Ed J Kuijper

Leiden University Medical Centre | LUMC · Department of Medical Microbiology

Clostridioides difficile PCR ribotype (RT) 002 is the second most prevalent RT in the Netherlands. In 2019, an increase in C. difficile infections (CDI) due to a clonal RT002 strains was reported in Ireland. In retrospect, a significant increase in the proportion of CDI due to RT002 was detected in the Netherlands between May 2017- May 2018 (11.9%...

Given the importance of gut microbial homeostasis in maintaining health, there has been considerable interest in developing innovative therapeutic strategies for restoring gut microbiota. One such approach, fecal microbiota transplantation (FMT), is the main “whole gut microbiome replacement” strategy and has been integrated into clinical practice...

Background Clostridioides difficile is a leading cause of infectious diarrhea in both humans and livestock. In particular, C. difficile strains belonging to sequence type (ST) 11 are common enteropathogens. The aim of this study was to determine the presence and genetic relatedness of C. difficile types in dairy cattle and calves. Method Dutch dai...

The diagnostic performance of a prospective, systematic screening strategy for COVID-19 associated pulmonary aspergillosis (CAPA) during the COVID-19 pandemic was investigated. Patients with COVID-19 admitted to the ICU were screened for CAPA twice weekly by collection of tracheal aspirate (TA) for Aspergillus culture and PCR. Subsequently, broncho...

Background Multidrug-resistant (MDR) bacteria are a growing global threat, especially in healthcare facilities. Faecal microbiota transplantation (FMT) is an effective prevention strategy for recurrences of Clostridioides difficile infections and can also be useful for other microbiota-related diseases. Methods We study the effect of FMT in patien...

Methicillin-resistant Staphylococcus aureus (MRSA) colonization increases the risk of infection. Response to decolonization treatment is highly variable and determinants for successful decolonization or failure of eradication treatment are largely unknown. Insight into genetic predictors of eradication failure is potentially useful in clinical prac...

Clostridioides difficile (C. difficile) is a major nosocomial pathogen but is also increasingly recognised as an important diarrhoeal pathogen in the community, not always associated with antibiotics. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for C. difficile (ESGCD) is a group of clinicians, scienti...

Diagnosis of Clostridioides difficile infection (CDI) can be challenging. First of all, there has been debate on which of the two reference assays, cell cytotoxicity neutralization assay (CCNA) or toxigenic culture (TC), should be considered the gold standard for CDI detection. Although the CCNA suffers most from suboptimal storage conditions and s...

Background The COVID-19 pandemic resulted in adaptation in infection control measures, increased patient transfer, high occupancy of intensive cares, downscaling of non-urgent medical procedures and decreased travelling. Aim To gain insight in the influence of these changes on antimicrobial resistance (AMR) prevalence in the Netherlands, a country...

Aim: The bacterial microbiota is well-recognized for its role in Clostridioides difficile colonization and infection, while fungi and yeasts remain understudied. The aim of this study was to analyze the predictive value of the mycobiota and its interactions with the bacterial microbiota in light of C. difficile colonization and infection. Methods:...

Background Infections with multidrug-resistant organisms (MDRO) are increasing at an alarming rate in hospitals worldwide. MDRO infections are often preceded by asymptomatic intestinal colonization and growth by the MDRO. Treatments such as non-absorbable antibiotics and fecal microbiota transplantation (FMT), which decrease the abundance of MDRO i...

Background Fecal microbiota transplantation (FMT) can effectively decolonize multidrug-resistant organisms but its efficacy is variable. We evaluated the impact of FMT treatment at eliminating carbapenemase-producing Enterobacterales (CPE) carriage compared to spontaneous decolonization and identified microbial signatures of successful decolonizati...

Here, we describe the epidemiology, diagnostics, and treatment of Clostridioides difficile infection (CDI) in the primary health care setting. CDI is traditionally considered as a healthcare associated infection. However, infections with onset in the community represent a large proportion of CDI. Traditional CDI risk factors apply to the population...

