Jan Kluytmans | University Medical Center Utrecht (original) (raw)

Papers by Jan Kluytmans

Journal of Antimicrobial Chemotherapy, Jan 10, 2016

The objectives of this study were to determine the prevalence of carriage of ESBL-producing Enter... more The objectives of this study were to determine the prevalence of carriage of ESBL-producing Enterobacteriaceae (ESBL-E) in a representative sample of the general adult Dutch community, to identify risk factors and to gain understanding of the epidemiology of these resistant strains. Methods: Adults enrolled in five general practices in Amsterdam were approached by postal mail and asked to fill in a questionnaire and to collect a faecal sample. Samples were analysed for the presence of ESBL-E. ESBL genes were characterized by PCR and sequencing. Strains were typed using MLST and amplified fragment length polymorphism (AFLP) and plasmids were identified by PCR-based replicon typing. Risk factors for carriage were investigated by multivariate analysis. Results: ESBL-E were found in 145/1695 (8.6%) samples; 91% were Escherichia coli. Most ESBL genes were of the CTX-M group (bla CTX-M-1 and bla CTX-M-15). MLST ST131 was predominant and mainly associated with CTX-M-15-producing E. coli. One isolate with reduced susceptibility to ertapenem produced OXA-48. In multivariate analyses, use of antimicrobial agents, use of antacids and travel to Africa, Asia and Northern America were associated with carriage of ESBL-E, in particular strains with bla CTX-M-14/15. Conclusions: This study showed a high prevalence of ESBL-E carriage in the general Dutch community. Also, outside hospitals, the use of antibiotics was a risk factor; interestingly, use of antacids increased the risk of carriage. A major risk factor in the general population was travel to countries outside Europe, in particular to Asia, Africa and Northern America.

Emerging Infectious Diseases, Mar 1, 2011

To estimate the proportion of methicillin-resistant Staphylococcus aureus (MRSA) isolates from hu... more To estimate the proportion of methicillin-resistant Staphylococcus aureus (MRSA) isolates from humans that were sequence type (ST) 398, we surveyed 24 laboratories in 17 countries in Europe in 2007. Livestock-associated MRSA ST398 accounted for only a small proportion of MRSA isolates from humans; most were from the Netherlands,

PLOS ONE, 2015

This prospective cohort study describes carriage of livestock-associated methicillin-resistant St... more This prospective cohort study describes carriage of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) in household members from 49 farrowing pig farms in the Netherlands (2010-2011). Of 171 household members, 4% were persistent MRSA nasal carriers, and the MRSA prevalence on any given sampling moment was 10% (range 7-11%). Working in the stables (of which 98% was MRSA-positive, prevalence ratio (PR) = 2.11 per 10 hours), working with sows (PR=1.97), and living with an MRSA-positive pig farmer (PR=4.63) were significant determinants for MRSA carriage. Significant protective factors were carriage of methicillin-susceptible Staphylococcus aureus (MSSA) (PR=0.50), and wearing a facemask when working in the stables (37% decreased prevalence). All MRSA strains during the study period were known livestock-associated types. The bacteriophage φ3 was not found in household members. Transmission from pigs and the environment appeared to be important determinants; human-to-human transmission could not sufficiently be differentiated. Wearing a facemask when working in the stables and carriage of MSSA are potential interventional targets.

