Participatory eHealth development to support nurses in antimicrobial stewardship.

BACKGROUND: Antimicrobial resistance poses a threat to patient safety worldwide. To stop antimicrobial resistance, Antimicrobial Stewardship Programs (ASPs; programs for optimizing antimicrobial use), need to be implemented. Within these programs, nurses are important actors, as they put antimicrobial treatment into effect. To optimally support nurses in ASPs, they should have access to information that supports them in their preparation, administration and monitoring tasks. In addition, it should help them to detect possible risks or adverse events associated with antimicrobial therapy. In this formative study, we investigate how nurses' can be supported in ASPs by means of an eHealth intervention that targets their information needs. METHODS: We applied a participatory development approach that involves iterative cycles in which health care workers, mostly nurses, participate. Focus groups, observations, prototype evaluations (via a card sort task and a scenario-based information searching task) and interviews are done with stakeholders (nurses, managers, pharmacist, and microbiologist) on two pulmonary wards of a 1000-bed teaching hospital. RESULTS: To perform the complex antimicrobial-related tasks well, nurses need to consult various information sources on a myriad of occasions. In addition, the current information infrastructure is unsupportive of ASP-related tasks, mainly because information is not structured to match nurse tasks, is hard to find, out of date, and insufficiently supportive of awareness. Based our findings, we created a concept for a nurse information application. We attuned the application's functionality, content, and structure to nurse work practice and tasks. CONCLUSIONS: By applying a participatory development approach, we showed that task support is a basic need for nurses. Participatory development proved useful regarding several aspects. First, it allows for combining bottom-up needs (nurses') and top-down legislations (medical protocols). Second, it enabled us to fragmentise and analyse tasks and to reduce and translate extensive information into task-oriented content. Third, this facilitated a tailored application to support awareness and enhance patient safety. Finally, the involvement of stakeholders created commitment and ownership, and helped to weigh needs from multiple perspectives.

Novel organization of the arginine catabolic mobile element and staphylococcal cassette chromosome mec composite island and its horizontal transfer between distinct Staphylococcus aureus genotypes.

In this study, 425 methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered in the Dutch-German Euregio were investigated for the presence of the arginine catabolic mobile element (ACME). Sequence analysis by whole-genome sequencing revealed an entirely new organization of the ACME-staphylococcal cassette chromosome mec composite island (SCCmec-CI), with truncated ACME type II located downstream of SCCmec. An identical nucleotide sequence of ACME-SCCmec-CI was found in two distinct MRSA lineages (t064-ST8 and t002-ST5), which has not been reported previously in S. aureus.

Infection prevention in a connected world: the case for a regional approach.

Results from microbiological and epidemiological investigations, as well as mathematical modelling, show that the transmission dynamics of nosocomial pathogens, especially of multiple antibiotic-resistant bacteria, is not exclusively amenable to single-hospital infection prevention measures. Crucially, their extent of spread depends on the structure of an underlying "healthcare network", as determined by inter-institutional referrals of patients. The current trend towards centralized healthcare systems favours the spread of hospital-associated pathogens, and must be addressed by coordinated regional or national approaches to infection prevention in order to maintain patient safety. Here we review recent advances that support this hypothesis, and propose a "next-generation" network-approach to hospital infection prevention and control.

Detection of new methicillin-resistant Staphylococcus aureus strains that carry a novel genetic homologue and important virulence determinants.

In this study, 18 methicillin-resistant Staphylococcus aureus (MRSA) isolates harboring staphylococcal cassette chromosome mec (SCCmec) type XI, recovered in the Dutch-German Euregio, were characterized by DNA microarrays. In contrast to previous data, we found two MRSA strains of different clonal lineages possessing SCCmec XI that carried important virulence determinants. The worrisome emergence of such toxigenic MRSA strains raises concerns that MRSA strains with enhanced virulence potential and impaired detectability by standard molecular assays may spread in Europe.

