Antimicrobial resistance of Clostridioides difficile in veterinary medicine around the world: A scoping review of minimum inhibitory concentrations.

Objective: To provide a comprehensive characterization of Clostridioides difficile antimicrobial resistance (AMR) data in veterinary medicine based on the minimum inhibitory concentrations (MICs) of all antimicrobial agents tested in relation to the techniques used. Methods: A systematic scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews (PRISMA-ScR) and its associated checklist. The objective was to provide a synthesis of the evidence in a summarized and analyzed format.To this end, three scientific databases were consulted: Scopus, PubMed, and Web of Science, up until December 2021. Subsequently, all identified literature was subjected to screening and classification in accordance with the established study criteria, with the objective of subsequent evaluation. Study selection and data extraction: A comprehensive analysis was conducted on studies regarding Clostridioides difficile antimicrobial resistance (AMR) in veterinary medicine across various animal species and related sources. The analysis included studies that presented data on antimicrobial susceptibility testing using the E-test, agar dilution, or broth microdilution techniques. The extracted data included minimum inhibitory concentration (MIC) values and a comprehensive characterization analysis. Results: A total of 1582 studies were identified in scientific databases, of which only 80 were subjected to analysis. The research on Clostridioides difficile antimicrobial resistance (AMR) in veterinary medicine is most prolific in Europe and North America. The majority of isolates originate from production animals (55%) and pets (15%), with pigs, horses, and cattle being the most commonly studied species. The tested agents' minimum inhibitory concentrations (MICs) and resulting putative antimicrobial resistance profiles exhibited considerable diversity across animal species and sources of isolation. Additionally, AMR characterization has been conducted at the gene and genomic level in animal strains. The E-test was the most frequently utilized method for antimicrobial susceptibility testing (AST). Furthermore, the breakpoints for interpreting the MICs were found to be highly heterogeneous and frequently observed regardless of the geographical origin of the publication. Conclusions: Antimicrobial susceptibility testing techniques and results were found to be diverse and heterogeneous. There is no evidence of an exclusive antimicrobial resistance pattern in any animal species. Despite the phenotypic and genomic data collected over the years, further interdisciplinary studies are necessary. Our findings underscore the necessity for international collaboration to establish uniform standards for C. difficile antimicrobial susceptibility testing (AST) methods and reporting. Such collaboration would facilitate a "One Health" approach to surveillance and control, which is of paramount importance.

Prevalence of tick-borne bacterial pathogens in Germany-has the situation changed after a decade?

Introduction: Tick-borne pathogens, such as Borreliella spp., Rickettsia spp., and Anaplasma spp., are frequently detected in Germany. They circulate between animals and tick vectors and can cause mild to severe diseases in humans. Knowledge about distribution and prevalence of these pathogens over time is important for risk assessment of human and animal health. Methods: Ixodes ricinus nymphs were collected at different locations in 2009/2010 and 2019 in Germany and analyzed for tick-borne pathogens by real-time PCR and sequencing. Results: Borreliella spp. were detected with a prevalence of 11.96% in 2009/2010 and 13.10% in 2019 with B. afzelii and B. garinii as dominant species. Borrelia miyamotoi was detected in seven ticks and in coinfection with B. afzelii or B. garinii. Rickettsia spp. showed a prevalence of 8.82% in 2009/2010 and 1.68% in 2019 with the exclusive detection of R. helvetica. The prevalence of Anaplasma spp. was 1.00% in 2009/2010 and 7.01% in 2019. A. phagocytophilum was detected in seven tick samples. None of the nymphs were positive for C. burnetii. Discussion: Here, observed changes in prevalence were not significant after a decade but require longitudinal observations including parameters like host species and density, climatic factors to improve our understanding of tick-borne diseases.

Key summary of German national guideline for adult patients with nosocomial pneumonia- Update 2024 Funding number at the Federal Joint Committee (G-BA): 01VSF22007.

