Presence of hypervirulence-associated determinants in Klebsiella pneumoniae from hospitalised patients in Germany.

BACKGROUND: Klebsiella (K.) pneumoniae is a ubiquitous Gram-negative bacterium and a common coloniser of animals and humans. Today, K. pneumoniae is one of the most persistent nosocomial pathogens worldwide and poses a severe threat/burden to public health by causing urinary tract infections, pneumonia and bloodstream infections. Infections mainly affect immunocompromised individuals and hospitalised patients. In recent years, a new type of K. pneumoniae has emerged associated with community-acquired infections such as pyogenic liver abscess in otherwise healthy individuals and is therefore termed hypervirulent K. pneumoniae (hvKp). The aim of this study was the characterisation of K. pneumoniae isolates with properties of hypervirulence from Germany. METHODS: A set of 62 potentially hypervirulent K. pneumoniae isolates from human patients was compiled. Inclusion criteria were the presence of at least one determinant that has been previously associated with hypervirulence: (I) clinical manifestation, (II) a positive string test as a marker for hypermucoviscosity, and (III) presence of virulence associated genes rmpA and/or rmpA2 and/or magA. Phenotypic characterisation of the isolates included antimicrobial resistance testing by broth microdilution. Whole genome sequencing (WGS) was performed using Illumina® MiSeq/NextSeq to investigate the genetic repertoire such as multi-locus sequence types (ST), capsule types (K), further virulence associated genes and resistance genes of the collected isolates. For selected isolates long-read sequencing was applied and plasmid sequences with resistance and virulence determinants were compared. RESULTS: WGS analyses confirmed presence of several signature genes for hvKp. Among them, the most prevalent were the siderophore loci iuc and ybt and the capsule regulator genes rmpA and rmpA2. The most dominant ST among the hvKp isolates were ST395 capsule type K2 and ST395 capsule type K5; both have been described previously and were confirmed by our data as multidrug-resistant (MDR) isolates. ST23 capsule type K1 was the second most abundant ST in this study; this ST has been described as commonly associated with hypervirulence. In general, resistance to beta-lactams caused by the production of extended-spectrum beta-lactamases (ESBL) and carbapenemases was observed frequently in our isolates, confirming the threatening rise of MDR-hvKp strains. CONCLUSIONS: Our study results show that K. pneumoniae strains that carry several determinants of hypervirulence are present for many years in Germany. The detection of carbapenemase genes and hypervirulence associated genes on the same plasmid is highly problematic and requires intensified screening and molecular surveillance. However, the non-uniform definition of hvKp complicates their detection. Testing for hypermucoviscosity alone is not specific enough to identify hvKp. Thus, we suggest that the classification of hvKp should be applied to isolates that not only fulfil phenotypical criteria (severe clinical manifestations, hypermucoviscosity) but also (I) the presence of at least two virulence loci e.g. iuc and ybt, and (II) the presence of rmpA and/or rmpA2.

Improving leadership skills of infection prevention and control teams by psychological empowerment: study protocol for a cluster randomised controlled trial (IP-POWER).

INTRODUCTION: Infection prevention and control (IPC) teams are routinely confronted with intense emotions in their daily work, as they are involved in many change processes with front-line medical staff, for example, when promoting compliance with basic IPC measures. In addition, they are confronted with challenges due to their role as intermediaries. Based on former research, this study aims to empower IPC teams to promote clinicians' compliance through interventions focusing on the IPC teams' leadership skills. METHODS AND ANALYSIS: The IP-POWER study (Infection Prevention with head and heart: Psychological empowerment of IPC teams), a multicentre, two-arm, non-blinded, cluster-randomised controlled trial with a parallel waiting control group, is planned to be conducted in Germany as of February to November 2024. A group of 10 voluntary hospitals is going to participate in a multistage intervention programme, including 2 days of intense psychological training; 5 hospitals will be randomly assigned to the waiting control group. After the workshops, there will be a 12-week follow-up period during which the contents learnt within the workshops can be applied and internalised into IPC practice. The proposed outcomes (both self-assessed and other-assessed leadership competencies of IPC team members and their task profiles, perceived workload, motivation to act in order to implement IP measures and goal attainment) are going to be collected with an online questionnaire, followed by an analysis with IBM SPSS (Statistics 29 (or later)) using descriptive analyses and multiple linear regressions. Additionally, as external data sources, hand hygiene compliance rates from the study hospitals' monitoring systems will be analysed using χ² tests. ETHICS AND DISSEMINATION: This study was reviewed and approved by the ethics committee of the University of Leipzig (184/23-ek; vote from 4 July 2023). Findings will be disseminated via peer-review publications, and national and international conference presentations. TRIAL REGISTRATION NUMBER: DRKS00031879.

