Propionic Acid Shapes the Multiple Sclerosis Disease Course by an Immunomodulatory Mechanism.

Short-chain fatty acids are processed from indigestible dietary fibers by gut bacteria and have immunomodulatory properties. Here, we investigate propionic acid (PA) in multiple sclerosis (MS), an autoimmune and neurodegenerative disease. Serum and feces of subjects with MS exhibited significantly reduced PA amounts compared with controls, particularly after the first relapse. In a proof-of-concept study, we supplemented PA to therapy-naive MS patients and as an add-on to MS immunotherapy. After 2 weeks of PA intake, we observed a significant and sustained increase of functionally competent regulatory T (Treg) cells, whereas Th1 and Th17 cells decreased significantly. Post-hoc analyses revealed a reduced annual relapse rate, disability stabilization, and reduced brain atrophy after 3 years of PA intake. Functional microbiome analysis revealed increased expression of Treg-cell-inducing genes in the intestine after PA intake. Furthermore, PA normalized Treg cell mitochondrial function and morphology in MS. Our findings suggest that PA can serve as a potent immunomodulatory supplement to MS drugs.

Multicenter study to assess the use of BL-DetecTool for the detection of CTX-M-type ESBLs and carbapenemases directly from clinical specimens.

Antimicrobial resistance (AMR) is one of the major public health problems worldwide. Multiple strategies have been put in place to address this problem. One of them is the rapid detection of the mechanisms of resistance, such as extended-spectrum beta-lactamases (ESBLs) and/or carbapenemases. We conducted a multicenter study that included nine European centers for the assessment of prototypes of a novel lateral flow immunoassay-based device (BL-DetecTool) for a rapid detection of ESBL (NG-Test CTX-M-MULTI DetecTool) and/or carbapenemases (NG-Test CARBA 5 DetecTool) from Enterobacterales and Pseudomonas aeruginosa in positive urine, positive blood cultures, and rectal swabs. We performed a prospective analysis between January 2021 and June 2022, including overall 22,010 samples. Based on each hospital information, the sensitivity to detect CTX-M was 84%-100%, 90.9%-100%, and 75%-100% for urine, positive blood cultures, and enriched rectal swabs, respectively. On the other hand, the sensitivity to detect carbapenemases was 42.8%-100%, 75%-100%, and 66.6%-100% for urine, positive blood cultures, and enriched rectal swab, respectively. BL-DetecTool allows a rapid and reliable detection of ESBL and carbapenemases directly from urine, positive blood cultures, or enriched rectal swabs, being an easy technique to implement in the workflow of clinical microbiology laboratories. IMPORTANCE: The assessed rapid assay to detect CTX-M beta-lactamases and carbapenemases directly from clinical samples can favor in the rapid detection of these mechanisms of resistance and hence the administration of a more adequate antimicrobial treatment.

Prolonged carriage of OXA-244-carbapenemase-producing Escherichia coli complicates epidemiological investigations.

The rapid increase of OXA-244-producing Escherichia coli, predominantly driven by genetically clustered isolates of sequence type (ST)38, has been observed in at least nine European countries, including Germany. However, the reasons for the spread of OXA-244-producing E. coli remain unclear. Here, we aim to evaluate the possibility of prolonged carriage. We identified a total of six different patients with repeated detection of OXA-244-producing E. coli isolates, which were subjected to both short and long-read whole-genome sequencing (WGS). Besides allelic differences using core genome multilocus sequence typing (cgMLST) analyses, we obtained numbers of single-nucleotide polymorphisms (SNPs) to calculate individual base-pair substitution (BPS) rates. To assess possible re-exposure and risk factors for prolonged carriage, case interviews were conducted. The time between detections ranged from eleven months to more than three years. Initial isolates originated in three+ out of six cases from clinical samples, whereas remaining samples were from screening, mostly in the inpatient setting. As expected, cgMLST analyses showed low numbers of allelic differences between isolates of each case ranging from 1 to 4, whereas numbers of SNPs were between 2 and 99 (mean = 36), thus clearly highlighting the discrepancy between these different bacterial typing approaches. For five out of six cases, observed BPS rates suggest that patients can be colonized with OXA-244-producing E. coli, including ST38 cluster isolates, for extensively long times. Thus, we may have previously missed the epidemiological link between cases because exposure to OXA-244-producing E. coli could have occurred in a time frame, which has not been evaluated in previous investigations. Our results may help to guide future epidemiological investigations as well as to support the interpretation of genetic diversity of OXA-244-producing E. coli, particularly among ST38 cluster isolates.

