Background
Staphylococcus aureus (SA) can cause various infections and is associated with high morbidity and mortality rates of up to 40%. Antibiotic treatment often fails to eradicate SA infections even if the causative strain has been tested susceptible in vitro. The mechanisms leading to this persistence is still largely unknown. In our work, we hypothesize that interactions with host cells allow SA to persist at the site of infection.

Methods
We established a sampling workflow to receive tissue samples from patients requiring surgical debridement due to SA bone-and joint or soft-tissue infections. We developed a multiplex immunofluorescent staining protocol which allowed us to stain for SA, leukocytes, neutrophils, macrophages, B-cells, T-cells, DAPI and cytoplasmatic marker on the same sample slide. Further, distance of SA to cell nuclei was measured. Interaction of immune cells and SA on a single cell level was investigated with high-resolution 3D microscopy. We then validated our findings applying fluorescence-activated cell sorting (FACS) on digested patient samples. Finally, we aimed to reproduce our ex vivo patient results in an in vitro co-culture model of primary macrophages and clinical SA strains, where we used live cell microscopy and high-resolution microscopy to visualize SA-immune cell interactions and a gentamicin protection assay to assess viability of SA.

Results
Here, we revealed that CD68+ macrophages were the immune cells closest to SA with a mean distance of 56μm (SD=36.4μm). Counting the amount of SA, we found in total >7000 single SA in nine patients. Two-thirds of SA were located intracellularly. Two-thirds of the affected immune cells with intracellular SA were macrophages. The distribution of intra- to extracellular SA was independent of ongoing antibiotic therapy and underlying infection type. FACS confirmed these findings. In our co-culture model, intracellular SA remained alive in a non-replicative state for the whole observation period of sixty-two hours and resided in RAB5+ early phagosomes.

Conclusion
Our study suggests an essential role of intracellular survival in macrophages in SA infections. These findings may have major implication for future treatment strategies.

Background. Herpes simplex virus type 1 (HSV-1) usually causes mild mucocutaneous lesions but can also reach the central nervous system (CNS), leading to herpes simplex encephalitis (HSE). HSE occurs at an annual rate of 2-4 per million individuals with a bimodal age distribution including children, mainly after a first infection in life, and adults over the age of 50 years, due to a viral reactivation. Genetic studies have shown that childhood HSE results from monogenic inborn errors of immunity, leading to impaired interferon production and uncontrolled infection or reactivation.

Methods. Following genome-wide genetic analyses, we identified an uncharacterized and very rare gain-of-function heterozygous variant in a 14-month-old girl who developed HSE. Its impact on the TLR3-mediated signaling and viral replication was determined by both in vitro and ex vivo approaches and further confirmed by using brain specific-cell differentiation technology from human’s induced pluripotent stem cells (hiPSCs) as well as the CRISPR-Cas9 technology.

Results. The variant impaired TLR3-mediated signaling in vitro, in TLR3-expressing 293T cells, ex vivo, in peripheral blood mononuclear cells and in hiPSCs -derived neural precursor cells and neurons. Cells bearing this mutation were also more susceptible to HSV-1 infection compared to control cells. Antiviral immunity was rescued following the correction of mutation by CRISPR-Cas9 technology. Reciprocally, the introduction of mutation in wild type cells abolished such immunity, demonstrating that this mutation is directly linked to the observed phenotypes.

Conclusion. We describe here a novel gain of function variant regulating the TLR3- dependent control of HSV-1 in the CNS.

Beim Room of Horrors (ROH) handelt es sich um einen Trainingsraum mit gestellten Szenen, in dem die Teilnehmenden nach Fehlern und Risiken suchen (Patientensicherheit Schweiz). Im Frühling 2023 wurde für die Abteilung Pädiatrische Intensivbehandlung einen ROH mit hygienerelevanten Fehlern durchgeführt. Die Betreuung eines ROH vor Ort mit direkter Personalpräsenz ist aufwändig, weshalb wir einer Hybridumsetzung explorierten. Die Mitarbeitenden wurden in der Umsetzung der Kontaktisolation geschult und für hygienerelevante Themen sensibilisiert. Um den ROH mit flexiblen Öffnungszeiten anbieten zu können, wurde eine Variante gewählt, bei der nicht durchgehend jemand für die Instruktion Vorort sein musste. Der ROH erfolgte als Hybridvariante (Kombination aus digitalen mit physischen Elementen). Teilnehmende konnten sich mittels QR Code für den Besuch anmelden. Empfohlen war, den Raum zu zweit oder max. zu viert zu besuchen. Als Einstieg wurde ein Instruktionsvideo auf dem Handy gezeigt. Anschliessend suchten die Teams fünfzehn Minuten im Raum nach Fehlern. Durch Klicken auf Fotos des Raumsetups in einem Onlinetool konnten die Fehler mittels Freitexteingabe erfasst werden. Die Fehler standen für die Auswertung als Excel Datei zur Verfügung. Es wurden 22 hygienerelevante Fehler integriert. Nach Ablauf der Zeit wurde im Auflösungsvideo die Hygienefehler präsentiert. Zum Schluss wurden die Mitarbeitenden gebeten eine kurze Auswertung auszufüllen. Insgesamt haben 76 Mitarbeitende in 36 Gruppen von zwei bis vier Personen während zwei Wochen den ROH besucht. Bei der Auswertung gaben 30/36 (83%) Gruppen an, dass ihnen der ROH sehr gut gefallen hat und sie mit dem Instruktionsvideo und der Erfassung der Fehler gut zurechtgekommen sind. 25/36 (69%) Gruppen gaben an, dass sie mindestens eine neue Erkenntnis gewonnen haben. Keine der Gruppen hatte Probleme mit der digitalen Methode. Durch die digitale Auswertung der Fehler und die videogestützte Instruktion war eine durchgehende Präsenz auf der Station durch die Spitalhygiene nicht notwendig. Bei der Analyse der erfassten Fehler fiel auf, welche Fehler nicht oder nur selten erkannt wurden. Daraus können in Zukunft weitere Schulungen angeboten werden.Eine hybride Umsetzung eines ROH stellt eine ressourcensparende Alternative zu einer voll physischen Umsetzung dar und ermöglicht flexiblere Öffnungszeiten. Die Methode wird von den Teilnehmenden gut akzeptiert und erlaubt eine Analyse der erfassten Fehler.

Aims: Surveillance of healthcare associated infections (HAI) is crucial for prevention and control. Catheter-associated urinary tract infections (CAUTI) are among the most common HAI. We investigated the potential use of OpenAI's GPT-4 model in detecting CAUTI cases in a cohort of fictitious patients based on the NHSN criteria (1).
Methods: A dataset of 79 fictitious patients, including demographics, body temperature, urine culture results, hospitalization- and catheterization dates was created in Microsoft Excel and provided to GPT-4 as a comma-separated values file. According to NHSN criteria five patients had a CAUTI. GPT-4 was asked to analyze the data and identify patients with CAUTIs based on NHSN criteria. Sensitivity, specificity, predictive values of CAUTI detection by GPT-4 were calculated. GPT-4 was further instructed to retrieve patient- and catheter days and calculate catheter utilization ratio.
Results: Initially, GPT-4 identified six patients with CAUTIs, four of which met the criteria. One patient with a CAUTI was not detected, and two patients with catheter reinsertion were falsely identified as having CAUTIs. The analysis yielded a sensitivity of 80% and a specificity of 97.3%. After repeated training, GPT-4 correctly recognized all five patients with CAUTIs, but still falsely reported a CAUTI for one patient with reinsertion. The final results showed a sensitivity of 100%, specificity of 98.6%, positive predictive value of 83.3%, and negative predictive value of 100%. GPT-4 managed to retrieve the correct number of patient- and catheter days (869 and 114) as well as catheter utilization ratio (13.12%). However, it encountered difficulties with data structure in this case and initially erroneously counted empty Excel cells as 1 catheter day.
Conclusions: Our results indicate that OpenAI GPT-4 model could potentially be used in the detection and real time surveillance of HAI such as CAUTI. Repeated training of the OpenAI model is required, to ensure consistent and reliable detection of nosocomial infections. In the future, the model could potentially be employed at the interface level to analyze data directly from the electronic medical record, enabling an efficient approach to HAI surveillance. Thereby it could become an essential tool in infection prevention and control. Before implementation in clinical medicine, legal issues such as data privacy and protection need to be addressed (2).

