CHROMAgar™ LIN-R as an efficient screening tool to assess the prevalence of linezolid-resistant enterococci in German hospital patients-a multicentre study approach, 2021-2022.

BACKGROUND: In recent years, an increasing number of linezolid-resistant enterococci (LRE) was recognized at the German National Reference Centre (NRC) for Enterococci. National guidelines on infection prevention recommend screening for LRE in epidemiologically linked hospital settings without referring to a reliable and rapid diagnostic method. Since 2020, CHROMAgar™ provide a chromogenic linezolid screening agar, LIN-R, suitable to simultaneously screen for linezolid-resistant staphylococci and enterococci. OBJECTIVES: To assess the applicability of CHROMAgar™ LIN-R in clinical settings for detecting LRE directly from patient material and to infer prevalence rates of LRE amongst German hospital patients. METHODS: During the 3-month trial period, clinical samples were plated on CHROMAgar™ LIN-R. Antimicrobial susceptibility testing was performed using VITEK2 or disc diffusion. At the NRC, linezolid resistance was determined by broth microdilution, multiplex-PCR for cfr/optrA/poxtA and by a restriction-based assay for 23S rDNA mutations. RESULTS: The 12 participating study sites used 13 963 CHROMAgar™ LIN-R plates during the study period. Of 442 presumptive LRE, 192 were confirmed by phenotypic methods. Of these, 161 were received by the NRC and 121 (75%) were verified as LRE. Most of LR-E. faecium 53/81 (65%) exhibited a 23S rRNA gene mutation as the sole resistance-mediating mechanism, whereas optrA constituted the dominant resistance trait in LR-E. faecalis [39/40 (98%)]. Prevalence of LRE across sites was estimated as 1% (ranging 0.18%-3.7% between sites). CONCLUSIONS: CHROMAgar™ LIN-R represents a simple and efficient LRE screening tool in hospital settings. A high proportion of false-positive results demands validation of linezolid resistance by a reference method.

Environmental Contamination and Persistence of Clostridioides difficile in Hospital Wastewater Systems.

Clostridioides difficile produces an environmentally resistant dormant spore morphotype that infected patients shed to the hospital environment. C. difficile spores persist in clinical reservoirs that are not targeted by hospital routine cleaning protocols. Transmissions and infections from these reservoirs present a hazard to patient safety. This study aimed to assess the impact of patients acutely suffering from C. difficile-associated diarrhea (CDAD) on C. difficile environmental contamination to identify potential reservoirs. Twenty-three hospital rooms accommodating CDAD inpatients with corresponding soiled workrooms of 14 different wards were studied in a German maximum-care hospital. Additionally, four rooms that never accommodated CDAD patients were examined as negative controls. Stagnant water and biofilms from sinks, toilets, and washer disinfector (WD) traps as well as swabs from cleaned bedpans and high-touch surfaces (HTSs) were sampled. For detection, a culture method was used with selective medium. A latex agglutination assay and a Tox A/B enzyme-linked immunosorbent assay were performed with suspect colonies. Stagnant water and biofilms in hospital traps (29%), WDs (34%), and HTSs (37%) were found to be reservoirs for large amounts of C. difficile during the stay of CDAD inpatients that decreased but could persist 13 ± 6 days after their discharge (13%, 14%, and 9.5%, respectively). Control rooms showed none or only slight contamination restricted to WDs. A short-term cleaning strategy was implemented that reduced C. difficile in stagnant water almost entirely. IMPORTANCE Wastewater pipes are microbial ecosystems. The potential risk of infection emanating from the wastewater for individuals is often neglected, since it is perceived to remain in the pipes. However, sewage systems start with siphons and are thus naturally connected to the outside world. Wastewater pathogens do not only flow unidirectionally to wastewater treatment plants but also retrogradely, e.g., through splashing water from siphons to the hospital environment. This study focused on the pathogen C. difficile, which can cause severe and sometimes fatal diarrheas. This study shows how patients suffering from such diarrheas contaminate the hospital environment with C. difficile and that contamination persists in siphon habitats after patient discharge. This might pose a health risk for hospitalized patients afterward. Since this pathogen's spore morphotype is very environmentally resistant and difficult to disinfect, we show a cleaning measure that can almost entirely eliminate C. difficile from siphons.

