A pseudo-outbreak of MRSA due to laboratory contamination related to MRSA carriage of a laboratory staff member.

BACKGROUND: Methicillin resistant Staphylococcus aureus (MRSA) is a major burden for hospitals globally. However, in the Netherlands, the MRSA prevalence is relatively low due to the 'search and destroy' policy. Routine multiple-locus variable-number of tandem repeat analysis (MLVA) of MRSA isolates supports outbreak detection. However, whole genome multiple locus sequence typing (wgMLST) is superior to MLVA in identifying (pseudo-)outbreaks with MRSA. The present study describes a pseudo-outbreak of MRSA at the bacteriology laboratory of a large Dutch teaching hospital. METHODS: All staff members of the bacteriology laboratory of the Elisabeth-TweeSteden hospital were screened for MRSA carriage, after a laboratory contamination with MRSA was suspected. Clonal relatedness between the index isolate and the MRSA isolates from laboratory staff members and all previous MRSA isolates from the Elisabeth-TweeSteden hospital with the same MLVA-type as the index case was examined based on wgMLST using whole genome sequencing. RESULTS: One of the staff members was identified as the probable source of the laboratory contamination, because of carriage of a MRSA possessing the same MLVA-type as the index case. Eleven other isolates with the same molecular characteristics were found in the database, of which seven were retrospectively suspected of contamination. Clonal relatedness was found between ten isolates, including the isolate found in the staff member and the MRSA found in the index patient with a maximum of eleven alleles difference. All isolates were epidemiologically linked through the laboratory staff member, who had worked on all these cultures. CONCLUSIONS: The present study describes a MRSA pseudo-outbreak over a 2.5-year period due to laboratory contamination caused by a MRSA carrying laboratory staff member involving nine patients. In case of unexpected bacteriological findings, the possibility of a laboratory contamination should be considered.

The burden of bacteremic and non-bacteremic Gram-negative infections: A prospective multicenter cohort study in a low-resistance country.

Objectives There is a global increase in infections caused by Gram-negative bacteria. The majority of research is on bacteremic Gram-negative infections (GNI), leaving a knowledge gap on the burden of non-bacteremic GNI. Our aim is to describe characteristics and determine the burden of bacteremic and non-bacteremic GNI in hospitalized patients in the Netherlands. Methods We conducted a prospective cohort study of patients in eight hospitals with microbiologically confirmed GNI, between June 2013 and November 2015. In each hospital the first five adults meeting the eligibility criteria per week were enrolled. We estimated the national incidence and mortality of GNI by combining the cohort data with a national surveillance database for antimicrobial resistance. Results 1,954 patients with GNI were included of which 758 (39%) were bloodstream infections (BSI). 243 GNI (12%) involved multi-drug resistant pathogens. 30-day mortality rate was 11.1% (n = 217) Estimated national incidences of non-bacteremic GNI and bacteremic GNI in hospitalized adults were 74 (95% CI 58 - 89) and 86 (95% CI 72-100) per 100,000 person years, yielding estimated annual numbers of 30-day all-cause mortality deaths of 1,528 (95% CI 1,102-1,954) for bacteremic and 982 (95% CI 688 - 1,276) for non-bacteremic GNI. Conclusion GNI form a large mortality burden in a low-resistance country. A third of the associated mortality occurs after non-bacteremic GNI.

Development of a SARS-CoV-2 Total Antibody Assay and the Dynamics of Antibody Response over Time in Hospitalized and Nonhospitalized Patients with COVID-19.

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infections often cause only mild disease that may evoke relatively low Ab titers compared with patients admitted to hospitals. Generally, total Ab bridging assays combine good sensitivity with high specificity. Therefore, we developed sensitive total Ab bridging assays for detection of SARS-CoV-2 Abs to the receptor-binding domain (RBD) and nucleocapsid protein in addition to conventional isotype-specific assays. Ab kinetics was assessed in PCR-confirmed, hospitalized coronavirus disease 2019 (COVID-19) patients (n = 41) and three populations of patients with COVID-19 symptoms not requiring hospital admission: PCR-confirmed convalescent plasmapheresis donors (n = 182), PCR-confirmed hospital care workers (n = 47), and a group of longitudinally sampled symptomatic individuals highly suspect of COVID-19 (n = 14). In nonhospitalized patients, the Ab response to RBD is weaker but follows similar kinetics, as has been observed in hospitalized patients. Across populations, the RBD bridging assay identified most patients correctly as seropositive. In 11/14 of the COVID-19-suspect cases, seroconversion in the RBD bridging assay could be demonstrated before day 12; nucleocapsid protein Abs emerged less consistently. Furthermore, we demonstrated the feasibility of finger-prick sampling for Ab detection against SARS-CoV-2 using these assays. In conclusion, the developed bridging assays reliably detect SARS-CoV-2 Abs in hospitalized and nonhospitalized patients and are therefore well suited to conduct seroprevalence studies.

