Seroprevalence of SARS-CoV-2 antibodies among healthcare workers in Dutch hospitals after the 2020 first wave: a multicentre cross-sectional study with prospective follow-up.

BACKGROUND: We aimed to estimate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence and describe its determinants and associated symptoms among unvaccinated healthcare workers (HCWs) after the first wave of the pandemic. METHODS: HCWs from 13 Dutch hospitals were screened for antibodies against the spike protein of SARS-CoV-2 in June-July 2020 and after three months. Participants completed a retrospective questionnaire on determinants for occupational and community exposure to SARS-CoV-2 and symptoms suggestive of COVID-19 experienced since January 2020. The seroprevalence was calculated per baseline characteristic and symptom at baseline and after follow-up. Adjusted odds ratios (aOR) for seropositivity were determined using logistic regression. RESULTS: Among 2328 HCWs, 323 (13.9%) were seropositive at enrolment, 49 of whom (15%) reported no previous symptoms suggestive of COVID-19. During follow-up, only 1% of the tested participants seroconverted. Seroprevalence was higher in younger HCWs compared to the mid-age category (aOR 1.53, 95% CI 1.07-2.18). Nurses (aOR 2.21, 95% CI 1.34-3.64) and administrative staff (aOR 1.87, 95% CI 1.02-3.43) had a higher seroprevalence than physicians. The highest seroprevalence was observed in HCWs in the emergency department (ED) (aOR 1.79, 95% CI 1.10-2.91), the lowest in HCWs in the intensive, high, or medium care units (aOR 0.47, 95% CI 0.31-0.71). Chronic respiratory disease, smoking, and having a dog were independently associated with a lower seroprevalence, while HCWs with diabetes mellitus had a higher seroprevalence. In a multivariable model containing all self-reported symptoms since January 2020, altered smell and taste, fever, general malaise/fatigue, and muscle aches were positively associated with developing antibodies, while sore throat and chills were negatively associated. CONCLUSIONS: The SARS-CoV-2 seroprevalence in unvaccinated HCWs of 13 Dutch hospitals was 14% in June-July 2020 and remained stable after three months. A higher seroprevalence was observed in the ED and among nurses, administrative and young staff, and those with diabetes mellitus, while a lower seroprevalence was found in HCWs in intensive, high, or medium care, and those with self-reported lung disease, smokers, and dog owners. A history of altered smell or taste, fever, muscle aches and fatigue were independently associated with the presence of SARS-CoV-2 antibodies in unvaccinated HCWs.

A comparison of five Illumina, Ion Torrent, and nanopore sequencing technology-based approaches for whole genome sequencing of SARS-CoV-2.

Rapid identification of the rise and spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern remains critical for monitoring of the efficacy of diagnostics, therapeutics, vaccines, and control strategies. A wide range of SARS-CoV-2 next-generation sequencing (NGS) methods have been developed over the last years, but cross-sequence technology benchmarking studies have been scarce. In the current study, 26 clinical samples were sequenced using five protocols: AmpliSeq SARS-CoV-2 (Illumina), EasySeq RC-PCR SARS-CoV-2 (Illumina/NimaGen), Ion AmpliSeq SARS-CoV-2 (Thermo Fisher), custom primer sets (Oxford Nanopore Technologies (ONT)), and capture probe-based viral metagenomics (Roche/Illumina). Studied parameters included genome coverage, depth of coverage, amplicon distribution, and variant calling. The median SARS-CoV-2 genome coverage of samples with cycle threshold (Ct) values of 30 and lower ranged from 81.6 to 99.8% for, respectively, the ONT protocol and Illumina AmpliSeq protocol. Correlation of coverage with PCR Ct values varied per protocol. Amplicon distribution signatures differed across the methods, with peak differences of up to 4 log10 at disbalanced positions in samples with high viral loads (Ct values ≤ 23). Phylogenetic analyses of consensus sequences showed clustering independent of the workflow used. The proportion of SARS-CoV-2 reads in relation to background sequences, as a (cost-)efficiency metric, was the highest for the EasySeq protocol. The hands-on time was the lowest when using EasySeq and ONT protocols, with the latter additionally having the shortest sequence runtime. In conclusion, the studied protocols differed on a variety of the studied metrics. This study provides data that assist laboratories when selecting protocols for their specific setting.

Effectiveness of Different Antimicrobial Strategies for Staphylococcal Prosthetic Joint Infection: Results From a Large Prospective Registry-Based Cohort Study.