Legionella in drinking water: the detection method matters.

Legionella concentrations in drinking water have been regulated for decades and are evaluated with regard to their concentrations in drinking water plumbing systems (DWPS). The respective action levels differ at the international level. In Germany, the Federal Environment Agency (UBA) specifies the application of ISO 11731 for the detection of legionella in drinking water and gives a binding recommendation for the methods to be used for culturing and evaluation. Effective from 01 March 2019, the UBA recommendation was revised. The utilized culture media in the culture approach were altered, consequently affecting the spectrum of legionella colonies detected in drinking water. Using data from a routine legionella monitoring of a large laboratory, over a period of 6 years and 17,270 individual drinking water samples, allowed us to assess the impact of the alteration on the assessment of DWPS. By comparing the amount of action level exceedances before and after the method change, it could be demonstrated that exceedances are reported significantly more often under the new method. Consequently, the corresponding action level for evaluation of legionella contamination and the resulting risk to human health needs to be revised to avoid the misleading impression of increased health risk.

OutbreakFlow: Model-based Bayesian inference of disease outbreak dynamics with invertible neural networks and its application to the COVID-19 pandemics in Germany.

Mathematical models in epidemiology are an indispensable tool to determine the dynamics and important characteristics of infectious diseases. Apart from their scientific merit, these models are often used to inform political decisions and interventional measures during an ongoing outbreak. However, reliably inferring the epidemical dynamics by connecting complex models to real data is still hard and requires either laborious manual parameter fitting or expensive optimization methods which have to be repeated from scratch for every application of a given model. In this work, we address this problem with a novel combination of epidemiological modeling with specialized neural networks. Our approach entails two computational phases: In an initial training phase, a mathematical model describing the epidemic is used as a coach for a neural network, which acquires global knowledge about the full range of possible disease dynamics. In the subsequent inference phase, the trained neural network processes the observed data of an actual outbreak and infers the parameters of the model in order to realistically reproduce the observed dynamics and reliably predict future progression. With its flexible framework, our simulation-based approach is applicable to a variety of epidemiological models. Moreover, since our method is fully Bayesian, it is designed to incorporate all available prior knowledge about plausible parameter values and returns complete joint posterior distributions over these parameters. Application of our method to the early Covid-19 outbreak phase in Germany demonstrates that we are able to obtain reliable probabilistic estimates for important disease characteristics, such as generation time, fraction of undetected infections, likelihood of transmission before symptom onset, and reporting delays using a very moderate amount of real-world observations.

The role of routine SARS-CoV-2 screening of healthcare-workers in acute care hospitals in 2020: a systematic review and meta-analysis.

BACKGROUND: Healthcare workers (HCW) are at increased risk of infection with SARS-CoV-2. Vulnerable patient populations in particular must be protected, and clinics should not become transmission hotspots to avoid delaying medical treatments independent of COVID. Because asymptomatic transmission has been described, routine screening of asymptomatic HCW would potentially be able to interrupt chains of infection through early detection. METHODS: A systematic search was conducted in the Cochrane COVID-19 Study Register, Web of Science and WHO COVID-19 Global literature on coronavirus with regard to non-incident related testing of healthcare workers using polymerase chain reaction on May 4th 2021. Studies since January 2020 were included. An assessment of risk of bias and representativeness was performed. RESULTS: The search identified 39 studies with heterogeneous designs. Data collection of the included studies took place from January to August 2020. The studies were conducted worldwide and the sample size of the included HCW ranged from 70 to 9449 participants. In total, 1000 of 51,700 (1.9%) asymptomatic HCW were tested positive for SARS-CoV-2 using PCR testing. The proportion of positive test results ranged between 0 and 14.3%. No study reported on HCW-screening related reductions in infected person-days. DISCUSSION AND CONCLUSIONS: The heterogeneous proportions might be explained by different regional incidences, lock-downs, and pre-analytical pitfalls that reduce the sensitivity of the nasopharyngeal swab. The very high prevalence in some studies indicates that screening HCW for SARS-CoV-2 may be important particularly in geographical regions and pandemic periods with a high-incidence. With low numbers and an increasing rate of vaccinated HCW, a strict cost-benefit consideration must be made, especially in times of low incidences. Since we found no studies that reported on HCW-screening related reductions in infected person-days, re-evaluation should be done when these are available.