Attributable mortality of antibiotic resistance in gram-negative infections in the Netherlands: a parallel matched cohort study.

OBJECTIVES: Antibiotic resistance in Gram-negative bacteria has been associated with increased mortality. This was demonstrated mostly for third-generation cephalosporin-resistant (3GC-R) Enterobacterales bacteraemia in international studies. Yet, the burden of resistance specifically in the Netherlands and created by all types of Gram-negative infection has not been quantified. We therefore investigated the attributable mortality of antibiotic resistance in Gram-negative infections in the Netherlands. METHODS: In eight hospitals, a sample of Gram-negative infections was identified between 2013 and 2016, and separated into resistant and susceptible infection cohorts. Both cohorts were matched 1:1 to non-infected control patients on hospital, length of stay at infection onset, and age. In this parallel matched cohort set-up, 30-day mortality was compared between infected and non-infected patients. The impact of resistance was then assessed by dividing the two separate risk ratios (RRs) for mortality attributable to Gram-negative infection. RESULTS: We identified 1954 Gram-negative infections, of which 1190 (61%) involved Escherichia coli, 210 (11%) Pseudomonas aeruginosa, and 758 (39%) bacteraemia. Resistant Gram-negatives caused 243 infections (12%; 189 (78%) 3GC-R Enterobacterales, nine (4%) multidrug-resistant P. aeruginosa, no carbapenemase-producing Enterobacterales). Subsequently, we matched 1941 non-infected controls. After adjustment, point estimates for RRs comparing mortality between infections and controls were similarly higher than 1 in case of resistant infections and susceptible infections (1.42 (95% confidence interval 0.66-3.09) and 1.32 (1.06-1.65), respectively). By dividing these, the RR reflecting attributable mortality of resistance was calculated as 1.08 (0.48-2.41). CONCLUSIONS: In the Netherlands, antibiotic resistance did not increase 30-day mortality in Gram-negative infections.

[COVID-19: patient zero in the Netherlands]. / COVID-19: patiënt nul in Nederland.

BACKGROUND: Since December 2019, the world is captivated by SARS-CoV-2, a new coronavirus that shows a lot of similaritieswith previous coronaviruses such as SARS and MERS. Although it was initially seen mainly in China and the surrounding countries, now it also reached Europe, where a large region in northern Italy, in particular, encountered many infections. CASE DESCRIPTION: Here we describe the first Dutch patient with COVID-19, a 56-year-old man whose infection appeared to be related to a trip to Northern Italy one week before presentation. In the days that followed, the brother of the patient with whom he had traveled, his wife and daughter also tested positive. CONCLUSION: At the moment much is still unclear and it is particularly important to quickly identify patients with an increased risk of complications and to prevent unrestrained spread in the Netherlands.

COVID-19 in health-care workers in three hospitals in the south of the Netherlands: a cross-sectional study.

BACKGROUND: 10 days after the first reported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the Netherlands (on Feb 27, 2020), 55 (4%) of 1497 health-care workers in nine hospitals located in the south of the Netherlands had tested positive for SARS-CoV-2 RNA. We aimed to gain insight in possible sources of infection in health-care workers. METHODS: We did a cross-sectional study at three of the nine hospitals located in the south of the Netherlands. We screened health-care workers at the participating hospitals for SARS-CoV-2 infection, based on clinical symptoms (fever or mild respiratory symptoms) in the 10 days before screening. We obtained epidemiological data through structured interviews with health-care workers and combined this information with data from whole-genome sequencing of SARS-CoV-2 in clinical samples taken from health-care workers and patients. We did an in-depth analysis of sources and modes of transmission of SARS-CoV-2 in health-care workers and patients. FINDINGS: Between March 2 and March 12, 2020, 1796 (15%) of 12 022 health-care workers were screened, of whom 96 (5%) tested positive for SARS-CoV-2. We obtained complete and near-complete genome sequences from 50 health-care workers and ten patients. Most sequences were grouped in three clusters, with two clusters showing local circulation within the region. The noted patterns were consistent with multiple introductions into the hospitals through community-acquired infections and local amplification in the community. INTERPRETATION: Although direct transmission in the hospitals cannot be ruled out, our data do not support widespread nosocomial transmission as the source of infection in patients or health-care workers. FUNDING: EU Horizon 2020 (RECoVer, VEO, and the European Joint Programme One Health METASTAVA), and the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Prevalence and Clinical Presentation of Health Care Workers With Symptoms of Coronavirus Disease 2019 in 2 Dutch Hospitals During an Early Phase of the Pandemic.

