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Objective Phenotypes are important for patient classification, disease prognostication, and treatment customization. We aimed to identify distinct clinical phenotypes of children and adolescents hospitalized with SARS-CoV-2 infection, and to evaluate their prognostic differences. Methods The German Society of Pediatric Infectious Diseases (DGPI) registry is a nationwide, prospective registry for children and adolescents hospitalized with a SARS-CoV-2 infection in Germany. We applied hierarchical clustering for phenotype identification with variables including sex, SARS-CoV-2-related symptoms on admission, pre-existing comorbidities, clinically relevant coinfection, and SARS-CoV-2 risk factors. Outcomes of this study were: discharge status and ICU admission. Discharge status was categorized as: full recovery, residual symptoms, and unfavorable prognosis (including consequential damage that has already been identified as potentially irreversible at the time of discharge and SARS-CoV-2-related death). After acquiring the phenotypes, we evaluated their correlation with discharge status by multinomial logistic regression model, and correlation with ICU admission by binary logistic regression model. We conducted an analogous subgroup analysis for those aged < 1 year (infants) and those aged ⩾ 1 year (non-infants). Results The DGPI registry enrolled 6983 patients, through which we identified six distinct phenotypes for children and adolescents with SARS-CoV-2 which can be characterized by their symptom pattern: phenotype A had a range of symptoms, while predominant symptoms of patients with other phenotypes were gastrointestinal (95.9%, B), asymptomatic (95.9%, C), lower respiratory tract (49.8%, D), lower respiratory tract and ear, nose and throat (86.2% and 41.7%, E), and neurological (99.2%, F). Regarding discharge status, patients with D and E phenotype had the highest odds of having residual symptoms (OR: 1.33 [1.11, 1.59] and 1.91 [1.65, 2.21], respectively) and patients with phenotype D were significantly more likely (OR: 4.00 [1.95, 8.19]) to have an unfavorable prognosis. Regarding ICU, patients with phenotype D had higher possibility of ICU admission than staying in normal ward (OR: 4.26 [3.06, 5.98]), compared to patients with phenotype A. The outcomes observed in the infants and non-infants closely resembled those of the entire registered population, except infants did not exhibit typical neurological/neuromuscular phenotypes. Conclusions Phenotypes enable pediatric patient stratification by risk and thus assist in personalized patient care. Our findings in SARS-CoV-2-infected population might also be transferable to other infectious diseases.

Background The burden of antimicrobial-resistance, specifically carbapenem-resistance in gram-negative bacteria (CRGN), presents a serious public health threat worldwide. In Europe, Southern and Eastern countries (SEC) display a higher CRGN-prevalence as compared to Northern and Western countries (NWC). Since SEC also display lower nurse-density on average, we hypothesized that the occurrence of CRGN might correlate with nurse understaffing and therefore aimed at quantifying a potential independent effect of nurse-density on total CRGN in Europe. Methods A 30-country cross-sectional study was conducted. Cumulative six-year CRGN-prevalence (2011–2016) in four gram-negative bacterial species was determined based on > 700 k clinical invasive isolates (EARS-net). We performed multivariable log-linear regression to provide estimations of the effect of nurse-density while adjusting to various health-system variables. Results Multivariable analysis (adj.-R 2  ~ 93%) suggested an average 0.4% [95%-CI 0.2–1.0%] CRGN-increase due to a decrement of one practicing nurse per week of hospital-stay of one population individual. Our modeling provided CRGN-estimations in two non-EARS-net countries (Switzerland and Turkey), which were almost equal to empirically estimated values (CAESAR-Network). Furthermore, a nurse-density-dependent moderation of the inter-species distribution balance was a likely pathway of the observed effect. These observations were specific for CRGN, in contrast to other resistance types in the same species. Conclusions This is the first attempt of quantifying potential nurse-density effects on antimicrobial-resistance at national level. Our results suggest an increase in CRGN by decreasing nurse-density. Nurse-density is thus a novel factor that might improve our understanding of the unbalanced CRGN-distribution among sub-European regions. Consequently, integrating nurse-density in future AMR-policies could be beneficial.