Why business modeling is crucial in the development of eHealth technologies.

The impact and uptake of information and communication technologies that support health care are rather low. Current frameworks for eHealth development suffer from a lack of fitting infrastructures, inability to find funding, complications with scalability, and uncertainties regarding effectiveness and sustainability. These issues can be addressed by defining a better implementation strategy early in the development of eHealth technologies. A business model, and thus business modeling, help to determine such an implementation strategy by involving all important stakeholders in a value-driven dialogue on what the technology should accomplish. This idea also seems promising to eHealth, as it can contribute to the whole development of eHealth technology. We therefore suggest that business modeling can be used as an effective approach to supporting holistic development of eHealth technologies. The contribution of business modeling is elaborated in this paper through a literature review that covers the latest business model research, concepts from the latest eHealth and persuasive technology research, evaluation and insights from our prior eHealth research, as well as the review conducted in the first paper of this series. Business modeling focuses on generating a collaborative effort of value cocreation in which all stakeholders reflect on the value needs of the others. The resulting business model acts as the basis for implementation. The development of eHealth technology should focus more on the context by emphasizing what this technology should contribute in practice to the needs of all involved stakeholders. Incorporating the idea of business modeling helps to cocreate and formulate a set of critical success factors that will influence the sustainability and effectiveness of eHealth technology.

Relation between amoxicillin concentration in sputum of COPD patients and length of hospitalization.

Amoxicillin is a widely used antibiotic in COPD. Little is known about the transfer of amoxicillin into sputum of COPD patients. The objective was to investigate the relationship between the concentration of amoxicillin in sputum in hospitalized COPD patients and length of hospitalization. To be effective against bacterial pathogens, the amoxicillin concentration in target tissues should be higher than the Minimal Inhibiting Concentration (MIC) of 2 mg/l. Therefore, this was also used as the cut-off value for the amoxicillin concentration in sputum, as a marker for lung tissue concentration. Fifty-two COPD in-patients with an exacerbation, treated with amoxicillin clavulanic acid, were included in this cohort study. Of these patients 7 also had pneumonia. Patients were divided in patients with an amoxicillin sputum concentration ≥ 2 mg/l and < 2 mg/l. Furthermore, inflammation markers in sputum and serum and clinical parameters were obtained. Of the 33 patients with usable sputum, 11 had a concentration in sputum ≥ 2 mg/l. The mean length of hospitalization for patients with concentrations below the MIC90 to common respiratory pathogens was 11.0 days, while for patients with concentrations at or above the MIC90 this was 7.0 days (p = 0.005). COPD patients admitted for an acute exacerbation of COPD, with a sputum concentration of amoxicillin ≥ 2 mg/l had a markedly reduced length of hospitalization compared to patients with a concentration < 2 mg/l. It is worthwhile testing whether individualized treatment based on sputum amoxicillin concentrations of patients during hospitalization for acute exacerbations can effectively reduce hospital stay.

Tenosynovitis caused by a pseudallescheria boydii infection and symptoms of reflex sympathetic dystrophy after a dog bite.

Tenosynovitis caused by a Pseudallescheria boydii infection is an extremely rare complication after a dog bite and is easily misdiagnosed, leading to a delay in treatment. Careful history taking and adequate cultures can lead to a timely diagnosis, and longstanding antimycotic treatment can successfully eradicate the fungus.

How nurses seek and evaluate clinical guidelines on the Internet.

