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.

Heat-Related Mortality in the Extreme Summer of 2022.

BACKGROUND: Estimating the excess mortality attributable to heat is a central element of the documentation of the consequences of climate change for human health. Until now, estimates of heatrelated deaths in Germany by the Robert Koch Institute (RKI) have been based on weekly mortality records. METHODS: Our study is the first to use higher resolution data-i.e. daily all-cause mortality linked to daily mean temperatures-from each of the German federal states to assess the heat-related mortality from 2000 to 2023 in Germany, employing quasi-Poisson models and multivariate meta-regression analyses. We focus our analysis on the extreme summer of 2022. RESULTS: Our analysis yielded an estimate of 9100 (95% CI: [7300; 10 700]) heat-related deaths in Germany for the summer of 2022, whereas previous studies of the RKI estimated the number of heatrelated deaths at 4500 [2100; 7000]. When we set a higher temperature threshold in the definition of the heat risk, we arrived at a figure of 6900 [5500; 8100] heat-related deaths in 2022. In other summers that-similarly to 2022-were characterized by large fluctuations in daily mean temperatures, we also robustly estimated higher numbers of heat-related deaths than the RKI did. The exclusion of reported deaths due to COVID-19 had only a minor effect on our estimates. CONCLUSION: Our findings suggest that previous studies based on weekly mortality data have underestimated the full extent of heat-related mortality in Germany, particularly in the extreme summer of 2022. The monitoring of heat-related mortality should be systematic and as comprehensive as possible if it is to enable the development of effective heat-health action plans.

Impact of climate change on non-communicable diseases due to increased ambient air pollution.

Background: The impacts of air pollutants on health range from short-term health impairments to hospital admissions and deaths. Climate change is leading to an increase in air pollution. Methods: This article addresses, based on selected literature, the relationship between climate change and air pollutants, the health effects of air pollutants and their modification by air temperature, with a focus on Germany. Results: Poor air quality increases the risk of many diseases. Climate change is causing, among other things, more periods of extreme heat with simultaneously increased concentrations of air pollutants. The interactions between air temperature and air pollutants, as well as their combined effects on human health, have not yet been sufficiently studied. Limit, target, and guideline values are of particular importance for health protection. Conclusions: Measures to reduce air pollutants and greenhouse gases must be more strictly implemented. An essential step towards improving air quality is setting stricter air quality limit values in Europe. Prevention and adaptation measures should be accelerated in Germany, as they contribute to climate-resilient and sustainable healthcare systems.

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.

[Health and Social Status in Hamburg's Urban Quarters - An Approach to Mapping Social Status with Health-Related Routine Data]. / Gesundheit und soziale Lage in Hamburger Quartieren ­ Ein Ansatz zur Abbildung von Soziallagen mit gesundheitsbezogenen Routinedaten.

AIM OF THE STUDY: The aim of this study was to test an innovative approach to the small-scale and social situation-sensitive localisation and analysis of health-related routine data. For this purpose, SHI billing data and deployment data of the ambulance service were supplemented with a small-scale neighbourhood-related indicator of the social situation of the place of residence and/or deployment as a proxy for the personal social situation. METHODS: Anonymised accounting data from three statutory health insurances and deployment data from the rescue service of the Hamburg fire brigade, each from the year 2017, were used. The social situation of the place of residence of the insured or transported persons (in the case of the rescue service data, also the deployment location) was mapped with the help of the so-called status index classes (high - medium - low - very low) of the Hamburg social monitoring. The allocation via the addresses of the persons concerned was carried out by the respective data owners with the help of an allocation procedure developed in the project. RESULTS: Exemplary results of descriptive analysis of accident occurrence and acute inpatient care of children and adolescents showed that known social situation dependencies from primary studies can also be depicted in the secondary data used. This would speak for the suitability of the social indicator, e. g. in the context of extended social and health reporting. CONCLUSION: The neighbourhood-based indicator we used seems promising and should be validated in further analyses. Based on this, approaches can be developed for its use in the context of health services research and health reporting as well as in the sense of a comprehensive health-in-all-policies strategy for designing health-promoting and needs-oriented political decisions and programmes.

[Physicians at the Interface to the Non-Medical Sector of Home- and Community-Based Services for People with Dementia]. / Ärztinnen und Ärzte an der Schnittstelle zum nicht-medizinischen Hilfs- und Unterstützungssektor für Menschen mit Demenz.

OBJECTIVE: The study examined the function of physicians between the medical and nonmedical sector of home- and community-based services in the ambulatory care of people with dementia and their relatives. Therefore, the study took a differentiated look at the status quo of physicians' activities regarding non-medical home- and community-based services as well as approaches for optimizing the current situation from the physicians' perspective. METHODS: An explorative cross-sectional study was conducted using a standardized postal survey (based on a qualitative preliminary study with 6 physicians). Data from 177 GPs and specialists in Hamburg could be collected and analyzed with descriptive statistics. RESULTS: The majority of physicians (88.1%) inform their patients with dementia and their carers about home- and community-based services. 'Home care' presents the most often and 'services for carers' the least considered aspect. Approaches that address the optimization of information material are assessed as most supportive. CONCLUSION: The results can be used as a basis for further development of the care landscape in Hamburg. What has to be discussed is the monoperspective data collection only from physician's point of view. The utilization of the results requires an inclusion of the perspective of affected persons themselves as well as other actors in the non-medical care landscape.

