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Introduction: Candidemia is a severe condition associated with high mortality, and fungi are often not covered by empiric antimicrobial regimes for sepsis. Therefore, the shortest possible time to detection of yeast in the blood is of the essence. Materials and methods: We performed a cohort study of blood culture flasks drawn from patients aged 18 or older in the capital region of Denmark. In 2018 a blood cultures set consisted of two aerobic and two anaerobic flasks. This was changed in 2020 to two aerobic, one anaerobic, and one mycosis flask. We used time-to-event statistics to model time to positivity and compared 2018 with 2020; further, we stratified analyses on the blood culture system used (BacTAlert™ vs. BACTEC™) and high-risk vs. low-risk departments. Results: We included 175,416 blood culture sets and 107,077 unique patients. We found an absolute difference in the likelihood of identifying fungi in a blood culture set of 1.2 (95% CI: 0.72; 1.6) pr. 1.000 blood culture sets corresponding to the number needed to treat 853 (617; 1382). In high-risk departments, the absolute difference was profound, whereas it was negligible and statistically non-significant in low-risk departments 5.2 (95% CI: 3.4; 7.1) vs. 0.16 (−0.17; 0.48) pr. 1.000 blood culture sets. Conclusions: We found that including a mycosis flask in a blood culture set increases the likelihood of identifying candidemia. The effect was mainly seen in high-risk departments.

BACKGROUND: We wish to study disparities in bloodstream infections in migrants and non-migrants by comparing the distribution of pathogens and their resistance patterns in long-term migrants with that in non-migrants in Denmark.METHODS: The study is based on a cohort of migrants, who received residency in Denmark between 1993 and 2015 and a control group of non-migrants. The cohort was linked to a database of bloodstream infections from 2000 to 2015 covering two regions in Denmark. First-time bloodstream infections in individuals ≥18 years of age at the time of sampling were included. We calculated odds ratios adjusted for age, sex, year of sampling, comorbidity, and place of acquisition (hospital- or community-acquired).RESULTS: We identified 4,703 bloodstream infection cases. Family-reunified migrants and refugees had higher odds of Escherichia coli than non-migrants (OR 1.89 95%CI: 1.46-2.44 and OR 1.55 95%CI: 1.25-1.92) and lower odds of Streptococcus pneumoniae (OR 0.38 95%CI: 0.21-0.67 and OR 0.52 95%CI: 0.34-0.81). Differences in pathogen distribution were only prevalent in community-acquired bloodstream infections. Refugees had higher odds of Escherichia coli resistant to piperacillin-tazobactam, ciprofloxacin, and gentamicin compared with non-migrants. Family-reunified migrants had higher odds of Escherichia coli and other Enterobacterales resistant to ciprofloxacin.CONCLUSIONS: Migrants had a higher proportion of community-acquired bloodstream infections with Escherichia coli as well as higher odds of bloodstream infections with resistant Escherichia coli compared with non-migrants. These novel results are relevant for improving migrant health by focussing on preventing and treating infections especially with Escherichia coli such as urinary tract and abdominal infections.