Objectifs : Les jeux sérieux sont reconnus comme outils pédagogiques efficaces. Plus particulièrement, les escapes games offrent un format favorisant la collaboration par le partage des connaissances. Ils restent néanmoins peu utilisés dans le domaine de l’hygiène, prévention et contrôle de l’infection (HPCi). Dans le cadre de la campagne de promotion de l’hygiène des mains 2023, l’unité HPCi du CHUV a développé un jeu innovant et conçu pour optimiser la portée des messages de prévention, fondé sur le modèle d’escape game.
Méthode : Le principe du jeu consiste, en équipe de 4-5 personnes, à rechercher des indices cachés dans une pièce et résoudre des énigmes dans un temps imparti, en lien avec la thématique cantonale définie, soit l’utilisation appropriée des gants. L’équipe en charge du projet a conçu un scénario court et ciblé, s’inspirant de situations concrètes. Afin que les énigmes reflètent au mieux l’activité de chaque participant, des versions spécifiques pour le personnel médical et les techniciens en radiologie ont été élaborées. Le matériel nécessaire pour une partie a été limité afin de faciliter son transport et sa mise en place. Le jeu, nommé « Ne restez pas prisonniers de vos gants », peut se dérouler dans n’importe quelle salle et ainsi être proposé au plus près des équipes dans les services de soins. Le concept a été testé au sein de l’équipe HPCi du CHUV, avant d’obtenir une validation auprès de la direction de l’hôpital. Une marche à suivre, visant à homogénéiser l’animation et le débriefing du jeu, a été rédigé ainsi qu’un bref formulaire d’évaluation donné en fin de partie. Une communication institutionnelle a été mise en place lors du lancement de la campagne et s’est accompagnée d’une planification en amont auprès des cadres pour la constitution des équipes et la réservation des salles.
Résultats : Dès le 01 mai 2023 et durant plusieurs semaines, l’équipe HPCI du CHUV s’est mobilisée pour animer dans les différents secteurs de soins adultes et pédiatriques des sessions d’escape game de 20 minutes. Chaque animateur disposait d’un kit de jeu transportable dans une caisse. Le déploiement des sessions au-delà du 5 mai a permis de s’adapter à l’organisation interne de chaque service et d’être présents dans tous les départements.
Conclusion : Le caractère ludique, immersif et facilement déployable de cet escape game en fait un outil de campagne particulièrement intéressant et innovant. Les premiers retours sont très positifs.

Aim: Core elements of antibiotic stewardship programs (ASP) are well defined and widely accepted. However, there was no formal ASP in our institution prior to 2022 and important elements were lacking. In a concerted initiative, we aimed to secure leadership commitment for the implementation of a formal ASP, to rise visibility of ASP activities and to start interventions.
Method: First, with support of hospital leadership, we established an ASP core team consisting of infectious diseases/control specialists, a pharmacist and a microbiologist, who is fully accountable for ASP activities. Second, we developed an overarching, institution-wide project that aims to establish missing ASP core elements in a stepwise approach over two years. As part of the project we elaborated a communication concept with our corporate communications office.
Result: The implementation of a formal ASP through a preceding project was accepted by our hospital executive board. Leadership commitment included the provision of personnel resources. The website of our division was adapted, providing regular news about ASP. During the WHO World Antimicrobial Awareness Week, we conducted an information campaign, shared posts on social media and operated a booth at the main entrance.
Using a participatory approach, we began an intervention together with the division of palliative medicine, consisting of goal-directed counselling about infection management in terminally ill patients. We developed a guidance on challenges and preferences when caring for patients with presumed infection near the end of life. We are also about to start a large interprofessional intervention in collaboration with the nursing department, with the aim to strengthen the role of nurses in ASP. Third, a project on early outpatient treatment of diverticulitis patients has been established with colleagues from the department of surgery.
Conclusion: Implementation of a formal ASP through a carefully elaborated project phase might help to secure leadership commitment, probably the most important condition providing necessary acceptance and resources to run an ASP. Systematic collaboration with corporate communications rises visibility and awareness of ASP and fosters networking. Innovative elements include fostering a participatory approach to antibiotic stewardship, interventions addressing neglected patient populations, and focusing on interprofessional and interdisciplinary care teams, rather than on prescribers only.

Aims: Triggered by the COVID-19 pandemic, a group of LTCF sought cooperation in the area of IPC with our institution (KSSG), while the cantonal authorities responsible for LTCFs requested guidelines and education in IPC for all LTCFs.
To establish an institutionalized IPC (structure, organisation, guidelines, education, surveillance) for a pilot group of LTCF with secondary roll-out to other institutions and to provide education and guidelines for all cantonal LTCF.
Methods: Our interdisciplinary and interprofessional network included IPC experts (physician, nurse), representatives of the institutions (link-nurse, manager), geriatrician, stakeholders from the cantonal authorities and from CURAVIVA (national association of service providers for people in old age). We performed a systematic literature review on effective IPC measures in LTCF in outbreak and non-outbreak settings. Furthermore, we decided to adapt and to implement the following WHO-core components of IPC in a first step: structure/organisation, guidelines, teaching/education and surveillance. Baseline data based on the HALT-3 questionnaire für LTCF1 were collected and outbreak surveillance for respiratory viruses was performed.
Results: The systematic literature review showed that data for effective IPC measures in LTCF are scarce, except for hand and oral hygiene. Baseline data showed that a person qualified and trained in IPC is available in 43% (3/7) of LTCF. Neither systematic surveys of HAI nor regular training in IPC were established in the participating institutions. Guidelines on specific topics (standard precautions, hand hygiene and acute respiratory viral infections) were drafted by IPC experts and consulted with and implemented by the link nurses. Training sessions on the same topics were developed in parallel by the IPC team, the employees in the institutions were trained by the local link nurse. The main focus was primarily on practical, occupational--specific examples. Outbreak surveillance of respiratory viruses identified five outbreaks during the influenza season. After successful implementation of IPC in the pilot institutions, education and training was offered for all cantonal LTCF.
Conclusion: Targeted IPC with core elements can be established in LTCFs using a multimodal, practice-oriented approach that takes the baseline level of knowledge of the trainees into account. The number of outbreaks underlines the great need for intensified IPC measures in this setting.

Zielsetzung
Jährliche Audits im Akutspital zum Erkennen von Defiziten in Bezug auf Standardhygiene und Umgang mit Medizinprodukten und Medikamenten sind Bestandteil der strukturellen Mindestanforderungen Strategie Noso. Solche Audits sollten ab dem Jahr 2020 auf allen Bettenstationen, diagnostischen und interventionellen Bereichen des Regionalspitals eingeführt werden. Eine zeitnahe Auswertung und Rückmeldung an die Verantwortlichen wurde angestrebt, damit die Einleitung und Zuweisung von Verbesserungsaufträgen schnell erfolgen und Fehler und Mängel rasch behoben werden können.

Methoden
2020: Formierung einer Arbeitsgruppe: Audit-Hygiene-Apotheke-Materialwirtschaft (HAM).
2020: Durchführung erster Hygienestruktur-Audits mittels Checklisten in Papierform. Es wurden die Hygiene-Strukturen überprüft (Räumlichkeiten, Händedesinfektionsmittel, Lagerung von Sterilgut, Medikamenten und Medizinprodukten) und das Erscheinungsbild der anwesenden Mitarbeitenden und das Basiswissen in Bezug auf Händehygiene und Isolations-Richtlinien).
2021: Internetrecherche über mögliche webbasierte Tools und Auswahl sowie Test eines Audit-Tools
2022: Anpassung der Checklisten auf die für die Cleanhands-Beobachtungen bereits im Spital vorhandenen Tablets

Ergebnisse
In den Jahren 2020 und 2021 wurden je 5 Begehungen durchgeführt. Die Auswertung erfolgte nicht einheitlich, der Zeitaufwand für die Auswertung und Rückmeldung der Ergebnisse war hoch.
Im Jahr 2022 konnten mit dem neuen Audit-Tool 10 Begehungen durchgeführt werden. Die Auswertung, Rückmeldung und die Zuordnung von Verbesserungsaufträgen war einheitlich möglich. Die Nachbereitungszeit konnte deutlich verringert werden. Aufträge für Verbesserungen erfolgten umgehend und in einer standardisierten Darstellung. Der Stand der Themen-Bearbeitung war einheitlich ersichtlich und ermöglicht die zukünftige Vergleichbarkeit.

Konklusion
Das webbasierte Tool ermöglichte die unkomplizierte Erstellung von auf die Institution angepassten Checklisten.
Vor Ort war das Erfassen der angetroffenen Situationen einfach und die Eingabe mittels Tablet intuitiv und schnell möglich. So konnten sich die auditierenden Fachpersonen in hohem Mass auf die Situation konzentrieren und wesentliche Themen erkennen. Hygiene-Audits gemäss den strukturellen Mindestanforderungen können durch den Einsatz von elektronischen Hilfsmitteln ressourcenschonender, zielführender und jährlich wiederkehrend durchgeführt werden.

Background. The penetration of broad-spectrum beta-lactams and antifungals within intra-abdominal abscesses (IAA) in humans is poorly investigated. This study aims at comparing the antimicrobial drug concentration in IAA versus that measured in plasma.
Methods. Patients who underwent drainage of an IAA and who were receiving antimicrobial therapy for > 48h were prospectively enrolled. Antimicrobial drug concentration was measured in the IAA and in a plasma sample drawn at the time of the intervention in order to assess the IAA/plasma ratio. The pharmacologic target was defined as an IAA concentration equal or superior to the clinical breakpoints of susceptibility of the expected pathogens.
Results. We collected 46 antimicrobial drug measurements from 27 peritoneal and 7 hepatic abscesses. Among carbapenems, meropenem and ertapenem showed higher IAA/plasma ratios compared to imipenem, but only meropenem could achieve sufficient concentrations in intra-abdominal abscesses (83% target achievement vs 0% for imipenem/ertapenem, p < 0.01). Piperacillin-tazobactam exhibited the highest IAA/plasma ratio and achieved the target in 71% cases. Among antifungals, fluconazole had a higher IAA/plasma ratio compared to echinocandins. The target was achieved in the majority of cases for both antifungals, with the exception of echinocandins in hepatic abscesses (n=3).
Conclusions. These results of antimicrobial drug penetration in IAA showed variable results. Among antibiotics, meropenem and piperacillin-tazobactam could achieve appropriate concentrations within IAA in a majority of cases, which was not the case for imipenem and ertapenem. Among antifungals, the pharmacologic target was achieved for all cases, except for echinocandins in hepatic abscesses.

