Dutch outcome in implantable cardioverter-defibrillator therapy (DO-IT): registry design and baseline characteristics of a prospective observational cohort study to predict appropriate indication for implantable cardioverter-defibrillator.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are widely used for the prevention of sudden cardiac death. At present, both clinical benefit and cost-effectiveness of ICD therapy in primary prevention patients are topics of discussion, as only a minority of these patients will eventually receive appropriate ICD therapy. METHODS/DESIGN: The DO-IT Registry is a nationwide prospective cohort with a target enrolment of 1,500 primary prevention ICD patients with reduced left ventricular function in a setting of structural heart disease. The primary outcome measures are death and appropriate ICD therapy for ventricular tachyarrhythmias. Secondary outcome measures are inappropriate ICD therapy, death of any cause, hospitalisation for ICD related complications and for cardiovascular reasons. As of December 2016, data on demographic, clinical, and ICD characteristics of 1,468 patients have been collected. Follow-up will continue up to 24 months after inclusion of the last patient. During follow-up, clinical and ICD data are collected based on the normal follow-up of these patients, assuming ICD interrogations take place every six months and clinical follow-up is once a year. At baseline, the mean age was 66 (standard deviation [SD] 10) years and 27% were women. CONCLUSION: The DO-IT Registry represents a real-world nationwide cohort of patients receiving ICDs for primary prevention of sudden cardiac death with reduced left ventricular function in a setting of structural heart disease. The registry investigates the efficacy of the current practice and aims to develop prediction rules to identify subgroups who will not (sufficiently) benefit from ICD implantation and to provide results regarding costs and budget impact of targeted supply of primary preventions ICDs.

Newly identified risk factors for MRSA carriage in The Netherlands.

OBJECTIVES: To elucidate new risk factors for MRSA carriers without known risk factors (MRSA of unknown origin; MUO). These MUO carriers are neither pre-emptively screened nor isolated as normally dictated by the Dutch Search & Destroy policy, thus resulting in policy failure. METHODS: We performed a prospective case control study to determine risk factors for MUO acquisition/carriage (Dutch Trial Register: NTR2041). Cases were MUO carriers reported by participating medical microbiological laboratories to the RIVM from September 1st 2011 until September 1st 2013. Controls were randomly selected from the community during this period. RESULTS: Significant risk factors for MUO in logistic multivariate analysis were antibiotic use in the last twelve months, aOR 8.1 (5.6-11.7), screened as contact in a contact tracing but not detected as a MRSA carrier at that time, aOR 4.3 (2.1-8.8), having at least one foreign parent, aOR 2.4 (1.4-3.9) and receiving ambulatory care, aOR 2.3 (1.4-3.7). Our found risk factors explained 83% of the MUO carriage. CONCLUSIONS: Identifying new risk factors for MRSA carriers remains crucial for countries that apply a targeted screening approach as a Search and Destroy policy or as vertical infection prevention measure.

Antibiotic resistance in the southeastern Mediterranean - preliminary results from the ARMed project.

Sporadic reports from centres in the south and east of the Mediterranean have suggested that the prevalence of antibiotic resistance in this region appears to be considerable, yet pan-regional studies using comparable methodology have been lacking in the past. Susceptibility test results from invasive isolates of Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Enterococcus faecium and faecalis routinely recovered from clinical samples of blood and cerebrospinal fluid within participating laboratories situated in Algeria, Cyprus, Egypt, Jordan, Lebanon, Malta, Morocco, Tunisia and Turkey were collected as part of the ARMed project. Preliminary data from the first two years of the project showed the prevalence of penicillin non-susceptibility in S. pneumoniae to range from 0% (Malta) to 36% (Algeria) [median: 29%] whilst methicillin resistance in Staphylococcus aureus varied from 10% in Lebanon to 65% in Jordan [median: 43%]. Significant country specific resistance in E. coli was also seen, with 72% of isolates from Egyptian hospitals reported to be resistant to third generation cephalosporins and 40% non-susceptible to fluoroquinolones in Turkey. Vancomycin non-susceptibility was only reported in 0.9% of E. faecalis isolates from Turkey and in 3.8% of E. faecium isolates from Cyprus. The preliminary results from the ARMed project appear to support previous sporadic reports suggesting high antibiotic resistance in the Mediterranean region. They suggest that this is particularly the case in the eastern Mediterranean region where resistance in S. aureus and E. coli seems to be higher than that reported in the other countries of the Mediterranean.