PURPOSE: This executive summary of a German national guideline aims to provide the most relevant evidence-based recommendations on the diagnosis and treatment of nosocomial pneumonia. METHODS: The guideline made use of a systematic assessment and decision process using evidence to decision framework (GRADE). Recommendations were consented by an interdisciplinary panel. Evidence analysis and interpretation was supported by the German innovation fund providing extensive literature searches and (meta-) analyses by an independent methodologist. For this executive summary, selected key recommendations are presented including the quality of evidence and rationale for the level of recommendation. RESULTS: The original guideline contains 26 recommendations for the diagnosis and treatment of adults with nosocomial pneumonia, thirteen of which are based on systematic review and/or meta-analysis, while the other 13 represent consensus expert opinion. For this key summary, we present 11 most relevant for everyday clinical practice key recommendations with evidence overview and rationale, of which two are expert consensus and 9 evidence-based (4 strong, 5 weak and 2 open recommendations). For the management of nosocomial pneumonia patients should be divided in those with and without risk factors for multidrug-resistant pathogens and/or Pseudomonas aeruginosa. Bacterial multiplex-polymerase chain reaction (PCR) should not be used routinely. Bronchoscopic diagnosis is not considered superior to´non-bronchoscopic sampling in terms of main outcomes. Only patients with septic shock and the presence of an additional risk factor for multidrug-resistant pathogens (MDRP) should receive empiric combination therapy. In clinically stabilized patients, antibiotic therapy should be de-escalated and focused. In critically ill patients, prolonged application of suitable beta-lactam antibiotics should be preferred. Therapy duration is suggested for 7-8 days. Procalcitonin (PCT) based algorithm might be used to shorten the duration of antibiotic treatment. Patients on the intensive care unit (ICU) are at risk for invasive pulmonary aspergillosis (IPA). Diagnostics for Aspergillus should be performed with an antigen test from bronchial lavage fluid. CONCLUSION: The current guideline focuses on German epidemiology and standards of care. It should be a guide for the current treatment and management of nosocomial pneumonia in Germany.

How are Long-Covid, Post-Sepsis-Syndrome and Post-Intensive-Care-Syndrome related? A conceptional approach based on the current research literature.

Long-Covid (LC), Post-Sepsis-Syndrome (PSS) and Post-Intensive-Care-Syndrome (PICS) show remarkable overlaps in their clinical presentation. Nevertheless, it is unclear if they are distinct syndromes, which may co-occur in the same patient, or if they are three different labels to describe similar symptoms, assigned on the basis on patient history and professional perspective of the treating physician. Therefore, we reviewed the current literature on the relation between LC, PSS and PICS. To date, the three syndromes cannot reliably be distinguished due similarities in clinical presentation as they share the cognitive, psychological and physical impairments with only different probabilities of occurrence and a heterogeneity in individual expression. The diagnosis is furthermore hindered by a lack of specific diagnostic tools. It can be concluded that survivors after COVID-19 sepsis likely have more frequent and more severe consequences than patients with milder COVID-19 courses, and that are some COVID-19-specific sequelae, e.g. an increased risk for venous thromboembolism in the 30 days after the acute disease, which occur less often after sepsis of other causes. Patients may profit from leveraging synergies from PICS, PSS and LC treatment as well as from experiences gained from infection-associated chronic conditions in general. Disentangling molecular pathomechanisms may enable future targeted therapies that go beyond symptomatic treatment.

Frequency and clinical significance of Herpes simplex virus type 1/2 reactivation in adult patients with mild to moderately severe community-acquired pneumonia: a multicentre cohort study.