Introduction Experimental studies suggest a role of gut microbiota in the pathophysiology of Parkinson’s disease (PD) via the gut–brain axis. The gut microbiota can also influence the metabolism of levodopa, which is the mainstay of treatment of PD. Therefore, modifying the gut microbiota by faecal microbiota transplantation (FMT) could be a suppor...

Background: Although the Netherlands is a country with a low endemic level, methicillin-resistant Staphylococcus aureus (MRSA) poses a significant health care problem. Therefore, high coverage national MRSA surveillance has been in place since 1989. To monitor possible changes in the type-distribution and emergence of resistance and virulence, MRS...

Multidrug-resistant (MDR) bacteria are a growing global threat, especially in healthcare facilities. Faecal microbiota transplantation (FMT) is an effective prevention strategy for recurrences of _Clostridioides difficile _infections (rCDI) and can also be useful for other microbiota-related diseases. We study the effect of FMT in patients with rCD...

Objectives The bacterial microbiota is well-recognised for its role in Clostridioides difficile colonisation and infection, while fungi and yeasts remain understudied. The aim of this study was to analyse the mycobiota and its interactions with the bacterial microbiota in light of C. difficile colonisation and infection. Methods The mycobiota was...

Clostridioides difficile, the primary cause of nosocomial antibiotic-associated diarrhea, has a complex relationship with antibiotics. While the use of broad-spectrum antibiotics disrupts the gut microbiota and increases the risk of C. difficile infection (CDI), antibiotics are also the primary treatment for CDI. However, only a few antibiotics, in...

With the approval and development of narrow-spectrum antibiotics for the treatment of Clostridioides difficile infection (CDI), the primary endpoint for treatment success of CDI antibiotic treatment trials has shifted from treatment response at end of therapy to sustained response 30 days after completed therapy. The current definition of a success...

Objective: This study aimed to assess the value of C. difficile colonization (CDC) screening at hospital admission in an endemic setting. Methods: A multi-centre study was performed in 4 hospitals located across the Netherlands. Newly admitted patients were screened for CDC. The risk to develop C. difficile infection (CDI) during admission and o...

Short-chain fatty acids, including butyrate, have multiple metabolic benefits in individuals who are lean but not in individuals with metabolic syndrome, with the underlying mechanisms still being unclear. We aimed to investigate the role of gut microbiota in the induction of metabolic benefits of dietary butyrate. We performed antibiotic-induced m...

Since March 2022, there has been an emergence of multidrug-resistant organisms (MDRO) in the Netherlands in patients originating from Ukraine (58 patients, 75 isolates). For about half of these patients, recent hospitalisation in Ukraine was reported. Genomic surveillance revealed that the majority of the MDRO represent globally spread epidemic lin...

Background Clostridioides difficile infection (CDI) research is limited by a lack of standardized definitions for clinical response and disease outcomes, which impacts clinical drug development and results comparison between studies. We aimed to assess outcome definitions in CDI therapeutic trials to propose new versions that are clinically relevan...

In this retrospective observational study, we analysed a community outbreak of impetigo with meticillin-resistant Staphylococcus aureus (MRSA), with additional resistance to fusidic acid (first-line treatment). The outbreak occurred between June 2018 and January 2020 in the eastern part of the Netherlands with an epidemiological link to three cases...

Background Awareness and compliance to international guidelines for diagnosis and clinical management of Clostridioides difficile infection (CDI) are unknown. Aim To compare the awareness and compliance with the recommended strategies for diagnosis and clinical management of CDI across Europe in 2018-2019. Methods Hospital sites and their associa...

A subset of clinical isolates of Clostridioides difficile contains one or more plasmids and these plasmids can harbor virulence and antimicrobial resistance determinants. Despite their potential importance, C. difficile plasmids remain poorly characterized. Here, we provide the complete genome sequence of a human clinical isolate that carries three...