Our purpose was to determine the dynamics of livestock-associated methicillin-resistant Staphyloc... more Our purpose was to determine the dynamics of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) carriage and its determinants in persons working at pig farms, in order to identify targets for interventions. This prospective cohort study surveyed 49 pig farms in the Netherlands on six sampling dates in 1 year (2010-11). Nasal and oropharyngeal swabs were collected, as well as environmental surface samples from stables and house. Of 110 pig farmers, 38% were persistent MRSA nasal carriers. The average cross-sectional MRSA prevalence was 63%. Methicillin-susceptible S. aureus (MSSA) nasal carriage was associated with fewer MRSA acquisitions (prevalence rate (PR) = 0.47, p 0.02). In multivariate analysis, an age of 40-49 years (PR = 2.13, p 0.01), a working week of ≥40 h (PR=1.89, p 0.01), giving birth assistance to sows (PR=2.26, p 0.03), removing manure of finisher pigs (PR=0.48, p 0.02), and wearing a facemask (PR = 0.13, p 0.02) were significantly related with persistent MRSA nasal carriage. A higher MRSA exposure in stables was associated with MRSA in pig farmers (p <0.0001). This study describes a very high prevalence of LA-MRSA carriage in pig farmers, reflecting extensive exposure during work. We identified the possible protective effects of MSSA carriage and of continuously wearing a facemask during work.

Epidemiology and Infection, Jan 6, 2016

There is limited knowledge about the effect of livestock-associated methicillin-resistant Staphyl... more There is limited knowledge about the effect of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) carriage on health-related quality of life (QoL). With this study, we explored whether LA-MRSA causes infections or affects health-related QoL in pig farmers. This prospective cohort study surveyed persons working on 49 farrowing pig farms in The Netherlands for 1 year (2010-2011). On six sampling moments, nasal swabs, environmental samples and questionnaires on activities and infections were collected. At the end of the study year, persons were asked about their QoL using the validated SF-36 and EQ-5D questionnaires. Of 120 persons, 44 (37%) were persistent MRSA carriers. MRSA carriage was not associated with infections, use of antimicrobials, healthcare contact and health-related QoL items in univariate or multivariate analysis, most likely due to the 'healthy worker effect'. Despite high carriage rates, the impact of LA-MRSA carriage in this population of relatively healthy pig farmers on health and health-related QoL appears limited; more research is needed for confirmation.

Clinical Infectious Diseases, Dec 14, 2012

Background. The worldwide prevalence of extended-spectrum β-lactamase (ESBL)-producing Enterobact... more Background. The worldwide prevalence of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae is increasing rapidly both in hospitals and in the community. A connection between ESBL-producing bacteria in food animals, retail meat, and humans has been suggested. We previously reported on the genetic composition of a collection of ESBL-producing Escherichia coli (ESBL-EC) from chicken meat and humans from a restricted geographic area. Now, we have extended the analysis with plasmid replicons, virulence factors, and highly discriminatory genomic profiling methods. Methods. One hundred forty-five ESBL-EC isolates from retail chicken meat, human rectal carriers, and blood cultures were analyzed using multilocus sequence typing, phylotyping, ESBL genes, plasmid replicons, virulence genes, amplified fragment length polymorphism (AFLP), and pulsed-field gel electrophoresis (PFGE). Results. Three source groups overlapped substantially when their genetic composition was compared. A combined analysis using all variables yielded the highest resolution (Wilks lambda [Λ]: 0.08). Still, a prediction model based on the combined data classified 40% of the human isolates as chicken meat isolates. AFLP and PFGE showed that the isolates from humans and chicken meat could not be segregated and identified 1 perfect match between humans and chicken meat. Conclusions. We found significant genetic similarities among ESBL-EC isolates from chicken meat and humans according to mobile resistance elements, virulence genes, and genomic backbone. Therefore, chicken meat is a likely contributor to the recent emergence of ESBL-EC in human infections in the study region. This raises serious food safety questions regarding the abundant presence of ESBL-EC in chicken meat.

PLOS ONE, Oct 1, 2018

The objective of this study is to determine the prevalence of rectal carriage of plasmid-and chro... more The objective of this study is to determine the prevalence of rectal carriage of plasmid-and chromosome-encoded AmpC β-lactamase-producing Escherichia coli and Klebsiella spp. in patients in a Dutch teaching hospital between 2013 and 2016.

