Occurrence and trends of Clostridioides difficile infections in hospitalized patients: a prospective multicentre cohort study in six German university hospitals, 2016-2020.

BACKGROUND: For Clostridioides difficile infections (CDI) in Germany no longitudinal multicentre studies with standardized protocols for diagnosing CDI are available. Recent evaluations of general surveillance databases in Germany indicate a downward trend in CDI rates. We aimed to describe the actual burden and trends of CDI in German university hospitals from 2016 to 2020. METHODS: Our study is a prospective multicentre study covering six German university hospitals. We report the data in total, stratified by year, by medical specialty as well as by CDI severity. Multivariable regression analyses were performed to assess risk factors for severe CDI. RESULTS: We registered 3,780 CDI cases among 1,436,352 patients. The median length of stay (LOS) of CDI cases was 20 days (IQR 11-37) compared with a general LOS of 4.2 days. In-hospital all-cause mortality in CDI patients was 11.7% (n=444/3780), while mortality attributed to CDI was 0.4% (n=16/3761). CDI recurrence rate was comparatively low at 7.2%. The incidence density of severe healthcare-associated healthcare onset (HAHO)-CDI showed a significant decrease from 2.25/10,000 patient days (pd) in 2016 to 1.49/10,000 pd in 2020 (trend calculation p = 0.032). CONCLUSIONS: Compared with a European point-prevalence study in 2013/2014, where overall CDI incidence density was 11.2 cases/10,000 pd in Germany (EUCLID), we see in our study halved overall CDI rates of 5.6 cases/10,000 pd in 2020. Our study shows current data on the distribution of CDI cases in German university hospitals and thus provides international comparative data on the key indicators of CDI.

Epidemiological trends and susceptibility patterns of bloodstream infections caused by Enterococcus spp. in six German university hospitals: a prospectively evaluated multicentre cohort study from 2016 to 2020 of the R-Net study group.

PURPOSE: To analyse recent epidemiological trends of bloodstream infections (BSI) caused by Enterococcus spp. In adult patients admitted to tertiary care centres in Germany. METHODS: Epidemiological data from the multicentre R-NET study was analysed. Patients presenting with E. faecium or E. faecalis in blood cultures in six German tertiary care university hospitals between October 2016 and June 2020 were prospectively evaluated. In vancomycin-resistant enterococci (VRE), the presence of vanA/vanB was confirmed via molecular methods. RESULTS: In the 4-year study period, 3001 patients with BSI due to Enterococcus spp. were identified. E. faecium was detected in 1830 patients (61%) and E. faecalis in 1229 patients (41%). Most BSI occurred in (sub-) specialties of internal medicine. The pooled incidence density of enterococcal BSI increased significantly (4.0-4.5 cases per 10,000 patient days), which was primarily driven by VRE BSI (0.5 to 1.0 cases per 10,000 patient days). In 2020, the proportion of VRE BSI was > 12% in all study sites (range, 12.8-32.2%). Molecular detection of resistance in 363 VRE isolates showed a predominance of the vanB gene (77.1%). CONCLUSION: This large multicentre study highlights an increase of BSI due to E. faecium, which was primarily driven by VRE. The high rates of hospital- and ICU-acquired VRE BSI point towards an important role of prior antibiotic exposure and invasive procedures as risk factors. Due to limited treatment options and high mortality rates of VRE BSI, the increasing incidence of VRE BSI is of major concern.

Association of ward-level antibiotic consumption with healthcare-associated Clostridioides difficile infections: an ecological study in five German university hospitals, 2017-2019.

OBJECTIVES: To analyse the influence of antibiotic consumption on healthcare-associated healthcare onset (HAHO) Clostridioides difficile infection (CDI) in a German university hospital setting. METHODS: Monthly ward-level antibiotic consumption measured in DDD/100 patient days (pd) and CDI surveillance data from five university hospitals in the period 2017 through 2019 were analysed. Uni- and multivariable analyses were performed with generalized estimating equation models. RESULTS: A total of 225 wards with 7347 surveillance months and 4 036 602 pd participated. With 1184 HAHO-CDI cases, there was a median incidence density of 0.17/1000 pd (IQR 0.03-0.43) across all specialties, with substantial differences among specialties. Haematology-oncology wards showed the highest median incidence density (0.67/1000 pd, IQR 0.44-1.01), followed by medical ICUs (0.45/1000 pd, IQR 0.27-0.73) and medical general wards (0.32/1000 pd, IQR 0.18-0.53). Multivariable analysis revealed carbapenem (mostly meropenem) consumption to be the only antibiotic class associated with increased HAHO-CDI incidence density. Each carbapenem DDD/100 pd administered increased the HAHO-CDI incidence density by 1.3% [incidence rate ratio (IRR) 1.013; 95% CI 1.006-1.019]. Specialty-specific analyses showed this influence only to be valid for haematological-oncological wards. Overall, factors like ward specialty (e.g. haematology-oncology ward IRR 2.961, 95% CI 2.203-3.980) or other CDI cases on ward had a stronger influence on HAHO-CDI incidence density (e.g. community-associated CDI or unknown association case in same month IRR 1.476, 95% CI 1.242-1.755) than antibiotic consumption. CONCLUSIONS: In the German university hospital setting, monthly ward-level carbapenem consumption seems to increase the HAHO-CDI incidence density predominantly on haematological-oncological wards. Furthermore, other patient-specific factors seem to be equally important to control HAHO-CDI.

