Genetic Determinants in MRSA Carriage and Their Association with Decolonization Outcome.

Methicillin-resistant Staphylococcus aureus (MRSA) colonization increases the risk of infection. Response to decolonization treatment is highly variable and determinants for successful decolonization or failure of eradication treatment are largely unknown. Insight into genetic predictors of eradication failure is potentially useful in clinical practice. The aim of this study was to explore genetic characteristics that are associated with MRSA decolonization failure. This cohort study was performed in a tertiary care hospital in the Netherlands. Patients with ≥ 1 positive MRSA culture from any site and with available whole -genome sequencing data of the MRSA isolate between 2017 and 2022 were included. Lineages, resistance, and virulence factors were stratified by MRSA decolonization outcome. In total, 56 patients were included: 12/56 (21%) with treatment failure and 44/56 (79%) with successful decolonization (with or without preceding treatment). A significant association was found between ciprofloxacin-resistant lineages and failure of eradication (OR 4.20, 95%CI 1.11-15.96, P = 0.04). Furthermore, livestock-associated MRSA and the major community-associated MRSA lineages ST6-t304 and ST8-t008 were associated with successful eradication treatment or spontaneous clearance. In conclusion, this explorative study showed a higher eradication failure rate in complicated MRSA carriers with ciprofloxacin-resistant MRSA lineages, which are predominantly healthcare-associated. Further studies are warranted to confirm the higher eradication failure risk of ciprofloxacin-resistant lineages, and identify the underlying mechanisms.

Immunogenicity of an Additional mRNA-1273 SARS-CoV-2 Vaccination in People With HIV With Hyporesponse After Primary Vaccination.

BACKGROUND: The COVIH study is a prospective coronavirus disease 2019 (COVID-19) vaccination study in 1154 people with HIV (PWH), of whom 14% showed reduced antibody levels after primary vaccination. We evaluated whether an additional vaccination boosts immune responses in these hyporesponders. METHODS: The primary end point was the increase in antibodies 28 days after additional mRNA-1273 vaccination. Secondary end points included neutralizing antibodies, S-specific T-cell and B-cell responses, and reactogenicity. RESULTS: Of the 66 participants, 40 previously received 2 doses ChAdOx1-S, 22 received 2 doses BNT162b2, and 4 received a single dose Ad26.COV2.S. The median age was 63 years (interquartile range [IQR], 60-66), 86% were male, and median CD4+ T-cell count was 650/µL (IQR, 423-941). The mean S1-specific antibody level increased from 35 binding antibody units (BAU)/mL (95% confidence interval [CI], 24-46) to 4317 BAU/mL (95% CI, 3275-5360) (P < .0001). Of all participants, 97% showed an adequate response and the 45 antibody-negative participants all seroconverted. A significant increase in the proportion of PWH with ancestral S-specific CD4+ T cells (P = .04) and S-specific B cells (P = .02) was observed. CONCLUSIONS: An additional mRNA-1273 vaccination induced a robust serological response in 97% of PWH with a hyporesponse after primary vaccination. Clinical Trials Registration. EUCTR2021-001054-57-N.

Global Differences in the Management of Staphylococcus aureus Bacteremia: No International Standard of Care.

BACKGROUND: Despite being the leading cause of mortality from bloodstream infections worldwide, little is known about regional variation in treatment practices for Staphylococcus aureus bacteremia (SAB). The aim of this study was to identify global variation in management, diagnostics, and definitions of SAB. METHODS: During a 20-day period in 2022, physicians throughout the world were surveyed on SAB treatment practices. The survey was distributed through listservs, e-mails, and social media. RESULTS: In total, 2031 physicians from 71 different countries on 6 continents (North America [701, 35%], Europe [573, 28%], Asia [409, 20%], Oceania [182, 9%], South America [124, 6%], and Africa [42, 2%]) completed the survey. Management-based responses differed significantly by continent for preferred treatment of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) bacteremia, use of adjunctive rifampin for prosthetic material infection, and use of oral antibiotics (P < .01 for all comparisons). The 18F-FDG PET/CT scans were most commonly used in Europe (94%) and least frequently used in Africa (13%) and North America (51%; P < .01). Although most respondents defined persistent SAB as 3-4 days of positive blood cultures, responses ranged from 2 days in 31% of European respondents to 7 days in 38% of Asian respondents (P < .01). CONCLUSIONS: Large practice variations for SAB exist throughout the world, reflecting the paucity of high-quality data and the absence of an international standard of care for the management of SAB.