Little information is available on the local epidemiology of mobile genetic elements such as plasmids harboring acquired beta-lactamase genes in Western African Ghana. In the present study, we screened for plasmids in three Escherichia coli and four Klebsiella pneumoniae isolates expressing extended spectrum beta-lactamases (ESBL) mediated by the blaCTX-M-15 gene from chronically infected wounds of Ghanaian patients. Bacterial isolates were subjected to combined short-read and long-read sequencing to obtain the sequences of their respective plasmids. In the blaCTX-M-15-gene-carrying plasmids of the four ESBL-positive K. pneumoniae isolates, IncFIB/IncFII (n = 3) and FIA (n = 1) sequences were detected, while in the blaCTX-M-15-gene-carrying plasmids of the three ESBL-positive E. coli isolates, IncFIA/IncFIB (n = 2) and IncFIB (n = 1) sequences were found. The three IncFIB/IncFII sequence-containing plasmids were almost identical to a K. pneumoniae plasmid reported from France. They belonged to the clonal lineages ST17, ST36 and ST39 of K. pneumoniae, suggesting transversal spread of this obviously evolutionary successful plasmid in Ghana. Other resistance gene-encoding plasmids observed in the assessed Enterobacterales harbored IncFIA/IncR and IncFII sequences. International spread was confirmed by the high genetic similarity to resistance-mediating plasmids published from Asia, Australia, Europe and Northern America, including a blaCTX-M-15-gene-carrying plasmid isolated from a wild bird in Germany. In conclusion, the study contributed to the scarcely available information on the epidemiology of third-generation cephalosporine resistance-mediating plasmids in Ghana. Furthermore, the global spread of resistance-mediating plasmids provided hints on the evolutionary success of individual resistance-harboring plasmids by transversal spread among K. pneumoniae lineages in Ghana.

The spread of multidrug resistant organisms (MDRO) is a global healthcare challenge. Nosocomial outbreaks caused by MDRO are an important contributor to this threat. Computer-based applications facilitating outbreak detection can be essential to address this issue. To allow application reusability across institutions, the various heterogeneous microbiology data representations needs to be transformed into standardised, unambiguous data models. In this work, we present a multi-centric standardisation approach by using openEHR as modelling standard. Data models have been consented in a multicentre and international approach. Participating sites integrated microbiology reports from primary source systems into an openEHR-based data platform. For evaluation, we implemented a prototypical application, compared the transformed data with original reports and conducted automated data quality checks. We were able to develop standardised and interoperable microbiology data models. The publicly available data models can be used across institutions to transform real-life microbiology reports into standardised representations. The implementation of a proof-of-principle and quality control application demonstrated that the new formats as well as the integration processes are feasible. Holistic transformation of microbiological data into standardised openEHR based formats is feasible in a real-life multicentre setting and lays the foundation for developing cross-institutional, automated outbreak detection systems.

There are no investigations on hand hygiene during cardiopulmonary resuscitation (CPR), even though these patients are at high risk for healthcare-associated infections. We aimed to evaluate the number of indicated hand hygiene per CPR case in general and the fraction that could be accomplished without delay for other life-saving techniques through standardized observations. In 2022, we conducted Advanced Cardiovascular Life Support (ACLS) courses over 4 days, practicing 33 ACLS case vignettes with standard measurements of chest compression fractions and hand hygiene indications. A total of nine healthcare workers (six nurses and three physicians) participated. A total of 33 training scenarios resulted in 613 indications for hand disinfection. Of these, 150 (24%) occurred before patient contact and 310 (51%) before aseptic activities. In 282 out of 310 (91%) indications, which have the highest impact on patient safety, the medication administrator was responsible; in 28 out of 310 (9%) indications, the airway manager was responsible. Depending on the scenario and assuming 15 s to be sufficient for alcoholic disinfection, 56-100% (mean 84.1%, SD ± 13.1%) of all indications could have been accomplished without delaying patient resuscitation. Percentages were lower for 30-s of exposure time. To the best of our knowledge, this is the first study investigating the feasibility of hand hygiene in a manikin CPR study. Even if the feasibility is overestimated due to the study setup, the fundamental conclusion is that a relevant part of the WHO indications for hand disinfection can be implemented without compromising quality in acute care, thus increasing the overall quality of patient care.

