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Introduction: The global increase of multidrug-resistant organisms (MDROs) is one of the most urgent public health threats affecting both humans and animals. The One Health concept emphasizes the interconnectedness of human, animal and environmental health and highlights the need for integrated approaches to combat antimicrobial resistance (AMR). Although the sharing of environments and antimicrobial agents between companion animals and humans poses a risk for MDRO transmission, companion animals have been studied to a lesser extent than livestock animals. This study therefore used core genome multilocus sequence typing (cgMLST) to investigate the genetic relationships and putative transmission of MDROs between humans and pets., Methods: This descriptive integrated typing study included 252 human isolates, 53 dog isolates and 10 cat isolates collected from 2019 to 2022 at the Charité University Hospital in Berlin, Germany. CgMLST was performed to characterize methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and multidrug-resistant gram-negative bacteria. The genetic diversity of the MDROs of the different host populations was determined and compared based on sequence type and core genome complex type., Results: Within this study the majority of samples from pets and humans was genetically distinct. However, for some isolates, the number of allelic differences identified by cgMLST was low. Two cases of putative household transmission or shared source of VR E. faecium and MDR E. coli between humans and pets were documented., Conclusions: The interaction between humans and their pets appears to play a minor role in the spread of the MDROs studied. However, further research is needed. This study emphasizes the importance of comprehensive molecular surveillance and a multidisciplinary One Health approach to understand and contain the spread of MDROs in human and animal populations., Trial Registration: The study is registered with the German Clinical Trials Register (DRKS00030009)., (© 2024. The Author(s).)

Competing Interests: The authors declare that they have no conflict of interest.

An increasing amount of evidence has linked critical illness with dysbiotic microbiome signatures in different body sites. The disturbance of the indigenous microbiota structures has been further associated with disease severity and outcome and has been suggested to pose an additional risk for complications in intensive care units (ICUs), including hospital-acquired infections. A better understanding of the microbial dysbiosis in critical illness might thus help to develop strategies for the prevention of such complications. While most of the studies addressing microbiome changes in ICU patients have focused on the gut, the lung, or the oral cavity, little is known about the microbial communities on the skin of ICU patients. Since the skin is the outermost organ and the first immune barrier against pathogens, its microbiome might play an important role in the risk management for critically ill patients. This observational study characterizes the skin microbiome in ICU patients covering five different body sites at the time of admission. Our results show a profound dysbiosis on the skin of critically ill patients, which is characterized by a loss of site specificity and an overrepresentation of gut bacteria on all skin sites when compared to a healthy group. This study opens a new avenue for further investigations on the effect of skin dysbiosis in the ICU setting and points out the need of strategies for the management of dysbiosis in critically ill patients.IMPORTANCEUnbalanced gut microbiota in critically ill patients has been associated with poor outcome and complications during the intensive care unit (ICU) stay. Whether the disturbance of the microbial communities in these patients is extensive for other body sites, such as the skin, is largely unknown. The skin not only is the largest organ of the body but also serves as the first immune barrier against potential pathogens. This study characterized the skin microbiota on five different body sites in ICU patients at the time of admission. The observed disturbance of the bacterial communities might help to develop new strategies in the risk management of critically ill patients., Competing Interests: The authors declare no conflict of interest.

