The development and implementation of a guideline-based clinical decision support system to improve empirical antibiotic prescribing.

BACKGROUND: To describe and evaluate a clinical decision support system (CDSS) for empirical antibiotic therapy using a systematic framework. METHODS: A reporting framework for behavior change intervention implementation was used, which includes several domains: development, evaluation and implementation. Within the development domain a description is given of the engagement of stakeholders, a rationale for how the CDSS may influence antibiotic prescribing and a detailed outline of how the system was developed. Within the evaluation domain a technical validation is performed and the interaction between potential users and the CDSS is analyzed. Within the domain of implementation a description is given on how the CDSS was tested in the real world and the strategies that were used for implementation and adoption of the CDSS. RESULTS: Development: a CDSS was developed, with the involvement of stakeholders, to assist empirical antibiotic prescribing by physicians. EVALUATION: Technical problems were determined during the validation process and corrected in a new CDSS version. A usability study was performed to assess problems in the system-user interaction. IMPLEMENTATION: In 114 patients the antibiotic advice that was generated by the CDSS was followed. For 54 patients the recommendations were not adhered to. CONCLUSIONS: This study describes the development and validation of a CDSS for empirical antibiotic therapy and shows the usefulness of the systematic framework for reporting CDSS interventions. In addition it shows that CDSS recommendations are not always adhered to which is associated with incorrect use of the system.

A usability study to improve a clinical decision support system for the prescription of antibiotic drugs.

OBJECTIVE: A clinical decision support system (CDSS) for empirical antibiotic treatment has the potential to increase appropriate antibiotic use. Before using such a system on a broad scale, it needs to be tailored to the users preferred way of working. We have developed a CDSS for empirical antibiotic treatment in hospitalized adult patients. Here we determined in a usability study if the developed CDSS needed changes. METHODS: Four prespecified patient cases, based on real life clinical scenarios, were evaluated by 8 medical residents in the study. The "think-aloud" method was used, and sessions were recorded and analyzed afterwards. Usability was assessed by 3 evaluators using an augmented classification scheme, which combines the User Action Framework with severity rating of the usability problems and the assessment of the potential impact of these problems on the final task outcomes. RESULTS: In total 51 usability problems were identified, which could be grouped into 29 different categories. Most (n = 17/29) of the usability problems were cosmetic problems or minor problems. Eighteen (out of 29) of the usability categories could have an ordering error as a result. Classification of the problems showed that some of the problems would get a low priority based on their severity rating, but got a high priority for their impact on the task outcome. This effectively provided information to prioritize system redesign efforts. CONCLUSION: Usability studies improve lay-out and functionality of a CDSS for empirical antibiotic treatment, even after development by a multidisciplinary system.

Urinary tract infections in a university hospital: pathogens and antibiotic susceptibility.

BACKGROUND: A substantial group of patients visit the emergency department (ED) with complaints of urinary tract infections (UTI). Treatment advice is based on national and local public health surveillance data. It is unclear whether this advice is adequate for hospitals with selected patient populations, such as university hospitals. METHODS: We performed a retrospective study on patients visiting the ED of the Erasmus University Medical Center (Erasmus MC) in the Netherlands from January 1st, 2013 until December 31st, 2014 with a suspected complicated UTI (cUTI) and positive urinary cultures. Patient data, data concerning the ED visit and microbiological data were analysed. RESULTS: 439 patients visited the ED, of whom 429 had a cUTI. Our results were compared with NethMap data. Distribution of uropathogens was comparable with the overall distribution in the Netherlands. Antibiotic susceptibility was comparable for intravenous antibiotics, but was lower for oral antibiotics. Susceptibility for empiric antibiotic therapy (i.e., cefuroxime and gentamyicin) was 96.2%. Pathogens differed from the index culture in 56.2% 104/185) of the urinary cultures available from the previous year. Using logistic regression, we found that a shorter time between last admission to the initiated antibiotic regimen was associated with lower susceptibility of cultured uropathogens. CONCLUSION: The distribution and antibiotic susceptibility of uropathogens for intravenous antibiotics in a Dutch university hospital is comparable with overall distribution in the Netherlands. Empiric antibiotic therapy in our local guideline appears to be an adequate antibiotic regimen for cUTI and we therefore recommend treating patients accordingly. Extension of the chosen regimen based on earlier cultured pathogens is advised, and narrowing of the antibiotic regimen strongly discouraged.

