Defining Multidrug Resistance of Gram-Negative Bacteria in the Dutch-German Border Region-Impact of National Guidelines

Preventing the spread of multidrug-resistant Gram-negative bacteria (MDRGNB) is a public health priority. However, the definition of MDRGNB applied for planning infection prevention measures such as barrier precautions differs depending on national guidelines. This is particularly relevant in the Dutch–German border region, where patients are transferred between healthcare facilities located in the two different countries, because clinicians and infection control personnel must understand antibiograms indicating MDRGNB from both sides of the border and using both national guidelines. This retrospective study aimed to compare antibiograms of Gram-negative bacteria and classify them using the Dutch and German national standards for MDRGNB definition. A total of 31,787 antibiograms from six Dutch and four German hospitals were classified. Overall, 73.7% were no MDRGNB according to both guidelines. According to the Dutch and German guideline, 7772/31,787 (24.5%) and 4586/31,787 (12.9%) were MDRGNB, respectively (p < 0.0001). Major divergent classifications were observed for extended-spectrum β-lactamase (ESBL) -producing Enterobacteriaceae, non-carbapenemase-producing carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa and Stenotrophomonas maltophilia. The observed differences show that medical staff must carefully check previous diagnostic findings when patients are transferred across the Dutch–German border, as it cannot be assumed that MDRGNB requiring special hygiene precautions are marked in the transferred antibiograms in accordance with both national guidelines

Compliance to Screening Protocols for Multidrug-Resistant Microorganisms at the Emergency Departments of Two Academic Hospitals in the Dutch-German Cross-Border Region

Infections caused by multidrug-resistant organisms (MDROs) are associated with prolonged hospitalization and higher risk of mortality. Patients arriving in the hospital via the emergency department (ED) are screened for the presence of MDROs in compliance with the screening protocols in order to apply the correct isolation measures. In the Dutch-German border region, local hospitals apply their own screening protocols which are based upon national screening protocols. The contents of the national and local MDRO screening protocols were compared on vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and carbapenemase-producing and carbapenem-resistant Enterobacteriaceae (CPE/CRE). The practicality of the screening protocols was evaluated by performing an audit. As a result, the content of the MDRO screening protocols differed regarding risk factors for MDRO carriage, swab site, personal protective equipment, and isolation measures. The observations and questionnaires showed that the practicality was sufficient; however, the responsibility was not designated clearly and education regarding the screening protocols was deemed inappropriate. The differences between the MDRO screening protocols complicate patient care in the Dutch-German border region. Arrangements have to be made about the responsibility of the MDRO screening, and improvements are necessary concerning education regarding the MDRO screening protocols

A prospective multicentre screening study on multidrug-resistant organisms in intensive care units in the Dutch-German cross-border region, 2017 to 2018:the importance of healthcare structures

BACKGROUND: Antimicrobial resistance poses a risk for healthcare, both in the community and hospitals. The spread of multidrug-resistant organisms (MDROs) occurs mostly on a local and regional level, following movement of patients, but also occurs across national borders. AIM: The aim of this observational study was to determine the prevalence of MDROs in a European cross-border region to understand differences and improve infection prevention based on real-time routine data and workflows. METHODS: Between September 2017 and June 2018, 23 hospitals in the Dutch (NL)–German (DE) cross-border region (BR) participated in the study. During 8 consecutive weeks, patients were screened upon admission to intensive care units (ICUs) for nasal carriage of meticillin-resistant Staphylococcus aureus (MRSA) and rectal carriage of vancomycin-resistant Enterococcus faecium/E. faecalis (VRE), third-generation cephalosporin-resistant Enterobacteriaceae (3GCRE) and carbapenem-resistant Enterobacteriaceae (CRE). All samples were processed in the associated laboratories. RESULTS: A total of 3,365 patients were screened (median age: 68 years (IQR: 57–77); male/female ratio: 59.7/40.3; NL-BR: n = 1,202; DE-BR: n = 2,163). Median screening compliance was 60.4% (NL-BR: 56.9%; DE-BR: 62.9%). MDRO prevalence was higher in DE-BR than in NL-BR, namely 1.7% vs 0.6% for MRSA (p = 0.006), 2.7% vs 0.1% for VRE (p < 0.001) and 6.6% vs 3.6% for 3GCRE (p < 0.001), whereas CRE prevalence was comparable (0.2% in DE-BR vs 0.0% in NL-BR ICUs). CONCLUSIONS: This first prospective multicentre screening study in a European cross-border region shows high heterogenicity in MDRO carriage prevalence in NL-BR and DE-BR ICUs. This indicates that the prevalence is probably influenced by the different healthcare structures

The phylogenetic landscape and nosocomial spread of the multidrug-resistant opportunist Stenotrophomonas maltophilia