AIM: This paper is a report of a study conducted to assess nurses' information-seeking strategies and problems encountered when seeking clinical guidelines on the Internet, and to investigate the criteria they apply when evaluating the guidelines and the websites communicating the guidelines. BACKGROUND: As nurses are increasingly taking on clinical responsibilities, they should be able to use the Internet to access up-to-date clinical guidelines. Currently, nurses' information-seeking skills remain rather limited. METHOD: In 2008, a convenience sample of 20 nurses solved scenario-based tasks using the Internet to seek clinical guidelines regarding methicillin-resistant Staphylococcus aureus while thinking aloud. RESULTS: General background information and universal precautions were successfully identified by participants, in contrast to more specific precautions. Nurses' information-seeking skills appeared rather basic, as they employed a limited number of search terms and consulted a limited number of websites. Ineffective searches were mainly caused by a mismatch between the guidelines and nurses' tacit knowledge. Perceived practical relevance and information completeness were the most frequently applied quality criteria. Accuracy and disclosures, which are emphasized in existing e-health literature, were considered less important. As long as information matched nurses' practical and experiential wisdom, they were satisfied. CONCLUSION: Nurses appeared to rely predominantly on tacit knowledge during the search process and while evaluating the retrieved guidelines. This is dangerous because nurses' reliance on inaccurate information might result in inadequate behaviour. It is therefore essential to expand nurses' current information base by tailoring both navigation structure and the guideline communication to dovetail with nurses' tacit knowledge.

Is time to closure a factor in the occurrence of infection in traumatic wounds? A prospective cohort study in a Dutch level 1 trauma centre.

BACKGROUND: The dogma that traumatic wounds should not be sutured after 6 h is based on an animal experiment by P L Friedrich in 1898. There is no adequately powered prospective study on this cut-off of 6 h to confirm or disprove the dogma. The aim of this study was to provide evidence against the dogma that wounds should be sutured within 6 h after trauma. METHOD: 425 patients were included in a prospective cohort study. Patients' wounds were closed, independent of time after trauma. All patients were seen after 7-10 days for removal of stitches and wound control on infection. RESULTS: Of the 425 patients, 17 were lost to follow-up. Of the remaining 408 patients, 45 had wounds older than 6 h after trauma. At follow-up 372 patients (91%) had no infection and 36 patients had redness of the suture sites or worse. 11 patients (2.7%) had general redness or pus. Of those with a wound older than 6 h, three of 45 (6.7%) wounds were infected, versus 30 of 363 (9.1%) in wounds younger than 6 h (p=0.59). CONCLUSION: In everyday practice wounds are sutured regardless of elapsed time. Here an attempt was made to present the evidence for this daily routine, contrary to Friedrich's Dogma.

Prevention and Control of Multidrug-Resistant Bacteria in The Netherlands and Germany-The Impact of Healthcare Structures.

The Netherlands and Germany are neighbouring countries within the European Union but are differently affected by multidrug-resistant microorganisms (MDRO). In this narrative review, we summarize data about antibiotic use, the occurrence of MDRO and healthcare-associated infections in these two countries, as well as data about organizational and structural differences between the Dutch and German healthcare systems. These results are discussed with a focus on whether or how the organization of healthcare influences MDRO prevention. We found that from the point of view of MDRO prevention, a higher density of inpatient care, a higher number of hospitals, a longer length of stay and lower staffing ratios might facilitate MDRO dissemination in German hospitals.

A multi-center blinded study on the efficiency of phenotypic screening methods to detect glycopeptide intermediately susceptible Staphylococcus aureus (GISA) and heterogeneous GISA (h-GISA).

