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Sana Dastgheyb,1 Keith Fishlock,2 Constantine Daskalakis,1 Jami Kessel,3 Paul Rosen2 1Thomas Jefferson University, Philadelphia, PA, 2Nemours Children’s Health System, Wilmington, DE, 3Nationwide Children’s Hospital Columbus, OH, USA Introduction: Management of pediatric pain from medical procedures is of great importance for improving both patient care and experience. In this study, we investigated methods of managing acute pain in infants and children by studying the correlation between the number of attempts to complete painful procedures, given different comfort measures. Methods: The study is a retrospective review of 74,276 procedures performed at two pediatric hospitals in an integrated academic children’s health system between 2013 and 2016. We compared three comfort measures most frequently offered: positions of comfort (POC), distraction (DIST), and pharmacological (PHARM). These methods were compared in the setting of four procedures: peripheral intravenous (PIV) catheter insertion, gastrointestinal tube placement, incision procedures, and bladder catheterization. We used the number of attempts needed to complete a procedure as a measure of efficacy minimizing distressing experience in an acutely painful setting (single attempt vs repeat attempts). Results: Among younger children, DIST appears superior to the other two methods; it performs significantly better for three of the four procedures (PIV catheterization, incision wound, and urinary catheterization) among infants aged

Establishing the etiology of invasive fungal infections is important to guide therapeutic options and for epidemiologic purposes. Formalin-fixed, paraffin-embedded (FFPE) tissue specimens from patients with proven invasive fungal infections are valuable to determine the etiology of systemic fungal infections. We compared different polymerase chain reaction (PCR) amplification strategies from FFPE tissue blocks to identify agents of invasive fungal infections. We found that specific PCR assays show superior sensitivity in the identification of DNA of Mucorales and Aspergillus and mixed infections caused by both as compared to broad-range PCR assays. Shorter amplicon lengths and less detection of contaminating fungal DNA are potential factors involved. However, detection of fungal DNA by highly sensitive specific PCR assays in the absence of demonstration of fungal elements in tissue suggests that PCR results should be interpreted in the context of the histopathology and clinical findings. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance has become a major public health concern, and animal agriculture is often implicated as a source of resistant bacteria. The primary objective of this study was to determine prevalence of antimicrobial resistance in Salmonella and E. coli from healthy animals on dairy farms in Pennsylvania. Confidence intervals (CI) of farm prevalence were calculated for resistance, and the comparisons between different animal groups were adjusted for within-farm clustering. The secondary objective was to identify potential risk factors associated with antimicrobial resistance. In particular, we investigated the correlations between previous antimicrobial use and current resistance in E. coli using multiple logistic regression models. A total of 444 composite manure samples were collected from 80 herds in Pennsylvania. Four age and production groups were included: pre-weaned calves, post-weaned calves, dry cows, and lactating cows. E. coli (n = 2370) and Salmonella (n = 1095), when isolated from the manure composite samples (n = 444), were screened for resistance on antimicrobial supplemented agar. Isolates of interest were further assayed against 14 antimicrobials using a broth microdilution method. Salmonella was isolated from at least one composite manure sample from 51 (67%) farms, with 99% being pan-susceptible, and was detected more frequently in lactating cows and dry cows than pre- and post-weaned calves. The most prevalent Salmonella serogroups were K, C1, and C2. Among the E. coli isolates, resistance was more frequently detected in pre-weaned and post-weaned calves than in dry and lactating cows for all 14 antimicrobials tested (P < 0.05). Multi-drug resistance (resistant to ≥3 antimicrobial classes) in E. coli was detected in 66 farms (83%) and was detected more often in pre-weaned calves (P < 0.05). The blaCTX-M and blaCMY genes were found in cephalosporin-resistant E. coli from 5% and 35% of the farms surveyed, respectively. A number of risk factors, including antimicrobial use, were found to be associated with an increased likelihood of resistance in E. coli, and these associations were not limited to the same antimicrobial classes. The results of this study showed dairy farms, especially pre-weaned calves and their environment, are significant reservoirs for antimicrobial resistance, and antimicrobial use may aggravate the resistance problem. [ABSTRACT FROM AUTHOR]