A clinical decision support system algorithm for intravenous to oral antibiotic switch therapy: validity, clinical relevance and usefulness in a three-step evaluation study.

Objectives: To evaluate a clinical decision support system (CDSS) based on consensus-based intravenous to oral switch criteria, which identifies intravenous to oral switch candidates. Methods: A three-step evaluation study of a stand-alone CDSS with electronic health record interoperability was performed at the Erasmus University Medical Centre in the Netherlands. During the first step, we performed a technical validation. During the second step, we determined the sensitivity, specificity, negative predictive value and positive predictive value in a retrospective cohort of all hospitalized adult patients starting at least one therapeutic antibacterial drug between 1 and 16 May 2013. ICU, paediatric and psychiatric wards were excluded. During the last step the clinical relevance and usefulness was prospectively assessed by reports to infectious disease specialists. An alert was considered clinically relevant if antibiotics could be discontinued or switched to oral therapy at the time of the alert. Results: During the first step, one technical error was found. The second step yielded a positive predictive value of 76.6% and a negative predictive value of 99.1%. The third step showed that alerts were clinically relevant in 53.5% of patients. For 43.4% it had already been decided to discontinue or switch the intravenous antibiotics by the treating physician. In 10.1%, the alert resulted in advice to change antibiotic policy and was considered useful. Conclusions: This prospective cohort study shows that the alerts were clinically relevant in >50% (n = 449) and useful in 10% (n = 85). The CDSS needs to be evaluated in hospitals with varying activity of infectious disease consultancy services as this probably influences usefulness.

Development of operationalized intravenous to oral antibiotic switch criteria.

OBJECTIVES: Despite huge overlap in suggested criteria for a safe intravenous (iv)-to-oral antibiotic switch, there is considerable variation in their operationalization. The objective of this study was to develop a set of measurable conditions that should be met in adult hospitalized patients for a safe iv-to-oral switch. METHODS: A RAND-modified Delphi procedure was performed to develop a set of operationalized iv-to-oral switch criteria. Switch criteria and their accompanying suggested measurable conditions were extracted from the literature and appraised by a multidisciplinary expert panel during two questionnaire rounds with a face-to-face meeting between these two rounds. In a final step, the experts could approve the set of developed operationalized switch criteria. RESULTS: Seven switch criteria and 41 accompanying measurable conditions extracted from the literature were appraised. Sixteen measurable conditions that operationalize six switch criteria were selected: (i) stable systolic blood pressure; and the absence of (ii) fever, (iii) temperature <36°C, (iv) malabsorption syndrome, (v) short bowel syndrome, (vi) severe gastroparesis, (vii) ileus, (viii) continuous nasogastric suction, (ix) vomiting, (x) (severe) sepsis, (xi) fasciitis necroticans, (xii) CNS infection, (xiii) Staphylococcus aureus bacteraemia, and (xiv) endovascular infection. In addition, (xv) the patient should be cooperative and (xvi) adequate antimicrobial concentration should be achievable at the site of infection by oral administration. CONCLUSIONS: These operationalized criteria can be used in daily clinical practice. Future use of these criteria in audits and as rules in clinical decision support systems will facilitate the performance and evaluation of iv-oral switch programmes.

Point prevalence of appropriate antimicrobial therapy in a Dutch university hospital.

Antimicrobial stewardship teams have been shown to increase appropriate empirical antibiotic therapy and reduce medical errors and costs in targeted populations, but the effect in non-targeted populations is still unclear. The aim of this study was to determine the prevalence of inappropriate antibiotic use in a large university hospital and identify areas in which antimicrobial stewardship will be the most effective. In a point prevalence survey we assessed the appropriateness of antibiotic therapy using an electronic surveillance system in combination with a standardized method for duration of therapy, dosage, dosage interval, route of administration, and choice of antibiotic drug. Patients using at least one antibiotic drug were included. Among 996 patients admitted in the surveyed wards, 337 patients (33.8 %) used one or more antibiotic drugs. Two hundred and twenty-one patients (22.2 %) used antibiotic medication therapeutically, with a total of 307 antibiotic prescriptions. Antibiotic therapy was deemed inappropriate in 90 (29.3 %) of these prescribed antibiotics, with an unjustified prescription as the most common reason for an inappropriate prescription. Use of fluoroquinolones and amoxicillin/clavulanic acid and a presumed diagnosis of fever of unknown origin, urinary tract infection, and respiratory tract infection were associated with inappropriate antibiotic therapy. Our study provides insight into the (in)appropriateness of antibiotic prescriptions in a tertiary care center in the Netherlands and identifies areas for improvement. The use of an electronic surveillance system for this point prevalence study is easy and may serve as a baseline measurement for the future effect of antibiotic stewardship.