PLOS ONE, Oct 18, 2012

Background: Recently, a clone of MRSA with clonal complex 398 (CC398) has emerged that is related... more Background: Recently, a clone of MRSA with clonal complex 398 (CC398) has emerged that is related to an extensive reservoir in animals, especially pigs and veal calves. It has been reported previously that methicillin-susceptible variants of CC398 circulate among humans at low frequency, and these have been isolated in a few cases of bloodstream infections (BSI). The purpose of this study was to determine the prevalence of S. aureus CC398 in blood cultures taken from patients in a geographic area with a high density of pigs. Methodology/Principal Findings: In total, 612 consecutive episodes of S. aureus BSI diagnosed before and during the emergence of CC398 were included. Three strains (2 MSSA and 1 MRSA) that were isolated from bacteremic patients between 2010-2011 were positive in a CC398 specific PCR. There was a marked increase in prevalence of S. aureus CC398 BSI isolated between 2010-2011 compared to the combined collections that were isolated between 1996-1998 and 2002-2005 (3/157, 1.9% vs. 0/455, 0.0%; p = 0.017). Conclusions/Significance: In conclusion, in an area with a relative high density of pigs, S. aureus CC398 was found as a cause of BSI in humans only recently. This indicates that S. aureus CC398 is able to cause invasive infections in humans and that the prevalence is rising. Careful monitoring of the evolution and epidemiology of S. aureus CC398 in animals and humans is therefore important.

Clinical Microbiology and Infection, Mar 1, 2014

Recently, chicken meat was identified as a plausible source of extended-spectrum b-lactamase (ESB... more Recently, chicken meat was identified as a plausible source of extended-spectrum b-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 â (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.

PLOS ONE, May 18, 2015

Infection Control and Hospital Epidemiology, Oct 1, 2009

Infection Control and Hospital Epidemiology, Apr 1, 2011

Clinical Microbiology and Infection, Jun 1, 2013

The aim of this study was to determine the rate of carriage of ESBL-producing Enterobacteriaceae ... more The aim of this study was to determine the rate of carriage of ESBL-producing Enterobacteriaceae (ESBL-E) in the community in the Netherlands and to gain understanding of the epidemiology of these resistant strains. Faecal samples from 720 consecutive patients presenting to their general practitioner, obtained in May 2010, and between December 2010 and January 2011, were analysed for presence of ESBL-E. Species identification and antibiotic susceptibility testing were performed according to the Dutch national guidelines. PCR, sequencing and microarray were used to characterize the genes encoding for ESBL. Strain typing was performed with amplified fragment length polymorphism (AFLP) and multilocus sequence typing (MLST). Seventy-three of 720 (10.1%) samples yielded ESBL-producing organisms, predominantly E. coli. No carbapenemases were detected. The most frequent ESBL was CTX-M-15 (34/73, 47%). Co-resistance to gentamicin, ciprofloxacin and cotrimoxazole was found in (9/73) 12% of the ESBL-E strains. AFLP did not show any clusters, and MLST revealed that CTX-M-15-producing E. coli belonged to various clonal complexes. Clonal complex ST10 was predominant. This study showed a high prevalence of ESBL-producing Enterobacteriaceae in Dutch primary care patients with presumed gastrointestinal discomfort. Hence, also in the Netherlands, a country with a low rate of consumption of antibiotics in humans, resistance due to the expansion of CTX-M ESBLs, in particular CTX-M-15, is emerging. The majority of ESBL-producing strains do not appear to be related to the international clonal complex ST131.