Key summary of German national guideline for adult patients with nosocomial pneumonia- Update 2024 Funding number at the Federal Joint Committee (G-BA): 01VSF22007.

PURPOSE: This executive summary of a German national guideline aims to provide the most relevant evidence-based recommendations on the diagnosis and treatment of nosocomial pneumonia. METHODS: The guideline made use of a systematic assessment and decision process using evidence to decision framework (GRADE). Recommendations were consented by an interdisciplinary panel. Evidence analysis and interpretation was supported by the German innovation fund providing extensive literature searches and (meta-) analyses by an independent methodologist. For this executive summary, selected key recommendations are presented including the quality of evidence and rationale for the level of recommendation. RESULTS: The original guideline contains 26 recommendations for the diagnosis and treatment of adults with nosocomial pneumonia, thirteen of which are based on systematic review and/or meta-analysis, while the other 13 represent consensus expert opinion. For this key summary, we present 11 most relevant for everyday clinical practice key recommendations with evidence overview and rationale, of which two are expert consensus and 9 evidence-based (4 strong, 5 weak and 2 open recommendations). For the management of nosocomial pneumonia patients should be divided in those with and without risk factors for multidrug-resistant pathogens and/or Pseudomonas aeruginosa. Bacterial multiplex-polymerase chain reaction (PCR) should not be used routinely. Bronchoscopic diagnosis is not considered superior to´non-bronchoscopic sampling in terms of main outcomes. Only patients with septic shock and the presence of an additional risk factor for multidrug-resistant pathogens (MDRP) should receive empiric combination therapy. In clinically stabilized patients, antibiotic therapy should be de-escalated and focused. In critically ill patients, prolonged application of suitable beta-lactam antibiotics should be preferred. Therapy duration is suggested for 7-8 days. Procalcitonin (PCT) based algorithm might be used to shorten the duration of antibiotic treatment. Patients on the intensive care unit (ICU) are at risk for invasive pulmonary aspergillosis (IPA). Diagnostics for Aspergillus should be performed with an antigen test from bronchial lavage fluid. CONCLUSION: The current guideline focuses on German epidemiology and standards of care. It should be a guide for the current treatment and management of nosocomial pneumonia in Germany.

SARS-CoV-2 infections in patients, health care workers and hospital outbreaks during the first 3 waves of the pandemic: a retrospective analysis in a secondary care hospital network in Germany.