Rectal colonization is predictive for surgical site infections with multidrug-resistant bacteria in abdominal surgery.

PURPOSE: Superficial surgical site infections (SSI) are a common complication after abdominal surgery. Additionally, multidrug-resistant organisms (MDRO) have shown an increasing spread in recent years with a growing importance for health care. As there is varying evidence on the importance of MDRO in different surgical fields and countries as causative agents of SSI, we report our findings of MDRO-caused SSI. METHODS: We assembled an institutional wound register spanning the years 2015-2018 including all patients with abdominal surgery and SSI only, including demographics, procedure-related data, microbiological data from screenings, and body fluid samples. The cohort was examined for the frequency of different MDRO in screenings, body fluids, and wound swabs and assessed for risk factors for MDRO-positive SSI. RESULTS: A total of 138 out of 494 patients in the register were positive for MDRO, and of those, 61 had an MDRO isolated from their wound, mainly multidrug-resistant Enterobacterales (58.1%) followed by vancomycin-resistant Enterococcus spp. (19.7%). As 73.2% of all MDRO-carrying patients had positive rectal swabs, rectal colonization could be identified as the main risk factor for an SSI caused by a MDRO with an odds ratio (OR) of 4.407 (95% CI 1.782-10.896, p = 0.001). Secondly, a postoperative ICU stay was also associated with an MDRO-positive SSI (OR 3.73; 95% CI 1.397-9.982; p = 0.009). CONCLUSION: The rectal colonization status with MDRO should be taken into account in abdominal surgery regarding SSI prevention strategies. Trial registration Retrospectively registered in the German register for clinical trials (DRKS) 19th December 2019, registration number DRKS00019058.

ICU infection surveillance can be based on electronic routine data: results of a case study.

BACKGROUND: The surveillance of hospital-acquired infections in Germany is usually conducted via manual chart review; this, however, proves resource intensive and is prone to a certain degree of subjectivity. Documentation based on electronic routine data may present an alternative to manual methods. We compared the data derived via manual chart review to that which was derived from electronic routine data. METHODS: Data used for the analyses was obtained from five of the University of Leipzig Medical Center's (ULMC) ICUs. Clinical data was collected according to the Protection against Infection Act (IfSG); documentation thereof was carried out in hospital information systems (HIS) as well as in the ICU-KISS module provided by the National Reference Center for the Surveillance of Nosocomial Infections (NRZ). Algorithmically derived data was generated via an algorithm developed in the EFFECT study; ward-movement data was linked with microbiological test results, generating a data set that allows for evaluation as to whether or not an infection was ICU-acquired. RESULTS: Approximately 75% of MDRO cases and 85% of cases of sepsis/primary bacteremia were classified as ICU-acquired by both manual chart review and EFFECT. Most discrepancies between the manual and algorithmic approaches were due to differentiating definitions regarding the patients' time at risk for acquiring MDRO/bacteremia. CONCLUSIONS: The concordance between manual chart review and algorithmically generated data was considerable. This study shows that hospital infection surveillance based on electronically generated routine data may be a worthwhile and sustainable alternative to manual chart review.

Compliance assessment regarding the PVC management on normal wards of a university hospital.

