Risk Factors and Transmission of Healthcare-Related Pathogens

The literature reviews and observational studies in this thesis are about the role of epidemiology in describing, identifying and controlling transmission of healthcare-related pathogens. The ultimate goal of conducting these studies is to optimize care and to provide safer care for p

VIM-positive Pseudomonas aeruginosa in a large tertiary care hospital: Matched case-control studies and a network analysis

Background: Emergence of multidrug-resistant Pseudomonas aeruginosa is of global concern. We aimed to identify epidemiological relationships, the most common way of transmission, and risk factors for presence of Verona Integron-encoded Metallo-β-lactamase (VIM)-positive P. aeruginosa (VIM-PA). Methods: We conducted a network analysis and matched case-control studies (1:2:2). Controls were hospital-based and matched with cases for ward, day of admission (control group 1 and 2) and time between admission and the identification of VIM-PA (control group 1). The network was visualized using Cytoscape, an

Mortality associated with carbapenem-susceptible and Verona Integron-encoded Metallo-β-lactamase-positive Pseudomonas aeruginosa bacteremia

BACKGROUND: Studies on various Gram-negative bacteria suggest that resistance to carbapenem antibiotics is responsible for increased mortality in patients; however, results are not conclusive. We first assessed the 28-day in-hospital all-cause mortality in patients with Verona Integron-encoded Metallo-β-lactamase-positive Pseudomonas aeruginosa (VIM-PA) bacteremia compared to patients with VIM-negative, carbapenem-susceptible P. aeruginosa (CS-PA) bacteremia. Second, we identified determinants for mortality and survival. METHODS: All patients with a positive blood culture with VIM-PA or CS-PA between January 2004 and January 2016 were included. Kaplan-Meier survival curves were constructed, and survivors and non-survivors were compared on relevant clinical parameters using univariate analyses, and multivariable analyses using a Cox-proportional hazard model. RESULTS: In total, 249 patients were included, of which 58 (23.3%) died. Seventeen out of 40 (42.5%) patients with VIM-PA died, compared to 41 out of 209 (19.6%) patients with CS-PA (difference = 22.9%, P-value = 0.001). Assumed acquisition of the bacterium at the intensive care unit was significantly associated with mortality (HR = 3.32, 95%CI = 1.60-6.87), and having had adequate antibiotic therapy in days 1-14 after the positive blood culture was identified as a determinant for survival (HR = 0.03, 95%CI = 0.01-0.06). VIM-PA vs CS-PA was not identified as an independent risk factor for mortality. CONCLUSIONS: The crude mortality rate was significantly higher in patients with a VIM-PA bacteremia compared to patients with a CS-PA bacteremia; however, when analyzing the data in a multivariable model this difference was non-significant. Awareness of the presence of P. aeruginosa in the hospital environment that may be transmitted to patients and rapid microbiological diagnostics are essential for timely administration of appropriate antibiotics. Acquisition of P. aeruginosa should be prevented, independent of resistance profile

An outbreak of Clostridium difficile infections due to new PCR ribotype 826

__Objectives:__ To investigate an unusual outbreak of five patients with a total of eight episodes of a Clostridium difficile infection on a gastrointestinal surgical ward of a Dutch tertiary-care, university-affiliated hospital. __Methods:__ Clinical case investigations and laboratory analyses were performed. Laboratory analyses included PCR ribotyping, multiple-locus variable-number tandem repeat analysis typing, toxin typing, antimicrobial susceptibility testing and whole genome sequencing. __Results:__ The outbreak was associated with recurrent and severe disease in two of five patients. All episodes were due to a unique ribotype that was not recognized in the collection of an international network of reference laboratories and was assigned PCR ribotype 826. PCR ribotype 826 is a toxin A-, toxin B- and binary toxin-positive ribotype which according to molecular typing belongs to clade 5 and resembles the so-called hypervirulent ribotype 078. The presence of a clonal outbreak was confirmed by whole genome sequencing, yet the source of this newly identified ribotype remained unclear. __Conclusions:__ This newly identified C. difficile PCR ribotype 826 is part of clade 5 and might also have increased virulence. The recognition of this outbreak highlights the need for ongoing C. difficile infection surveillance to monitor new circulating ribotypes with assumed increased virulence

Acquisition of multidrug-resistant Enterobacterales during international travel: A systematic review of clinical and microbiological characteristics and meta-analyses of risk factors

Background: International tourism increased from 25 million tourist arrivals in 1950 to over 1.3 billion in 2017. These travelers can be exposed to (multi) resistant microorganisms, may become colonized, and bring them back home. This systematic review aims to identify the carriage rates of multidrug-resistant Enterobacterales (MDR-E) among returning travelers, to identify microbiological methods used, and to identify the leading risk factors for acquiring MDR-E during international travel. Methods: Articles related to our research question were identified through a literature search in multiple databases (until June 18, 2019)-Embase, Medline Ovid, Cochrane, Scopus, Cinahl, Web of Science, and Google Scholar. Results: Out of 3211 potentially relevant articles, we included 22 studies in the systematic review, and 12 studies in 7 random-effects meta-analyses. Highest carriage rates of MDR-E were observed after travel to Southern Asia (median 71%), followed by travel to Northern Africa (median 42%). Carbapenemase-producing Enterobacterales (CPE) were identified in 5 out of 22 studies, from a few patients. However, in only eight out of 22 studies (36.4%) the initial laboratory method targeted detection of the presence of CPE in the original samples. The risk factor with the highest pooled odds ratio (OR) for MDR-E was travel to Southern Asia (pooled OR = 14.16, 95% confidence interval [CI] = 5.50 to 36.45), followed by antibiotic use during travel (pooled OR = 2.78, 95% CI = 1.76 to 4.39). Conclusions: Risk of acquiring MDR-E while travelling increases depending on travel destination and if antibiotics are used during travel. This information is useful for the development of guidelines for healthcare facilities with low MDR-E prevalence rates to prevent admission of carriers without appropriate measures. The impact of such guidelines should be assessed