Background Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in organ transplant recipients that may be prevented by antibiotic prophylaxis. We aimed to investigate the incidence rate (IR) of PCP and the related hospitalization and mortality rates in liver transplant recipients in an era of routine prophylaxis. Methods We included all adult liver transplant recipients transplanted at Rigshospitalet between January 1, 2011 and October 1, 2019. Microbiology data were obtained from the Danish Microbiology Database (MiBa), a national database containing all data from all Departments of Clinical Microbiology in Denmark receiving samples from both hospitals and general practices. According to local guidelines, PCP prophylaxis was initiated 1 week posttransplantation and discontinued after 6 months or sooner in patients experiencing side effects. Results We included 343 liver transplant recipients with 1153 person‐years of follow‐up (PYFU), of which 269 (78%) received PCP prophylaxis during the first 6 months posttransplantation. Seven (2%) recipients were diagnosed with PCP during follow‐up. In the first 6 months posttransplantation and in 269 transplant recipients who received prophylaxis there were zero PCP events while the IR was 32 (95% confidence interval [CI] 2.9–148) per 1000 PYFU in 74 recipient who did not receive prophylaxis. During 7th to 12th month posttransplantation the IR was 20 (95% CI: 5.5–53) per 1000 PYFU. All seven (100%) recipients diagnosed with PCP were hospitalized, however none died. Conclusions PCP was not detected in liver transplant recipients while on prophylaxis. Though, it worth mentioning that two out of the seven PCP patients received high‐dose prednisolone before the PCP event. All liver transplant recipients with PCP were hospitalized, but none died. Randomized clinical trials to determine the optimal duration of prophylaxis are warranted., We investigated the incidence of Pneumocystis jirovecii pneumonia (PCP) in a cohort of liver transplant recipients in an era with the use of routine PCP prophylaxis. There were no cases of PCP in recipients while on prophylaxis. Furthermore, no case with PCP infection was reported after 15th month posttransplantation. This underlines the need for randomized clinical trials to determine the optimal duration of prophylaxis.

Background: The risk of pyelonephritis following uncomplicated lower urinary tract infection (cystitis) in women has not been studied in well-powered samples. This is likely due to the previous lack of nationwide primary healthcare data. We aimed to examine the risks of pyelonephritis following cystitis in women and explore if antibiotic treatment, cervical cancer, parity, and sociodemographic factors are related to these risks. Methods: This was a nationwide cohort study (2006–2018) of 752,289 women diagnosed with uncomplicated cystitis in primary healthcare settings. Of these, 404 696 did not redeem an antibiotic prescription within five days from cystitis. Logistic regression models were used to calculate odds ratios for pyelonephritis within 30 days and 90 days following the cystitis event. Results: Around one percent (7454) of all women with cystitis were diagnosed with pyelonephritis within 30 days, of which 78.2% had not redeemed an antibiotic for their cystitis. Antibiotic treatment was inversely associated with both outpatient registration and hospitalization due to pyelonephritis, with odds ratios of 0.85 (95% CI 0.80 to 0.91) and 0.65 (95% CI 0.55 to 0.77), respectively. Sociodemographic factors, parity, and cervical cancer were, with few exceptions (e.g., age and region of residency), not associated with pyelonephritis. Conclusions: Antibiotic treatment was inversely associated with pyelonephritis, but the absolute risk reduction was low. Non-antibiotic treatment for cystitis might be a safe option for most women. Future studies identifying the women at the highest risks will help clinicians in their decision making when treating cystitis, while keeping the ecological costs of antibiotics in mind.

BACKGROUND Stenotrophomonas maltophilia is an opportunistic pathogen and a dreaded cause of bacteraemia with 30-day mortality rates ranging from 14 to 69%. The purpose of this cohort study was to evaluate outcomes of S. maltophilia bacteraemia, at Rigshospitalet, a tertiary hospital in Copenhagen, Denmark. METHODS We included all patients with a blood culture positive for S. maltophilia, from January 1, 2015 to April 1, 2020. We extracted data on antimicrobial susceptibility, treatment, central venous catheter intervention and severe haematological disease. RESULTS Sixty-one cases of S. maltophilia bacteraemia were identified. The overall 90-day mortality was 18%. Sixty percent of patients had a central venous catheter intervention performed. Seventy-nine percent of patients were treated with trimethoprim/sulfamethoxazole (TMP/SMX). Patients with central venous catheter intervention had significantly better survival than those without (HR: 0.16 [95% CI: 0.03-0.73]). Severe haematological disease and patients, who received intensive care unit (ICU) care, were at higher risk of death than other patients (HR: 5.93 [95% CI: 1.18 - 29.94] and HR: 8.37 [95% CI: 1.79 - 39.20], respectively). We found no evidence that any antibiotic regime was superior with regard to 90-day mortality. CONCLUSIONS We did not find evidence to support a change in the current standard-of-care regimen of TMP/SMX and CVC removal. Larger clinical trials are needed to guide such recommendations.