Transmission of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae: the role of infection control.

BACKGROUND: The worldwide spread of carbapenemase-producing Gram-negative bacteria (GNB) in healthcare settings is worrying. Of particular concern is the occurrence of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KP). In recent years, several guidelines and recommendations have focused on the control of carbapenem-resistant GNB. It remains, however, unknown to what extent individual infection control measures are effective. Our aim was to critically review the recent evidence regarding the effectiveness of measures to control KPC-KP spread in healthcare settings. METHODS: Critical review of the literature aiming to evaluate, in accordance with published recommendations, all available studies reporting infection control (IC) measures to control KPC-KP published in the past 5 years. RESULTS: Among 11 included studies, the majority consisted of outbreak reports, where application of measures was reported in the absence of control groups. Variability was observed related to the frequency of application of recommended measures for control of KPC-KP. Additional measures were recorded, such as environmental sampling and staff screening, whereas compliance with hand hygiene was measured in relatively few studies. Finally, mortality in patients harbouring KPC-KP was notable, reaching 42.9% of included patients. CONCLUSIONS: Despite successful control of KPC-KP spread during outbreaks, the impact of individual IC measures is difficult to assess, as the quality of published evidence is low and controlled intervention studies are lacking. The distribution of studies, the number of reported cases and the high mortality rates, clearly show that KPC-KP remains a major healthcare problem worldwide.

White Paper: Bridging the gap between surveillance data and antimicrobial stewardship in long-term care facilities-practical guidance from the JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks.

BACKGROUND: In long-term care facilities (LTCFs) residents often receive inappropriate antibiotic treatment and infection prevention and control practices are frequently inadequate, thus favouring acquisition of MDR organisms. There is increasing evidence in the literature describing antimicrobial stewardship (AMS) activities in LTCFs, but practical guidance on how surveillance data should be linked with AMS activities in this setting is lacking. To bridge this gap, the JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks joined their efforts to provide practical guidance for linking surveillance data with AMS activities. MATERIALS AND METHODS: Considering the three main topics [AMS leadership and accountability, antimicrobial usage (AMU) and AMS, and antimicrobial resistance (AMR) and AMS], a literature review was performed and a list of target actions was developed. Consensus on target actions was reached through a RAND-modified Delphi process involving 40 experts from 18 countries and different professional backgrounds adopting a One Health approach. RESULTS: From the 25 documents identified, 25 target actions were retrieved and proposed for expert evaluation. The consensus process produced a practical checklist including 23 target actions, differentiating between essential and desirable targets according to clinical relevance and feasibility. Flexible proposals for AMS team composition and leadership were provided, with a strong emphasis on the need for well-defined and adequately supported roles and responsibilities. Specific antimicrobial classes, AMU metrics, pathogens and resistance patterns to be monitored are addressed. Effective reporting strategies are described. CONCLUSIONS: The proposed checklist represents a practical tool to support local AMS teams across a wide range of care delivery organization and availability of resources.

White Paper: Bridging the gap between surveillance data and antimicrobial stewardship in the animal sector-practical guidance from the JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks.

