No more government-imposed societal-level COVID-19 control measures but still significant self-experienced burden for severely immunocompromised individuals - A cross-sectional survey in the Netherlands.

Objectives: In March 2023, all societal-level COVID-19 control measures were lifted by the Dutch government. This study was performed to understand the self-experienced burden of this new phase of COVID-19 on the perspectives and behaviors of severely immunocompromised individuals. Methods: This is an observational, descriptive, cross-sectional study in The Netherlands. An online survey was completed by severely immunocompromised individuals, to capture their general well-being (score from 1 = worst to 10 = best), mental and physical health, and daily and social activities during survey conduct and retrospectively for before onset of COVID-19. The survey was open for completion from May 24th until August 7nd, 2023. Results: Of the 236 respondents, 96.6 % had been vaccinated against COVID-19 and 24.6 % were shielding to avoid COVID-19 during survey conduct. The general well-being score for all respondents was 7.5 (±1.2 SD) before onset of the COVID-19 pandemic and 6.9 (±1.6 SD) during survey conduct (P<0.001). For the shielding group (n = 58), these scores were 7.6 (±1.0 SD) and 5.7 (±1.6 SD), respectively (P<0.001). Generally, for all questions about mental and physical health and daily and social activities, there was a trend towards more negative answers during survey conduct, compared with before onset of the COVID-19 pandemic, which was more pronounced for the shielding group. Conclusions: Despite absence of government-imposed societal measures, COVID-19 avoidance still had a self-experienced burden on perspectives and behaviors of immunocompromised individuals in The Netherlands, with a significantly lower general well-being during survey conduct, compared with before onset of COVID-19.

Improving Safety and Comfort of Healthcare Workers Caring for Patients With High-Consequence Infectious Diseases in a High-Level Isolation Unit Using Innovative Approaches.

Patients with high-consequence infectious diseases (HCIDs) require high-quality care by specially trained staff in a high-level isolation unit (HLIU) that follows strict infection prevention and control (IPC) measures. Caring for patients with (suspected) HCID is challenging, mainly because of the strict personal protective equipment (PPE) and IPC protocols healthcare workers (HCW) must adhere to for protection. The Radboud University Medical Center, located in Nijmegen, the Netherlands, has been a dedicated HLIU facility since 2008. A newly built HLIU opened in May 2022, and encouraged us to review the existing PPE selection, IPC protocols, and HCID training program to improve safety and comfort for HCWs working in the HLIU. Based on a systematic search through (inter)national HCID PPE guidelines and semistructured interviews with end users, we selected an improved, more comfortable set of PPE. Additionally, we developed a more concise and easier-to-use patient care process flow and implemented a new teaching strategy. The new way of working was tested in October 2022 when the first 2 patients with suspected HCID were admitted to our unit. We used surveys to evaluate the experiences of HCWs involved in this care to further improve the workflow of the unit. When optimizing safety and comfort for HCWs, it is important to consider (inter)national guidelines as well as user preferences. By systematically evaluating recent experiences of patient admission to the HLIU and then adjusting protocols and training, we can ensure that the quality of provided healthcare and the safety of HCWs working in the HLIU remains high.

Recommendations for Updating Fever and Inflammation of Unknown Origin From a Modified Delphi Consensus Panel.

Background: Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are syndromes commonly used as medical diagnoses. Since the existing literature has a mixture of diagnostic approaches, developing consensus-based recommendations would be helpful for clinicians, researchers, and patients. Methods: A modified Delphi process was performed from October 2022 to July 2023, involving 4 rounds of online surveys and 2 live video conferences. The panel comprised international experts recruited based on peer-reviewed published publications and studies. Results: Among 50 invited experts, 26 (52.0%) agreed to participate. Twenty-three panelists completed round 1 of the survey, 21 completed rounds 2 and 3, 20 completed round 4, and 7 participated in round 5 live video discussions. Of the participants, 18 (78.3%) were academic-based clinicians and researchers, 5 (21.7%) practiced in a community-based hospital, and 6 (26.1%) were female. Consensus was reached on 5 themes: (1) incorporating epidemiologic factors, such as geographic location and travel history; (2) updated criteria for classifying FUO or IUO; (3) initial evaluation approaches; (4) a classification system for diagnoses; and (5) recommendations for judicious limitation of empiric therapies. Experts strongly disagreed with using 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography/computed tomography as part of the diagnostic criteria for FUO. There were mixed opinions about the importance of the temperature measurement site, the 3-week minimum illness criterion, the need for a standard definition of relapsing fevers, and the use of similar evaluation strategies for FUO and IUO. Conclusions: These Delphi-generated consensus-based recommendations offer potential improvements compared with earlier definitions and a guide for clinical practice and future research.

