Mental health and its consequences in people living with HIV: A network approach.

OBJECTIVES: Psychiatric symptoms occur frequently in people living with human immunodeficiency virus (PLWH), which may affect quality of life, sexual risk behavior, and adherence to antiretroviral therapy (ART). Data from large cohorts are limited, and symptoms are often analyzed in isolation. Therefore, we applied a network analysis to assess the interrelatedness of mental health indicators in a large cohort of PLWH. METHODS: We included 1615 PLWH on ART. Participants reported on the severity of depression, anxiety, impulsivity, substance use, quality of life, sexual risk behavior, and ART adherence. An Ising network model was constructed to analyze interrelations between mental health indicators and connections with clinical consequences. RESULTS: Our network analysis revealed that symptoms of depression, anxiety, and indicators of impulsivity were interrelated. Substance use was prevalent and strongly connected with sexual risk behavior. Quality of life was most strongly connected with symptoms of depression. Unexpectedly, ART adherence did not display connections with any of the mental health indicators. CONCLUSION: In PLWH, the interrelatedness between symptoms of depression and anxiety and indicators of impulsivity is high. Mainly, depressive symptoms seem to impact quality of life, which warrants attention for depression in PLWH. We did not observe evidence for the common assumption that patients suffering from psychiatric symptoms are less adherent to HIV treatment.

Liver Steatosis is Prevalent in Lean People With HIV and Associated With Exposure to Antiretroviral Treatment-A Cross-sectional Study.

Background: Steatotic liver disease is suggested to have a higher prevalence and severity in people with HIV (PHIV), including in those with a normal body mass index (BMI). In this study, we used data from the 2000HIV cohort to (1) assess the prevalence of liver steatosis and fibrosis in lean versus overweight/obese PHIV and (2) assess associations in these subgroups between steatosis and fibrosis with traditional risk factors and HIV-specific characteristics. Methods: The 2000HIV study cohort comprises 1895 virally suppressed PHIV that were included between 2019 and 2021 in 4 HIV treatment centers in the Netherlands. The majority (58.5%) underwent vibration-controlled transient elastography for the assessment of liver steatosis and fibrosis. The prevalence of steatosis (controlled attenuation parameter ≥263 dB/m) and fibrosis (liver stiffness measurement ≥7.0 kPa) was estimated. Multiple factors including HIV characteristics and antiretroviral drugs were tested in a logistic regression model for association with steatosis and fibrosis. Analyses were performed separately for lean (Asian descent: BMI < 23 kg/m2, other descent: BMI < 25 kg/m2) and overweight/obese (other BMI) participants. Results: Of 1050 PHIV including 505 lean and 545 overweight/obese PHIV, liver steatosis was observed in 37.7% of the overall study population, 19.7% of lean, and 54% of overweight/obese PHIV, whereas fibrosis was observed in 9.0% of the overall study population, 5.9% of lean, and 12.0% of overweight/obese PHIV.All associations with fibrosis and most associations with steatosis concerned metabolic factors such as type 2 diabetes mellitus (overall population: adjusted odds ratio [aOR] for steatosis: 2.3 [1.21-4.4], P = .011; aOR for fibrosis: 3.7 [1.82-7.53], P < .001). Furthermore, in lean PLHIV, liver steatosis was associated with CD4 and CD8 counts at enrollment, dual therapy, and history of treatment with raltegravir (aOR: 3.6 [1.53-8.47], P = .003), stavudine (aOR: 3.73 [1.69-8.2], P = .001), and indinavir (aOR: 3.86 [1.59-9.37], P = .003). These associations were not observed in overweight/obese PHIV. Conclusions: Liver steatosis was highly prevalent, affecting approximately one-fifth of lean PHIV and half of overweight/obese PHIV. Fibrosis was observed in a minority. Both steatosis and fibrosis were associated with traditional metabolic risk factors. In addition, (prior) exposure to specific antiretroviral drugs was associated liver steatosis in lean, but not in overweight/obese PHIV. Implementing increased screening protocols could enhance the identification of steatotic liver disease in lean PHIV.

Low-Risk Staphylococcus aureus Bacteremia Patients Do Not Require Routine Diagnostic Imaging: A Multicenter, Retrospective, Cohort Study.