In view of the importance of neurosyphilis and the difficulties encountered in diagnosing it, the S1 guideline \"Neurosyphilis\" has been published by the German Society for Neurology (DGN) in accordance with the stipulations of the Association of the Scientific Medical Societies in Germany (AWMF). The present article is an abridged translation of that German guideline. (a) Neurosyphilis can manifest as early neurosyphilis (meningitis, meningovascular neurosyphilis or syphilitic gummas) or late neurosyphilis (tabes dorsalis, general paresis). (b) The following diagnostic criteria help to establish the presence of probable neurosyphilis (always point iv, accompanied by any two of points i to iii): (i) subacute or chronic neuro-psychiatric symptoms; (ii) increased cerebrospinal fluid (CSF) cell count or signs of blood-CSF barrier disruption; (iii) positive effect of anti-neurosyphilis antibiotic therapy on clinical course and CSF findings; (iv) positive TPHA/TPPA or FTA test in serum. (c) The diagnosis of neurosyphilis is confirmed by the subsequent detection of intrathecal production of antibodies against . (d) In neurosyphilis, treatment with intravenous penicillin or ceftriaxone for 14 days is recommended. (e) The following parameters can be used to assess a therapeutic effect: clinical findings, serum VDRL, and CSF cell count. The German guideline on the diagnosis and treatment of neurosyphilis is a practical tool to support clinicians in diagnosing and treating patients with neurosyphilis. This article is an abridged translation of this guideline (Klein MW, J.; Angstwurm, K.; Esser, S.; Hahn, K.; Matschke, M.; Scheithauer, S.; Schoefer, H.; Sturzenegger, M.; Wildemann, B. Neurosyphilis, S1-Leitlinie. Deutsche Gesellschaft für Neurologie, Leitlinien für Diagnostik und Thearpie in der Neurologie 2020).

The present study aims to develop and discuss an extension of hospital-acquired severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections (HA-SIs) definition which goes beyond the use of time parameters alone. A confirmatory factor analysis was carried out to test a suitable definition for HA-SI. A two-center cohort study was carried out at two tertiary public hospitals in the German state of lower Saxony. The study involved a population of 366 laboratory-confirmed SARS-CoV-2-infected inpatients enrolled between March 2020 and August 2023. The proposed model shows adequate fit indices (CFI.scaled = 0.959, RMSEA = 0.049). A descriptive comparison with existing classifications revealed strong features of our model, particularly its adaptability to specific regional outbreaks. The use of the regional incidence as a proxy variable to better define HA-SI cases represents a pragmatic and novel approach. The model aligns well with the latest scientific results in the literature. This work successfully unifies, within a single model, variables which the recent literature described as significant for the onset of HA-SI. Further potential improvements and adaptations of the model and its applications, such as automating the categorization process (in terms of hospital acquisition) or employing a comparable model for hospital-acquired influenza classification, are subjects open for discussion.