The application of virtual reality exposure versus relaxation training in music performance anxiety: a randomized controlled study.

BACKGROUND: Performance anxiety is the most frequently reported anxiety disorder among professional musicians. Typical symptoms are - on a physical level - the consequences of an increase in sympathetic tone with cardiac stress, such as acceleration of heartbeat, increase in blood pressure, increased respiratory rate and tremor up to nausea or flush reactions. These symptoms can cause emotional distress, a reduced musical and artistical performance up to an impaired functioning. While anxiety disorders are preferably treated using cognitive-behavioral therapy with exposure, this approach is rather difficult for treating music performance anxiety since the presence of a public or professional jury is required and not easily available. The use of virtual reality (VR) could therefore display an alternative. So far, no therapy studies on music performance anxiety applying virtual reality exposure therapy have investigated the therapy outcome including cardiovascular changes as outcome parameters. METHODS: This mono-center, prospective, randomized and controlled clinical trial has a pre-post design with a follow-up period of 6 months. 46 professional and semi-professional musicians will be recruited and allocated randomly to an VR exposure group or a control group receiving progressive muscle relaxation training. Both groups will be treated over 4 single sessions. Music performance anxiety will be diagnosed based on a clinical interview using ICD-10 and DSM-5 criteria for specific phobia or social anxiety. A behavioral assessment test is conducted three times (pre, post, follow-up) in VR through an audition in a concert hall. Primary outcomes are the changes in music performance anxiety measured by the German Bühnenangstfragebogen and the cardiovascular reactivity reflected by heart rate variability (HRV). Secondary outcomes are changes in blood pressure, stress parameters such as cortisol in the blood and saliva, neuropeptides, and DNA-methylation. DISCUSSION: The trial investigates the effect of VR exposure in musicians with performance anxiety compared to a relaxation technique on anxiety symptoms and corresponding cardiovascular parameters. We expect a reduction of anxiety but also a consecutive improvement of HRV with cardiovascular protective effects. TRIAL REGISTRATION: This study was registered on clinicaltrials.gov. (ClinicalTrials.gov Number: NCT05735860).

Increasing numbers and complexity of Staphylococcus aureus bloodstream infection-14 years of prospective evaluation at a German tertiary care centre with multi-centre validation of findings.

OBJECTIVES: Staphylococcus aureus bloodstream infection (SAB) is a common and severe infection. This study aims to describe temporal trends in numbers, epidemiological characteristics, clinical manifestations, and outcomes of SAB. METHODS: We performed a post-hoc analysis of three prospective SAB cohorts at the University Medical Centre Freiburg between 2006 and 2019. We validated our findings in a large German multi-centre cohort of five tertiary care centres (R-Net consortium, 2017-2019). Time-dependent trends were estimated using Poisson or beta regression models. RESULTS: We included 1797 patients in the mono-centric and 2336 patients in the multi-centric analysis. Overall, we observed an increasing number of SAB cases over 14 years (6.4%/year and 1000 patient days, 95% CI: 5.1% to 7.7%), paralleled by an increase in the proportion of community-acquired SAB (4.9%/year [95% CI: 2.1% to 7.8%]) and a decrease in the rate of methicillin-resistant-SAB (-8.5%/year [95% CI: -11.2% to -5.6%]). All of these findings were confirmed in the multi-centre validation cohort (6.2% cases per 1000 patient cases/year [95% CI: -0.6% to 12.6%], community-acquired-SAB 8.7% [95% CI: -1.2% to 19.6%], methicillin-resistant S. aureus-SAB -18.6% [95% CI: -30.6 to -5.8%]). Moreover, we found an increasing proportion of patients with multiple risk factors for complicated/difficult-to-treat SAB (8.5%/year, 95% CI: 3.6% to 13.5%, p < 0.001), alongside an overall higher level of comorbidities (Charlson comorbidity score 0.23 points/year, 95% CI: 0.09 to 0.37, p 0.005). At the same time, the rate of deep-seated foci such as osteomyelitis or deep-seated abscesses significantly increased (6.7%, 95% CI: 3.9% to 9.6%, p < 0.001). A reduction of in-hospital mortality by 0.6% per year (95% CI: 0.08% to 1%) was observed in the subgroup of patients with infectious diseases consultations. DISCUSSION: We found an increasing number of SAB combined with a significant increase in comorbidities and complicating factors in tertiary care centres. The resulting challenges in securing adequate SAB management in the face of high patient turnover will become an important task for physicians.