The extent to which carriage of antibiotic resistant bacteria in food animals is responsible for the burden of antibiotic resistance in human infections is currently not well known. Thus, there is a need to further evaluate the genomic diversity of multidrug resistant (MDR) bacteria and the microbial communities in which they are found within these animals. To further evaluate the prevalence of antibiotic resistance in the feces of dairy animals, we sequenced the genomes of 160 antibiotic resistant Escherichia coli and 28 fecal metagenomes isolated from adult dairy cows, veal calves, and pre-weaned calves. E. coli isolates were collected from composite fecal samples and fecal grab samples taken directly from the animal. Isolates were screened for susceptibility to a panel of 14 antibiotics, and 150 showing resistance to at least one antibiotic and 10 antibiotic-susceptible isolates were selected for whole genome shotgun sequencing using a paired-end sequencing approach on an Illumina NextSeq 500. Twenty-eight fecal grab samples collected from animals shedding variable levels of antibiotic resistant E. coli were selected for shotgun metagenomics sequencing. Phylogenetic relationships among the E. coli genomes were inferred using a maximum likelihood approach in RAxML, and sequence types were determined in silico. At least four E. coli isolates from each of the major phylogroups were detected. The most frequently detected sequence types were ST88 (10% of all isolates), ST10 (9%), and ST117 (6%). Within these sequence types, isolates from different animals on the same farm and isolates from different farms were closely related, indicating that some strains of antibiotic resistant E. coli may be circulating among dairy herds within the same region. Interestingly, several MDR ST117 isolates were closely related to human ExPEC isolates and isolates recovered from chickens with colibacillosis. Metagenomic analyses indicated that for all samples tetracycline resistance genes were the most frequently identified resistance genes (61% of all resistance genes), followed by aminoglycoside (20%), macrolide (8%), beta-lactam (3%), sulfonamide (0.8%), and trimethoprim (0.6%) resistance genes. In veal calf fecal samples trimethoprim and fluoroquinolone resistance genes were more frequently detected than in pre-weaned dairy calf samples. Future work will identify genomic features that may confer persistence of high frequency antibiotic resistant E. coli strains and sequence types in the dairy cow hindgut and factors that influence the presence of antibiotic resistance in pre-weaned calves. [ABSTRACT FROM AUTHOR]

The emergence and ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the need for rapid vaccine development platforms that can be updated to counteract emerging variants of currently circulating and future emerging coronaviruses. Here we report the development of a "train model" subunit vaccine platform that contains a SARS-CoV-2 Wuhan S1 protein (the "engine") linked to a series of flexible receptor binding domains (RBDs; the "cars") derived from SARS-CoV-2 variants of concern (VOCs). We demonstrate that these linked subunit vaccines when combined with Sepivac SWE™, a squalene in water emulsion (SWE) adjuvant, are immunogenic in Syrian hamsters and subsequently provide protection from infection with SARS-CoV-2 VOCs Omicron (BA.1), Delta, and Beta. Importantly, the bivalent and trivalent vaccine candidates offered protection against some heterologous SARS-CoV-2 VOCs that were not included in the vaccine design, demonstrating the potential for broad protection against a range of different VOCs. Furthermore, these formulated vaccine candidates were stable at 2-8 °C for up to 13 months post-formulation, highlighting their utility in low-resource settings. Indeed, our vaccine platform will enable the development of safe and broadly protective vaccines against emerging betacoronaviruses that pose a significant health risk for humans and agricultural animals., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Arinjay Banerjee reports a relationship with Canadian Institutes of Health Research that includes: funding grants. Trina Racine reports a relationship with Coalition for Epidemic Preparedness Innovations that includes: funding grants. Darryl Falzarano reports a relationship with Canadian Institutes of Health Research that includes: funding grants. Arinjay Banerjee, Qiang Liu, Darryl Falzarano has patent fusion polypeptides, immunogenic compositions, methods and uses thereof pending to VIDO, University of Saskatchewan. The findings from this study have led to a patent application: fusion polypeptides, immunogenic compositions, methods and uses thereof. USPTO Patent application, United States of America. USPTO Patent application #63/452,586 (March 16, 2023). The authors declare no other conflict of interest. Morgane Joessel, Falko Apel, Thomas Courant, and Nicolas Collin from VFI used their trademarked Sepivac SWE™, a squalene in water emulsion (SWE) adjuvant in this study to formulate the vaccine candidates. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.]., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Gamma-delta (γδ) T cells are a major immune cell subset in pigs. Approximately 50% of circulating T cells are γδ T cells in young pigs and up to 30% in adult sows. Despite this abundance, the functions of porcine γδ T cells are mostly unidentified. In humans and mice, activated γδ T cells exhibit broad innate cytotoxic activity against a wide variety of stressed, infected, and cancerous cells through death receptor/ligand-dependent and perforin/granzyme-dependent pathways. However, so far, it is unknown whether porcine γδ T cells have the ability to perform cytotoxic functions., Methods: In this study, we conducted a comprehensive phenotypic characterization of porcine γδ T cells isolated from blood, lung, and nasal mucosa. To further analyze the cytolytic potential of γδ T cells, in vitro cytotoxicity assays were performed using purified γδ T cells as effector cells and virus-exposed or mock-treated primary porcine alveolar macrophages as target cells., Results: Our results show that only CD2 + γδ T cells express cytotoxic markers (CD16, NKp46, perforin) with higher perforin and NKp46 expression in γδ T cells isolated from lung and nasal mucosa. Moreover, we found that γδ T cells can exhibit cytotoxic functions in a cell-cell contact and degranulation-dependent manner. However, porcine γδ T cells did not seem to specifically target Porcine Reproductive and Respiratory Syndrome Virus or swine Influenza A Virus-infected macrophages, which may be due to viral escape mechanisms., Conclusion: Porcine γδ T cells express cytotoxic markers and can exhibit cytotoxic activity in vitro. The specific mechanisms by which porcine γδ T cells recognize target cells are not fully understood but may involve the detection of cellular stress signals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Bettin, Darbellay, van Kessel, Dhar and Gerdts.)

Background : Infectious endocarditis (IE) remains a critical condition despite all the medical advances in recent decades. Reliable pathogen identification is indispensable for precise therapy. The aim of this study was to evaluate the diagnostic and therapeutic benefit of additional polymerase chain reaction (PCR) in comparison with microbiological culture alone based on intraoperative tissue sampling for patients operated on due to IE. Methods : A total of 224 patients diagnosed with acute or subacute IE were analyzed. Intraoperatively resected infectious tissue was analyzed using both PCR and microbiological culture. Subsequently, the results of the detection of bacteria obtained based on intraoperative measurements from tissue via culture and PCR were compared with preoperative blood culture results. Furthermore, we evaluated the therapeutic impact of the culture and/or PCR results obtained from cardiac tissue. Results : The 224 patients were 63 ± 17 years old, and 64 (29%) were female. In total, 149 (67%) suffered from aortic valve endocarditis, 45 (45%) had mitral valve endocarditis, and 39 (18%) were afflicted with double-valve endocarditis. Prosthetic valve endocarditis was present in 70 (31%) patients. Pathogens were detected in 70% of the cases analyzed via PCR using cardiac valve tissue and in 25% of those analyzed via a culture of cardiac valve tissue; this figure was only 64% for preoperative blood culture. Overall, a pathogen was identified in 197 patients (88%), leading to antibiotic therapy. Targeted antibiotic therapy, based on the PCR results, was carried out in 37 cases and was conducted based on a culture from cardiac valve tissue in three cases. Finally, in 12% of patients, the causative pathogen remained unclear. Conclusions : For patients suffering endocarditis, PCR analysis is indispensable and superior to preoperative blood culture and intraoperative culture in detecting bacteria. Based on PCR testing, antibiotic therapy can be individually adjusted. The high precision of pathogen identification may lead to a significant reduction in IE-associated morbidity and mortality.

