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Sepsis, a life-threatening organ dysfunction, continues to cause considerable morbidity. Reliable animal models to evaluate therapeutic options are urgently required, however, some of the most esta...

Antibiotic resistance represents a major global concern. The rapid spread of opportunistically pathogenic carbapenemase-encoding bacteria (CEB) requires clinicians, researchers, and policy-makers to swiftly find solutions to reduce transmission rates and the associated health burden. Epidemiological data is key to planning control measures. Our study aims to contribute by providing an analysis of 397 unique CEB isolates detected in a tertiary hospital in Germany. We propose new findings on demographic variables to support preventive sanitary precautions in routine clinical practice. Data on detected CEB was combined with patient’s demographic and clinical information for each isolate. Multiple regression techniques were applied to estimate the predictive quality of observed differences. Our findings confirm the role of age and gender in CEB colonization patterns and indicate a role for ethnicity and domicile. Also, carbapenemase-encoding A. baumannii was most frequently introduced to the hospital, while the risk of colonization with VIM-encoding P. aeruginosa rose with the length of hospital stay. P. aeruginosa remains an important complication of prolonged hospital stays. The strong link to hospital-wastewater may have implications for hospital-built environments. A. baumannii can be efficiently controlled from spreading at hospital admission. OXA-encoding CEB being harder to detect in routine screening, targeted preventive measures, such as culture media selective for carbapenem-resistant bacteria, would be opportune for patients from selected regions. The CEB differences linked to ethnicity found in our study may further be supporting the tailoring of diagnostic approaches, as well as health policies upon confirmation by other studies and a better understanding of their global distribution.

In 2018, the European Centre for Disease Prevention and Control reported the first cases of extensively drug-resistant Neisseria gonorrhoeae infections in Europe. Seeking new options for antimicrobial therapy we investigated the susceptibility of N. gonorrhoeae to nitroxoline (NIT) and mecillinam (MCM), both of which are currently only indicated to treat uncomplicated urinary tract infections. Clinical N. gonorrhoeae isolates with non-susceptibility to penicillin from two German medical centres were included (n =27). Most isolates were also non-susceptible to a range of other anti-gonococcal antimicrobials (cefotaxime, ciprofloxacin, azithromycin, tetracycline). All isolates were further characterized by multi-locus sequence typing. MICs of penicillin and cefotaxime were determined by agar gradient diffusion. Production of penicillinase was tested by cefinase disk test. Susceptibility of MCM was investigated by agar dilution, NIT by agar dilution and disk diffusion. Penicillin MICs ranged from 0.125 to 64 mg l−1 and MICs of cefotaxime ranged from 128 mg l−1 whereas MICs of NIT ranged from 0.125 to 2 mg l−1 . NIT disk diffusion (median zone diameter 32 mm) correlated well with results from agar dilution. We demonstrated excellent in vitro activity of NIT against clinical N. gonorrhoeae isolates with non-susceptibility to standard anti-gonococcal antibiotics. MCM activity was unsatisfactory. Correlation of agar dilution and disk diffusion in NIT susceptibility testing is an important aspect with potential clinical implications.

Berichtet wird uber den bemerkenswerten Verlauf eines fazialen Ulkus bei einer Patientin unter Therapie mit Prednisolon im Rahmen eines M. Crohn. Bei initial unklarer Diagnose zeigte sich ein rasch progredienter Befund trotz dreifach antiinfektiver Therapie (antiviral, antibiotisch, antimykotisch). Eine Infektion mit Orthopoxviren konnte anhand umfangreicher Diagnostik im Verlauf bestatigt werden, relevante Differentialdiagnosen wurden ausgeschlossen. Nach umfangreicher nekrotischer Umwandlung kam es nach Monaten zu einer narbigen Abheilung. Kuhpockeninfektionen kommen in Deutschland immer wieder vor und sind eine klinisch relevante Zoonose. Am haufigsten erfolgt die Ubertragung durch Katzen und Nagetiere. Differenzialdiagnostisch kommen verschiedenste teilweise seltene Erreger ursachlich in Betracht, die hier anhand klinischer und histopathologischer Merkmale diskutiert werden. Hierzu zahlen bakterielle, mykobakterielle, mykotische und parasitare Infektionen. Insbesondere die kutane Leishmaniose ist aufgrund steigender Inzidenz hierzulande explizit zu nennen. Da infektiose faziale Ulzera bei inadaquater Therapie zu lebensgefahrlichen Komplikationen und ausgedehnter entstellender Narbenbildung fuhren konnen, ist eine zeitkritische kalkulierte Therapieeinleitung vordringlich.