Background: Treatment of staphylococcal prosthetic joint infection (PJI) usually consists of surgical debridement and prolonged rifampicin combination therapy. Tailored antimicrobial treatment alternatives are needed due to frequent side effects and drug-drug interactions with rifampicin combination therapy. We aimed to assess the effectiveness of several alternative antibiotic strategies in patients with staphylococcal PJI. Methods: In this prospective, multicenter registry-based study, all consecutive patients with a staphylococcal PJI, treated with debridement, antibiotics and implant retention (DAIR) or 1-stage revision surgery between January 1, 2015 and November 3, 2020, were included. Patients were treated with a long-term rifampicin combination strategy (in 2 centers) or a short-term rifampicin combination strategy (in 3 centers). Antimicrobial treatment strategies in these centers were defined before the start of the registry. Patients were stratified in different groups, depending on the used antimicrobial strategy. Cox proportional hazards models were used to compare outcome between the groups. Results: Two hundred patients were included and stratified in 1 long-term rifampicin group (traditional rifampicin combination therapy) or 1 of 3 short-term rifampicin groups (clindamycin or flucloxacillin or vancomycin monotherapy, including rifampicin for only 5 postoperative days). Adjusted hazard ratios (aHRs) for failure in patients treated with short-term rifampicin and either flucloxacillin or clindamycin were almost equal to patients treated with long-term rifampicin combination therapy (aHR = 1.21; 95% confidence interval, .34-4.40). Conclusions: A short-term rifampicin strategy with either clindamycin or flucloxacillin and only 5 days of rifampicin was found to be as effective as traditional long-term rifampicin combination therapy. A randomized controlled trial is needed to further address efficacy and safety of alternative treatment strategies for staphylococcal PJI.

A longitudinal analysis of nosocomial bloodstream infections among preterm neonates.

Nosocomial bloodstream infections (NBSIs), commonly due to central-line associated bloodstream infections (CLABSI), contribute substantially to neonatal morbidity and mortality. We aimed to identify longitudinal changes in incidence of NBSI, microbiological-spectrum, and antibiotic exposure in a large cohort of preterm neonates admitted to the neonatal intensive care unit. We retrospectively assessed differences in annual rates of NBSI (per 1000 patient-days), CLABSI (per 1000 central-line days), and antibiotic consumption (per 1000 patient-days) among preterm neonates (< 32 weeks' gestation) hospitalized between January 2012 and December 2020. Multi-state Markov models were created to model states of progression of NBSI and infection risk given a central-line on days 0, 3, 7, and 10 of admission. Of 1547 preterm infants, 292 (19%) neonates acquired 310 NBSI episodes, 99 (32%) of which were attributed to a central-line. Over the years, a significant reduction in central-line use was observed (p < 0.001), although median dwell-time increased (p = 0.002). CLABSI incidence varied from 8.83 to 25.3 per 1000 central-line days, with no significant difference between years (p = 0.27). Coagulase-negative staphylococci accounted for 66% of infections. A significant decrease was found in antibiotic consumption (p < 0.001). Probability of NBSI decreased from 16% on day 3 to 6% on day 10. NBSI remains a common problem in preterm neonates. Overall antibiotic consumption decreased over time despite the absence of a significant reduction in infection rates. Further research aimed at reducing NBSI, in particular CLABSI, is warranted, particularly with regard to limiting central-line dwell-time and fine-tuning insertion and maintenance practices.

Reducing Inappropriate Urinary Catheter Use by Involving Patients Through the Participatient App: Before-and-After Study.

BACKGROUND: The risk of urinary tract infections is increased by the inappropriate placement and unnecessary prolongation of the use of indwelling urinary catheters. Sustained behavior change in infection prevention could be promoted by empowering patients through a smartphone app. OBJECTIVE: The aim of this study is to assess the feasibility and efficacy of implementation actions on patients' use of the Participatient app on a clinical ward and to compare 3 survey methods for urinary catheter use. METHODS: Participatient was introduced for all admitted patients at the surgical nursing ward in a university hospital in the Netherlands. Over a period of 3 months, the number of new app users, days of use, and sessions were recorded. In a comparison of urinary catheter use before and after the implementation of the app, 3 methods for point prevalence surveys of catheter use were tested. Surveys were conducted through manual parsing of the text in patients' electronic medical records, parsing a survey of checkbox items, and parsing nursing notes. RESULTS: In all, 475 patients were admitted to the ward, 42 (8.8%) installed the app, with 1 to 5 new users per week. The actions with the most ensuing app use were the kick-off with the clinical lesson and recruiting of the intake nurse. Between the survey methods, there was considerable variation in catheter use prevalence. Therefore, we used the standard method of manual parsing in further analyses. Catheter use prevalence decreased from 38% (36/96) to 27% (23/86) after app introduction (OR 0.61, 95% CI 0.32-1.14). CONCLUSIONS: The clinical application of Participatient, the infection prevention app for patients, could be feasible when implementation actions are also used. For surveying indwelling urinary catheter use prevalence, manual parsing is the best approach.

