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Pyogenic liver abscess (PLA) is a rare but potentially life-threatening disease, and estimates suggest a gradual increase in the incidence during the last decades. The primary aim of this study was to report the incidence, trend and aetiology of PLA during a decade in Southern Sweden. This was a population-based observational cohort study between 2011 and 2020 in Skåne, Southern Sweden. Data were retrieved from the Swedish National Board of Health and Welfare for all individuals diagnosed with liver abscess (K750) according to ICD-10 (International Statistical Classification of Diseases, 10th revision). A total of 456 episodes of PLA occurred in 364 patients during the study period. The median age of the first PLA episode was 71 years (range 3–97) and 57% (n = 206) were men. The mean incidence of all patients was 3.4/100,000 person-years (range 1.8–5.2). The incidence increased almost three times, from 1.8/100,000 person-years in 2011 to 5.2/100,000 person-years in 2020. Streptococcus species, Escherichia coli and Klebsiella species accounted for the vast majority of both mono- and polymicrobial findings in both blood and local abscess cultures. 16s rDNA added information about aetiology in 37% of episodes. The incidence of PLA increased during the study period, and Streptococcus spp., Klebsiella spp. and E. coli dominated both blood and local cultures. Despite antimicrobial therapy, pathogens could be found in local abscess cultures several weeks into treatment. Increased use of 16s rDNA in the management of PLA could be beneficial.

Background Bloodstream infections (BSI) are a public health concern, and infections caused by resistant bacteria further increase the overall BSI burden on healthcare. Aim To provide a population-based estimate of BSI incidence and relate this to the forthcoming demographic ageing western population change. Methods We retrieved positive blood cultures taken from patients in the Skåne region, southern Sweden, 2006–2019 from the Clinical Microbiology Department database and estimated incidence rates (IR), stratified by age (0–49, 50–64, 65–79, ≥ 80 years), sex, year, and species and described antimicrobial susceptibility for Enterobacterales. Results We identified 944,375 blood culture sets, and 129,274 (13.7%) were positive. After deduplication and removal of contaminants, 54,498 separate BSI episodes remained. In total, 30,003 BSI episodes (55%) occurred in men. The overall IR of BSI was 307/100,000 person-years, with an average annual increase of 3.0%. Persons ≥ 80 years had the highest IR, 1781/100,000 person-years, as well as the largest increase. Escherichia coli (27%) and Staphylococcus aureus (13%) were the most frequent findings. The proportion of Enterobacterales isolates resistant to fluoroquinolones and third generation cephalosporins increased from 8.4% to 13.6%, and 4.9% to 7.3%, (p for trend Conclusion We report among the highest BSI IRs to date worldwide, with a higher proportion among elderly persons and males, including resistant isolates. Given expected demographic changes, these results indicate a possible substantial future BSI burden, for which preventive measures are needed.

To report trends and characteristics of post-prostate biopsy (PBx) infections, with regard to aetiology and resistance patterns, in a large unique cohort from a single-centre using the same antibiotic prophylactic regimens during a 15-year period.An observational cross-sectional cohort study, including all patients who underwent transrectal ultrasonography-guided PBx (TRUS PBx) for the suspicion of prostate cancer at the Department of Urology, Skåne University Hospital between 1 May 2003 and 31 December 2017. Positive blood and urinary cultures were considered markers of bloodstream infection (BSI) and urinary tract infection (UTI), respectively. For all patients, details regarding blood or urine cultures from the date of the TRUS PBx and 14 days onwards were retrieved.In total, 8973 TRUS PBx procedures were performed in 6597 men during the study period. Over time, there was a trend towards a changing case-mix, with PBx procedures increasingly being performed in older patients, patients with lower prostate-specific antigen values, and higher prostate volumes. During the study period, the number of PBx procedures performed increased for each time period and we found an increasing rate of infectious complications in the last period. Overall, the rates of BSI and UTI with at least one relevant pathogen were 1% (88/8973) and 1.8% (159/8973), respectively. In total, 16 of 90 strains (18%) were extended spectrum beta-lactamases producing, with an increasing proportion over time. The proportion of ciprofloxacin-resistant pathogens did not increase over time.During the 15 years of this study, BSI and UTI after TRUS PBx increased. The rise of infectious complications after TRUS PBx in this population is unlikely to be explained by quinolone-resistance, as ciprofloxacin-resistance did not increase in the blood and urinary samples obtained during the study period. Future longitudinal studies are warranted to investigate why infectious complications after TRUS PBx are increasing.

