBL concentrations with CVD in SLE patients. Plasma MBL levels SLE patients included in the Swiss SLE Cohort Study were quantified by ELISA. Five different CV organ manifestations were documented. Of 373 included patients (85.5% female) 62 patients had at least one CV manifestation. Patients with MBL deficiency (levels below 500 ng/ml or 1000 ng/ml) had no significantly increased frequency of CVD (19.4% vs. 15.2%, P = 0.3 or 17.7% vs. 15.7%, P = 0.7). After adjustment for traditional CV risk factors, MBL levels and positive antiphospholipid serology (APL+) a significant association of CVD with age, hypertension, disease duration and APL+ was demonstrated. In our study of a large cohort of patients with SLE, we could not confirm previous studies suggesting MBL deficiency to be associated with an increased risk for CVD.

Evaluation of existing and desired antimicrobial stewardship activities and strategies in Swiss hospitals.

Antimicrobial stewardship (AMS) is an important component in the fight against antimicrobial resistance. Currently, few hospitals have an ongoing institutional AMS programme. Swissnoso - the national centre for infection prevention - has launched a national Swiss AMS initiative supported by the office of public health. To guide AMS priorities and resources, current AMS activities in Switzerland were assessed. We distributed an internet-based questionnaire directed mainly to board-certified infectious diseases specialists and, if not available, senior internal medicine staff. Responses were received from 63/134 hospitals surveyed. More than 90% were in favour of national treatment guidelines currently in development under the umbrella of the Swiss society for infectious diseases. Many AMS activities - such as antimicrobial formulary restrictions and approval systems, review of antimicrobial prescriptions with point of care intervention, and direct feedback or therapeutic drug monitoring - are currently lacking in the majority of Swiss hospitals surveyed. Development of a modular formal AMS standard for Swiss hospitals may aid in advancing current AMS strategies and in introducing AMS programmes in Switzerland. In combination with the surveillance of antimicrobial use and resistance by ANRESIS, the national antimicrobial resistance surveillance system, this approach may reduce the use of antimicrobial agents and consequently the risk of emergence of multi-resistant pathogens.

Impact of MALDI-TOF-MS-based identification directly from positive blood cultures on patient management: a controlled clinical trial.

OBJECTIVES: Rapid identification of pathogens directly from positive blood cultures (BC) in combination with an antimicrobial stewardship programme (ASP) is associated with improved antibiotic treatment and outcomes, but the effect of each individual intervention is less clear. The current study investigated the impact of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) versus conventional identification on antibiotic management in a setting with a well-established ASP and low resistance rates. METHODS: In this single-centre open label, controlled clinical trial 425 patients with positive BCs were allocated by weekday during a 1-year period to either MALDI-TOF directly from positive BCs or conventional processing. ASP was identical throughout the study period. The primary outcome was duration of intravenous antimicrobial therapy and was analysed in an intention-to-treat approach. RESULTS: In all, 368 patients were analysed (MALDI-TOF n = 168; conventional n = 200) with similar baseline characteristics. Mean duration of intravenous antimicrobial therapy (12.9 versus 13.2 days, p 0.9) and length of stay (16.1 versus 17.9 days, p 0.3) were comparable. In the clinically significant bloodstream infection subgroup (n = 242) mean time from Gram-stain to active treatment was significantly shorter (3.7 versus 6.7 h, p 0.003). Admission to the intensive care unit after bloodstream infection onset was less frequent in the MALDI-TOF group (23.1 versus 37.2%, p 0.02). CONCLUSIONS: Rapid identification of contaminated BCs (n = 126) resulted in a shorter duration of intravenous antimicrobial therapy (mean 4.8 versus 7.5 days, p 0.04). Rapid identification using MALDI-TOF directly from positive BCs did not impact on duration of intravenous antimicrobial therapy, but provided fast and reliable microbiological results and may improve treatment quality in the setting of an established ASP.

Louse-borne relapsing fever (Borrelia recurrentis) in an Eritrean refugee arriving in Switzerland, August 2015.

We report an imported case of louse-borne relapsing fever in a young adult Eritrean refugee who presented with fever shortly after arriving in Switzerland. Analysis of blood smears revealed spirochetes identified as Borrelia recurrentis by 16S rRNA gene sequencing. We believe that louse-borne relapsing fever may be seen more frequently in Europe as a consequence of a recent increase in refugees from East Africa travelling to Europe under poor hygienic conditions in confined spaces.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) directly from positive blood culture flasks allows rapid identification of bloodstream infections in immunosuppressed hosts.

INTRODUCTION: In immunosuppressed hosts, rapid identification of microorganisms of bloodstream infections is crucial to ensuring effective antimicrobial therapy. Conventional culture requires up to 72 h from sample collection to pathogen identification. METHODS: We used the SepsiTyper Kit and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF; Microflex, Bruker) directly from positive blood culture (BacT/ALERT 3D, FN/FA vials; bioMérieux) in comparison to standard culture methodology (VITEK 2; bioMérieux) for species identification. RESULTS: A total of 62 consecutive positive blood cultures from immunosuppressed patients (solid organ or hematopoietic transplant recipients, or with febrile neutropenia) were analyzed. Culture yielded gram-negative bacteria (GNB) in 27/62 (43.5%) and gram-positive (GPB) in 35/62 (56.5%) vials. For GNB, the predominant species identified by MALDI-TOF and confirmed by VITEK were Escherichia coli (16/16 correctly identified) and Enterobacter cloacae (4/4), with a sensitivity and specificity of 92.6% and 100%, respectively. For GPB, predominant species were Staphylococcus aureus (3/3), coagulase-negative staphylococci (12/24), and Enterococcus faecium (6/6) with a sensitivity of 100%, 60%, and 100%, respectively. The median time from blood collection to species identification was 27.4 h with MALDI-TOF identification and 46.6 h with conventional methodology. CONCLUSION: Using MALDI-TOF directly from positive blood cultures allowed a shorter time to identification with high sensitivity and specificity in immunosuppressed patients.