The plasmid pCD-METRO confers metronidazole resistance in Clostridioides difficile. We showed high sequence similarity among pCD-METRO plasmids from different isolates and identified pCD-METRO and associated metronidazole-resistant isolates in clinical and veterinary reservoirs in the Americas. We recommend using PCR or genomic assays to detect pCD...

Clostridioides difficile infection (CDI) is an important cause of diarrhea in hospitals worldwide. The incidence of CDI in Latin America has not yet been standardized. To fill this gap, the present study performed a daily active surveillance, for three months, between April to July of 2021, at a quaternary referral university hospital in Brazil. Th...

Background Data from the past decade indicates that Clostridioides difficile infection (CDI) is not only a nosocomial infection but is also increasingly recognized as a disease in the community. Objective We aimed to study community-onset (CO) CDI in the various age groups in south Serbia with its clinical characteristics, risk factors and microbi...

Background Clostridioides difficile is a Gram-positive anaerobic bacterium that can produce the toxins TcdA and/or TcdB and is considered an opportunistic pathogen. C. difficile is mainly transmitted as endospores, which germinate to produce the pathogenic vegetative cells under suitable conditions in the gut. To efficiently screen novel therapeuti...

Emergence of urine-associated Escherichia coli ST38 producing OXA-244 harbouring putative uropathogenicity factors in the Netherlands.

We show that MRSArg has been circulating in the Netherlands since at least 2008. Although MRSArg is distinct from MRSA, it has a comparable population structure and carries similar resistance and virulence genes. The Dutch national MRSA surveillance has been expanded to include other methicillin-resistant members of the S. aureus complex, such as S...

We report a patient case with pseudomembranous colitis associated with a mono-toxin producing Clostridioides difficile belonging to the very rarely diagnosed PCR ribotype (RT) 151. The infection was difficult to diagnose, since the isolate and the feces sample tested negative for toxin-encoding genes using a routine commercial test. This prompted u...

A subset of clinical isolates of Clostridioides difficile contains one or more plasmids and these plasmids can harbor virulence and antimicrobial resistance determinants. Despite their potential importance, C. difficile plasmids remain poorly characterized. Here, we describe a human clinical isolate that carries three plasmids from three different...

Infections with hypervirulent Klebsiella pneumoniae (hvKp) commonly presents with primary liver infection, bacteremia, and metastatic abscesses. Here, we present 2 cases of severe community-acquired pulmonary infections by hvKp in patients in the Netherlands without recent travel history. Both bacterial isolates are closely related to an archetype...

Fecal microbiota transplantation (FMT) has been reported to decrease the incidence of recurrent urinary tract infections (UTIs), presumably by restoring microbiome diversity and/or uropathogen competition. We report a 16-year-old female with recurrent UTIs caused by multidrug-resistant Klebsiella pneumoniae, for which frequent intravenous broad-spe...

Background During the COVID-19 pandemic, several factors, such as improved hand hygiene, social distancing, and restricted hospital referral, may have had an influence on the epidemiology of Clostridioides difficile infections (CDI). Methods The annual CDI incidence rate of nine hospitals participating in the Dutch sentinel CI surveillance with co...

Several experimental studies suggest a role of the gut microbiota in the pathophysiology of Parkinson’s disease (PD) via the gut-brain axis. In addition, the gut microbiota can influence the metabolism of levodopa, which is the mainstay of treatment of PD. Therefore, modifying the gut microbiota by fecal microbiota transplantation (FMT) could be a...

Background Colistin is a last-resort treatment option for infections with multidrug-resistant Gram-negative bacteria. However, colistin resistance is increasing. Methods A six-month prospective matched case-control study was performed in which 22 Dutch laboratories with 32 associated hospitals participated. Laboratories were invited to send a maxi...

