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Filip Jansåker,1,2 Jonas Bredtoft Boel,3 Sara Thønnings,1,2 Frederik Boëtius Hertz,3 Katrine Hartung Hansen,2 Niels Frimodt-Møller,2 Jenny Dahl Knudsen1,21Department of Clinical Microbiology, Hvidovre Hospital, University of Copenhagen, 2650 Hvidovre, Denmark; 2Department of Clinical Microbiology, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark; 3Department of Clinical Microbiology, Herlev and Gentofte Hospital, University of Copenhagen, 2730 Herlev, DenmarkObjectives: To compare the therapeutic effect of pivmecillinam and other common oral antibiotics for community-acquired urinary tract infections (UTIs) caused by Extended Spectrum Beta-Lactamase (ESBL)- or non-ESBL-producing Escherichia coli.Methods: Retrospective cohort study from 2010 to mid-2016 with data from the regional Laboratory Database and three national databases on antibiotic prescriptions, hospital admission, and mortality, respectively. Primary care patients (≥18 years) empirically treated for UTI caused by non-ESBL- or ESBL-producing E. coli (non-ESBL and ESBL E. coli) were included. Seven antibiotics, commonly used empirically for UTI, were investigated. Treatment failure measured as the redemption of a new antibiotic prescription or admission to hospital due to UTI. Cox proportional hazard ratios and adjusted risk differences along with 95% confidence intervals were calculated for 14 and 30 days, respectively.Results: Thirty-six thousand two hundred and ninety-three (95.7%) and 1624 (4.3%) cases were included in the non-ESBL and ESBL groups, respectively. Male sex, high age, ESBL production, and resistance to empirical therapy were found to independently increase the risk of treatment failure. Compared to pivmecillinam, ciprofloxacin had significantly lower treatment failure for non-ESBL E. coli, but significantly higher treatment failure in ESBL E. coli. There was no significant difference between nitrofurantoin and pivmecillinam.Conclusion: All antibiotics seem to have a higher risk of treatment failure for UTI caused by ESBL-producing E. coli as compared to non-ESBL-producing E. coli. At present, nitrofurantoin and pivmecillinam seem to be the most relevant orally available therapies for E. coli UTI. Local resistance data should guide which of the two that should be the contemporary first-line option. Keywords: UTI, ESBL, E. coli, pivmecillinam, nitrofurantoin, cohort

Sara Thønnings,1,2 Filip Jansåker,1,3 Kim Oren Gradel,4,5 Bjarne Styrishave,2 Jenny Dahl Knudsen11Department of Clinical Microbiology, Copenhagen University Hospital, Hvidovre, Denmark; 2Toxicology Laboratory, Analytical BioSciences, Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark; 3Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 4Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark; 5Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, DenmarkObjectives: On January 18, 2010, a part of the capital region of Denmark shifted the empirical treatment of febrile conditions from cefuroxime to piperacillin/tazobactam. We compare empirical treatment with piperacillin/tazobactam versus cefuroxime for Escherichia coli bacteremia with regard to 14 days mortality, in a low prevalence cohort of Extended-spectrum beta-lactamase-producing E. coli.Methods: From January 18, 2010 to December 31, 2012, we conducted a retrospective cohort study including patients with E. coli bacteremia from six university hospitals in Copenhagen, Denmark. Clinical and laboratory information was obtained from a bacteremia research database, including information on comorbidity, and we used Cox proportional hazard analysis to asses all-cause 14 days mortality.Results: A total of 568 patients receiving either cefuroxime (n=377) or piperacillin/tazobactam (n=191) as empirical therapy were included. In the Cox proportional hazard model, cefuroxime treatment was significantly associated with death (mortality rate ratio 3.95, CI 1.12–13.90). Other variables associated with death were health care related infection (MRR 3.20, CI 1.67–6.15), hospital-acquired infection (MRR 2,17, CI 1.02–4.62), admission at intensive care unit (MRR 20.45, 5.31–78.82), and combination therapy with ciprofloxacin (MRR 2.14, CI 0.98–4.68).Conclusion: Empiric cefuroxime treatment of E. coli bacteremia was significantly associated with higher 14 days mortality in comparison with piperacillin/tazobactam.Keywords: piperacillin/tazobactam, cefuroxime, E. coli, bacteremia, mortality