BACKGROUND: The JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks have joined efforts to formulate a set of target actions to link the surveillance of antimicrobial usage (AMU) and antimicrobial resistance (AMR) with antimicrobial stewardship (AMS) activities in four different settings. This White Paper focuses on the veterinary setting and embraces the One Health approach. METHODS: A review of the literature was carried out addressing research questions in three areas: AMS leadership and accountability; AMU surveillance and AMS; and AMR surveillance and AMS. Consensus on target actions was reached through a RAND-modified Delphi process involving over 40 experts in infectious diseases, clinical microbiology, AMS, veterinary medicine and public health, from 18 countries. RESULTS/DISCUSSION: Forty-six target actions were developed and qualified as essential or desirable. Essential actions included the setup of AMS teams in all veterinary settings, building government-supported AMS programmes and following specific requirements on the production, collection and communication of AMU and AMR data. Activities of AMS teams should be tailored to the local situation and capacities, and be linked to local or national surveillance systems and infection control programmes. Several research priorities were also identified, such as the need to develop more clinical breakpoints in veterinary medicine. CONCLUSIONS: This White Paper offers a practical tool to veterinary practitioners and policy makers to improve AMS in the One Health approach, thanks to surveillance data generated in the veterinary setting. This work may also be useful to medical doctors wishing to better understand the specificities of the veterinary setting and facilitate cross-sectoral collaborations.

White Paper: Bridging the gap between surveillance data and antimicrobial stewardship in the outpatient sector-practical guidance from the JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks.

BACKGROUND: The outpatient setting is a key scenario for the implementation of antimicrobial stewardship (AMS) activities, considering that overconsumption of antibiotics occurs mainly outside hospitals. This publication is the result of a joint initiative by the JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks, which is aimed at formulating a set of target actions for linking surveillance data with AMS activities in the outpatient setting. METHODS: A scoping review of the literature was carried out in three research areas: AMS leadership and accountability; antimicrobial usage and AMS; antimicrobial resistance and AMS. Consensus on the actions was reached through a RAND-modified Delphi process involving over 40 experts in infectious diseases, clinical microbiology, AMS, veterinary medicine or public health, from 18 low-, middle- and high-income countries. RESULTS: Evidence was retrieved from 38 documents, and an initial 25 target actions were proposed, differentiating between essential or desirable targets according to clinical relevance, feasibility and applicability to settings and resources. In the first consultation round, preliminary agreement was reached for all targets. Further to a second review, 6 statements were re-considered and 3 were deleted, leading to a final list of 22 target actions in the form of a practical checklist. CONCLUSIONS: This White Paper is a pragmatic and flexible tool to guide the development of calibrated surveillance-based AMS interventions specific to the outpatient setting, which is characterized by substantial inter- and intra-country variability in the organization of healthcare structures, maintaining a global perspective and taking into account the feasibility of the target actions in low-resource settings.

Linking antimicrobial resistance surveillance to antibiotic policy in healthcare settings: the COMBACTE-Magnet EPI-Net COACH project.

OBJECTIVES: To systematically summarize the evidence on how to collect, analyse and report antimicrobial resistance (AMR) surveillance data to inform antimicrobial stewardship (AMS) teams providing guidance on empirical antibiotic treatment in healthcare settings. METHODS: The research group identified 10 key questions about the link between AMR surveillance and AMS using a checklist of 9 elements for good practice in health research priority settings and a modified 3D combined approach matrix, and conducted a systematic review of published original studies and guidelines on the link between AMR surveillance and AMS. RESULTS: The questions identified focused on AMS team composition; minimum infrastructure requirements for AMR surveillance; organisms, samples and susceptibility patterns to report; data stratification strategies; reporting frequency; resistance thresholds to drive empirical therapy; surveillance in high-risk hospital units, long-term care, outpatient and veterinary settings; and surveillance data from other countries. Twenty guidelines and seven original studies on the implementation of AMR surveillance as part of an AMS programme were included in the literature review. CONCLUSIONS: The evidence summarized in this review provides a useful basis for a more integrated process of developing procedures to report AMR surveillance data to drive AMS interventions. These procedures should be extended to settings outside the acute-care institutions, such as long-term care, outpatient and veterinary. Without proper AMR surveillance, implementation of AMS policies cannot contribute effectively to the fight against MDR pathogens and may even worsen the burden of adverse events from such interventions.