Clinical management of liver cyst infections: an international, modified Delphi-based clinical decision framework.

Liver cyst infections often necessitate long-term hospital admission and are associated with considerable morbidity and mortality. We conducted a modified Delphi study to reach expert consensus for a clinical decision framework. The expert panel consisted of 24 medical specialists, including 12 hepatologists, from nine countries across Europe, North America, and Asia. The Delphi had three rounds. The first round (response rate 21/24 [88%]) was an online survey with questions constructed from literature review and expert opinion, in which experts were asked about their management preferences and rated possible management strategies for seven clinical scenarios. Experts also rated 14 clinical decision-making items for relevancy and defined treatment outcomes. During the second round (response rate 13/24 [54%]), items that did not reach consensus and newly suggested themes were discussed in an online panel meeting. In the third round (response rate 16/24 [67%]), experts voted on definitions and management strategies using an online survey based on previous answers. Consensus was predefined as a vote threshold of at least 75%. We identified five subclassifications of liver cyst infection according to cyst phenotypes and patient immune status and consensus on episode definitions (new, persistent, and recurrent) and criteria for treatment success or failure was reached. The experts agreed that fever and elevated C-reactive protein are pivotal decision-making items for initiating and evaluating the management of liver cyst infections. Consensus was reached on 26 management statements for patients with liver cyst infections across multiple clinical scenarios, including two treatment algorithms, which were merged into one after comments. We provide a clinical decision framework for physicians managing patients with liver cyst infections. This framework will facilitate uniformity in the management of liver cyst infections and can constitute the basis for the development of future guidelines.

ddPCR enables rapid detection of bloodstream infections in patients on home parenteral nutrition: A prospective cohort study.

INTRODUCTION: Chronic intestinal failure patients (CIF) require a central venous access device (CVAD) to administer parenteral nutrition. Most serious complication related to a CVAD is a central line-associated bloodstream infection (CLABSI). The golden standard to diagnose a CLABSI are blood cultures, however, they may require 1-5 days before getting a result. Droplet digital polymerase chain reaction (ddPCR) for the detection of pathogen 16S/28S rRNA is a novel culture-independent molecular technique that has been developed to enhance and expedite infection diagnostics within two and a half hours. In this study, we prospectively compared ddPCR with blood cultures to detect pathogens in whole blood. METHODS: We included adult CIF patients with a clinical suspicion of CLABSI in this prospective single-blinded clinical study. Blood cultures were routinely collected and subsequently two central samples from the CVAD and two peripheral samples from a peripheral venous access point. Primary outcome was the sensitivity and specificity of ddPCR. RESULTS: In total, 75 patients with 126 suspected CLABSI episodes were included, with 80 blood samples from the CVAD and 114 from peripheral veins. The central ddPCR samples showed a sensitivity of 91% (95%CI 77-98), and specificity of 96% (95%CI 85-99). Peripheral ddPCR samples had a sensitivity of 63% (95%CI 46-77) and specificity of 99% (95%CI 93-100). CONCLUSION: ddPCR showed a high sensitivity and specificity relative to blood cultures and enables rapid pathogen detection and characterization. Clinical studies should explore if integrated ddPCR and blood culture outcomes enables a more rapid pathogen guided CLABSI treatment and enhancing patient outcomes.

Comparison of diagnostic spectrum between inflammation of unknown origin and fever of unknown origin: A systematic review and meta-analysis.

