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Background: The prevention of methicillin-resistant S. aureus (MRSA) transmission in the healthcare setting is a priority in Infection Control practices. A cornerstone of this policy is contact tracing of nosocomial contacts after an unexpected MRSA finding. The objective of this retrospective study was to quantify the rates of MRSA transmission in different clinical settings., Methods: This multi-centre study included MRSA contact screening results from two regional hospitals and one academic hospital. MRSA contact tracing investigations from 2000 until 2019 were reviewed and post-contact screening results were included of index patients with an MRSA-positive culture and their unprotected contacts. Available typing results were used to rule out incidental findings., Results: Of 27,377 contacts screened after MRSA exposure, 21,488 were Health Care Workers (HCW) and 4816 patients. Post-contact screening was initiated for a total of 774 index cases, the average number of screened contacts per index case was 35.7 (range 1 to 640). MRSA transmission was observed in 0.15% (41) of the contacts, 19 (0.09%) HCW and 22 (0.46%) patients. The number needed to screen to detect one MRSA transmission was 667. The highest risk of MRSA transmission occurred during patient-to-patient contacts, with transmission rates varying from 0.32 to 1.32% among the participating hospitals. No transmissions were detected in HCW (n=2834) in the outpatient setting, and the rate of transmissions among HCW contacts on the wards was 0.13% (19 of 15,874). Among 344 contacts of patients with contact precautions, no transmissions were detected., Conclusions: Reconsidering current MRSA contact tracing practices may lead to a more targeted approach with a lower number needed to screen., (© 2024. The Author(s).)

Background: Serratia marcescens is known to cause outbreaks in neonatal intensive care units (NICUs). Traditionally epidemiological data, antimicrobial resistance patterns and epidemiological typing have been used to guide infection prevention methods. Whole-genome sequencing (WGS) applications such as core-genome multi-locus sequence typing (cgMLST) applied during an outbreak would potentially yield more information., Aim: To use cgMLST to acquire detailed information on the source and spread of bacteria, enabling more efficient control measures during an S. marcescens outbreak at a NICU., Methods: Neonates admitted to the NICU of the Leiden University Medical Center (LUMC) during an outbreak between September 2023 and January 2024, with S. marcescens being cultured, were included. Environmental samples were taken to search for a common source, antibiotic susceptibility testing was performed, and antimicrobial resistance genes were analysed., Findings: S. marcescens strains from 17 of the 20 positive patients were available for molecular typing. The cgMLST scheme revealed five different complex types consisting of four separate clusters. Multiple clusters made an unidentified persistent environmental source as cause of the outbreak less likely, leading to a quick downscaling of infection prevention measures. Differences were shown in aminoglycoside resistance patterns of isolates within the same complex types and patients., Conclusion: The use of ad-hoc cgMLST provided timely data for rational decision-making during an S. marcescens outbreak at the NICU. Antibiotic phenotyping alone was found not to be suitable for studying clonal spread during this outbreak with S. marcescens., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

BackgroundEffective pandemic preparedness requires robust severe acute respiratory infection (SARI) surveillance. However, identifying SARI patients based on symptoms is time-consuming. Using the number of reverse transcription (RT)-PCR tests or contact and droplet precaution labels as a proxy for SARI could accurately reflect the epidemiology of patients presenting with SARI.AimWe aimed to compare the number of RT-PCR tests, contact and droplet precaution labels and SARI-related International Classification of Disease (ICD)-10 codes and evaluate their use as surveillance indicators.MethodsPatients from all age groups hospitalised at Leiden University Medical Center between 1 January 2017 up to and including 30 April 2023 were eligible for inclusion. We used a clinical data collection tool to extract data from electronic medical records. For each surveillance indicator, we plotted the absolute count for each week, the incidence proportion per week and the correlation between the three surveillance indicators.ResultsWe included 117,404 hospital admissions. The three surveillance indicators generally followed a similar pattern before and during the COVID-19 pandemic. The correlation was highest between contact and droplet precaution labels and ICD-10 diagnostic codes (Pearson correlation coefficient: 0.84). There was a strong increase in the number of RT-PCR tests after the start of the COVID-19 pandemic.DiscussionAll three surveillance indicators have advantages and disadvantages. ICD-10 diagnostic codes are suitable but are subject to reporting delays. Contact and droplet precaution labels are a feasible option for automated SARI surveillance, since these reflect trends in SARI incidence and may be available real-time.