Microbiological Control of Cellular Products: The Relevance of the Cellular Matrix, Incubation Temperature, and Atmosphere for the Detection Performance of Automated Culture Systems.

BACKGROUND: The microbiological control of cellular products sometimes causes significant procedural issues for quality control laboratories. According to the European Pharmacopoeia (EP), the microbiological control of cellular products requires a 7- to 14-day incubation period at two different incubation temperatures using aerobic and anaerobic growth media. However, the suitability of these test conditions for efficient quality control can be influenced by many conditions, such as the expected microbial spectrum of contamination or the texture and composition of the cellular product. Because of interference, direct inoculation and membrane filtration as reference methods of pharmacopoeia are largely unsuitable for the microbiological control of cellular products; therefore, alternative and, above all, automated methods are the focus of interest. OBJECTIVE: The aim of our study was to evaluate the method suitability and possible effects of cell matrix, incubation temperature, and oxygen pressure on the detection performance of automated culture systems. METHODS: The BacT/ALERT® 3DTM Dual T system (bioMérieux, Nürtingen, Germany) was used to evaluate the factors influencing automated microbiological control of cellular products. The tests were performed using microbial strains recommended by the EP for microbiological method suitability testing and additional relevant possible contaminants of human-derived stem-cell products under varying culture and cell matrix conditions. RESULTS: All contaminants were detected by the system in the required period of 2-5 days. Low incubation temperatures (22°C) had overall negative effects on the detection kinetics of each type of microbial contamination. The adverse effects of the accompanying cell matrix on the detection properties of the system could be compensated in our study by incubation at 32°C in both the aerobic and the anaerobic culture conditions. CONCLUSION: Automated culture techniques represent a sufficient approach for the microbiological control of cellular products. The negative effects of the cell matrix and microbial contamination on the detection performance can be compensated by the application of variable culture conditions in the automated culture system.

Molecular characterization of carbapenem-resistant Acinetobacter baumannii using WGS revealed missed transmission events in Germany from 2012-15.

BACKGROUND: Infection and colonization with multi-resistant Acinetobacter baumannii causes therapeutic and economic problems in the nosocomial setting. Due to the sensitivity issue of screening schemes for A. baumannii, it is difficult to implement adequate transmission prevention measures. The high discriminatory power of WGS for transmission-chain analysis provides us with the necessary tool to study and identify transmission events. We retrospectively sequenced and analysed 39 A. baumannii isolates from 2012-15 to search for possible missed transmission events. METHODS: Molecular typing by WGS was performed for non-repetitive (n=39) carbapenem-resistant A. baumannii. Retrospective assessment of patient records was performed to investigate and confirm possible transmission events. RESULTS: Between July 2012 and September 2015, A. baumannii was isolated from 268 patients, of which 16% (42/268) were carbapenem resistant. Thirty-nine of these isolates were recoverable and sequenced. Fifteen percent (6/39) of these were resistant to all antibiotics tested. Most isolates belong to the circulating IC2 clonal type. SNP analysis revealed four potential outbreak clusters. Two of these clusters showed high concordance with the local spatio-temporal epidemiology, suggesting that transmission events were very likely. CONCLUSIONS: Our data suggest that there were two independent transmission events, which would have been missed by conventional MLST owing to high clonality. The routine implementation of WGS can optimize surveillance and initiation of suitable containment measures. In addition, emerging resistance to salvage therapy is a major therapeutic problem and should be monitored closely.

Distribution of carbapenem resistance mechanisms in clinical isolates of XDR Pseudomonas aeruginosa.