Objective: The risk of peripheral venous catheter (PVC) infections in inpatients is often underestimated, even if it is lower than that for central venous catheters. Guidelines for the prevention of PVC-associated infections describe the evidence-based management of PVCs. The aims of this study were the development of standardized methods for compliance assessment regarding PVC management and the evaluation of self-reported knowledge and implementations among healthcare providers regarding PVC care. Method: We developed a checklist based on the recommendation of the Commission of Hospital Hygiene and Infection Prevention at the Robert Koch Institute (KRINKO) Berlin for the standardized evaluation of PVC management. The following parameters were collected and evaluated: condition of the puncture site, condition of the bandage, presence of an extension set, presence of a plug, and documentation. The checklist was applied in 14 normal wards in 2019. After feedback of the ward staff on the results, it was applied again in 2020 in the same wards. For retrospective data analysis, we used a newly developed PVC-quality index. After the second evaluation in 2020, we carried out an anonymous survey among the healthcare providers. Results: The evaluation of 627 indwelling PVCs showed a significant increase in compliance related to the presence of an extension set (p=0.049) and documentation (p<0.001) in the 2nd year. The quality index increased in 12 out of 14 wards. The participants of the survey were aware of the in-house standard "Prevention of vascular catheter-associated infections", with a mean score of 4.98 on a Likert scale (1=not aware, 7=completely aware). The main barrier to implementation of the preventive measures was the time factor. Survey participants were more aware of PVC placement than PVC care. Conclusion: The PVC quality index is a valuable tool for the assessment of compliance regarding PVC management in daily practice. Feedback from the ward staff on the results of compliance assessment improves PVC management, but the outcome is very heterogeneous.

[Resource conservation from the perspective of infection prevention]. / Ressourcenschonung aus Sicht der Hygiene.

BACKGROUND: Procedures to prevent surgical site infections require a high input of human, technical and natural resources. This paper explores ways to optimize the use of resources in caring for patients who undergo a surgical procedure without compromising patient safety. METHODS: Review of the contribution of selected procedures for infection prevention in surgical patients considering current evidence and recommendations by comparing current guidelines and results of clinical trials. Analysis of interventions to implement and increase compliance. RESULTS: Knowledge of current evidence-based recommendations enables not only the identification of procedures with proven effect on infection prevention but also those that are ineffective and thus dispensable. There is still need for further controlled studies, e.g. on the use of antiseptics, that can confirm the evidence level of preventive procedures. Infection surveillance in combination with process and compliance monitoring by infection prevention specialists with a feedback system to healthcare workers are suitable control instruments for infection control management. In the case of increased infection rates, the implementation of evidence-based recommended measures through tailored bundle interventions is successful. Technical measures to maintain environmental conditions must be included in the control process. CONCLUSION: The reduction of healthcare-associated infections by implementing tailored interventions of infection prevention measures and elimination of ineffective procedures conserves resources and promotes patient safety.

Best practice approaches to outpatient management of people living with Parkinson's disease during the COVID-19 pandemic.

The prevalence of Parkinson's disease (PD) is rising, rendering it one of the most common neurodegenerative diseases. Treatment and monitoring of patients require regular specialized in- and outpatient care. Patients with PD are more likely to have a complicated disease course if they become infected with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Regular in-hospital appointments place these patients at risk of exposure to SARS-CoV-2 due to travel and contact with other patients and staff. However, guidelines for the management of outpatients with PD during times of increased risk of infection are currently lacking. These are urgently needed to conduct risk-benefit evaluations to recommend the best medical treatment. This article discusses best practice approaches based on the current literature, as suggested by the multidisciplinary Network of University Medicine (NUM) in Germany. These include measures such as mask-wearing, hand hygiene, social distancing measures, and appropriate testing strategies in outpatient settings, which can minimize the risk of exposure. Furthermore, the urgency of appointments should be considered. Visits of low urgency may be conducted by general practitioners or via telemedicine consultations, whereas in-person presentation is required in case of moderate and high urgency visits. Classification of urgency should be carried out by skilled medical staff, and telemedicine (telephone or video consultations) may be a useful tool in this situation. The currently approved vaccines against SARS-CoV-2 are safe and effective for patients with PD and play a key role in minimizing infection risk for patients with PD.

Tailoring implementation interventions of different order in infection prevention and control: A cascadic logic model (IPC-CASCADE).