Antimicrobial Resistance and Infection Control, 2015

Background: In all European countries, hospital-acquired infections caused by Gram-negative multi... more Background: In all European countries, hospital-acquired infections caused by Gram-negative multidrug-resistant microorganisms (GN-MDRO) are a major health threat, as these pathogens cannot be adequately treated anymore, or the start of effective antibiotic treatment is delayed. The efforts to limit the selection and spread of GN-MDRO remains a problem in cross-border healthcare, as the national guidelines on hygiene standards applicable for patients colonized or infected with GN-MDRO in hospitals are not harmonized between European countries. Methods: In order to point out the similarities and differences in the national guidelines of Germany and The Netherlands regarding GN-MDRO, guidelines were compared and an expert workshop was organized by the INTERREG IVa project EurSafety Health-net. Results: Both guidelines divide the Gram-negative organisms into subgroups based on bacterial species and antibiotic susceptibility patterns in order to define multidrug-resistant variants of these bacteria. However, the Dutch guideline defines that GN-MDRO Enterobacteriaceae requires testing for certain mechanisms causing antibiotic resistance, whereas the German guideline makes use of a newly created classification scheme, based on phenotypic characterization. Besides diagnostic issues, the main difference between the Dutch and German guideline is the divergent evaluation of ESBL-producing Enterobacteriaceae. Special hygiene measures are required for all patients with ESBL-producing Enterobacteriaceae in The Netherlands, whereas the German guideline recommends special precautions only for those cases in which patients are colonized or infected with strains showing co-resistance to ciprofloxacin ("3MRGN"). Conclusions: The usage of consistent terminology and harmonized diagnostic procedures would improve the possibilities for infection prevention, treatment and patient safety. Prevention of severe non-treatable infections and outbreaks due to MDRO, caused by an increased population seeking medical treatment abroad together with an increased number of highly susceptible individuals demands gathering of regional data, and data comparable between the two sides of the Dutch-German border. The necessity to cooperate multidisciplinary and across borders is required to prevent a post-antibiotic erain which common infections and minor injuries may lead to death.

Nature Medicine, 2020

, a cluster of cases of pneumonia of unknown etiology were reported linked to a market in Wuhan, ... more , a cluster of cases of pneumonia of unknown etiology were reported linked to a market in Wuhan, China 1. The causative agent was identified as the species Severe acute respiratory syndrome-related coronavirus and was named SARS-CoV-2 (ref. 2). By 16 April the virus had spread to 185 different countries, infected over 2,000,000 people and resulted in over 130,000 deaths 3. In the Netherlands, the first case of SARS-CoV-2 was notified on 27 February. The outbreak started with several different introductory events from Italy, Austria, Germany and France followed by local amplification in, and later also outside, the south of the Netherlands. The combination of near to real-time whole-genome sequence analysis and epidemiology resulted in reliable assessments of the extent of SARS-CoV-2 transmission in the community, facilitating early decision-making to control local transmission of SARS-CoV-2 in the Netherlands. We demonstrate how these data were generated and analyzed, and how SARS-CoV-2 whole-genome sequencing, in combination with epidemiological data, was used to inform public health decision-making in the Netherlands. Whole-genome sequencing (WGS) is a powerful tool to understand the transmission dynamics of outbreaks and inform outbreak control decisions 4-7. Evidence of this was seen during the 2014-2016 West African Ebola outbreak when real-time WGS was used to help public health decision-making, a strategy dubbed 'precision public health pathogen genomics' 8,9. Immediate sharing and analysis of data during outbreaks is now recommended as an integral part of outbreak response 10-12. Feasibility of real-time WGS requires access to sequence platforms that provide reliable sequences, access to metadata for interpretation, and data analysis at high speed and low cost. Therefore, WGS for outbreak support is an active area of research. Nanopore sequencing has been employed in recent outbreaks of Usutu, Ebola, Zika and yellow fever virus owing to the ease of use and relatively low start-up cost 4-7. The robustness of this method has recently been validated using Usutu virus 13,14. In the Netherlands, the first COVID-19 case was confirmed on 27 February and WGS was performed in near to real-time using an amplicon-based sequencing approach. From 22 January, symptomatic travelers from countries where SARS-CoV-2 was known to circulate were routinely tested. The first case of SARS-CoV-2 infection in the Netherlands was identified on 27 February in a person with recent travel history to Italy and an additional case was identified one day later, also in a person with recent travel history to Italy. The genomes of these first two positive samples were generated and analyzed by 29 February. These two viruses clustered differently in the phylogenetic tree, confirming separate introductions (Fig. 1a). The advice to test hospitalized patients with serious respiratory infections was issued on 24 February and subsequent attempts to identify possible local transmission chains triggered testing for SARS-CoV-2 on a large scale in hospitals. By 9 March local clusters of epidemiologically related cases of SARS-CoV-2 started to appear in the province of Noord-Brabant. The increase in cases was caused by several co-circulating viruses, and is likely to have been triggered by multiple introductions of the virus following the spring holidays (from 13 to 23 February) with travel to ski resorts in Northern Italy (Fig. 1b). The first intervention was put in place on 9 and 10 March when the prime minister advised people to stop shaking hands and events attended by more than 1,000 visitors were banned in the province of Noord-Brabant. Subsequent analysis identified clusters with local amplification of viruses from patients without any travel history, also outside Noord-Brabant (Fig. 2). This information, combined with the increase in the total number of infections in the Netherlands, led to the decision to implement stricter measures for the whole country to prevent further spread of SARS-CoV-2 on 12 March. All events with more than 100 people attending were canceled, people were requested to work from home as much as possible and people with symptoms such as a fever or cough had to stay at home. On 15 March, this was followed by the closure of schools, catering industries and sport clubs. In the third phase, sequencing of new cases with emphasis on health-care workers (HCWs) and hospitalized cases was continued.