Physicians of all specialties must be familiar with important principles of infectious diseases, but curricular time for this content is limited and clinical teaching requires considerable resources in terms of available patients and teachers. Serious games are scalable interventions that can help standardize teaching. This study assessed whether knowledge and skills acquired in a serious game translate to better performance in a clinical examination. Fifth-year undergraduate medical students ( = 100) at Goettingen Medical School were randomized to three groups receiving different levels of exposure to virtual patients presenting with signs and symptoms of either infective endocarditis or community-acquired pneumonia in a serious game simulating an accident and emergency department. Student performance was assessed based on game logfiles and an objective standardized clinical examination (OSCE). Higher exposure to virtual patients in the serious game did not result in superior OSCE scores. However, there was good agreement between student performance in the OSCE and in game logfiles ( = 0.477, = 0.005). An Item Response Theory analysis suggested that items from the serious game covered a wider range of ability, thus better differentiating between students within a given cohort. Repeated exposure to virtual patients with infectious diseases in a serious game did not directly impact on exam performance but game logfiles might be good and resource-sparing indicators of student ability. One advantage of using serious games in medical education is standardized content, a lower inhibition threshold to learn, and a need of less staff time compared to small-group clinical teaching.

Colonization and infection with bacteria with acquired antibiotic resistance are among the risks for soldiers on international deployments. Enterobacterales with resistance against third-generation cephalosporines are amongst the most frequently imported microorganisms. To contribute to the scarcely available epidemiological knowledge on deployment-associated resistance migration, we assessed the molecular epidemiology of third-generation cephalosporine-resistant Escherichia coli isolated between 2007 and 2016 from German soldiers after deployments, with a particular focus on the African Sahel region. A total of 51 third-generation cephalosporine-resistant E. coli isolated from 51 military returnees from deployment collected during the assessment period between 2007 and 2016 were subjected to short-read next-generation sequencing analysis. Returnees from the Sahel region (Djibouti, Mali, South Sudan, Sudan, Sudan, and Uganda) comprised a proportion of 52.9% (27/51). Repeatedly isolated sequence types according to the Warwick University scheme from returnees from the Sahel region were ST38, ST131, and ST648, confirming previous epidemiological assessments from various sub-Saharan African regions. Locally prevalent resistance genes in isolates from returnees from the Sahel region associated with third-generation resistance were blaCTX-M-15, blaCTX-M-27, blaCTX-M-1, blaTEM-169, blaCTX-M-14, blaCTX-M-99-like, blaCTX-M-125, blaSHV-12, and blaDHA-1, while virulence genes were east1, sat, and tsh in declining order of frequency of occurrence each. In line with phenotypically observed high resistance rates for aminoglycosides and trimethoprim/sulfamethoxazole, multiple associated resistance genes were observed. A similar, slightly more diverse situation was recorded for the other deployment sites. In summary, this assessment provides first next-generation sequencing-based epidemiological data on third-generation cephalosporine-resistant E. coli imported by deployed German soldiers with a particular focus on deployments to the Sahel region, thus serving as a small sentinel. The detected sequence types are well in line with the results from previous epidemiological assessments in sub-Saharan Africa.

Wound infections are common medical problems in sub-Saharan Africa but data on the molecular epidemiology are rare. Within this study we assessed the clonal lineages, resistance genes and virulence factors of Gram-negative bacteria isolated from Ghanaian patients with chronic wounds. From a previous study, 49 Pseudomonas aeruginosa, 21 Klebsiellapneumoniae complex members and 12 Escherichia coli were subjected to whole genome sequencing. Sequence analysis indicated high clonal diversity with only nine P. aeruginosa clusters comprising two strains each and one E. coli cluster comprising three strains with high phylogenetic relationship suggesting nosocomial transmission. Acquired beta-lactamase genes were observed in some isolates next to a broad spectrum of additional genetic resistance determinants. Phenotypical expression of extended-spectrum beta-lactamase activity in the Enterobacterales was associated with blaCTX-M-15 genes, which are frequent in Ghana. Frequently recorded virulence genes comprised genes related to invasion and iron-uptake in E. coli, genes related to adherence, iron-uptake, secretion systems and antiphagocytosis in P. aeruginosa and genes related to adherence, biofilm formation, immune evasion, iron-uptake and secretion systems in K. pneumonia complex. In summary, the study provides a piece in the puzzle of the molecular epidemiology of Gram-negative bacteria in chronic wounds in rural Ghana.