PURPOSE: This study assessed the frequency, clinical significance, and risk factors for Herpes simplex virus (HSV) reactivation in immunocompetent patients with community-acquired pneumonia (CAP). METHODS: The study included adult CAP-patients who were enrolled in the CAPNETZ study between 2007 and 2017 and had a residual sputum sample available for analysis. In addition to routine diagnostics, sputum and blood samples were tested for HSV-1/2 using PCR. Demographics, comorbidities, and CRB-65 score were compared between HSV-positive and negative patients using Fisher exact or Mann Whitney test. Logistic regression analyses investigated the influence of HSV reactivation on a modified hospital recovery scale (HRS) until day 7, divided into 3 categories (no oxygen therapy, oxygen therapy, ICU admission or death). RESULTS: Among 245 patients, HSV-1 and HSV-2 were detected in 30 patients (12.2%, 95%CI 8.7-16.9) and 0 patients, respectively. All HSV-positive patients were hospitalized, had a CRB-65 severity score of 0-2 and survived the first 28 day. In the HSV-positive group, patients had a non-significantly higher median age (70.5 versus 66 years) and a higher rate of oncological comorbidities (16.7% versus 8.8%) compared to the HSV-negative group. Distribution of co-pathogens and outcome parameters did not significantly differ between both groups. In a multivariate logistic regression model, age (AOR 1.029, p = 0.012) and CRB-65 score (AOR 1.709, p = 0.048), but not HSV-1 as single or co-pathogen were independently associated with higher HRS. CONCLUSION: Our study suggests that HSV-1 reactivation is common in CAP but might not be associated with specific risk factors or a complicated disease course.

A practice-based approach to teaching antimicrobial therapy using artificial intelligence and gamified learning.

Objectives: Scalable teaching through apps and artificial intelligence (AI) is of rising interest in academic practice. We focused on how medical students could benefit from this trend in learning antibiotic stewardship (ABS). Our study evaluated the impact of gamified learning on factual knowledge and uncertainty in antibiotic prescription. We also assessed an opportunity for AI-empowered evaluation of freeform answers. Methods: We offered four short courses focusing on ABS, with 46 participating medical students who self-selected themselves into the elective course. Course size was limited by the faculty. At the start of the course, students were given a questionnaire about microbiology, infectious diseases, pharmacy and qualitative questions regarding their proficiency of selecting antibiotics for therapy. Students were followed up with the same questionnaire for up to 12 months. We selected popular game mechanics with commonly known rules for teaching and an AI for evaluating freeform questions. Results: The number of correctly answered questions improved significantly for three topics asked in the introductory examination, as did the self-assessed safety of prescribing antibiotics. The AI-based review of freeform answers was found to be capable of revealing students' learning gaps and identifying topics in which students needed further teaching. Conclusions: We showed how an interdisciplinary short course on ABS featuring gamified learning and AI could substantially improve learning. Even though large language models are a relatively new technology that sometimes fails to produce the anticipated results, they are a possible first step in scaling a tutor-based teaching approach in ABS.

Long versus short course anti-microbial therapy of uncomplicated Staphylococcus aureus bacteraemia: a systematic review.

BACKGROUND: Current guidelines recommend at least 2 weeks duration of antibiotic therapy (DOT) for patients with uncomplicated Staphylococcus aureus bacteraemia (SAB) but the evidence for this recommendation is unclear. OBJECTIVES: To perform a systematic literature review assessing current evidence for recommended DOT for patients with SAB. METHODS: The following are the methods used for this study. DATA SOURCES: We searched MEDLINE, ISI Web of Science, the Cochrane Database and clinicaltrials.gov from inception to March 30, 2024. References of eligible studies were screened and experts in the field contacted for additional articles. STUDY ELIGIBILITY CRITERIA: All clinical studies, regardless of design, publication status and language. PARTICIPANTS: Adult patients with uncomplicated SAB. INTERVENTIONS: Long (>14 days; >18 days; 11-16 days) vs. short (≤14 days; 10-18 days; 6-10 days, respectively) DOT with the DOT being defined as the first until the last day of antibiotic therapy. ASSESSMENT OF RISK OF BIAS: Risk of bias was assessed using the ROBINS-I-tool. METHODS OF DATA SYNTHESIS: The primary outcome was 90-day all-cause mortality. Only studies presenting results of adjusted analyses for mortality were included. Data synthesis could not be performed. RESULTS: Eleven nonrandomized studies were identified that fulfilled the pre-defined inclusion criteria, of which three studies reported adjusted effect ratios. Only these were included in the final analysis. We did not find any RCT. Two studies with 1230 patients reported the primary endpoint 90-day all-cause mortality. Neither found a statistically significant superiority for longer (>14 days; 11-16 days) or shorter DOT (≤14 days; 6-10 days, respectively) for patients with uncomplicated SAB. Two studies investigated the secondary endpoint 30-day all-cause mortality (>18 days; 11-16 days vs. 10-18 days; 6-10 days, respectively) and did not find a statistically significant difference. All included studies had a moderate risk of bias. CONCLUSIONS: Sound evidence that supports any duration of antibiotic treatment for patients with uncomplicated SAB is lacking.

