Practice testing of generic quality indicators for responsible antibiotic use in nine hospitals in the Dutch-Belgian border area.

BACKGROUND: Inpatient quality indicators (IQIs) were previously developed to assess responsible antibiotic use. AIM: Practice testing of these QIs in the hospital setting. METHOD: This study was performed within a Dutch-Belgian border network of hospitals implementing the Infection Risk Scan (IRIS) point prevalence survey (PPS) as part of the i-4-1-Health project. Twenty out of 51 DRIVE-AB IQIs, including 13 structure and seven process IQIs, were tested. Data on structure IQIs were obtained through a web-based questionnaire sent to the hospital medical microbiologists. PPS data from October to December 2018 were used to calculate performance scores for the process QIs. FINDINGS: Nine hospitals participated. Regarding structure IQIs: the lowest performance scores were observed for recommendations for microbiological investigations in the guidelines and the use of an approval system for restricted antibiotics. In addition, most hospitals reported that some antibiotics were out of stock due to shortages. Regarding process IQIs: 697 systemic antibiotic prescriptions were used to calculate performance scores. The lowest score was observed for documentation of an antibiotic plan in the medical file (58.8%). Performance scores for IQIs on guideline compliance varied between 74.1% and 82.3% for different aspects of the antibiotic regimen (duration, choice, route, timing). CONCLUSION: This multicentre practice testing of IQIs identified improvement targets for stewardship efforts for both structure and process aspects of antibiotic care (approval system for restricted antibiotics, documentation of antibiotic plan). These results can guide the design of future PPS studies and a more extensive evaluation of the clinimetric properties of the IQIs.

[The Infection RIsk Scan in clinical practice: improving infection prevention and antibiotic use through transparency]. / De Infectierisicoscan in de praktijk.

OBJECTIVE: The increase in Highly Resistant Micro-Organisms (HRMO) in hospitals and nursing homes requires an intensification of infection prevention measures. This paper describes a new, standardised approach to infection prevention and monitoring of antibiotic use. DESIGN: Cross-sectional, observational study. METHOD: The Infection RIsk Scan (IRIS) measures a number of objectifiable variables in the field of infection prevention, including the dissemination of HRMO, the use of antibiotics and indwelling medical devices, environmental contamination, hand hygiene and personal hygiene of healthcare workers, and various infection control preconditions. The scan converts the measurements into a risk profile and an improvement chart, a graphic presentation that is easy to understand for care professionals, managers and patients. Based on the results, targeted improvements can be made by a department or institution, and a quality cycle can be started in which the scans are repeated. RESULTS: The IRIS has been successfully applied in 5 hospital departments, a rehabilitation clinic and 19 nursing homes. In the hospital departments, 3 IRIS cycles resulted in a significant improvement in hand hygiene compliance (43% to 66%, p<0.001) and a significant reduction in environmental contamination. In one nursing home, the IRIS resulted in a previously undetected outbreak of HRMO being discovered. CONCLUSION: The IRIS method makes it possible to compare departments and institutions and can therefore provide an impetus for standardization of measurements of risks and results in the field of infection prevention, antibiotic use and resistance.

Next-generation sequencing for typing and detection of resistance genes: performance of a new commercial method during an outbreak of extended-spectrum-beta-lactamase-producing Escherichia coli.

Next-generation sequencing (NGS) has the potential to provide typing results and detect resistance genes in a single assay, thus guiding timely treatment decisions and allowing rapid tracking of transmission of resistant clones. We evaluated the performance of a new NGS assay (Hospital Acquired Infection BioDetection System; Pathogenica) during an outbreak of sequence type 131 (ST131) Escherichia coli infections in a nursing home in The Netherlands. The assay was performed on 56 extended-spectrum-beta-lactamase (ESBL) E. coli isolates collected during 2 prevalence surveys (March and May 2013). Typing results were compared to those of amplified fragment length polymorphism (AFLP), whereby we visually assessed the agreement of the BioDetection phylogenetic tree with clusters defined by AFLP. A microarray was considered the gold standard for detection of resistance genes. AFLP identified a large cluster of 31 indistinguishable isolates on adjacent departments, indicating clonal spread. The BioDetection phylogenetic tree showed that all isolates of this outbreak cluster were strongly related, while the further arrangement of the tree also largely agreed with other clusters defined by AFLP. The BioDetection assay detected ESBL genes in all but 1 isolate (sensitivity, 98%) but was unable to discriminate between ESBL and non-ESBL TEM and SHV beta-lactamases or to specify CTX-M genes by group. The performance of the hospital-acquired infection (HAI) BioDetection System for typing of E. coli isolates compared well with the results of AFLP. Its performance with larger collections from different locations, and for typing of other species, was not evaluated and needs further study.