BACKGROUND: Hospital infections with SARS-CoV-2 continued during the initial waves of the pandemic worldwide. So far, Data on the dynamics of these infections and the economic burden of outbreaks are rare. METHODS: We retrospectively analysed SARS-CoV-2 infections in patients, hospital employees and nosocomial infections resulting in outbreaks in two hospitals of a secondary care hospital network in Germany during the initial 3 pandemic waves (03/2020-06/2021). In addition to hospital infections, we evaluated infection prevention strategies and the economic burden of hospital outbreaks. RESULTS: A total of 396 patients with SARS-CoV-2 infection were hospitalized in both hospitals. The risk factors for severe disease and death increased with age, male sex and a CRB-65 score > 0. The most frequent symptom was dyspnoea (30.1%). Sixty-five patients died, most of whom were in the 2nd wave. A total of 182 (12.5%) hospital employees were infected, 63 (34.6%) of whom were involved in outbreaks. An occupational risk of infection during outbreaks was particularly common among nurses and HCWs working on regular wards. Eleven hospital outbreaks led to high economic impact on both hospitals through the loss of manpower as result of infected employees, temporary locked wards, blocked beds, a reduced number of total hospitalized patients and increased personnel costs. CONCLUSION: Continuously adaptation of infection prevention strategies is a valuable tool to keep hospitals safe places for patients and employees. We do need more analyses of the different pandemic waves and applied infection prevention strategies to learn from weak points. TRIAL REGISTRATION: This research was conducted in accordance with the Declaration of Helsinki and national standards. The study protocol was approved by the relevant ethics committee of the Chamber of Physicians Westphalia-Lippe and University of Münster (no. 2021-475-f-S). The study was registered on 25th August 2021 at the German Clinical Trials Register (DRKS00025865).

Emergence of OXA-48-like producing Citrobacter species, Germany, 2011 to 2022.

BackgroundCarbapenemase-producing Enterobacterales are a public health threat worldwide and OXA-48 is the most prevalent carbapenemase in Germany and western Europe. However, the molecular epidemiology of OXA-48 in species other than Escherichia coli and Klebsiella pneumoniae remains poorly understood.AimTo analyse the molecular epidemiology of OXA-48 and OXA-48-like carbapenemases in Citrobacter species (spp.) in Germany between 2011 and 2022.MethodsData of 26,822 Enterobacterales isolates sent to the National Reference Centre (NRC) for Gram-negative bacteria were evaluated. Ninety-one Citrobacter isolates from 40 German hospitals harbouring bla OXA-48/OXA-48­like were analysed by whole genome sequencing and conjugation experiments.ResultsThe frequency of OXA-48 in Citrobacter freundii (CF) has increased steadily since 2011 and is now the most prevalent carbapenemase in this species in Germany. Among 91 in-depth analysed Citrobacter spp. isolates, CF (n = 73) and C. koseri (n = 8) were the most common species and OXA-48 was the most common variant (n = 77), followed by OXA-162 (n = 11) and OXA­181 (n = 3). Forty percent of the isolates belonged to only two sequence types (ST19 and ST22), while most other STs were singletons. The plasmids harbouring bla OXA­48 and bla OXA-162 belonged to the plasmid types IncL (n = 85) or IncF (n = 3), and plasmids harbouring bla OXA­181 to IncX3 (n = 3). Three IncL plasmid clusters (57/85 IncL plasmids) were identified, which were highly transferable in contrast to sporadic plasmids.ConclusionIn CF in Germany, OXA-48 is the predominant carbapenemase. Dissemination is likely due to distinct highly transmissible plasmids harbouring bla OXA­48 or bla OXA-48-like and the spread of the high-risk clonal lineages ST19 and ST22.

Dissemination of extensively drug-resistant NDM-producing Providencia stuartii in Europe linked to patients transferred from Ukraine, March 2022 to March 2023.