Importance: On February 27, 2020, the first patient with coronavirus disease 2019 (COVID-19) was reported in the Netherlands. During the following weeks, at 2 Dutch teaching hospitals, 9 health care workers (HCWs) received a diagnosis of COVID-19, 8 of whom had no history of travel to China or northern Italy, raising the question of whether undetected community circulation was occurring. Objective: To determine the prevalence and clinical presentation of COVID-19 among HCWs with self-reported fever or respiratory symptoms. Design, Setting, and Participants: This cross-sectional study was performed in 2 teaching hospitals in the southern part of the Netherlands in March 2020, during the early phase of the COVID-19 pandemic. Health care workers employed in the participating hospitals who experienced fever or respiratory symptoms were asked to voluntarily participate in a screening for infection with the severe acute respiratory syndrome coronavirus 2. Data analysis was performed in March 2020. Main Outcomes and Measures: The prevalence of severe acute respiratory syndrome coronavirus 2 infection was determined by semiquantitative real-time reverse transcriptase-polymerase chain reaction on oropharyngeal samples. Structured interviews were conducted to document symptoms for all HCWs with confirmed COVID-19. Results: Of 9705 HCWs employed (1722 male [18%]), 1353 (14%) reported fever or respiratory symptoms and were tested. Of those, 86 HCWs (6%) were infected with severe acute respiratory syndrome coronavirus 2 (median age, 49 years [range, 22-66 years]; 15 [17%] male), representing 1% of all HCWs employed. Most HCWs experienced mild disease, and only 46 (53%) reported fever. Eighty HCWs (93%) met a case definition of fever and/or coughing and/or shortness of breath. Only 3 (3%) of the HCWs identified through the screening had a history of travel to China or northern Italy, and 3 (3%) reported having been exposed to an inpatient with a known diagnosis of COVID-19 before the onset of symptoms. Conclusions and Relevance: Within 2 weeks after the first Dutch case was detected, a substantial proportion of HCWs with self-reported fever or respiratory symptoms were infected with severe acute respiratory syndrome coronavirus 2, likely as a result of acquisition of the virus in the community during the early phase of local spread. The high prevalence of mild clinical presentations, frequently not including fever, suggests that the currently recommended case definition for suspected COVID-19 should be used less stringently.

Within-patient plasmid dynamics in Klebsiella pneumoniae during an outbreak of a carbapenemase-producing Klebsiella pneumoniae.

INTRODUCTION: Knowledge of within-patient dynamics of resistance plasmids during outbreaks is important for understanding the persistence and transmission of plasmid-mediated antimicrobial resistance. During an outbreak of a Klebsiella pneumoniae carbapenemase-producing (KPC) K. pneumoniae, the plasmid and chromosomal dynamics of K. pneumoniae within-patients were investigated. METHODS: During the outbreak, all K. pneumoniae isolates of colonized or infected patients were collected, regardless of their susceptibility pattern. A selection of isolates was short-read and long-read sequenced. A hybrid assembly of the short-and long-read sequence data was performed. Plasmid contigs were extracted from the hybrid assembly, annotated, and within patient plasmid comparisons were performed. RESULTS: Fifteen K. pneumoniae isolates of six patients were short-read whole-genome sequenced. Whole-genome multi-locus sequence typing revealed a maximum of 4 allele differences between the sequenced isolates. Within patients 1 and 2 the resistance gene- and plasmid replicon-content did differ between the isolates sequenced. Long-read sequencing and hybrid assembly of 4 isolates revealed loss of the entire KPC-gene containing plasmid in the isolates of patient 2 and a recombination event between the plasmids in the isolates of patient 1. This resulted in two different KPC-gene containing plasmids being simultaneously present during the outbreak. CONCLUSION: During a hospital outbreak of a KPC-producing K. pneumoniae isolate, plasmid loss of the KPC-gene carrying plasmid and plasmid recombination was detected within the isolates from two patients. When investigating outbreaks, one should be aware that plasmid transmission can occur and the possibility of within- and between-patient plasmid variation needs to be considered.

Contact precautions in single-bed or multiple-bed rooms for patients with extended-spectrum ß-lactamase-producing Enterobacteriaceae in Dutch hospitals: a cluster-randomised, crossover, non-inferiority study.