Objective Open and endovascular aortic repair may be complicated by aortic vascular graft or endograft infection (VGEI). Confirming the microbiological aetiology is a key element in providing the best available treatment to patients with a VGEI. The primary aim of this study was to describe the technique of direct aneurysm sac guided aspiration (DASGA) in determining the microbiological aetiology in a cohort of patients with VGEIs, and to report its diagnostic value. Methods This was a retrospective observational single centre study performed between the years 2011 to 2020 in Malmo, Sweden. Patients with a suspected aortic VGEI, where a DASGA was performed at the Vascular Centre, were included in the study. Results In total, 31 guided aspirations were performed in 27 patients (25 male [93%]; median age 77 years [range 57 – 82 years]). The combination of culture and 16S rRNA/18S rRNA gave a microbial aetiology in 25/31 (81%) DASGAs. Importantly, excluding three cases where infection was ruled out, this rate increases up to 89%. A polymicrobial aetiology was found in six (24 %) cases. The most common bacteria found were Cutibacterium spp. (n = 8) and Listeria monocytogenes (n = 4). In total, the dominant aetiology could be further characterised into normal gut flora (n = 12; 48%) or skin commensals (n = 8; 32%). No patients had persistent morbidity related to the DASGA. Conclusion DASGA can be used successfully to determine the microbiological aetiology of open and endovascular graft infections. This method appears to be safe, with a high success rate for confirming the microbiological aetiology of VGEIs, particularly if standard culturing methods are combined with 16S rRNA/18S rRNA. Finding the causative microbial aetiology is crucial, and in the vast majority of cases translumbar puncture can be used without serious complications.

Background Transient elastography (TE) has largely replaced liver biopsy to evaluate fibrosis stage and cirrhosis in chronic hepatitis C. Previous studies report excellent reliability of TE but agreement metrics have not been reported. This study aimed to assess inter-rater agreement and reliability of repeated TE measurements. Methods Two operators performed TE independently, directly after each other. The primary outcome was disagreement, defined as a difference in TE results between operators of ≥ 33%, as well as the smallest detectable change, SDC95 (i.e., the difference between measurements needed to state with 95% certainty that there is a difference in underlying stiffness). Secondary outcomes included reliability, measured as intra-class correlation, and patient and examination characteristics associated with agreement. Results In total, 65 patients were included, with a mean liver stiffness of 9.7 kPa. Of these, 21 (32%) had a disagreement in TE results of ≥ 33% between the two operators. The SDC95 on the log scale was 1.97, indicating that an almost twofold increase or decrease in liver stiffness would be required to confidently represent a change in the underlying fibrosis. Reliability, estimated using the intra-class correlation, was acceptable at 0.86. In a post-hoc analysis, fasting less than 5 hours before TE was associated with a higher degree of disagreement (48% vs 19%, p = 0.03). Conclusions In our clinical setting, agreement in directly repeated TE measurements was surprisingly low. It is essential to further investigate the reliability and agreement of TE to determine its validity and usefulness.

HIV-associated infective native aortic aneurysms (INAA) constitute a subcategory of the disease INAA. This is a very rare group of patients. The aim of this systematic literature review was to compile a description of patient characteristics with HIV-associated INAA. A systematic literature review was performed using the search terms HIV and aortic aneurysm in Ovid MEDLINE and Embase databases, on articles published between 1981 and 2022. Using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, articles were scrutinized according to a predefined protocol including age, sex, comorbidities, microbiological pathogens, CD4-count, HIV/AIDS state, aortic segment involved, treatment and outcome. Thirty-three studies, all case reports with a total of 39 patients, were included. The median age was 48 years (range 27-79), most were male n = 35 (90%), and the median follow-up was n = 6 months (range 0-63). Cardiovascular comorbidity was present in n = 1 (3%), median CD4-count was 216 (range 6-1236), and n = 12 (31%) had AIDS. The most common microbiological pathogens were Treponema pallidum, n = 12 (31%), Salmonella spp. n = 10 (26%), Mycobacterium species n = 5 (12%) and Staphylococcal spp. n = 5 (13%). The HIV-associated INAAs were localized in the abdominal aorta n = 32 (82%), in the thoracic aorta n = 5 (13%) and in the thoraco-abdominal aorta n = 2 (5%). Open surgery was performed in n = 23 (59%) patients, endovascular aortic repair n = 6 (15%), and n = 7 (18%) did not receive surgery. Infection-related complications were reported in n = 2 (7%) patients, both with postoperative development of fatal sepsis. Patients with HIV-associated INAAs were younger, had lower rate of cardiovascular comorbidity, demonstrated low CD4 counts as a measure of immunosuppression, and demonstrated diverse microbiological pathogens compared with other INAAs. Treponema pallidum and Mycobacterium spp. were common pathogens, which are very rare microbiological pathogens in other INAAs.