BackgroundThe war in Ukraine led to migration of Ukrainian people. Early 2022, several European national surveillance systems detected multidrug-resistant (MDR) bacteria related to Ukrainian patients.AimTo investigate the genomic epidemiology of New Delhi metallo-ß-lactamase (NDM)-producing Providencia stuartii from Ukrainian patients among European countries.MethodsWhole-genome sequencing of 66 isolates sampled in 2022-2023 in 10 European countries enabled whole-genome multilocus sequence typing (wgMLST), identification of resistance genes, replicons, and plasmid reconstructions. Five bla NDM-1-carrying-P. stuartii isolates underwent antimicrobial susceptibility testing (AST). Transferability to Escherichia coli of a bla NDM-1-carrying plasmid from a patient strain was assessed. Epidemiological characteristics of patients with NDM-producing P. stuartii were gathered by questionnaire.ResultswgMLST of the 66 isolates revealed two genetic clusters unrelated to Ukraine and three linked to Ukrainian patients. Of these three, two comprised bla NDM-1-carrying-P. stuartii and the third bla NDM-5-carrying-P. stuartii. The bla NDM-1 clusters (PstCluster-001, n = 22 isolates; PstCluster-002, n = 8 isolates) comprised strains from seven and four countries, respectively. The bla NDM-5 cluster (PstCluster-003) included 13 isolates from six countries. PstCluster-001 and PstCluster-002 isolates carried an MDR plasmid harbouring bla NDM-1, bla OXA-10, bla CMY-16, rmtC and armA, which was transferrable in vitro and, for some Ukrainian patients, shared by other Enterobacterales. AST revealed PstCluster-001 isolates to be extensively drug-resistant (XDR), but susceptible to cefiderocol and aztreonam-avibactam. Patients with data on age (n = 41) were 19-74 years old; of 49 with information on sex, 38 were male.ConclusionXDR P. stuartii were introduced into European countries, requiring increased awareness and precautions when treating patients from conflict-affected areas.

An appeal for strengthening genomic pathogen surveillance to improve pandemic preparedness and infection prevention: the German perspective.

The SARS-CoV-2 pandemic has highlighted the importance of viable infection surveillance and the relevant infrastructure. From a German perspective, an integral part of this infrastructure, genomic pathogen sequencing, was at best fragmentary and stretched to its limits due to the lack or inefficient use of equipment, human resources, data management and coordination. The experience in other countries has shown that the rate of sequenced positive samples and linkage of genomic and epidemiological data (person, place, time) represent important factors for a successful application of genomic pathogen surveillance. Planning, establishing and consistently supporting adequate structures for genomic pathogen surveillance will be crucial to identify and combat future pandemics as well as other challenges in infectious diseases such as multi-drug resistant bacteria and healthcare-associated infections. Therefore, the authors propose a multifaceted and coordinated process for the definition of procedural, legal and technical standards for comprehensive genomic pathogen surveillance in Germany, covering the areas of genomic sequencing, data collection and data linkage, as well as target pathogens. A comparative analysis of the structures established in Germany and in other countries is applied. This proposal aims to better tackle epi- and pandemics to come and take action from the "lessons learned" from the SARS-CoV-2 pandemic.

Microbiome composition and central serotonergic activity in patients with depression and type 1 diabetes.

The role of gut-brain axis functioning gains growing attention in research on the pathophysiology of major depressive disorders. Here, especially consequences of altered microbiota composition on tryptophan metabolism resulting in altered serotonergic neurotransmission in the central nervous system (CNS) have reached a central position. Previous research, however, mainly focused on either microbiota and peripheral serotonin levels or central serotonergic neurotransmission. The present study aimed to combine the analysis of microbiota composition and central serotonergic activity using a valid neurophysiological indicator. We recruited 19 adult patients with type 1 diabetes and depression (D + D; 7 males), 19 patients with type 1 diabetes (D-; 7 male), and 20 healthy participants (HC; 7 males). Next to the analysis of fecal microbiota regarding α- and ß-diversity, the loudness dependence of auditory evoked potential (LDAEP) was investigated, a non-invasive measurement of central serotonergic activity. High α-diversity was associated with high LDAEP, i.e., low serotonergic activity, in patients with diabetes and additional depression. Furthermore, relative abundances of bacterial families belonging to Bacteroidetes, Proteobacteria and Firmicutes were shown to have an impact on central serotonergic activity. This finding was supported by a tendency indicating an association of central serotonergic activity with the Bacteroidetes-Firmicutes ratio in both patients' groups. Together, this data suggests that the guts' microbiota composition might play an important role in regulating the central serotonergic activity in the brain.

Molecular surveillance reveals the emergence and dissemination of NDM-5-producing Escherichia coli high-risk clones in Germany, 2013 to 2019.