Hospital transmission of borderline oxacillin-resistant Staphylococcus aureus evaluated by whole-genome sequencing.

Introduction. Staphylococcus aureus is a major cause of hospital infections worldwide. Awareness towards methicillin-resistant S. aureus (MRSA) infections is high but attention towards borderline oxacillin-resistant S. aureus (BORSA) is limited, possibly due to an underestimated clinical relevance, presumption of low incidence and diagnostic limitations.Gap statement. BORSA surveillance has not been routinely implemented, and thus consensus with regard to a definition and infection control measures is lacking.Aim. Our goals were to investigate the occurrence, molecular characteristics and clinical manifestations of BORSA infections in the hospital setting.Methodology. Following an increased incidence in 2016, BORSA cases in 2014/2016 (in our institution) were more specifically evaluated. Medical records were reviewed to investigate epidemiological links, clinical characteristics and outcomes. Resistance and virulence markers were assessed by whole genome sequencing (WGS). Conventional methods: amplified fragment length polymorphism (AFLP) ; multilocus sequence typing (MLST) and multiple locus variable-number tandem repeat analysis (MLVA) were compared with core genome MLST (cgMLST) and whole-genome single nucleotide polymorphism (wgSNP) analysis to confirm genetic clusters.Results. From 2009 to 2013, BORSA comprised 0.1 % of all clinical S. aureus strains. In 2016, the incidence was six-fold higher in comparison to the baseline. Whole-genome SNP and cgMLST confirmed two BORSA clusters among patients with dermatological conditions. Patients with BORSA presented with skin infections, and one case developed a severe invasive infection with a fatal outcome. Infection control measures successfully prevented further transmission in both clusters. WGS findings showed that BORSA strains carried multiple resistance and virulence genes with increased pathogenic potential.Conclusion. WGS and cgMLST effectively characterized and confirmed BORSA clusters among at-risk patients with clinical manifestations ranging from mild skin infections to life-threatening bacteraemia. Clinical awareness and active monitoring are therefore warranted for the timely implementation of infection control measures to prevent BORSA transmission in high-risk patients.

The road to zero nosocomial infections in neonates-a narrative review.

AIM: Nosocomial infections (NI) in neonates are associated with prolonged hospitalisation, adverse neurodevelopmental outcome and high mortality. Over the past decade, numerous prevention strategies have resulted in significant reductions in NI rates. In this review, we aim to provide an overview of current NI rates from large, geographically defined cohorts. METHODS: PubMed, Web of Science, EMBASE and Cochrane Library were searched for evidence regarding epidemiology and prevention of NI in neonates. Extracted studies were synthesised in a narrative form with experiential reflection. RESULTS: Despite the abundance of geographically defined incidence proportions, an epidemiological overview of NI is difficult to provide, given the lack of consensus definition for neonatal NI and different baseline populations being compared. Successful prevention efforts have focused on implementing evidence-based practices while eliminating outdated strategies. The most promising model for reduction in infection rates is based on quality improvement (QI) collaboratives and benchmarking, involving identification and implementation of best practices, selection of measurable outcomes and fostering a sense of community and transparency. CONCLUSION: The preventative rather than curative approach forms the new paradigm for reducing the burden of neonatal infections. Despite progress achieved, continued work towards improved prevention practices is required in the strive towards zero NIs.

A Smartphone App for Engaging Patients With Catheter-Associated Urinary Tract Infections: Protocol for an Interrupted Time-Series Analysis.

BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) are the main cause of health care-associated infections, and they increase the disease burden, antibiotic usage, and hospital stay. Inappropriate placement and unnecessarily prolonged usage of a catheter lead to an elevated and preventable risk of infection. The smartphone app Participatient has been developed to involve hospitalized patients in communication and decision-making related to catheter use and to control unnecessary (long-term) catheter use to prevent CAUTIs. Sustained behavioral changes for infection prevention can be promoted by empowering patients through Participatient. OBJECTIVE: The primary aim of our multicenter prospective interrupted time-series analysis is to reduce inappropriate catheter usage by 15%. We will evaluate the efficacy of Participatient in this quality improvement study in clinical wards. Our secondary endpoints are to reduce CAUTIs and to increase patient satisfaction, involvement, and trust with health care services. METHODS: We will conduct a multicenter interrupted time-series analysis-a strong study design when randomization is not feasible-consisting of a pre- and postintervention point-prevalence survey distributed among participating wards to investigate the efficacy of Participatient in reducing the inappropriate usage of catheters. After customizing Participatient to the wards' requirements, it will be implemented with a catheter indication checklist among clinical wards in 4 large hospitals in the Netherlands. We will collect clinical data every 2 weeks for 6 months in the pre- and postintervention periods. Simultaneously, we will assess the impact of Participatient on patient satisfaction with health care services and providers and the patients' perceived involvement in health care through questionnaires, and the barriers and facilitators of eHealth implementation through interviews with health care workers. RESULTS: To reduce the inappropriate use of approximately 40% of catheters (currently in use) by 15%, we aim to collect 9-12 data points from 70-100 patients per survey date per hospital. Thereafter, we will conduct an interrupted time-series analysis and present the difference between the unadjusted and adjusted rate ratios with a corresponding 95% CI. Differences will be considered significant when P<.05. CONCLUSIONS: Our protocol may help reduce the inappropriate use of catheters and subsequent CAUTIs. By sharing reliable information and daily checklists with hospitalized patients via an app, we aim to provide them a tool to be involved in health care-related decision-making and to increase the quality of care. TRIAL REGISTRATION: Netherlands Trial Register NL7178; https://www.trialregister.nl/trial/7178. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/28314.

[Rational use of respiratory protective equipment: advice for health care professionals in time of COVID-19]. / Rationeel gebruik van ademhalingsbeschermingsmaskers.

The current COVID-19 pandemic has led to a worldwide shortage of respiratory protective equipment. In order to offer maximum protection against infection for all healthcare workers, we need to optimise our use of the available equipment. This article provides practical advice on which type of mask is indicated in what specific situation, what requirements the mask should meet and how to optimise the local workflow, including the re-use of masks after decontamination.

Public health response to two imported, epidemiologically related cases of Lassa fever in the Netherlands (ex Sierra Leone), November 2019.

On 20 November 2019, Lassa fever was diagnosed in a physician repatriated from Sierra Leone to the Netherlands. A second physician with suspected Lassa fever, repatriated a few days later from the same healthcare facility, was confirmed infected with Lassa virus on 21 November. Comprehensive contact monitoring involving high- and low-risk contacts proved to be feasible and follow-up of the contacts did not reveal any case of secondary transmission in the Netherlands.

Neonatal Meningitis and Subdural Empyema Caused by an Unusual Pathogen.

We report a case of neonatal meningitis with subdural empyema, caused by Ureaplasma parvum. In this case, diagnosis was made by genus-specific polymerase chain reaction, after regularly used diagnostic techniques failed. This unusual pathogen should be considered in cases that do not respond to therapy and/or where cultures for typical pathogens in neonatal sepsis and meningitis remain negative.

Repetitive urinary tract infections and two prostatic masses: Prostatic soft tissue infection with Actinomyces neuii.

Actinomyces infection is a tissue destructive, low-grade infection that often resembles malignancy. We report the case of a 70-year-old male with repeated, culture-negative urinary tract infections while intermittently catheterized. At presentation, the patient reported a new episode of urinary tract infection with white discharge in his urine. Transrectal ultrasonography showed two lesions in the prostate, suspect for prostate cancer. However, biopsy did not show cancer, and anaerobic culture grew Actinomyces neuii. A 3-month antibiotic course of amoxicillin eventually cured the infection. This is a case of prostatic soft tissue infection with A. neuii. It is important to consider Actinomyces infection in patients with a non-malignant prostatic mass. Although ß-lactam antibiotics do not penetrate the prostate well, the Actinomyces infection was cured by prolonged amoxicillin treatment in this case. It is possible that the tissue damage enhanced the amoxicillin concentration in the infected prostate.

[Prosthetic joint infection]. / Geïnfecteerde gewrichtsprothese.