Recent studies portend a rising global spread and adaptation of human- or healthcare-associated pathogens. Here, we analyse an international collection of the emerging, multidrug-resistant, opportunistic pathogen Stenotrophomonas maltophilia from 22 countries to infer population structure and clonality at a global level. We show that the S. maltophilia complex is divided into 23 monophyletic lineages, most of which harbour strains of all degrees of human virulence. Lineage Sm6 comprises the highest rate of human-associated strains, linked to key virulence and resistance genes. Transmission analysis identifies potential outbreak events of genetically closely related strains isolated within days or weeks in the same hospitals

PHIP-associated Chung-Jansen syndrome: Report of 23 new individuals

In 2016 and 2018, Chung, Jansen and others described a new syndrome caused by haploinsufficiency of PHIP (pleckstrin homology domain interacting protein, OMIM *612,870) and mainly characterized by developmental delay (DD), learning difficulties/intellectual disability (ID), behavioral abnormalities, facial dysmorphism and obesity (CHUJANS, OMIM #617991). So far, PHIP alterations appear to be a rare cause of DD/ID. “Omics” technologies such as exome sequencing or array analyses have led to the identification of distinct types of alterations of PHIP, including, truncating variants, missense substitutions, splice variants and large deletions encompassing portions of the gene or the entire gene as well as adjacent genomic regions. We collected clinical and genetic data of 23 individuals with PHIP-associated Chung-Jansen syndrome (CHUJANS) from all over Europe. Follow-up investigations (e.g. Sanger sequencing, qPCR or Fluorescence-in-situ-Hybridization) and segregation analysis showed either de novo occurrence or inheritance from an also (mildly) affected parent. In accordance with previously described patients, almost all individuals reported here show developmental delay (22/23), learning disability or ID (22/23), behavioral abnormalities (20/23), weight problems (13/23) and characteristic craniofacial features (i.e. large ears/earlobes, prominent eyebrows, anteverted nares and long philtrum (23/23)). To further investigate the facial gestalt of individuals with CHUJANS, we performed facial analysis using the GestaltMatcher approach. By this, we could establish that PHIP patients are indistinguishable based on the type of PHIP alteration (e.g. missense, loss-of-function, splice site) but show a significant difference to the average face of healthy individuals as well as to individuals with Prader-Willi syndrome (PWS, OMIM #176270) or with a CUL4B-alteration (Intellectual developmental disorder, X-linked, syndromic, Cabezas type, OMIM #300354). Our findings expand the mutational and clinical spectrum of CHUJANS. We discuss the molecular and clinical features in comparison to the published individuals. The fact that some variants were inherited from a mildly affected parent further illustrates the variability of the associated phenotype and outlines the importance of a thorough clinical evaluation combined with genetic analyses for accurate diagnosis and counselling

Sex differences in vancomycin-resistant enterococci bloodstream infections—a systematic review and meta-analysis

Background!#!Vancomycin-resistant enterococci (VRE) have emerged in the healthcare setting worldwide. Infections with these pathogens, i.e., bloodstream infections (BSI), are accompanied with an impaired patient outcome. Diverse factors comprising patient characteristics, therapeutic strategies, and infection control measures are positively or negatively associated with VRE BSI occurrence. However, whether sex-specific differences influence the frequency of VRE BSI is yet unknown. The aim of this systematic review was to comprehensively summarize and analyze sex prevalence in VRE BSI patients.!##!Main text!#!A systematic search for relevant articles was conducted in PubMed and Web of Science. After screening for eligibility, data extraction from included articles and risk of bias assessment were processed. The prevalence of male/female sex in VRE BSI patients and 95% CI were calculated for each study and summarized as pooled estimated effect. In total, nine articles met the inclusion criteria. Risk of bias assessment resulted in low (six studies) to moderate bias (three studies). The pooled prevalence of male patients suffering from VRE BSI was 59% resulting in a 1.4 male/female prevalence ratio.!##!Conclusions!#!Current literature suggests sex differences with male preference (59%) in the distribution of VRE BSI cases. Further primary studies should address the question of male-specific factors favoring the enhanced frequency of VRE BSI

Impact of the COVID-19 Pandemic on the Management of <i>Staphylococcus aureus</i> Bloodstream Infections in a Tertiary Care Hospital