Aims: Since the publication of the Duke criteria for infective endocarditis (IE) diagnosis, several modifications have been proposed. We aimed to evaluate the diagnostic performance of the new 2023 Duke-ISCVID criteria for IE compared to the two previous versions, one from 2000 (Duke-Li 2000) and the other from the European Society of Cardiology (ESC) in 2015 (Duke-ESC 2015).
Methods: This study was conducted at two University Hospitals in Switzerland between 2014-2022 among patients with suspected IE. A case was classified as IE (final IE diagnosis) by the Endocarditis Team from each center. Sensitivity for each version of the Duke criteria was calculated among patients with confirmed IE based on pathological, surgical and microbiological data. Specificity for each version of the Duke criteria was calculated among patients with suspected IE for whom IE diagnosis was ruled out.
Results: In total 2132 episodes with suspected IE were included; of which 1101 (52%) had final diagnosis of IE. Among the 1031 patients without IE, other infectious diagnoses predominated (855; 83%). Definite IE by pathologic criteria was found among 285 (13%), 285 (13%), and 345 (16%) patients using the Duke-Li 2000, Duke-ESC 2015 or the Duke-ISCVID 2023 criteria, respectively. IE was excluded by histopathology or macroscopic evidence at surgery or autopsy with antibiotic treatment for less than 4 days among 25 (1%) patients. The 2023 Duke-ISCVID criteria for IE showed a higher sensitivity (84%) compared to the previous versions (70%). However, the specificity of the new clinical criteria showed lower specificity (60%) compared to previous versions (74%).
Conclusion: The 2023 Duke-ISCVID criteria for IE led to an increase in sensitivity compared to previous versions. Further studies are needed to evaluate items that could increase sensitivity by reducing the number of IE patients misclassified as possible, but without having detrimental effect on specificity of Duke criteria, which are not primarily intended for clinical practice, but for research application.

Aim
Numerous clinical parameters link to severe COVID-19, but factors that prevent symptomatic disease, particularly in SARS-CoV-2-naive individuals, remain unknown. Here, we investigated the influence of SARS-CoV-2 specific and pre-existing human coronaviruses (HCoV) humoral immunity in saliva and plasma on disease severity.
Methods
We quantified the impact of SARS-CoV-2 and HCoV antibody responses in children (n=2917) and adults (n=882) first exposed to SARS-CoV-2 between 03/2020-03/2021 in Switzerland. Saliva (n=4993) and plasma (n=7486) antibody reactivity to the four HCoVs (S1) and SARS-CoV-2 (S1, RBD, S2, N) was measured along with neutralizing activity against SARS-CoV-2 Wuhan, Alpha, Delta and Omicron (BA.2) in a subset of individuals.
Results
Inferred recent SARS-CoV-2 infection was associated with a strong correlation between mucosal and systemic SARS-CoV-2 anti-spike responses. Intriguingly, pre-existing HCoV reactivity was significantly associated with higher SARS-CoV-2 plasma (IgM/A/G, p < 0.001) and saliva (IgG, p=0.03) responses. Underscoring the impact of salivary defenses on disease manifestation, viral load in saliva was inversely associated with four saliva SARS-CoV-2 antibody parameters: total immunoglobulin (Ig) S2, total Ig S1, IgA S2 and IgM S1 (p= 0.01 to p= < 0.001). Saliva neutralization activity was modest but surprisingly broad retaining activity against Wuhan, Alpha and Delta, whereas plasma activity declined for Alpha, Delta and Omicron. In line with a rapid mucosal defense triggered by cross-reactive HCoV immunity, asymptomatic individuals presented with higher pre-existing HCoV-S1 activity in plasma (IgG HKU1, p=0.04) and saliva (total HCoV, p=0.02) and higher SARS-CoV-2 reactivity in saliva (IgG S2 p=0.03).
Conclusion
Overall, our results unravel the crucial impact of pre-existing mucosal HCoV immunity on the development of SARS-CoV-2-specific immunity and the influence of mucosal antibody response on symptoms development upon SARS-CoV-2 infection.

Aims: The aim of this study was to assess the incidence of Streptococcus pyogenes isolates reported to ANRESIS, the Swiss surveillance program that collects data on antibiotic resistance nationwide, before, during and after the restrictions measures due to the COVID-19 pandemic in Switzerland.
Methods: The monthly number of Streptococcus pyogenes isolates with a special focus on strains from blood cultures reported to ANRESIS, was analysed during the following three periods: P1; from January 2016 to March 2020 (before the pandemic), P2; from April 2020 to March 2022 (during the pandemic) and P3; from April 2022 to March 2023 (after the pandemic). Only the first sample per patient was included in the analysis. In a sensitivity analysis, the percentage of Streptococcus pyogenes isolates in all positive blood cultures reported to ANRESIS was analysed to correct for possible changes in coverage or blood sampling policies during the study period.
Results: From January 2016 to March 2022, 11'496 Streptococcus pyogenes isolates were reported to ANRESIS; 6972 (60.1%) originated from swabs, 1865 (16.2 %) from biopsies and punctures, 1247 (10.8%) from blood cultures, and 1412 (12.2%) from other sides. The monthly median number of all reported isolates were 136.4 in P1, 67.2 in P2 and 244.1 in P3. The monthly median number of reported Streptococcus pyogenes isolates in blood cultures were 14.6 in P1, 5.7 in P2 and 30.7 in P3. The ratio of positive blood cultures compared to the total number of Streptococcus pyogenes isolates was 11% in P1, 8% in P2 and 13% in P3. The decrease of positive blood cultures with Streptococcus pyogenes in P2 and the rise in P3 compared to P1 was observed in paediatric and adult age groups and in all geographical regions of Switzerland. The sensitivity analysis confirmed the results of the main analysis: in P1, the positive blood cultures with Streptococcus pyogenes accounted for 1.2 % all positive blood cultures reported to ANRESIS, in P2 for 0.71% and in P3 for 2.3%.
Conclusions: Our study confirms a significant decrease of invasive and non-invasive infections with Streptococcus pyogenes during the COVID-19 pandemic with a rapid increase above pre-pandemic levels after the pandemic period. Awareness of the growing number of invasive infections with GAS is important to prompt diagnosis and treatment in suspicious cases. Further studies including whole-genome sequencing are needed to understand the reason of the current increase.

Aims: Following the recommendation of the World Health Organization in 2018, country programmes across Africa have transitioned most people living with HIV from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based to dolutegravir (DTG)-based antiretroviral therapy (ART). This study assessed virologic outcomes over a two-year follow-up after transition to DTG-based ART in a routine care setting in Lesotho.

Methods: Data was derived from the Viral Load Cohort North-East Lesotho (VICONEL, data closure: 1 March 2023).
This study includes VICONEL participants who transitioned from ART containing an NNRTI alongside two nucleoside reverse transcriptase inhibitor (NRTIs) to DTG plus two NRTIs, were ≥ 18 years old at transition to DTG, and had at least one recorded viral load (VL) both before and after transitioning.
We report on the VL < 12 month before, 12 months after (window: 6-18 months), and 24 months after transitioning (window: 18-30 months), as well as adjusted odds ratios (aOR) and 95% confidence intervals (CI) from a logistic regression model with the outcome being a VL ≥ 50 copies/mL 24 months post-transition including relevant demographic and virologic variables as dependent variables.

Results: Among 14’077 included participants, 9’201 (65.4%) were female and the median age at transition was 44.2 years (IQR: 36.1-54.5).
A VL before, 12 and 24 months after transitioning to DTG was available for 8’048/14’077 (57.2%) participants: at these time points, 6’811/8’048 (84.6%), 7’549/8’048 (93.8%) and 7’665/8’048 (95.2%) participants, respectively, were suppressed to < 50 copies/mL. Among 285/8’048 (3.5%) participants with a VL > 999 copies/mL before transition, 238 (83.5%) were suppressed to < 50 copies/mL at 12 months, and 236 (82.8%) at 24 months.
Correlates of 24-month viremia included (N=10’765): male sex (vs female; aOR [95% CI]: 1.39 [1.16-1.66]); being 18-24 years old at transition (vs 25-44 years; 1.81 [1.21-2.63]); no documented VL (1.4 [1.08-1.78]), viremia 50-999 copies/mL (1.82 [1.4-2.33]), or viremia > 999 copies/mL (3.76 [2.64-5.26]) < 12 months before transition (vs < 50 copies/mL).

Conclusion: The vast majority of participants, including those with viremia before transition, achieved viral suppression with DTG. Together with the increased rates of suppression after transition to DTG, these findings suggest a net benefit of programmatic DTG roll-out regardless of pre-transition VL in settings without access to resistance testing.