Teaching prudent antibiotic use on the go: a descriptive report on development, utilization and listener satisfaction of an educational podcast format for medical students and young professionals.

BACKGROUND: An important component in fostering the responsible use of antibiotics is training of new and future prescribers in this interdisciplinary topic. Because podcasts are playing an increasing role in medical education, we aimed to develop and evaluate a podcast format with practice and guideline-oriented learning content on antibiotic therapy for medical students and young medical professionals. METHODS: We developed the concept for the podcast with the direct involvement of medical students and medical experts with teaching experience. We used video conferencing when recording the episodes in order to have quick, easy, and nationwide access to the experts involved. We released an episode every 2 to 4 weeks on the popular podcast platforms. The podcast was promoted through mailing lists, social and print media, and at conferences. The evaluation of episodes was based on user data provided by the platforms and an anonymous feedback questionnaire linked to each episode in the podcast notes. RESULTS: Between December 2021 and December 2022 19 episodes of InfectEd: der Antibiotika-Podcast were released. The mean duration of an episode was 91 min. By March 9, 2023, a total of 38,829 downloads and streams had been recorded. The majority of users listened to the podcast on a mobile device. The average playing time per episode was 65%. The feedback questionnaire was completed 135 times. 60.7% of respondents were female, 38.5% male. The majority of respondents were in their twenties and thirties (66.7%). 31.1% were medical students, 25.9% were residents, and 25.2% were specialists. Listeners were asked to rate episodes on a scale from 1 to 6, where 1 was "very good" and 6 was "insufficient." Ratings did not differ significantly between female and male respondents or between medical students and others. 118 respondents (87.4%) reported an increase in knowledge. Free-text feedback frequently emphasized clinical and also exam relevance. CONCLUSION: Our podcast format, developed with a user-centered approach, was broadly distributed and has been well accepted by both medical students and physicians alike. It provides a large number of learners with low-threshold access to current, guideline-orientated content and could be a useful supplement to conventional teaching formats.

Comparison of clinical outcomes in hospitalized patients with COVID-19 or non-COVID-19 community-acquired pneumonia in a prospective observational cohort study.

PURPOSE: Coronavirus disease 2019 (COVID-19) and non-COVID-19 community-acquired pneumonia (NC-CAP) often result in hospitalization with considerable risks of mortality, ICU treatment, and long-term morbidity. A comparative analysis of clinical outcomes in COVID-19 CAP (C-CAP) and NC-CAP may improve clinical management. METHODS: Using prospectively collected CAPNETZ study data (January 2017 to June 2021, 35 study centers), we conducted a comprehensive analysis of clinical outcomes including in-hospital death, ICU treatment, length of hospital stay (LOHS), 180-day survival, and post-discharge re-hospitalization rate. Logistic regression models were used to examine group differences between C-CAP and NC-CAP patients and associations with patient demography, recruitment period, comorbidity, and treatment. RESULTS: Among 1368 patients (C-CAP: n = 344; NC-CAP: n = 1024), C-CAP showed elevated adjusted probabilities for in-hospital death (aOR 4.48 [95% CI 2.38-8.53]) and ICU treatment (aOR 8.08 [95% CI 5.31-12.52]) compared to NC-CAP. C-CAP patients were at increased risk of LOHS over seven days (aOR 1.88 [95% CI 1.47-2.42]). Although ICU patients had similar in-hospital mortality risk, C-CAP was associated with length of ICU stay over seven days (aOR 3.59 [95% CI 1.65-8.38]). Recruitment period influenced outcomes in C-CAP but not in NC-CAP. During follow-up, C-CAP was linked to a reduced risk of re-hospitalization and mortality post-discharge (aOR 0.43 [95% CI 0.27-0.70]). CONCLUSION: Distinct clinical trajectories of C-CAP and NC-CAP underscore the need for adapted management to avoid acute and long-term morbidity and mortality amid the evolving landscape of CAP pathogens.