Background: The risk of urinary tract infections (UTIs) is increased by unnecessary placement and prolonged use of urinary catheters., Aim: To assess whether inappropriate use of catheters and catheter-associated UTI were reduced through patient participation., Methods: In this multicentre, interrupted time-series and before-and-after study, we implemented a patient-centred app which provides catheter advice for patients, together with clinical lessons, feedback via e-mails and support rounds for staff members. Data on catheter use and infections were collected during a six-month baseline and a six-month intervention period on 13 wards in four hospitals in the Netherlands. Dutch Trial Register: NL7178., Findings: Between June 25 th , 2018 and August 1 st , 2019, 6556 patients were included in 24 point-prevalence surveys, 3285 (50%) at baseline and 3271 (50%) during the intervention. During the intervention 249 app users and a median of seven new app users per week were registered (interquartile range: 5.5-13.0). At baseline, inappropriate catheter use was registered for 175 (21.9%) out of 798 catheters, compared to 55 (7.0%) out of 786 during the intervention. Time-series analysis showed a non-significant decrease of inappropriate use of 5.8% (95% confidence interval: -3.76 to 15.45; P = 0.219), with an odds ratio of 0.27 (0.19-0.37; P < 0.001). Catheter-associated UTI decreased by 3.0% (1.3-4.6; P = 0.001), with odds ratio 0.541 (0.408-0.716; P < 0.001)., Conclusion: Although UTI significantly decreased after the implementation, patient participation did not significantly reduce the prevalence of inappropriate urinary catheter use. However, the inappropriate catheter reduction of 5.8% and an odds ratio of 0.27 suggest a positive trend. Patient participation appears to reduce CAUTI and could reduce other healthcare-associated infections., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2023. The Author(s).)

Background: It was shown previously that changing the design of a hospital neonatal intensive care unit (NICU) from open bay units (OBUs) to single room units (SRUs) was not associated with a reduction in Gram-negative multi-drug-resistant organism (MDRO) colonization rates. It was therefore hypothesized that colonization mainly occurs vertically, or through parents and healthcare workers, and not through environmental factors, and that transition to SRUs would not decrease the number of clusters of MDROs with an epidemiological link. To investigate this, core-genome multi-locus sequence typing (cgMLST) was applied on MDROs cultured from infants at the study hospital., Methods: This retrospective cohort study included all infants carrying MDROs admitted to the NICU of a tertiary care academic hospital 2 years prior to the transition from OBUs to SRUs in May 2017, and 1.5 years after the transition (2018-2020)., Results: In total, 55 infants were diagnosed with MDRO carriership. Isolates were available from 49 infants for cgMLST. In the OBU period, one cluster involving four of 20 (20%) infants was identified, and in the SRU period, four clusters involving nine of 29 (31%) infants were identified. It was possible to make an epidemiological link in all four SRU MDRO clusters, but this was not possible for the OBU cluster. In the latter case, transmission from an environmental source on the ward seemed likely., Conclusion: After transition to SRUs, there was no decrease in the number of clusters of MDROs with an epidemiological link, suggesting that nursing infants in an NICU with an SRU design is not, in itself, protective against the acquisition of MDROs., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 log 10 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., (© 2023. The Author(s).)

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., (© 2022. The Author(s).)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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., (©Robbert G Bentvelsen, Marguerite L Bruijning, Niels H Chavannes, Karin Ellen Veldkamp. Originally published in JMIR Formative Research (https://formative.jmir.org), 04.04.2022.)