Background The microbiota of the gut contributes to human mental health through the gut-brain axis. Treatment with fecal microbiota transplantation (FMT) offers the opportunity to explore the effects of modification of the microbiota on mental health in patients with a perturbed gut microbiota after multiple recurrent Clostridioides difficile infec...

Background The Netherlands is currently considered a low endemic country for carbapenem-resistant Enterobacterales (CRE) and carbapenemase-producing Enterobacterales (CPE), experiencing only sporadic hospital outbreaks. This study aims to describe susceptibility to carbapenems and the epidemiology of carbapenemase production in Enterobacterales in...

Manipulation of the gut microbiota via fecal microbiota transplantation (FMT) has shown clinical promise in diseases such as recurrent Clostridioides difficile infection (rCDI). However, the variable nature of this approach makes it challenging to describe the relationship between fecal strain colonization, corresponding microbiota changes, and cli...

Background Gut colonisation by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is a risk factor for developing overt infection. The gut microbiome can provide colonisation resistance against enteropathogens, but it remains unclear whether it confers resistance against ESBL-producing E coli. We aimed to identify a potential role of t...

Invasive fungal infections pose an important threat to public health and are an under-recognized component of antimicrobial resistance, an emerging crisis worldwide. Across a period of profound global environmental change and expanding at-risk populations, human-infecting pathogenic fungi are evolving resistance to all licensed systemic antifungal...

Background Faecal microbiota transplantation (FMT) is an efficacious treatment for patients with recurrent Clostridioides difficile infections (rCDI). Stool banks facilitate FMT by providing screened faecal suspensions from highly selected healthy donors. Due to the ongoing coronavirus disease 2019 (COVID-19) pandemic and the potential risk of SARS...

Objective: Description of the changing patterns of antibiotic resistance in Helicobacter pylori infection in the Netherlands. Design: Retrospective database study using the Dutch infectious disease surveillance information system-antibiotic resistance (ISIS-AR). Method: In the ISIS-AR database antibiotic resistance data are reported by 46 micr...

Intestinal helminths are highly prevalent in low-SES children and could contribute to poor health outcomes either directly or via alteration of the gut microbiome and gut barrier function. We analysed parasitic infections and gut microbiota composition in 325 children attending high- and low-SES schools in Makassar, Indonesia before and after alben...

Veterinary healthcare workers are in close contact with many different animals and might be at an increased risk of acquiring Clostridioides difficile. In this cross-sectional study, we assessed the prevalence and risk factors of C. difficile carriage in Dutch veterinary healthcare workers. Participants provided a faecal sample and filled out a que...

Clostridioides difficile is often resistant to the actions of antibiotics to treat other bacterial infections and the resulting C. difficile infection (CDI) is among the leading causes of nosocomial infectious diarrhea worldwide. The primary virulence mechanism contributing to CDI is the production of toxins. Treatment failures and recurrence of CD...

Purpose of review: Antimicrobial resistance is a rising threat to global health and is associated with increased mortality. Intestinal colonisation with multidrug-resistant organisms (MDRO) can precede invasive infection and facilitates spread within communities and hospitals. Novel decolonisation strategies, such as faecal microbiota transplantat...

Background Clostridioides difficile infection (CDI), its subsequent recurrences (rCDI), and severe CDI (sCDI) provide a significant burden for both patients and the healthcare system. Identifying patients diagnosed with initial CDI who are at increased risk of developing sCDI/rCDI could lead to more cost-effective therapeutic choices. Objectives I...

Clostridioides difficile is the most common cause of antibiotic-associated gastrointestinal infections. Capillary-electrophoresis (CE)-PCR ribotyping is currently the gold standard for C. difficile typing but lacks discriminatory power to study transmission and outbreaks in detail. New molecular methods have the capacity to differentiate better, bu...

Background Faecal microbiota transplantation (FMT) is an emerging treatment modality, but its current clinical use and organisation are unknown. We aimed to describe the clinical use, conduct, and potential for FMT in Europe. Methods We invited all hospital-based FMT centres within the European Council member states to answer a web-based questionn...