Aims
Antibiotic prophylaxis (AP) targeting viridans streptococci (VGS) during dental procedures was restricted to patients at high risk of infective endocarditis (IE) in Swiss and international guidelines in 2007/8. We aimed to evaluate factors associated with IE due to VGS among the different IE risk groups using data of the USZ (Zurich, Switzerland).
Methods
We assessed patients ≥18 years old with any type of IE from 1.1.00 to 30.9.22 and categorized patients as “high risk” in case of a history of IE, a prosthetic/repaired valve, a cyanotic congenital heart condition (CHC), or certain repaired CHC. Patients with a history of rheumatic fever or non-rheumatic valve disease were classified as “moderate risk”. In order to study the possible impact of the 2008 AP guidelines, we divided the observation period as follows: period one 1.1.00 to 31.12.08; period two 1.1.09 to 30.9.22. We analysed prevalence differences of VGS IE among different IE risk groups and fit univariable and multivariable logistic regression models for the odds (OR) of IE due to VGS. Final models were adjusted for age, sex, Charlson Comorbidity Index (CCI), intravenous drug abuse (IVDU), poor oral hygiene, high-risk dental procedures, IE risk category and time period.
Results
Overall, 752 cases of IE were identified (163 cases in period one, 589 in period two). Compared to other pathogens, the overall proportion of IE due VGS was 21%. Proportions for period one vs. two were 24% vs. 16%, 24% vs. 37%, 33% vs. 7% and 18% vs.13% for the high, moderate, unknown/low or no risk group, respectively. Participants in the moderate risk group and an IE episode in period two had a 21% [95% CI 4.5-38] higher chance of an IE due to VGS. Univariable associations with IE due to VGS were: Age (per 10y older OR 0.80 [0.72-0.88]), CCI >5 (OR 0.47 [0.27-0.81]), IVDU (OR 0.47 [0.25-0.89]) and dental procedure (OR 2.28 [1.40-3.69]). After multivariable adjustment, the moderate risk group had a twofold risk of developing an endocarditis due to VGS (OR 2.38 [1.07-5.29]) in period two compared to period one. The other associations such as age (OR 0.79 [0.70-0.89]), dental procedures (OR 2.50 [1.34-4.65]), and IVDU (OR 0.35 [0.17-0.71]) remained unchanged.
Conclusion
An association was found between IE due to VGS with the moderate risk group and the period after the guideline change. While the guidelines currently do not recommend AP, we propose annual dental review and education about IE risk for these patients.

Aims:
Epstein Barr virus (EBV)-driven lymphomas and diseases are associated with poor prognosis with limited therapeutic options in patients who fail standard therapies, representing an area of significant unmet need. EBV latency proteins are a target of T cells, making EBV-driven lymphomas good candidates for treatment with EBV-specific T-cell therapy. EBV-specific cytotoxic T-cell lines (CTLs) seems promising in increasing overall survival, yet still ~30% of patients fail this therapy.
This might be largely due to the use of highly differentiated EBV-specific T cells for adoptive transfer which is a result of conventional long-term expansion protocol with repeated stimulations. Recent findings show that adoptively transferred early differentiated T cells (stem cell memory T cells, TSCM) improve the prognosis in chronic viral diseases and are associated with effective and durable anti-tumor response in cancer patients. TSCM might be superior to highly differentiated T cells because of their longevity and robust proliferative potential. Thus, we aimed at developing a clinically scalable rapid expansion protocol with enriched stem cell memory EBV-specific CD4+ and CD8+ T cells.

Methods:
To enrich stem cell memory T cells, rapid expansion approach was used. PBMCs were stimulated with EBV Consensus peptide pool (Miltenyi Biotec) and expanded using different culture conditions in the G-Rex production platform for 10 days. For conventional long-term expansion, PBMCs were stimulated with with EBV-transformed lymphoblastoid cell lines (LCLs) in several rounds and cultured in total up to 35 days. T cells expanded with both protocols were compared phenotypically and functionally in vitro and in vivo.

Results:
We developed a clinically-scalable protocol for expansion of Epstein-Barr virus (EBV)-specific TSCM-enriched T cells with high proportions of CD4+ T cells and broad EBV antigen coverage. These cells showed tumor control in a xenograft model of post-transplant lymphoproliferative disorder (PTLD) and were superior to previous adoptive cell therapy protocols in terms of tumor infiltration, in vivo proliferation, persistence, proportion of functional CD4+ T cells, and diversity of EBV antigen specificity.

Conclusion:
Our new protocol may pave the way for the next generation of potent unmodified antigen-specific cell therapies for EBV-associated diseases, including tumors, and other indications.

Aims: A transplant infectious disease (TID) assessment is essential to select recipients for an allogeneic-hematopoietic cell transplant (HCT) and tailor prophylactic and empirical treatment recommendations. International consensus recommendations suggest serology screening of the recipient for a number of infectious diseases before HCT, however there is no universal guidelines in the need and type of a TID consultation prior to an allogeneic HCT. In Geneva University Hospital a systematic infectious diseases consultation prior to transplantation in the context of a global evaluation before HCT is systematically performed since 2018.This study aims to describe this model of care and interventions prompted by the TID consultation in a large contemporary cohort of allogeneic HCT recipients.
Methods: We performed a retrospective single-center study to describe our model of care based on a routine TID consultation prior to an allogeneic-HCT between 2018 and 2022 in 292 adult (≥18-year-old) consecutive patients. We described the impact of the TID consultation, arbitrarily defined as major (HCT-postponement, procedure, cytomegalovirus recipient (CMV-R) serology reinterpretation) and minor.
Results: Overall, 772 interventions in 257/292 (88%) patients were observed: 95 (12.3%) major and 677 (87.7%) minor interventions. Amongst major interventions, HCT was postponed in 8 (2.7%) patients and a procedure was requested in 18 (6.2%) patients. The CMV-R serostatus was changed from positive to negative in 67 (22.9%) patients. Amongst 677 minor interventions, there were: 68 (8.8%) additional consultations with other services requested, 260 (33.7%) additional diagnostic tests requested, 102 (13.2%) additional treatments recommended, 60 (7.8%) non-CMV serology reinterpretations performed, 115 (14.9%) deviations from routine prophylaxis, and 72 (9.3%) deviations from routine antibiotic treatment recommendations in case of neutropenic fever.
Conclusion: We are proposing a structured, clearly defined, and comprehensive pre-transplant checklist for an efficient and accurate assessment of ID risks and complications prior to an allogeneic-HCT. This could potentially streamline patient care and have a positive clinical impact. Further studies or experiences like ours could help to define a global strategy or new models of care to be implemented in HCT centers worldwide in the future.

Aims: Describe our experience of baseline cytomegalovirus (CMV) serology interpretation in allogeneic hematopoietic cell transplantation recipients (HCTr), focusing on potentially false-positive (FP) CMV serology reinterpretation.
Methods: This is an observational single-center cohort study of all consecutive adult allogeneic HCTr (01. 2018-12.2022). Patients with a positive “pre-transplant” CMV serology with IgG titer < 50IU/mL (positivity cutoff: > 3IU/mL) were screened and considered FP, due to post-transfusional passive immunity, if they had low “pre-transplant” titers and/or negative CMV serology at the time of malignancy diagnosis (“baseline”), and were labeled as CMV R-negative. Plasma quantitative CMV DNAemia results during the first 6-months post-HCT were reviewed and compared between CMV FP-R and patients with negative “pre-transplant” CMV serology (true negative, TN).
Results: There were 91/292 (31%) patients with “pre-transplant” CMV serology < 50IU/mL. Among them, CMV serology (median: 6.3 IU/mL, IQR: 3.35, 11.45) was considered FP in 67/292 (22.9%) patients: 62/67 (92.5%), 2/67 (3%), and 3/67 (4.5%) had a negative, positive, and unknown “baseline” CMV serology, respectively. Donors (D) were CMV-positive (14, 20.9 %) and CMV-negative (53; 79.1 %). Plasma CMV DNAemia (mean: 15.3 tests/patient, range: 1,18) was positive in 2/67 (3%) patients at a mean of 35 days (range 33,37) post-HCT. The remaining 24/91 (26.4%) patients with positive “pre-transplant” CMV serology < 50IU/mL not reclassified as FP, due to variable reasons, had negative (2/24, 8.3%), positive (16/24, 66.7%), and unknown (6/24, 25%) “baseline” CMV serology. Plasma CMV DNAemia (mean: 18.7 tests/patient, range: 4, 34) was positive in 15/24 (62.5%) patients; none of the 2 patients with negative “baseline” CMV serology developed CMV DNAemia. There were 44/292 (15%) CMV R-TN patients; donors were CMV-negative in 33 (75%) and CMV-positive in 11 (25%) patients. Plasma CMV DNAemia (mean: 15.6 tests/patient, range: 7, 27) was positive in 3/44 (6.8%) patients at a mean of 62 days (range: 25,126) post-HCT.
Conclusion: Our data suggest that low-positive CMV serology titers prior to an allogeneic HCT may be FP, particularly in the setting of negative prior CMV serology, with significant impact on donor selection and letermovir associated costs. Additional studies are required to establish criteria that could allow HCTr CMV serology status reclassification.

The continuous spread of infectious diseases of zoonotic origin is a major concern. Tick-borne encephalitis virus (TBEV), an arthropod-borne flavivirus, represents an increasing heath risk in the endemic regions. Currently, the pathological mechanisms driving acute neurological manifestations in patients affected by neurotropic flavivirus infections remain poorly understood. Here, we developed and optimized the use of organotypic brain slices cultures to get a better insight on the mechanism of flaviviral infection.