BackgroundCarbapenemase-producing Enterobacterales (CPE) are rapidly increasing worldwide, also in Europe. Although prevalence of CPE in Germany is comparatively low, the National Reference Centre for Multidrug-resistant Gram-negative Bacteria noted annually increasing numbers of NDM-5-producing Escherichia coli isolates.AimAs part of our ongoing surveillance programme, we characterised NDM-5-producing E. coli isolates received between 2013 and 2019 using whole genome sequencing (WGS).MethodsFrom 329 identified NDM-5-producing E. coli, 224 isolates from known geographical locations were subjected to Illumina WGS. Analyses of 222 sequenced isolates included multilocus sequence typing (MLST), core genome (cg)MLST and single-nucleotide polymorphism (SNP)-based analyses.ResultsResults of cgMLST revealed genetically distinct clusters for many of the 43 detected sequence types (ST), of which ST167, ST410, ST405 and ST361 predominated. The SNP-based phylogenetic analyses combined with geographical information identified sporadic cases of nosocomial transmission on a small spatial scale. However, we identified large clusters corresponding to clonal dissemination of ST167, ST410, ST405 and ST361 strains in consecutive years in different regions in Germany.ConclusionOccurrence of NDM-5-producing E. coli rose in Germany, which was to a large extent due to the increased prevalence of isolates belonging to the international high-risk clones ST167, ST410, ST405 and ST361. Of particular concern is the supra-regional dissemination of these epidemic clones. Available information suggest community spread of NDM-5-producing E. coli in Germany, highlighting the importance of epidemiological investigation and an integrated surveillance system in the One Health framework.

[Establishment of genomic pathogen surveillance to strengthen pandemic preparedness and infection prevention in Germany]. / Etablierung der Genomischen Erreger-Surveillance zur Stärkung des Pandemie- und Infektionsschutzes in Deutschland.

The SARS-CoV­2 pandemic has shown a deficit of essential epidemiological infrastructure, especially with regard to genomic pathogen surveillance in Germany. In order to prepare for future pandemics, the authors consider it urgently necessary to remedy this existing deficit by establishing an efficient infrastructure for genomic pathogen surveillance. Such a network can build on structures, processes, and interactions that have already been initiated regionally and further optimize them. It will be able to respond to current and future challenges with a high degree of adaptability.The aim of this paper is to address the urgency and to outline proposed measures for establishing an efficient, adaptable, and responsive genomic pathogen surveillance network, taking into account external framework conditions and internal standards. The proposed measures are based on global and country-specific best practices and strategy papers. Specific next steps to achieve an integrated genomic pathogen surveillance include linking epidemiological data with pathogen genomic data; sharing and coordinating existing resources; making surveillance data available to relevant decision-makers, the public health service, and the scientific community; and engaging all stakeholders. The establishment of a genomic pathogen surveillance network is essential for the continuous, stable, active surveillance of the infection situation in Germany, both during pandemic phases and beyond.

Aspergillus niger pneumonia as superinfection in a patient with pulmonary tuberculosis.

We report a patient with severe cavitary pulmonary tuberculosis and Aspergillus niger superinfection, whose only comorbidity was untreated diabetes mellitus. A. niger pneumonia was proven by PCR, sequencing and culture of pleural and respiratory secretions. The patient was successfully treated with a four-drug antituberculous regimen, liposomal amphotericin B (up to 5 mg/kg/d) and pleuro-pneumonectomy. Histology of the resected lung revealed destroyed lung tissue with inflammatory cells and fungal conidia. There were large deposits of polarising material, which was found to be calcium oxalate. There was also nodular caseating necrosis bordered by epitheloid cells and connective tissue. Thus, all diagnostic criteria for invasive A. niger infection were met. Several local risk factors, such as extensive lung damage and tissue acidification, may have favoured superinfection by A. niger. This case highlights the diagnostic value of calcium oxalate crystals in lung tissue and the need for combined antimicrobial and surgical treatment in extensive invasive aspergillosis caused by A. niger.