Correction: Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV in the Netherlands: A nationwide prospective cohort study.

[This corrects the article DOI: 10.1371/journal.pmed.1003979.].

Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV in the Netherlands: A nationwide prospective cohort study.

BACKGROUND: Vaccines can be less immunogenic in people living with HIV (PLWH), but for SARS-CoV-2 vaccinations this is unknown. In this study we set out to investigate, for the vaccines currently approved in the Netherlands, the immunogenicity and reactogenicity of SARS-CoV-2 vaccinations in PLWH. METHODS AND FINDINGS: We conducted a prospective cohort study to examine the immunogenicity of BNT162b2, mRNA-1273, ChAdOx1-S, and Ad26.COV2.S vaccines in adult PLWH without prior COVID-19, and compared to HIV-negative controls. The primary endpoint was the anti-spike SARS-CoV-2 IgG response after mRNA vaccination. Secondary endpoints included the serological response after vector vaccination, anti-SARS-CoV-2 T-cell response, and reactogenicity. Between 14 February and 7 September 2021, 1,154 PLWH (median age 53 [IQR 44-60] years, 85.5% male) and 440 controls (median age 43 [IQR 33-53] years, 28.6% male) were included in the final analysis. Of the PLWH, 884 received BNT162b2, 100 received mRNA-1273, 150 received ChAdOx1-S, and 20 received Ad26.COV2.S. In the group of PLWH, 99% were on antiretroviral therapy, 97.7% were virally suppressed, and the median CD4+ T-cell count was 710 cells/µL (IQR 520-913). Of the controls, 247 received mRNA-1273, 94 received BNT162b2, 26 received ChAdOx1-S, and 73 received Ad26.COV2.S. After mRNA vaccination, geometric mean antibody concentration was 1,418 BAU/mL in PLWH (95% CI 1322-1523), and after adjustment for age, sex, and vaccine type, HIV status remained associated with a decreased response (0.607, 95% CI 0.508-0.725, p < 0.001). All controls receiving an mRNA vaccine had an adequate response, defined as >300 BAU/mL, whilst in PLWH this response rate was 93.6%. In PLWH vaccinated with mRNA-based vaccines, higher antibody responses were predicted by CD4+ T-cell count 250-500 cells/µL (2.845, 95% CI 1.876-4.314, p < 0.001) or >500 cells/µL (2.936, 95% CI 1.961-4.394, p < 0.001), whilst a viral load > 50 copies/mL was associated with a reduced response (0.454, 95% CI 0.286-0.720, p = 0.001). Increased IFN-γ, CD4+ T-cell, and CD8+ T-cell responses were observed after stimulation with SARS-CoV-2 spike peptides in ELISpot and activation-induced marker assays, comparable to controls. Reactogenicity was generally mild, without vaccine-related serious adverse events. Due to the control of vaccine provision by the Dutch National Institute for Public Health and the Environment, there were some differences between vaccine groups in the age, sex, and CD4+ T-cell counts of recipients. CONCLUSIONS: After vaccination with BNT162b2 or mRNA-1273, anti-spike SARS-CoV-2 antibody levels were reduced in PLWH compared to HIV-negative controls. To reach and maintain the same serological responses as HIV-negative controls, additional vaccinations are probably required. TRIAL REGISTRATION: The trial was registered in the Netherlands Trial Register (NL9214). https://www.trialregister.nl/trial/9214.

Hypokalaemia in patients treated with intravenous flucloxacillin: Incidence and risk factors.

INTRODUCTION: Hypokalaemia is a potentially life-threatening adverse event of flucloxacillin with unknown incidence. The risk of flucloxacillin-induced hypokalaemia has recently been suggested to be increased among females compared to males. The aim of this study is to describe the incidence and to determine the influence of sex and other risk factors on flucloxacillin-induced hypokalaemia. METHODS: A retrospective single-centre cohort study was performed. Patients treated with intravenous flucloxacillin for >24 hours between January 2017 and October 2020, a baseline potassium level of ≥3.5 mmol/L and potassium measurement during treatment were included. The primary endpoint was incidence of hypokalaemia defined as the percentage of patients with a potassium measurement <3.5 mmol/L during flucloxacillin treatment. Logistic regression modelling was used to establish risk factors for hypokalaemia. RESULTS: A total of 835 patients were included, 58.2% male and median age 71.0 years (interquartile range 61.0-81.0). The incidence of hypokalaemia was 23.7% (28.4% in females vs 20.4% in males). A dose-dependent relation between sex and the incidence of hypokalaemia was found. The risk of hypokalaemia was 4.41 (95% confidence interval 1.47-13.24) times higher in females compared to males when receiving a flucloxacillin dose of >8 g/24 h. No sex differences were found for lower daily doses. Other risk factors for hypokalaemia were older age, concomitant antibiotic use, lower bodyweight, lower baseline plasma potassium concentration and longer treatment duration. CONCLUSION: Hypokalaemia is a frequent complication in patients treated with intravenous flucloxacillin. Females receiving >8 g intravenous flucloxacillin per day are more prone to develop hypokalaemia compared to males.