[Automated surveillance and risk prediction with the aim of risk-stratified infection control and prevention (RISK PRINCIPE)]. / Automatisierte Surveillance und Risikovorhersage mit dem Ziel einer risikostratifizierten Infektionskontrolle und -prävention (RISK Prediction for Risk-stratified Infection Control and Prevention).

Healthcare-associated infections (HCAIs) represent an enormous burden for patients, healthcare workers, relatives and society worldwide, including Germany. The central tasks of infection prevention are recording and evaluating infections with the aim of identifying prevention potential and risk factors, taking appropriate measures and finally evaluating them. From an infection prevention perspective, it would be of great value if (i) the recording of infection cases was automated and (ii) if it were possible to identify particularly vulnerable patients and patient groups in advance, who would benefit from specific and/or additional interventions.To achieve this risk-adapted, individualized infection prevention, the RISK PRINCIPE research project develops algorithms and computer-based applications based on standardised, large datasets and incorporates expertise in the field of infection prevention.The project has two objectives: a) to develop and validate a semi-automated surveillance system for hospital-acquired bloodstream infections, prototypically for HCAI, and b) to use comprehensive patient data from different sources to create an individual or group-specific infection risk profile.RISK PRINCIPE is based on bringing together the expertise of medical informatics and infection medicine with a focus on hygiene and draws on information and experience from two consortia (HiGHmed and SMITH) of the German Medical Informatics Initiative (MII), which have been working on use cases in infection medicine for more than five years.

Resurgence of common respiratory viruses in patients with community-acquired pneumonia (CAP)-A prospective multicenter study.

BACKGROUND: Community-acquired pneumonia (CAP) is a major global cause of death and hospitalization. Bacteria or community-acquired viruses (CARVs) cause CAP. COVID-19 associated restrictions effectively reduced the circulation of CARVs. OBJECTIVES: The aim of this study was to analyze the proportion of CARVs in adult patients with CAP from mid-2020 to mid-2023. Specifically, we aimed to compare the rate of influenza virus, SARS-CoV-2, and RSV detections in patients aged 18-59 years and ≥60 years. STUDY DESIGN: We analyze the proportion of 21 community-acquired respiratory viruses (CARVs) and three atypical bacteria (Bordetella pertussis, Legionella pneumophila, and Mycoplasma pneumoniae) in nasopharyngeal swab samples using molecular multiplex methods within the prospective, multicentre, multinational study of the German study Group CAPNETZ. We used stringent inclusion criteria throughout the study. RESULTS: We identified CARVs in 364/1,388 (26.2 %) patients. In detail, we detected SARS-CoV-2 in 210/1,388 (15.1 %), rhino-/enterovirus in 64/1,388 (4.6 %), influenza virus in 23/1,388 (1.6 %) and RSV in 17/1,388 (1.2 %) of all patients. We detected RSV and influenza more frequently in patients ≥60 years, especially in 22/23 compared to the previous season. None of the atypical bacteria were detected. CONCLUSIONS: Beginning in 2023, we demonstrate a re-emergence of CARVs in CAP patients. Effective vaccines or specific antiviral therapies for more than two thirds of the detected viral infections are currently available. High detection rates of vaccine-preventable viruses in older age groups support targeted vaccination campaigns.

Ultraviolet C inactivation of Coxiella burnetii for production of a structurally preserved whole cell vaccine antigen.

