Interobserver agreement on definition of the target volume in stereotactic radiotherapy for pancreatic adenocarcinoma using different imaging modalities

PURPOSE The aim of this study was to evaluate interobserver agreement (IOA) on target volume definition for pancreatic cancer (PACA) within the Radiosurgery and Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (DEGRO) and to identify the influence of imaging modalities on the definition of the target volumes. METHODS Two cases of locally advanced PACA and one local recurrence were selected from a large SBRT database. Delineation was based on either a planning 4D CT with or without (w/wo) IV contrast, w/wo PET/CT, and w/wo diagnostic MRI. Novel compared to other studies, a combination of four metrics was used to integrate several aspects of target volume segmentation: the Dice coefficient (DSC), the Hausdorff distance (HD), the probabilistic distance (PBD), and the volumetric similarity (VS). RESULTS For all three GTVs, the median DSC was 0.75 (range 0.17-0.95), the median HD 15 (range 3.22-67.11) mm, the median PBD 0.33 (range 0.06-4.86), and the median VS was 0.88 (range 0.31-1). For ITVs and PTVs the results were similar. When comparing the imaging modalities for delineation, the best agreement for the GTV was achieved using PET/CT, and for the ITV and PTV using 4D PET/CT, in treatment position with abdominal compression. CONCLUSION Overall, there was good GTV agreement (DSC). Combined metrics appeared to allow a more valid detection of interobserver variation. For SBRT, either 4D PET/CT or 3D PET/CT in treatment position with abdominal compression leads to better agreement and should be considered as a very useful imaging modality for the definition of treatment volumes in pancreatic SBRT. Contouring does not appear to be the weakest link in the treatment planning chain of SBRT for PACA

Integrated genomic surveillance enables tracing of person-to-person SARS-CoV-2 transmission chains during community transmission and reveals extensive onward transmission of travel-imported infections, Germany, June to July 2021

BackgroundTracking person-to-person SARS-CoV-2 transmission in the population is important to understand the epidemiology of community transmission and may contribute to the containment of SARS-CoV-2. Neither contact tracing nor genomic surveillance alone, however, are typically sufficient to achieve this objective.AimWe demonstrate the successful application of the integrated genomic surveillance (IGS) system of the German city of Düsseldorf for tracing SARS-CoV-2 transmission chains in the population as well as detecting and investigating travel-associated SARS-CoV-2 infection clusters.MethodsGenomic surveillance, phylogenetic analysis, and structured case interviews were integrated to elucidate two genetically defined clusters of SARS-CoV-2 isolates detected by IGS in Düsseldorf in July 2021.ResultsCluster 1 (n = 67 Düsseldorf cases) and Cluster 2 (n = 36) were detected in a surveillance dataset of 518 high-quality SARS-CoV-2 genomes from Düsseldorf (53% of total cases, sampled mid-June to July 2021). Cluster 1 could be traced back to a complex pattern of transmission in nightlife venues following a putative importation by a SARS-CoV-2-infected return traveller (IP) in late June; 28 SARS-CoV-2 cases could be epidemiologically directly linked to IP. Supported by viral genome data from Spain, Cluster 2 was shown to represent multiple independent introduction events of a viral strain circulating in Catalonia and other European countries, followed by diffuse community transmission in Düsseldorf.ConclusionIGS enabled high-resolution tracing of SARS-CoV-2 transmission in an internationally connected city during community transmission and provided infection chain-level evidence of the downstream propagation of travel-imported SARS-CoV-2 cases

Importance of pre-enrichment for detection of third-generation cephalosporin-resistant Enterobacteriaceae (3GCREB) from rectal swabs

Screening for multidrug-resistant Enterobacteriaceae is performed in many institutions as part of infection control measures. However, the sensitivity of current standard diagnostics is modest. Furthermore, patients are usually screened by rectal swabs (mostly rayon based), which have been shown to be sub-optimal for the recovery of Enterobacteriaceae. Therefore, it is likely that many patients colonised with multidrug-resistant Enterobacteriaceae remain undetected. The present study aimed to analyse if the detection of multidrug-resistant Enterobacteriaceae can be improved when screening with rayon swabs is done in combination with an additional pre-enrichment step. The detection of third-generation cephalosporin-resistant Enterobacteriaceae (3GCREB) was assessed in 514 rectal samples by the standard diagnostic approach (direct plating of swabs on selective ESBL agar) and after pre-enrichment in 5 mL of a semi-selective MacConkey broth. The recovery rate of 3GCREB and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E), patient characteristics and isolate characteristics were evaluated for both diagnostic approaches. Overall, by pre-enrichment, the detection of 3GCREB carriers increased by 22.8% (13/57, p = 0.004) and the detection of ESBL-E carriers by 21.4% (9/42, p = 0.01). This study demonstrates the low sensitivity of rectal screening by direct plating and the improvement by pre-enrichment. We believe that it is no longer acceptable to refrain from pre-enrichment as, with the standard approach, more than 20% of 3GCREB and ESBL-E carriers remain undetected

Changes in Clostridium (Clostridioides) difficile PCR-Ribotype Distribution and Antimicrobial Resistance in a German Tertiary Care Hospital Over the Last 10Years