Resolving colistin resistance and heteroresistance in Enterobacter species.

Species within the Enterobacter cloacae complex (ECC) include globally important nosocomial pathogens. A three-year study of ECC in Germany identified Enterobacter xiangfangensis as the most common species (65.5%) detected, a result replicated by examining a global pool of 3246 isolates. Antibiotic resistance profiling revealed widespread resistance and heteroresistance to the antibiotic colistin and detected the mobile colistin resistance (mcr)-9 gene in 19.2% of all isolates. We show that resistance and heteroresistance properties depend on the chromosomal arnBCADTEF gene cassette whose products catalyze transfer of L-Ara4N to lipid A. Using comparative genomics, mutational analysis, and quantitative lipid A profiling we demonstrate that intrinsic lipid A modification levels are genospecies-dependent and governed by allelic variations in phoPQ and mgrB, that encode a two-component sensor-activator system and specific inhibitor peptide. By generating phoPQ chimeras and combining them with mgrB alleles, we show that interactions at the pH-sensing interface of the sensory histidine kinase phoQ dictate arnBCADTEF expression levels. To minimize therapeutic failures, we developed an assay that accurately detects colistin resistance levels for any ECC isolate.

Vancomycin-resistant Enterococcus faecium: admission prevalence, sequence types and risk factors-a cross-sectional study in seven German university hospitals from 2014 to 2018.

OBJECTIVES: Assessment of vancomycin-resistant Enterococcus faecium (VREfm) prevalence upon hospital admission and analysis of risk factors for colonization. METHODS: From 2014 to 2018, patients were recruited within 72 hours of admission to seven participating German university hospitals, screened for VREfm and questioned for potential risk factors (prior multidrug-resistant organism detection, current/prior antibiotic consumption, prior hospital, rehabilitation or long-term care facility stay, international travel, animal contact and proton pump inhibitor [PPI]/antacid therapy). Genotype analysis was done using cgMLST typing. Multivariable analysis was performed. RESULTS: In 5 years, 265 of 17,349 included patients were colonized with VREfm (a prevalence of 1.5%). Risk factors for VREfm colonization were age (adjusted OR [aOR], 1.02; 95% CI, 1.01-1.03), previous (aOR, 2.71; 95% CI, 1.87-3.92) or current (aOR, 2.91; 95% CI, 2.60-3.24) antibiotic treatment, prior multidrug-resistant organism detection (aOR, 2.83; 95% CI, 2.21-3.63), prior stay in a long-term care facility (aOR, 2.19; 95% CI, 1.62-2.97), prior stay in a hospital (aOR, 2.91; 95% CI, 2.05-4.13) and prior consumption of PPI/antacids (aOR, 1.29; 95% CI, 1.18-1.41). Overall, the VREfm admission prevalence increased by 33% each year and 2% each year of life. 250 of 265 isolates were genotyped and 141 (53.2%) of the VREfm were the emerging ST117. Multivariable analysis showed that ST117 and non-ST117 VREfm colonized patients differed with respect to admission year and prior multidrug-resistant organism detection. DISCUSSION: Age, healthcare contacts and antibiotic and PPI/antacid consumption increase the individual risk of VREfm colonization. The VREfm admission prevalence increase in Germany is mainly driven by the emergence of ST117.

Attack Rate for Wild-Type SARS-CoV-2 during Air Travel: Results from 46 Flights Traced by German Health Authorities, January-March and June-August 2020.

Background: Evidence on the risk of SARS-CoV-2 transmission during air travel is scarce. We aimed to estimate the attack rate for wild-type SARS-CoV-2 to improve the evidence base for the adaptation of nonpharmaceutical intervention (NPI) strategies aboard airplanes. Methods: In collaboration with German Public Health Authorities (PHA), we conducted a follow-up of in-flight SARS-CoV-2 contact persons. We included those contact persons whom the Emergency Operations Centre at the Robert Koch-Institute had forwarded to PHA between January to March 2020 (before masking on flights became mandatory) and June to August 2020 (after the introduction of mandatory masking). We retrospectively collected data on whether these contact persons had been successfully contacted, had become symptomatic and had been tested for SARS-CoV-2, and whether alternative exposures other than the flight were known. Results: Complete data that allowed for the calculation of attack rates were available for 108 contact persons (median age of 36 (IQR 24-53), 40% female), traveling on 46 flights with a median flight duration of 3 hours (IQR 2-3.5). 62 of these persons travelled after masking on flights became mandatory. 13/87 developed symptoms, 44/77 were tested (no data for 21 and 31). 13 persons (9 of whom had been SARS-CoV-2 positive) were excluded from the analysis of attack rates due to a likely alternative exposure. We thus identified 4 probable in-flight transmissions (2 of which occurred after the introduction of mandatory masking). The overall attack rate resulted in 4.2% (4/95; 95% CI: 1.4%-11.0%). Considering flights after mandatory masking, the attack rate was 3.6% (2/56, 95% CI 0.6%-13.4%), before masking 5.1% (2/39, 95% CI 0.9%-18.6%). Conclusions: The risk of wild-type SARS-CoV-2 transmission during air travel seemed low, but not negligible. In order to formulate an effective, evidence-based NPI protocol for air travel, further studies considering the different transmissibility of SARS-CoV-2 variants of concern and vaccination status are needed.