Abstract Background Optimal antibiotic treatment strategies of Haemophilus infections are still needed. Therefore, 30-day case fatality rate (CFR) of Haemophilus bacteremia and efficacy of various antibiotic treatment regimes were studied. Methods All episodes of Haemophilus bacteremia in the former Copenhagen County during the period 2000-9 were included in the study. Clinical and biochemical findings and outcome were collected retrospectively from medical records. Results 105 consecutive episodes were identified (median age: 69 years, with only 4 children H. influenzae, and 11% to other Haemophilus species. Pneumonia was the most common primary focus (in 48%), and 58% of the patients had Charlson comorbidity index > 1. Definitive antibiotic therapy was in 26 cases benzylpenicillin, in 12 cases aminopenicillins, in 50 cases cefuroxime and in 16 cases broadspectrum antibiotics, whereas 1 palliative case died without start of therapy. Whereas the use of broadspectrum antibiotics was related to the severity of the disease (admittance to ICU, need for assisted ventilation or hemodialysis, septic shock), no significant difference in clinical features was demonstrated for therapy with benzylpenicillin, aminopenicillin or cefuroxime, except benzylpenicillin was rarely administered to immunosuppressed patients. The CFR was 22% (23/105). The choice of empiric antibiotic therapy was not significantly associated with mortality (adequate vs. inadequate treatment: 23% (21/93) vs. 17% (2/12), respectively, P > 0.05). In contrast, definite antibiotic therapy with cefuroxime or aminopenicillins resulted in a significantly lower CFR than treatment with benzylpenicillin (12% (6/50) or 0% (0/12) vs. 39% (10/26), respectively, Log rank test P < 0.02). When adjustments were made for other identified risk factors in bivariate logistic regression analysis, treatment with cefuroxime was still were found to be associated with a significantly lower CFR than for benzylpenicillin: OR: 0.21 (0.06-0.69), P = 0.01 (hospital-acquired bacteremia), OR: 0.27 (0.08-0.91), P = 0.04 (polymicrobial episodes), OR: 0.16 (0.04-0.59), P = 0.006 (admittance at intensive care unit), OR: 0.22 (0.06-0.82), P = 0.02 (alcohol abuse), OR: 0.15 (0.04-0.60), P = 0.008 (altered mental state), OR: 0.22 (0.07-0.71), P = 0.01 (temperature P = 0.02 (septic shock), OR: 0.21 (0.06-0.69), P = 0.01 (mechanical ventilation). Conclusion Our results suggest that, after susceptibility testing, cefuroxime or aminopenicillins are preferable to benzylpenicillins as definitive therapy for Haemophilus bacteremia.

The global strategy to eradicate Hepatitis B (HBV), Hepatitis C (HCV), and HIV by 2030 is critical due to their impact and challenges to healthcare systems. HCV is curable, but HBV and HIV are only suppressible, with a vaccine available solely for HBV. Innovative diagnostic methods are needed, especially for high-risk populations like people who inject drugs (PWID). This study validates a dried blood spot (DBS) nucleic acid amplification test (NAAT) using the Hologic Panther system for detecting HBV, HCV, and HIV. The method was used to screen among PWID in the Capital Region of Denmark. The DBS method demonstrated high sensitivity, with a 95 % limit of detection (LoD) of 2711 IU/mL for HBV, 525 IU/mL for HCV, and 4022 copies/mL for HIV. Screening of 83 PWID in Denmark revealed a 13 % prevalence of active HCV infection, offering significant benefits in settings where traditional venous access is difficult., Competing Interests: Declaration of competing interest The authours/co-authours have no personal, financial, or other competing interest in the study conducted on the development of the dry blood spot method. The department of Clinical Microbiology, Copenhagen University Hospital, Herlev, Denmark have received speakers’ fees for a presentation by Stephen Strunge Nilsson. Henrik Westh has received speakers’ fees and has been on an Advisory Board for Hologic. Hologic Netherlands B. V., Kingsfordweg 151, 1043 GR Amsterdam, the Netherlands provided Aptima for validations and screening of PWID. The sponsor had no influence on study design, data generation, data interpretation, or writing of the manuscript., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors have no funding or conflicts of interests to disclose.