BACKGROUND: Stratification to categorize patients with Staphylococcus aureus bacteremia (SAB) as low or high risk for metastatic infection may direct diagnostic evaluation and enable personalized management. We investigated the frequency of metastatic infections in low-risk SAB patients, their clinical relevance, and whether omission of routine imaging is associated with worse outcomes. METHODS: We performed a retrospective cohort study at 7 Dutch hospitals among adult patients with low-risk SAB, defined as hospital-acquired infection without treatment delay, absence of prosthetic material, short duration of bacteremia, and rapid defervescence. Primary outcome was the proportion of patients whose treatment plan changed due to detected metastatic infections, as evaluated by both actual therapy administered and by linking a adjudicated diagnosis to guideline-recommended treatment. Secondary outcomes were 90-day relapse-free survival and factors associated with the performance of diagnostic imaging. RESULTS: Of 377 patients included, 298 (79%) underwent diagnostic imaging. In 15 of these 298 patients (5.0%), imaging findings during patient admission had been interpreted as metastatic infections that should extend treatment. Using the final adjudicated diagnosis, 4 patients (1.3%) had clinically relevant metastatic infection. In a multilevel multivariable logistic regression analysis, 90-day relapse-free survival was similar between patients without imaging and those who underwent imaging (81.0% versus 83.6%; adjusted odds ratio, 0.749; 95% confidence interval, .373-1.504). CONCLUSIONS: Our study advocates risk stratification for the management of SAB patients. Prerequisites are follow-up blood cultures, bedside infectious diseases consultation, and a critical review of disease evolution. Using this approach, routine imaging could be omitted in low-risk patients.

Traditional Cardiovascular Risk Factors Are Stronger Related to Carotid Intima-Media Thickness Than to Presence of Carotid Plaques in People Living With HIV.

Background Cardiovascular disease is a major cause of morbidity and mortality in people living with HIV, who are at higher risk than the general population. We assessed, in a large cohort of people living with HIV, which cardiovascular, HIV-specific, and lipoproteomic markers were associated with carotid intima-media thickness (cIMT) and carotid plaque presence. We also studied guideline adherence on lipid-lowering medication in individuals with high and very high risk for cardiovascular disease. Methods and Results In 1814 individuals with a median (interquartile range) age of 53 (44-60) years, we found a carotid plaque in 909 (50.1%) and a median (interquartile range) intima-media thickness of 0.66 (0.57-0.76) mm. Ultrasonography was used for the assessment of cIMT and plaque presence. Univariable and multivariable regression models were used for associations with cIMT and presence of plaques. Age, Black race, body mass index, type 2 diabetes, and smoking (pack years) were all positively associated with higher cIMT. Levels of high-density lipoprotein cholesterol, specifically medium and large high-density lipoprotein subclasses, were negatively associated with higher cIMT. Only age and prior myocardial infarction were positively related to the presence of a carotid plaque. Lipid-lowering treatment was prescribed in one-third of people living with HIV, who are at high and very high risk for cardiovascular disease. Conclusions Traditional cardiovascular risk factors were significantly associated with higher cIMT but not with carotid plaques, except for age. HIV-specific factors were not associated with both ultrasound measurements. Future studies are needed to elucidate which factors contribute to plaque formation. Improvement of guideline adherence on prescription of lipid-lowering treatment in high- and very high-risk patients for cardiovascular disease is recommended. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03994835.

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 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.

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.

Survey of delivery of parenteral antimicrobials in non-inpatient settings across Europe.