Good performance of the SpectraCellRA system for typing of methicillin-resistant Staphylococcus aureus isolates.

Typing of methicillin-resistant Staphylococcus aureus (MRSA) remains necessary in order to assess whether transmission of MRSA occurred and to what extent infection prevention measures need to be taken. Raman spectroscopy (SpectraCellRA [SCRA]; RiverD International, Rotterdam, The Netherlands) is a recently developed tool for bacterial typing. In this study, the performance (typeability, discriminatory power, reproducibility, workflow, and costs) of the SCRA system was evaluated for typing of MRSA strains isolated from patients and patients' household members who were infected with or colonized by MRSA. We analyzed a well-documented collection of 113 MRSA strains collected from 54 households. The epidemiological relationship between the MRSA strains within one household was used as the gold standard. Pulsed-field gel electrophoresis (PFGE) was used for discrepancy analysis. The results of SCRA analysis on the strain level corresponded with epidemiological data for 108 of 113 strains, a concordance of 95.6%. When analyzed at the household level, the results of SCRA were correct for 49 out of 54 households, a concordance of 90.7%. Concordance on the strain level with epidemiological data for PFGE was 93.6% (103/110 isolates typed). Concordance on the household level with epidemiological data for PFGE was 93.5% (49/53 households analyzed). With PFGE regarded as the reference standard, the conclusions reached with Raman spectroscopy were identical to those reached with PFGE in 100 of 105 cases (95.2%). The reproducibility of SCRA was found to be 100%. We conclude that the SpectraCellRA system is a fast, easy-to-use, and highly reproducible typing platform for outbreak analysis that can compete with the currently used typing techniques.

Immune evasion cluster-positive bacteriophages are highly prevalent among human Staphylococcus aureus strains, but they are not essential in the first stages of nasal colonization.

The Staphylococcus aureus immune evasion cluster (IEC), located on ß-haemolysin-converting bacteriophages (ßC-Φs), encodes the immune-modulating proteins chemotaxis inhibitory protein, staphylococcal complement inhibitor (SCIN), staphylococcal enterotoxin A and staphylokinase. Its precise role in S. aureus colonization is unclear. We studied the presence of the IEC-carrying bacteriophages in human and animal S. aureus isolates, using PCR for the gene encoding SCIN (scn). Human isolates were obtained by collecting serial nasal swabs from 21 persistent carriers. S. aureus strains from 19 (90%) persistent carriers contained an IEC that was present and indistinguishable in 95% of cases at all five sampling moments over a 3-month period. Of the 77 infectious animal strains included in the study, only 26 strains (34%) were IEC-positive. Integration of these IEC-positive strains into an amplified fragment length polymorphism genotype database showed that 24 of 53 (45%) strains were human-associated and only two of 24 (8%) were 'true' animal isolates (p < 0.001). The high prevalence and stability of IEC-carrying ßC-Φs in human strains suggested a role for these ßC-Φs in human nasal colonization. To test this hypothesis, 23 volunteers were colonized artificially with S. aureus strain NCTC 8325-4 with or without the IEC type B-carrying ßC-Φ13. Intranasal survival was monitored for 28 days after inoculation. The strain harbouring ßC-Φ13 was eliminated significantly faster (median 4 days; range 1-14 days) than the strain without ßC-Φ13 (median 14 days; range 2-28 days; p 0.011). In conclusion, although IEC-carrying ßC-Φs are highly prevalent among human colonizing S. aureus strains, they are not essential in the first stages of S. aureus nasal colonization.

High-throughput typing of Staphylococcus aureus by amplified fragment length polymorphism (AFLP) or multi-locus variable number of tandem repeat analysis (MLVA) reveals consistent strain relatedness.