Purpose: Antistaphylococcal penicillins and cefazolin have been used as first line therapy in Methicillin-susceptible Staphylococcus aureus bloodstream infection. While efficacy of both regimens seems to be similar, the compounds may differ with regard to tolerability. This study aims to describe the clinical use of cefazolin and flucloxacillin, focussing on discontinuation or change of anti-infective agent due to adverse events., Methods: This observational prospective study was conducted at two German tertiary care centres with an internal recommendation of flucloxacillin for MSSA-BSI in one, and of cefazolin in the other centre. Adverse events were registered weekly under treatment and at a 90-day follow-up. Descriptive analysis was complemented by a propensity score analysis comparing adverse events (stratified rank-based test applied to the sum of Common Terminology Criteria for adverse events ratings per patient)., Results: Of 71 patients included, therapy was initiated with flucloxacillin in 56 (79%), and with cefazolin in 15 (21%). The propensity score analysis indicates a statistically significant difference concerning the severity of adverse events between the treatment groups in favour of cefazolin (p = 0.019). Adverse events led to discontinuation of flucloxacillin in 7 individuals (13% of all patients receiving flucloxacillin). Clinical outcome was not different among treatment groups., Conclusion: Using cefazolin rather than flucloxacillin as a first line agent for treatment of MSSA-BSI is supported by these clinical data., (© 2024. The Author(s).)

Introduction: Falciparum malaria remains one of the deadliest infectious diseases worldwide. In Germany, it is mainly an imported infection among travellers. Rates of coinfection are often unknown, and a clinical rationale for the beneficial use of calculated antibiotic therapy in patients with malaria and suspected coinfection is lacking., Methods: We conducted an analysis of all in-patients treated with falciparum malaria at a German infectious diseases centre in vicinity to one of Europe's major airports for 2010-2019. Logistic regression and time-to-event analysis were used to evaluate predictors for bacterial coinfection, the use of antibacterial substances, as well as their influence on clinical course., Results: In total, 264 patients were included. Of those, 64% received an additional antibacterial therapy (n = 169). Twenty-nine patients (11.0%) were found to have suffered from a relevant bacterial coinfection, while only a small fraction had relevant bacteremia (n = 3, 1.4%). However, patients with severe malaria did not suffer from coinfections more frequently (p = 0.283). CRP levels were not a reliable predictor for a bacterial coinfection (OR 0.99, 95% CI 0.94-1.06, p = 0.850), while another clinical focus of infection was positively associated (OR 3.86, 95% CI 1.45-11.55, p  = 0.010)., Conclusion: Although bacterial coinfections were rare in patients with malaria at our centre, the risk does not seem negligible. These data point rather towards individual risk assessment in respective patients than to general empiric antibiotic use., (© 2023. The Author(s).)

Background: Antimicrobial stewardship (AMS) programmes are established across the world to treat infections efficiently, prioritize patient safety, and reduce the emergence of antimicrobial resistance. One of the core elements of AMS programmes is guidance to support and direct physicians in making efficient, safe and optimal decisions when prescribing antibiotics. To optimize and tailor AMS, we need a better understanding of prescribing physicians' experience with AMS guidance., Objectives: To explore the prescribing physicians' user experience, needs and targeted improvements of AMS guidance in hospital settings., Methods: Semi-structured interviews were conducted with 36 prescribing physicians/AMS guidance users from hospital settings in Canada, Germany, Israel, Latvia, Norway and Sweden as a part of the international PILGRIM trial. A socioecological model was applied as an overarching conceptual framework for the study., Results: Research participants were seeking more AMS guidance than is currently available to them. The most important aspects and targets for improvement of AMS guidance were: (i) quality of guidelines; (ii) availability of infectious diseases specialists; and (iii) suitability of AMS guidance to department context., Conclusions: Achieving prudent antibiotic use not only depends on individual and collective levels of commitment to follow AMS guidance but also on the quality, availability and suitability of the guidance itself. More substantial commitment from stakeholders is needed to allocate the required resources for delivering high-quality, available and relevant AMS guidance to make sure that the prescribers' AMS needs are met., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Cryptococcosis is the most prevalent fungal infection of the central nervous system worldwide. We performed a retrospective multicenter cohort study to gain insights into the epidemiology of cryptococcosis in Germany. We describe the use of diagnostic tests, clinical management and patient outcome. We included 64 patients with underlying HIV infection (55%) or other predispositions. Molecular typing by MLST documented 20 individual sequence types among 42 typed isolates. A fatal outcome was documented in 14% of patients in the first two months after diagnosis., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background incidence of pyogenic spinal infections has increased in recent years. In addition to treating the spinal infection, optimal care also includes identifying the source of the pyogenic spinal infection and the presence of other infections. The aim of this study is to elucidate the prevalence of oral cavity infection (OCI) within this patient cohort. Methods As part of a prospective study conducted from 2016 to 2021, the number of patients with dental infections was investigated by means of an orthopantomogram (OPG) and subsequent dental examination. Results The presence of an oral infection was investigated in 55 (47%) of 118 patients by an OPG, 29 (53%) of whom had a corresponding abnormality of the oral cavity. In addition to the spinal infection, patients with an oral cavity infection revealed an increased incidence of endocarditis, sepsis and brain abscess. A spinal epidural abscess, a multilevel affection of the infection, and an elevated CRP value were also found in patients with a co-existing oral cavity infection. Back pain assessed at admission and 3 months after surgery was also more pronounced in patients with an oral cavity infection. Neurological deficits were often present in patients with spinal and oral cavity infection. Conclusions The presence of an oral cavity infection has proven to be one of the important factors in the detection of the source of the pyogenic spinal infection. In addition, a pronounced spinal affection and frequent co-infections were seen in patients with an oral cavity infection.