Chiral three-nucleon forces and bound excited states in neutron-rich oxygen isotopes

We study the spectra of neutron-rich oxygen isotopes based on chiral two- and three-nucleon interactions. First, we benchmark our many-body approach by comparing ground-state energies to coupled-cluster results for the same two-nucleon interaction, with overall good agreement. We then calculate bound excited states in 21,22,23O, focusing on the role of three-nucleon forces, in the standard sd shell and an extended sdf7/2p3/2 valence space. Chiral three-nucleon forces provide important one- and two-body contributions between valence neutrons. We find that both these contributions and an extended valence space are necessary to reproduce key signatures of novel shell evolution, such as the N = 14 magic number and the low-lying states in 21O and 23O, which are too compressed with two-nucleon interactions only. For the extended space calculations, this presents first work based on nuclear forces without adjustments. Future work is needed and open questions are discussed.Comment: 6 pages, 4 figures, published versio

Ab-initio calculation of the 6Li{}^6Li binding energy with the Hybrid Multideterminant scheme

We perform an ab-initio calculation for the binding energy of ${}^6Li$ using the CD-Bonn 2000 NN potential renormalized with the Lee-Suzuki method. The many-body approach to the problem is the Hybrid Multideterminant method. The results indicate a binding energy of about $31 MeV$, within a few hundreds KeV uncertainty. The center of mass diagnostics are also discussed.Comment: 18 pages with 3 figures. More calculations added, to be published in EPJ

An outbreak of ST307 extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae in a rehabilitation center: An unusual source and route of transmission

Objective: Nosocomial outbreaks due to multidrug-resistant microorganisms in rehabilitation centers have rarely been reported. We report an outbreak of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae (ESBL-K. pneumoniae) on a single ward in a rehabilitation center in Rotterdam, The Netherlands.Design: Outbreak description.Setting: A 40-bed ward of a rehabilitation center in the Netherlands.Methods: In October 2016, 2 patients were found to be colonized by genetically indistinguishable ESBL-K. pneumoniae isolates. Therefore, an outbreak management team was installed, by whom a contact tracing plan was made. In addition to general outbreak measures, specific measures were formulated to allow continuation of the rehabilitation process. Also, environmental cultures were taken. Multiple-locus variable-number tandem-repeat analysis and amplification fragment-length polymorphism were used to determine strain relatedness. Selected isolates were subjected to whole-genome multilocus sequence typing.Results: The outbreak lasted 8 weeks. In total, 14 patients were colonized with an ESBL-K. pneumoniae, of whom 11 patients had an isolate belonging to

The daily direct costs of isolating patients identified with highly resistant micro-organisms in a non

Background: Isolation precautions are recommended when caring for patients identified with highly resistant micro-organisms (HRMOs). However, the direct costs of patients in isolation are largely unknown. Aim: To obtain detailed information on the daily direct costs associated with isolating patients identified with HRMOs. Methods: This study was performed from November until December 2017 on a 12-bed surgical ward. This ward contained solely isolation rooms with anterooms. The daily direct costs of isolation were based on three cost items: (1) additional personal protective equipment (PPE), measured by counting the consumption of empty packaging materials; (2) cleaning and disinfection of the isolation room, based on the costs of an outsourced cleaning company; and (3) additional workload for healthcare workers, based on literature and multiplied by the average gross hourly salary of nurses. A distinction was made between the costs for strict isolation, contact-plus isolation, and contact isolation. Findings: During the study period, 26 patients were nursed in isolation because of HRMO carriage. Time for donning and doffing of PPE was 31 min per day. The average daily direct costs of isolation were the least expensive for contact isolation (gown, gloves), €28/$31, and the most expensive for strict isolation (surgical mask, gloves, gown, cap), €41/$47. Conclusion: Using a novel, easy method to estimate consumption of PPE, we conclude that the daily direct costs of isolating a patient differ per type of isolation. Insight into the direct costs of isolation is of utmost importance when developing or updating infection prevention policies

The nuclear energy density functional formalism

The present document focuses on the theoretical foundations of the nuclear energy density functional (EDF) method. As such, it does not aim at reviewing the status of the field, at covering all possible ramifications of the approach or at presenting recent achievements and applications. The objective is to provide a modern account of the nuclear EDF formalism that is at variance with traditional presentations that rely, at one point or another, on a {\it Hamiltonian-based} picture. The latter is not general enough to encompass what the nuclear EDF method represents as of today. Specifically, the traditional Hamiltonian-based picture does not allow one to grasp the difficulties associated with the fact that currently available parametrizations of the energy kernel $E[g',g]$ at play in the method do not derive from a genuine Hamilton operator, would the latter be effective. The method is formulated from the outset through the most general multi-reference, i.e. beyond mean-field, implementation such that the single-reference, i.e. "mean-field", derives as a particular case. As such, a key point of the presentation provided here is to demonstrate that the multi-reference EDF method can indeed be formulated in a {\it mathematically} meaningful fashion even if $E[g',g]$ does {\it not} derive from a genuine Hamilton operator. In particular, the restoration of symmetries can be entirely formulated without making {\it any} reference to a projected state, i.e. within a genuine EDF framework. However, and as is illustrated in the present document, a mathematically meaningful formulation does not guarantee that the formalism is sound from a {\it physical} standpoint. The price at which the latter can be enforced as well in the future is eventually alluded to.Comment: 64 pages, 8 figures, submitted to Euroschool Lecture Notes in Physics Vol.IV, Christoph Scheidenberger and Marek Pfutzner editor