Our study aims to define the epidemiology of carbapenem resistance mechanisms in clinical isolates of Pseudomonas aeruginosa (PA). We evaluated 11,457 clinical PA strains isolated between 2009 and 2015 at the tertiary care University Hospital in Heidelberg, Germany. Thirty-four percent of the isolates (3867/11,457) were MDR (multidrug-resistant), 16% (1816/11,457) were XDR (extensively drug resistant), and less than 1% (82/11,457) had a PDR (pandrug-resistant) profile. Of those, 23% carried a carbapenemase gene (CPM positive) with 12% VIM-2, 10% VIM-1, and less than 1% IMP-1. Comparing MIC (minimal inhibitory concentration) distributions, the mean rank for meropenem, imipenem, gentamicin, and fosfomycin was significantly higher in the CPM-positive group than in the CPM-negative XDR group (p ≤ 0.004). oprD (outer membrane protein) mutations were found in 19/19 tested strains; 12/19 carried a CPM and had a higher mutation rate. Meropenem resistance was mostly associated with the presence of CPM. Only 1/19 strains was meropenem resistant in the absence of CPM genes; nevertheless, it carried an oprD mutation in a strategic site (loop 2). Of 19 CPM-negative strains tested, 7 (36%) showed EP (efflux pumps) hyperexpression versus 12 in the CPM-positive strains. In our study, nearly 50% of the PA isolates exhibited resistance to the tested first-line antibiotics. Our study also demonstrates that carbapenemase genes can be isolated in approximately 23% of XDR PA strains in our population. This finding supports the clinical relevance of PA driven by the possible presence of multiple resistance mechanisms acquired under exposure to antibiotics or by horizontal transfer of resistance genes.

Organization and training at national level of antimicrobial stewardship and infection control activities in Europe: an ESCMID cross-sectional survey.

Antimicrobial stewardship (AMS) and Infection prevention and control (IPC) are two key complementary strategies that combat development and spread of antimicrobial resistance. The ESGAP (ESCMID Study Group for AMS), EUCIC (European Committee on Infection Control) and TAE (Trainee Association of ESCMID) investigated how AMS and IPC activities and training are organized, if present, at national level in Europe. From February 2018 to May 2018, an internet-based cross-sectional survey was conducted through a 36-item questionnaire, involving up to three selected respondents per country, from 38 European countries in total (including Israel), belonging to the ESGAP/EUCIC/TAE networks. All 38 countries participated with at least one respondent, and a total of 81 respondents. Education and involvement in AMS programmes were mandatory during the postgraduate training of clinical microbiology and infectious diseases specialists in up to one-third of countries. IPC was acknowledged as a specialty in 32% of countries. Only 32% of countries had both guidance and national requirements regarding AMS programmes, in contrast to 61% for IPC. Formal national staffing standards for AMS and IPC hospital-based activities were present in 24% and 63% of countries, respectively. The backgrounds of professionals responsible for AMS and IPC programmes varied tremendously between countries. The organization and training of AMS and IPC in Europe are heterogeneous and national requirements for activities are frequently lacking.

Measuring the in-hospital costs of Pseudomonas aeruginosa pneumonia: methodology and results from a German teaching hospital.

BACKGROUND: Pseudomonas aeruginosa-related pneumonia is an ongoing healthcare challenge. Estimating its financial burden is complicated by the time-dependent nature of the disease. METHODS: Two hundred thirty-six cases of Pseudomonas aeruginosa-related pneumonia were recorded at a 2000 bed German teaching hospital between 2011 and 2014. Thirty-five cases (15%) were multidrug-resistant (MDR) Pseudomonas aeruginosa. Hospital- and community-acquired cases were distinguished by main diagnoses and exposure time. The impact of Pseudomonas aeruginosa-related pneumonia on the three endpoints cost, reimbursement, and length of stay was analyzed, taking into account (1) the time-dependent nature of exposure, (2) clustering of costs within diagnostic groups, and (3) additional confounders. RESULTS: Pseudomonas aeruginosa pneumonia is associated with substantial additional costs that are not fully reimbursed. Costs are highest for hospital-acquired cases (€19,000 increase over uninfected controls). However, community-acquired cases are also associated with a substantial burden (€8400 when Pseudomonas aeruginosa pneumonia is the main reason for hospitalization, and €6700 when not). Sensitivity analyses for hospital-acquired cases showed that ignoring or incorrectly adjusting for time-dependency substantially biases results. Furthermore, multidrug-resistance was rare and only showed a measurable impact on the cost of community-acquired cases. CONCLUSIONS: Pseudomonas aeruginosa pneumonia creates a substantial financial burden for hospitals. This is particularly the case for nosocomial infections. Infection control interventions could yield significant cost reductions. However, to evaluate the potential effectiveness of different interventions, the time-dependent aspects of incremental costs must be considered to avoid introduction of bias.