Extended-spectrum ß-lactamase producing Klebsiella spp. in chicken meat and humans: a comparison of typing methods.

Recently, chicken meat was identified as a plausible source of extended-spectrum ß-lactamase (ESBL) -producing Escherichia coli in humans. We investigated the relatedness of ESBL-producing Klebsiella spp. in chicken meat and humans. Furthermore, we tested the performance of SpectraCell RA(®) (River Diagnostics), a new typing method based on Raman spectroscopy, in comparison with multilocus sequence typing (MLST) for Klebsiella pneumoniae. Twenty-seven phenotypically and genotypically confirmed ESBL-producing Klebsiella spp. isolates were typed with MLST and SpectraCell RA. The isolates derived from chicken meat, human rectal swabs and clinical blood cultures. In the 22 ESBL-producing K. pneumoniae isolates, CTX-M15 was the predominant genotype, found in five isolates of human origin and in one chicken meat isolate. With MLST, 16 different STs were found, including five new STs. Comparing the results of SpectraCell RA with MLST, we found a sensitivity of 70.0% and a specificity of 81.8% for the new SpectraCell RA typing method. Therefore, we conclude that SpectraCell RA is not a suitable typing method when evaluating relationships of ESBL-producing Klebsiella spp. at the population level. Although no clustering was found with isolates of chicken meat and human origin containing the same ESBL genes, MLST showed no clustering into distinctive clones of isolates from chicken meat and human origin. More studies are needed to elucidate the role of chicken meat in the rise of ESBL-producing Klebsiella spp. in humans.

Comparison of SpectraCell RA typing and multilocus sequence typing for extended-spectrum-ß-lactamase-producing Escherichia coli.

Multilocus sequence typing (MLST) is one of the most reliable methods for typing of Escherichia coli, including extended-spectrum-ß-lactamase-producing E. coli (ESBL-EC). We investigated the performance of a new typing method, SpectraCell RA (River Diagnostics, Madison, WI), in comparison on MLST on a well-defined collection of ESBL-EC isolates obtained from chicken meat and humans. Ninety-two ESBL-EC isolates obtained from meat and 59 ESBL-EC isolates obtained from human rectal swabs and clinical blood cultures were typed using MLST and SpectraCell RA. The sensitivity and specificity of SpectraCell RA were calculated, using MLST as a reference method. Subsequently, the results of SpectraCell RA were used to determine the relatedness of ESBL-EC isolates from chicken and humans. Using MLST as the gold standard, the performance of SpectraCell RA was evaluated for 3 different cutoff values: 0.99975, 0.99955, and 0.99935. Depending on the cutoff value, the sensitivity was mediocre to unacceptably low, with values of 9.4%, 43.9%, and 66.7%, respectively. When sensitivity increased, the specificity decreased rapidly, from 95.6% to 69.8% and 34.4%, respectively. Also, the number of clusters containing both human and meat samples varied from 0 (0.0%) to 14 (38.9%). Our study shows that SpectraCell RA is not a suitable typing method for ESBL-EC when evaluating relationships of ESBL-EC at the population level.

Evaluation of the DiversiLab typing method in a multicenter study assessing horizontal spread of highly resistant gram-negative rods.

The worldwide prevalence of highly resistant Gram-negative rods (HR-GNR) is increasing rapidly. Reliable typing methods are needed to detect and control outbreaks and to monitor the effectiveness of infection control programs in endemic situations. In this study, we investigated the performance of the DiversiLab typing method in comparison with the amplified fragment length polymorphism (AFLP) typing method. Six hundred fifty-three HR-GNR isolates, which were obtained during a 6-month prospective survey in 18 Dutch hospitals, were typed by AFLP and DiversiLab. Subsequently, the sensitivity and specificity of DiversiLab were calculated, using AFLP as the reference method. In addition, results were compared by means of epidemiological linkage, and Cohen's kappa for agreement was calculated. DiversiLab considered significantly more isolates (275) to belong to a cluster than AFLP (198) (P < 0.001). In direct comparison, the sensitivity was 83.8%, and the specificity was 78.6%. When epidemiological linkage was included in the analysis, DiversiLab considered eight isolates as secondary cases, which were considered unique in AFLP. Only two secondary cases, according to AFLP, were missed by DiversiLab. This results in a kappa for agreement of 0.985. In daily practice, a typing method has to be used in combination with epidemiological information. When this was done, DiversiLab was shown to be a reliable method for the typing of HR-GNR. This, in combination with the ease of use and the speed, makes DiversiLab an appropriate method for screening in routine clinical practice. When a cluster is suspected and the consequences of these findings are substantial, a confirmatory analysis should be performed.