Airport malaria is uncommon but increasing in Europe and often difficult to diagnose. We describe the clinical, epidemiological and environmental investigations of a cluster of airport malaria cases and measures taken in response. Three Frankfurt International Airport employees without travel histories to malaria-endemic areas were diagnosed with Plasmodium falciparum malaria in Germany in 2022. Two cases were diagnosed within 1 week, and the third one after 10 weeks. Two cases had severe disease, all three recovered fully. The cases worked in separate areas and no specific location for the transmissions could be identified. No additional cases were detected among airport employees. In June and July, direct flights from Equatorial Guinea, Nigeria and Angola and one parcel originating in Ghana arrived at Frankfurt airport. No vector-competent mosquitoes could be trapped to identify the source of the outbreak. Whole genome sequencing of P. falciparum genomes showed a high genetic relatedness between samples of the three cases and suggested the geographical origin closest to Ghana. A diagnosis of airport malaria should prompt appropriate and comprehensive outbreak investigations to identify the source and to prevent severe forms of falciparum malaria.

Aim: The present study examined the relationship between addiction and hikikomori (extreme social withdrawal) symptoms., Method: A group of clinically referred addiction patients ( n = 31) and a group of age- and gender-matched non-clinical controls ( n = 34) completed a self-report scale for measuring hikikomori symptoms (the Hikikomori Questionnaire-25) along with some other questionnaires assessing substance use (frequency and severity) and quality of life., Results: The results showed that addiction patients displayed significantly higher levels of hikikomori symptoms than the non-clinical control (Cohen's d = 3.41); 87.1% even showed such a high score that they were identified as being at risk for the hikikomori syndrome (vs. only 2.9% in the non-clinical control group). Correlational analyses revealed that within the addiction group, the severity of the substance use problem (as quantified by an index of craving) correlated positively with the level of hikikomori symptoms and negatively with quality of life. In other words, the more severe the addiction, the more extreme the social withdrawal tendencies and the lower the quality of life., Conclusion: Altogether, the findings provide further support for the marked social impairments of people with substance use problems and underline that this should be an important target of intervention., Competing Interests: VP, JK, and JP were employed by Changes GGZ Weert. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Muris, van de Pasch, van Kessel and Peet.)

Objective: Outpatient parenteral antimicrobial therapy (OPAT) is a well-established and cost-effective method for improving the efficient use of healthcare resources. However, only a few centres in Germany perform it. Here we analysed OPAT for the treatment of patients with cranial infections in our neurosurgical department., Methods: This retrospective study analysed patients with cranial infections and the need for intravenous (i.v.) antimicrobial treatment between 2018 and 2021.All diagnosed intracranial infections were defined into two infection categories such as long-term antimicrobial treatment and short-term antimicrobial treatment. All included patients were discharged with a peripherally inserted central catheter (PICC) line. Prior to discharge, all patients received training in the safe administration of their medications via the PICC line. The duration of OPAT and the rate of readmission after OPAT were analysed., Results: We identified a total of 45 patients treated with OPAT for cranial infections. Intradural involvement was present in 40 cases (88.9%). The average length of hospital stay for this cohort after surgical treatment was 45 ± 15 days. 5 patients were treated for soft tissue/skin infection. Surgery was not required in this cohort. The mean hospital stay for this cohort was 8 ± 6 days. Gram-positive organisms were isolated in most cases (53.3%). The most common pathogens were Staphylococcus aureus followed by other Staphylococcus species . For all included patients, OPAT was performed after discharge for an average of 43.1 ± 14 days. There were five cases of readmission due to treatment failure. No serious adverse events or complications of OPAT were observed., Conclusion: OPAT enables better patient-centred healthcare close to home. The length of hospital stay can be reduced and adverse events due to prolonged hospitalisation can be avoided., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kilinc, Setzer, Behmanesh, Jussen, Gessler, Bayerl, Kempf, Kessel, Czabanka and Prinz.)