Background: To contain intra-hospital transmission of third-generation cephalosporin-resistant Enterobacterales (3GCR-E), contact isolation precautions are recommended., Aim: To quantify transmissions of 3GCR Escherichia coli and 3GCR Klebsiella pneumoniae within a hospital., Methods: An automated outbreak detection system (AODS) was used to identify clusters (N≥2) of 3GCR Enterobacterales for the years 2016, 2018 and 2020. Clusters were defined by phenotypic agreement of microbiological results and spatial and temporal relationship. Core genome multi-locus sequence typing (cgMLST) was used to confirm whether the cluster isolates were transmitted between patients., Findings: A total of 4343 3GCR E. coli and 1377 K. pneumoniae isolates were analysed. Among the 3GCR E. coli isolates, the AODS identified 304 isolates as cluster isolates, the median cluster size was two (range: 2-5). The cgMLST analysis revealed that a total of 23 (7.5%) 3GCR E. coli cluster isolates were transmission-associated, of which 20 isolates (87%) were detected in intensive care patients. Among the 3GCR K. pneumoniae isolates, the AODS identified 73 isolates as cluster isolates, the median cluster size was two (range: 2-4). CgMLST revealed that 35 (48%) 3GCR K. pneumoniae cluster isolates were transmission associated, of which 27 isolates (77%) were detected in intensive care patients., Conclusion: For 3GCR K. pneumoniae, cgMLST confirmed the AODS results more frequently than for 3GCR E. coli. Therefore, contact isolation precautions for 3GCR K. pneumoniae may be appropriate on intensive care units, but only in certain circumstances, such as outbreaks, for Enterobacterales with lower transmissibility, such as E. coli., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The antiseptic agent octenidine dihydrochloride (OCT) is used for skin preparation, for Staphylococcus aureus decolonization, and within bundles for the prevention of catheter-related or surgical site infections (SSIs). Here, we review the evidence for the effects of OCT from clinical studies., Methods: Review of studies published in the Medline, Scopus, and Cochrane databases until August 2022, performed in clinical settings and reporting on effects of OCT on S. aureus carriage/transmission, SSI prevention, and prevention of intensive care unit (ICU)-related or catheter-related bloodstream and insertion site infections., Results: We included 31 articles. The success of S. aureus decolonization with OCT-containing therapies ranged between 6 and 87%. Single studies demonstrated that OCT application led to a reduction in S. aureus infections, acquisition, and carriage. No study compared OCT for skin preparation before surgical interventions to other antiseptics. Weak evidence for the use of OCT for pre-operative washing was found in orthopedic and cardiac surgery, if combined with other topical measures. Mostly, studies did not demonstrate that daily OCT bathing reduced ICU-/catheter-related bloodstream infections with one exception., Conclusions: There is a need to perform studies assessing the clinical use of OCT compared with other antiseptics with respect to its effectiveness to prevent nosocomial infections.

The increase of Vancomycin-resistant Enterococcus faecium (VREfm) in recent years has been partially attributed to the rise of specific clonal lineages, which have been identified throughout Germany. To date, there is no gold standard for the interpretation of genomic data for outbreak analyses. New genomic approaches such as split k-mer analysis (SKA) could support cluster attribution for routine outbreak investigation. The aim of this project was to investigate frequent clonal lineages of VREfm identified during suspected outbreaks across different hospitals, and to compare genomic approaches including SKA in routine outbreak investigation. We used routine outbreak laboratory data from seven hospitals and three different hospital networks in Berlin, Germany. Short-read libraries were sequenced on the Illumina MiSeq system. We determined clusters using the published Enterococcus faecium -cgMLST scheme (threshold ≤20 alleles), and assigned sequence and complex types (ST, CT), using the Ridom SeqSphere+ software. For each cluster as determined by cgMLST, we used pairwise core-genome SNP-analysis and SKA at thresholds of ten and seven SNPs, respectively, to further distinguish cgMLST clusters. In order to investigate clinical relevance, we analysed to what extent epidemiological linkage backed the clusters determined with different genomic approaches. Between 2014 and 2021, we sequenced 693 VREfm strains, and 644 (93 %) were associated within cgMLST clusters. More than 74 % ( n =475) of the strains belonged to the six largest cgMLST clusters, comprising ST117, ST78 and ST80. All six clusters were detected across several years and hospitals without apparent epidemiological links. Core SNP analysis identified 44 clusters with a median cluster size of three isolates (IQR 2-7, min-max 2-63), as well as 197 singletons (41.4 % of 475 isolates). SKA identified 67 clusters with a median cluster size of two isolates (IQR 2-4, min-max 2-19), and 261 singletons (54.9 % of 475 isolates). Of the isolate pairs attributed to clusters, 7 % ( n =3064/45 596) of pairs in clusters determined by standard cgMLST, 15 % ( n =1222/8500) of pairs in core SNP-clusters and 51 % ( n =942/1880) of pairs in SKA-clusters showed epidemiological linkage. The proportion of epidemiological linkage differed between sequence types. For VREfm, the discriminative ability of the widely used cgMLST based approach at ≤20 alleles difference was insufficient to rule out hospital outbreaks without further analytical methods. Cluster assignment guided by core genome SNP analysis and the reference free SKA was more discriminative and correlated better with obvious epidemiological linkage, at least recently published thresholds (ten and seven SNPs, respectively) and for frequent STs. Besides higher overall discriminative power, the whole-genome approach implemented in SKA is also easier and faster to conduct and requires less computational resources.