Background: The influence of the neonatal intensive care unit (NICU) design on the acquisition of multidrug-resistant organisms (MDROs) has not been well-documented., Aim: To examine the effect of single room unit (SRU) versus open bay unit (OBU) design on the incidence of colonization with MDROs and third-generation cephalosporin-resistant bacteria (3G-CRB) in infants admitted to the NICU., Methods: Retrospective cohort study, including all infants admitted to the NICU of a tertiary care academic hospital two years prior to and two years following the transition from OBU to SRU in May 2017. Weekly cultures of throat and rectum were collected to screen for MDRO carriership. Incidence of colonization (percentage of all infants and incidence density per 1000 patient-days) with MDROs and 3G-CRB were compared between OBU and SRU periods., Findings: Incidence analysis of 1293 NICU infants, identified 3.2% MDRO carriers (2.5% OBU, 4.0% SRU, not significant), including 2.3% extended-spectrum β-lactamase-producing Enterobacterales carriers, and 18.6% 3G-CRB carriers (17% OBU, 20% SRU, not significant). No differences were found in MDRO incidence density per 1000 patient-days between infants admitted to OBU (1.56) compared to SRU infants (2.63)., Conclusion: Transition in NICU design from open bay to SRUs was not associated with a reduction in colonization rates with MDROs or 3G-CRB in our hospital. Further research on preventing the acquisition and spread of resistant bacteria at high-risk departments such as the NICU, as well as optimal ward design, are needed., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (©2021 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

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.

Background: The increase in smartphone use and mobile health applications (apps) holds potential to use apps to reduce and detect healthcare-associated infections (HAIs) in clinical practice., Aim: To obtain an overview of available apps for HAI prevention, by selecting the clinically relevant apps and scoring functionality, quality and usefulness., Methods: This scoping review of available apps in the iOS and Android app stores uses an in-house-developed tool (scraper https://holtder.github.io/talos) to systematically aggregate available apps relevant for HAI prevention. The apps are evaluated on functionality, assessed on quality using the 'Mobile Application Rating Scale' (MARS), and assessed on potential use in clinical infection prevention., Findings: Using the scraper with CDC HAI topics through 146 search terms resulted in 92,726 potentially relevant apps, of which 28 apps met the inclusion criteria. The majority of these apps have the functionality to inform (27 of 28 apps) or to instruct (20/28). MARS scores for the 28 apps were high in the following domains: functionality (4.19/5), aesthetics (3.49/5), and information (3.74/5), with relatively low scores in engagement (2.97/5), resulting in a good average score (3.57/5)., Conclusion: Low engagement scores restrict apps that intend to inform or instruct, possibly explained by the often-academic nature of the development of these apps. Although the number of HAI prevention apps increased by 60% in 5 years, the proportion of clinically relevant apps is limited. The variation in HAI app quality and lack of user engagement, could be improved by co-creation and development in the clinical setting., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., (©Robbert Gerard Bentvelsen, Karin Ellen Veldkamp, Niels H Chavannes. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 23.03.2021.)

Introduction: Nosocomial infections (NIs) are a major source of iatrogenic harm in neonatal intensive care units (NICUs). The influence of the infrastructure of NICUs on NIs is not well documented. This study aims to examine the effect of single-room units (SRU) versus open-bay units (OBU) on the incidence of NIs, including central-line-associated bloodstream infections (CLABSI), in preterm neonates., Methods: All preterm neonates (< 32 weeks gestational age) admitted to our NICU were included. Two study periods were compared: one prior to (May 2015-May 2017) and one following (May 2017-May 2019) transition from OBU to SRU. Incidence density (number of infections per 1000 patient-days) and cumulative incidence (number of infections per 100 neonates) for NIs were calculated. CLABSIs were calculated per 1000 central-line days. U chart analysis was performed to determine special-cause variation in quarterly CLABSI and NI rates. Multivariate competing risk regression was performed to identify independent NI risk factors., Results: Of the 712 included infants, 164 (23%) infants acquired ≥ 1 NIs. No differences were found in incidence density (13.68 vs. 12.62, p = 0.62) or cumulative incidence of NI (23.97 vs. 22.02, p = 0.59) between OBU and SRU. CLABSIs showed a similar non-significant reduction after the move (14.00 vs. 10.59, p = 0.51). U chart analysis did not identify unit transition as a potential source of special-cause variation for CLABSI and NI. Competing risks regression analysis revealed longer duration of invasive mechanical ventilation as a significant risk factor for NI (subhazards ratio: 1.03 per day on ventilation, p = 0.01)., Conclusion: Single-rooms are not associated with a significant reduction in NIs in the NICU. This study therefore does not add evidence that could support the transition to SRUs if based only on a large multimodal infection control strategy. Recommendations to build SRUs would require a wider justification, also taking into account other SRU benefits.