Antibiotic resistance in the southeastern Mediterranean--preliminary results from the ARMed project.

Sporadic reports from centres in the south and east of the Mediterranean have suggested that the prevalence of antibiotic resistance in this region appears to be considerable, yet pan-regional studies using comparable methodology have been lacking in the past. Susceptibility test results from invasive isolates of Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Enterococcus faecium and faecalis routinely recovered from clinical samples of blood and cerebrospinal fluid within participating laboratories situated in Algeria, Cyprus, Egypt, Jordan, Lebanon, Malta, Morocco, Tunisia and Turkey were collected as part of the ARMed project. Preliminary data from the first two years of the project showed the prevalence of penicillin non-susceptibility in S. pneumoniae to range from 0% (Malta) to 36% (Algeria) [median: 29%] whilst methicillin resistance in Staphylococcus aureus varied from 10% in Lebanon to 65% in Jordan [median: 43%]. Significant country specific resistance in E. coli was also seen, with 72% of isolates from Egyptian hospitals reported to be resistant to third generation cephalosporins and 40% non-susceptible to fluoroquinolones in Turkey. Vancomycin non-susceptibility was only reported in 0.9% of E. faecalis isolates from Turkey and in 3.8% of E. faecium isolates from Cyprus. The preliminary results from the ARMed project appear to support previous sporadic reports suggesting high antibiotic resistance in the Mediterranean region. They suggest that this is particularly the case in the eastern Mediterranean region where resistance in S. aureus and E. coli seems to be higher than that reported in the other countries of the Mediterranean.

Effect of hospitalization on the antibiotic resistance of fecal Enterococcus faecalis of surgical patients over time.

The prevalence of antibiotic resistant Enterococcus faecalis was determined in fecal samples of 263 patients admitted to the surgical wards of three university-affiliated hospitals on admission, at discharge, and at 1 and 6 months after discharge. A slight increase in the prevalence of antibiotic resistance of E. faecalis was found at discharge for the antibiotics tested compared to those on admission, vancomycin excepted. At 6 months after discharge, the prevalence of resistance for amoxicillin (0%), ciprofloxacin (3%), erythromycin (47%), and oxytetracycline (60%) decreased to the level on admission (respectively 0%, 8%, 45%, and 64%). Gentamicin resistance was the same at discharge (10%) as 1 month later (12%), but decreased 6 months after discharge (8%) to the level on admission (7%). In conclusion, hospitalization resulted in the study population in a slight increase in the prevalence of resistant fecal E. faecalis isolates at discharge, which decreased again (slowly) to the level on admission 6 months after discharge. Thus, the influence of hospitalization on the prevalence of antibiotic resistance in the extramural situation disappears between 1 and 6 months after discharge in this population.

Antibiotic usage and resistance in different regions of the Dutch community.

Regional differences of antibiotic use and antibiotic resistance in the fecal indicator bacteria Escherichia coli and enterococci were determined in different cities in the south, west, and north of The Netherlands. In 1999, differences in antibiotic consumption were observed between the different regions: 11.19, 10.84, and 7.16 DDD (defined daily dosage) per 1,000 inhabitants per day, respectively. No significant regional differences were found in the prevalence of antibiotic resistance for both E. coli and enterococci. However, the differences in antibiotic consumption observed might lead to changes in antibiotic resistance in the near future. Surveillance of antibiotic use and antibiotic resistance is strongly recommended to control the development of antibiotic resistance because it provides epidemiological data to set up and control antibiotic guidelines.

Subcutaneous ventricular catheter reservoir and ventriculoperitoneal drain-related infections in preterm infants and young children.

