Adolescent-onset major depressive disorder (MDD) is associated with an increased risk of recurrent depressive episodes, suicidal behaviors, and psychiatric morbidity throughout the lifespan. The objective of the present study was to investigate brain structural and functional changes in adolescent patients with MDD. Furthermore, we aimed to clarify the influence of early-life stress on brain function and structure. The study investigated adolescent patients with severe MDD (n=20, mean age=16.0, range=15-18 years) and a control sample of matched healthy adolescents (n=21, mean age=16.6, range=15-18 years). Functional MRI data were obtained using a face-matching paradigm to investigate emotion processing. Structural MRI data were analyzed using voxel-based morphometry (VBM). In line with previous studies on adult MDD, adolescent patients showed elevated amygdala activity to negative and reduced amygdala activity to positive emotional stimuli. Furthermore, MDD patients showed smaller hippocampal volumes compared to healthy adolescents. Higher levels of childhood maltreatment were associated with smaller hippocampal volumes in both depressed patients and healthy controls, whereby no associations between amygdala reactivity and childhood maltreatment were found. Our results suggest that hippocampal alterations in youth MDD patients may at least partly be traced back to higher occurrence of early-life adverse experiences. Regarding the strong morphometric impact of childhood maltreatment and its distinctly elevated prevalence in MDD populations, this study provides an alternative explanation for frequently observed limbic structural abnormalities in depressed patients.

Vancomycin-resistant enterococci (VRE) are relevant nosocomial pathogens with an increasing incidence in the last decades. Their transmission is optimal in the hospital setting, as it offers two potential, large reservoirs that are closely related: susceptible patients and their environment. Here we investigate the role of the hospital environment in the nosocomial transmission of VRE by establishing concrete links between contaminated surfaces and colonized/infected patients in outbreak and non-outbreak settings. Environmental and patient VRE isolates were collected between 2013 and 2019 and analyzed by whole-genome sequencing (WGS), subsequent multilocus sequence typing (MLST), and core genome (cg) MLST. Pairs of isolates differing in <3 alleles were rated as closely related, making a transmission likely. Fifty-three environmental VRE isolates were analyzed. MLST sequence types (ST) ST203 (50.0%), ST192 (21.3%), ST117 (17.3%), ST721 (8.8%), ST80 (2%), and ST1489 (0.7%) were detected, carrying the resistance determinants vanA (72.7%), vanB (24%), or both (3.3%). Of the 53 environmental isolates, 51 were found to form five clusters with genetically related patient isolates (n = 97 isolates). WGS confirms the role of the environment in the transmission dynamics of VRE in both the outbreak and non-outbreak settings, highlighting the importance of prevention and control of VRE spread.

Staphylococcus schweitzeri belongs to the Staphylococcus aureus-related complex and is mainly found in African wildlife; no infections in humans are reported yet. Hence, its medical importance is controversial. The aim of this work was to assess the virulence of S. schweitzeri in vitro. The capacity of African S. schweitzeri (n = 58) for invasion, intra- and extracellular cytotoxicity, phagolysosomal escape, coagulase activity, biofilm formation and host cell activation was compared with S. aureus representing the most common clonal complexes in Africa (CC15, CC121, CC152). Whole genome sequencing revealed that the S. schweitzeri isolates belonged to five geographical clusters. Isolates from humans were found in two different clades. S. schweitzeri and S. aureus showed a similar host cell invasion (0.9 vs. 1.2 CFU/Vero cell), host cell activation (i.e. expression of pro-inflammatory cytokines, 4.1 vs. 1.7 normalized fold change in gene expression of CCL5; 7.3 vs. 9.9 normalized fold change in gene expression of IL8, A549 cells) and intracellular cytotoxicity (31.5% vs. 25% cell death, A549 cells). The extracellular cytotoxicity (52.9% vs. 28.8% cell death, A549 cells) was higher for S. schweitzeri than for S. aureus. Nearly all tested S. schweitzeri (n = 18/20) were able to escape from phagolysosomes. In conclusion, some S. schweitzeri isolates display virulence phenotypes comparable to African S. aureus. S. schweitzeri might become an emerging zoonotic pathogen within the genus Staphylococcus.

Stenotrophomonas maltophilia is an important nosocomial pathogen in immunocom-promised individuals and characterized by intrinsic resistance to broad-spectrum antibacterial agents. Limited data exists on its clinical relevance in immunocompromised pediatric patients, particularly those with hematological or oncological disorders. In a retrospective single center cohort study in pediatric patients receiving care at a large european pediatric hematology and oncology department, ten cases of invasive S.maltophilia infections (blood stream infections (BSI), 4; BSI and pneumonia, 3, or soft tissue infection, 2; and pneumonia, 1) were identified between 2010 and 2020. Seven patients had lymphoblastic leukemia and/or were post allogeneic hematopoietic cell transplantation. Invasive S.maltophilia infections occurred in a setting of indwelling central venous catheters, granulocytopenia, defective mucocutaneous barriers, treatment with broad-spectrum antibacterial agents, and admission to the intensive care unit. Whole genome sequencing based typing revealed no genetic relationship among four individual S.maltophilia isolates. The case fatality rate and mortality at 100 days post diagnosis were 40 and 50%, respectively, and three patients died from pulmonary hemorrhage. Invasive S.maltophilia infections are an emerging cause of infectious morbidity in patients receiving care at departments of pediatric hematology and oncology and carry a high case fatality rate.