Background: During a meticillin-resistant Staphylococcus aureus contact tracing and screening investigation, two borderline oxacillin-resistant Staphylococcus aureus (BORSA)-positive screening cultures were encountered among neonatal intensive care unit (NICU) healthcare workers (HCWs). This finding led to further investigations., Aim: To assess the likelihood of an outbreak with direct transmission among HCWs., Methods: An infection control team was initiated after the discovery. The team initiated additional infection control measures and evaluated new findings. All NICUs and paediatric ward HCWs were screened for BORSA carriage, and a prospective BORSA seven-week monitoring period for patients was observed. To assess the likelihood of an outbreak with direct transmission among HCWs, the BORSA isolates were analysed using augmented fragment length polymorphism and whole-genome sequencing (WGS)., Findings: Positive HCWs were prohibited from clinical work while awaiting the results from the screening programme. In all, 127 NICU and 77 general paediatric ward HCWs were screened for BORSA carriage; five HCWs were BORSA positive. Seventy-two patients were screened during the seven-week period yielding a total of 138 cultures, ranging from one to nine cultures per patient. No spread from HCWs to patients occurred, and the BORSA screening programme was discontinued. WGS analysis with core genome multi-locus sequence typing of all five BORSA strains showed relatedness between two NICU strains., Conclusion: During a seven-week period, no transmission from BORSA-positive HCWs to neonates was observed in either screening or clinical cultures. More vigilance and experience is needed to design adequate evidence-based interventions in the future for this vulnerable population., (Copyright © 2020. Published by Elsevier Ltd.)

Introduction: Nosocomial infections (NIs) are a major source of iatrogenic harm in neonatal intensive care units (NICUs). The influence of the infrastructure of NICUs on NIs is not well documented. This study aims to examine the effect of single-room units (SRU) versus open-bay units (OBU) on the incidence of NIs, including central-line-associated bloodstream infections (CLABSI), in preterm neonates., Methods: All preterm neonates (< 32 weeks gestational age) admitted to our NICU were included. Two study periods were compared: one prior to (May 2015-May 2017) and one following (May 2017-May 2019) transition from OBU to SRU. Incidence density (number of infections per 1000 patient-days) and cumulative incidence (number of infections per 100 neonates) for NIs were calculated. CLABSIs were calculated per 1000 central-line days. U chart analysis was performed to determine special-cause variation in quarterly CLABSI and NI rates. Multivariate competing risk regression was performed to identify independent NI risk factors., Results: Of the 712 included infants, 164 (23%) infants acquired ≥ 1 NIs. No differences were found in incidence density (13.68 vs. 12.62, p  = 0.62) or cumulative incidence of NI (23.97 vs. 22.02, p  = 0.59) between OBU and SRU. CLABSIs showed a similar non-significant reduction after the move (14.00 vs. 10.59, p  = 0.51). U chart analysis did not identify unit transition as a potential source of special-cause variation for CLABSI and NI. Competing risks regression analysis revealed longer duration of invasive mechanical ventilation as a significant risk factor for NI (subhazards ratio: 1.03 per day on ventilation, p  = 0.01)., Conclusion: Single-rooms are not associated with a significant reduction in NIs in the NICU. This study therefore does not add evidence that could support the transition to SRUs if based only on a large multimodal infection control strategy. Recommendations to build SRUs would require a wider justification, also taking into account other SRU benefits., Supplementary Information: The online version contains supplementary material available at 10.1007/s40121-020-00380-9., (© The Author(s) 2020.)