Q fever, a worldwide-occurring zoonotic disease, can cause economic losses for public and veterinary health systems. Vaccines are not yet available worldwide and currently under development. In this regard, it is important to produce a whole cell antigen, with preserved structural and antigenic properties and free of chemical modifications. Thus, inactivation of Coxiella burnetii with ultraviolet light C (UVC) was evaluated. C. burnetii Nine Mile phase I (NMI) and phase II (NMII) were exposed to decreasing intensities in a time-dependent manner and viability was tested by rescue cultivation in axenic medium or cell culture. Effects on the cell structure were visualized by transmission electron microscopy and antigenicity of UVC-treated NMI was studied by immunization of rabbits. NMI and NMII were inactivated at UVC intensities of 250 µW/cm2 for 5 min or 100 µW/cm2 for 20 min. Reactivation by DNA repair was considered to be unlikely. No morphological changes were observed directly after UVC inactivation by transmission electron microscopy, but severe swelling and membrane degradation of bacteria with increasing severity occurred after 24 and 48 h. Immunization of rabbits resulted in a pronounced antibody response. UVC inactivation of C. burnetii resulted in a structural preserved, safe whole cell antigen and might be useful as antigen for diagnostic purposes or as vaccine candidate.

Effect of acyclovir therapy on the outcome of mechanically ventilated patients with lower respiratory tract infection and detection of herpes simplex virus in bronchoalveolar lavage: protocol for a multicentre, randomised controlled trial (HerpMV).

INTRODUCTION: Herpes simplex virus (HSV) is frequently detected in the respiratory tract of mechanically ventilated patients and is associated with a worse outcome. The aim of this study is to determine whether antiviral therapy in HSV-positive patients improves outcome. METHODS AND ANALYSIS: Prospective, multicentre, open-label, randomised, controlled trial in parallel-group design. Adult, mechanically ventilated patients with pneumonia and HSV type 1 detected in bronchoalveolar lavage (≥105 copies/mL) are eligible for participation and will be randomly allocated (1:1) to receive acyclovir (10 mg/kg body weight every 8 hours) for 10 days (or until discharge from the intensive care unit if earlier) or no intervention (control group). The primary outcome is mortality measured at day 30 after randomisation (primary endpoint) and will be analysed with Cox mixed-effects model. Secondary endpoints include ventilator-free and vasopressor-free days up to day 30. A total of 710 patients will be included in the trial. ETHICS AND DISSEMINATION: The trial was approved by the responsible ethics committee and by Germany's Federal Institute for Drugs and Medical Devices. The clinical trial application was submitted under the new Clinical Trials Regulation through CTIS (The Clinical Trials Information System). In this process, only one ethics committee, whose name is unknown to the applicant, and Germany's Federal Institute for Drugs and Medical Devices are involved throughout the entire approval process. Results will be published in a journal indexed in MEDLINE and CTIS. With publication, de-identified, individual participant data will be made available to researchers. TRIAL REGISTRATION NUMBER: NCT06134492.

Exploring secretory proteome and cytokine kinetic of human peripheral blood mononuclear cells exposed to methicillin-resistant Staphylococcus aureus biofilms and planktonic bacteria.

Staphylococcus aureus is a highly successful pathogen infecting various body parts and forming biofilms on natural and artificial surfaces resulting in difficult-to-treat and chronic infections. We investigated the secreted cytokines and proteomes of isolated peripheral blood mononuclear cells (PBMCs) from healthy volunteers exposed to methicillin-resistant S. aureus (MRSA) biofilms or planktonic bacteria. Additionally, the cytokine profiles in sera from patients with community-acquired pneumonia (CAP) caused by S. aureus were investigated. The aim was to gain insights into the immune response involved and differentiate between the planktonic and sessile MRSA forms. We identified 321 and 298 targets that were significantly differently expressed in PBMCs when exposed to planktonic or biofilm-embedded bacteria, respectively. PBMCs exposed to planktonic MRSA cells secreted increased levels of TNF-α, while IL-18 was elevated when exposed to the biofilm. The machine-learning analyses of the cytokine profiles obtained for the in vitro PBMCs and CAP sera distinguished between the two types of bacteria forms based on cytokines IL-18, IL12, and IL-17, and with a lower importance IL-6. Particularly, IL-18 which has not been correlated with S. aureus biofilms so far might represent a suitable marker for monitoring chronification during MRSA infection to individualize the therapy, but this hypothesis must be proved in clinical trials.