BACKGROUND The incidence of community-acquired pleural empyema is increasing. Knowledge of the bacterial aetiology is important in order to base recommendations on empirical antimicrobial treatment. The primary aim of the present study was to describe the bacterial aetiology of adult patients with culture proven and/or 16S rRNA-positive community-acquired pleural infection. METHODS We performed a retrospective, population-based observational cohort study in Skane County, south of Sweden. We included all patients with pleural samples obtained between 1st of January 2011 to 31st of December 2017 in Skane, south of Sweden, with a positive culture and/or 16S rRNA result. Exclusion criteria were patients with culture-negative and/or 16S rRNA-negative pleural samples, age < 18 years, pleural empyema caused by trauma or iatrogenesis, pleural infection caused by tuberculosis or fungi, simultaneous lung- or abscess of the abdomen and bacterial species considered to be contaminants. RESULTS A total of 291 patients were included in the study, of which 63% were men and the median age was 69 years. The dominating bacterial aetiology was viridans streptococci (36%), followed by Streptococcus pneumoniae (14%) and anaerobic bacteria (12%). 16S rRNA added information of bacterial aetiology in addition to standard culturing methods in 63% of the patients. CONCLUSION We found that the aetiology of adult patients with culture proven and/or 16S rRNA-positive community-acquired pleural empyema is dominated by viridans streptococci, S. pneumoniae and anaerobic bacteria. Our study shows that 16S rRNA is a valuable tool in finding the bacterial aetiology of community-acquired pleural empyema.

Background Immunosuppressed patients are particularly vulnerable to severe infection from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), risking prolonged viremia and symptom duration. In this study we describe clinical and virological treatment outcomes in a heterogeneous group of patients with severe immunosuppression due to various causes suffering from COVID-19 infection, who were all treated with convalescent plasma (CCP) along with standard treatment. Methods We performed an observational, retrospective case series between May 2020 to March 2021 at three sites in Skåne, Sweden, with a population of nearly 1.4 million people. All patients hospitalized for COVID-19 who received CCP with the indication severe immunosuppression as defined by the treating physician were included in the study (n = 28). Results In total, 28 severely immunocompromised patients, half of which previously had been treated with rituximab, who had received in-hospital convalescent plasma treatment of COVID-19 were identified. One week after CCP treatment, 13 of 28 (46%) patients had improved clinically defined as a decrease of at least one point at the WHO-scale. Three patients had increased score points of whom two had died. For 12 patients, the WHO-scale was unchanged. Conclusion As one of only few studies on CCP treatment of COVID-19 in hospitalized patients with severe immunosuppression, this study adds descriptive data. The study design prohibits conclusions on safety and efficacy, and the results should be interpreted with caution. Prospective, randomized trials are needed to investigate this further.

Background: The aim of this study was to provide a descriptive account of carbapenem resistance and risk factors for mortality from invasive Acinetobacter infections in the south of Sweden. Methods: Blood isolates with growth of Acinetobacter species between 2010 and 2019 in Skåne county were subtyped using MALDI-TOF and subjected to susceptibility testing against clinically relevant antibiotics. Association between risk factors and 30-day mortality were analysed in univariate and multivariate logistic regression models. Results: There were 179 bacteraemia episodes in 176 patients included in the study. The 30-day all-cause mortality was 16%. In all, two percent of Acinetobacter strains were carbapenem resistant. Independent risk factors associated with 30-day mortality in the multivariate regression model were Acinetobacter growth in all blood cultures drawn at the day of bacteraemia onset (OR 5.0, 95% CI: 1.8 to 13.7, p= 0.002), baseline functional capacity (1–4 points, OR 2.0, 95% CI: 1.2 to 3.4, p= 0.010) and correct empiric antibiotics at time of culture (OR 3.5 95% CI: 1.0 to 11.8, p= 0.045). Conclusion: This study on Acinetobacter bacteraemia in South Sweden found low 30-day mortality and low carbapenem-resistance rates compared to previous international studies which may be due to a higher rate of contaminant findings.