Various Gram staining automated systems are available to accelerate and standardize the staining process but a systematic comparison of different systems is largely lacking. The objective of this study was to evaluate two devices in comparison to manual Gram staining. Clinical samples (n=500, University Hospital Münster, Germany, May-June 2020) were simultaneously Gram stained manually and with two automated Gram strainers (PREVI® Color Gram, bioMérieux and ColorAX2, Axonlab). The quality was assessed based on four criteria: (i) homogeneous staining of bacteria/fungi, (ii) uniform staining of the background, (iii) absence of staining artifacts and (iv) congruency between culture and microscopy. Each criterion was rated with “0” (absence) or “1” (presence) point to calculate a quality score (0–4 points). The costs for each staining procedure were calculated based on consumables and hands-on time (applying the average wage of a laboratory technician in the public service for Germany and the US). The mean (±SD) quality scores were comparable for manual staining (3.06±0.91) and PREVI® Color Gram (3.04±0.90, p=0.6) while significantly lower scores were achieved by ColorAX2 (2.57±1.09, p<0.0001). The total cost per Gram staining was 1.13 €/1.34 $ (PREVI® Color Gram), 0.80 €/0.83 $ (manual) and 0.60 €/0.71 $ (ColorAX2), respectively. The quality and costs per slide vary significantly between instruments of different manufacturers.

We report a case of a soft-tissue infection with Francisella philomiragia , a rare opportunistic pathogen in individuals with chronic granulomatous disease.

Background Staphylococcus aureus can colonize various host species, and human-animal interaction is a significant factor for cross-species transmission. However, data on S. aureus colonization in animals, particularly on ruminants in close contact with humans, is limited. The West African Dwarf (WAD) goat is among the earliest domesticated ruminant associated with rural dwellers and small-holder farmers in sub-Saharan Africa. This study aimed to investigate the population structure, antibiotic resistance, and virulence gene determinants of S. aureus from the WAD goat in Nigeria. Methods Nasal samples were obtained from the WAD goat in five markets in Osun State, South-West Nigeria. S. aureus was characterized by antibiotic susceptibility testing, detection of virulence determinants, spa typing, and multilocus sequence typing (MLST). Representative isolates were selected for whole-genome sequencing, biofilm, and cytotoxicity assay. Results Of the 726 nasal samples obtained from the WAD goat, 90 S. aureus (12.4%) were recovered. Overall, 86 isolates were methicillin-susceptible, and four were mecA-positive (i.e., methicillin-resistant S. aureus [MRSA]). A diverse S. aureus clonal population was observed (20 sequence types [STs] and 37 spa types), while 35% (13/37) and 40% (8/20) were new spa types and STs, respectively. Eleven MLST clonal complexes (CC) were identified (CC1, CC5, CC8, CC15, CC30, CC45, CC97, CC121, CC133, CC152, CC522). The MRSA isolates were designated as t127-ST852-CC1-SCCmec type VII, t4690-ST152-CC152-SCCmec type Vc, and t8821-ST152-CC152-SCCmec type Vc. Phylogenetic analysis revealed that 60% (54/90) of all isolates were associated with ruminant lineages (i.e., CC133, CC522). Panton-Valentine Leukocidin (PVL)-positive S. aureus was identified in CC1, CC30, CC121, and CC152. For the CC522 isolates, we illustrate their pathogenic potential by the detection of the toxic shock syndrome gene and hemolysins, as well as their strong cytotoxicity and ability to form biofilms. Conclusions This is the first detailed investigation on the genomic content of S. aureus from the WAD goat in Nigeria. The S. aureus population of the WAD goat consists mainly of ruminant-associated lineages (e.g., CC133, CC522), interspersed with human-associated clones, including PVL-positive MRSA CC1 and CC152.

Objectives: Staphylococcus aureus bacteriuria (SABU) is rare but can be an indicator of S. aureus bacteremia (SAB). The objective of this study was to assess the proportion of SAB in patients with SABU and identify risk factors in a hospital-based population. Methods: We used electronic databases to identify eligible patients to be enrolled in a retrospective cohort study. Inclusion criteria were (i) SABU, (ii) !18 years of age, and (iii) !1 blood culture sampled AE3 months of SABU. Patients with missing values for demographic (e.g., age, sex) or clinical characteristics (e.g., comorbidities) and laboratory analyses were excluded. Results: In total, 245 patients attending the University Hospital Münster, Germany, between 1 January 2012 and 31 December 2019 met the inclusion/exclusion criteria. Of the 245 patients with SABU, 66 had a concomitant SAB (26.9%). Elevated C-reactive protein (CRP) levels were associated with SAB. Other parameters (e.g., leukocytes, comorbidities) were not associated with SAB in a multivariate analysis. Conclusion:The frequency of SAB in patients with SABU was high and warrants active screening for bloodstream infections in hospitalized patients, particularly if CRP levels are elevated.