OBJECTIVE: In the period January 1990 to September 1997, 70 patients, aged under 6 years were treated for hydrocephalus with a subcutaneous ventricular catheter reservoir and/or a ventriculoperitoneal drain at the University Hospital of Maastricht. METHODS: By means of a retrospective chart analysis, the number of shunt infections and related risk factors were analyzed. RESULTS: Twenty-one patients (30%) developed one or more infections, with an infection rate of 15.2% per surgical event. For an implanted reservoir or drain, the infection rates were 15.9 and 16.4%, respectively. The study group consisted of 39 (55.7%) preterm infants (< 37 weeks) and 31 (44.3%) full-term infants (> or = 37 weeks), with infection rates of 33.3 and 25.8%, respectively. At the first surgical intervention 28 patients (40%) had a postmenstrual age less than 37 weeks, with an infection rate of 46.4%. At the time of surgery, 69.7% of the patients were aged less than 6 months, with an infection rate of 19.6%. The most frequent causative microorganism of the shunt infections was Staphylococcus epidermidis (42.1%). CONCLUSIONS: Prematurity is an important risk factor for ventricular catheter reservoir and ventriculoperitoneal drain-related infections, especially for patients with a postmenstrual age of less than 37 weeks at their initial shunt placement and extreme low birth weight infants have a high risk for infection. In our opinion the use of adequate antibiotic prophylaxis and optimal infection control measures are necessary to keep the rate of infection as low as possible.

Clinical breakpoint changes and their impact on surveillance of antimicrobial resistance in Escherichia coli causing bacteraemia.

Dutch laboratories are currently changing their breakpoint criteria from mostly Clinical Laboratory and Standards Institute (CLSI) breakpoints to European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. To evaluate the impact of these changes, we studied antimicrobial resistance trends of Escherichia coli in blood specimens from January 2008 to January 2012 using CLSI and EUCAST breakpoints and compared them with the antimicrobial susceptibility test (AST) interpretations reported by Dutch laboratories participating in the Infectious Disease Surveillance Information System for Antibiotic Resistance (ISIS-AR). ISIS-AR collects AST interpretations, including underlying minimal inhibitory concentrations (MICs) of routinely cultured bacterial species on a monthly basis from Dutch laboratories. MICs of Etests or automated systems were reinterpreted according to the CLSI 2009 and EUCAST 2010 guidelines. Trends in non-susceptibility (i.e. intermediate resistant and resistant) over time were analysed by the Cochran-Armitage test for trend. The effects of the change from CLSI to EUCAST breakpoints on non-susceptibility were small. There were no differences in non-susceptibility to amoxicillin, amoxicillin/clavulanic acid, cefuroxim, gentamicin and co-trimoxazol and only small differences (1-1.5%) for ciprofloxacin between AST interpretations by CLSI or EUCAST. However, for ceftazidime, and cefotaxime/ceftriaxone the proportion of non-susceptibility was substantially higher when EUCAST breakpoints were used (2-3%). The effects on time trends of the change in guidelines were limited, with only substantial differences for the oxymino-cephalosporins. Our study shows that the implementation of EUCAST breakpoints has a limited effect on the proportion of non-susceptible isolates and time trends in E. coli for most, but not all, antimicrobial agents.

Emergence of MRSA of unknown origin in the Netherlands.

The Netherlands is known for its low methicillin-resistant Staphylococcus aureus (MRSA) prevalence. Yet MRSA with no link to established Dutch risk factors for acquisition, MRSA of unknown origin (MUO), has now emerged and hampers early detection and control by active screening upon hospital admittance. We assessed the magnitude of the problem and determined the differences between MUO and MRSA of known origin (MKO) for CC398 and non-CC398. National MRSA Surveillance data (2008-2009) were analysed for epidemiological determinants and genotypic characteristics (Panton-Valentine leukocidin, spa). A quarter (24%) of the 5545 MRSA isolates registered were MUO, i.e. not from defined risk groups. There are two genotypic MUO groups: CC398 MUO (352; 26%) and non-CC398 MUO (998; 74%). CC398 MUO needs further investigation because it could suggest spread, not by direct contact with livestock (pigs, veal calves), but through the community. Non-CC398 MUO is less likely to be from a nursing home than non-CC398 MKO (relative risk 0.55; 95% CI 0.42-0.72) and Panton-Valentine leukocidin positivity was more frequent in non-CC398 MUO than MKO (relative risk 1.19; 95% CI 1.11-1.29). Exact transmission routes and risk factors for non-CC398 as CC398 MUO remain undefined.