This study investigates aspects of the general assumption that, in bacteria, genetic variation in functionally-constrained genomic regions accumulates at a lower rate than in regions of hypermutability such as DNA repeat loci. We compared whole genome polymorphism (using high-throughput amplified fragment length polymorphism [ht-AFLP]) as well as short sequence repeat length variation (using multi-locus variable number of tandem repeat analysis [MLVA]) for 994 Staphylococcus aureus strains isolated from both healthy carriers and invasive infections. MLVA and ht-AFLP minimum spanning trees (MSTs) were similar in their identification of totally different types of genetic variants. This suggests that, despite the enhanced inherent variability of repeats, clusters of strains remain traceable. Finally, no specific molecular marker of epidemicity or virulence was identified in this large strain collection by the MLVA approach. We demonstrate that there is a difference in the rates of cross-genome mutation versus regional repeat variability in the clonal bacterial pathogen S. aureus. Despite these dynamic differences, a conservation of type assignments as based upon these two inherently different typing techniques was observed.

Successful control of widespread methicillin-resistant Staphylococcus aureus colonization and infection in a large teaching hospital in the Netherlands.

OBJECTIVE: The low prevalence of infection and colonization with methicillin-resistant Staphylococcus aureus (MRSA) in The Netherlands is ascribed to a national "search-and-destroy" policy. We describe the measures that were implemented to control widespread MRSA colonization and infection in a Dutch hospital. DESIGN: Descriptive intervention study. SETTING: Teaching medical center with a capacity of 679 beds, including 16 intensive care beds. INTERVENTIONS: MRSA colonization and infection were identified using conventional culture with a selective broth. Isolates were typed using pulsed-field gel electrophoresis. Measures to control the epidemic included screening of contacts (patients and hospital staff), screening of patients at readmission or discharge, strict isolation of MRSA-positive patients, decolonization of colonized staff and patients, the development of an electronic signal identifying MRSA-positive patients, and the development of a culture information-system for hospital personnel. RESULTS: Awareness of uncontrolled dissemination of MRSA began in November 2001. Because the clone involved had a low minimum inhibitory concentration for oxacillin, at first it was not recognized as MRSA. In February 2002, when major screening efforts started, it appeared that MRSA had spread all over the hospital and that many staff members were colonized. By the end of December 2005, a total of 600 patients and 135 staff members were found to be newly colonized. The yearly incidence of cases of MRSA colonization and infection decreased from 351 in 2002 to 56 in 2005. Typing of the isolates showed that 3 MRSA clones were predominant. Outbreaks of colonization involving these clones did not occur after 2003. CONCLUSION: Our observations show that strict application of "search-and-destroy" measures can effectively control a huge epidemic of MRSA colonization and infection.

[Outbreak of methicillin-resistant Staphylococcus aureus (MRSA) in the Rijnmond region: the largest outbreak in the Netherlands]. / Uitbraak van meticillineresistente Staphylococcus aureus (MRSA) in de regio Rijnmond: grootste MRSA-epidemie in Nederland.

UNLABELLED: EPIDEMIC: The annual number of new MRSA isolates in the Netherlands tripled in 2002 compared with previous years. This increase was in part due to a MRSA outbreak in the Rijnmond region. The outbreak occurred in two merged hospitals and is the largest ever to occur in the Netherlands. From November 2001 till June 2003 MRSA was isolated from 381 patients and 113 hospital employees. The worst affected departments were Surgery and Internal Medicine. One MRSA strain (pulsed-field gel electroforesis (PFGE) type 16) remained initially unrecognised and was therefore able to spread unnoticed. Soon two additional epidemic MRSA strains (types 37 and 38) were discovered. DISCUSSION: Multiple factors played a role in the extent and duration of the outbreak. Because of the delayed detection and rapid spread of MRSA type 16, the outbreak grew too large once recognised to be resolved within the available infrastructure. Investments were needed at various fields, including the infection-control service and the microbiology laboratory. Employees had to be informed and motivated, and a separate MRSA ward and OPD were provided. New MRSA outbreaks occurred, despite extensive MRSA (contact) screening among patients and employees. The numbers of isolates began falling as from the beginning of 2003.

Prevention of infections in hyposplenic and asplenic patients: an update.

Patients with functional or anatomic asplenia are at a significantly increased risk of overwhelming infection, particularly involving the encapsulated bacteria Streptococcus pneumoniae and Haemophilus influenzae. The risk is highest in infants and young children, but adults also have an increased risk of infection. Preventive strategies are very important and fall into three major categories: immunoprophylaxis, antibiotic prophylaxis and education. Studies have shown that many asplenic patients are unaware of their increased risk for serious infection and the appropriate health precautions that should be undertaken. In this article we emphasise the need for preventive measures in hyposplenic and asplenic patients. We discuss the value of newly developed conjugate vaccines and the need for revaccination. Finally we draw up a recommendation for the preventive management in functional and anatomical asplenic patients.