BACKGROUND: Patients with inflammation of unknown origin (IUO) and fever of unknown origin (FUO) are commonly considered a single population. Differences in underlying causes between both groups may steer the diagnostic work-up. METHODS: PubMed, Embase, Web of Science, and ClinicalTrials.gov were searched from July 2009 through December 2023. Studies including both FUO and IUO patients with a sample size of ≥20 were considered. The primary outcome was the difference in the rate of patients affected by predefined diagnostic categories according to meeting FUO or IUO criteria. Data were pooled using random-effects models. RESULTS: A total of 8 studies met criteria for inclusion, with a total of 1452 patients (466 with IUO and 986 with FUO). The median rate of IUO patients among the included studies was 32 % (range 25-39 %). Patients with IUO had a lower likelihood of infection (OR 0.59 [95 % CI; 0.36-0.95]; I2 0 %). There were no significant differences in the rate of noninfectious inflammatory disorders, malignancies, miscellaneous disorders, or remaining undiagnosed. Comparison of diagnostic subgroups revealed that IUO patients were less likely to have systemic autoinflammatory disorders (OR 0.17 [95 % CI, 0.05-0.58]; I2 42 %) and more likely to have vasculitis (OR 2.04 [95 % CI, 1.23-3.38]; I2 21 %) and rheumatoid arthritis or spondylarthritis (OR 3.52 [95 % CI, 1.16-10.69]; I2 0 %). CONCLUSION: Based on our findings, there is little reason to assume that FUO and IUO patients would benefit from a different initial diagnostic approach.

Development of a Consensus-Based List of Potential Quality Indicators for Fever and Inflammation of Unknown Origin.

With a growing emphasis on value-based reimbursement, developing quality indicators for infectious diseases has gained attention. Quality indicators for fever of unknown origin and inflammation of unknown origin are lacking. An assembled group of international experts developed 12 quality measures for these conditions, which could be validated with additional study.

Update on imaging in fever and inflammation of unknown origin: focus on infectious disorders.

BACKGROUND: Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are diagnostic challenges that often require an extensive work-up. When first-line tests do not provide any or only misleading clues, second-line investigations such as specialized imaging techniques are often warranted. OBJECTIVES: To provide an overview of the diagnostic value of imaging techniques that are commonly used in patients with FUO/IUO. SOURCES: MEDLINE database was searched to identify the most relevant studies, trials, reviews, or meta-analyses until 31 March 2023. CONTENT: The most important types of second-line imaging tests for FUO and IUO are outlined, including [67Ga]-citrate single-photon emission computed tomography/computed tomography (CT), labelled leukocyte imaging, [18F]-fluorodeoxyglucose positron emission tomography CT ([18F]-FDG-PET), and whole-body magnetic resonance imaging. This review summarizes the diagnostic yield, extends on potential future imaging techniques (pathogen-specific bacterial imaging and [18F]-FDG-PET/magnetic resonance imaging), discusses cost-effectiveness, highlights practical implications and pitfalls, and addresses future perspectives. Where applicable, we provide additional data specifically for the infection subgroup. IMPLICATIONS: Although many imaging examinations are proven to be useful in FUO and IUO, [18F]-FDG-PET/CT is the preferred second-line test when available as it provides a high diagnostic yield in a presumably cost-effective way.

Genomic characterization of methicillin-susceptible Staphylococcus aureus carriage in patients on home parenteral nutrition and their caregivers.

In this prospective study, patients on home parenteral nutrition were twice as likely to be colonized with Staphylococcus aureus if their caregivers were also carriers. Among S. aureus-positive patients and their caregivers, molecular analysis showed 68% genetically related strains. Despite decolonization, genetically related strains reappeared in 70% of patients.

Oral antimicrobial agents in patients with short bowel syndrome: worth a try!

BACKGROUND: The use of oral antimicrobial agents in patients with short bowel syndrome (SBS) is challenging due to the changes in gastrointestinal anatomy that may result in diminished absorption and altered drug bioavailability. Prospective studies evaluating bioavailability of antimicrobial agents after oral administration in SBS patients are lacking. OBJECTIVES: To determine the bioavailability of orally administered antimicrobial agents commonly used for treatment in SBS patients to guide clinical decision making when faced with infections. METHODS: We performed an explorative, clinical study investigating the pharmacokinetics (PK) of clindamycin, ciprofloxacin, flucloxacillin and fluconazole in SBS patients with intestinal failure. Participants received a combination of two antimicrobial agents simultaneously. To determine the oral bioavailability, participants received a single oral and IV dose of both agents on two occasions, after which they underwent intensive PK sampling on six predefined time points up to 12 hours after administration. Primary outcome was the oral bioavailability of these antimicrobial agents. Secondary outcomes were intravenous PK characteristics following non-compartmental analysis. RESULTS: Eighteen SBS patients were included: the mean (SD) age was 59 (17) years and 61% of participants were female. The median observed (IQR) bioavailability of ciprofloxacin, clindamycin, flucloxacillin and fluconazole were 36% (24-50), 93% (56-106), 50% (32-76) and 98% (61-107), respectively. CONCLUSION: The bioavailability of selected antimicrobial agents in certain patients with SBS appeared to be better than expected, providing a feasible treatment option. Due to the large observed differences between patients, therapeutic drug monitoring should be part of the treatment to safeguard adequate exposure in all patients. TRIAL REGISTRATION: Registered in the Dutch Trial Register (NL7796) and EudraCT number 2019-002587-28.