Aims

We postulate that the extent of the damage and the long-term sequelae of neurotropic flavivirus infections are influenced by their ability to invade the central nervous system, to efficiently replicate in various cell types, and to induce strong inflammation and neuronal damages. By using organotypic cultures we aim to compare different TBEV strains in term of neuro-invasiveness, neurovirulence, and neuronal pathomechanisms.

Methods

350 μm thick slices were prepared from the cerebellum of 10-day old rat and cultured as organotypic cultures (OCs) on semipermeable membrane inserts. Slices were infected by adding TBEV-infected medium in the culture medium and on the surface of the slices. Medium was replaced after 1 hour. At different timepoints (24/48/72/96h) after infection, the viral replication was assessed in supernatant (TCID50 using Vero cells), while the tropism was determined by immunohistochemistry performed on PFA fixated whole slices. Finally, the slices were cleared to improve 3D visualization and visualized with fluorescent microscopy.

Results

By immunohistochemistry, TBEV proliferation was visible in both tissue types: in cerebellar OCs the infection mainly targeted Purkinje cells and granule cells, while in hippocampal OCs the virus was mainly detected in progenitor cells of the dentate gyrus. Measurements of the viral concentration via TCID50 showed an increase in concentration overtime in both tissue types.

Conclusions

Organotypic cultures, together with tissue clearing staining, are a well-suited model to investigate cellular tropism and replication of flaviviral infection ex vivo. Similar to observation in patients with TBE, the virus proliferates in different cell types of the cerebellum (Purkinje cells, granule cells). In contrast, TBEV replication in the hippocampus is only poorly documented in humans and warrant further investigations.

Aims: Listeria monocytogenes is primarily transmitted through consumption of contaminated food. Though invasive listeriosis is rare, symptoms are tipically severe with bacteriemia and meningitis leading to a mortality > 30%, especially in immunocompromised individuals.

Methods: We describe here an outbreak of invasive Listeria monocytogenes infections in Ticino region, a small canton of approximately 350.000 inhabitants located in the South of Switzerland, close to the Italian border. This area is served by four main hospitals located in Lugano, Bellinzona, Mendrisio and Locarno. In this context, we observed 6 cases of invasive listeriosis hospitalized from July to September 2022: one epidural abscess, one bacteraemia and 4 meningitis.

Results: Table 1 describes demographic and clinical characteristics of the patients. Though most subjects had several co-morbidities, only one received chronic immune-suppressive treatment for a previous kidney transplantation. Tests on Listeria monocytogenes specimens showed that 4 patients had serotype 4b (3 meningitis and one epidural abscess) and 2 had serotipe 1/2b, suggesting that the cases had at least two different origins. Some weeks before this outbreak, a similar event occurred in Italy; two patients, both infected with serotype 4b, revealed that they had bought fresh cheese in Italy from the same grocery store. No significant exposure for other patients was identified; they denied assumption of cheese or pork derivates in the weeks before hospitalization and co-habitants did not refer symptoms possibly correlated with listeriosis. Antibiotic treatment with amoxicillin and gentamycin was highly effective and no death was observed. Only one patient stopped gentamycin prematurely due to acute kidney failure.

Conclusions: Sporadic outbreak of Listeria monocytogenes are periodically reported. A more effective tracking of the products could be implemented and a thorough analysis of each patient’s environment should be carried out; microbiological assessment of the likely involved food could be scheduled as soon as one case is reported. This intervention, together with a detailed questioning should be performed to identify any possible source of infection. Epidemiological studies should be carried out as most accurately as possible and, finally, the joint effort between local microbiological laboratories and hospitals could be mandatory to better deal with new outbreaks.

Background
We assessed the evolution of symptoms compatible with a post-COVID condition (PCC) in healthcare workers (HCW) and the influence of reinfections and SARS-CoV-2 vaccinations after Wild-type infection.

Methods
In a prospective cohort from nine Swiss healthcare networks, HCW reported dates of positive SARS-CoV-2 swabs and vaccinations. SARS-CoV-2 anti-nucleocapsid antibodies were measured to identify uninfected HCW (ie, controls). Seropositive individuals without positive swab or with infection during Alpha/Delta circulation were excluded. In March/21 (Q1), September/21 (Q2), and June/22 (Q3), PCC symptoms and the Fatigue Severity Scale (FSS) score were asked. Number of PCC symptoms and FSS in participants after Wild-type and primary Omicron BA.1 infection relative to controls were analyzed with negative binomial mixed-effects models. For those after Wild-type infection, we assessed the impact of Omicron reinfection and vaccinations. We performed multivariable analysis (outcome: PCC symptoms at Q3), adjusting for important co-variables.

Results We included 1’201 persons (81% female, median age 43). The rate ratio (RR) regarding PCC symptoms after Wild-type infection (n=157, median follow-up 18.5 months) compared to controls decreased from Q1 (1.67, 95% confidence interval [CI] 1.31-2.13) to Q3 (RR 1.37, 95% CI 1.08-1.73). The same was observed for the FSS (Q1: RR 1.45, 95% CI 1.18-1.80; Q3: RR 1.11, 95% CI 0.90-1.37). HCW with primary Omicron infection were similar to controls (overall RR 1.00 for symptoms, 95% CI 0.86-1.17; RR 1.08 for FSS, 95% CI 0.951.22). After Wild-type infection, neither Omicron BA.1 reinfections nor vaccination had an effect on the outcomes (Fig2/Fig3). In multivariable analysis, PCC symptom number at Q1 (adjusted RR [aRR] 5.59, 95% CI 3.96-8.08) showed the strongest association with symptom number at Q3, whereas vaccination (aRR 0.96 per dose, 95% CI 0.51-1.83) and Omicron reinfection (aRR 1.19, 95% CI 0.74-1.91) did not.

Conclusions
In this HCW cohort, PCC symptoms after Wild-type infection declined over time, but were still present at 18 months, whereas primary Omicron infection did not increase symptoms. Neither Omicron reinfections nor SARS-CoV-2 vaccination had any influence.

Background: Following an international outbreak of invasive Mycobacterium chimaera infections related to aerosolization from contaminated heater-cooler-devices (HCD) of the manufacturer Sorin in 2013, regularity authorities mandated microbiological monitoring of HCDs in Switzerland. We report aerosolization of Mycobacterium chelonae detected by routine surveillance of HCDs of a different design and manufacturer.

Methods: Since 01/2016, four HCDs of the type Maquet HCU40 (Getinge) have been in use at the University Hospital Basel, Switzerland. Filtered water (≤0.22μm) is used to fill their water tanks and HCDs are located in a closed room, outside the operating room, except for emergency operations. Water from HCD-tanks is cultured monthly for mycobacteria and gram-negative bacteria. Two water pipes used to fill the devices were additionally sampled. Intermittent monthly air sampling for mycobacteria was carried out to assess the risk of aerosolization after detection of M. chelonae in HCD-water tanks.

Results: From 01/2016-05/2018, various nonfermenters but no atypical mycobacteria were cultured from the water samples of the HCDs. From 06/2018, M. chelonae was successively detected in all four HCDs (figure 1). Cultures from the water pipes remained negative. Air samples performed sporadically in 2018 and 2019 did not grow mycobacteria. From 01/2022 on, intensified disinfection measures were performed without achieving eradication of M. chelonae. Consequently, air sampling was routinely performed from 03/2022 and detected M. chelonae in 07/2022, in samples taken at 30cm and 120cm height beside three of the four running HCDs. Sequencing of the isolates showed a cluster of M. chelonae with a maximum difference of four single nucleotide polymorphisms (figure 2) and confirmed the identity of strains recovered from water and air samples. To date, no infections with M. chelonae have been related to contaminated HCDs at our institution so far.

Conclusions: Our data confirm the risk for aerosolization of mycobacteria by HCDs during cardiac surgery, irrespective of HCD-design and manufacturer. These findings highlight the need to perform routine microbiological surveillance by water and air sampling and to implement additional measures to prevent exposure of the operating field to the air exhausts of HCDs.

Aims
We assessed the prevalence of extended-spectrum β-lactamase producing Enterobacterales (ESBL-E), carbapenemase-producing Enterobacterales (CPE), and vancomycin-resistant enterococci (VRE) in rectal swabs of healthcare workers (HCW), and identified risk factors for carriage of these multidrug-resistant organisms (MDRO).

Methods
In September/October 2022, consenting participants of the SURPRISE+ study (ie, prospective multicenter HCW study from Eastern Switzerland launched during COVID-19 pandemic) answered an electronic questionnaire on occupational (including involvement in patient care) and non-occupational risk factors for MDRO (in the last 12 months) and provided a self-collected rectal swab. Screening for ESBL-E, CPE, and VRE was performed using routine diagnostic procedures. Prevalence of MDRO-carriage was calculated as percentage of participants with detection of ESBL-E, CPE, or VRE; univariable and multivariable logistic regression was used to identify risk factors for MDRO carriage; adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated.