Delivery of parenteral antimicrobials in non-inpatient settings (DPANS) may be through a dedicated outpatient parenteral antimicrobial therapy (OPAT) service, co-ordinated by hospital- or community-based specialised teams, or via an infusion service involving community-based health professionals (nurses, general practitioners) without centralised hospital oversight, or through ad hoc arrangements. DPANS varies among countries. Our objective was to describe how DPANS is organised at a national level in European countries. A survey (65-item self-administered questionnaire) was conducted from February-June 2019 among infection specialists in 34 European countries on behalf of the ESCMID Study Group for Antimicrobial Stewardship (ESGAP) and the British Society for Antimicrobial Chemotherapy (BSAC) OPAT initiative. Most countries (28/34; 82.4%) participated in the survey. DPANS was available in almost all (27/28; 96.4%) responding countries. DPANS was predominantly provided either via specialised OPAT services (17/28; 60.7%) or via infusion services (16/28; 57.1%), with 11 countries (39.3%) providing both services. A formal OPAT team structure with specifically trained staff was reported in only six countries (6/17; 35.3%). Some countries (4/28; 14.3%) had no structured services but practiced DPANS via ad hoc arrangements. The costs of all stages of the process were covered for patients managed by specialised OPAT/infusion services, either completely, partially or for specific patient groups in the majority (20/28; 71.4%) of countries. The main barriers to implement OPAT/infusion services were lack of organisational structure or guidelines. In conclusion, DPANS with respect to availability and organisation is highly heterogeneous in Europe. National/European guidelines may help improve and standardise DPANS.

The 2000HIV study: Design, multi-omics methods and participant characteristics.

Background: Even during long-term combination antiretroviral therapy (cART), people living with HIV (PLHIV) have a dysregulated immune system, characterized by persistent immune activation, accelerated immune ageing and increased risk of non-AIDS comorbidities. A multi-omics approach is applied to a large cohort of PLHIV to understand pathways underlying these dysregulations in order to identify new biomarkers and novel genetically validated therapeutic drugs targets. Methods: The 2000HIV study is a prospective longitudinal cohort study of PLHIV on cART. In addition, untreated HIV spontaneous controllers were recruited. In-depth multi-omics characterization will be performed, including genomics, epigenomics, transcriptomics, proteomics, metabolomics and metagenomics, functional immunological assays and extensive immunophenotyping. Furthermore, the latent viral reservoir will be assessed through cell associated HIV-1 RNA and DNA, and full-length individual proviral sequencing on a subset. Clinical measurements include an ECG, carotid intima-media thickness and plaque measurement, hepatic steatosis and fibrosis measurement as well as psychological symptoms and recreational drug questionnaires. Additionally, considering the developing pandemic, COVID-19 history and vaccination was recorded. Participants return for a two-year follow-up visit. The 2000HIV study consists of a discovery and validation cohort collected at separate sites to immediately validate any finding in an independent cohort. Results: Overall, 1895 PLHIV from four sites were included for analysis, 1559 in the discovery and 336 in the validation cohort. The study population was representative of a Western European HIV population, including 288 (15.2%) cis-women, 463 (24.4%) non-whites, and 1360 (71.8%) MSM (Men who have Sex with Men). Extreme phenotypes included 114 spontaneous controllers, 81 rapid progressors and 162 immunological non-responders. According to the Framingham score 321 (16.9%) had a cardiovascular risk of >20% in the next 10 years. COVID-19 infection was documented in 234 (12.3%) participants and 474 (25.0%) individuals had received a COVID-19 vaccine. Conclusion: The 2000HIV study established a cohort of 1895 PLHIV that employs multi-omics to discover new biological pathways and biomarkers to unravel non-AIDS comorbidities, extreme phenotypes and the latent viral reservoir that impact the health of PLHIV. The ultimate goal is to contribute to a more personalized approach to the best standard of care and a potential cure for PLHIV.

Individualizing the use of [18F]FDG-PET/CT in patients with complicated Staphylococcus aureus bacteremia: experiences from a tertiary care center.

PURPOSE: [18F]FDG-PET/CT scanning can help detect metastatic infectious foci and reduce mortality in patients with Staphylococcus aureus bacteremia (SAB), but it is unknown if patients with SAB and an indication for prolonged treatment because of possible endovascular, orthopaedic implant, or other metastatic infection still need [18F]FDG-PET/CT. METHODS: In a retrospective single-center cohort study, we included all consecutive adult patients with SAB between 2013 and 2020 if an [18F]FDG-PET/CT scan was performed and antibiotic treatment was planned for ≥ 6 weeks prior to [18F]FDG-PET/CT. We aimed to identify patients for whom treatment was adjusted due to the results of [18F]FDG-PET/CT, and assessed concordance of [18F]FDG-PET/CT and clinical diagnosis for infected prosthetic material. RESULTS: Among 132 patients included, the original treatment plan was changed after [18F]FDG-PET/CT in 22 patients (16.7%), in the majority (n = 20) due to diagnosing or rejecting endovascular (graft) infection. Antibiotic treatment modifications were shortening in 2, iv-oral switch in 3, extension in 13, and addition of rifampicin in 4 patients. Ninety additional metastatic foci based on [18F]FDG-PET/CT results were found in 69/132 patients (52.3%). [18F]FDG-PET/CT suggested vascular graft infection in 7/14 patients who lacked clinical signs of infection, but showed no infection of prosthetic joints or osteosynthesis material in eight patients who lacked clinical signs of such an infection. CONCLUSION: [18F]FDG-PET/CT can help refine treatment for SAB in patients with clinically suspected endovascular infection or vascular grafts, even if 6 weeks treatment is already indicated, but can be safely omitted in other patients who are clinically stable.