Efficacy of Cognitive-Behavioral Therapy Targeting Severe Fatigue Following Coronavirus Disease 2019: Results of a Randomized Controlled Trial.

BACKGROUND: Severe fatigue following coronavirus disease 2019 (COVID-19) is prevalent and debilitating. This study investigated the efficacy of cognitive-behavioral therapy (CBT) for severe fatigue following COVID-19. METHODS: A multicenter, 2-arm randomized controlled trial was conducted in the Netherlands with patients being severely fatigued 3-12 months following COVID-19. Patients (N = 114) were randomly assigned (1:1) to CBT or care as usual (CAU). CBT, targeting perpetuating factors of fatigue, was provided for 17 weeks. The primary outcome was the overall mean difference between CBT and CAU on the fatigue severity subscale of the Checklist Individual Strength, directly post-CBT or CAU (T1), and after 6 months (T2). Secondary outcomes were differences in proportions of patients meeting criteria for severe and/or chronic fatigue, differences in physical and social functioning, somatic symptoms, and problems concentrating between CBT and CAU. RESULTS: Patients were mainly nonhospitalized and self-referred. Patients who received CBT were significantly less severely fatigued across follow-up assessments than patients receiving CAU (-8.8 [95% confidence interval {CI}, -11.9 to -5.8]); P < .001), representing a medium Cohen's d effect size (0.69). The between-group difference in fatigue severity was present at T1 (-9.3 [95% CI, -13.3 to -5.3]) and T2 (-8.4 [95% CI, -13.1 to -3.7]). All secondary outcomes favored CBT. Eight adverse events were recorded during CBT, and 20 during CAU. No serious adverse events were recorded. CONCLUSIONS: Among patients, who were mainly nonhospitalized and self-referred, CBT was effective in reducing fatigue. The positive effect was sustained at 6-month follow-up. CLINICAL TRIALS REGISTRATION: Netherlands Trial Register NL8947.

Randomized clinical trial: Long-term Staphylococcus aureus decolonization in patients on home parenteral nutrition.

BACKGROUND & AIMS: Staphylococcus aureus decolonization has proven successful in prevention of S. aureus infections and is a key strategy to maintain venous access and avoid hospitalization in patients receiving home parenteral nutrition (HPN). We aimed to determine the most effective and safe long-term S. aureus decolonization regimen. METHODS: A randomized, open-label, multicenter clinical trial was conducted. Adult intestinal failure patients with HPN support and carrying S. aureus were randomly assigned to a 'continuous suppression' (CS) strategy, a repeated chronic topical antibiotic treatment or a 'search and destroy' (SD) strategy, a short and systemic antibiotic treatment. Primary outcome was the proportion of patients in whom S. aureus was totally eradicated during a 1-year period. Secondary outcomes included risk factors for decolonization failure and S. aureus infections, antimicrobial resistance, adverse events, patient compliance and cost-effectivity. RESULTS: 63 participants were included (CS 31; SD 32). The mean 1-year S. aureus decolonization rate was 61% (95% CI 44, 75) for the CS group and 39% (95% CI 25, 56) for the SD group with an OR of 2.38 (95% CI 0.92, 6.11, P = 0.07). More adverse effects occurred in the SD group (P = 0.01). Predictors for eradication failure were a S. aureus positive caregiver and presence of a (gastro)enterostomy. CONCLUSION: We did not demonstrate an increased efficacy of a short and systemic S. aureus decolonization strategy over a continuous topical suppression treatment. The latter may be the best option for HPN patients as it achieved a higher long-term decolonization rate and was well-tolerated (NCT03173053).

Low SARS-CoV-2 Cq values in healthcare workers with symptomatic COVID-19 infections, regardless of symptom severity, The Netherlands, January to August 2022.