Implementation interventions in infection prevention and control (IPC) differ by recipients. The two target groups are healthcare workers directly involved in patient care ("frontline") and IPC professionals as proxy agents, that is, implementation support practitioners. While both types of implementation interventions aim to promote compliance with clinical interventions to prevent healthcare-associated infections (HAI), their tailoring may be vastly different, for example, due to different behavioural outcomes. Additionally, IPC teams, as recipients of empowering tailored interventions, are under-researched. To overcome this gap and improve conceptual clarity, we proposed a cascadic logic model for tailored IPC interventions (IPC-CASCADE). In the model, we distinguished between interventions by IPC professionals targeting clinicians and those targeting IPC professionals (first- and second-order implementation interventions, respectively). Tailoring implies selecting behaviour change techniques matched to prospectively-assessed determinants of either clinician compliance (in first-order interventions) or interventions by IPC professionals for frontline workers (in second-order interventions). This interventional cascade is embedded in the prevailing healthcare system. IPC-CASCADE is horizontally structured over time and vertically structured by hierarchy or leadership roles. IPC-CASCADE aims to highlight the potential of increasing the impact of tailored interventions by IPC professionals for clinicians (to improve their compliance) via tailored interventions for IPC professionals (to improve their work as proxy agents). It underlines the links that IPC professionals define between macro contexts (healthcare and hospitals) and frontline workers in HAI prevention. It is specific, i.e., "tailored" to IPC, and expected to assist implementation science to better conceptualise tailoring.

Characterization of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Clusters Based on Integrated Genomic Surveillance, Outbreak Analysis and Contact Tracing in an Urban Setting.

BACKGROUND: Tracing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission chains is still a major challenge for public health authorities, when incidental contacts are not recalled or are not perceived as potential risk contacts. Viral sequencing can address key questions about SARS-CoV-2 evolution and may support reconstruction of viral transmission networks by integration of molecular epidemiology into classical contact tracing. METHODS: In collaboration with local public health authorities, we set up an integrated system of genomic surveillance in an urban setting, combining a) viral surveillance sequencing, b) genetically based identification of infection clusters in the population, c) integration of public health authority contact tracing data, and d) a user-friendly dashboard application as a central data analysis platform. RESULTS: Application of the integrated system from August to December 2020 enabled a characterization of viral population structure, analysis of 4 outbreaks at a maximum care hospital, and genetically based identification of 5 putative population infection clusters, all of which were confirmed by contact tracing. The system contributed to the development of improved hospital infection control and prevention measures and enabled the identification of previously unrecognized transmission chains, involving a martial arts gym and establishing a link between the hospital to the local population. CONCLUSIONS: Integrated systems of genomic surveillance could contribute to the monitoring and, potentially, improved management of SARS-CoV-2 transmission in the population.

Long-Term, Low-Frequency Cluster of a German-Imipenemase-1-Producing Enterobacter hormaechei ssp. steigerwaltii ST89 in a Tertiary Care Hospital in Germany.

Enterobacter cloacae complex is a common cause of hospital outbreaks. A retrospective and prospective molecular analysis of carbapenem-resistant clinical isolates in a tertiary care center demonstrated an outbreak of a German-imipenemase-1 (GIM-1) metallo-beta-lactamase-producing Enterobacter hormaechei ssp. steigerwaltii affecting 23 patients between 2009 and 2016. Thirty-three isolates were sequence type 89 by conventional multilocus sequence typing (MLST) and displayed a maximum difference of 49 out of 3,643 targets in the ad-hoc core-genome MLST (cgMLST) scheme (SeqSphere+ software; Ridom, Münster, Germany). The relatedness of all isolates was confirmed by further maximum-likelihood phylogeny. One clonal complex of highly related isolates (≤15 allele difference in cgMLST) contained 17 patients, but epidemiological data only suggested five transmission events. The blaGIM-1-gene was embedded in a class-1-integron (In770) and the Tn21-subgroup transposon Tn6216 (KC511628) on a 25-kb plasmid. Environmental screening detected one colonized sink trap in a service room. The outbreak was self-limited as no further blaGIM-1-positive E. hormaechei has been isolated since 2016. Routine molecular screening of carbapenem-nonsusceptible gram-negative isolates detected a long-term, low-frequency outbreak of a GIM-1-producing E. hormaechei ssp. steigerwaltii clone. This highlights the necessity of molecular surveillance.

Species Diversity of Environmental GIM-1-Producing Bacteria Collected during a Long-Term Outbreak.