Highly resistant gram-negative microorganisms: incidence density and occurrence of nosocomial transmission (TRIANGLe Study).

OBJECTIVES: The objectives of this study were to determine the incidence density and the occurrence of horizontal spread of highly resistant gram-negative rods (HR-GNRs) in Dutch hospitals. The factors that influence these outcome measures were also investigated. METHODS: All patients with HR-GNRs, as determined by sample testing, who were hospitalized in 1 of 18 hospitals during a 6-month period (April through October 2007) were included in this study. For all available isolates, the species was identified, susceptibility was determined (including the presence of extended-spectrum ß-lactamases [ESBLs]), and molecular typing was performed. On the basis of a combination of species identification, molecular typing, and epidemiological data, the occurrence of nosocomial transmission was determined. RESULTS: The mean incidence density of patients with HR-GNRs was 55 per 100,000 patient-days (cumulative incidence, 39 per 10,000 patients admitted). A facility being a university hospital was a statistically significant (P = .03) independent determinant of a higher incidence of patients with HR-GNRs. The majority of HR-GNR isolates were ESBL producers. The adjusted transmission index-the ratio between secondary and primary cases-in the participating hospitals ranged from 0.0 to 0.2. The overall adjusted transmission index of HR-GNRs was 0.07. No determinants for a higher transmission index were identified. DISCUSSION: The nosocomial transmission rate of HR-GNRs was relatively low in all hospitals where well-established transmission-based precautions were used. The incidence density of patients with HR-GNRs was higher in university hospitals, probably due to the patient population and the complexity of the care provided.

Laboratory detection of extended-spectrum-beta-lactamase-producing Enterobacteriaceae: evaluation of two screening agar plates and two confirmation techniques.

The worldwide prevalence of extended-spectrum-beta-lactamase-producing ESBL-producing Enterobacteriaceae (ESBL-E) is increasing, making the need for optimized detection techniques more urgent. In this study we investigated the performance of two ESBL-E screening and two ESBL-E confirmation techniques. In accordance with the Dutch national guidelines (www.wip.nl), a collection of 642 highly resistant Enterobacteriaceae strains, as identified by Vitek2, was used to test the performances of two screening techniques (EbSA ESBL agar plate and ChromID ESBL agar plate) and of two confirmation techniques (MIC-strip ESBL and Vitek2 ESBL test panel). The individual test results were compared by using Etest, followed by a combination disk test if Etest results were inconclusive. Among group 1 isolates (Escherichia coli, Klebsiella spp., Proteus spp., Salmonella spp., and Shigella spp.) 291 (57.6%) were ESBL-E, versus 65 (47.4%) in group 2 (Enterobacter spp., Citrobacter spp., Morganella morganii, Serratia spp., and Providencia spp.). The sensitivities of all four tests for group 1 were comparable (EbSA, 96.6%; ChromID, 97.3%; MIC-strip, 99.6%; and Vitek2, 95.1%). The specificities of the EbSA and ChromID were the same (93.9%). However, the confirmation techniques produced many inconclusive test results, which reduces the applicability in routine laboratories. Only the two screening agar plates were validated for ESBL testing of group 2 microorganisms. They showed comparable sensitivities; however, the EbSA screening agar plate had a significantly higher specificity (78.6% versus 44.3%). In conclusion the screening agar plates performed better than the two confirmation techniques. The EbSA agar plate had the best overall performance.

Appropriateness of antimicrobial therapy: a multicentre prevalence survey in the Netherlands, 2008-2009.

A survey was carried out to determine the prevalence and appropriateness of antimicrobial therapy (AMT) in the Netherlands and to identify determinants for inappropriate AMT. Prevalence surveys of patients hospitalised in the Netherlands were performed three times in 2008 and 2009. Patients' demographic, infection-related and AMT-related data were collected from hospital wards. A total of 19 hospitals participated, consisting of a mix of university, teaching and general hospitals, which were distributed evenly across the country. The appropriateness of AMT was assessed using a standardised algorithm based on local AMT prescription guidelines. A total of 7,853 patients were included, of which 2,327 (29.6%) patients were on AMT (range: 20.8­39.5%). In 372 patients (16% of patients on AMT), treatment was considered inappropriate. In 265 (11.4%) patients on AMT, appropriateness of treatment was not judged because of insufficient information. The percentage of patients without a judgment varied considerably between the participating hospitals (range: 1.3­36.2%). Appropriate AMT use was significantly associated with a patient being in an intensive care unit, having a central venous catheter and being given beta-lactamase-sensitive penicillins. The use of fluoroquinolones was significantly associated with more frequent inappropriate use. There was considerable and significant variation between the participating hospitals in the amount of antimicrobials prescribed and the appropriateness of their use. To improve the completeness and reliability of such surveys, there is a need for intensive training of observers and medical staff in recording information.