Delftia acidovorans (D. acidovorans) is a Gram-negative bacteria and an uncommon cause of human infections. This retrospective cohort study investigated clinical and microbiological characteristics and outcomes of patients with D. acidovorans infections. We included patients with culture-confirmed D. acidovorans infections attending Rigshospitalet, during 2002-2020. Fifty-nine patients with a median interquartile ranges (IQR) age of 47 (15-67) years were included. Thirty-five (59%) were males, and 57 (97%) had at least one comorbidity, including 25 (42%) with solid or hematologic malignancies. Eight (14%) were admitted to ICU, and 15 (25%) died within 365 days after infection. Persistent infection was found in 4 (6.8%) patients, and 41 (70%) had polymicrobial cultures, mainly with Pseudomonas spp. and Stenotrophomonas maltophilia. More than 85% of the D. acidovorans isolates were susceptible to meropenem or ceftazidime. Although, 88% and 62% of the isolates were resistant to gentamicin and colistin, respectively. D. acidovorans infections mainly affect patients with preexisting comorbidities, including malignancies. In the first year, all-cause mortality is considerable, polymicrobial cultures are common, and meropenem or cephalosporins with antipseudomonal activity could be the antibiotics of choice. IMPORTANCE Delftia acidovorans (D. acidovorans) is a Gram-negative bacteria that can cause infection in immunocompetent and immunocompromised individuals. The current knowledge comes mainly from case reports and case series. In this retrospective cohort study, we found that D. acidovorans infections mainly affect male patients with preexisting comorbidities, including malignancies. Persistent infections were not common, and most of the patients had polymicrobial cultures, mainly with Pseudomonas spp. and Stenotrophomonas maltophilia. More than 85% of the D. acidovorans isolates were susceptible to meropenem or ceftazidime. In contrast, 88% and 62% of the isolates were resistant to gentamicin and colistin, respectively.

Background The recommended duration of antimicrobial treatment for Staphylococcus aureus bacteremia (SAB) is a minimum of 14 days. We compared the clinical outcomes of patients receiving short-course (SC; 6–10 days), or prolonged-course (PC; 11–16 days) antibiotic therapy for low-risk methicillin-susceptible SAB (MS-SAB). Methods Adults with MS-SAB in 1995–2018 were included from 3 independent retrospective cohorts. Logistic regression models fitted with inverse probability of treatment weighting were used to assess the association between the primary outcome of 90-day mortality and treatment duration for the individual cohorts as well as a pooled cohort analysis. Results A total of 645, 219, and 141 patients with low-risk MS-SAB were included from cohorts I, II, and III. Median treatment duration in the 3 SC groups was 8 days (interquartile range [IQR], 7–10), 9 days (IQR, 8–10), and 8 days (IQR, 7–10). In the PC groups, patients received a median therapy of 14 days (IQR, 13–15), 14 days (IQR, 13–15), and 13 days (IQR, 12–15). No significant differences in 90-day mortality were observed between the SC and PC group in cohort I (odds ratio [OR], 0.85 [95% confidence interval {CI}, .49–1.41]), cohort II (OR, 1.24 [95% CI, .60–2.62]), or cohort III (OR, 1.15 [95% CI, .24–4.01]). This result was consistent in the pooled cohort analysis (OR, 1.05 [95% CI, .71–1.51]). Furthermore, duration of therapy was not associated with the risk of relapse. Conclusions In patients with low-risk MS-SAB, shorter courses of antimicrobial therapy yielded similar clinical outcomes as longer courses of therapy.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has been associated with a high risk of adverse outcomes in solid organ transplant (SOT) recipients in the pre-vaccination era. In this retrospective cohort study, we examined the incidence and severity of COVID-19 in kidney and liver transplant recipients in Denmark in the post-vaccination era, from December 27, 2020, to December 27, 2021. We included 1428 SOT recipients with 143 cases of first-positive SARS-CoV-2 PCR test. The cumulative incidence of first-positive SARS-CoV-2 PCR test 1 year after initiation of vaccination was 10.4% (95% CI: 8.8–12.0), and the incidence was higher in kidney than in liver transplant recipients (11.6% [95% CI: 9.4–13.8] vs. 7.4% [95% CI: 5.1–9.8], p =.009). After the first-positive SARS-CoV-2 PCR test, the hospitalization rate was 31.5% (95% CI: 23.9–39.1), and 30-day all-cause mortality was 3.7% (95% CI: 0.5–6.8). Hospitalization was lower in vaccinated than in unvaccinated SOT recipients (26.4% [95% CI: 18.1–34.6] vs. 48.5% [95% CI: 31.4–65.5], p =.011), as was mortality (1.8% [95% CI: 0.0–4.3] vs. 9.1% [95% CI: 0.0–18.9], p =.047). In conclusion, SOT recipients remain at high risk of adverse outcomes after SARS-CoV-2 infections, with a lower risk observed in vaccinated than in unvaccinated SOT recipients.