This study assessed the diagnostic performance of the new coronavirus disease 2019 (COVID-19) SEROSpeed IgM/IgG Rapid Test (BioSpeedia, a spinoff of the Pasteur Institute of Paris) for the detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in comparison to other commercial antibody assays through a large cross-European investigation. The clinical specificity was assessed on 215 prepandemic sera (including some from patients with viral infections or autoimmune disorders)., This study assessed the diagnostic performance of the new COVID19SEROSpeed IgM/IgG rapid test (BioSpeedia, a spinoff of the Pasteur Institute of Paris) for the detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in comparison to other commercial antibody assays through a large cross-European investigation. The clinical specificity was assessed on 215 prepandemic sera (including some from patients with viral infections or autoimmune disorders). The clinical sensitivity was evaluated on 710 sera from 564 patients whose SARS-CoV-2 infection was confirmed by quantitative reverse transcription-PCR (qRT-PCR) and whose antibody response was compared to that measured by five other commercial tests. The kinetics of the antibody response were also analyzed in seven symptomatic patients. The specificity of the test (BioS) on prepandemic specimens was 98.1% (95% confidence interval [CI], 96.2% to 99.4%). When tested on the 710 pandemic specimens, BioS showed an overall clinical sensitivity of 86.0% (95% CI, 0.83 to 0.89), with good concordance with the Euroimmun assay (overall concordance of 0.91; Cohen’s kappa coefficient of 0.62). Due in part to simultaneous detection of IgM and IgG for both S1 and N proteins, BioS exhibited the highest positive percent agreement at ≥11 days post-symptom onset (PSO). In conclusion, the BioS IgM/IgG rapid test was highly specific and demonstrated a higher positive percentage of agreement than all the enzyme-linked immunosorbent assay/chemiluminescence immunoassay (ELISA/CLIA) commercial tests considered in this study. Moreover, by detecting the presence of antibodies prior to 11 days PSO in 78.2% of the patients, the BioS test increased the efficiency of the diagnosis of SARS-CoV-2 infection in the early stages of the disease.

In their outstanding study, Wei et al 1 compared the intestinal microbiota (IM) of well-defined autoimmune hepatitis (AIH) patients to healthy controls. They reported significantly reduced IM alpha diversity and disparate IM compositional heterogeneity (beta diversity) with enrichment of Streptococcus , Veillonella , Klebsiella and Lactobacillus in AIH. The excellent achievement of this study is to have characterised the IM of untreated patients with AIH. However, differentiation between IM changes caused by AIH in particular and by chronic liver disease (CLD) in general was not possible because this study lacked a control group with CLD other than AIH. In a pilot study, we analysed the IM of patients with CLD of mixed aetiology in comparison to healthy controls to clarify alterations across different stages of CLD (table 1 and online supplementary data). In contrast to the study by Wei et al , patients with recent intake of antibiotics were excluded. Additionally, only patients on proton pump inhibitors (PPIs), which are frequently taken by patients with CLD, were included to avoid a bias due to mixed PPI use, because PPI can alter the IM, in particular, the abundance of Veillonellaceae and Streptococcaceae.2 Based on investigations of normalised relative reads (n-RR) per IM taxon as well as IM alpha-diversity and beta-diversity analyses, we detected Veillonella …