Sepsis is a severe condition, representing a significant public health concern, especially in the elderly. There is, however, little insight into the potential effects of sociodemographic factors and comorbidities on sepsis incidence and how these factors interact. This was a nationwide open cohort study including individuals (N = 6 746 010) in Sweden ≥ 18 years of age spanning from 1997 to 2018, with 116 175 995 person years of follow-up. The outcome was time to first occurrence of sepsis. The following variables were included in the analysis: sociodemographic factors (age, sex, income, education, marital status, region of residency, and country of origin), severe mental disorders (schizophrenia and bipolar disorders), and Charlson Comorbidity Index. Interaction tests were conducted. A total of 161 558 individuals were diagnosed with sepsis during the study period, corresponding to an incidence rate of 13.9 per 10 000 person years (95% CI: 13.8 - 14.0). The main findings were that male sex, high age, low education, and comorbid conditions were positively associated with sepsis, after adjustments for the other covariates. Being aged 80 years and above yielded a HR of 18.19 (95% CI: 17.84 - 18.55) and the effect of high age was more than twice as high in men than in women. In conclusion, this large nationwide cohort found that several sociodemographic factors and comorbid conditions were independently associated with sepsis and men were more affected by higher age than women. These findings can help improve sepsis awareness and preventive work in risk groups., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background: People who inject drugs (PWID) have increased risk of acquiring blood-transmitted chronic viral infections such as Hepatitis B (HBV), Hepatitis C (HCV) and Human Immunodeficiency Virus (HIV) as well as increased risk of acquiring bacterial infections. We aimed to identify and describe bacteraemic episodes, their recurrence rates, predictive and prognostic factors amongst hospitalised PWID., Methods: In this retrospective cohort study, we included 257 hospitalised PWID during 2000-2006 with follow up at the Department of Infectious Diseases, Hvidovre Hospital, Denmark. Data collection included comorbidity (HBV-, HCV-, HIV-, and psychiatric comorbidities), social information (contact to an addiction treatment centre, homelessness), opioid substitution treatment (OST), treatment completion and microbiology findings. There was a 10-years follow-up regarding mortality., Results: The study identified 257 patients classified as PWID. Of these, 58 (22.6%) had at least one episode of bacteraemia during their first hospital admission. Recurrence was found in 29 (50.0%) of the bacteraemia cases. Staphylococcus aureus was the dominant microorganism of both first and recurrent episodes with 24 (41.4%) and nine (31.4%) of cases, respectively. A psychiatric diagnose was significantly associated with a lower risk of bacteraemia in the multivariate analysis (OR: 0.29, [95%CI: 0.11-0.77], P = 0.01). Mortality was significantly higher in patients with bacteraemia (17.2% vs. 3.0%, P < 0.01, OR: 6.67 [95%CI: 2.33-20], P < 0.01)., Conclusions: In hospitalised PWID, bacteraemia was found in 22.6% and was associated with at higher mortality. The most common microorganism of bacteraemia was S. aureus. Psychiatric comorbidity was significantly associated with a lower risk of bacteraemia.

Introduction. Cefuroxime is an important antibiotic to treat several serious infections. Rapid elimination through the kidneys and the variation in MICs of various susceptible pathogens such as Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Streptococcus pneumoniae give rise to dosing issues, especially in otherwise healthy patients. Aim. To investigate the probability of target attainment (PTA) for obtaining the optimal dosage regimens for cefuroxime in healthy young people. Methodology. Two weeks apart 750 and 1500 mg cefuroxime were administered as an intravenous bolus to 20 healthy volunteers (mean age: 27 years). Population modelling and simulation studies were done based on the obtained data for cefuroxime plasma concentration. Results. With a target value of time above MIC ( T >MIC ) greater than 50 % the simulations revealed that a PTA of >99 % is obtained for S. pneumoniae with a dosage regimen of 750 mg q12h. For E. coli and K. pneumoniae the PTA was <90 % even with the highest, simulated dosage of 1500 mg q6h. For S. aureus a dosage of 1500 mg q8h gave a PTA above 97 %. Conclusions. S. pneumoniae is most likely treatable with a two-daily dose of 750 mg cefuroxime. Not treatable are K. pneumoniae and E. coli . For S. aureus 1500 mg q8h constitutes an optimal dosing schedule.