Background: The SARS-CoV-2 pandemic has resulted in massive testing by Rapid Antigen Tests (RAT) without solid independent data regarding clinical performance being available. Thus, decision on purchase of a specific RAT may rely on manufacturer-provided data and limited peer-reviewed data. Methods: This study consists of two parts. In the retrospective analytical part, 33 RAT from 25 manufacturers were compared to RT-PCR on 100 negative and 204 positive deep oropharyngeal cavity samples divided into four groups based on RT-PCR Cq levels. In the prospective clinical part, nearly 200 individuals positive for SARS-CoV-2 and nearly 200 individuals negative for SARS-CoV-2 by routine RT-PCR testing were retested within 72 h for each of 44 included RAT from 26 manufacturers applying RT-PCR as the reference method.Results: The overall analytical sensitivity differed significantly between the 33 included RAT; from 2.5% (95% CI 0.5–4.8) to 42% (95% CI 35–49). All RAT presented analytical specificities of 100%. Likewise, the overall clinical sensitivity varied significantly between the 44 included RAT; from 2.5% (95% CI 0.5–4.8) to 94% (95% CI 91–97). All RAT presented clinical specificities between 98 and 100%. Conclusion: The study presents analytical as well as clinical performance data for 44 commercially available RAT compared to the same RT-PCR test. The study enables identification of individual RAT that has significantly higher sensitivity than other included RAT and may aid decision makers in selecting between the included RAT. Funding: The study was funded by a participant fee for each test and the Danish Regions.

IntroductionInfectious spondylodiscitis is a rare infection of the intervertebral disc and the adjacent vertebral bodies that often disseminates and requires long-term antibiotic therapy. Immunologic profiling of patients with infectious spondylodiscitis could allow for a personalized medicine strategy. We aimed to examine the induced immune response in patients with infectious spondylodiscitis during and after antibiotic therapy. Furthermore, we explored potential differences in the induced immune response depending on the causative pathogen and the dissemination of the disease.MethodsThis was a prospective observational cohort study that enrolled patients with infectious spondylodiscitis between February 2018 and August 2020. A blood sample was collected at baseline, after four to six weeks of antibiotic therapy (during antibiotic therapy), and three to seven months after end of antibiotic therapy (post-infection). The induced immune response was assessed using the standardized functional immune assay TruCulture®. We used a panel of three immune cell stimuli (lipopolysaccharide, Resiquimod and polyinosinic:polycytodylic acid) and an unstimulated control. For each stimulus, the induced immune response was assessed by measuring the released concentration of Interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p40, IL-17A, Interferon-γ (IFN-γ) and Tumor necrosis factor-α (TNF-α) in pg/mL.ResultsIn total, 49 patients with infectious spondylodiscitis were included. The induced immune responses were generally lower than references at baseline, but the cytokine release increased in patients after treatment with antibiotic therapy. Post-infection, most of the released cytokine concentrations were within the reference range. No significant differences in the induced immune responses based on stratification according to the causative pathogen or dissemination of disease were found.ConclusionWe found lower induced immune responses in patients with infectious spondylodiscitis at baseline. However, post-infection, the immune function normalized, indicating that an underlying immune deficiency is not a prominent factor for spondylodiscitis. We did not find evidence to support the use of induced immune responses as a tool for prediction of the causative pathogen or disease dissemination, and other methods should be explored to guide optimal treatment of patients with infectious spondylodiscitis.