BACKGROUND: Use of single-bed rooms for control of extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae is under debate; the added value when applying contact precautions has not been shown. We aimed to assess whether an isolation strategy of contact precautions in a multiple-bed room was non-inferior to a strategy of contact precautions in a single-bed room for preventing transmission of ESBL-producing Enterobacteriaceae. METHODS: We did a cluster-randomised, crossover, non-inferiority study on medical and surgical wards of 16 Dutch hospitals. During two consecutive study periods, either contact precautions in a single-bed room or contact precautions in a multiple-bed room were applied as the preferred isolation strategy for patients with ESBL-producing Enterobacteriaceae cultured from a routine clinical sample (index patients). Eligible index patients were aged 18 years or older, had no strict indication for barrier precautions in a single-bed room, had a culture result reported within 7 days of culture and before discharge, and had no wardmate known to be colonised or infected with an ESBL-producing Enterobacteriaceae isolate of the same bacterial species with a similar antibiogram. Hospitals were randomly assigned in a 1:1 ratio by computer to one of two sequences of isolation strategies, stratified by university or non-university hospital. Allocation was masked for laboratory technicians who assessed the outcomes but not for patients, treating doctors, and infection-control practitioners enrolling index patients. The primary outcome was transmission of ESBL-producing Enterobacteriaceae to wardmates, which was defined as rectal carriage of an ESBL-producing Enterobacteriaceae isolate that was clonally related to the index patient's isolate in at least one wardmate. The primary analysis was done in the per-protocol population, which included patients who were adherent to the assigned room type. A 10% non-inferiority margin for the risk difference was used to assess non-inferiority. This study is registered with Nederlands Trialregister, NTR2799. FINDINGS: 16 hospitals were randomised, eight to each sequence of isolation strategies. All hospitals randomised to the sequence single-bed room then multiple-bed room and five of eight hospitals randomised to the sequence multiple-bed room then single-bed room completed both study periods and were analysed. From April 24, 2011, to Feb 27, 2014, 1652 index patients and 12 875 wardmates were assessed for eligibility. Of those, 693 index patients and 9527 wardmates were enrolled and 463 index patients and 7093 wardmates were included in the per-protocol population. Transmission of ESBL-producing Enterobacteriaceae to at least one wardmate was identified for 11 (4%) of 275 index patients during the single-bed room strategy period and for 14 (7%) of 188 index patients during the multiple-bed room strategy period (crude risk difference 3·4%, 90% CI -0·3 to 7·1). INTERPRETATION: For patients with ESBL-producing Enterobacteriaceae cultured from a routine clinical sample, an isolation strategy of contact precautions in a multiple-bed room was non-inferior to a strategy of contact precautions in a single-bed room for preventing transmission of ESBL-producing Enterobacteriaceae. Non-inferiority of the multiple-bed room strategy might change the current single-bed room preference for isolation of patients with ESBL-producing Enterobacteriaceae and, thus, broaden infection-control options for ESBL-producing Enterobacteriaceae in daily clinical practice. FUNDING: Netherlands Organisation for Health Research and Development.

[Meningitis after a mouse bite]. / Meningitis na muizenbeet.

BACKGROUND: Infection with the lymphocytic choriomeningitis virus is a human zoonosis caused by a rodent-borne arenavirus and is often seen in autumn and winter when mice retreat into houses. Infection in humans is acquired after inhalation of aerosols or direct contact with excreta of an infected rodent. CASE DESCRIPTION: A 37-year-old woman was referred to St. Elisabeth hospital in Tilburg, Netherlands, complaining of severe progressive headache, nausea and vomiting. Three weeks before presentation a mouse had bitten her finger. On neurological examination there were no abnormalities. Cerebrospinal fluid investigations indicated viral meningitis. Immunofluorescence serological testing confirmed the diagnosis of lymphocytic choriomeningitis. CONCLUSION: Infection by lymphocytic choriomeningitis virus after contact with rodents can cause viral meningitis. The acquired form of the disease is known to be self-limiting in immunocompetent patients.

Report of two in situ reconstructions with a saphenous spiral vein graft of Coxiella burnetii-infected aneurysms of the abdominal aorta.

Coxiella burnetii is a rare cause of vascular infections. Yet, Q fever is endemic in the southern part of The Netherlands. This report describes two patients--from the southern part of The Netherlands--with infected aneurysms of the abdominal aorta caused by Coxiella burnetii. Both patients underwent surgical debridement, in situ reconstruction with a great saphenous vein spiral graft, and a transmesenteric omentumplasty. One patient fully recovered, while the other died due to ischemic complications. A multidisciplinary work-up approach to treat infected abdominal aneurysms is proposed, including adequate surgical treatment and long-term antibiotic administration.