Background: Isolation precautions are applied to control the risk of transmission of multi-drug resistant organisms (MDROs). These precautions have been associated with adverse effects, such as anxiety and depression. This study aimed to quantify stigma among MDRO carriers and its association with perceived mental health and experienced quality of care., Methods: A quantitative questionnaire study was performed in MDRO carriers exposed to ≥3 days of isolation precautions during hospitalization. Items derived from the Consumer Quality Index questionnaire (CQI) were used to assess perception of care. Stigma scores were calculated using the recently modified Berger Stigma Scale for meticillin-resistant Staphylococcus aureus (MRSA). Mental health was measured with the RAND Mental Health Inventory. The Spearman rank correlation test was used to assess the association between stigma score and RAND mental health score., Findings: Of the 41 included carriers, 31 (75.6%) completed both questionnaires. The experienced quality of care was 'good' according to CQI score. Twenty-four percent reported not to have received proper explanation about MDRO carriership from healthcare workers (HCWs). MDRO-associated stigma was reported in 1/31 (3.2%). Poor mental health was self-reported in 3/31 (9.7%). There was no correlation between stigma score and RAND mental health score (Spearman correlation coefficient: 0.347)., Conclusions: In this study, MDRO carriers exposed to ≥3 days of isolation precautions did not report stigma. This contrasts with a recent study that investigated MRSA-associated stigma and may be explained by contact plus airborne isolation protocols in MRSA compared with contact isolation alone in most other MDROs. Also, the psychological impact may be of a different magnitude due to as yet unknown reasons., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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.

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.

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 β-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., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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.

Background: Sink drains in intensive care units (ICUs) are frequently colonized with bacteria such as Pseudomonas aeruginosa., Aim: To study the influence of installing disinfecting devices on sink drains on colonization of sinks and patients in an ICU during a prolonged outbreak of multidrug-resistant P. aeruginosa., Methods: From 2010, there was a clonal outbreak of multidrug-resistant P. aeruginosa (MDR-PA). In April 2013, in ICU subunit A, the siphons draining these sinks were replaced by devices applying heat and electromechanical vibration to disinfect the draining fluid. In the other units, siphons were replaced by new polyvinyl chloride plastic siphons (control). In February 2016 the disinfecting devices were also placed at ICU subunit B., Findings: Baseline colonization rate of sinks was 51% in ICU A and 46% in ICU B. In ICU A colonization decreased to 5% (P < 0.001) after the intervention whereas it was 62% in ICU B (control). After installing the disinfection devices in ICU B, colonization rate was 8.0 and 2.4% in ICU A and B, respectively (both P < 0.001 compared with baseline). Colonization in ICU patients decreased from 8.3 to 0 per 1000 admitted patients (P < 0.001) and from 2.7 to 0.5 per 1000 admitted patients (P = 0.1) in ICU A and B respectively., Conclusion: Colonization with MDR-PA in sink drains in an ICU was effectively managed by installing disinfection devices to the siphons of sinks. Colonization of patients was also significantly reduced, suggesting that sink drains can be a source of clinical outbreaks with P. aeruginosa and that disinfecting devices may help to interrupt these outbreaks., (Copyright © 2019 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

The emergence of the plasmid-mediated mcr colistin resistance gene in the community poses a potential threat for treatment of patients, especially when hospitalized. The aim of this study was to determine the prevalence of all currently known mcr mediated colistin resistance gene in fecal samples of patients attending a tertiary care hospital. From November 2014 until July 2015, fecal samples of patients attending the Leiden University Medical Center were collected and screened for presence of mcr using real-time PCR. Two of 576 patients were positive for mcr-1, resulting in a prevalence of 0.35%, whereas no mcr-2 was found. One of these samples was culture negative, the second sample contained a blaCMY-2 and mcr-1 containing E.coli. This strain belonged to Sequence Type 359 and serotype O177:H21. The mcr-1 containing E.coli was phenotypically susceptible to colistin with a MIC of ≤ 0.25mg/l, due to a 1329bp transposon IS10R inserted into the mcr-1 gene as identified by WGS. This prevalence study shows that mcr-1 is present in low levels patients out of the community attending a hospital. Furthermore the study underlines the importance of phenotypical confirmation of molecular detection of a mcr-1 gene.