Correlation between antibiotic use and resistance in a hospital: temporary and ward-specific observations.

OBJECTIVES: The objectives of this study were to determine (1) the increase in antimicrobial resistance to frequently used antibiotics in the hospital setting over time and (2) the correlation between the amount of use of an antibiotic in a specific medical specialty and the observed resistance to that antibiotic in that specialty. METHOD: The total use of antibiotics and the use of ciprofloxacin (CIP), co-amoxicillin + clavulanic acid (AMCL) and first and second-generation cephalosporins (CEF), respectively, in individual medical specialties were measured between 2001 and 2006 by means of prevalence surveys (two per year). The antimicrobial susceptibility patterns among E. coli isolated from hospitalized patients between 2003 and 2006 were obtained from the Laboratory Information System. Trends over time and correlation between use and resistance were calculated. RESULTS: 6,639 patients were included in the prevalence surveys, of whom 3.0% (195) were treated with CIP, 9.7% (642) with AMCL, and 3.5% (232) with CEF. 4,790 E. coli isolates were obtained from hospitalized patients. Resistance to all antibiotics significantly increased over time, with the regression line showing that the strongest increase in resistance was for CIP (2.6% per year). There were large variations in antimicrobial use between various medical specialties. A significant correlation was found between the ward-specific prevalence of use and the percentage of resistance for CIP (R = 0.81, p < 0.001) and AMCL (R = 0.82, p = 0.003). CONCLUSION: At the level of individual medical specialties within one hospital, a higher prevalence of antimicrobial use among patients was associated with a significantly higher observed antimicrobial resistance. The use of CIP was associated with a stronger increase in resistance than the use of beta-lactams.

A standardized protocol for perioperative antibiotic prophylaxis is associated with improvement of timing and reduction of costs.

The objectives of this study were to implement a uniform guideline for perioperative antibiotic prophylaxis (PAP) and to measure the impact on timing and costs of PAP. The effects of implementation of the new guideline describing the application of PAP were measured by comparing the choice of agents and their timing in a random sample of procedures before and after implementation. Before the intervention, 153 procedures from different specialties were observed; eight different antibiotics in different dosages were used and in 20% of the procedures, PAP was given after the incision. Two months after the intervention, 147 procedures were observed; three different antibiotics were given and all were used in the correct dosage. There was a significant reduction of administration of PAP after the incision from 20 to 7% (P=0.002). Besides the quality improvements, the modified PAP protocol resulted in a net annual savings of at least 112,000 US dollars. This study shows that the implementation of a uniform, simple and clear protocol for PAP is associated with improved dosing and timing. The costs of PAP were also reduced.

The toxic effect of deltamethrin on linyphiid and erigonid spiders in connection with ambient temperature, humidity, and predation.

The first part of this study concerns the effect of temperature and air humidity on the toxicity of deltamethrin to the erigonid Oedothorax apicatus. The second part concerns the effect of deltamethrin on behavior of linyphiids and erigonids with respect to their ability to escape from predators and to select between unfavorable (dry) and favorable (moist) habitat conditions. The toxic effect of deltamethrin was highest at the combination of high temperature and low air humidity. It was concluded that the spider's sensitivity to drought is increased by this pyrethroid. Affected spiders, however, are less able to select moist habitat conditions than unaffected ones. Walking speed of spiders was decreased by exposure to deltamethrin and their predation by carabid beetles was increased. It was concluded that the effect observed under field conditions is the result of a combination of neurological, physiological, and behavioral disturbance.

[Selective disturbance in lexical knowledge in the elderly with or without dementia]. / Selectieve verstoring van lexicale kennis bij normale en demente ouderen.

In elderly with and without dementia a facilitating effect of word imagery on word association was found, as was in younger subjects with whom Dutch word association norms were assembled. Words with high imagery values evoke more common responses and less blanks than words with low imagery values. In the younger group also an interaction of imagery and age of acquisition was found, i.e. the effect of imagery on commonality in this group was only present in late acquired words. The absence of this interaction in both elderly with and without dementia indicates a disturbance of lexical knowledge dependent on the age of acquisition of words. Early acquired words have a strong sensorimotor basis, whereas words acquired later are predominantly based on verbal definition (conceptual versus propositional knowledge). Both subject groups have difficulties in retrieving words that specify a property relationship to a late acquired stimulus word, as in 'desert-sand', while words that specify an 'is a' relationship with the stimulus word, as in 'dagger-knife', are easily retrieved. The main difference between elderly with and without dementia was the large number of multiword responses in dementia, a result that indicates a loss of lexical strategies in word finding. Whether the incidentally reported increase in multiword responses in some normal elderly forecasts an approaching dementia needs further research.