This study explored all-cause mortality of bacteremia diagnosed during a 60-day non-physician healthcare worker strike in 2008. A significant change, with 5.0% (95% confidence interval [CI] 1.2–8.7%, P < .01) absolute risk increase, was seen in 90-day mortality during the strike (n = 598) compared with the rest of the study period 2000–2015 (n = 75 647).

BACKGROUND The SARS-CoV-2 pandemic has resulted in an unprecedented level of worldwide testing for epidemiologic and diagnostic purposes, and due to the extreme need for tests, the gold-standard Reverse Transcription Polymerase Chain Reaction (RT-PCR) testing capacity has been unable to meet the overall worldwide testing demand. Consequently, although the current literature has shown the sensitivity of rapid antigen tests (RATs) to be inferior to RT-PCR, RATs have been implemented on a large scale without solid data on performance. OBJECTIVE This study will compare analytical and clinical sensitivities and specificities of 50 lateral flow– or laboratory-based RATs and 3 strand invasion–based amplification (SIBA)-RT-PCR tests from 30 manufacturers to RT-PCR testing of samples obtained from the deep oropharynx. In addition, the study will compare sensitivities and specificities of the included RATs as well as RT-PCR on clinical samples obtained from the deep oropharynx, the anterior nasal cavity, saliva, the deep nasopharynx, and expired air to RT-PCR on deep oropharyngeal samples. METHODS In the prospective part of the study, 200 individuals found SARS-CoV-2 positive and 200 individuals found SARS-CoV-2 negative by routine RT-PCR testing will be retested with each RAT, applying RT-PCR as the reference method. In the retrospective part of the study, 304 deep oropharyngeal cavity swabs divided into 4 groups based on RT-PCR quantification cycle (Cq) levels will be tested with each RAT. RESULTS The results will be reported in several papers with different aims. The first paper will report retrospective (analytical sensitivity, overall and stratified into different Cq range groups) and prospective (clinical sensitivity) data for RATs, with RT-PCR as the reference method. The second paper will report results for RAT based on anatomical sampling location. The third paper will compare different anatomical sampling locations by RT-PCR testing. The fourth paper will focus on RATs that rely on central laboratory testing. Tests from 4 different manufacturers will be compared for analytical performance data on retrospective deep oropharyngeal swab samples. The fifth paper will report the results of 4 RATs applied both as professional use and as self-tests. The last paper will report the results from 2 breath tests in the study. A comparison of sensitivity and specificity between RATs will be conducted using the McNemar test for paired samples and the chi-squared test for unpaired samples. Comparison of the positive predictive value (PPV) and negative predictive value (NPV) between RATs will be performed by the bootstrap test, and 95% CIs for sensitivity, specificity, PPV, and NPV will be calculated as bootstrap CIs. CONCLUSIONS The study will compare the sensitivities of a large number of RATs for SARS-CoV-2 to with those of RT-PCR and will address whether lateral flow–based RATs differ significantly from laboratory-based RATs. The anatomical test locations for both RATs and RT-PCR will also be compared. CLINICALTRIAL ClinicalTrials.gov NCT04913116; https://clinicaltrials.gov/ct2/show/NCT04913116 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/35706