Effect of sigma E on carbapenem resistance in OXA-48-producing Klebsiella pneumoniae.

OBJECTIVES: Resistance levels of Gram-negative bacteria producing OXA-48 carbapenemase can vary greatly and some of them can even be categorized as susceptible to imipenem and meropenem according to EUCAST breakpoints. This study aimed to reveal resistance mechanisms leading to varying levels of resistance to carbapenems in Klebsiella pneumoniae with blaOXA-48 submitted to the German National Reference Centre for MDR Gram-negative bacteria. METHODS: Meropenem-susceptible clinical blaOXA-48-bearing K. pneumoniae isolates were put under gradually increasing selective pressure of meropenem. Clinical isolates and spontaneous meropenem-resistant mutants were whole-genome sequenced with Illumina and Oxford Nanopore Technology. Identified mutations apart from porin mutations were genetically constructed in the original clinical isolates using CRISPR/Cas. Clinical isolates and mutants were analysed for MICs, growth rates and expression of porins on mRNA and protein levels. RESULTS: Mutations associated with meropenem resistance were predominantly found in ompK36, but in some cases ompK36 was unaffected. In two mutants, ISs within the rpoE (sigma factor E; σE) operon were detected, directly in or upstream of rseA. These IS1R elements were then inserted into the same position of the susceptible clinical isolates using CRISPR/Cas. CRISPR-rseA-rseB-rseC mutants showed higher resistance levels to carbapenems and cephalosporins, reduced growth rates and reduced expression of major porins OmpK36 and OmpK35 in quantitative RT-PCR and SDS-PAGE. CONCLUSIONS: Enhanced synthesis of σE leads to increased resistance to cephalosporins and carbapenems in clinical K. pneumoniae isolates. This effect could be based upon remodelling of expression patterns of outer membrane proteins. The up-regulated σE stress response also leads to a significant reduction in growth rates.

Characterization of GMB-1, a novel metallo-ß-lactamase (MBL) found in three different Enterobacterales species.

OBJECTIVES: To identify novel carbapenem resistance mechanisms and their potential to spread among clinical isolates. METHODS: Four clinical isolates of Citrobacter freundii, Serratia marcescens and Raoultella planticola (n = 2) from one hospital in Central Germany were sent to the German National Reference Centre for Multidrug-resistant Gram-negative Bacteria for carbapenemase detection. Phenotypic tests indicated the presence of a metallo-ß-lactamase (MBL), but PCR for various MBL genes could not identify any. Using WGS data, a putative bla gene was identified. Its carbapenemase activity was verified by heterologous expression in an Escherichia coli cloning strain, with subsequent MIC determination by broth microdilution, as well as by in vitro hydrolysis assays using purified enzyme. RESULTS: WGS indicated the presence of a putative ß-lactamase with 48% amino acid identity to the subclass B1 MBL SPM-1. MIC studies confirmed that the novel enzyme formed a functional MBL, which was therefore designated as GMB-1 (German MBL). In vitro hydrolysis assays showed a lack of activity not only against aztreonam but also against ertapenem. WGS revealed that in all three species the blaGMB-1 gene was located on the chromosome as part of a genetic island with multiple ISs. CONCLUSIONS: The finding of GMB-1 once again shows that novel carbapenemases continue to emerge and make their way into clinically relevant species. The occurrence of GMB-1 in three different species demonstrates the extraordinary mobility of such genetic islands and their potential to spread carbapenemase genes into diverse genetic environments.

Detection of OXA-181-producing Pseudomonas aeruginosa in Germany.