PLOS ONE, 2019

Take-down policy If you believe that this document breaches copyright please contact us providing... more Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

The Lancet Infectious Diseases, 2019

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 17, 2018

Direct health effects of antibiotic resistance are difficult to assess. We quantified the risk of... more Direct health effects of antibiotic resistance are difficult to assess. We quantified the risk of recurrent bacteremia associated with resistance. We extracted antimicrobial susceptibility testing data on blood isolates from the Dutch surveillance system for antimicrobial resistance between 2008 and 2017. First and first recurrent (4-30 days) bacteremia episodes were categorized as susceptible, single nonsusceptible, or co-nonsusceptible to third-generation cephalosporins without or with carbapenems (Enterobacteriaceae), ceftazidime without or with carbapenems (Pseudomonas species), aminopenicillins without or with vancomycin (Enterococcus species), or as methicillin-sensitive/-resistant S. aureus (MSSA/MRSA). We calculated risks of recurrent bacteremia after nonsusceptible vs susceptible first bacteremia, estimated the crude population attributable effect of resistance for the Netherlands, and calculated risks of nonsusceptible recurrent bacteremia after a susceptible first episode...

PLOS ONE, 2015

With the ultimate aim of containing the emergence of resistant bacteria, a Dutch policy was set i... more With the ultimate aim of containing the emergence of resistant bacteria, a Dutch policy was set in place in 2010 promoting a reduction of antimicrobial use (AMU) in food-producing animals. In this context, a study evaluated strategies to curb livestock-associated methicillin resistant Staphylococcus aureus (LA-MRSA). Fifty-one veal calf farms were assigned to one of 3 study arms: RAB farms reducing antimicrobials by protocol; RAB-CD farms reducing antimicrobials by protocol and applying a cleaning and disinfection program; and Control farms without interventions. MRSA carriage was tested in week 0 and week 12 of 2

PLOS ONE, 2015

Journal of Antimicrobial Chemotherapy, Jan 10, 2016

Emerging Infectious Diseases, Mar 1, 2011

PLOS ONE, 2015

Epidemiology and Infection, Jan 6, 2016

Clinical Infectious Diseases, Dec 14, 2012

PLOS ONE, Oct 1, 2018

PLOS ONE, Oct 18, 2012

Clinical Microbiology and Infection, Mar 1, 2014

PLOS ONE, May 18, 2015

Infection Control and Hospital Epidemiology, Oct 1, 2009

Infection Control and Hospital Epidemiology, Apr 1, 2011

Clinical Microbiology and Infection, Jun 1, 2013

Antimicrobial Resistance and Infection Control, 2015

Nature Medicine, 2020

PLOS ONE, 2019

The Lancet Infectious Diseases, 2019

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 17, 2018

PLOS ONE, 2015