OBJECTIVES: To investigate bloodstream infection (BSI) related to migrant status by comparing the incidence and mortality in migrants with that in non-migrants.METHODS: In this register-based cohort study we linked a cohort of migrants and non-migrants with a bacteraemia database covering two regions in Denmark. We included first-time BSI between January 2000 and December 2015 in individuals ≥18 years. Migrants were categorized according to status: refugees or family-reunified migrants. Incidence rate ratio and mortality rate ratio were analysed using Poisson regression.RESULTS: We identified 493 080 non-migrants, of which 3405 had BSI, and 80 740 migrants with 576 cases; of the latter, 40 222 were family-reunified migrants with 226 cases and 40 518 were refugees with 350 cases. Refugees had a higher risk of BSI than non-migrants (adjusted IRR 1.19, 95%CI 1.01-1.40). Family-reunified migrants and refugees had a higher risk of Gram-negative BSIs (adjusted IRR 1.23, 95%CI 1.00-1.51 and 1.57, 95%CI 1.32-1.86), respectively, and a lower risk of Gram-positive BSIs (adjusted IRR 0.65, 95%CI 0.51-0.83 and 0.77, 95%CI 0.63-0.95), respectively, compared to non-migrants. Originating from Southeast Asia and the Pacific was associated with an increased risk of BSI compared to non-migrants (adjusted IRR 1.26, 95%CI 1.07-1.49). We found no differences in the adjusted 30-day or 90-day mortality according to migrant status.CONCLUSIONS: Vulnerability towards BSI differs according to migrant status. Refugees had a higher risk of BSI overall. Both refugees and family-reunified migrants had a higher incidence of Gram-negative BSI than non-migrants. Similarly, migrants from Southeast Asia and the Pacific had a higher risk of BSI than non-migrants.

This study aimed to investigate the incidence of enterococcal infections and determine risk factors associated with enterococcal bloodstream infection (BSI) within the first year post-liver transplantation (LTx). We included 321 adult liver transplant recipients transplanted from 2011 to 2019 in a prospective cohort study. Cumulative incidence of enterococcal infections and risk factors associated with BSI were investigated in a competing risk model and time-updated Cox models, respectively. A total of 223 enterococcal infections were identified in 89 recipients. The cumulative incidences of first enterococcal infection and first enterococcal BSI were 28% (95% CI (23–33)) and 11% (CI (7–14)), respectively. Risk factors associated with enterococcal BSI were previous infections in the biliary tract (HR, 33, CI (15–74), p &lt, 0.001), peritoneum (HR, 8.1, CI (3–23), 0.001) or surgical site (HR, 5.5, CI (1.4–22), p = 0.02), recipient age (HR per 10 years increase, 1.2, CI (1.03–1.6), p = 0.03), and cold ischemia time (HR per one hour increase, 1.2, CI (1.1–1.3), 0.01). Enterococcal infections are highly prevalent the first year post-LTx, and recipients with enterococcal infections in the biliary tract, peritoneum, or surgical site are at increased risk of BSI. These findings may have implications for the choice of empiric antibiotics early post-LTx.

Background: Streptococcus pneumoniae (S. pneumoniae) and Hemophilus influenzae (H. influenzae) are among the main vaccine-preventable bacterial infections in immunocompromised individuals including solid organ transplant (SOT) recipients. There is a lack of information about incidence and outcomes of these infections in SOT recipients. Methods: We determined the incidence of S. pneumoniae and H. influenzae, the related hospitalization, and 30- and 180-days mortality in a large cohort of 1182 adult SOT recipients. We calculated 95% confidence intervals (CI) of incidence rate (IR) using Byar’s approximation to the Poisson distribution. Results: The overall IR of S. pneumoniae and H. influenzae were 1086 (95% CI, 796–1448) and 1293 (95% CI, 974–1687) per 100,000 person-years of follow-up (PYFU), respectively. The IR of invasive infections were 76 (95% CI, 21–202) and 25 (95% CI, 2.3–118) per 100,000 PYFU, respectively. Hospital admission was required in >50%, 30-days mortality was 0, and 180-days mortality was 8.8% and 4.5% after S. pneumoniae and H. influenzae infections, respectively. Conclusions: The IR of invasive S. pneumoniae and H. influenzae infections in SOT recipients were much higher than reports from the general population in Denmark. Furthermore, a large proportion of infected SOT recipients were hospitalized. These findings highlight the need for further studies to assess uptake and immunogenicity of vaccines against S. pneumoniae and H. influenzae in SOT recipients.