OBJECTIVES: To report the detection of the class D carbapenemase OXA-181 in an MDR clinical Pseudomonas aeruginosa isolate in Germany. METHODS: Carbapenemase detection was performed by using several phenotypic tests such as the modified Hodge test, a combined disc test with boronic acid, EDTA or cloxacillin, a lysate-based inhibition assays and by PCR for common and rare carbapenemase genes. Antibiotic susceptibilities were determined by broth microdilution. The genetic environment of blaOXA-181 in the clinical P. aeruginosa isolate was characterised by Illumina and MinION sequencing. RESULTS: An multidrug-resistant P. aeruginosa was isolated from a tracheal swab in 2019 and was sent to the German National Reference Centre for multidrug-resistant Gram-negative bacteria for carbapenemase detection. Several phenotypic tests indicated the presence of a carbapenemase which was not inhibited by EDTA nor by boronic acid. PCRs for common and rare carbapenemase genes revealed the presence of a blaOXA-181 gene. WGS data confirmed that the gene was located on the chromosome as part of a Tn2013 transposon. The genetic organisation of blaOXA-181 has already been described in a P. aeruginosa isolate from England, but both isolates differed significantly in their sequence types (ST111/ST235). Analysis of the genetic environment of the blaOXA-181 gene also revealed high homology to a plasmid from a Klebsiella pneumoniae isolate. CONCLUSIONS: To our knowledge, this is the first report of blaOXA-181 in a clinical P. aeruginosa isolate in Germany which emphasises the ongoing spread of yet unusual carbapenemases among different Gram-negative species and therefore complicating their detection in routine laboratories.

Gut microbiota differs in composition between adults with type 1 diabetes with or without depression and healthy control participants: a case-control study.

BACKGROUND: Individuals with type 1 diabetes and those with depression show differences in the composition of the gut microbiome from that of healthy people. However, these differences have not yet been studied in patients with both diseases. Therefore, we compared the gut microbiome of people with type 1 diabetes with or without depression with matched healthy controls. METHODS: A case-control study was conducted in 20 adults with type 1 diabetes (group A), 20 adults with type 1 diabetes and depression (group B), and 20 healthy adults (group C). Gut microbiota composition was determined by sequencing of the V3-V4 region of the bacterial 16S rDNA and alpha and beta diversity was compared between the groups. RESULTS: Groups A and B both showed higher alpha diversity than the healthy control group (P < 0.001) but alpha diversity did not differ significantly between groups A and B. Participants having type 1 diabetes with (P < 0.05) or without comorbid depression (P < 0.001) differed regarding beta diversity from healthy controls but not between each other. Group B (diabetes with depression) had significantly higher abundance of Megaspaera than groups A and C. Both diabetes groups had a higher abundance of Christensenellaceae, Succinivibrionaceae, and Rhodospirillaceae than the healthy group but similar between-group abundances. CONCLUSIONS: While differences in alpha and beta diversity and in some bacterial taxa occurred only between participants with diabetes and healthy controls, specific characteristics regarding the abundance of Megasphaera were observed in people with diabetes and comorbid depression. In summary, the study findings indicate a possible involvement of bacterial groups in depression in people with diabetes. The results suggest replication studies in larger samples to verify these findings.

Increase in NDM-1 and NDM-1/OXA-48-producing Klebsiella pneumoniae in Germany associated with the war in Ukraine, 2022.

In 2022, German surveillance systems observed rapidly increasing numbers of NDM-1- and NDM-1/OXA-48-producing Klebsiella pneumoniae, which may in part reflect recurring pre-pandemic trends. Among these cases, however, a presence in Ukraine before diagnosis was frequently reported. Whole genome sequencing of 200 isolates showed a high prevalence of sequence types ST147, ST307, ST395 and ST23, including clusters corresponding to clonal dissemination and suggesting onward transmission in Germany. Screening and isolation of patients from Ukraine may help avoid onward transmission.

Phenotypic Detection and Differentiation of Carbapenemase Classes Including OXA-48-Like Enzymes in Enterobacterales and Pseudomonas aeruginosa by a Highly Specialized Micronaut-S Microdilution Assay.