Acute kidney injury in Staphylococcus aureus bacteremia.

Acute kidney injury (AKI) is a frequent complication in patients with Staphylococcus aureus bacteremia (SAB), with a significant impact on patient management and outcome. This study aimed to provide insight in the proportion of patients with SAB that develop AKI, the risk factors for developing AKI in this population, and its reversibility. In this retrospective, multicenter cohort study, adult patients with SAB were eligible for inclusion. Patient characteristics, clinical variables, and laboratory results were retrieved from the electronic patient files. Primary outcome was development of AKI, defined as 1.5 times baseline creatinine. Secondary outcomes were reversibility of AKI and risk factors for AKI. A total of 315 patients with SAB were included, of whom 115/315 (37%) developed acute kidney injury. In 68/115 (59%), the AKI was reversible. If kidney function recovered, this occurred within 7 days in 56/68 (82%) of patients. In multivariable logistic regression analyses, independent risk factors for AKI were as follows: complicated SAB, use of diuretics, and hemodynamic instability. Development of AKI was associated with 30-day mortality (OR 3.9; CI 2.2-6.9; p < 0.01). Acute kidney injury is a frequent complication in patients with Staphylococcus aureus bacteremia. Considering the irreversibility in a relevant proportion of patients, future research into the underlying pathophysiology and potential interventions is warranted.

Diagnostic yield of bacteriological tests and predictors of severe outcome in adult patients with COVID-19 presenting to the emergency department.

BACKGROUND: Guidelines recommend maximal efforts to obtain blood and sputum cultures in patients with COVID-19, as bacterial coinfection is associated with worse outcomes. The aim of this study was to evaluate the yield of bacteriological tests, including blood and sputum cultures, and the association of multiple biomarkers and the Pneumonia Severity Index (PSI) with clinical and microbiological outcomes in patients with COVID-19 presenting to the emergency department (ED). METHODS: This is a substudy of a large observational cohort study (PredictED study). The PredictED included adult patients from whom a blood culture was drawn at the ED of Haga Teaching Hospital, The Netherlands. For this substudy, all patients who tested positive for SARS-CoV-2 by PCR in March and April 2020 were included. The primary outcome was the incidence of bacterial coinfection. We used logistic regression analysis for associations of procalcitonin, C reactive protein (CRP), ferritin, lymphocyte count and PSI score with a severe disease course, defined as intensive care unit admission and/or 30-day mortality. The area under the receiver operating characteristics curve (AUC) quantified the discriminatory performance. RESULTS: We included 142 SARS-CoV-2 positive patients. On presentation, the median duration of symptoms was 8 days. 41 (29%) patients had a severe disease course and 24 (17%) died within 30 days. The incidence of bacterial coinfection was 2/142 (1.4%). None of the blood cultures showed pathogen growth while 6.3% was contaminated. The AUCs for predicting severe disease were 0.76 (95% CI 0.68 to 0.84), 0.70 (0.61 to 0.79), 0.62 (0.51 to 0.74), 0.62 (0.51 to 0.72) and 0.72 (0.63 to 0.81) for procalcitonin, CRP, ferritin, lymphocyte count and PSI score, respectively. CONCLUSION: Blood cultures appear to have limited value while procalcitonin and the PSI appear to be promising tools in helping physicians identify patients at risk for severe disease course in COVID-19 at presentation to the ED.

Early differentiation between uncomplicated and complicated Staphylococcus aureus bacteraemia: Potential value and limitations of a clinical risk score.