Results
Of 3731 HCW registered in SURPRISE+, 1209 (32%) participated in this subproject. Median age was 46 years (range 16-69); 82% were female; 51% identified as nurses, 9% as physicians, and 40% as other professions. Among the 1209 participants, prevalence for ESBL-E (n=65) and CPE (n=1) was 5.4 % (95% CI 4.2-6.8) and 0.1% (95% CI 0.0-0.5), respectively; no VRE was detected. Involvement in patient care was not associated with the outcome (OR 0.60, 95% CI 0.32-1.16). In multivariable analysis, being of non-European ethnicity (aOR 6.97, 95% CI 1.40-27.30), recent travel to high-endemicity (mostly Northern Africa) countries (aOR 4.91, 95% CI 2.50-9.33), monthly (or more) sushi consumption (aOR 2.44, 95% CI 1.40-4.25), systemic antibiotics (aOR 2.07, 95% CI 1.12-3.73), and antibiotic eye drops (aOR 4.74, 95% CI 1.70-11.9) were all positively, and weekly (or more) alcohol consumption (aOR 0.50, 95% CI 0.27-0.88) negatively associated with MDRO carriage.

Conclusion
In this large cohort of over 1200 HCW from various institutions across Eastern Switzerland, MDRO carriage, mostly ESBL-E, was 5.5 %; patient contact was not a risk factor for MDRO carriage. Besides known factors such as travel to high-endemicity countries and exposure to systemic antibiotics, we identified antibiotic eye drops and regular consumption of sushi as potentially novel risk factors for ESBL-E carriage.

Aims
Triggered by an increase in scabies cases within municipal asylum centers, our institution (KSSG) was called upon to support center administrators through the cantonal medical service. Our aim was to mitigate the transmission of scabies by implementing standardized preventive and therapeutic measures in all asylum centers at federal, cantonal and municipal level, given the regular transfer of individuals between these institutions.

Methods
All relevant parties, including representatives from the asylum centers, cantonal medical service, state secretariat for migration (SEM), dermatology and infectious disease specialists, were actively engaged. A standardized electronic survey was carried out to determine the prevalence of scabies in 1 federal asylum center and in 4 municipal centers. Data on population characteristics, treatment regimens and non-pharmacological measures were gathered. Based on the survey results, a bundle of measures (standardized pharmacological and non-pharmacological treatment, guidelines and information material) were developed and implemented. Additionally, prospective surveillance in all centers was established.

Results:
In February 2023, scabies outbreaks were reported in 2 out of 5 centers, with a prevalence of 30.9% and 31.8%, while the remaining 3 had substantially lower rates of 5.4%, 10.5%, and 7.3%. Asylum seekers were not routinely examined or interviewed about symptoms suggestive of scabies at entry. None of the centres systematically provided treatment for close contacts of index patients. After the introduction of a bundle of interventions (clinical examination and assessment of scabies symptoms for all asylum seekers, standardized systemic treatment with ivermectin for symptomatic patients and close contacts, release of information material in various languages and uniform guidelines for all centres) the outbreaks in the two centers could be successfully controlled and the prevalence was kept at a low level in the other centers (respectively as of April 2023: 0%, 6.1%, 5.5%, 5.5% and 4%).

Conclusion
Effective control of scabies in asylum centers can be achieved through the implementation of a standardized bundle of measures. Close collaboration between all involved stakeholders enabled prompt implementation of the intervention package and successful outbreak control. Our regional experience could provide a model for a uniform national strategy to control scabies among asylum seeker

Background: The IPCAF questionnaire developed by the World Health Organization (WHO) is an instrument used worldwide to assess the implementation of WHO recommendations on the most important core components of IPC programs at the hospital level. It was also used as part of the Swiss Point Prevalence Survey (PPS) on healthcare-associated infections organized by Swissnoso. We wanted to determine to what extent the questionnaire was homogeneously completed within our IPC team at the Cantonal Hospital St. Gallen.

Methods: All IPC team members completed the IPCAF questionnaire independently and anonymously. The results were evaluated by an IPC team member who did not participate. The questionnaire contains a total of 110 questions. These questions were divided into eight key components: 1: Hygiene and infection prevention (IPC) strategy; 2: Guidelines and policies; 3: Education and training; 4: Surveillance of healthcare-associated infections; 5: IPC - interventions; 6: Monitoring/audits of hygiene/IPC practices and feedback; 7: Workload, staffing, and bed occupancy; Key component: Supplies and equipment.

Results: The questionnaire was sent to 12 staff members with a 100% response rate. Participants were two residents, seven IPC experts, and three attendings. Work experience varied from 0 to more than 10 years. The three attending physicians who participated had an overall agreement of 76%. The agreement of responses to the IPC expert questions was 55%. There was no significant difference between the IPC experts regarding their professional experience and consistency of responses. For the two residents, the consistency was 78%. Considering all answers together, the consistency of answers was 100% in 54 questions. For an additional 27 questions, agreement ranged from 99% to 74%. This included questions from all key components. In 6 questions, the agreement was 50%. The questions were from components 1, 4, 5, and 7.

Conclusion: In many cases, questionnaire responses were consistent. However, there were some questions where responses varied. Overall agreement was highest among senior physicians, suggesting that communication with other team members is sometimes poor. This may indicate that certain activities need to be communicated more transparently within the IPC team. It is also clear that there is room for interpretation on some questions. It remains to be seen to what extent the results are valid for other hospitals.

Background
Healthcare-associated infections in long-term care are associated with substantial morbidity and mortality. While infection prevention and control (IPC) guidelines are well-defined in the acute care setting, evidence of effectiveness for long-term care facilities (LTCF) is missing. We therefore performed a systematic literature review to examine the effect of IPC measures in the long-term care setting.
Methods
We systematically searched PubMed and Cochrane libraries for articles evaluating the effect of IPC measures in the LTCF setting since 2017, as earlier reviews on this topic covered the timeframe up to this date. Cross-referenced studies from identified articles and from mentioned earlier reviews were also evaluated. We included randomized-controlled trials, quasi-experimental, observational studies, and outbreak reports. The included studies were analyzed regarding study design, type of intervention, description of intervention, outcomes and quality. We distinguished between non-outbreak and outbreak settings.
Results
We included 74 studies, 34 (46%) in the non-outbreak setting and 40 (54%) in the outbreak setting. The most commonly studied interventions in the non-outbreak setting included the effect of hand hygiene (N = 10), oral hygiene (N = 6), antimicrobial stewardship (N = 4), vaccination of residents (N = 3), education (N= 2) as well as IPC bundles (N = 7). All but one study assessing hand hygiene interventions reported a reduction of infection rates. Further successful interventions were oral hygiene (N=6) and vaccination of residents (N = 3).
In outbreak settings, studies mostly focused on the effects of IPC bundles (N = 24) or mass testing (N = 11). In most of the studies evaluating an IPC bundle, containment of the outbreak was reported.
Overall, only four articles (5.4%) were rated as high quality.
Conclusion
In the non-outbreak setting in LTCF, especially hand hygiene and oral hygiene have a beneficial effect on infection rates. In contrast, IPC bundles, as well as mass testing seem to be promising in an outbreak setting.

Aims: To detect and describe an outbreak by Serratia marcescens colonizing patients and causing invasive infections in the pediatric intensive care unit (ICU) using whole genome sequencing (WGS); and to describe the measures implemented to overcome this outbreak.
Methods: Two infants with invasive S. marcescens infections in the ICU of the University Children’s Hospital Zurich prompted an outbreak investigation including infection control measures and screening in neonatal and pediatric ICU patients. S. marcescens isolates were characterized by whole WGS.
Results: Between July 2020 and December 2022, S. marcescens was detected in 41 critically ill children (age 4 days–14 years, 83 % < 1 year). 11 patients (27 %, median age 32 days) were infected and 30 patients (73 %, median age 84 days) were found to be colonized. The infections consisted of septic shock (n= 4), central venous catheter infection (1), meningitis (1), pleuritis (2), ventilator associated pneumonia (2) and urinary tract infection (1). WGS identified 4 different core genome mulitlocus sequence typing (cgMLST) based clusters of S. marcescens. Eight infected and 6 colonized patients belonged to cluster 1 (isolates with ≤ 8 cg allele differences) which occurred over a period of 15 months. One infected and 1 colonized infant belonged to cluster 2, and 2 colonized children each to cluster 3 and 4, respectively. Overall, in 30 of 533 screened patients (5.6 %) S. marcescens colonization was detected. 25 (61 %) colonized patients had a negative screening on admission indicating likely hospital transmission. Outbreak measures including strict patient zone control, reinforcement of hand hygiene, and sensibilization of staff members were implemented from October 2020 in an interdisciplinary team approach, and together with patient screening for colonization with S. marcescens were further escalated during a period of 15 months. Thereafter, screening during 11 months identified only individual S. marcescens genotypes not related to any outbreak.
Conclusion: We demonstrate the impact of screening and WGS to detect and manage an outbreak of S. marcescens. Screening combined with WGS permitted to identify the full extent of the outbreak and underlined the continued need for enhanced efforts for sustained implementation of infection control measures to end the outbreak. If clinical alertness for infections and readiness to promptly implement actions is optimized, nosocomial infections can be limited.