Dutch patients, retail chicken meat and poultry share the same ESBL genes, plasmids and strains.

Intestinal carriage of extended-spectrum beta-lactamase (ESBL) -producing bacteria in food-producing animals and contamination of retail meat may contribute to increased incidences of infections with ESBL-producing bacteria in humans. Therefore, distribution of ESBL genes, plasmids and strain genotypes in Escherichia coli obtained from poultry and retail chicken meat in the Netherlands was determined and defined as 'poultry-associated' (PA). Subsequently, the proportion of E. coli isolates with PA ESBL genes, plasmids and strains was quantified in a representative sample of clinical isolates. The E. coli were derived from 98 retail chicken meat samples, a prevalence survey among poultry, and 516 human clinical samples from 31 laboratories collected during a 3-month period in 2009. Isolates were analysed using an ESBL-specific microarray, sequencing of ESBL genes, PCR-based replicon typing of plasmids, plasmid multi-locus sequence typing (pMLST) and strain genotyping (MLST). Six ESBL genes were defined as PA (bla(CTX-M-1) , bla(CTX-M-2) , bla(SHV-2) , bla(SHV-12) , bla(TEM-20) , bla(TEM-52) ): 35% of the human isolates contained PA ESBL genes and 19% contained PA ESBL genes located on IncI1 plasmids that were genetically indistinguishable from those obtained from poultry (meat). Of these ESBL genes, 86% were bla(CTX-M-1) and bla(TEM-52) genes, which were also the predominant genes in poultry (78%) and retail chicken meat (75%). Of the retail meat samples, 94% contained ESBL-producing isolates of which 39% belonged to E. coli genotypes also present in human samples. These findings are suggestive for transmission of ESBL genes, plasmids and E. coli isolates from poultry to humans, most likely through the food chain.

Prevalence of penicillin and erythromycin resistance among invasive Streptococcus pneumoniae isolates reported by laboratories in the southern and eastern Mediterranean region.

Information about the epidemiology of resistance in Streptococcus pneumoniae within southern and eastern countries of the Mediterranean region is incomplete, as reports have been sporadic and difficult to compare. Over a 36-month period, from 2003 to 2005, the ARMed project collected 1298 susceptibility test results of invasive isolates of S. pneumoniae from blood and spinal fluid cultures routinely processed within 59 participating laboratories situated in Algeria, Cyprus, Egypt, Jordan, Lebanon, Malta, Morocco, Tunisia and Turkey. Overall, 26% (335) of isolates were reported as non-susceptible to penicillin, with the highest proportions being reported from Algeria (44%) and Lebanon (40%). During the same time period, the highest proportions of pneumococci that were not susceptible to erythromycin were reported from Malta (46%) and Tunisia (39%). Proportions of dual non-susceptibility in excess of 5% were found in laboratories in Algeria, Tunisia, Lebanon, Jordan and Turkey. ARMed data on the antimicrobial resistance epidemiology of S. pneumoniae in the southern and eastern Mediterranean region provided evidence of high rates of resistance, especially to penicillin. This evidence calls for a greater focus on the identification of relevant drivers of resistance and on the implemention of effective practices in order to address the problem of resistence.

Antimicrobial resistance in invasive strains of Escherichia coli from southern and eastern Mediterranean laboratories.

From January 2003 to December 2005, 5091 susceptibility test results from invasive isolates of Escherichia coli, collected from blood cultures and cerebrospinal fluid routinely processed within 58 participating laboratories, were investigated. These laboratories in turn serviced 64 hospitals in Algeria, Cyprus, Egypt, Jordan, Lebanon, Malta, Morocco, Tunisia and Turkey. The median proportion of resistance to third-generation cephalosporins for the duration of the project was 18.9% (interquartile range (IQR): 12.5-30.8%), and for fluoroquinolones 21.0% (IQR: 7.7-32.6%). A substantial proportion of strains reported by laboratories in countries east of the Mediterranean exhibited evidence of multiresistance, the highest proportion being from Egypt (31%). There is clearly a need for further investigation of potential causes of the significant resistance identified, as well as for strengthening of national and international surveillance initiatives within this region.;

Antibiotic use and the prevalence of antibiotic resistance in bacteria from healthy volunteers in the dutch community.