Purpose: Minimally invasive glaucoma surgery (MIGS), like Xen45 gel stents, is known as effective therapy in lowering intraocular pressure (IOP); however, fibrotic reactions are a common problem in postoperative management. It was the aim of this study to investigate the therapeutic success of Xen45 gel stents as a stand-alone technique (Xen) and combined with cataract surgery (XenPhaco), and with antimetabolites (mitomycin C, MMC) in open-angle glaucoma patients., Methods: Retrospective analysis was performed of 199 eyes of 177 glaucoma patients of the Department of Ophthalmology, University of Erlangen Nürnberg, and from the Erlangen Glaucoma Registry (NCT00494923; ISSN 2191-5008, CS-2011) who underwent implantation of a Xen45 gel stent. Therapeutic success was defined as IOP reduction of ≥ 20% on the same or less anti-glaucomatous medication after 12 months compared to preoperative and without any additional glaucoma-related surgery (except bleb needling). IOP reduction, reduction in local anti-glaucomatous eye drops, and intra- and postoperative complications were monitored., Results: Stand-alone Xen45 gel stent: therapeutic success was reached in 39% (-MMC) and 55% (+MMC). Failure rate was 61% (-MMC) and 45% (+MMC). XenPhaco: therapeutic success was achieved in 57% (-MMC) and 46% (+MMC). Failure rate was 43% (-MMC) and 54% (+MMC). Data were not different for group and subgroup analyses (p > 0.05)., Conclusions: The use of MMC seemed to increase the therapeutic success rate after stand-alone Xen45 gel stent implantation and combined with cataract surgery, yet statistical significant was not reached., Competing Interests: L. D.: none; B. H.: Mobius Therapeutics, Allergan; R. L.: Mobius Therapeutics, Allergan., (Thieme. All rights reserved.)

Background and Aim: Despite a safe and effective vaccine being available for many years, the number of measles cases has been increasing again worldwide since 2018. Our report aims to identify putative reasons for this development., Methods: We conducted a selective literature search. Further, current reports and data from the World Health Organization (WHO), the United Nations Children's Fund (UNICEF), and the World Bank were evaluated., Results: According to the WHO, Madagascar, the Ukraine, and Israel had the highest incidences of measles worldwide between 1 July 2018 and 30 June 2019. Measles outbreaks are a sign of inadequate vaccination rates caused by multiple structural and psychological barriers. Structural barriers to measles vaccination, such as a lack of routine vaccination programs, have been identified as the main cause of low measles vaccination rates, particularly in fragile countries e.g. due to armed conflicts, but also in some subpopulations of higher-income countries e.g. due to lacking resources for vaccination services. Psychological barriers leading to vaccination skepticism were prevalent mainly in developed countries with well-functioning health systems and a high standard of living., Conclusion: The reasons for the global measles crisis are manifold and in some cases have existed for decades. However, the consequences appear to be accumulating and have had a dramatic impact on case numbers since 2018. The goal of measles elimination and maintenance of the necessary vaccination programs is a constant challenge that requires strict and permanent compliance with WHO recommendations. The number of measles cases reported in Germany is still at a level above the key target for measles elimination specified in the national immunization plan. Timely and/or locally restricted as well as nationwide outbreaks continue to occur. Since infectious agents can be transmitted across borders, the international perspective is an essential component of national health policy in Germany.