[Update Hygiene: Prevention of Vascular Catheter-Associated Infections in Premature and Newborn Infants]. / Update Hygiene: Prävention von Gefäßkatheter-assoziierten Infektionen bei Früh- und Neugeborenen.

BACKGROUND: In May 2018, the commission on infection prevention and control in Germany (KRINKO) of the RKI published a guidance document providing recommendations on the prevention of catheter-associated infections in premature children and newborns. AIM: Summarized presentation, explanation and discussion of the KRINKO recommendations. METHODS: The recommendations of the KRINKO were summarized and discussed with reference to the original sources. RESULTS: In particular, statements were formulated for the insertion and maintenance of vascular catheters and for the preparation of infusions. Overall, however, the evidence of the recommendations is low. About 26% (19 out of 74) are classified under category IA or IB. However, 40% of the recommendations are category II only and therefore based on indicative clinical or epidemiological studies or comprehensible theoretical justifications. Accordingly, there is a lack of urgently needed clinical trials. DISCUSSION: Prevention strategies were discussed in detail and practical issues were addressed. The high number of recommendations, sometimes with low evidence levels, suggests a shared assessment of the infection control team and clinicians to ensure a successful implementation in practice and a focus on key content adapted to the local situation.

In-hospital costs of community-acquired colonization with multidrug-resistant organisms at a German teaching hospital.

BACKGROUND: Antibiotic resistance is a challenge in the management of infectious diseases and can cause substantial cost. Even without the onset of infection, measures must be taken, as patients colonized with multi-drug resistant (MDR) pathogens may transmit the pathogen. We aim to quantify the cost of community-acquired MDR colonizations using routine data from a German teaching hospital. METHODS: All 2006 cases of documented MDR colonization at hospital admission recorded from 2011 to 2014 are matched to 7917 unexposed controls with the same primary diagnosis. Cases with an onset MDR infection are excluded from the analysis. Routine data on costs per case is analysed for three groups of MDR bacteria: Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus (VRE), and multidrug-resistant gram-negative bacteria (MDR-GN). Multivariate analyses are conducted to adjust for potential confounders. RESULTS: After controlling for main diagnosis group, age, sex, and Charlson Comorbidity Index, MDR colonization is associated with substantial additional costs from the healthcare perspective (€1480.9, 95%CI €1286.4-€1675.5). Heterogeneity between pathogens remains. Colonization with MDR-GN leads to the largest cost increase (€1966.0, 95%CI €1634.6-€2297.4), followed by MRSA with €1651.3 (95%CI €1279.1-€2023.6), and VRE with €879.2 (95%CI €604.1-€1154.2). At the same time, MDR-GN is associated with additional reimbursements of €887.8 (95%CI €722.1-€1053.6), i.e. costs associated with MDR-colonization exceed reimbursement. CONCLUSIONS: Even without the onset of invasive infection, documented MDR-colonization at hospital admission is associated with increased hospital costs, which are not fully covered within the German DRG-based hospital payment system.

Hyaluronan-mediated mononuclear leukocyte binding to gingival fibroblasts.