Background Clostridioides difficile infection (CDI), its subsequent recurrences (rCDI), and severe CDI (sCDI) provide a significant burden for both patients and the healthcare system. Treatment consists of oral antibiotics. Fidaxomicin, bezlotoxumab and fecal microbiota transplantion (FMT) reduce the number of recurrences compared to vancomycin, bu...

We describe four secondary fungal infections caused by Mucorales species in COVID-19 patients. Three COVID-19 associated mucormycosis (CAM) occurred in ICU, one outside ICU. All were men aged > 50 years, three died. Clinical presentations included pulmonary, rhino-orbital cerebral and disseminated infection. Infections occurred in patients with and...

Background and aims Patients suffering from multiple recurrent Clostridioides difficile infections (rCDI) have a disturbed gut microbiota, which can be restored by faecal microbiota transplantation (FMT). Despite extensive screening, healthy faeces donors may carry bacteria in their intestinal tract that could have long-term health effects, such as...

Background Gut colonization by antibiotic resistant E. coli strains, including extended-spectrum beta-lactamase (ESBL)-producing E. coli is a risk factor for developing overt infection. The gut microbiome can provide colonization resistance against enteropathogens, but it remains unclear whether it confers resistance against potentially pathogenic...

Abnormal vaginal discharge may be caused by bacterial vaginosis, vulvovaginal candidiasis, trichomoniasis and/or aerobic vaginitis. For the development of a diagnostic algorithm, tree-based classification analysis was performed on symptoms, signs and bedside test results of 56 patients, and laboratory tests (culture, Nugent score, qPCRs) were compa...

Background Until recently, metronidazole was the first-line treatment for Clostridioides difficile infection and it is still commonly used. Though resistance has been reported due to the plasmid pCD-METRO, this does not explain all cases. Objectives To identify factors that contribute to plasmid-independent metronidazole resistance of C. difficile...

Background Carbapenemases produced by Enterobacterales are often encoded by genes on transferable plasmids and represent a major healthcare problem, especially if the plasmids contain additional antibiotic resistance genes. As part of Dutch national surveillance, 50 medical microbiological laboratories submit their Enterobacterales isolates suspect...

Background Nursing home residents have increased rates of intestinal colonisation with multidrug-resistant organisms (MDROs). We assessed the colonisation and spread of MDROs among this population, determined clinical risk factors for MDRO colonisation and investigated the role of the gut microbiota in providing colonisation resistance against MDRO...

We aimed to describe the clinical presentation, treatment, outcome and report on factors associated with mortality over a 90-day period in Clostridioides difficile infection (CDI). Descriptive, univariate, and multivariate regression analyses were performed on data collected in a retrospective case-control study conducted in nine hospitals from sev...

Background: Fecal microbiota transplantation is an emerging therapeutic option, particularly for the treatment of recurrent Clostridioides difficile infection. Stool banks that organise recruitment and screening of feces donors are being embedded within the regulatory frameworks described in the European Union Tissue and Cells Directive and the te...

Bacterial vaginosis (BV) is perceived as a condition of disrupted vaginal microbiota, but remains of unknown aetiology. In this study, vaginal microbiota composition was determined in twenty-one women with BV, before and after treatment with metro-nidazole or clindamycin. Microbiota composition varied greatly between women and defining a (un)health...

Background A high prevalence of COVID‐19 associated pulmonary aspergillosis (CAPA) has been reported, though histopathological evidence is frequently lacking. To assess the clinical significance of Aspergillus species in respiratory samples of mechanically ventilated COVID‐19 patients, we implemented routine screening for Aspergillus in tracheal as...

Background Clostridioides difficile is the most common cause of nosocomial diarrhea. Ribotyping of cultured strains by a PCR-based test is used to study potential transmission between patients. We aimed to develop a rapid test that can be applied directly on fecal samples for simultaneous detection and ribotyping of C. difficile , as well as detect...