UNLABELLED: Reports of outbreaks concerning carbapenemase-producing Gram-negative bacteria in which the main source of transmission is the hospital environment are increasing. This study describes the results of environmental sampling in a protracted polyspecies metallo-beta-lactamase GIM-1 outbreak driven by plasmids and bacterial clones of Enterobacter cloacae and Pseudomonas aeruginosa in a tertiary care center. Environmental sampling targeting wet locations (especially sinks) was carried out on a surgical intensive care unit and on a medical ward on several occasions in 2012 and 2013. We were able to demonstrate 43 blaGIM-1-carrying bacteria (mainly nonfermenters but also Enterobacteriaceae) that were either related or unrelated to clinical strains in 30 sinks and one hair washbasin. GIM-1 was found in 12 different species, some of which are described here as carriers of GIM-1. Forty out of 43 bacteria displayed resistance to carbapenems and, in addition, to various non-beta-lactam antibiotics. Colistin resistance was observed in two E. cloacae isolates with MICs above 256 mg/liter. The blaGIM-1 gene was harbored in 12 different class 1 integrons, some without the typical 3' end. The blaGIM-1 gene was localized on plasmids in five isolates. In vitro plasmid transfer by conjugation was successful in one isolate. The environment, with putatively multispecies biofilms, seems to be an important biological niche for multidrug-resistant bacteria and resistance genes. Biofilms may serve as a "melting pot" for horizontal gene transfer, for dissemination into new species, and as a reservoir to propagate future hospital outbreaks. IMPORTANCE: In Gram-negative bacteria, resistance to the clinically relevant broad-spectrum carbapenem antibiotics is a major public health concern. Major reservoirs for these resistant organisms are not only the gastrointestinal tracts of animals and humans but also the (hospital) environment. Due to the difficulty in eradicating biofilm formation in the latter, a sustained dissemination of multidrug-resistant bacteria from the environment can occur. In addition, horizontal transfer of resistance genes on mobile genetic elements within biofilms adds to the total "resistance gene pool" in the environment. To gain insight into the transmission pathways of a rare and locally restricted carbapenemases resistance gene (blaGIM-1), we analyzed the genetic background of the blaGIM-1 gene in environmental bacteria during a long-term polyspecies outbreak in a German hospital.

Detection and termination of an extended low-frequency hospital outbreak of GIM-1-producing Pseudomonas aeruginosa ST111 in Germany.

BACKGROUND: Metallo-ß-lactamase German imipenemase-1 (GIM-1)-mediated carbapenem resistance is emerging in Germany but has not spread beyond a very localized region. The aim of this study was to describe the first outbreak of an extensively drug-resistant GIM-1-carrying Pseudomonas aeruginosa strain affecting 29 patients in a tertiary care hospital from 2002-2013. METHODS: The outbreak was studied retrospectively and prospectively by a combination of molecular methods (carbapenemase polymerase chain reaction [PCR]), genotyping (DiversiLab, pulsed field gel electrophoresis and multi-locus sequence typing, bioMérieux, Marcy l'Etoile, France), descriptive epidemiology, and extensive environmental investigations using swabs with liquid transport medium, blaGIM-1 PCR, directly from the medium and culture. RESULTS: Of the 29 affected patients, 24 had been admitted to a surgical intensive care unit at some point, where environmental sampling revealed a high burden of blaGIM-1 in the wastewater system. The outbreak strain was found in several sinks and on a reusable hair washbasin. Initially, general infection control measures were applied; thereafter, specific measures were implemented, including the restriction of washbasin use. Continued surveillance over a period of 2 years has revealed no further case of GIM-1-carrying Pseudomonas aeruginosa. CONCLUSION: This long-term outbreak highlights the potential of molecular methods in surveillance for multidrug-resistant pathogens and in environmental sampling and the successful containment by application of specific control measures targeting biofilms within sink drains as potential environmental reservoirs for P aeruginosa.

International multicenter evaluation of the DiversiLab bacterial typing system for Escherichia coli and Klebsiella spp.