OBJECTIVE: A cornerstone in the management of Staphylococcus aureus bacteraemia (SAB) is the differentiation between a complicated and an uncomplicated SAB course. The ability to early and accurately identify patients with - and without - complicated bacteraemia may optimise the utility of diagnostics and prevent unnecessary prolonged antibiotic therapy. METHODS: Development and validation of a prediction score in SAB using demographic, clinical, and laboratory data from two independent Dutch cohorts; estimating the risk of complicated disease at the time of the first positive blood culture. Models were developed using logistic regression and evaluated by c-statistics, ie area under the ROC-curve, and negative predictive values (NPV). RESULTS: The development- and validation cohorts included 150 and 183 patients, respectively. The most optimal prediction model included: mean arterial pressure, signs of metastatic infection on physical examination, leucocyte count, urea level and time to positivity of blood cultures (c-statistic 0.82, 95% CI 0.74-0.89). In the validation cohort, the c-statistic of the prediction score was 0,77 (95% CI 0.69-0.84). The NPV for complicated disease for patients with a score of ≤2 was 0.83 (95% CI 0.68-0.92), with a negative likelihood ratio of 0.14 (95% CI 0.06-0.31). CONCLUSION: The early SAB risk score helps to identify patients with high probability of uncomplicated SAB. However, the risk score's lacked absolute discriminative power to guide decisions on the management of all patients with SAB on its own. The heterogenicity of the disease and inconsistency in definitions of complicated SAB are important challenges in the development of clinical rules to guide the management of SAB.

Postoperative pro-adrenomedullin levels predict mortality in thoracic surgery patients: comparison with Acute Physiology and Chronic Health Evaluation IV Score*.

OBJECTIVES: Risk assessment in ICU patients using commonly used prognostic models may be influenced using different data definitions and by errors in data collection. We investigated whether a set of biomarkers (procalcitonin, MR-pro-adrenomedullin, CT-pro-endothelin-1, CT-pro-arginine vasopressin, and MR-pro-atrial natriuretic peptide), alone or as a panel, could be useful in postoperative risk assessment for hospital mortality in comparison with the Acute Physiology and Chronic Health Evaluation IV score. DESIGN: In a prospective observational cohort study, we analyzed 800 consecutive patients undergoing elective cardiac surgery. We assessed biomarker levels on admission to the ICU and every 6 hours thereafter for 24 hours. For every postoperative time point and for every biomarker, we determined the predictive value for hospital mortality and made a comparison with the Acute Physiology and Chronic Health Evaluation IV score. SETTING: Intensive care of an academic referral hospital. PATIENTS: A total of 800 consecutive patients undergoing elective cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: MR-pro-adrenomedullin is a good predictor of mortality (c-statistic at time point 6 hr after admission to the ICU, 0.940; 95% CI, 0.918-0.956) and performed better than the Acute Physiology and Chronic Health Evaluation IV score (c-statistic, 0.842; 95% CI, 0.811-0.868). The c-statistic did not change significantly on the time points 6, 12, and 18 hours after admission. Using a cutoff value for proadrenomedullin taken 6 hours after admission on ICU (time point 2) of 3.2 nmol/L sensitivity was 81.8% and specificity 93.9%, the positive likelihood ratio was 13.3, positive predictive value was 31.0%, and negative predictive value was 99.4%. Patients with a MR-pro-adrenomedullin above this cutoff level had an odds ratio of 68.9 (95% CI, 22.2-213.1) for not surviving their hospital stay. The other biomarkers had less predictive power. CONCLUSIONS: In elective cardiac surgery, MR-pro-adrenomedullin measured between 6 and 18 hours after admission to the ICU is a better predictor of hospital mortality in comparison with the Acute Physiology and Chronic Health Evaluation IV score.

[Soft tissue infections]. / Wekedeleninfecties.

Soft tissue infections are common, but can be difficult to diagnose and manage. In this article, the classification of soft tissue infections is discussed, as well as the diagnostic possibilities and treatment options. Furthermore, the management of recurrent infections and necrotizing soft tissue infections are discussed. The added value of compression therapy is reviewed in more detail.