BACKGROUND: Although most antibiotics are consumed in the community (80%), the relation of antibiotic consumption and resistance in the community has not been thoroughly studied. MATERIALS AND METHODS: In the present study, antibiotic use was related to the prevalence of antibiotic resistance of Escherichia coli and enterococci isolated from healthy volunteers living in the southern part of the Netherlands in 1996 and 1999. RESULTS: No change in the total antibiotic use in the Dutch community was observed between 1996 and 1999 (3542 and 3598 defined daily doses [DDD] per 1000 inhabitants/year). However, the increased fluoroquinolone use (+ 18%) and the increased prevalence of ciprofloxacin resistance from 0 to 2% is a point of concern, especially since this was accompanied by a significant shift towards higher minimum inhibitory concentration (MIC) values (p < 0.05). A significant decrease in the prevalence of vancomycin-resistant enterococci (p < 0.05) was found in addition to a significant shift towards lower MIC valued for avoparcin, a glycopeptide previously used as growth promoter in animal husbandry (p < 0.05). This was very likely due to the banning of avoparcin for this purpose from April 1997 onwards. CONCLUSION: In order to maintain the low level of antibiotic use and resistance in The Netherlands, surveillance of antibiotic resistance in nonclinical isolates in relation to antibiotic use is very important.

Influence of population density on antibiotic resistance.

Antibiotic consumption and population density as a measure of crowding in the community were related to the prevalence of antibiotic resistance of three cities in three different countries: St Johns in Newfoundland (Canada), Athens in Greece and Groningen in The Netherlands. Antibiotic consumption was expressed in DDD (defined daily dose), as DID (DDD/1000 inhabitants/day) and as DSD (DDD/km(2)). The prevalence of antibiotic-resistant Escherichia coli and enterococci was determined in faecal samples of healthy volunteers. In both Newfoundland (28 DID) and Greece (29 DID) the overall consumption of antibiotics was more than three times higher compared with that of The Netherlands (9 DID). The lowest prevalence of resistant E. coli against the majority of antibiotics tested was found for the samples from Newfoundland and was significant (P < 0.05) for cefazolin, oxytetracycline and trimethoprim. A poor correlation between the number of DID and the prevalence of resistance was observed [the Pearson correlation coefficient (Pcc) ranged between -0.93 and 0.87]. However, when population density was taken into consideration and antibiotic consumption was expressed in DSD, a strong correlation was observed (and Pcc ranged between 0.86 and 1.00). This study suggests that population density is an important factor in the development of antibiotic resistance and warrants special attention as a factor in resistance epidemiology.

Hospitalization, a risk factor for antibiotic-resistant Escherichia coli in the community?

OBJECTIVE: The impact of hospitalization on the prevalence of resistant Escherichia coli in the intestinal flora of patients admitted to the surgical wards of three Dutch university-affiliated hospitals was analysed prospectively. METHODS: Faecal samples were obtained on admission to the hospital, at the time of discharge, and 1 and 6 months after discharge. All samples were examined for resistance to nine antibiotic agents. RESULTS: For the total patient population, no significant differences in the prevalence of resistance were observed at the different sampling intervals, except for a significant decrease in cefazolin resistance between the time of discharge and 6 months after discharge (10% to 3%, P < 0.05). This decrease was mainly observed in patients from the university hospital Maastricht (azM), in which a significant decrease from 17% to 6% was detected (P < 0.05). Moreover, despite dissimilarities in patient characteristics and the marked variations in antibiotic use, no significant differences in the prevalence of antibiotic resistance were observed between the three hospitals, except for the overall higher prevalence of cefazolin-resistant E. coli in azM patients (P < 0.05). CONCLUSION: In this study, hospitalization did not seem to have any substantial effect on the prevalence of antibiotic-resistant E. coli at the different time intervals. However, as our study population consisted of surgical patients with a relatively moderate antibiotic use, and the prevalence of antibiotic resistance was only analysed for faecal E. coli, further investigation should be encouraged, as the understanding of the interaction between different resistance reservoirs is important for directing future intervention studies.