Surveillance and Genomic Analysis of Third-Generation Cephalosporin-Resistant and Carbapenem-Resistant Klebsiella pneumoniae Complex in Germany.

To analyse the epidemiology and population structure of third-generation cephalosporin-resistant (3GCR) and carbapenem-resistant (CR) Klebsiella pneumoniae complex isolates, patients were screened for rectal colonisation with 3GCR/CR K. pneumoniae complex on admission to six German university hospitals (2016-2019). Also collected were 3GCR/CR and susceptible K. pneumoniae isolates from patients with bloodstream infections (2016-2018). Whole-genome sequencing was performed followed by multilocus sequencing typing (MLST), core-genome MLST, and resistome and virulome analysis. The admission prevalence of 3GCR K. pneumoniae complex isolates during the 4-year study period was 0.8%, and 1.0 bloodstream infection per 1000 patient admissions was caused by K. pneumoniae complex (3GCR prevalence, 15.1%). A total of seven K. pneumoniae complex bloodstream isolates were CR (0.8%). The majority of colonising and bloodstream 3GCR isolates were identified as K. pneumoniae, 96.7% and 98.8%, respectively; the remainder were K. variicola and K. quasipneumoniae. cgMLST showed a polyclonal population of colonising and bloodstream isolates, which was also reflected by MLST and virulome analysis. CTX-M-15 was the most prevalent extended-spectrum beta-lactamase, and 29.7% of the colonising and 48.8% of the bloodstream isolates were high-risk clones. The present study provides an insight into the polyclonal 3GCR K. pneumoniae population in German hospitals.

Development and validation of BLOOMY prediction scores for 14-day and 6-month mortality in hospitalised adults with bloodstream infections: a multicentre, prospective, cohort study.

BACKGROUND: The burden of bloodstream infections remains high worldwide and cannot be confined to short-term in-hospital mortality. We aimed to develop scores to predict short-term and long-term mortality in patients with bloodstream infections. METHODS: The Bloodstream Infection due to Multidrug-resistant Organisms: Multicenter Study on Risk Factors and Clinical Outcomes (BLOOMY) study is a prospective, multicentre cohort study at six German tertiary care university hospitals to develop and validate two scores assessing 14-day and 6-month mortality in patients with bloodstream infections. We excluded patients younger than 18 years or who were admitted to an ophthalmology or psychiatry ward. Microbiological, clinical, laboratory, treatment, and survival data were prospectively collected on day 0 and day 3 and then from day 7 onwards, weekly. Participants were followed up for 6 months. All patients in the derivation cohort who were alive on day 3 were included in the analysis. Predictive scores were developed using logistic regression and Cox proportional hazards models with a machine-learning approach. Validation was completed using the C statistic and predictive accuracy was assessed using sensitivity, specificity, and predictive values. FINDINGS: Between Feb 1, 2017, and Jan 31, 2019, 2568 (61·5%) of 4179 eligible patients were recruited into the derivation cohort. The in-hospital mortality rate was 23·75% (95% CI 22·15-25·44; 610 of 2568 patients) and the 6-month mortality rate was 41·55% (39·54-43·59; 949 of 2284). The model predictors for 14-day mortality (C statistic 0·873, 95% CI 0·849-0·896) and 6-month mortality (0·807, 0·784-0·831) included age, body-mass index, platelet and leukocyte counts, C-reactive protein concentrations, malignancy (ie, comorbidity), in-hospital acquisition, and pathogen. Additional predictors were, for 14-day mortality, mental status, hypotension, and the need for mechanical ventilation on day 3 and, for 6-month mortality, focus of infection, in-hospital complications, and glomerular filtration rate at the end of treatment. The scores were validated in a cohort of 1023 patients with bloodstream infections, recruited between Oct 9, 2019, and Dec 31, 2020. The BLOOMY 14-day score showed a sensitivity of 61·32% (95% CI 51·81-70·04), a specificity of 86·36% (83·80-88·58), a positive predictive value (PPV) of 37·57% (30·70-44·99), and a negative predictive value (NPV) of 94·35% (92·42-95·80). The BLOOMY 6-month score showed a sensitivity of 69·93% (61·97-76·84), a specificity of 66·44% (61·86-70·73), a PPV of 40·82% (34·85-47·07), and a NPV of 86·97% (82·91-90·18). INTERPRETATION: The BLOOMY scores showed good discrimination and predictive values and could support the development of protocols to manage bloodstream infections and also help to estimate the short-term and long-term burdens of bloodstream infections. FUNDING: DZIF German Center for Infection Research. TRANSLATION: For the German translation of the abstract see Supplementary Materials section.