Background: Limitations of current therapy of depression highlight the need for an immediately available, easily implementable add-on treatment option with high acceptance from patients. Hyperthermic baths (HTB) are a form of balneotherapy with head-out-of-water-immersion in a hot pool or tub at 40 °C for 15-20 min. A prior study suggests that HTB added to usual depression care can have antidepressant effects., Method: Single-site, open-label randomised controlled 8-week parallel-group pilot study at a university outpatient clinic. 45 medically stable outpatients with moderate depression as determined by the 17-item Hamilton Depression Rating Scale (HAM-D) score ≥ 18 and a score ≥ 2 on item 1 (Depressed Mood) were recruited. They were randomised to twice weekly HTB (n = 22) or a physical exercise program (PEP) of moderate intensity (n = 23). Primary outcome measure was the change in HAM-D total score from baseline (T0) to the 2-week time point (T1). Linear regression analyses, adjusted for baseline values, were performed to estimate intervention effects on an intention-to-treat (ITT) and per-protocol (PP) principle., Results: Forty-five patients (HTB n = 22; PEP n = 23) were analyzed according to ITT (mean age = 48.4 years, SD = 11.3, mean HAM-D score = 21.7, SD = 3.2). Baseline-adjusted mean difference after 2 weeks was 4.3 points in the HAM-D score in favor of HTB (p < 0.001). Compliance with the intervention and follow-up was far better in the HTB group (2 vs 13 dropouts). Per protocol analysis only showed superiority of HTB as a trend (p = 0.068). There were no treatment-related serious adverse events. Main limitation: the number of dropouts in the PEP group (13 of 23) was higher than in other trials investigating exercise in depression. Due to the high number of dropouts the effect in the ITT-analysis may be overestimated., Conclusions: HTB added to usual care may be a fast-acting, safe and easy accessible method leading to clinically relevant improvement in depression severity after 2 weeks; it is also suitable for persons who have problems performing exercise training., Trial Registration: German Clinical Trials Register (DRKS) with the registration number DRKS00011013 (registration date 2016-09-19) before onset of the study.

Objectives: Infections as a result of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) are considered infections with a high public health burden. In this study, we aimed to identify incidences of and risk factors for healthcare-associated infections (HAIs) after rectal colonization with ESBL-producing Escherichia coli (ESBL-EC) or Klebsiella pneumoniae (ESBL-KP)., Methods: This prospective cohort study was performed in 2014 and 2015. Patients colonized with ESBL-EC or ESBL-KP were monitored for subsequent HAI with ESBL-E and other pathogens. In the case of an ESBL-E infection, rectal and clinical isolates were compared using pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing (WGS) for ESBL-KP isolates. Proportional hazard models were applied to identify risk factors for HAIs, and to analyse competing risks., Results: Among all patients admitted to the hospital during the study period, 13.6% were rectally screened for third-generation cephalosporin-resistant Enterobacterales (3GCREB). A total of 2386 rectal carriers of ESBL-EC and 585 of ESBL-KP were included in the study. Incidence density (ID) for HAI with ESBL-E was 2.74 per 1000 patient days at risk (95% confidence interval (CI) 2.16-3.43) among carriers of ESBL-EC, while it was 4.44 per 1000 patient days at risk (95% CI 3.17-6.04) among carriers of ESBL-KP. In contrast, ID for HAI with other pathogens was 4.36 per 1000 patient days at risk (95% CI 3.62-5.21) among carriers of ESBL-EC, and 5.00 per 1000 patient days at risk (95% CI 3.64-6.69) among carriers of ESBL-KP. Cox proportional hazard regression analyses identified colonization with ESBL-KP (HR = 1.58, 95% CI 1.068-2.325) compared with ESBL-EC as independent risk factor for HAI with ESBL-E. The results were consistent over all competing risk analyses., Conclusions: Clinicians should be aware of the increased risk of ESBL-E infections among patients colonized with ESBL-KP compared with ESBL-EC that might be caused by underlying diseases, higher pathogenicity of ESBL-KP and other factors., (Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)