Beyond muscles: Investigating immunoregulatory myokines in acute resistance exercise - A systematic review and meta-analysis.

Myokines, released from the muscle, enable communication between the working muscles and other tissues. Their release during physical exercise is assumed to depend on immune-hormonal-metabolic interactions concerning mode (endurance or resistance exercise), duration, and intensity. This meta-analysis aims to examine the acute changes of circulating myokines inducing immunoregulatory effects caused by a bout of resistance exercise and to consider potential moderators of the results. Based on this selection strategy, a systematic literature search was conducted for resistance exercise intervention studies measuring interleukin (IL-) 6, IL-10, IL-1ra, tumor necrosis factor (TNF-) α, IL-15, IL-7, transforming growth factor (TGF-) ß1, and fractalkines (FKN) before and immediately after resistance exercise in healthy individuals. Random-effects meta-analysis was performed for each myokine. We identified a moderate positive effect of resistance exercise for IL-6 and IL-1ra. Regarding IL-15 and TNF-α, small to moderate effects were found. For IL-10, no significant effect was observed. Due to no data, meta-analyses for IL-7, TGF-ß1, and FKN could not be performed. No moderators (training status, type of exercise, risk of bias, age, sex, time of day, exercise volume, exercise intensity, exercise dose) of the results were detected for all tested myokines. Taken together, this systematic review and meta-analysis showed immediate positive effects of an acute resistance exercise session on IL-6, IL-1ra, TNF-α, and IL-15 levels.

Perioperative Antibiotic Prophylaxis.

BACKGROUND: Postoperative surgical site infections (SSI) account for almost 25% of all nosocomial infections in Germany and are a source of increased morbidity and mortality. METHODS: This review is based on pertinent publications retrieved by a selective search in PubMed and on national and international guidelines. RESULTS: The individual risk factors for SSI must be assessed before any surgical procedure. A body-mass index above 30 kg/m2 is associated with an unadjusted risk ratio of 1.35 [1.28; 1.41] for SSI, which rises to 3.29 [2.99; 3.62] if the patient is also immunosuppressed. The risk of SSI is also significantly higher with certain types of procedure. Perioperative antibiotic prophylaxis (PAP) is clearly indicated for operations that carry a high risk of SSI (e.g., colorectal surgery) and for those that involve the implantation of alloplastic material (e.g., hip endoprostheses). PAP can usually be administered with basic antibiotics such as cefazoline. The basic principles of PAP are that it should be given by the anesthesia team in the interval from 60 minutes preoperatively up to shortly before the incision, and that its administration should only be for a short period of time, usually as a single shot. Continuing PAP onward into the postoperative period leads to increased toxicity, bacterial superinfections, and antibiotic resistance. CONCLUSION: The evidence shows that perioperative antibiotic prophylaxis is a component of a bundle of measures that can help prevent SSI. Strict indications and adherence to the basic principles of PAP are essential for therapeutic success.

In vitro activity of cefiderocol against European Pseudomonas aeruginosa and Acinetobacter spp., including isolates resistant to meropenem and recent ß-lactam/ß-lactamase inhibitor combinations.

Carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter spp. represent major threats and have few approved therapeutic options. Non-|fermenting Gram-negative isolates were collected from hospitalized inpatients from 49 sites in 6 European countries between 01 January 2020 and 31 December 2020 and underwent susceptibility testing against cefiderocol and ß-lactam/ß-lactamase inhibitor combinations. Meropenem-resistant (MIC >8 mg/L), cefiderocol-susceptible isolates were analyzed by PCR, and cefiderocol-resistant isolates were analyzed by whole-genome sequencing to identify resistance mechanisms. Overall, 1,451 (950 P. aeruginosa; 501 Acinetobacter spp.) isolates were collected, commonly from the respiratory tract (42.0% and 39.3%, respectively). Cefiderocol susceptibility was higher than |ß|-|l|a|c|t|a|m|/|ß|-|l|a|c|t|a|mase| inhibitor combinations against P. aeruginosa (98.9% vs 83.3%-91.4%), and P. |aeruginosa resistant to meropenem (n = 139; 97.8% vs 12.2%-59.7%), ß-lactam/ß-lactamase inhibitor combinations (93.6%-98.1% vs 10.7%-71.8%), and both meropenem and ceftazidime-avibactam (96.7% vs 5.0%-||45.0%) or |ceftolozane-tazobactam (98.4% vs 8.1%-54.8%), respectively. Cefiderocol and sulbactam-durlobactam susceptibilities were high against Acinetobacter spp. (92.4% and 97.0%) and meropenem-resistant Acineto|bacter |spp. (n = 227; 85.0% and 93.8%) but lower against sulbactam-durlobactam- (n |= 15; 13.3%) and cefiderocol- (n = 38; 65.8%) resistant isolates, respectively. Among meropenem-resistant P. aeruginosa and Acinetobacter spp., the most common ß-||lactamase genes were metallo-ß-lactamases [30/139; blaVIM-2 (15/139)] and oxacillinases [215/227; blaOXA-23 (194/227)], respectively. Acquired ß-lactamase genes were identified in 1/10 and 32/38 of cefiderocol-resistant P. aeruginosa and Acinetobacter spp., and pirA-like or piuA mutations in 10/10 and 37/38, respectively. Conclusion: cefiderocol susceptibility was high against P. aeruginosa and Acinetobacter spp., including meropenem-resistant isolates and those resistant to recent ß-lactam/ß-lactamase inhibitor combinations common in first-line treatment of European non-fermenters. IMPORTANCE: This was the first study in which the in vitro activity of cefiderocol and non-licensed ß-lactam/ß-lactamase inhibitor combinations were directly compared against Pseudomonas aeruginosa and Acinetobacter spp., including meropenem- and ß-lactam/ß-lactamase inhibitor combination-resistant isolates. A notably large number of European isolates were collected. Meropenem resistance was defined according to the MIC breakpoint for high-dose meropenem, ensuring that data reflect antibiotic activity against isolates that would remain meropenem resistant in the clinic. Cefiderocol susceptibility was high against non-fermenters, and there was no apparent cross resistance between cefiderocol and ß-lactam/ß-lactamase inhibitor combinations, with the exception of sulbactam-durlobactam. These results provide insights into therapeutic options for infections due to resistant P. aeruginosa and Acinetobacter spp. and indicate how early susceptibility testing of cefiderocol in parallel with ß-lactam/ß-lactamase inhibitor combinations will allow clinicians to choose the effective treatment(s) from all available options. This is particularly important as current treatment options against non-fermenters are limited.

COVID-19 outbreak among employees of a German hospital: risk factor analysis based on a follow-up questionnaire and seroprevalence.

BACKGROUND: The Co-FriSero study describes a COVID-19 outbreak at the Friedrichroda hospital in Thuringia, Germany, with 185 beds and 404 employees, at the onset of the pandemic between March 30th, 2020, and April 13th, 2020. This study aimed to analyze potential sources of SARS-CoV-2 transmission amongst hospital employees. METHODS: After the outbreak, a comprehensive follow-up was conducted through a questionnaire and a seroprevalence study using two different immunoassays for IgG detection and a third for discordant results. RESULTS: PCR screenings confirmed SARS-CoV-2 infection in 25 of 229 employees, with an additional 7 detected through serology. Statistical analysis indicated that direct patient contact, exposure to high flow ventilation in non-isolated rooms, direct contact with colleagues, shared use of recreational rooms, and carpooling were associated with an increased infection risk. Conversely, contact with family and friends, public transportation, public events, and use of locker rooms were not associated with infection. Male gender showed a lower infection likelihood, independent of age and other risk factors. CONCLUSION: This study highlights the role of direct patient care and internal staff interactions in the spread of SARS-CoV-2 in the hospital setting. It suggests that non-traditional transmission routes like carpooling require consideration in pandemic preparedness.