Implementation of an automated cluster alert system into the routine work of infection control and hospital epidemiology: experiences from a tertiary care university hospital.

BACKGROUND: Early detection of clusters of pathogens is crucial for infection prevention and control (IPC) in hospitals. Conventional manual cluster detection is usually restricted to certain areas of the hospital and multidrug resistant organisms. Automation can increase the comprehensiveness of cluster surveillance without depleting human resources. We aimed to describe the application of an automated cluster alert system (CLAR) in the routine IPC work in a hospital. Additionally, we aimed to provide information on the clusters detected and their properties. METHODS: CLAR was continuously utilized during the year 2019 at Charité university hospital. CLAR analyzed microbiological and patient-related data to calculate a pathogen-baseline for every ward. Daily, this baseline was compared to data of the previous 14 days. If the baseline was exceeded, a cluster alert was generated and sent to the IPC team. From July 2019 onwards, alerts were systematically categorized as relevant or non-relevant at the discretion of the IPC physician in charge. RESULTS: In one year, CLAR detected 1,714 clusters. The median number of isolates per cluster was two. The most common cluster pathogens were Enterococcus faecium (n = 326, 19 %), Escherichia coli (n = 274, 16 %) and Enterococcus faecalis (n = 250, 15 %). The majority of clusters (n = 1,360, 79 %) comprised of susceptible organisms. For 906 alerts relevance assessment was performed, with 317 (35 %) alerts being classified as relevant. CONCLUSIONS: CLAR demonstrated the capability of detecting small clusters and clusters of susceptible organisms. Future improvements must aim to reduce the number of non-relevant alerts without impeding detection of relevant clusters. Digital solutions to IPC represent a considerable potential for improved patient care. Systems such as CLAR could be adapted to other hospitals and healthcare settings, and thereby serve as a means to fulfill these potentials.

CDON gene contributes to pituitary stalk interruption syndrome associated with unilateral facial and abducens nerve palsy.

The relationship between congenital defects of the brain and facial anomalies was proven. The Hedgehog signaling pathway plays a fundamental role in normal craniofacial development in humans. Mutations in the sonic hedgehog (SHH) signaling gene CDON have been recently reported in patients with holoprosencephaly and with pituitary stalk interruption syndrome (PSIS). This study's aim was an elucidation of an 18-year-old patient presenting PSIS, multiple pituitary hormone deficiency, and congenital unilateral facial and abducens nerve palsy. Additionally, bilateral sensorineural hearing loss, dominating at the right site, was diagnosed. From the second year of life, growth deceleration was observed, and from the age of eight, anterior pituitary hormone deficiencies were gradually confirmed and substituted. At the MRI, characteristic triad for PSIS (anterior pituitary hypoplasia, interrupted pituitary stalk and ectopic posterior lobe) was diagnosed. We performed a comprehensive genomic screening, including microarrays for structural rearrangements and whole-exome sequencing for a monogenic defect. A novel heterozygous missense variant in the CDON gene (c.1814G > T; p.Gly605Val) was identified. The variant was inherited from the mother, who, besides short stature, did not show any disease symptoms. The variant was absent in control databases and 100 healthy subjects originating from the same population. We report a novel variant in the CDON gene associated with PSIS and congenital cranial nerve palsy. The variant revealed autosomal dominant inheritance with incomplete penetrance in concordance with previous studies reporting CDON defects.

Prevalence and risk factors of colonisation with vancomycin-resistant Enterococci faecium upon admission to Germany's largest university hospital.