This collaborative meta-analysis was supported by the Swiss National Science Foundation and the Laura and John Arnold Foundation (grant supporting the post-doctoral fellowship at the Meta-Research Innovation Center at Stanford (METRICS), Stanford University). The funders had no role in the design of this collaborative meta-analysis; in the collection, analysis, and interpretation of data; or in the report writing., We would like to express our warm gratitude to all participating patients and convalescent plasma donors. We thank Katja Suter and Sina Ullrich, University of Basel, for their administrative assistance. For their helpful contribution to individual trials, we thank Erica Wood, Iain Gosbell, Richard Charlewood, Thomas Hills, Veronica Hoad, Kristina Kairaitis, Aikaj Jindal, John Gerrard, Hong Foo, Adam Stewart, and Nanette Trask (ASCOT trial); Amalia Bravo-Lindoro, Ral Carrillo-Esper, Karla Maldonado-Silva, Catalina Casillas-Suárez, Orlando Carrillo-Torres, Sandra Murrieta, Elizabeth Diaz-Padilla, Eli Omar Zavaleta, Yadira Bejar-Ramirez, and Evelyn Cortina-de la Rosa (CPC-SARS trial); Sheri Renaud, Roel Rolando-Almario, and Jacqueline Day (NCT04385199 trial); Sandra Tingsgrd, MD, Karen Brorup Heje Pedersen, MD, Michaela Tinggaard, MD, Louise Thorlacius-Ussing, MD, Clara Lundetoft Clausen, MD, Nichlas Hovmand, MD, Simone Bastrup Israelsen, MD, Cecilie Leding, MD, Katrine Iversen, MD, Maria Engel Miller, MD, Hkon Sandholdt, MSc biostatistician (CCAP-2 trial). On behalf of the IRCT20200310046736N1 trial, we thank the Khuzestan Blood Transfusion Organization for specialized assistance in the preparation and maintenance of plasma samples. On behalf of the NCT04332835 trial, we thank all the members of the "PC-COVID-19 Group" at the Clinica del Occidente and Hospital Universitario Mayor Mederi in Bogota, and Clinica CES in Medellin. On behalf of the NCT04403477 trial, we thank Miles Carroll for his support regarding the antibody testing in Bangladesh. The Co-CLARITY team would like to extend their gratitude to the Department of Science and Technology Philippine Council for Health Research and Development and the UP-Philippine General Hospital for all their support in the setting up and conduct of the trial. For helpfully communicating details of their trial, we thank members of the PlasmAr trial, NCT04359810 trial (Max O´Donnell), NCT04468009 trial, and CTRI/2020/05/025299 trial. Support for title page creation and format was provided by AuthorArranger, a tool developed at the National Cancer Institute (https://www.cancer.gov/)., During the conduct of the study, the following is reported: Dr. Berry reports being employee with ownership role at Berry Consultants (receives payments for statistical modeling and design of REMAP-CAP). Dr. Castillo reports grants from DOST PCHRD. Dr. Daly reports grants from Medical Research Future Fund (Australian Govt) and RBWH. Dr. Denkinger reports grants from German Ministry for Education and Research. Dr. Dumagay reports grants from Philippine Council for Health Research and Development. Dr. Dunachie reports grants from UK Department of Health and Social Care, grants from UK National Institute of Health Research. Dr. Gauiran reports grants from Department of Science and Technology—Philippine Council for Health Research and Development. Dr. Gordon reports grants from NIHR, grants from NIHR Research Professorship (RP-2015-06-18), and non-financial support from NIHR Clinical Research Network. Dr. Higgins reports grants from NHMRC and from the Minderoo Foundation. Dr. Hills reports grants from Health Research Council of New Zealand. Dr. Holm reports grants from Swedish Government Funds for Clinical Research (ALF). Dr. Janssen and Dr. Müller-Tidow report grants from the Federal Ministry of Education and Research in Germany (BMBF) to the RECOVER clinical trial. Dr. Krapp reports grants from Department of Foreign Affairs, Trade, and Development of Canada, grants from Fundación Telefónica del Perú. Dr. J. Lim reports grants from the Department of Science and Technology, Philippine Council for Health Research and Development. Dr. Lucero reports grants from Philippine Council for Health Research and Development. Dr Manrique reports economic support from Grupo ISA Intercolombia for the project development of trial NCT04332835. Drs. McQuilten and Wood report grants from Medical Research Future Fund. Dr. McVerry reports grants from The Pittsburgh Foundation, Translational Breast Cancer Research Consortium, and from UPMC Learning While Doing Program. Mr. Mouncey reports grants from National Institute for Health Research and from the European Union FP7: PREPARE. Dr. Najdovski reports payment from KUL Leuven to Belgian Red Cross for supply of convalescent plasma. Dr. Nichol reports grants from Health Research Board of Ireland. Dr. D. Roberts reports grants from the National Institute for Health (UKRIDHSC COVID-19 Rapid Response Rolling Call—Grant Reference Number COV19-RECPLAS) and the European Commission (SUPPORT-E #101015756). Dr. Rowan reports grants from the European Commission and from the UK National Institute for Health Research. Dr. Shankar-Hari reports grants from National Institute for Health Research UK, grants from UKRI-National Institute for Health Research UK. Dr. Turgeon reports grants from Canadian Institutes of Health Research. Dr. Venkatesh reports grants from Baxter. Dr. Webb reports grants from National Health and Medical Research Council, grants from Minderoo Foundation. Dr. Zacharowski reports grants from EU Horizon 2020. The ASCOT trial team (Drs Bowen, Daly, Davis, Denholm, Hammond, Jha, L. Lim, McQuilten, Molton, Morpeth, O’Sullivan, Paterson, Perry, Price, Rees, Roberts, Rogers, Sasadeusz, Snelling, Tong, Venkatesh, Wood) is funded by grants from from Royal Brisbane and Women’s Hospital Foundation, Pratt Foundation, Minderoo Foundation, BHP Foundation, Hospital Research Foundation, Macquarie Group Foundation, Health Research Council of New Zealand, Australian Partnership for Preparedness Research on Infectious Disease Emergencies (APPRISE), and the collection and supply of convalescent plasma was conducted within Lifeblood’s funding arrangements. The CONFIDENT trial is funded by the Belgian KCE (blood establishments received payment for the convalescent plasma supplied in the clinical trial). REMAP-CAP was supported in part by funding from UKRIDHSC COVID-19 Rapid Response Rolling Call (Grant Reference Number COV19-RECPLAS). Collection of convalescent plasma for REMAP-CAP was funded by the Department of Health and Social Care, UK. The IRCT20200310046736N1 trial was supported by the Ahvaz Jundishapur University of Medical Sciences (Grant No. R.AJUMS.REC.1399.003, Dr. Pouladzadeh). The PC-COVID-19 Group is supported by the Universidad del Rosario, IDCBIS, ISA Group and Suramericana (Colombia). Outside the submitted work, the following is reported: Dr. Axfors reports postdoctoral grants from the Knut and Alice Wallenberg Foundation, Uppsala University, the Swedish Society of Medicine, the Blanceflor Foundation, and the Sweden-America Foundation. Dr. Aomar reports personal fees from SOBI, GEDEON RICHTER, and GSK. Dr. Benfield reports grants from Novo Nordisk Foundation, Simonsen Foundation, Lundbeck Foundation, Kai Hansen Foundation, Erik and Susanna Olesen’s Charitable Fund; grants and personal fees from GSK, Pfizer, Gilead; and personal fees from Boehringer Ingelheim, MSD, and Pentabase ApS. Dr. Estcourt reports being an investigator on the RECOVERY trial. Dr. Gordon reports personal fees from GlaxoSmithKline, Bristol Myers Squibb, and 30 Respiratory. Dr. Jha reports grants and personal fees from Baxter Healthcare, personal fees from Astra Zeneca, grants from NephroPlus. Dr. Laterre reports personal fees from Adrenomed. Dr. McVerry reports grants from NIH/NHLBI and Bayer Pharmaceuticals, Inc. Dr. Mondragon reports financial activities outside the submitted work (employment at Johnson & Johnson). Dr. Perry reports partner being employed at CSL and owning shares in CSL. Dr. Paterson reports involvement with ALLIANCE trial of COVID-19 treatments. Dr. J. Roberts reports other COVID-19 related trials (in different patient groups): tocilizumab in ICU patients; hydroxychloroquine dosing in ICU patients; planned study of remdesivir pharmacokinetics in patients during expanded access program; and in silico evaluation of ivermectin dosing. Dr Sasadeusz reports grants from various Pharma companies including Gilead Sciences, Abvvie, Merck, and Takeda. Dr. Zacharowski reports personal fees from Biotest AG, CSL Behring, GE Heathcare, and is President of the ESAIC., Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care., Amalia Bravo-Lindoro, BHP Foundation, Blanceflor Foundation, Department of Foreign Affairs, Trade, and Development of Canada, Eli Omar Zavaleta, Erik and Susanna Olesen’s Charitable Fund, Federal Ministry of Education and Research in Germany, Fundación Telefónica del Perú, IDCBIS, ISA Group and Suramericana, Kai Hansen Foundation, Katja Suter and Sina Ullrich, Khuzestan Blood Transfusion Organization, Macquarie Group Foundation, Medical Research Future Fund, NephroPlus, RBWH, Roel Rolando-Almario NCT04385199, Royal Brisbane, Sheri Renaud, Simonsen Foundation, UKRI-National Institute for Health Research UK, UKRIDHSC COV19-RECPLAS, UP-Philippine General Hospital CTRI/2020/05/025299, NCT04359810, NCT04468009, Women’s Hospital Foundation, National Institutes of Health, National Heart, Lung, and Blood Institute, Pittsburgh Foundation, Pfizer, Baxter International, Stanford University, Gilead Sciences, National Institute on Handicapped Research RP-2015-06-18, Meso Scale Diagnostics, Universität Basel, Laura and John Arnold Foundation, Health Research Board, Pratt Foundation, Canadian Institutes of Health Research, National Institute for Health Research, Department of Health and Social Care, European Commission 101015756, National Health and Medical Research Council, Department of Science and Technology, Ministry of Science and Technology, India, Health Research Council of New Zealand, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Sweden-America Foundation, Bundesministerium für Bildung und Forschung, Lundbeckfonden, Knut och Alice Wallenbergs Stiftelse, Seventh Framework Programme, Ahvaz Jundishapur University of Medical Sciences, Université Pierre et Marie Curie, Uppsala Universitet, Horizon 2020, Svenska Läkaresällskapet, Universidad del Rosario, Pharmaceuticals Bayer, Novo Nordisk Fonden, Department of Science and Technology, Philippines, Philippine Council for Health Research and Development, Minderoo Foundation