Eradication of community-onset Methicillin-resistant Staphylococcus aureus carriage: a narrative review.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) colonization increases infection risk in both patients and healthy individuals. Decolonization therapy has been proven to reduce S. aureus infections, but data on the effectiveness of individual decolonization strategies in community-onset MRSA carriage are scarce. OBJECTIVES: The aim of this narrative review was to summarize the evidence on strategies for the elimination of MRSA colonization in community-onset MRSA carriers. SOURCES: PubMed database was searched for studies on MRSA eradication, from inception to July 2023. CONTENT: Topical therapy is proven to be effective in nasal-only carriage and in temporary load reduction. Mupirocin nasal ointment in combination with chlorhexidine body wash is highly effective in nasal-only MRSA carriers in the community as well. In patients with extra-nasal colonization, addition of orally administered antibiotics likely increases success rates compared with topical therapy alone. Studies on systemic treatment of extra-nasal MRSA decolonization are subject to a high heterogeneity of antimicrobial agents, treatment duration, and control groups. The majority of evidence supports the use of a combination of topical therapy with rifampin and another antimicrobial agent. Decolonization treatment with probiotics is a promising novel non-antibiotic strategy. However, achieving long-term decolonization is more likely in countries with low MRSA prevalence, given the risk of recolonization in a context of high MRSA prevalence. IMPLICATIONS: The decision to pursue community-onset MRSA eradication treatment in the individual patient should be based on the combination of the treatment objective (short-term bacterial load reduction in health care settings vs. long-term eradication in community settings), and the likelihood of successful decolonization. The latter is influenced by both individual risk factors for treatment failure, and the risk of recolonization. The addition of a combination of systemic antibiotics is rational for extra-nasal long-term decolonization. To determine the most effective systemic antimicrobial agents in MRSA decolonization, more research is needed.

[Intoxications with synthetic cannabinoids]. / Intoxicaties met synthetische cannabinoïden.

Synthetic Cannabinoid Receptor Agonists (SCRAs) are a group of New Psychoactive Substances. They are used recreationally to mimic the effects of THC in cannabis. However, THC is a partial agonist of the CB1-receptor and SCRAs are full agonists. Because of this specificity and potency serious adverse events may occur among which psychological, cardiovascular, and gastro-intestinal symptoms. Because of the low incidence in the Netherlands clinical information on SCRA intoxications is limited, making diagnosis and treatment difficult. In this clinical lesson, two cases of SCRA intoxications are described followed by treatment recommendations.

[Intoxications with synthetic cannabinoids]. / Intoxicaties met synthetische cannabinoïden.

Synthetic Cannabinoid Receptor Agonists (SCRAs) are a group of New Psychoactive Substances. They are used recreationally to mimic the effects of THC in cannabis. However, THC is a partial agonist of the CB1-receptor and SCRAs are full agonists. Because of this specificity and potency serious adverse events may occur among which psychological, cardiovascular, and gastro-intestinal symptoms. Because of the low incidence in the Netherlands clinical information on SCRA intoxications is limited, making diagnosis and treatment difficult. In this clinical lesson, two cases of SCRA intoxications are described followed by treatment recommendations.

[Needle spiking, injecting people with a substance without their knowledge or consent]. / Needle spiking, het drogeren met een injectienaald.

BACKGROUND: In the Netherlands therewereseveralreports on needlespiking: people have found themselvessubjectedtosurreptitiousinjections. CASE DESCRIPTION: A 23-year-old female was seenafterbeingsurroundedby a group of men andfeltwhatshethought was a jab. She was abletoevadethegroup. Several minutes later sheexperienceddizziness, nausea andvomiting. On physical examination, a bleedingpuncturewound was seen on her upper arm withaccompanying erythema. Toxicology on bloodand urine didnot show evidenceforintoxicationotherthan alcohol which was higherthanwouldbesuspectedbythenumber of drinks thevictimreported. CONCLUSION: There is evidencethatpeople are puncturedwithneedles in busy surroundings like thenightlife. Possiblealso drugs are injected. Experiencedsymptomsbyvictims (n=19) wereheterogeneousandnotlikelyattributedtooneandthesamecausal drug. Toxicologydidnotrevealanysubstanceuntilnow.

The association of female sex with management and mortality in patients with Staphylococcus aureus bacteraemia.