Clostridium (Clostridioides) difficile ribotype 027 (RT027) was detected in Germany for the first time in 2007 during an outbreak in the region of Trier, Rhineland-Palatinate and is today the most prevalent ribotype (RT) in Europe. We aimed to determine the changes in RT distribution and corresponding antimicrobial resistance in clinical C. difficile isolates between two time points (2007 and 2017) in one tertiary care hospital in Germany. C. difficile isolates recovered in 2007 and in 2017 (80 isolates per year, respectively) from patients at a Tertiary Care University Hospital in North-Rhine Westphalia were analyzed. Isolates were characterized by ribotyping and susceptibility testing using gradient tests (metronidazole, vancomycin) and the disk diffusion method (moxifloxacin). Between 2007 and 2017, a clear switch from RT001 [18.75% (n=15) in 2007 versus 3.75% (n=3) in 2017 P=0.003] to RT027 [0% in 2007 versus 21.25% (n=17) in 2017] was evident. While minimal inhibitory concentrations (MICs) of vancomycin were stable, a significant metronidazole MIC creep was determined (MIC50=0.047 in 2007 versus MIC50=0.094 in 2017, P<0.0001 using the Man-Whitney test). We detected one metronidazole-resistant isolate (0.6%). Interestingly, in total we encountered more isolates resistant to moxifloxacin in 2007 (42 (52.25%) than in 2017 [(30 (37.5%), P=0.06)]). We could demonstrate that RT027 replaced RT001 in the last 10years in our hospital. Furthermore, our data show a metronidazole MIC creep in C. difficile isolates over the last 10years and an unexpected decrease of isolates resistant to moxifloxacin

PCR based detection of tcdC Delta 117 in Clostridium difficile infection identifies patients at risk for recurrence - A hospital-based prospective observational study

Objectives: Increasing incidence and severity of Clostridium difficile infection (CDI) in the last decades has been attributed to the emergence of hypervirulent C. difficile strain PCR-ribotype 027 (RT027). Commercial multiplex real-time PCR tests allow the presumptive identification of RT027 by detecting a single-base deletion at nt117 in the tcdC gene (tcdC Delta 117). The clinical usefulness of the detection of tcdC Delta 117 is unclear. Therefore, we evaluated test performance and clinical association of the detection of tcdC Delta 117 in patients with CDI in a prospective observational study conducted in a tertiary care hospital in Germany. Methods: From June to October 2015, stool from all patients with suspected CDI was tested for C. difficile according to ESCMID guidelines. C difficile was cultured from positive samples and ribotyping was performed. Clinical data were collected prospectively from all C. difficile positive patients. Results: From 1121 tested stool samples 107 patients with CDI were included in the study. tcdC Delta 117 was detected in 18 (16.8%) of these patients. Multivariable logistic regression analysis revealed an independent association of detection of tcdC Delta 117 with a further episode of CDI (OR 14.6; 95% CI 3.6-58.3: p < 0.001) and death within 30 days of the positive test (OR 5.1; 95% CI 1.0-25.7; p = 0.046). As follow up data are limited, it remains unclear, whether the further episode of CDI was due to tcdC Delta 117 (recurrence) or another type. Conclusion: In our setting, PCR-based detection of tcdC Delta 117 identified patients at risk for recurrent CDI and increased mortality and thus may guide therapeutic choices in CDI patients at the time of diagnosis. (C) 2019 Elsevier Ltd. All rights reserved

Evaluation of the Use of Rectal Swabs for Laboratory Diagnosis of Clostridium difficile Infection

For the diagnosis of Clostridium difficile infection (CDI), microbiological testing is almost always accomplished through the analysis of stool specimens. We evaluated the performances of rectal swabs with liquid transport medium (FS) and nylon flocked dry swabs for the detection of C. difficile. Additionally, the impact on the diagnostic yield of storing swabs at -80 degrees C for up to 3 months was evaluated. Sixty clinical stool samples positive for C. difficile by PCR were used for simulating rectal swabbing. FS and dry swabs were dipped into the stool and tested by PCR directly after swabbing at 1 and 3 months after storage at -80 degrees C. Stool and the liquid medium of FS were additionally tested by a combination of glutamate dehydrogenase antigen (GDH) testing and toxin A/B enzyme immunoassay (EIA), as well as by toxigenic culture (TC). Using dry swabs, the PCR-based detection rate of C. difficile was equal to the rate using stool samples (30/3. [100%]), whereas the detection rate in FS was significantly lower (25/30 [83.2%]; P = 0.019). The sensitivities of FS for detecting C. difficile by PCR, TC, GDH testing, and toxin A/B EIA were 83.3%, 85.7%, 88%, and 68.9%, respectively. Storage of swabs at -80 degrees C had no impact on the detection rate. FS cannot replace stool samples in the two-step laboratory diagnosis of CDI, as the sensitivities were too low, probably due to diluting effects of the fecal sample in the liquid medium. For simple PCR-based detection of C. difficile, dry swabs proved to be a suitable alternative to the use of stool samples