Background Extended spectrum β-lactamase-producing Enterobacteriaceae (EPE) are responsible for a major part of the widespread antimicrobial resistance (AMR). Increased understanding of risk factors associated with intestinal colonization of EPE is crucial to implement adequate actions against AMR. The aim of this study was to define potential risk factors for prolonged intestinal colonization with EPE. A secondary aim was to analyze if patients were adequately informed about being infected or colonized by antibiotic-resistant bacteria. Methods Patients with a positive clinical EPE culture from urine, blood or feces were recruited in a region in the south of Sweden. Selective EPE fecal cultures were obtained at least three months after the initial positive culture. Prolonged intestinal colonization was defined as the prevalence of any EPE in the follow-up fecal sample. Risk factors for prolonged intestinal colonization were evaluated by using a questionnaire and by retrospective review of medical records. A univariate model and a multivariate regression analysis were performed to identify possible risk factors for intestinal EPE colonization. Results Out of 143 patients included in the study, 57% remained positive for EPE at the second sampling. In a multivariate regression model, urological intervention, history of EPE infection and travel to Africa and/or Asia within 2 years were found to be significantly associated with prolonged intestinal colonization of EPE. Before being approached by us, 50% of patients displayed inadequate knowledge of EPE infection or colonization. Conclusion In this prospective cohort study, urological intervention within 6 months and a history of EPE infection are independently associated with prolonged intestinal colonization with EPE. In contrast, travel to Africa and/or Asia within 2 years is associated with a decreased risk of prolonged intestinal colonization with EPE. There is room for improvement when it comes to patient information regarding EPE to decrease of spread.