Objectives: Patients with open pulmonary tuberculosis (opTB) are subject to strict isolation rules. Sputum smear microscopy is used to determine infectivity, but sensitivity is lower than for culture. This study aimed to investigate the clinical relevance of this mismatch in contemporary settings., Methods: Differential results between microscopy and culture were determined at the time of microscopic sputum conversion, from all patients with opTB between 01/2013 and 12/2017. In addition, data on HIV, multi/extensive drug-resistant TB status, time to smear- and cultural-negativity conversion were analyzed; and a Kaplan-Meier curve was developed., Results: Of 118 patients with opTB, 58 had demographic data available for microbiological and clinical follow-up analysis; among these, 26 (44.8%) had still at least one positive culture result. Median time from opTB-treatment initiation to full microscopic sputum- or culture conversion, was 16.5 days (range 2-105), and 20 days (1-105), respectively (median difference: +3.5 days). Sixteen days after de-isolation, >90% had converted culturally. HIV- or multi/extensive drug-resistant TB status did not impact conversion time., Conclusion: When patients with opTB were de-isolated after 3 negative sputum smear microscopy tests, a substantial part still revealed cultural growth of Mycobacterium tuberculosis complex, but it remains unclear, whether smear-negative and culturally-positive individuals on therapy are really infective. Thus, the clinical relevance of this finding warrants further investigation., Competing Interests: Declarations of Competing Interest Johanna Kessel and Nils Wetzstein declare no conflicts of interest; Michael Hogardt reports grants from Mukoviszidose Institut gGmbH and the German Federal Ministry of Health, lecture honoraria from Landesärztekammer Hessen, bioMérieux and Pfizer, and funding from Merck AG. Thomas A. Wichelhaus reports research grants from MSD, Deutsche Krebshilfe, as well as speaker fees and consulting honoraria from Insmed, Osartis; Christoph Stephan received speaker fees/consulting/scientific conference sponsoring from AbbVie, ViiV, Gilead, MSD, Janssen, TAD. All received grants and financial support from all authors are declared outside the submitted work., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Since 2013, heater-cooler unit (HCU) associated Mycobacterium chimaera infections linked to a global outbreak have been described. These infections were characterised by high morbidity and mortality due to delayed diagnosis, as well as challenges in antimycobacterial and surgical therapy. This study aimed to investigate the clinical characteristics and outcome of published cases of HCU-associated M. chimaera infections., Methods: We searched PubMed and the Web of Science until 15 June 2022 for case reports, case series, and cohort studies, without language restriction, on patients with M. chimaera infection and a prior history of cardiac surgery. In this systematic review of case reports, no risk of bias assessment could be performed. Clinical, microbiological, and radiological features were recorded. Logistic regression and time-to-event analyses were performed to identify the potential factors associated with better survival., Results: One hundred eighty patients from 54 publications were included. Most patients underwent surgical aortic valve (67.0%; 118/176 of patients with available data) or combined aortic valve and root replacement (15.3%; 27/176). The median period between the time point of surgery and the first symptoms was 17 months (interquartile range 13-26 months). The overall case fatality rate was 45.5% (80/176), with a median survival of 24 months after the initiation of antimycobacterial therapy or diagnosis. A reoperation (including the removal or exchange of foreign material) was associated with better survival in multivariate logistic regression (OR 0.32 for lethal events; 95% CI 0.12-0.79; p 0.015) and in time-to-event analysis (p 0.0094)., Discussion: This systematic review and meta-analysis confirm the high overall mortality of HCU -associated disseminated