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.

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 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.