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.

Polar Nature of Biomimetic Fluorapatite/Gelatin Composites: A Comparison of Bipolar Objects and the Polar State of Natural Tissue.

The correspondence of the state of alignment of macromolecules in biomimetic materials and natural tissues is demonstrated by investigating a mechanism of electrical polarity formation: An in vitro grown biomimetic FAp/gelatin composite is investigated for its polar properties by second harmonic (SHGM) and scanning pyroelectric microscopy (SPEM). Hexagonal prismatic seed crystals formed in gelatin gels represent a monodomain polar state, due to aligned mineralized gelatin molecules. Later growth stages, showing dumbbell morphologies, develop into a bipolar state because of surface recognition by gelatin functionality: A reversal of the polar alignment of macromolecules, thus, takes place close to that basal plane of the seed. In natural hard tissues (teeth and bone investigated by SPEM) and the biomimetic FAp/gelatin composite, we find a surprising analogy in view of growth-induced states of polarity: The development of polarity in vivo and in vitro can be explained by a Markov-type mechanism of molecular recognition during the attachment of macromolecules.

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.

Ferric carboxymaltose improves exercise capacity and quality of life in patients with pulmonary arterial hypertension and iron deficiency: a pilot study.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive condition harboring a poor prognosis. Iron deficiency in PAH correlates with disease severity and mortality. While replacement therapy may be beneficial, dietary iron absorption is impaired in PAH patients by hepcidin, a key regulatory protein of iron homoeostasis. We therefore assessed the therapeutic potential and safety of intravenous iron supplementation in patients with PAH and iron deficiency. METHODS: 20 patients with PAH and iron deficiency, who were on stable targeted PAH therapy, received a single infusion of ≤1000 mg ferric carboxymaltose. All patients were assessed at baseline and two months after iron treatment. Exercise capacity was evaluated based on the 6-minute-walking distance (6MWD), and quality of life (QoL) was assessed by the SF-36 questionnaire (100 point scale). The effects were compared to 20 matched patients with stable PAH without iron deficiency who did not receive ferric carboxymaltose. RESULTS: In iron deficient patients, iron supplementation led to a marked improvement of iron status (serum iron 5.7±0.4 to 11.1±1.1 µmol/L, ferritin 29.3±6.3 to 145.2±25.4 µg/L, transferrin saturation 7.5±0.7 to 19.3±2.3%, all p≤0.001). Iron-deficient patients receiving ferric carboxymaltose showed a significant increase of the 6MWD from 346.5±28.3 to 374.0±25.5 m (p=0.007), whereas no significant changes were found in the control group not receiving iron supplementation (6MWD 389.9±25.3 to 379.6±26.2 m; n.s.), resulting in a net increase in the 6MWD of 37.8m (p=0.003). This was associated with an improvement in QoL (SF-36 score from 44.3±3.7 to 50.6±3.6; p=0.01). Only minimal side-effects were reported. CONCLUSIONS: These data indicate that parenteral iron supplementation with ferric carboxymaltose significantly improves exercise capacity and QoL and is well tolerated in patients with PAH and iron deficiency, and when administered in addition to targeted PAH therapies. Our results provide proof of concept for further studies evaluating the potential of iron as an adjunct in PAH treatment on a larger scale.

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.

Delineation of brain tumor extent with [11C]L-methionine positron emission tomography: local comparison with stereotactic histopathology.

PURPOSE: Methyl-[11C]L-methionine ([11C]MET) positron emission tomography (PET) in brain tumors reflects amino acid transport and has been shown to be more sensitive than magnetic resonance imaging in stereotactic biopsy planning. It remains unclear whether the increased [11C]MET uptake is limited to solid tumor tissue or even detects infiltrating tumor parts. EXPERIMENTAL DESIGN: In 30 patients, a primary or recurrent brain tumor was suspected on magnetic resonance imaging. Patients were investigated with [11C]MET-PET before stereotactic biopsy. The biopsy trajectories were plotted into the [11C]MET-PET images with a newly designed C-based software program. The exact local [11C]MET uptake was determined within rectangular regions of interest of 4 mm in width and length aligned with the biopsy specimen. Individual histologic specimens were rated for the presence of solid tumor tissue, infiltration area, and nontumorous tissue changes. RESULTS: Receiver operating characteristics analysis demonstrated a sensitivity of 87% and specificity of 89% for the detection of tumor tissue at a threshold of 1.3-fold [11C]MET uptake relative to normal brain tissue. At this threshold, only 13 of 100 tumor positive specimen were false negative mainly in grade 2 astrocytoma. In grade 2 astrocytoma, mean [11C]MET uptake in the infiltration area was significantly higher than in solid tumor tissue (P < 0.003). CONCLUSIONS: [11C]MET-PET detects solid parts of brain tumors, as well as the infiltration area at high sensitivity and specificity. High [11C]MET uptake in infiltrating tumor of astrocytoma WHO grade 2 reflects high activity in this tumor compartment. Molecular imaging, with [11C]MET, will guide improved management of patients with brain tumors.