Background: Hospital-acquired infections due to vancomycin-resistant enterococci (VRE) are emerging globally. The aims of our study were to estimate VRE colonisation prevalence in patients upon admission, to determine possible risk factors for VR E. faecium acquisition that already exist in the outpatient setting, and to monitor whether VRE-colonised patients developed a VRE infection during their current hospital stay. Methods: In 2014 and 2015, patients admitted to non-intensive care units were screened for rectal VRE carriage. The study patients filled out a questionnaire on potential risk factors. Analyses were restricted to VR E. faecium carriage. All patients with VRE colonisation were retrospectively monitored for infections with VRE during their current hospital stay. Results: In 4,013 enrolled patients, the VRE colonisation prevalence upon admission was 1.2% (n=48), and colonisation prevalence was 1.1% (n=45) for VR E. faecium. Only one VRE-colonised patient developed an infection with the detection of a VRE, among others. Colonisation with VR E. faecium was associated with current antibiotic use. Risk factors of VR E. faecium colonisation upon admission were increasing age, previous colonisation or infection with multidrug resistant organisms, sampling year 2015, and, within the previous six months, antibiotic exposure, a stay at a rehabilitation center, and a hospital stay. Conclusions: We observed that antibiotic treatment which occurred prior admission influenced VR E. faecium prevalence upon admission. Thus, wise antibiotic use in outpatient settings plays a major role in the prevention of VR E. faecium acquisition.

COVID-19: cross-border contact tracing in Germany, February to April 2020.

IntroductionThe Robert Koch Institute (RKI) managed the exchange of cross-border contact tracing data between public health authorities (PHA) in Germany and abroad during the early COVID-19 pandemic.AimWe describe the extent of cross-border contact tracing and its challenges.MethodsWe analysed cross-border COVID-19 contact tracing events from 3 February to 5 April 2020 using information exchanged through the European Early Warning Response System and communication with International Health Regulation national focal points. We described events by PHA, number of contacts and exposure context.ResultsThe RKI processed 467 events, initiating contact to PHA 1,099 times (median = 1; interquartile range (IQR): 1-2) and sharing data on 5,099 contact persons. Of 327 (70%) events with known exposure context, the most commonly reported exposures were aircraft (n = 64; 20%), cruise ships (n = 24; 7%) and non-transport contexts (n = 210; 64%). Cruise ship and aircraft exposures generated more contacts with authorities (median = 10; IQR: 2-16, median = 4; IQR: 2-11) and more contact persons (median = 60; IQR: 9-269, median = 2; IQR: 1-3) than non-transport exposures (median = 1; IQR: 1-6 and median = 1; IQR: 1-2). The median time spent on contact tracing was highest for cruise ships: 5 days (IQR: 3-9).ConclusionIn the COVID-19 pandemic, cross-border contact tracing is considered a critical component of the outbreak response. While only a minority of international contact tracing activities were related to exposure events in transport, they contributed substantially to the workload. The numerous communications highlight the need for fast and efficient global outbreak communication channels between PHA.

Vancomycin-resistant Enterococcus faecium colonizing patients on hospital admission in Germany: prevalence and molecular epidemiology.

OBJECTIVES: To analyse the rectal carriage rate and the molecular epidemiology of vancomycin-resistant Enterococcus faecium (VREfm) recovered from patients upon hospital admission. METHODS: Adult patients were screened at six German university hospitals from five different federal states upon hospital admission for rectal colonization with VREfm between 2014 and 2018. Molecular characterization of VREfm was performed by WGS followed by MLST and core-genome MLST analysis. RESULTS: Of 16350 patients recruited, 263 were colonized with VREfm, with increasing prevalence rates during the 5 year study period (from 0.8% to 2.6%). In total, 78.5% of the VREfm were vanB positive and 20.2% vanA positive, while 1.2% harboured both vanA and vanB. The predominant ST was ST117 (56.7%) followed by ST80 (15%), ST203 (10.9%), ST78 (5.7%) and ST17 (3.2%). ST117/vanB VREfm isolates formed a large cluster of 96 closely related isolates extending across all six study centres and four smaller clusters comprising 13, 5, 4 and 3 isolates each. In contrast, among the other STs inter-regional clonal relatedness was rarely observed. CONCLUSIONS: To our knowledge, this is the largest admission prevalence and molecular epidemiology study of VREfm. These data provide insight into the epidemiology of VREfm at six German university hospitals and demonstrate the remarkable inter-regional clonal expansion of the ST117/vanB VREfm clone.

Prevalence of third-generation cephalosporin-resistant Enterobacterales colonization on hospital admission and ESBL genotype-specific risk factors: a cross-sectional study in six German university hospitals.