M. chimaera infections after cardiac surgery. A reoperation seems to be associated with better survival. Physicians have to stay aware of this infection, as patients might still be present today due to the long latency period., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Gamma-Delta T cells are a prominent subset of T cells in pigs. However, developmental changes, antigen recognition, cell migration, and their contributions to pathogen clearance remain largely unknown. We have recently shown that porcine γδ T cells express Toll-like receptors (TLRs), and that TLR7/8 stimulation can function as a co-stimulatory signal that complements cytokine-induced signals to enhance INFγ production. Nonetheless, the signaling pathways behind this increased cytokine responsiveness remained unclear. Here, we analyzed the signaling pathways by measuring cellular kinase activity and selective inhibition, confirming that the TLR7/8 expression by γδ T cells is indeed functional. Moreover, TLR downstream signaling responses showed a distinct age-dependency, emphasizing the importance of age in immune function. While the TLR7/8 co-stimulation depended on activation of IRAK1/4, p38 and JNK in adult-derived γδ T cells, γδ T cells from young pigs utilized only p38, indicating the existence of an alternative signaling pathway in young pigs. Overall, this data suggests that porcine γδ T cells could be able to recognize viral RNA through TLR7/8 and subsequently support the survival and activation of the adaptive immune response by cytokine production., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Porcine reproductive and respiratory syndrome (PRRS) remains one of the most important infectious diseases for the pig industry. A novel small-scale transmission experiment was designed to assess whether the WUR0000125 (WUR for Wageningen University and Research) PRRS resilience single nucleotide polymorphism (SNP) confers lower susceptibility and infectivity to pigs under natural porcine reproductive and respiratory syndrome virus (PRRSV-2) transmission., Methods: Commercial full- and half-sib piglets (n = 164) were assigned as either Inoculation, Shedder, or Contact pigs. Pigs were grouped according to their relatedness structure and WUR genotype, with R- and R+ referring to pigs with zero and one copy of the dominant WUR resilience allele, respectively. Barcoding of the PRRSV-2 strain (SD09-200) was applied to track pig genotype-specific transmission. Blood and nasal swab samples were collected and concentrations of PRRSV-2 were determined by quantitative (q)-PCR and cell culture and expressed in units of median tissue culture infectious dose (TCID 50 ). The Log 10 TCID 50 at each sampling event, derived infection status, and area under the curve (AUC) were response variables in linear and generalized linear mixed models to infer WUR genotype differences in Contact pig susceptibility and Shedder pig infectivity., Results: All Shedder and Contact pigs, except one, became infected through natural transmission. There was no significant (p > 0.05) effect of Contact pig genotype on any virus measures that would indicate WUR genotype differences in susceptibility. Contact pigs tended to have higher serum AUC (p = 0.017) and log 10 TCID 50 (p = 0.034) when infected by an R+ shedder, potentially due to more infectious R+ shedders at the early stages of the transmission trial. However, no significant Shedder genotype effect was found in serum (p = 0.274) or nasal secretion (p = 0.951) that would indicate genotype differences in infectivity., Conclusions: The novel design demonstrated that it is possible to estimate genotype effects on Shedder pig infectivity and Contact pig susceptibility that are not confounded by family effects. The study, however, provided no supportive evidence that genetic selection on WUR genotype would affect PRRSV-2 transmission. The results of this study need to be independently validated in a larger trial using different PRRSV strains before dismissing the effects of the WUR marker or the previously detected GBP5 gene on PRRSV transmission., (© 2023. The Author(s).)