Background Bacterial and fungal bloodstream infections (BSI) are common after pediatric liver and kidney transplantations and associated with morbidity and mortality. However, knowledge about incidence rates, pathogen composition, and resistance patterns is limited. We aimed to describe the pattern of bacterial and fungal BSI in a cohort of pediatric liver and kidney transplant recipients. Methods A prospective study of 85 pediatric liver and kidney transplant recipients transplanted from 2010 to 2017 with a total of 390 person-years of follow-up. Clinical characteristics and BSI were retrieved from national registries assuring nationwide follow-up for at least 1 year. BSI incidence rates and pathogen composition were investigated and stratified by the time post-transplantation and type of transplanted organ. Results A total of 29 BSI were observed within the first 5 years post-transplantation with 16 different pathogens. The overall incidence rate of first BSI was 1.91 per 100 recipients per month (95% CI, 1.1–3.1) in the first year post-transplantation. The most common pathogens were Enterococcus faecium, Candida albicans, Escherichia coli, and Klebsiella pneumoniae. The pathogen composition depended on the transplanted organ with a higher proportion of BSI with Enterobacterales in kidney transplant recipients than in liver transplant recipients (67% vs. 20%, p = 0.03), while multiple pathogens were detected in the liver transplant recipients. Conclusions BSI were common in pediatric liver and kidney transplant recipients and the pathogen composition differed between liver and kidney transplant recipients. Guidelines for empiric antibiotic therapy should consider the type of transplanted organ as well as the local resistance patterns.

Listeria monocytogenes meningitis in Danish children 1 month to 17 years from 2000 to 2017 was identified and patient files reviewed. There were 5 cases, equaling an annual incidence of 0.024 per 100,000 children or 0.014 when excluding 2 immunodeficient children. Even in a country with a high general incidence of listeriosis, Listeria meningitis is a rare event in healthy children.

Objectives 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.

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 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

Objectives: 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.

Relapse of neonatal meningitis is most commonly caused by Escherichia coli. Management to prevent relapse varies and evidence is limited. We present four cases of relapsing neonatal E. coli meningitis in Denmark in 2016–2017 and review the current literature on this subject. During the primary episodes, our patients received cephalosporin for 3 weeks and gentamicin for the first 3 days. The only identified risk factor was delayed CSF sterilization in three of four cases and no repeated lumbar puncture. Relapse occurred after 2–28 days; one case with ventriculitis and one with empyema. Relapses were treated for 6–14 weeks with monotherapy. No children had an underlying disease predisposing to E. coli meningitis. There is generally a trend towards reducing invasive procedures, e.g., lumbar puncture and the length of intravenous antibiotics in pediatric infectious diseases, but our cases highlight a condition where the opposite might be needed.