OBJECTIVES: To assess the admission prevalence of third-generation cephalosporin-resistant Enterobacterales (3GCREB) and to assess whether risk factors vary by ß-lactamase genotype. METHODS: Adult patients were recruited within 72 h of admission to general wards of six university hospitals in 2014 and 2015. Rectal swabs were screened for 3GCREB and isolates were analysed phenotypically and genotypically. Patients were questioned on potential risk factors. Multivariable analyses were performed to identify risk factors for 3GCREB colonization and for specific ß-lactamases. RESULTS: Of 8753 patients screened, 828 were 3GCREB positive (9.5%). Eight hundred and thirteen isolates were available for genotyping. CTX-M-15 was the most common ESBL (38.0%), followed by CTX-M-1 (22.5%), CTX-M-14 (8.7%), CTX-M-27 (7.5%) and SHV-ESBL (4.4%). AmpC was found in 11.9%. Interestingly, 18 Escherichia coli isolates were AmpC positive, 12 of which (67%) contained AmpC on a gene of plasmid origin [CMY (n = 10), DHA (n = 2)]. Risk factors for 3GCREB colonization varied by genotype. Recent antibiotic exposure and prior colonization by antibiotic-resistant bacteria were risk factors for all ß-lactamases except CTX-M-14 and CTX-M-27. Travel outside Europe was a risk factor for CTX-M-15 and CTX-M-27 [adjusted OR (aOR) 3.49, 95% CI 2.88-4.24 and aOR 2.73, 95% CI 1.68-4.43]. A previous stay in a long-term care facility was associated with CTX-M-14 (aOR 3.01, 95% CI 1.98-4.59). A preceding hospital stay in Germany increased the risk of CTX-M-15 (aOR 1.27, 95% CI 1.14-1.41), while a prior hospital stay in other European countries increased the risk of SHV-ESBL colonization (aOR 3.85, 95% CI 1.67-8.92). CONCLUSIONS: The detection of different ESBL types is associated with specific risk factor sets that might represent distinct sources of colonization and ESBL-specific dissemination routes.

Lean back and wait for the alarm? Testing an automated alarm system for nosocomial outbreaks to provide support for infection control professionals.

INTRODUCTION: Outbreaks of communicable diseases in hospitals need to be quickly detected in order to enable immediate control. The increasing digitalization of hospital data processing offers potential solutions for automated outbreak detection systems (AODS). Our goal was to assess a newly developed AODS. METHODS: Our AODS was based on the diagnostic results of routine clinical microbiological examinations. The system prospectively counted detections per bacterial pathogen over time for the years 2016 and 2017. The baseline data covers data from 2013-2015. The comparative analysis was based on six different mathematical algorithms (normal/Poisson and score prediction intervals, the early aberration reporting system, negative binomial CUSUMs, and the Farrington algorithm). The clusters automatically detected were then compared with the results of our manual outbreak detection system. RESULTS: During the analysis period, 14 different hospital outbreaks were detected as a result of conventional manual outbreak detection. Based on the pathogens' overall incidence, outbreaks were divided into two categories: outbreaks with rarely detected pathogens (sporadic) and outbreaks with often detected pathogens (endemic). For outbreaks with sporadic pathogens, the detection rate of our AODS ranged from 83% to 100%. Every algorithm detected 6 of 7 outbreaks with a sporadic pathogen. The AODS identified outbreaks with an endemic pathogen were at a detection rate of 33% to 100%. For endemic pathogens, the results varied based on the epidemiological characteristics of each outbreak and pathogen. CONCLUSION: AODS for hospitals based on routine microbiological data is feasible and can provide relevant benefits for infection control teams. It offers in-time automated notification of suspected pathogen clusters especially for sporadically occurring pathogens. However, outbreaks of endemically detected pathogens need further individual pathogen-specific and setting-specific adjustments.

Incidence of healthcare-associated Clostridioides difficile infections and association with ward-level antibiotic consumption in a German university hospital: an ecological study.

OBJECTIVES: Clostridioides difficile infection (CDI) is one of the most important healthcare-associated infections. We aimed to describe the incidence density of healthcare-associated CDI (HA-CDI) in Germany's largest hospital and to identify associations with ward-level antimicrobial consumption. METHODS: We used surveillance data on CDI and antimicrobial consumption from 2014 to 2017 and analysed a potential association by means of multivariable regression analysis. RESULTS: We included 77 wards with 404998 admitted patients and 1850862 patient-days. Six hundred and seventy-one HA-CDI cases were identified, resulting in a pooled mean incidence density of 0.36/1000 patient-days (IQR = 0.34-0.39). HA-CDI incidence density on ICU and haematological-oncological wards was about three times higher than on surgical wards [incidence rate ratio (IRR) = 3.00 (95% CI = 1.96-4.60) and IRR = 2.78 (95% CI = 1.88-4.11), respectively]. Ward-level consumption of third-generation cephalosporins was the sole antimicrobial risk factor for HA-CDI. With each DDD/100 patient-days administered, a ward's HA-CDI incidence density increased by 2% [IRR = 1.02 (95% CI = 1.01-1.04)]. Other risk factors were contemporaneous community-associated CDI cases [IRR = 1.32 (95% CI = 1.07-1.63)] and CDI cases in the previous month [IRR = 1.27 (95% CI = 1.07-1.51)]. Furthermore, we found a significant decrease in HA-CDI in 2017 compared with 2014 [IRR = 0.68 (95% CI = 0.54-0.86)]. CONCLUSIONS: We confirmed that ward-level antimicrobial use influences HA-CDI and specifically identified third-generation cephalosporin consumption as a risk factor.