Introduction/Aim: Multidrug-resistant organisms (MDRO) are the cause for difficult-to-treat infections and can be transmitted from patient to patient. Data on the prevalence of MDRO in rehabilitation patients, who were hospitalised in high-risk institutions such as intensive care units (ICU), stroke units, or medical institutions abroad prior to admission are scarce. The aim of this study was to evaluate our admission screening algorithm.
Method: In our rehabilitation clinic, we established systematic screenings for MDRO on admission and five days later. All patients with hospitalization in an ICU, an intermediate care unit (IMC), stroke unit, or in medical institutions abroad prior to admission to the rehabilitation clinic were screened. Data were analysed and a decision tree was created based on previous healthcare contacts of patients; numbers needed to screen (NNS) were calculated for different settings. Screening costs were calculated, assuming costs of 150 Swiss francs (CHF) for negative, and 200 CHF for positive screenings.
Results: Between April 2021 and January 2023, we detected six unknown MDRO carriers (1 VRE, 2 MRSA, 2 ESBL, 0 carbapenemase-producer) among 228 screened patients (2.6%). Three of 30 patients (10%) were hospitalized in medical institutions abroad before admission (NNS 10). One of 62 (1.6%) and two of 134 (1.5%) patients had a history of IMC/stroke unit or ICU stay, respectively (NNS 23 and 33). The overall NNS was 39. A decision tree model for differences between various wards in this rehabilitation institution did not show any significant differences. Total costs were ca. 50’000 Swiss francs (150 Sfr for negative, 200 Sfr for positive test), considering that about 100 patients were screened only once.
Conclusion: MDRO detection rate in admission screening was relatively low for patients with a history of hospitalization in a Swiss ICU, IMC, or stroke unit, but was higher for those with previous hospital admissions abroad. The latter population should be preferentially screened on admission due to increased risk for colonisation with MDRO, as recommended by national guidelines (Swissnoso). However, nearly half of MDRO carriers would be missed if screening is only limited to this population. Based on these results we adapted the screening regime by limiting to patients who were hospitalised abroad or in Swiss ICUs. Thereby, about 25% of screenings could be spared with still preserving a detection sensitivity of 83% (5/6 patient).

Aims: In Switzerland, surveillance systems for respiratory viruses exist for the outpatient (Sentinella) and hospitalized (CH-SUR) population, but not for inhabitants of LTCF. Reasons could be the low interest in this population group, the shortage of staff and little experience in data collection. The aim was to establish a surveillance system in LTCF that is feasible, resource-saving, and leads to actions that prevent outbreaks.
Methods: Within the framework of OSKAR (Ostschweizer Kompetenznetz für Infektionsprävention in Alters-und Pflegeheimen), surveillance was established in seven pilot institutions in Eastern Switzerland. Institutions agreed to participate in the outbreak-based surveillance, were informed and trained at the beginning and regularly reminded by email. Institutions were asked to report clusters, defined as >2 residents with symptoms of an acute respiratory infection that limited their daily activities within 5 days per department and to swab at least two affected residents (nasopharyngeal Sars-CoV2-PCR and multiplex-PCR for resp. virus). Depending on the size of the outbreak, infection prevention measures were recommended by the study team. Data on the number of affected employees and residents were collected at the end of each outbreak.
Results: Outbreak surveillance was conducted from week 40/2022 to week 12/2023 in 7 LTCFs in the canton of St.Gallen. At median 100 residents (67-220) lived in the institutions, and 190 employees (121-270) worked there. In total, there were 5 outbreaks, affecting 49 residents and 12 employees. The first outbreak occurred at 16.10.22, the last ended on the 24.2.23. at median they lasted 12 days (5 to 24 days) Among these, one large outbreak was caused by RSV, involving 22 residents and 1 employee, another was caused by Sars-CoV2 with 12 affected residents and 9 employees. The other three were smaller caused by influenza A, Sars-CoV2 and Rhinovirus. All outbreaks were rapidly controlled with intensified infection prevention measures such as wearing masks when in direct contact with residents.
Conclusion Outbreak-related surveillance is feasible in LTCF with reasonable facility effort and provides valuable information about the causing viruses. Underreporting cannot be excluded and was minimized by regular reminders which where necessary to obtain the most complete data possible. A high number of different viruses have caused outbreaks of varying extent.

BACKGROUND:
Excessive antibiotic use is common and a major contributor of antimicrobial resistance (Murray et al., 2022). We developed ePOCT+, a novel digital Clinical Decision Support Algorithm (CDSA) to guide health workers in the management of sick children in primary care (Tan et al., 2023).

AIM:
To evaluate the impact of the ePOCT+ CDSA on antibiotic prescribing and clinical cure compared to usual care, we conducted a pragmatic, open-label, parallel-group, cluster-randomized trial in 40 primary care facilities in 2 rural and semi urban areas of Tanzania (NCT05144763).

METHODOLOGY:
Eligible health facilities were randomized 1:1 stratified by location, attendance rate, and level of care. We included children under 15 years seeking care for an acute illness at participating health care facilities. The intervention consisted of the use of ePOCT+, additional point-of-care tests (C-reactive protein, hemoglobin, pulse oximeter), mentoring, and data feedback. Integrated Management of Childhood Illness training was provided to health facilities in both groups. The co-primary outcomes were 1) an absolute reduction in antibiotic prescription by 25%, and 2) non-inferiority in terms of day 7 clinical failure (upper limit of the adjusted relative risk (aRR) confidence interval at 1.3).

RESULTS:
Between December 2021 and October 2022, we included 23,593 cases in the 20 ePOCT+ health facilities, and 20,713 in the 20 usual care facilities. Antibiotic prescription in cases managed per-protocol was 23.2% in ePOCT+ facilities, and 70.1% in usual care facilities, corresponding to an absolute reduction of 46.9% (95% CI 45.9; 47.8), and aRR of 0.35 (95% CI 0.29, 0.43), p < 0.001. At day 7, additional medications were taken by 7.3% of cases in the ePOCT+ arm and 7.4% in the usual care arm. Per-protocol day 7 clinical failure in the ePOCT+ arm (3.7%) was non-inferior to the usual care arm (3.8%) [aRR 0.97 (95% CI 0.85; 1.10)]. Unplanned re-attendance visits were less common in ePOCT+ facilities compared to usual care facilities (1.7% vs 2.9%).

CONCLUSION:
The use of the ePOCT+ digital CDSA allowed clinicians to safely reduce antibiotic prescription by a factor of 3 in near programmatic conditions.

Background
In Sub-Saharan Africa, tuberculosis (TB) is a leading cause of mortality. There is a need to integrate sustainable triage and management strategies into standard care. We investigate the diagnostic performance of thoracic point-of-care ultrasound (POCUS) in the outpatient consultation of a referral hospital in urban Benin.
Methods
This 1-year prospective cohort study includes adult patients presenting with a lower respiratory tract infection (LRTI) according to the treating physician (October 2021 - 2022). Standardized ultrasound images and videos in 14 lung zones including 4 apical views and in the subxyphoid zone (pericardium) are collected. A blinded expert reviewed all images according to pre-specified categories. TB was defined as a GenXpert MTB/RIF® assay on sputum. We evaluate the association of these ultrasound categories with TB using univariate logistic regression. We conducted a multivariate logistic regresion using ultrasound findings to derive a diagnostic score. All patients had a screening for HIV (Alere Determine® HIV-1/2 ) and and Sars-CoV-2 (XPRESS®) on naso-pharyngeal swab.
Results
Out of 267 patients included, 91 (34%) were TB positive (TB+) and 176 (66%) TB negative (TB-). Overall, 57 (22%) patients had documented HIV, 9 (10%) among TB+ (median CD4 count/mm3 of 83 [IQR 48 - 492]) and 48 (28%) among TB- (median CD4 count/mm3 of 115 [IQR 49-397]) (p = 0.77). In total 41 (15%) patients were COVID-19 positive, 9 (10%) among TB+ and 32 (18%) among TB- (p = 0.069). TB+ was associated with consolidations larger than 1 cm in any quadrant (p < 0.001, odds ratio [OR] 11 95%CI 5.5-20), apical subpleural lesions < 1cm (p = 0.002, OR 2.2 95%CI1.3-3.9) apical coalescent B-lines (p = 0.04, OR 3.3 95%CI 1-10.5) and pericardial effusion of any size (p = 0.002, OR 2.4 95%CI1.4-4). Combining thoracic ultrasound features in a multivariate logistic regression score showed an area under the receiver-operating curve of 86% to detect TB. The optimal cut-point chosen with Youden index had a sensitivity of 91%, a specificity of 61%, a negative predictive value of 66 and a positive predictive value of 70.
Conclusion
With its high AUC, thoracic POCUS is a promising triage tool to exclude TB in the outpatient setting for patients with LRTI symptoms in a TB endemic region. Further multicentric data are necessary to validate these preliminary findings.

Background:
Traveller's diarrhoea remains one of the main causes of medical consultations after returning from travel.(1) Although the risk of acquisition has decreased with improved hygiene measures, the two-week incidence rate remains 10-40%.(1) In cases of moderate to severe travellers' diarrhoea, treatment with azithromycin antibiotic therapy is recommended.(2) Antibiotic therapy reduces the duration of symptoms from 50-93h to 16-30h.(3-4) In this context, it was usual in travel medicine, during pre-travel consultations, to prescribe stand-by-emergency treatment (SBET) in situations where access to care was possibly limited. However, antibiotic use during travel is predictive of asymptomatic carriage of multidrug-resistant enterobacteria, and reducing antibiotic prescribing is one of the main recommendations to address this problem. In 2017, it was decided at the Division of Tropical & Humanitarian Medicine (SMTH) of the Geneva University Hospitals to remove norfloxacin and azithromycin from pre-printed prescriptions for pre-travel consultations, in order to reduce the incentive to prescribe. We therefore evaluate the effectiveness of such an intervention.