Viral and bacterial aetiology of community-acquired pneumonia in adults.

BACKGROUND: Modern molecular techniques reveal new information on the role of respiratory viruses in community-acquired pneumonia. In this study, we tried to determine the prevalence of respiratory viruses and bacteria in patients with community-acquired pneumonia who were admitted to the hospital. METHODS: Between April 2008 and April 2009, 408 adult patients (aged between 20 and 94 years) with community-acquired pneumonia were tested for the presence of respiratory pathogens using bacterial cultures, real-time PCR for viruses and bacteria, urinary antigen testing for Legionella and Pneumococci and serology for the presence of viral and bacterial pathogens. RESULTS: Pathogens were identified in 263 (64·5%) of the 408 patients. The most common single organisms in these 263 patients were Streptococcus pneumoniae (22·8%), Coxiella burnetii (6·8%) and influenza A virus (3·8%). Of the 263 patients detected with pathogens, 117 (44·5%) patients were positive for one or more viral pathogens. Of these 117 patients, 52 (44·4%) had no bacterial pathogen. Multiple virus infections (≥2) were found in 16 patients. CONCLUSION: In conclusion, respiratory viruses are frequently found in patients with CAP and may therefore play an important role in the aetiology of this disease.

Preventing Staphylococcus aureus bacteremia and sepsis in patients with Staphylococcus aureus colonization of intravascular catheters: a retrospective multicenter study and meta-analysis.

Two previous studies in tertiary care hospitals identified Staphylococcus aureus colonization of intravascular (IV) catheters as a strong predictor of subsequent S. aureus bacteremia (SAB), even in the absence of clinical signs of systemic infection. Bacteremia was effectively prevented by timely antibiotic therapy. We conducted this study to corroborate the validity of these findings in non-university hospitals.Using the laboratory information management systems of the clinical microbiology departments in 6 Dutch hospitals, we identified patients who had IV catheters from which S. aureus was cultured between January 1, 2003, and December 31, 2008. Patients with demonstrated SAB between 7 days before catheter removal and 24 hours after catheter removal were excluded. We extracted clinical and demographic patient data from the patients' medical records. The primary risk factor was initiation of anti-staphylococcal antibiotic therapy within 24 hours, and the primary endpoint was SAB >24 hours after IV catheter removal. Subsequently, we performed a systematic review and meta-analysis of all observational studies evaluating the effect of antibiotic therapy for S. aureus IV catheter tip colonization.In the current study, 18 of the 192 included patients developed subsequent SAB, which was associated with not receiving antibiotic therapy within 24 hours (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.1-15.6) and with documented exit-site infection (OR, 3.3; 95% CI, 1.2-9.3). When we combined these results with results of a previous study in a university hospital, a third risk factor was also associated with subsequent SAB, namely corticosteroid therapy (OR, 2.9; 95% CI, 1.3-6.3). We identified 3 other studies, in addition to the present study, in a systematic review. In the meta-analysis of these studies, antibiotic therapy yielded an absolute risk reduction of 13.6% for subsequent SAB. The number needed to treat to prevent 1 episode of SAB was 7.4.We conclude that early initiation of antibiotic therapy for IV catheters colonized with S. aureus prevents subsequent SAB.

Outbreak of infection with a multiresistant Klebsiella pneumoniae strain associated with contaminated roll boards in operating rooms.

An outbreak with a multiresistant Klebsiella pneumoniae (MRKP) strain among seven patients admitted to the adult intensive care unit (ICU) of a regional teaching hospital in The Netherlands was investigated. Epidemiologic investigations revealed a short delay between an operation and the acquisition of the MRKP strain. A case-control study comprising 7 cases and 14 controls was conducted to identify the risk factors associated with the acquisition of the MRKP strain. An operation at each of two operation rooms was strongly associated with the acquisition of the MRKP strain: odds ratio of 36 (95% confidence interval, 2.7 to 481.2; P=0.003, Fisher exact two-tailed test). Cultures of environmental specimens of the operation rooms revealed contamination of the roll boards used to transport patients from the bed to the operation table with the MRKP strains. Molecular genotyping of the isolates revealed clonal similarity between the isolates of the seven cases, isolates from environmental specimen cultures, and in addition, an MRKP isolate from a re-patriated ICU patient from earlier that year. The outbreak ended after cleaning and replacement of the roll boards in the operation rooms and implementation of additional barrier precautions for colonized or infected patients. It was concluded that two operation rooms played a significant role in the transmission of an MRKP strain between ICU patients during the presented outbreak.