[Weight loss and chronic diarrhea in a 54-year-old man with HIV infection]. / Gewichtsverlust und chronische Diarrhö bei einem 54-jährigen Mann mit HIV-Infektion.

A 54-year-old man presented with a 6-week history of chronic diarrhea and weight loss of 11 kg after returning from a holiday in Thailand. The patient had a 9-year history of an untreated HIV infection. Despite treatment of a culture-proven Shigella enteritis and strongyloidiasis the symptoms persisted. Finally, cytomegalovirus (CMV) colitis was diagnosed by colonoscopy. The patient recovered completely after starting antiretroviral and valganciclovir treatment. An additional opportunistic infection with multiresistant pulmonary tuberculosis was diagnosed.

If there is an evolutionary selection pressure for the high frequency of MBL2 polymorphisms, what is it?

Either immune selection or stochastic processes may have influenced the frequency of highly polymorphic genes such as mannose-binding lectin 2 (MBL2). This pattern recognition receptor of the innate immune system recognizes and binds to pathogenic microorganisms and apoptotic cells leading to lectin pathway complement killing or clearance. In almost all of a large number of studies in different ethnic groups worldwide there is 20-25% carriage of low MBL2 haplotypes, with 8-10% of each population having no MBL detectable in the blood. The source of this high variability of MBL2 remains cryptic. It arises from six main snps in the prompter and exon regions of the gene that assort into seven common haplotypes under linkage disequilibrium. While global studies of MBL2 show that it is not under immune selection pressure, these results are not the same when the same population genetic tools are used on large national studies. Other analyses point to the silenced MBL1 pseudogene and development of promoter polymorphisms in humans as evidence of selection pressure favouring low-producing haplotypes. While these analyses cannot be reconciled readily, there are two processes by which MBL heterozygosity could have been advantageous in an evolutionary sense; protection against adverse effects of various infectious diseases and lethal manifestations of atherosclerosis - a disease that now seems to have a more ancient history than assumed previously. Ultimately, consideration of the context for possible future therapeutic manipulation of MBL means that this can proceed independently of resolution of the evolutionary forces that have shaped MBL2 polymorphism.

Disseminated toxoplasmosis after allogeneic stem cell transplantation in a seronegative recipient.

Toxoplasmosis is increasingly diagnosed after hematopoietic stem cell transplantation (HSCT) and is associated with considerable morbidity and mortality. In the majority of cases, reactivation of latent disease secondary to impaired cellular and humoral immunity after HSCT is believed to be the main pathogenetic mechanism. Hence, primary toxoplasmosis is rarely considered in the differential diagnosis of infections after HSCT in a recipient who is seronegative for Toxoplasma gondii pre-transplant. We herein report a seronegative patient with acute T-cell lymphoblastic leukemia, who developed primary disseminated toxoplasmosis 5 months after HSCT from a seronegative unrelated donor. A review of all reported cases of primary toxoplasmosis after HSCT revealed significantly increased morbidity and mortality. Patients with negative pre-transplant Toxoplasma serology should therefore be considered at risk for toxoplasmosis after allogeneic HSCT. Possible prevention and monitoring strategies for seronegative recipients are reviewed and discussed in detail.

Endogenous endophthalmitis with azole-resistant Candida albicans--Case report and review of the literature.

Candida endophthalmitis accounts for the majority of fungal endophthalmitis. Despite its clinical relevance there are no controlled trials on different treatment regimens. We report a case of endogenous endophthalmitis caused by azole-resistant Candida albicans following abdominal surgery in an otherwise healthy woman, and review the literature concerning treatment recommendations. In consideration of the serious outcome with loss of sight in insufficiently treated endophthalmitis we like to increase awareness to this disease entity and the possibility of azole-resistance, even in treatment-naive patients.

Serum antibodies in first-degree relatives of patients with IBD: a marker of disease susceptibility? A follow-up pilot-study after 7 years.

INTRODUCTION: Various disease-specific serum antibodies were described in patients with inflammatory bowel disease and their yet healthy first-degree relatives. In the latter, serum antibodies are commonly regarded as potential markers of disease susceptibility. The present long-term follow-up study evaluated the fate of antibody-positive first-degree relatives. PATIENTS AND METHODS: 25 patients with Crohn's disease, 19 patients with ulcerative colitis and 102 first-degree relatives in whom presence of ASCA, pANCA, pancreatic- and goblet-cell antibodies had been assessed were enrolled. The number of incident cases with inflammatory bowel disease was compared between antibody-positive and antibody-negative first-degree relatives 7 years after storage of serum samples. RESULTS: 34 of 102 (33%) first-degree relatives were positive for at least one of the studied serum antibodies. In the group of first-degree relatives, one case of Crohn's disease and one case of ulcerative colitis were diagnosed during the follow-up period. However, both relatives did not display any of the investigated serum antibodies (p=1). DISCUSSION: The findings of our pilot study argue against a role of serum antibodies as a marker of disease susceptibility in first-degree relatives of patients with inflammatory bowel disease. However, these data have to await confirmation in larger ideally prospective multicenter studies before definite conclusions can be drawn.