International audience; Acute respiratory tract infections (ARTI), including the common cold, pharyngitis, sinusitis, otitis media, bronchiolitis and pneumonia are the most common diagnoses among patients seeking medical care in western countries, and account for most antibiotic prescriptions. While a confirmed and fast ARTI diagnosis is key for antibiotic prescribing, empiric antimicrobial treatment remains common, because viral symptoms are often clinically similar and difficult to distinguish from those caused by bacteria. As a result, inappropriate antibiotic prescriptions are high and in certain settings likely higher than the commonly estimated 30%. The QIAstat Respiratory Panel® assay (QIAstat RP) is a multiplexed in vitro diagnostics test for the rapid simultaneous detection of 21 pathogens directly from respiratory samples, including human mastadenovirus A-G, primate bocaparvovirus 1+2, human coronavirus (HKU1, NL63, OC43, 229E), human metapneumovirus A/B, rhinovirus/enterovirus, influenza A virus (no subtype, subtype H1, H1N1/2009, H3), influenza B virus, human respirovirus 1+3, human orthorubulavirus 2+4, human orthopneumovirus, Bordetella pertussis, Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila. We describe the first multicenter study of 445 respiratory samples, collected through the 2016-2017 and 2018 respiratory seasons, with performance compared against BioFire FilmArray RP v1.7 and discrepancy testing by Seegene Allplex RP. The QIAstat RP demonstrated a positive percentage of agreement of 98.0% (95% CI: 96.0-99.1%) and a negative percentage agreement of 99.8% (95% CI: 99.6-99.9%). With use of this comprehensive and rapid test, improved patient outcomes and antimicrobial stewardship may potentially be achieved.

Acinetobacter baumannii is an important human pathogen usually associated with severe hospital-acquired infections. Here, we announce the draft genome sequences of two livestock-associated isolates recovered from sewage water from a poultry slaughterhouse in Germany. Short-read whole-genome sequencing was conducted to determine the genetic basis of their antimicrobial resistance phenotype.

In acute gastroenteritis (AGE), identification of the infectious agent is important for patient management. Since symptoms do not reliably identify the agent, microbiological diagnostics are important. Conventional methods lack sensitivity and often take days. Multiplex PCR panels offer fast and sensitive alternatives. Our aim was to assess the performance of the new QIAstat Gastrointestinal Panel (GIP) detecting 24 different gastroenteric pathogens from stool in Cary-Blair transport medium (Adenovirus F 40/41, Astrovirus, Norovirus GI/GII, Rotavirus A, Sapovirus, Campylobacter spp., Clostridium difficile, Plesiomonas shigelloides, Salmonella spp., Vibrio cholera, Vibrio parahaemolyticus, Vibrio vulnificus, Yersinia enterocolitica, enteroaggregative Escherichia coli, enteropathogenic E. coli, enterotoxigenic E. coli, Shiga-toxin-producing E. coli (stx1 and stx2) (including specific detection of E. coli O157), Shigella spp./enteroinvasive E. coli, Cryptosporidium spp., Cyclospora cayetanensis, Entamoeba histolytica and Giardia lamblia). We tested both prospective (n = 163) and retrospective (n = 222) stool samples sent for routine diagnostics by the QIAstat GIP comparing it to the FDA-approved BioFire FilmArray GIP. Seegene Allplex GIP was used for discrepancy testing. After discrepancy testing, QIAstat GIP detected 447 of 455 pathogens (98.2%, 95% confidence interval (CI) 96.6–99.1%). There were eight false positive detections. Multiple pathogens were detected in 32.5% of positive samples. The QIAstat GIP detected a large range of AGE pathogens with a high sensitivity. It offers an easy-to-use system for GI pathogen detection in stool within 70 min. An advantage of the QIAstat is the availability of cycle threshold (CT) values to aid in interpretation of results.