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.

In this paper we aim to provide insight into the complexity of outbreak management in an intensive care unit (ICU) setting. In October 2010 four patients on the ICU of our tertiary care centre were colonized or infected with a multidrug-resistant strain of Pseudomonas aeruginosa (MDR-PA). An outbreak investigation was carried out and infection control measures were taken in an attempt to identify a potential source and stop transmission. The outbreak investigation included descriptive epidemiology, comprising retrospective case finding by reviewing the laboratory information system back to 2004 and prospective case finding by patient screening for MDR-PA. Furthermore, microbiological analysis, environmental screening and a case-control study were carried out. Infection control measures consisted of re-education of healthcare personnel on basic hygiene measures, auditing of hygiene procedures used in daily practice by infection control practitioners, and stepwise up-regulation of isolation measures. From February 2009 to January 2012, 44 patients on our ICU were found to be MDR-PA positive. MDR-PA isolates of the 44 patients showed two distinct AFLP patterns, with homology within each of the AFLP clusters of more than 93%. The VIM metallo-β-lactamase gene was detected in 20 of 21 tested isolates. A descriptive epidemiology investigation identified the rooms with the highest numbers of MDR-PA positive patients. The case-control study showed three factors to be independently associated with MDR-PA positivity: admission to ICU subunit 1 (OR, 6.1; 95% CI, 1.7, 22), surgery prior to or during admission (OR, 5.7; 95% CI, 1.6, 20) and being warmed-up with the warm-air blanket (OR, 3.6; 95% CI, 1.2, 11). After three environmental screening rounds, with sampling of sinks, furniture and devices in the ICU, without revealing a clear common source, a fourth environmental investigation included culturing of faucet aerators. Two faucets were found to be positive for MDR-PA and were replaced. The occurrence of new cases decreased with the strengthening of infection control measures and declined further with the removal of the common source. With this integrated approach a prolonged outbreak of P. aeruginosa was controlled. Contaminated faucet aerators on the ICU probably served as a persisting source, while interpatient transmission by medical staff was a likely way of spread. Seven months after the last case (January 2012) and 3 months after cessation of extended isolation measures (May 2012), single cases started to occur on the ICU, with a total of seven patients in the past year. No common source has yet been found., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

A prospective cohort study was performed among travelers from the Netherlands to investigate the acquisition of carbapenemase-producing Enterobacteriaceae (CP-E) and extended-spectrum β-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.

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.

A 24-year-old immune-competent woman was admitted to hospital with a three-day history of fever and headache. On examination bilateral facial nerve palsy, lumbosacral radicular pain, reduced sacral sensibility and urinary retention were found. Open perianal lesions were suspect for genital herpes. The symptoms were compatible with a meningoradiculitis including a sacral polyradiculitis. On testing, cerebrospinal fluid was found to be abnormal with a lymphocytic cell reaction. Polymerase chain reaction (PCR) of cerebrospinal fluid and of the perianal lesions was positive for herpes simplex virus type 2 (HSV-2). An MRI scan showed colouration of part of the cauda equina. The patient was treated by intravenous injections of acyclovir 10 mg/kg t.i.d. for 21 days, after which she completely recovered. HSV-2 infection of the nervous system can cause lymphocytic, and sometimes recurrent meningitis as well as sacral polyradiculitis. It may also occur without any symptomatic genital herpes infection. A positive result from a PCR test of the cerebrospinal fluid confirms this diagnosis. Treatment with acyclovir should be started as soon as possible.

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.