Patients with traveler’s diarrhea (TD) can acquire extended-spectrum-beta-lactamase (ESBL)-producing members of the Enterobacterales (EPE) during travel to areas of endemicity. The aim of the present study was to investigate the prevalence and characteristics of EPE carriage in travelers from southern Sweden who were sampled for bacterial diagnostics of TD compared to those of EPE carriage 10 years ago. Clinical samples sent for culture of common causes of bacterial enterocolitis, if the referral stated foreign travel, were included in the study., Patients with traveler’s diarrhea (TD) can acquire extended-spectrum-beta-lactamase (ESBL)-producing members of the Enterobacterales (EPE) during travel to areas of endemicity. The aim of the present study was to investigate the prevalence and characteristics of EPE carriage in travelers from southern Sweden who were sampled for bacterial diagnostics of TD compared to those of EPE carriage 10 years ago. Clinical samples sent for culture of common causes of bacterial enterocolitis, if the referral stated foreign travel, were included in the study. Antimicrobial susceptibility testing was done according to the EUCAST disk diffusion test method. EPE strains were subjected to whole-genome sequencing (WGS). Eighty-four of 303 patients carried a total of 92 ESBL-producing members of the Enterobacterales. The overall prevalence of EPE in tested samples was thus 28%, compared to 24% 10 years earlier (P = 0.33). Among 86 strains available for WGS, 47 different sequence types (STs) were identified, and there were only 5 ST131 strains. Of the 79 Escherichia coli isolates, 76% carried at least one fim (type 1 fimbria) gene, 29% carried at least one pap (p-fimbriae) gene, and 43% were extraintestinal pathogenic E. coli (ExPEC) or uropathogenic E. coli (UPEC). Over half of the E. coli strains (57%) were intestinal pathogenic E. coli, most commonly enteroaggregative E. coli (EAEC) (33%), and enteroinvasive E. coli EIEC (22%). A relatively high proportion of patients with traveler’s diarrhea carry EPE, but there was no significant increase compared to 10 years ago. Most E. coli strains were intestinal pathogenic strains. A comparatively high proportion of the strains were ExPEC/UPEC, many expressing the virulence genes pap and/or fim. (This project was assigned ClinicalTrials.gov number NCT03866291.)