The diagnostic value of [18F]FDG-PET/CT in detecting septic thrombosis in patients with central venous catheter-related Staphylococcus aureus bacteremia.

PURPOSE: Septic thrombosis often complicates Staphylococcus aureus bacteremia (SAB) in patients with a central venous catheter. Currently there is no reference standard for diagnosis. We describe the diagnostic value of [18F]FDG-PET/CT imaging in a patient cohort and the potential contribution of quantitative measurements in detecting septic thrombosis. METHODS: We selected patients with catheter-related SAB from our institutional database (2013-2020). The contribution of [18F]FDG-PET/CT on clinical diagnosis of septic thrombosis was evaluated. Standardized Uptake Values (SUV) were measured and compared with a composite reference standard (clinical signs, initial [18F]FDG-PET/CT result, Multidisciplinary Team (MDT) meeting outcome) to identify a cut-off value for detecting septic thrombosis. RESULTS: We identified 93 patients with a catheter-related SAB. Quantitative measurements were possible for 43/56 patients in whom a [18F]FDG-PET/CT scan was performed. Septic thrombosis was clinically diagnosed in 30% (13/43) of the cases. In 85% of these cases, significant [18F]FDG-PET/CT uptake at the site of the thrombus was the deciding factor for diagnosis of septic thrombosis during the MDT meeting. All mean SUV's of thrombotic lesions were higher in patients with clinically proven septic thrombosis compared to patients in whom this diagnosis was rejected (p < 0.001). A SUVpeak thrombus/SUVmean blood ratio of 1.6 (AUC-ROC value 0.982) as cut-off to differentiate between septic thrombosis and non-septic thrombosis had a sensitivity of 92% (95% CI 64-100) and specificity of 89% (95% CI 65-99). An algorithm was designed to guide diagnosis of septic thrombosis. CONCLUSION: Quantitative [18F]FDG-PET/CT-derived parameters seem helpful to differentiate between septic and non-septic thrombosis in patients with catheter-related SAB.

Test, trace, isolate: evidence for declining SARS-CoV-2 PCR sensitivity in a clinical cohort.

Real-time reverse transcription-polymerase chain reaction (RT-PCR) on upper respiratory tract (URT) samples is the primary method to diagnose SARS-CoV-2 infections and guide public health measures, with a supportive role for serology. We reinforce previous findings on limited sensitivity of PCR testing, and solidify this fact by statistically utilizing a firm basis of multiple tests per individual. We integrate stratifications with respect to several patient characteristics such as severity of disease and time since onset of symptoms. Bayesian statistical modelling was used to retrospectively determine the sensitivity of RT-PCR using SARS-CoV-2 serology in 644 COVID-19-suspected patients with varying degrees of disease severity and duration. The sensitivity of RT-PCR ranged between 80% - 95%; increasing with disease severity, it decreased rapidly over time in mild COVID-19 cases. Negative URT RT-PCR results should be interpreted in the context of clinical characteristics, especially with regard to containment of viral transmission based on 'test, trace and isolate'. Keywords: SARS-CoV-2, RT-PCR, serology, sensitivity, public health.

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.

Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

Intravenous to Oral Switch in Complicated Staphylococcus aureus Bacteremia Without Endovascular Infection: A Retrospective Single-Center Cohort Study.