Outpatient parenteral antimicrobial therapy (OPAT) is a cost-effective method of administering intravenous antimicrobial therapy. Although OPAT is well established in the UK and US healthcare systems, few centres in Europe perform it. Here we analysed OPAT for the treatment of patients with spinal infections at our institution. In this retrospective study, patients with spinal infection who required intravenous (i.v.) antimicrobial treatment between 2018 and 2021 were analysed. The duration of short-term antimicrobial treatment for skin and soft tissue infections and complex infections requiring long-term antimicrobial treatment, such as spinal bone or joint infections, were analysed. All patients were discharged with a peripherally inserted central catheter (PICC) line. Prior to discharge, all patients received training in the safe administration of their medications via the PICC line. The duration of OPAT and the rate of readmission after OPAT were analysed. For this study a total of 52 patients who were treated via OPAT due to spinal infections were analyzed. In 35 cases (69.2%) complex spinal infection was reason for i.v. antimicrobial therapy. Surgery was required in 23 of these 35 patients (65.7%). The average hospital stay for these patients was 12 ± 6 days. The remaining 17 patients were treated for an infection of the soft tissue or the skin and hospital stay for these patients was on average 8 ± 4 days. Gram-positive organisms were isolated in 64.4%. Staphylococcus aureus followed by other Staphylococcus species, was the most common detected organism. After discharging i.v. antimicrobial treatment was given for an average of 20 ± 14 days. The duration of antimicrobial treatment for soft tissue was 10.8 ± 8 days, and for complex infections 25.1 ± 18 days. The mean follow-up was 21 ± 14 months. There was one case of readmission due to treatment failure. There were no difficulties encountered in implementing OPAT. OPAT is a feasible and effective option for delivering intravenous antimicrobial therapy to patients with spinal infections who can be managed without hospitalisation. OPAT offers patient-centred treatment at home while avoiding the risks associated with hospitalisation, with high levels of patient satisfaction., (© 2023. The Author(s).)

The ongoing evolution of SARS-CoV-2 continues to raise new questions regarding the duration of immunity to reinfection with emerging variants. To address these knowledge gaps, controlled investigations in established animal models are needed to assess duration of immunity induced by each SARS-CoV-2 lineage and precisely evaluate the extent of cross-reactivity and cross-protection afforded. Using the Syrian hamster model, we specifically investigated duration of infection acquired immunity to SARS-CoV-2 ancestral Wuhan strain over 12 months. Plasma spike- and RBD-specific IgG titers against ancestral SARS-CoV-2 peaked at 4 months post-infection and showed a modest decline by 12 months. Similar kinetics were observed with plasma virus neutralizing antibody titers which peaked at 2 months post-infection and showed a modest decline by 12 months. Reinfection with ancestral SARS-CoV-2 at regular intervals demonstrated that prior infection provides long-lasting immunity as hamsters were protected against severe disease when rechallenged at 2, 4, 6, and 12 months after primary infection, and this coincided with the induction of high virus neutralizing antibody titers. Cross-neutralizing antibody titers against the B.1.617.2 variant (Delta) progressively waned in blood over 12 months, however, re-infection boosted these titers to levels equivalent to ancestral SARS-CoV-2. Conversely, cross-neutralizing antibodies to the BA.1 variant (Omicron) were virtually undetectable at all time-points after primary infection and were only detected following reinfection at 6 and 12 months. Collectively, these data demonstrate that infection with ancestral SARS-CoV-2 strains generates antibody responses that continue to evolve long after resolution of infection with distinct kinetics and emergence of cross-reactive and cross-neutralizing antibodies to Delta and Omicron variants and their specific spike antigens., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Facciuolo, Van Kessel, Kroeker, Liao, Lew, Falzarano, Kelvin, Gerdts and Napper.)

Gamma-Delta (γδ) T cells represent a prominent lymphocyte subset in pigs. Their role and function, however, remains largely unknown. Toll-like receptors (TLR) are key receptors for the recognition of pathogens, but so far, it is unknown if porcine γδ T cells express TLRs and therefore have the innate ability to recognize pathogens through pattern recognition receptors. In this study, we compared γδ T cells in different age groups of pigs and investigated the functional relevance of TLR7/8 expression. We found that the major γδ T cell phenotype shifts from CD2 - CD8α -/dim CD27 + in young pigs to CD2 + CD8α high CD27 - in 3-year-old pigs impacting their ability to produce IFN-γ upon cytokine and TLR stimulation. Furthermore, we report that stimulation with TLR7/8 ligand R848 increased IFN-γ production in purified γδ T cells upon co-stimulation with IL-2 and IL-12. However, the effect of R848 as a co-activator of γδ T cells was abrogated by the addition of monocytes or within PBMCs, suggesting that γδ T cells respond to multiple direct and indirect stimulations. Thus, our results indicate that γδ T cells express TLRs, are modulated by TLR7/8 ligand R848 and have subset-specific responses., (Copyright © 2022 Elsevier Ltd. All rights reserved.)