OBJECTIVES: The association of biological female sex with outcome in patients with Staphylococcus aureus bacteraemia remains unresolved. The aim of this study was to determine the independent association of female sex with management and mortality in patients with S. aureus bacteraemia. METHODS: This is a post hoc analysis of prospectively collected data from the S. aureus Bacteraemia Group Prospective Cohort Study. Adult patients with monomicrobial S. aureus bacteraemia at Duke University Medical Center were enrolled from 1994 to 2020. Univariable and multivariable Cox regression analyses were performed to assess differences in management and mortality between females and males. RESULTS: Among 3384 patients with S. aureus bacteraemia, 1431 (42%) were women. Women were, as compared with men, more often Black (581/1431 [41%] vs. 620/1953 [32%], p < 0.001), haemodialysis dependent (309/1424 [22%] vs. 334/1940 [17%], p 0.001) and more likely to be infected with methicillin-resistant S. aureus (MRSA) (697/1410 [49%] MRSA in women vs. 840/1925 [44%] MRSA in men, p 0.001). Women received shorter durations of antimicrobial treatment (median 24 [interquartile range 14-42] vs. 28 [interquartile range 14-45] days, p 0.005), and were less likely to undergo transesophageal echocardiography as compared with men (495/1430 [35%] vs. 802/1952 [41%], p < 0.001). Despite these differences, female sex was not associated with 90-day mortality in either univariable (388/1431 [27%] in women vs. 491/1953 [25%] in men, p 0.204) or multivariable analysis (adjusted hazard ratio for women 0.98 [95% CI, 0.85-1.13]). DISCUSSION: Despite significant differences in patient characteristics, disease characteristics, and management, women and men with S. aureus bacteraemia have a similar mortality risk.

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.

Analysis of Variation Between Diagnosis at Admission vs Discharge and Clinical Outcomes Among Adults With Possible Bacteremia.

Importance: Misdiagnosis of infection is among the most commonly made diagnostic errors and is associated with increased morbidity and mortality. Little is known about how often misdiagnosed site of infection occurs and its association with clinical outcomes. Objectives: To evaluate the discrepancy between admission and discharge site of infection diagnoses among patients with suspected bacteremia, to explore factors associated with discrepant diagnoses, and to evaluate the association with clinical outcomes. Design, Setting, and Participants: This cohort study used electronic records of 1477 adult patients who were admitted to the hospital for suspected bacteremia from April 1, 2019, to May 31, 2020, and who had blood cultures taken at the emergency department at Haga Teaching Hospital, The Hague, the Netherlands. Suspected infection sites were classified into 8 categories at admission and discharge. Misdiagnosed site was defined as a discrepancy between the suspected site of infection at admission and at discharge. Main Outcomes and Measures: Clinical outcomes were 30-day mortality, intensive care unit admission, length of hospital stay, and antibiotic use, analyzed with logistic and linear regression. Risk factors for misdiagnosed site were determined using regression analysis. Results: A total of 1477 patients (820 [55.5%] male; median [IQR] age, 68 [56-78] years) were analyzed. The rate of misdiagnosed site of infection was 11.6% (171 of 1477); 3.1% of all patients (46 of 1477) ultimately had no infection. No association was found between misdiagnosis and 30-day mortality (adjusted odds ratio [aOR], 0.8; 95% CI, 0.3-1.9; P = .60), intensive care unit admission (aOR, 1.3; 95% CI, 0.6-3.0; P = .54), and hospital length of stay (adjusted increase of stay, 15.5%; 95% CI, -3.1% to 37.7%; P = .11). Misdiagnosed site was associated with receiving broad-spectrum antibiotics (aOR, 4.0; 95% CI, 1.8-8.8; P < .001). Older age, dementia, a positive urine sediment test result without urinary symptoms, and suspicion of an intravascular, central nervous system, or bone and joint infection were risk factors for misdiagnosed site of infection. Conclusions and Relevance: In this cohort study, misdiagnosed site of infection occurred in 1 of 9 patients and was not associated with worse short-term clinical outcomes. Clinicians should be aware of risk factors associated with misdiagnosed site of infection and potential inappropriate antibiotic use.

Exploring the Barriers in the Uptake of the Dutch MRSA 'Search and Destroy' Policy Using the Cascade of Care Approach.

The Dutch 'search and destroy' policy consists of screening patients with an increased risk of methicillin-resistant Staphylococcus aureus (MRSA) carriership and subsequent decolonization treatment when carriership is found. Decolonization therapy of individual MRSA carriers is effective. However, the effectiveness of the national 'search and destroy' policy is dependent on the entire cascade of care, including identification, referral, and subsequent treatment initiation in MRSA carriers. The aim of this study was to evaluate the leakages in the cascade of MRSA decolonization care. We assessed familiarity with the 'search and destroy' policy and the barriers in the uptake of MRSA eradication care using a questionnaire among 114 Dutch general practitioners. The main reasons for treatment were planned hospital visits, occupational reasons, and infections. The main reasons for refraining from eradication treatment were unfamiliarity with the 'search and destroy' policy and the assumption that MRSA carriership is often self-limiting. To optimize the continuity of the cascade of care, interventions should be aimed at supporting general practitioners and facilitating treatment and referral.

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.