BACKGROUND: To determine the true incidence of hGISA/GISA and its consequent clinical impact, methods must be defined that will reliably and reproducibly discriminate these resistant phenotypes from vancomycin susceptible S. aureus (VSSA). METHODS: This study assessed and compared the ability of eight Dutch laboratories under blinded conditions to discriminate VSSA from hGISA/GISA phenotypes and the intra- and inter-laboratory reproducibility of agar screening plates and the Etest method. A total of 25 blinded and unique strains (10 VSSA, 9 hGISA and 6 GISA) were categorized by the PAP-AUC method and PFGE typed to eliminate clonal duplication. All strains were deliberately added in quadruplets to evaluate intra-laboratory variability and reproducibility of the methods. Strains were tested using three agar screening methods, Brain Heart Infusion agar (BHI) + 6 microg/ml vancomycin, Mueller Hinton agar (MH) + 5 microg/ml vancomycin and MH + 5 microg/ml teicoplanin) and the Etest macromethod using a 2 McFarland inoculum. RESULTS AND DISCUSSION: The ability to detect the hGISA/GISA phenotypes varied significantly between methods and phenotypes. BHI vancomycin and MH vancomycin agar screens lacked the ability to detect hGISA. The MH teicoplanin agar screen was more sensitive but still inferior to Etest that had a sensitivity of 98.5% and 99.5%, for hGISA and GISA, respectively. Intra- and inter-laboratory reproducibility varied between methods with poorest performance seen with BHI vancomycin. CONCLUSION: This is the first multi-center blinded study to be undertaken evaluating various methods to detect GISA and hGISA. These data showed that the ability of clinical laboratories to detect GISA and hGISA varied considerably, and that screening plates with vancomycin have a poor performance in detecting hGISA.

The value of participatory development to support antimicrobial stewardship with a clinical decision support system.

BACKGROUND: Current clinical decision support systems (CDSSs) for antimicrobial stewardship programs (ASPs) are guideline- or expert-driven. They are focused on (clinical) content, not on supporting real-time workflow. Thus, CDSSs fail to optimally support prudent antimicrobial prescribing in daily practice. Our aim was to demonstrate why and how participatory development (involving end-users and other stakeholders) can contribute to the success of CDSSs in ASPs. METHODS: A mixed-methods approach was applied, combining scenario-based prototype evaluations (to support verbalization of work processes and out-of-the-box thinking) among 6 medical resident physicians with an online questionnaire (to cross-reference findings of the prototype evaluations) among 54 Dutch physicians. RESULTS: The prototype evaluations resulted in insight into the end-users and their way of working, as well as their needs and expectations. The online questionnaire that was distributed among a larger group of medical specialists, including lung and infection experts, complemented the findings of the prototype evaluations. It revealed a say/do problem concerning the unrecognized need of support for selecting diagnostic tests. CONCLUSIONS: Low-fidelity prototypes of a technology allow researchers to get to know the end-users, their way of working, and their work context. Involving experts allows technology developers to continuously check the fit between technology and clinical practice. The combination enables the participatory development of technology to successfully support ASPs.

Technology to Support Integrated Antimicrobial Stewardship Programs: A User Centered and Stakeholder Driven Development Approach.

The rise of antimicrobial resistance (AMR) is a severe global health problem. Tackling this problem requires the prudent prescribing of antimicrobials. This is promoted through Antimicrobial Stewardship Programs (ASPs). In this position paper we describe i) how a socio-technical multidisciplinary approach (based on the CeHRes Roadmap) can be applied in the development and implementation of Antimicrobial Stewardship technologies and ii) how this approach can be of value to support Antimicrobial Stewardship in practice. The CeHRes Roadmap entails five different phases to explore and test how an eHealth technology can be tailored to the target group and successfully implemented in practice: i) contextual inquiry, ii) value specification, iii) design, iv) operationalization, v) evaluation. In this position paper we describe the lessons learned from research and practice to guide future developments of technology based ASP interventions. Since AMR is a huge wicked problem on a global level, it requires innovative methods and models to empower general public and professionals to be proactive rather than reactive in a digitalized world. We highlight how to combat the dangerous rise of antimicrobial resistance in the future.