The objective of this study was to evaluate the Micronaut-S carbapenemase detection microtiter plate assay for the detection of carbapenemases and Ambler class determination. The Micronaut-S carbapenemase detection microtiter plate was tested using a challenging collection of 154 carbapenemase-producing and 150 carbapenemase-negative clinical strains of Enterobacterales and Pseudomonas aeruginosa The Micronaut-S carbapenemase detection assay was able to detect 148/154 carbapenemase producers correctly, whereas 5/150 non-carbapenemase-producing isolates tested as false positive. This resulted in an overall sensitivity of 96% and a specificity of 97%. Regarding the detection of the carbapenemase class, the sensitivities and specificities were 93%/100%, 96%/100%, and 97%/99% for class A (n = 27), class B (n = 54), and class D (n = 73) carbapenemases, respectively. The Micronaut-S carbapenemase detection microtiter plate represents an easy-to-use and valuable tool for accurate and reliable detection of carbapenemases. In addition, it provides identification of the class of carbapenemase in most cases which can provide significant therapy guidance.

GPC-1, a novel class A carbapenemase detected in a clinical Pseudomonas aeruginosa isolate.

OBJECTIVES: To investigate the carbapenem resistance mechanism of a carbapenem-resistant clinical Pseudomonas aeruginosa isolate. METHODS: A carbapenem-resistant P. aeruginosa isolate was recovered from a tracheal swab from a patient of a general ward in central Germany. Various phenotypic tests confirmed production of a carbapenemase that could not be identified further by PCR. A novel bla gene was identified by WGS and its carbapenemase activity was verified by heterologous expression in an Escherichia coli cloning strain. Kinetic parameters of the novel ß-lactamase were determined by spectrophotometric measurements using purified enzyme. RESULTS: WGS confirmed the presence of a novel class A carbapenemase. The novel bla gene was named GPC-1 (GPC standing for German Pseudomonas Carbapenemase) and exhibited 77% amino acid identity to BKC-1. WGS also showed that blaGPC-1 was located on the chromosome surrounded by multiple ISs as part of a 26 kb genetic island. Heterologous expression of GPC-1 in E. coli TOP10 led to increased MICs of penicillins, oxyimino-cephalosporins, aztreonam and imipenem, but not of meropenem or ertapenem. Spectrophotometric measurements supported the MIC studies, but detected a slight hydrolysis of ertapenem and meropenem when using high concentrations of purified enzyme. CONCLUSIONS: The biochemical characterization of GPC-1 emphasizes the ongoing emergence of novel carbapenemases. Strains expressing a weak carbapenemase like GPC-1 might go unrecognized by routine diagnostics due to low MICs for the bacterial strains producing such enzymes.

New EUCAST definitions of S, I and R from 2019 - German physicians are largely not aware of the changes.

PURPOSE: On January 1st 2019, the new EUCAST definitions of susceptibility testing categories S, I and R took effect. The changes in the I category have considerable clinical impact because they lead to major changes in the antibiogram, and misinterpretation may result in inappropriate selection and dosing of antibiotics hampering effective treatment of infectious diseases. We assessed if German physicians are aware of the new definitions and their consequences. METHODS: We conducted a nationwide web-based survey to assess the knowledge on the new definitions of S, I and R. The survey was addressed to clinicians across all medical specialties working in Germany and was open from May 9th to July 30th 2019. RESULTS: The answers of 902 participants were included in the analysis. Most participants were employed at hospitals (79.3%) and had already completed specialist training (86.1%). The predominant specialty was internal medicine (50.6%). Of all participants, 45.7% did not know that there was a change in the definitions of S, I and R, and 65.4% did not feel well-informed about the changes. When the participants had to identify true and false statements regarding the new I, substantial knowledge gaps were apparent. Worst results were achieved by those physicians who are not employed in a hospital but work in their own practice. CONCLUSION: Our survey shows that German physicians are insufficiently informed about the new definitions of S, I and R. Further education is strongly needed to ensure optimal treatment of infectious diseases.