In a previous study, we showed that Staphylococcus aureus supernate (SaS) is a potent agonist for both neutrophils and mononuclear cells. To further investigate the immunomodulating effects of SaS, the effect on different neutrophil receptors was studied. Expression of various neutrophil receptors, before and after treatment with SaS, was quantified by flow cytometry. We found that SaS treatment of neutrophils resulted in a specific and total downregulation of the C5a and the fMLP receptor, both serpentine receptors, while other receptors were totally unaffected. Since these two receptors are both involved in chemotaxis, we tested the effect of SaS in calcium flux and chemotaxis assays. We showed that preincubation with SaS abrogated the rise in intracellular calcium concentration upon triggering with fMLP and C5a. We also showed that SaS is a potent inhibitor of neutrophil chemotaxis towards fMLP and C5a, but does not interfere with chemotaxis towards interleukin-8. These findings indicate that S. aureus produces a virulence factor extracellularly, which impairs chemotaxis towards the infected site.

In this study, 29 patients were hospitalized with a diabetic foot infection and were treated with piperacillin/tazobactam. Of these 23 patients who were evaluated for efficacy of treatment, 22 patients improved or were clinically cured. In seven patients (30%), there was persistence of one of the baseline pathogens. Adverse events were reported in 15 patients (58%), three of which were serious. Piperacillin/tazobactam may be useful as monotherapy in diabetic foot infection giving an adequate clinical response and the level of side effects equivalent to those of other broad-spectrum antibiotics.

Delta-toxin from Staphylococcus aureus is responsible for various pathophysiologic effects. By studying different cell types in binding of delta-toxin in low, noncytotoxic concentrations, a specific binding of fluorescein-labeled delta-toxin to neutrophils and monocytes was found. Studying direct effects of delta-toxin on neutrophils, a dose-dependent up-regulation of complement receptor 3 expression was found. Oxygen radical production, as determined by Luminol-enhanced chemiluminescence, was not directly induced by delta-toxin, and this toxin was also unable to prime neutrophils for an enhanced response to FMLP or complement-opsonized zymosan. However, the priming response induced by lipopolysaccharide or tumor necrosis factor-alpha (TNF-alpha) was significantly further enhanced in the presence of delta-toxin. Furthermore, as a direct effect on human monocytes, delta-toxin induced TNF-alpha production. These data provide evidence that delta-toxin has direct and indirect effects on the activity of neutrophils and monocytes with regard to its proinflammatory capacity.

Phagocytes play a major role in host defense against staphylococci as well as in the pathophysiology of Gram-positive septic shock. In Gram negative sepsis, the main mediator, LPS exerts its effects as easily suspendable mediator. In Gram positive sepsis the main mediator is still not found, therefore we studied the interaction of soluble staphylococcal products with phagocytes. Staphylococcus aureus supernates (SaS) were harvested from several laboratory and clinical strains that were grown to late-log phase. These supernates upregulated CD11b/CD18 expression on human neutrophils even in a 100-fold dilution. SaS also induced the release of TNF-alpha and IL-1 beta by human monocytes. Control experiments excluded peptidoglycan, lipoteichoic acid, alpha and delta toxin, leucocidin, TSST-1 and all enterotoxins as sole mediators. Endotoxin contamination was also excluded. SaS was heat-stable; incubation for 45 minutes at 100 degrees C did not affect its activity. Compared to purified peptidoglycan and intact bacteria per bacterium, SaS had a higher potency in stimulating phagocytes. We hypothesize that there are more--yet unknown--soluble staphylococcal products which are very important in phagocyte stimulation.

Patients with chronic renal failure on intermittent dialysis sometimes develop an acute diffuse conjunctival and episcleral hyperaemia. In this study the hypothesis was tested whether the precipitation of hydroxyapatite crystals could result in an inflammatory reaction mediated by enzymes liberated from polymorphonuclear leucocytes (PMN). Ingestion of the crystals by PMN's can result in cell death and membranolysis and subsequent release of intracellular enzymes into the surrounding tissues. This 'suicide sac' hypothesis for the inflammatory reactions of the conjunctiva and episclera was rejected after histopathological examination of conjunctival biopsies failed to show complement activation or crystal ingestion by PMN's despite the presence of small subepithelial hydroxyapatite crystals.