Prosthetic joint infection A prosthetic joint infection (PJI) is a serious complication that can lead to lengthy hospitalization, significant limitations in mobility, and a reduced quality of life. For acute PJI, the aim is to cure the infection whilst retaining the prosthesis; this can be achieved by means of thorough surgical debridement, cleaning of the artificial material, replacement of exchangeable prosthesis parts and adjuvant antibiotic therapy. In cases of chronic PJI, the prosthetic joint needs to be replaced. For patients in whom surgery is not feasible, or who refuse surgical intervention, chronic suppressive antibiotic therapy can be applied if the infection persists. In order to increase the likelihood of a favourable outcome, it is important to take a multidisciplinary approach.

Typing Pseudomonas aeruginosa Isolates with Ultrahigh Resolution MALDI-FTICR Mass Spectrometry.

The introduction of standardized matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) platforms in the medical microbiological practice has revolutionized the way microbial species identification is performed on a daily basis. To a large extent, this is due to the ease of operation. Acquired spectra are compared to profiles obtained from cultured colonies present in a reference spectra database. It is fast and reliable, and costs are low compared to previous diagnostic approaches. However, the low resolution and dynamic range of the MALDI-TOF profiles have shown limited applicability for the discrimination of different bacterial strains, as achieved with typing based on genetic markers. This is pivotal in cases where certain strains are associated with, e.g., virulence or antibiotic resistance. Ultrahigh resolution MALDI-FTICR MS allows the measurement of small proteins at isotopic resolution and can be used to analyze complex mixtures with increased dynamic range and higher precision than MALDI-TOF MS, while still generating results in a similar time frame. Here, we propose to use ultrahigh resolution 15T MALDI-Fourier transform ion cyclotron resonance (FTICR) MS to discriminate clinically relevant bacterial strains after species identification performed by MALDI-TOF MS. We used a collection of well characterized Pseudomonas aeruginosa strains, featuring distinct antibiotic resistance profiles, and isolates obtained during hospital outbreaks. Following cluster analysis based on amplification fragment length polymorphism (AFLP), these strains were grouped into three different clusters. The same clusters were obtained using protein profiles generated by MALDI-FTICR MS. Subsequent intact protein analysis by electrospray ionization (ESI)-collision-induced dissociation (CID)-FTICR MS was applied to identify protein isoforms that contribute to the separation of the different clusters, illustrating the additional advantage of this analytical platform.

Extended-spectrum ß-lactamase-producing enterobacteriaceae among travelers from the Netherlands.

A prospective cohort study was performed among travelers from the Netherlands to investigate the acquisition of carbapenemase-producing Enterobacteriaceae (CP-E) and extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) and associated risk factors. Questionnaires were administered and rectal swab samples were collected and tested before and after traveler return. Of 370 travelers, 32 (8.6%) were colonized with ESBL-E before trave,; 113 (30.5%) acquired an ESBL-E during travel, and 26 were still colonized 6 months after return. No CP-E were found. Independent risk factors for ESBL-E acquisition were travel to South and East Asia. Multilocus sequence typing showed extensive genetic diversity among Escherichia coli. Predominant ESBLs were CTX-M enzymes. The acquisition rate, 30.5%, of ESBL-E in travelers from the Netherlands to all destinations studied was high. Active surveillance for ESBL-E and CP-E and contact isolation precautions may be recommended at admission to medical facilities for patients who traveled to Asia during the previous 6 months.

Innate immune evasion by staphylococci.

When bacteria invade the human host, they are directly confronted with a serious threat, the human innate immune system. This chapter describes the challenge that a staphylococci face and recent findings on how this bacterium counteracts the massive attack of this innate immune system. In order to survive within the human host, staphylococci have evolved a wide variety of small, excreted proteins that interfere with subsequent steps of the human innate immune system cascade.

Chemotaxis inhibitory protein of Staphylococcus aureus, a bacterial antiinflammatory agent.

Leukocyte migration is a key event both in host defense against invading pathogens as well as in inflammation. Bacteria generate chemoattractants primarily by excretion (formylated peptides), complement activation (C5a), and subsequently through activation of leukocytes (e.g., leukotriene B4, platelet-activating factor, and interleukin 8). Here we describe a new protein secreted by Staphylococcus aureus that specifically impairs the response of neutrophils and monocytes to formylated peptides and C5a. This chemotaxis inhibitory protein of S. aureus (CHIPS) is a 14.1-kD protein encoded on a bacteriophage and is found in >60% of clinical isolates. CHIPS reduces the neutrophil recruitment toward C5a in a mouse peritonitis model, even though its activity is much more potent on human than on mouse cells. These findings suggest a new immune escape mechanism of S. aureus and put forward CHIPS as a potential new antiinflammatory therapeutic compound.