Method:
Comparison of the proportion of reserve antibiotic prescriptions for traveller's diarrhoea between 2014 and 2019. A total of 280 patients are included (140 in each arm). Information collected about them is: age, gender, comorbidity, destination and duration of travel, prescriber of the pre-travel consultation and presence or absence of antibiotic prescription as well as class. Descriptive analyses were performed to describe the socio-demographic characteristics of the included travellers and the type of travel.

Results:
In 2014, 37 (26.4%) travellers were prescribed a back-up antibiotic compared to 0 (0%) in 2019. No differences in prescribing were identified by socio-demographic characteristics of the travellers as well as by type of travel and prescriber.

Conclusion:
Removing antibiotics from the pre-printed prescription is an effective measure to reduce antibiotic prescribing. Thus, the recommendations of the Swiss Society of Tropical Medicine and Travel Medicine were followed.(5)

Background: Changes in sexual decision-making during travel are common and can put travelers at risk of HIV and other sexually transmitted infections (STIs). Integrating sexual health counselling into pre-travel consultations may mitigate such risks, however, little is known about such interventions, especially in regards to HIV Pre-Exposure Prophylaxis (PrEP).
Objectives: This qualitative study aimed to describe the experiences, perceptions and practices of travelers and health professionals on integrated sexual health pre-travel counseling at the University of Zurich’s Centre for Travel Medicine (CRM). This study was undertaken to inform practice.
Methods: 24 semi-structured interviews were conducted with 13 travelers (7 women/5 men/1 other) who attended CRM for pre-travel consultations and 11 health professionals (3 nurses, 7 physicians, 1 other) who provided pre-travel counseling, 7 had experience in STI counseling too. Data were analyzed using reflexive thematic analysis.
Results: Travelers’ and health professionals' experiences, perceptions, and practices are described by 1 constituting theme and 3 subthemes. “The ambiguity to talk about sexual health in relation to traveling" was found across all data. Travelers and health professionals describe mixed feelings when talking about sexual health, travelers find sex when traveling normal, but don’t want to expose themselves, while health professionals find sexual health important to address, but don’t want to offend their clients. This ambiguity runs through the subthemes. First, “Sexual health counseling is a sideshow", both travelers and health professionals find sexual health counseling insufficiently addressed or marginalized. Second, “Finding a way into the play of sexual health counseling” demonstrates that it is challenging to reflect on or start interactions on sexual health and risks. Third, "Sexual health counseling is improvisational theater" describes the high degree of flexibility and skill required by health professionals to meet the diverse demands of travelers. Whereas most professionals focus on vaccinations and condoms, other risk minimizing strategies, in particular HIV-PrEP, are poorly addressed.
Conclusions: Integrating sexual health counseling into pre-travel practices requires travelers to be prepared for awareness, and professionals benefit from reflection on attitudes as well as structures and training to increase knowledge and skills, e.g. in prevention strategies as HIV-PrEP.

Introduction: Despite that, Japanese encephalitis (JE) is the most important viral encephalitis in Asia, most travelers to endemic countries are at low risk for clinical JE. It is important for clinicians to consider this rare diagnosis in returning travelers from endemic countries with acute encephalitis.

Case report: We describe the case of a 53 years old male who was brought to hospital unconscious after being found at home in status epilepticus in July 2021. Three days prior, the patient had returned from a two-week trip to Indonesia, where he spent five days in Jakarta, mandatorily confined to a COVID-19 quarantine hotel, and eight days travelling in Ubud in Bali. Upon arrival to hospital, the patient was already intubated. His temperature was 38.3°C. Laboratory testing revealed a leucocytosis of 18'700 /ul, with lymphopenia of 500 cells/ul, acute kidney injury and elevated transaminases. Lumbar puncture revealed 52 mononuclear cells/ul, one polymorphic cell/ul, protein of 494mg/L, lactate of 4mmol/L. Meningitis was suspected, and treatment with ceftriaxone, amoxicillin and acyclovir was initiated. Bacterial cultures and the multiplex PCR for neurotropic pathogens of the CFS were negative. The MRI showed diffuse edema in the mesencephalon and diencephalon compatible with a viral encephalitis. Tick born encephalitis (TBE) IgM antibody titers were high, IgG was negative. Due to the travel history, an acute infection with TBE virus was very improbable, therefore a cross reaction with another flavivirus was suspected. Further antibody testing revealed positive IgM titers for dengue virus, West Nile virus, yellow fever and Japanese encephalitis. However, IgG was positive only for Japanese encephalitis, which led us to the diagnosis. The patient had a severe clinical course, with prolonged coma requiring ventilator assistance for one month. In addition, he developed tetraplegia due to an axonal sensorimotor polyneuropathy. After six months of inpatient rehabilitation, the patient was able to walk with a walker, and had mild cognitive impairments. He remains unable to work until now.
Conclusion: Although the risk of Japanese encephalitis in travelers is very low, the decision whether to vaccinate should consider the potential high morbidity of the infection. Travelers should be informed of this condition as an additional reason to adopt personal protective measures to prevent mosquito bites in endemic regions.

Background:
The number of immunosuppressed travelers has been increasing in recent years. They present an increased risk of travel-related illnesses and complications[1]. One of the main preventive measures against infection before travel remains vaccination. However, vaccine response is impaired and live attenuated vaccines are contraindicated. Pre-travel consultations can be complicated due to the heterogeneity of patients and treatment[2]. Basic vaccination recommendations for transplanted patients are documented[3]. But the heterogeneity of biotherapies and their immune effect added to the fear of the vaccination in Multiple Sclerosis (MS) patients explains the absence of clear recommendation[4].Since 2013, the division of Tropical and Humanitarian Medicine (SMTH) in Geneva University Hospitals (HUG) have set up a specialized consultation for immunosuppressed travelers[5]. After few years of experience, we developed practical expertise, and could collect immunogenicity data of our patients. The aim of this study is to present the cohort of MS patients managed in our division and the systematic structure of the consultation than was created. Further studies targeting the vaccine immunogenicity according to MS treatment will follow.
Method:
Retrospective analysis of the number of patients with MS who visited the SMTH in HUG between 2016 and 2019. Patients aged >18 years with a diagnosis of MS planned or treated with fingolimod or natalizumab were included. Patients had pre- and post-vaccination serologies for HAV, HBV, rabies, diphtheria and tetanus. Depending on the degree of immunosuppression and immune response, the vaccination regimen included increased number of vaccine doses.
Results:
A total of 324 patients were screened. Only 227 had received vaccines and had serologies and could be included. The average age was 40 years old. 67% were women and 89% were from Switzerland or Europe. 82% had relapsing-remitting MS. 44%, 41% and 96% of patients were never vaccinated against HBV, HAV and rabies. On the other hand, 89% of patients had a complete vaccination schedule against diphtheria and tetanus.
Conclusion:
This is the first retrospective study of vaccination in MS patients planned to be or already treated with fingolimod or natalizumab. Vaccine response data that will emerge from this analysis will allow to optimize vaccination in immunosuppressed MS patients.

Introduction
Immunocompromised hosts, particularly with cellular immunodeficiency, are at higher risk to reactivate asymptomatic infections with Leishmania spp. We report 2 cases of visceral leishmaniasis with delayed diagnosis due to suspicion of lymphoma recurrence and 1 of treatment refractory cutaneous leishmaniasis complicating completion of lymphoma treatment. All reported a history of travel to the Mediterranean region.
Case 1
A 54 y.o. male was treated for Hodgkin’s lymphoma. During the last chemotherapy cycles he started to experience a new type of fevers - different from the ones he knew from lymphoma. Also, he developed bicytopenia and weight loss of 5kg. In the following 6 months, several diagnostic procedures could not confirm lymphoma relapse. Finally, diagnosis of L. infantum was confirmed through serology and bone marrow biopsy (BMB). Given his recent immunosuppressive treatment, he was treated with liposomal amphotericin B (L-AmB). Daily fevers subsided after the 2nd dose, while splenomegaly and bicytopenia resolved over the following weeks.
Case 2
A 63 y.o. male was diagnosed with lymphoplasmocytic lymphoma and treated with Rituximab-Bendamustin. He was in remission until 8 months later, when he developed recurrent fever, weight loss of 3 kg over 2 months and new onset of progressive pancytopenia. A PET-CT showed hypermetabolic splenomegaly without lymphadenopathy. BMB showed no features of lymphoma recurrence but intracellular organisms in macrophages. PCR for Leishmania spp. was positive. He was traeated with L-AmB for 7 days (cumulative dose 21mg/kg) with resolution of fever after day 3.
Case 3
A 72 y.o. male was treated with two cycles of DA-EPOCH-R chemotherapy for a progressing Burkitt-like lymphoma. In staging PET-CT hypermetabolic activity was detected over the mid upper arm. Biopsy revealed no manifestations of lymphoma, but L. tropica. The lesion increased and developed secondary central ulceration despite treatment with L-AmB up to 40mg/kg. Second line treatment with local cryotherapy and infiltration of the lesion with N-Methylglucamin-Antimonat followed by 2° prophylaxis with L-AmB every three weeks finally lead to resolution of the lesion. Further treatment of his lymphoma was paused, also due to marked asthenia.
Discussion
Clinicians caring for patients with predominant cellular immunodeficiency should remain aware of this possible and well treatable differential diagnosis that may mimic a relapse or refractory lymphoma.