Staphylococcus aureus bacteremia (SAB) is associated with a high mortality rate. The clinical outcome of SAB patients highly depends on early diagnosis, adequate antibiotic therapy and source control. In the context of the COVID-19 pandemic, the health care system faced additional organizational challenges and the question arose whether structured screening and triaging for COVID-19 and shifting resources influence the management of SAB. Patients (n = 115) with SAB were enrolled in a retrospective comparative study with historical controls (March 2019–February 2021). The quality of SAB therapy was assessed with a point score, which included correct choice of antibiotic, adequate dosage of antibiotic, sufficient duration of therapy, early start of therapy after receipt of findings, focus search and taking control blood cultures 3–4 days after starting adequate antibiotic therapy. The quality of treatment before and after the onset of the COVID-19 pandemic were compared. No significant differences in the total score points were found between the pre-COVID-19 and COVID-19 cohort. All quality indicators, except the correct duration of antibiotic therapy, showed no significant differences in both cohorts. Furthermore, there were no significant differences in the outcome between both cohorts. The treatment quality of SAB therapy was comparable before and during the COVID-19 pandemic

Role of Efflux in Antibiotic Resistance of Achromobacter xylosoxidans and Achromobacter insuavis Isolates From Patients With Cystic Fibrosis

Achromobacter genus (including Achromobacter xylosoxidans, the most prevalent Achromobacter species in patients with cystic fibrosis) is poorly susceptible to most conventional antibiotics. Contribution of efflux by AxyABM, AxyXY-OprZ, and AxyEF-OprN and of target mutations were studied in clinical isolates of A. xylosoxidans and Achromobacter insuavis. Forty-one isolates longitudinally collected from 21 patients with CF were studied by whole-genome sequencing (WGS)-typing, determination of minimum inhibitory concentrations (MICs) of β-lactams, aminoglycosides, colistin, azithromycin, ciprofloxacin, chloramphenicol, and doxycycline, and expression (quantitative RT-PCR) and function (measure of the uptake of a fluorescent substrate) of efflux pumps. WGS-based typing resulted in 10 clusters comprising 2 or 3 isolates and 20 singletons. The efflux activity was high in strains with elevated MICs for amikacin or azithromycin. This work sheds a new light on the impact of efflux and target mutations in resistance of Achromobacter to several drugs

Weekly screening supports terminating nosocomial transmissions of vancomycin-resistant enterococci on an oncologic ward – a retrospective analysis

Abstract Background To investigate the impact of weekly screening within the bundle of infection control measures to terminate vancomycin-resistant enterococci (VRE) transmissions on an oncologic ward. Methods A cluster of 12 VRE colonisation and five infections was detected on an oncologic ward between January and April 2015. Subsequently, the VRE point prevalence was detected and, as part of a the bundle of infection control strategies to terminate the VRE cluster, we isolated affected patients, performed hand hygiene training among staff on ward, increased observations by infection control specialists, intensified surface disinfection, used personal protective equipment and initiated an admission screening in May 2015. After a further nosocomial VRE infection in August 2015, a weekly screening strategy of all oncology patients on the respective ward was established while admission screening was continued. Whole genome sequencing (WGS)-based typing was applied to determine the clonal relationship of isolated strains. Results Initially, 12 of 29 patients were VRE colonised; of these 10 were hospital-acquired. During May to August, on average 7 of 40 patients were detected to be VRE colonised per week during the admission screening, showing no significant decline compared to the initial situation. WGS-based typing revealed five different clusters of which three were due to vanB- and two vanA-positive enterococci. After an additional weekly screening was established, the number of colonised patients significantly declined to 1/53 and no further nosocomial cases were detected. Conclusions Weekly screening helped to differentiate between nosocomial and community-acquired VRE cases resulting in earlier infection control strategies on epidemic situations for a successful termination of nosocomial VRE transmissions

A nosocomial cluster of vancomycin resistant enterococci among COVID-19 patients in an intensive care unit

Background!#!Currently, hospitals have been forced to divert substantial resources to cope with the ongoing coronavirus disease 2019 (COVID-19) pandemic. It is unclear if this situation will affect long-standing infection prevention practices and impact on healthcare associated infections. Here, we report a nosocomial cluster of vancomycin-resistant enterococci (VRE) that occurred on a COVID-19 dedicated intensive care unit (ICU) despite intensified contact precautions during the current pandemic. Whole genome sequence-based typing (WGS) was used to investigate genetic relatedness of VRE isolates collected from COVID-19 and non-COVID-19 patients during the outbreak and to compare them to environmental VRE samples.!##!Methods!#!Five VRE isolated from patients (three clinical and two screening samples) as well as 11 VRE and six vancomycin susceptible Enterococcus faecium (E. faecium) samples from environmental sites underwent WGS during the outbreak investigation. Isolate relatedness was determined using core genome multilocus sequence typing (cgMLST).!##!Results!#!WGS revealed two genotypic distinct VRE clusters with genetically closely related patient and environmental isolates. The cluster was terminated by enhanced infection control bundle strategies.!##!Conclusions!#!Our results illustrate the importance of continued adherence to infection prevention and control measures during the COVID-19 pandemic to prevent VRE transmission and healthcare associated infections