Real-life data on antibiotic prescription and sputum culture diagnostics in acute exacerbations of COPD in primary care.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are generally treated with optimization of bronchodilation therapy and a course of oral corticosteroids, mostly without antibiotics. The Dutch guidelines recommend prudent use of antibiotics, with amoxicillin or doxycycline as first choice. Here we evaluate adherence to these guidelines with regard to antibiotic prescription in AECOPD in primary care and the use of sputum cultures. METHODS: We retrospectively analyzed a longitudinal cohort of patients in three primary care practices in the north-eastern region of the Netherlands from 2009 to 2013 (n=36,172 subjects) participating in the Registration Network Groningen. Antibiotics prescribed for AECOPD -10/+28 days from the start date of corticosteroid courses were evaluated. In addition, we assessed regional data on the susceptibility of respiratory pathogens from COPD patients. RESULTS: We identified 1,297 patients with COPD. Of these, 616 experienced one or more exacerbations, resulting in a total of 1,558 exacerbations, for which 1,594 antibiotic courses were prescribed. The recommended antibiotics doxycycline and amoxicillin accounted for 56% of the prescribed antibiotics overall and for 35% in subsequent antibiotic courses. The alternative choices were not based on culture results because only in 67 AECOPD events (2.9%) sputum samples were taken. Regional data including 3,638 sputum samples showed that pathogens relevant in AECOPD were detected in 19% of cultures. CONCLUSION: Our study shows that guidelines regarding the prescription of antibiotics are poorly followed, particularly in recurrent exacerbations. Sputum cultures were performed in a small minority of cases. Performing sputum diagnostics in patients with early treatment failure or a repeated exacerbation when antibiotic treatment is started may further rationalize antibiotic treatment.

Targeted next-generation sequencing of the 16S-23S rRNA region for culture-independent bacterial identification - increased discrimination of closely related species.

The aim of this study was to develop an easy-to-use culture-free diagnostic method based on next generation sequencing (NGS) of PCR amplification products encompassing whole 16S-23S rRNA region to improve the resolution of bacterial species identification. To determine the resolution of the new method 67 isolates were subjected to four identification methods: Sanger sequencing of the 16S rRNA gene; NGS of the 16S-23S rRNA region using MiSeq (Illumina) sequencer; Microflex MS (Bruker) and VITEK MS (bioMérieux). To evaluate the performance of this new method when applied directly on clinical samples, we conducted a proof of principle study with 60 urine samples from patients suspected of urinary tract infections (UTIs), 23 BacT/ALERT (bioMérieux) positive blood culture bottles and 21 clinical orthopedic samples. The resolution power of NGS of the 16S-23S rRNA region was superior to other tested identification methods. Furthermore, the new method correctly identified pathogens established as the cause of UTIs and blood stream infections with conventional culture. NGS of the 16S-23S rRNA region also showed increased detection of bacterial microorganisms in clinical samples from orthopedic patients. Therefore, we conclude that our method has the potential to increase diagnostic yield for detection of bacterial pathogenic species compared to current methods.

Measuring the impact of antimicrobial stewardship programs.

Antimicrobial Stewardship Programs (ASPs) are being implemented worldwide to optimize antimicrobial therapy, and thereby improve patient safety and quality of care. Additionally, this should counteract resistance development. It is, however, vital that correct and timely diagnostics are performed in parallel, and that an institution runs a well-organized infection prevention program. Currently, there is no clear consensus on which interventions an ASP should comprise. Indeed this depends on the institution, the region, and the patient population that is served. Different interventions will lead to different effects. Therefore, adequate evaluations, both clinically and financially, are crucial. Here, we provide a general overview of, and perspective on different intervention strategies and methods to evaluate these ASP programs, covering before mentioned topics. This should lead to a more consistent approach in evaluating these programs, making it easier to compare different interventions and studies with each other and ultimately improve infection and patient management.

MRSA Prevalence and Associated Risk Factors among Health-Care Workers in Non-outbreak Situations in the Dutch-German EUREGIO.