Successful multidrug-resistant clones are increasing in prevalence globally, which makes the ability to identify these clones urgent. However, adequate, easy-to-perform, and reproducible typing methods are lacking. We investigated whether DiversiLab (DL), an automated repetitive-sequence-based PCR bacterial typing system (bioMérieux), is suitable for comparing isolates analyzed at different geographic centers. A total of 39 Escherichia coli and 39 Klebsiella species isolates previously typed by the coordinating center were analyzed. Pulsed-field gel electrophoresis (PFGE) confirmed the presence of one cluster of 6 isolates, three clusters of 3 isolates, and three clusters of 2 isolates for each set of isolates. DL analysis was performed in 11 centers in six different countries using the same protocol. The DL profiles of 425 E. coli and 422 Klebsiella spp. were obtained. The DL system showed a lower discriminatory power for E. coli than did PFGE. The local DL data showed a low concordance, as indicated by the adjusted Rand and Wallace coefficients (0.132 to 0.740 and 0.070 to 1.0 [E. coli] and 0.091 to 0.864 and 0.056 to 1.0 [Klebsiella spp.], respectively). The central analysis showed a significantly improved concordance (0.473 to 1.0 and 0.290 to 1.0 [E. coli] and 0.513 to 0.965 and 0.425 to 1.0 [Klebsiella spp.], respectively). The misclassifications of profiles for individual isolates were mainly due to inconsistent amplification, which was most likely due to variations in the quality and amounts of the isolated DNA used for amplification. Despite local variations, the DL system has the potential to indicate the occurrence of clonal outbreaks in an international setting, provided there is strict adherence to standardized, reproducible DNA isolation methods and analysis protocols, all supported by a central database for profile comparisons.

Quantitative bedside testing of troponin T: is it equal to laboratory testing? The Cardiac Reader Troponin T (CARE T) study.

The progressive evolution of cardiac marker testing in patients with acute coronary syndromes has extended their role into risk stratification and guidance of therapeutic regimen. To provide utilization of cardiac markers around the clock and facilitate the diagnostic work-up of patients with acute chest pain in the emergency room, a point-of-care system for quantitative troponin T and myoglobin testing in whole blood samples was developed. Aim of this multicenter study was to evaluate bedside quantitative determination of myoglobin and troponin T in chest pain patients in a clinical routine setting. Five hospitals in Germany were contributing to blood sampling and 741 patients were included four hours (median) after onset of cardiac pain. Comparison between the rapid test and the established laboratory-based method showed a sufficient agreement of results with a correlation of r = 0.89 (Y = 0.856x + 0.029) for troponin T and r = 0.912 (Y= +1.145x + 3.457) for myoglobin. Diagnostic sensitivity and prognostic power of the troponin T results obtained in the emergency unit were thoroughly equivalent to the laboratory-based method. The results show that the cardiac reader system represents a promising alternative to central laboratory testing with an accuracy sufficiently for rapid decision making in the emergency room. Myoglobin results in this study did not add supplementary information to the cardiac reader troponin result. However, point-of-care testing of troponin T is advantageous whenever marker results could positively effect initial triage decisions and interventional management choices.

Multicenter evaluation of a fully mechanized soluble transferrin receptor assay on the Hitachi and cobas integra analyzers. the determination of reference ranges.

Soluble transferrin receptor (sTfR) is reported to be a reliable marker for the diagnosis of iron deficiency, especially when iron metabolism is influenced by inflammatory disorders such as infection, chronic inflammation and cancer-related anemia. In the present multicenter study the analytical performance of a recently introduced, latex-enhanced immunoturbidimetric assay for the determination of soluble transferrin receptor (Tina quant [a] sTfR, Roche Diagnostics) on different fully mechanized analyzers such as Hitachi 917 and 911, and Cobas Integra 400 and 700 was evaluated. Within-run and between-run imprecision showed good results (CV<5% and <7%, respectively). The assay was found to be linear over a wide measuring range (0.4-35 mg/l). Endogenous substances did not interfere with the test results. Comparison of serum sTfR concentrations with those of heparinized plasma revealed good correlation (r>0.976). Method comparison with an existing fully mechanized method as well as with ELISA tests for sTfR showed very good correlation (r>0.987). Because of the lack of international standardization the results differed from each other up to 2.5-fold. The 95% of serum levels in healthy individuals ranged from 1.9 to 4.4 mg/l (n=427). However, the reference ranges should be reported in a sex-dependent manner, as 2.2-5.0 mg/l for men (n=211) and as 1.9-4.4 mg/l for premenopausal (n=216) and postmenopausal (n=45) women. The Tina quant [a] sTfR assay enables the precise, accurate, rapid and convenient determination of sTfR concentrations for routine clinical chemistry purposes.