Objectives The adaptive humoral immune response following clinical infection with extended spectrum beta-lactamase (ESBL)-producing Enterobacterales (EPE) has not been thoroughly investigated. The aim of this study was to investigate the presence of anti-CTX-M-15 and/or anti-CTX-M-27 IgG antibodies in bacteremia patients diagnosed with EPE compared to a control group consisting of patients suffering from bacteremia with third generation cephalosporin-susceptible Escherichia coli (3GCSE). Methods Patientswith EPE (n = 59) or 3GCSE (n = 42) bacteremia were recruited in this case control study in the Skane County (South of Sweden). Sera were collected 1–26 months after bacteremia. Enzyme-linked immunosorbent assay (ELISA) was used for detection of specific IgG antibodies directed against recombinant beta-lactamases CTX-M-15 and CTX-M-27. The beta-lactamase resistance genes of the corresponding EPE blood isolates were determined by DNA sequencing. Results The majority (n = 47; 80 %) of the 59 EPE blood isolates carried blaCTX-M-15 or blaCTX-M-27 genes. IgG antibodies reacting to the corresponding CTX-M enzyme was seen in 28 % (13/47) of patients suffering from EPE-bacteremia, while antibodies were detected in only 9.5 % (4/42) of patients with 3GCSE (p = 0.03). Patients with EPE had a statistically significantly higher median Charlson comorbidity index and prevalence of renal disease (p = 0.01), compared to the 3GCSE control group. Conclusion This study implies that EPE bacteremia can trigger production of IgG antibodies targeting ESBL. Further investigations are required to determine the functional role of anti-ESBL antibodies against EPE bacteremia.