An App to Improve Eating Habits of Adolescents and Young Adults (Challenge to Go): Systematic Development of a Theory-Based and Target Group-Adapted Mobile App Intervention.

BACKGROUND: Due to the widespread use of mobile phones, dietary mobile apps are promising tools for preventing diet-related noncommunicable diseases early in life. However, most of the currently available nutrition apps lack scientific evaluation and user acceptance. OBJECTIVE: The objective of this study was the systematic design of a theory-driven and target group-adapted dietary mobile app concept to promote healthy eating habits with a focus on drinking habits as well as consumption of fruits and vegetables in adolescents and young adults, especially from disadvantaged backgrounds. METHODS: The design process was guided by the behavior change wheel (BCW). The development process comprised 3 stages. In stage 1, the target behavior was specified, and facilitators and barriers were identified. Furthermore, important insights into target group interests, needs, and values in the field of nutrition and apps were revealed. To this end, 2 empirical studies were conducted with the target group. In stage 2, results of stage 1 were translated into behavior change techniques (BCTs) and, finally, into app functionalities and features. Consequently, in stage 3, the concept was evaluated and optimized through expert interviews. RESULTS: Facilitators and barriers for achieving the target behavior were psychological capabilities (eg, self-efficacy), reflective motivation (eg, fitness), automatic motivation, social support, and physical opportunity (eg, time). Target group interests, needs, and values in the field of nutrition were translated into target group preferences for app usage, for example, low usage effort, visual feedback, or recipes. Education, training, incentives, persuasion, and enablement were identified as relevant intervention functions. Together with the target group preferences, these were translated via 14 BCTs, such as rewards, graded tasks, or self-monitoring into the app concept Challenge to go (C2go). The expert evaluation suggested changes of some app features for improving adherence, positive health effects, and technical feasibility. The C2go concept comprises 3 worlds: the (1) drinking, (2) vegetable, and (3) fruit worlds. In each world, the users are faced with challenges including feedback and a quiz. Tips were developed based on the health action process approach and to help users gain challenges and, thereby, achieve the target behavior. Challenges can be played alone or against someone in the community. Due to different activities, points can be collected, and levels can be achieved. Collected points open access to an Infothek (information section), where users can choose content that interests them. An avatar guides user through the app. CONCLUSIONS: C2go is aimed at adolescents and young adults and aims to improve their fruit and vegetable consumption as well as drinking habits. It is a theory-driven and target group-adapted dietary mobile intervention concept that uses gamification and was systematically developed using the BCW.

Admission prevalence of colonization with third-generation cephalosporin-resistant Enterobacteriaceae and subsequent infection rates in a German university hospital.

BACKGROUND: Many patients admitted to a hospital are already colonized with multi-drug resistant organisms (MDRO) including third-generation cephalosporin-resistant Enterobacteriaceae (3GCREB). The aim of our study was to determine the prevalence of rectal 3GCREB colonization at admission to a large German university hospital and to estimate infection incidences. In addition, risk factors for 3GCREB colonization were identified. MATERIALS/METHODS: In 2014 and 2015, patients were screened for rectal colonization with 3GCREB and filled out a questionnaire on potential risk factors at admission to a non-intensive care unit (non-ICU). All patients were retrospectively monitored for bacterial infections. Descriptive, univariable and multivariable logistic regression analyses were conducted to identify risk factors for 3GCREB colonization at admission. RESULTS: Of 4,013 patients included, 10.3% (n = 415) were rectally colonized with 3GCREB at admission. Incidence of nosocomial infections was 3.5 (95% CI 2.0-6.1) per 100 patients rectally colonized with 3GCREB compared to 2.3 (95% CI 1.8-3.0, P = 0.213) per 100 3GCREB negative patients. Independent risk factors for 3GCREB colonization were prior colonization / infection with MDRO (OR 2.30, 95% CI 1.59-3.32), prior antimicrobial treatment (OR 1.97, 95% CI 1.59-2.45), male sex (OR 1.38, 95% CI 1.12-1.70), prior travelling outside Europe (OR 2.39, 95% CI 1.77-3.22) and places of residence in the Berlin districts Charlottenburg-Wilmersdorf (OR 1.52, 95% CI 1.06-2.18), Friedrichshain-Kreuzberg (OR 2.32, 95% CI 1.44-3.74) and Mitte (OR 1.73, 95% CI 1.26-2.36). CONCLUSIONS: Admission prevalence of rectal colonization with 3GCREB was high, while infection incidence did not significantly differ between patients rectally colonized or not with 3GCREB at hospital admission. In consequence, hospitals should prioritize improvement of standard precautions including hand hygiene to prevent infections among all patients irrespective of their 3GCREB status at hospital admission.