We analysed SARS-CoV-2 PCR Cq values from 3,183 healthcare workers who tested positive between January and August 2022. Median Cq values were lower in symptomatic than in asymptomatic HCW. The difference in Cq values between HCW with mild vs moderate/severe symptoms was statistically significant but negligibly small. To prevent nosocomial infections, all symptomatic HCW should be tested irrespective of symptom severity. This information can support decisions on testing and isolation, in the context of ongoing pressure on healthcare systems.

Success rates of MRSA decolonization and factors associated with failure.

BACKGROUND: We evaluated the success rate of MRSA decolonization directly after treatment and after one year in patients who were treated at the outpatient MRSA clinic of a large university medical centre to identify potential contributing factors to treatment success and failure. METHODS: Data from November 1, 2013 to August 1, 2020 were used. Only patients who had undergone complete MRSA decolonization were included. Risk factors for MRSA treatment failure were identified using a multivariable logistic regression model. RESULTS: In total, 127 MRSA carriers were included: 7 had uncomplicated carriage, 91 had complicated carriage, and 29 patients had complicated carriage in combination with an infection. In complicated carriers and complicated carriers with an infection final treatment was successful in 75.0%. Risk factors for initial treatment failure included having one or more comorbidities and not testing the household members. Risk factors for final treatment failure were living in a refugee centre, being of younger age (0-17 years), and having one or more comorbidities. CONCLUSIONS: The results of this study indicate that patients with a refugee status and children treated at the paediatric clinic have a higher risk of MRSA decolonisation treatment failure. For this reason, it might be useful to revise decolonization strategies for these subgroups and to refer these patients to specialized outpatient clinics in order to achieve higher treatment success rates.

Catheter-related bloodstream infection management in patients receiving home parenteral nutrition: An observational cohort study.

BACKGROUND AND AIMS: Patients with intestinal failure receiving home parenteral nutrition (HPN) are susceptible to central-line associated bloodstream infections (CLABSIs), with crucial roles for adequate (empiric) antimicrobial therapy and effective catheter management strategies. Our aim was to link recent epidemiologic CLABSI data with clinical outcomes and to identify risk factors for therapeutic failure to decide on the safest and most accurate CLABSI management in patients receiving HPN. METHODS: A retrospective observational cohort study was conducted. All data on CLABSIs (period 2010-2020) in adult patients receiving HPN were retrieved. The efficacy of attempted catheter salvage and empiric antimicrobial treatment (ß-lactam antibiotics) in our center, with a low prevalence of methicillin-resistant staphylococci, was investigated. Multivariate cox-regression analysis was performed to identify risk factors for recurrent CLABSI. RESULTS: 389 CLABSIs occurred in 149 patients. The overall infection rate was 0.64 per 1000 central venous catheter (CVC) days. Most CLABSIs were caused by Coagulase-negative staphylococci (37%). Attempted CVC salvage was successful in 70% of the cases. Empiric antimicrobial therapy was found to be adequate in only 47% of cases, mainly because of insufficient Coagulase-negative staphylococci coverage. According to the Cox model, patients with a replaced CVC had a 50% lower risk of a new CLABSI than patients with a retained (salvaged) CVC during follow-up (HR 0.50; 95% CI 0.35-0.72, P < 0.001). CONCLUSIONS: CVC salvage can be achieved in most CLABSI cases but seems associated with a shorter CLABSI-free survival. Importantly, based on our findings, a glycopeptide containing antibiotic treatment regimen will increase the likelihood of adequate empiric coverage.

Targeted Screening for Chronic Q Fever, the Netherlands.

Early detection of and treatment for chronic Q fever might prevent potentially life-threatening complications. We performed a chronic Q fever screening program in general practitioner practices in the Netherlands 10 years after a large Q fever outbreak. Thirteen general practitioner practices located in outbreak areas selected 3,419 patients who had specific underlying medical conditions, of whom 1,642 (48%) participated. Immunofluorescence assay of serum showed that 289 (18%) of 1,642 participants had a previous Coxiella burnetii infection (IgG II titer >1:64), and 9 patients were suspected of having chronic Q fever (IgG I y titer >1:512). After medical evaluation, 4 of those patients received a chronic Q fever diagnosis. The cost of screening was higher than estimated earlier, but the program was still cost-effective in certain high risk groups. Years after a large Q fever outbreak, targeted screening still detected patients with chronic Q fever and is estimated to be cost-effective.