Increasing isolation rates of resistant bacteria in the last years require identification of potential infection reservoirs in healthcare facilities. Especially the clinical wastewater network represents a potential source of antibiotic resistant bacteria. In this work, the siphons of the sanitary installations from 18 hospital rooms of two German hospitals were examined for antibiotic resistant bacteria and antibiotic residues including siphons of showers and washbasins and toilets in sanitary units of psychosomatic, haemato-oncological, and rehabilitation wards. In addition, in seven rooms of the haemato-oncological ward, the effect of 24 h of stagnation on the antibiotic concentrations and MDR (multi-drug-resistant) bacteria in biofilms was evaluated. Whereas no antibiotic residues were found in the psychosomatic ward, potential selective concentrations of piperacillin, meropenem and ciprofloxacin were detected at a rehabilitation ward and ciprofloxacin and trimethoprim were present at a haemato-oncology ward. Antibiotic resistant bacteria were isolated from the siphons of all wards, however in the psychosomatic ward, only one MDR strain with resistance to piperacillin, third generation cephalosporins and quinolones (3MRGN) was detected. In contrast, the other two wards yielded 11 carbapenemase producing MDR isolates and 15 3MRGN strains. The isolates from the haemato-oncological ward belonged mostly to two specific rare sequence types (ST) (P. aeruginosa ST823 and Enterobacter cloacae complex ST167). In conclusion, clinical wastewater systems represent a reservoir for multi-drug-resistant bacteria. Consequently, preventive and intervention measures should not start at the wastewater treatment in the treatment plant, but already in the immediate surroundings of the patient, in order to minimize the infection potential.

Background Spontaneous bacterial peritonitis (SBP) can be life-threatening in patients with liver cirrhosis. In contrast to community-acquired SBP, no standard treatment has been established for healthcare-related and nosocomial SBP. Patients and methods We prospectively collected healthcare-related and nosocomial SBP cases from March 2012 till February 2016 at the Department of Internal Medicine I of the University of Bonn and analysed the prevalence of antibiotic resistance among the isolated bacteria. SBP was diagnosed according to international guidelines. Ciprofloxacin, ceftriaxone and meropenem were used as reference substance for resistance to quinolones, third-generation cephalosporins and carbapenems, respectively. Results Ninety-two SBP episodes in 86 patients were identified: 63 episodes (69%) were nosocomial. Escherichia coli, Klebsiella species, enterococci and streptococci were most frequently isolated. Frequency of these microorganisms were comparable for healthcare-related and nosocomial SBP (14 vs. 11%, 14 vs. 8%, 14 vs. 5% and 10 vs. 6%, respectively). In general, antibiotic resistance was higher in isolates from nosocomial than from healthcare-related SBP (50% vs. 18% for quinolones, 30 vs. 11% for piperacillin-tazobactam; p>0.05), but comparable concerning third-generation cephalosporins (30 vs. 33%). All microorganisms were sensitive to carbapenems apart from nosocomial infections with Enterococcus faecium (n=3) and Candida albicans (n=1) due to intrinsic resistance or lack of microbiological efficacy, respectively. No multidrug-resistant microorganisms were detected. Resistance to initial antibiotic treatment affected 30-day survival negatively (18% vs. 68%; p=0.002). Conclusion Resistance to initial antibiotic treatment was associated with increased mortality. With resistance to cephalosporins being frequent, piperacillin-tazobactam or carbapenems might be preferred as treatment of SBP. This article is protected by copyright. All rights reserved.

BackgroundRifaximin is a non-absorbable antibiotic used to prevent relapses of hepatic encephalopathy which may also be a candidate for prophylaxis of spontaneous bacterial peritonitis (SBP).AimTo detect the impact of rifaximin on the occurrence and characteristics of SBP.MethodsWe prospectively studied all hospitalized patients that underwent a diagnostic paracentesis in our department from March 2012 to April 2013 for SBP and recorded all clinical data including type of SBP prophylaxis, prior use of rifaximin, concomitant complications of cirrhosis, as well as laboratory results and bacteriological findings. Patients were divided into the following three groups: no antibiotic prophylaxis, prophylaxis with rifaximin or with systemically absorbed antibiotic prophylaxis.ResultsOur study cohort comprised 152 patients with advanced liver cirrhosis, 32 of whom developed SBP during the study period. As expected, our study groups differed regarding a history of hepatic encephalopathy and SBP before inclusion into the study. None of the 17 patients on systemic antibiotic prophylaxis developed SBP while 8/27 patients on rifaximin and 24/108 without prophylaxis had SBP (p = 0.02 and p = 0.04 versus systemic antibiotics, respectively). In general, episodes of SBP were similar for patients treated with rifaximin and those without any prophylaxis. However, Escherichia coli and enterococci were dominant in the ascites of patients without any prophylaxis, while mostly klebsiella species were recovered from the ascites samples in the rifaximin group.ConclusionRifaximin pretreatment did not lead to a reduction of SBP occurrence in hospitalized patients with advanced liver disease. However, the bacterial species causing SBP were changed by rifaximin.