In this retrospective cohort study, selected patients with disseminated Staphylococcus aureus bacteremia, but without endovascular infection on echocardiography and 18F-FDG-PET/CT, were free of relapse after IV-oral switch. Mortality was low and similar to patients who received prolonged intravenous treatment. IV-oral switch was associated with a shorter length of hospital stay.

A novel haemocytometric COVID-19 prognostic score developed and validated in an observational multicentre European hospital-based study.

COVID-19 induces haemocytometric changes. Complete blood count changes, including new cell activation parameters, from 982 confirmed COVID-19 adult patients from 11 European hospitals were retrospectively analysed for distinctive patterns based on age, gender, clinical severity, symptom duration, and hospital days. The observed haemocytometric patterns formed the basis to develop a multi-haemocytometric-parameter prognostic score to predict, during the first three days after presentation, which patients will recover without ventilation or deteriorate within a two-week timeframe, needing intensive care or with fatal outcome. The prognostic score, with ROC curve AUC at baseline of 0.753 (95% CI 0.723-0.781) increasing to 0.875 (95% CI 0.806-0.926) on day 3, was superior to any individual parameter at distinguishing between clinical severity. Findings were confirmed in a validation cohort. Aim is that the score and haemocytometry results are simultaneously provided by analyser software, enabling wide applicability of the score as haemocytometry is commonly requested in COVID-19 patients.

Clinical Characteristics and Outcomes of S. Aureus Bacteremia in Patients Receiving Total Parenteral Nutrition.

Background: Patients on total parenteral nutrition (TPN) are at risk of developing central line-associated infections. Specifically, Staphylococcus aureus bacteremia (SAB) is feared for its high complication rates. This prospective cohort study compares characteristics, clinical course and outcome of SAB in patients with and without TPN support. Methods: Clinical and microbiological data from all patients with positive blood cultures for S. aureus from two facilities, including our referral center for TPN support, were retrieved (period 2013-2020). Primary outcome was overall mortality, and included survival analysis using a multivariate Cox regression model. Secondary outcomes comprised a comparison of clinical characteristics and outcomes between both patient groups and analysis of factors associated with complicated outcome (e.g., endocarditis, deep-seated foci, relapse and death) in patients on TPN specifically. Results: A total of 620 SAB cases were analyzed, of which 53 cases received TPN at the moment the blood culture was taken. Patients in the TPN group were more frequently female, younger and had less comorbidity (p < 0.001). In-hospital death and overall mortality were significantly lower in TPN patients (4% vs. 18%, p = 0.004 and 10% vs. 34%, p < 0.001, respectively). Positive follow-up blood cultures, delayed onset of therapy and previous catheter problems were associated with a higher incidence of complicated SAB outcome in patients on TPN. Conclusion: Our data show that patients on TPN have a milder course of SAB with lower mortality rates compared to non-TPN SAB patients.

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

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

Quality Indicators for Appropriate Outpatient Parenteral Antimicrobial Therapy in Adults: A Systematic Review and RAND-modified Delphi Procedure.

BACKGROUND: Our aim in this study was to develop quality indicators (QIs) for outpatient parenteral antimicrobial therapy (OPAT) care that can be used as metrics for quality assessment and improvement. METHODS: A RAND-modified Delphi procedure was used to develop a set of QIs. Recommendations on appropriate OPAT care in adults were retrieved from the literature using a systematic review and translated into potential QIs. These QIs were appraised and prioritized by a multidisciplinary panel of international OPAT experts in 2 questionnaire rounds combined with a meeting between rounds. RESULTS: The procedure resulted in 33 OPAT-specific recommendations. The following QIs that describe recommended OPAT care were prioritized by the expert panel: the presence of a structured OPAT program, a formal OPAT care team, a policy on patient selection criteria, and a treatment and monitoring plan; assessment for OPAT should be performed by the OPAT team; patients and family should be informed about OPAT; there should be a mechanism in place for urgent discussion and review of emergent clinical problems, and a system in place for rapid communication; laboratory results should be delivered to physicians within 24 hours; and the OPAT team should document clinical response to antimicrobial management, document adverse events, and monitor QIs for OPAT care and make these data available. CONCLUSIONS: We systematically developed a set of 33 QIs for optimal OPAT care, of which 12 were prioritized by the expert panel. These QIs can be used to assess and improve the quality of care provided by OPAT teams.