Preventing the spread of methicillin-resistant Staphylococcus aureus (MRSA) in healthcare facilities is a major infection control target. However, only a few studies have assessed the potential role of healthcare workers (HCWs) for MRSA dissemination. To investigate the MRSA prevalence and the risk factors for MRSA colonization among HCWs, nasopharyngeal swabs were taken between June 2010 and January 2011 from 726 employees from nine acute care hospitals with different care levels within the German part of a Dutch-German border region (EUREGIO). The isolated MRSA strains were investigated using spa typing. The overall MRSA prevalence among HCWs in a non-outbreak situation was 4.6% (33 of 726), and was higher in nurses (5.6%, 29 of 514) than in physicians (1.2%, 1 of 83). Possible risk factors associated with MRSA colonization were a known history of MRSA carriage and the presence of acne. Intensive contact with patients may facilitate MRSA transmission between patients and HCWs. Furthermore, an accumulation of risk factors was accompanied by an increased MRSA prevalence in HCW.

Cross-border comparison of antibiotic prescriptions among children and adolescents between the north of the Netherlands and the north-west of Germany.

BACKGROUND: Antibiotic resistance is a worldwide problem and inappropriate prescriptions are a cause. Especially among children, prescriptions tend to be high. It is unclear how they differ in bordering regions. This study therefore examined the antibiotic prescription prevalence among children in primary care between northern Netherlands and north-west of Germany. METHODS: Two datasets were used: The Dutch (IADB) comprises representative data of pharmacists in North Netherland and the German (BARMER GEK) includes nationwide health insurance data. Both were filtered using postal codes to define two comparable bordering regions with patients under 18 years for 2010. RESULTS: The proportion of primary care patients receiving at least one antibiotic was lower in northern Netherlands (29.8 %; 95 % confidence interval [95 % CI]: 29.3-30.3), compared to north-west Germany (38.9 %; 95 % CI: 38.2-39.6). Within the respective countries, there were variations ranging from 27.0 to 44.1 % between different areas. Most profound was the difference in second-generation cephalosporins: for German children 25 % of the total prescriptions, while for Dutch children it was less than 0.1 %. CONCLUSIONS: This study is the first to compare outpatient antibiotic prescriptions among children in primary care practices in bordering regions of two countries. Large differences were seen within and between the countries, with overall higher prescription prevalence in Germany. Considering increasing cross-border healthcare, these comparisons are highly valuable and help act upon antibiotic resistance in the first line of care in an international approach.

An integrated stewardship model: antimicrobial, infection prevention and diagnostic (AID).

Considering the threat of antimicrobial resistance and the difficulties it entails in treating infections, it is necessary to cross borders and approach infection management in an integrated, multidisciplinary manner. We propose the antimicrobial, infection prevention and diagnostic stewardship model comprising three intertwined programs: antimicrobial, infection prevention and diagnostic stewardship, involving all stakeholders. The focus is a so-called 'theragnostics' approach. This leads to a personalized infection management plan, improving patient care and minimizing resistance development. Furthermore, it is important that healthcare regions nationally and internationally work together, ensuring that the patient (and microorganism) transfers will not cause problems in a neighboring institution. This antimicrobial, infection prevention and diagnostic stewardship model can serve as a blue print to implement innovative, integrative infection management.

Driving Forces of Mechanisms Regulating Oxacillin-Resistance Phenotypes of MRSA: Truly Oxacillin-Susceptible mecA-Positive Staphylococcus aureus Clinical Isolates also Exist.

As MRSA are considered Staphylococcus aureus isolates with oxacillin minimum inhibitory concentration (MIC) of ≥4 mg/L or harboring the mecA gene. However, the presence of mecA does not necessarily lead to oxacillin resistance and mecA gene-carrying isolates may have oxacillin MIC within the susceptible range (≥2 mg/L). During the last few years it has become apparent that oxacillin-susceptible (OS) mecA-positive S. aureus isolates (commonly called OS-MRSA) are rather commonly detected worldwide and may remain undiagnosed using phenotypic susceptibility testing methods. This review will summarize the current reports on OS-MRSA isolations and the underlying mechanisms regulating the expression of oxacillin resistance and also oxacillin susceptibility in mecA-positive S. aureus isolates. As MRSA commonly cause severe infections against which effective therapies are limited, understanding of these mechanisms could enable the identification of new targets for the treatment or reversion of the MRSA phenotype.