Objectives: To evaluate the importance of treatment duration for therapeutic efficacy of pivmecillinam for community-acquired urinary tract infections (UTIs) caused by Escherichia coli., Methods: A retrospective cohort study was conducted between 1 January 2010 and 30 September 2016 in adults with community-acquired E. coli bacteriuria, treated empirically with pivmecillinam. Regimens of 3, 5 and 7 days were compared using clinical treatment failure (i.e. redemption of a new antibiotic or hospitalization due to UTI) within 14 and 30 days as outcome. HR and risk difference with 95% CI were estimated for treatment failure. Results were stratified by age (18-50, 51-70, >70 years) and sex., Results: Of the 21864 cases of E. coli UTI that were analysed, 2524 (11.5%) were in men. In 954 cases (4.4%) E. coli produced ESBL and 125 (13.1%) of the cases were in men. The 3 day regimen increased the risk of treatment failure for all groups. The risk differences between the 3 and 5 day regimens were <10% for women, but >10% for men. Comparing the 7 day and 5 day regimens, only women aged >50 years demonstrated an increased risk of treatment failure within 14 days with the 5 day regimen, but not within 30 days., Conclusions: With the current data, where data on clinical classification of the E. coli UTI were missing, a 5 day treatment with pivmecillinam at 400 mg three times daily seems to be the rational recommendation for lower UTI in men, pregnant women and women >50 years old. A 3 day regimen seems sufficient for non-pregnant women <50 years old., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: To investigate if a 5-day course pivmecillinam (amdinocillin pivoxil) 400 mg three times daily is superior to a 3-day course in women with uncomplicated urinary tract infection (UTI)., Methods: A randomised, double-blind, placebo-controlled trial conducted at nine primary care centres in Denmark. 368 women (18-70 years) with symptoms compatible with UTI were randomised to blinded therapy of 5 days [5d] or 3 days followed by 2 days of placebo [3d] from May 2015 to November 2017. Clinical data were assessed using a validated questionnaire at inclusion (day-0), daily the following 7 days and once again within the 2nd to 6th week after intervention. Bacteriological data were collected prior to intervention and twice between day 7 and 42. Main clinical endpoints were days to symptom resolution within 7 days after inclusion and proportions with clinical success at the end of intervention. Main bacteriological endpoint was proportion of participants with significant reduction of bacteriuria (≥ 10 2 CFU/mL) in 1st control urine sample. ClinicalTrialsRegister.eu: 2014-001321-32., Findings: 180 (5d) and 188 (3d) participants were included in the study (mean age: 35.4 [5d] and 34.9 [3d]). Of these, 125 (70% [5d]) and 122 (66% [3d]) had a positive baseline urine culture. Forty-four participants were lost to follow-up, leaving 161 [5d] and 163 [3d] participants for analysis, respectively. Mean time to symptom resolution was 2.91 (SD 1.46; [5d]) days and 2.94 (SD 1.42; [3d]) days (P = .894). Clinical success at the end of treatment occurred for 117 of 153 (76%) receiving the 5d-course and for 115 of 157 (73%) receiving the 3d course (difference 3.2% [95% CI -7.1% - 13.5%]; P = .601). Bacteriological success was seen in 92 of 104 (88%) participants given the 5d course and in 86 of 99 (87%) given the 3d course (difference 1.6% [95% CI -8.4%-11.6%]; P = .895)., Interpretations: A 5-day course of pivmecillinam was not superior to a 3-day course in clinical or bacteriological outcomes for UTI., Primary Funding Source: The Danish Regions [no. 14/217].