OBJECTIVES: Binding of mononuclear leukocytes to hyaluronan cable structures is a well-known pathomechanism in several chronic inflammatory diseases, but has not yet described for chronic oral inflammations. The aim of this study was to evaluate if and how binding of mononuclear leukocytes to pathologic hyaluronan cable structures can be induced in human gingival fibroblasts. MATERIAL AND METHODS: Experiments were performed with human gingival fibroblasts and peripheral blood mononuclear cells (PBMCs) from three healthy blood donors. Gingival fibroblasts were stimulated with (1) tunicamycin, (2) polyinosinic/polycytidylic acid (Poly:IC), and (3) lipopolysaccharides (LPS) to simulate (1) ER stress and (2) viral and (3) bacterial infections, respectively. Fibroblasts were then co-incubated with PBMCs, and the number of bound and fluorescently labeled PBMCs was assessed using a fluorescence reader and microscopy. For data analysis, a linear mixed model was used. RESULTS: Hyaluronan-mediated binding of PBMCs to gingival fibroblasts was increased by tunicamycin and Poly(I:C) but not by LPS. Hyaluronidase treatment and co-incubation with hyaluronan transport inhibitors reduced this binding. CONCLUSIONS: Results suggest that hyaluronan-mediated binding of blood cells might play a role in oral inflammations. A potential superior role of viruses needs to be confirmed in further clinical studies. CLINICAL RELEVANCE: The linkage between pathological hyaluronan matrices and oral infections opens up potential applications of hyaluronan transport inhibitors in the treatment of chronic oral inflammations.

[New ß­lactam antibiotics and ß­lactamase inhibitors against multidrug-resistant Gram-negative bacteria]. / Neue ß­Laktam-Antibiotika und ß­Laktamase-Inhibitoren gegen multiresistente Gram-negative Erreger.

BACKGROUND: The worldwide spread of multidrug-resistant Gram-negative bacteria (MDR-GN) continues. Treatment options for infections caused by MDR-GN remain scarce and only few new substances are currently in clinical phase II/III studies or have already been granted market approval. OBJECTIVES: To provide an overview about current data on new ß­lactam antibiotics and ß­lactamase inhibitor combinations, respectively. New macrolides, ketolides and aminoglycosides are not addressed. MATERIALS AND METHODS: Selective literature research regarding published data on ceftazidim/avibactam, ceftolozan/tazobactam, imipenem/cilastatin + relebactam, meropenem/vaborbactam, aztreonam/avibactam and cefiderocol, as well as registered trials. RESULTS: The development of new antimicrobials for the treatment of MDR-GN infections offers new options for attending physicians. ß­Lactamase producers are inhibited by these new substances, though with varying efficacy; however, there are still no adequate treatment options for metallo-ß-lactamase (MBL) producers. CONCLUSIONS: Clinical data are still indifferent and come from heterogeneous patient collectives. Direct comparisons with established treatment strategies, such as the "last-resort use" of polymyxins are hardly possible. Cases of early development of resistance have already been described. Finally, the importance of toxicity and optimal dosing-in organ failure or organ replacement procedures such as dialysis-remain unclear.

Contact Precautions for Preventing Nosocomial Transmission of Extended-Spectrum ß Lactamase-Producing Escherichia coli: A Point/Counterpoint Review.

Contact precautions have been recommended for hospitalized patients colonized or infected with extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-EC). Despite such recommendations, a steady, worldwide increase of ESBL-EC has been reported. We discuss arguments in favor of and against contact precautions for ESBL-EC carriers. Healthcare settings with high ESBL-EC colonization pressure, extended hospital stay, and close contact between patients may serve as amplification platforms, further accelerating transmission. However, the evidence base for justifying the implementation of contact precautions for all ESBL-EC carriers remains weak. Until more high-level evidence is available, we support the attitude that hospitals and countries should carefully evaluate their decision on whether to implement contact precautions for ESBL-EC carriers. It is likely that a majority of patients and wards do not need to rely on contact precautions for preventing nosocomial ESBL-EC transmission in nonepidemic settings, without harming patient safety, providing sufficient compliance with standard precautions and ongoing surveillance.