Objectives Infections with extended spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (EPE) are a major healthcare concern. Our goal was to investigate whether a probiotic mixture could be used for eradication therapy in patients with prolonged intestinal EPE carriage. Methods We performed a randomized, placebo-controlled, single-blinded clinical superiority trial in the south of Sweden between February 2017 and April 2019. Probiotic Vivomixx®, a mixture of 8 different living bacterial strains or placebo was given to adult outpatients intestinally colonized for at least 3 months with EPE. Patients with suspected active infections at the time of evaluation were excluded, and also those with immunosuppression, severe psychiatric disorder, drug abuse or dementia. Each patient in the probiotic arm was administered 2 sachets (9.0 × 1011 live bacteria) twice daily for 2 months. The primary outcome was intestinal EPE eradication at the end of the 1-year follow-up, as shown by 3 consecutive negative EPE rectal swabs during the follow-up year. The per protocol follow-up for all patients was 1, 3, 6 and 12 months after the initiation of the intervention. ClinicalTrials.gov Identifier: NCT03860415. Results In total, the target size of 80 patients were included. The median age was 68 years in both groups. The number of females in the probiotics group was 23 (58%) and in the placebo group 28 (70%). At the end of the trial, 12.5% (5 out of 40) of the patients in the probiotic group had achieved successful eradication of EPE, as defined by the primary outcome, in the intention to treat analysis. In the placebo group, 5% (2 out of 40) of the patients had achieved successful eradication of EPE (odds ratio 2.71; 95% confidence interval (CI), 0.49–14.9; p 0.24). Conclusions Successful EPE eradication was observed in very few individuals. This trial did not support Vivomixx® as being superior to placebo for intestinal decolonization in adult patients with chronic colonization of EPE, but was limited in power.

Background Extended spectrum β-lactamase-producing Enterobacteriaceae (EPE) are responsible for a major part of the widespread antimicrobial resistance (AMR). Increased understanding of risk factors associated with intestinal colonization of EPE is crucial to implement adequate actions against AMR. The aim of this study was to define potential risk factors for prolonged intestinal colonization with EPE. A secondary aim was to analyze if patients were adequately informed about being infected or colonized by antibiotic-resistant bacteria. Methods Patients with a positive clinical EPE culture from urine, blood or feces were recruited in a region in the south of Sweden. Selective EPE fecal cultures were obtained at least three months after the initial positive culture. Prolonged intestinal colonization was defined as the prevalence of any EPE in the follow-up fecal sample. Risk factors for prolonged intestinal colonization were evaluated by using a questionnaire and by retrospective review of medical records. A univariate model and a multivariate regression analysis were performed to identify possible risk factors for intestinal EPE colonization. Results Out of 143 patients included in the study, 57% remained positive for EPE at the second sampling. In a multivariate regression model, urological intervention, history of EPE infection and travel to Africa and/or Asia within 2 years were found to be significantly associated with prolonged intestinal colonization of EPE. Before being approached by us, 50% of patients displayed inadequate knowledge of EPE infection or colonization. Conclusion In this prospective cohort study, urological intervention within 6 months and a history of EPE infection are independently associated with prolonged intestinal colonization with EPE. In contrast, travel to Africa and/or Asia within 2 years is associated with a decreased risk of prolonged intestinal colonization with EPE. There is room for improvement when it comes to patient information regarding EPE to decrease of spread.

Background : Extended-spectrum cephalosporin-resistant Enterobacteriaceae (ESCRE) are an increasing healthcare problem in both human and veterinary medicine. The spread of ESCRE is complex with multiple reservoirs and different transmission routes. The aim of this study was to investigate if ESCRE carriage in dogs is more prevalent in households with a known human carrier, compared to households where humans are known to be negative for ESCRE. Identical ESCRE strains in humans and dogs of the same household would suggest a possible spread between humans and dogs. Methods : Twenty-two dog owners with a positive rectal culture for ESCRE each collected a rectal sample from their dog. In addition, a control group of 29 healthy dog owners with a documented negative rectal culture for ESCRE each sampled their household dog. Samples were cultivated for ESCRE using selective methods. In households where both humans and dogs carried ESCRE, isolates were further analysed for antimicrobial susceptibility by disc diffusion or microdilution and for genotype and genetic relatedness using molecular methods. Results : In 2 of 22 households studied, identical ESCRE strains with respect to bacterial species, antibiogram, genotype, and MLVA type were found in humans and dogs. The ESCRE found in the two households were ESBL-producing E. coli with the resistance gene bla CTX-M-27 and AmpC-producing E. coli with bla CMY-2 , bla TEM-1 . ESCRE were not found in dogs in the control group. Conclusions : In households where humans are carrying ESCRE, identical strains were to a limited extent found also in household dogs, indicating a transfer between humans and dogs. In contrast, ESCRE were not found in dogs in households without human carriers. Keywords: animal; human; antimicrobial resistance; Escherichia coli; cephalosporin (Published: 20 June 2016) Citation: Infection Ecology and Epidemiology 2016, 6: 31514 - http://dx.doi.org/10.3402/iee.v6.31514