Spontaneous bacterial peritonitis (SBP) is a life-threatening complication of liver cirrhosis. Recently, rifaximin, a non-absorbable antibiotic which is used to prevent recurrent hepatic encephalopathy, has been proposed as effective prophylaxis for SBP. Here, we present an unusual case of SBP under treatment with rifaximin. A 50-year-old woman with liver cirrhosis was admitted because of tense ascites and abdominal pain. She was under long-term oral prophylaxis with rifaximin due to hepatic encephalopathy. Paracentesis revealed SBP caused by Pasteurella multocida, which was sensitive to multiple antibiotics, including rifaximin. Treatment with ceftriaxone resulted in rapid resolution of the peritonitis and restoration of the patient. Since P. multocida is usually transmitted from pets, the patient’s cat was tested and could be identified as the most likely source of infection. This case should elicit our awareness that uncommon pathogens and unusual routes of transmission may lead to SBP, despite antibacterial prophylaxis with non-absorbable antibiotics. Nevertheless, such infections may still remain sensitive to systemic therapy with conventional antibiotics.

While several characteristics of systemic lupus erythematosus (SLE) have been investigated, the distinct pathogenetic mechanisms leading to autoimmunity and chronic inflammation are not understood yet. A central role for apo has been implicated in the pathogenesis of SLE and an increased rate of apo or a defective clearance of apo cells have repeatedly been described in SLE patients, which show elevated levels of alpha-interferon (alphaIFN) as well as an enhanced expression of alphaIFN-alpha inducible genes referred to as alphaIFN signature. Recent publications link alphaIFN and apo: apo cell-derived microparticles can directly stimulate plasmacytoid dendritic cells to secret alphaIFN. This review highlights the role of apo material as source for AAg and as a trigger for chronic inflammation in the pathogenesis of SLE.

BACKGROUND/OBJECTIVES: This study addressed the question whether the composition of supposedly ‘healthy’ or ‘unhealthy’ dietary regimes has a calorie-independent short-term effect on biomarkers of metabolic stress and vascular risk in healthy individuals. SUBJECTS/METHODS: Healthy male volunteers (age 29.5 ± 5.9 years, n = 39) were given a standardized baseline diet for two weeks before randomization into three groups of different dietary regimes: fast food, Mediterranean and German cooking style. Importantly, the amount of calories consumed per day was identical in all three groups. Blood samples were analyzed for biomarkers of cardiovascular risk and metabolic stress after two weeks of the baseline diet and after two weeks of the assigned dietary regime. RESULTS: No dietary intervention affected the metabolic or cardiovascular risk profile when compared in-between groups or compared to baseline. Subjects applied to the Mediterranean diet showed a statistically significant increase of uric acid compared to baseline and compared to the German diet group. Plasma concentrations of urea were significantly higher in both the fast food group and the Mediterranean group, when compared to baseline and compared to the German diet group. No significant differences were detected for the levels of vitamins, trace elements or metabolic stress markers (8-hydroxy-2-deoxyguanosine, malondialdehyde and methylglyoxal, a potent glycating agent). Established parameters of vascular risk (e.g. LDL-cholesterol, lipoprotein(a), homocysteine) were not significantly changed in-between groups or compared to baseline during the intervention period. CONCLUSIONS: The calorie-controlled dietary intervention caused neither protective nor harmful short-term effects regarding established biomarkers of vascular or metabolic risk. When avoiding the noxious effects of overfeeding, healthy individuals can possess the metabolic capacity to compensate for a potentially disadvantageous composition of a certain diet.