Background: Positive expiratory pressure (PEP) has been shown to prevent pneumonia in leukaemia patients. We hypothesised that PEP selfcare could be effective in reducing respiratory symptoms and urgent care visits among non-hospitalised individuals with SARS-CoV-2 infection and COVID-19 symptoms. Methods: PEP-CoV was a randomised, controlled, open-label trial with two parallel groups, comparing PEP selfcare as add-on to usual care to usual care only. The randomisation was based on permuted random blocks in a 1:1 ratio, stratified for sex and age (< 60 or ≥ 60 years). The intervention group was instructed to use a PEP flute three times daily during the 30-day intervention. The primary outcome was 30-day change in the COPD Assessment Test (CAT)-score, a validated questionnaire designed to evaluate respiratory symptom severity. Secondary outcomes were self-reported urgent care visits due to COVID-19 during the observation period, number of COVID-19 related symptoms, and 30-day change in self-rated health. The study is registered with ClinicalTrials.gov, NCT04530435. Findings: Between Oct 6, 2020, and Feb 26, 2021, 378 participants were randomly assigned to the PEP intervention (n=190) or usual care (n=188). In the PEP selfcare group, the median number of days with PEP flute use was 21 days (IQR 13-25). For the intention-to-treat population, we observed a group difference in changes from baseline in CAT-scores of -1.2 points (95%CI, -2.1 to -0.2; P=0.017) in favour of the PEP selfcare group. This group also reported less chest tightness, less dyspnoea, more vigour, and higher level of daily activities at day 30. We found no consistent effects on the secondary outcomes. No serious adverse events were reported. Interpretation: PEP flute-selfcare is safe at low cost and appears to have small beneficial effects on respiratory symptom severity in early COVID-19. Trial Registration: NCT04530435 Funding: Innovation Fund Denmark, the Danish Nursing Council and the Oak Foundation. Declaration of Interests: None of the authors declared any conflict of interest. Ethics Approval Statement:The study was approved by the local Health Research Ethics Committee (H-20035929) and the Danish Data Protection Agency (Capital Region: P-2020-879). Although the PEP flute is classified as a medical device, no approval from the Danish Medicines Agency was needed, as the device was applied for purposes within the CE- classification (Agency reference number: 2020051572).

ObjectiveTo determine whether positive expiratory pressure (PEP) by PEP flute self-care is effective in reducing respiratory symptoms among community dwelling adults with SARS-CoV-2 infection and early stage covid-19.DesignNon-drug, open label, randomised controlled trial.SettingCapital Region and Region Zealand in Denmark from 6 October 2020 to 26 February 2021.ParticipantsCommunity dwelling adults, able to perform self-care, with a new SARS-CoV-2 infection (verified by reverse transcription polymerase chain reaction tests) and symptoms of covid-19.InterventionParticipants were randomised to use PEP flute self-care in addition to usual care or have usual care only. Randomisation was based on permuted random blocks in a 1:1 ratio, stratified for sex and age (Main outcome measuresPrimary outcome was a change in symptom severity from baseline to day 30, as assessed by the self-reported COPD (chronic obstructive pulmonary disease) assessment test (CAT), which was adjusted for baseline values and stratification factors. Participants completed the CAT test questionnaire every day online. Secondary outcomes were self-reported urgent care visits due to covid-19, number of covid-19 related symptoms, and change in self-rated health, all within 30-days’ follow-up.Results378 participants were assigned to the PEP flute self-care intervention (n=190) or usual care only (n=188). In the PEP self-care group, the median number of days with PEP flute use was 21 days (interquartile range 13-25). For the intention-to-treat population, a group difference was observed in changes from baseline in CAT scores of −1.2 points (95% confidence interval −2.1 to −0.2; P=0.017) in favour of the PEP flute self-care group. At day 30, the PEP flute self-care group also reported less chest tightness, less dyspnoea, more vigour, and higher level of daily activities, but these differences were small, and no consistent effects were seen on the secondary outcomes. No serious adverse events were reported.ConclusionsIn community dwelling adults with early covid-19, PEP flute self-care had a significant, yet marginal and uncertain clinical effect on respiratory symptom severity, as measured by CAT scores.Trial registrationClinicalTrials.govNCT04530435.

During the latest decades, the efficacy and safety of an early switch from intravenous to oral antibiotics has been the topic of several investigations. In this review, we summarise the results of studies, which have shown that it is safe to treat mild infections with oral antibiotics only. For more severe infections, three days of intravenous antibiotics followed by oral antibiotics is typically sufficient. There are several benefits of early switch therapy including easier administration and lower expenses. The most frequently prescribed intravenous antibiotics have oral formulations or oral alternatives with a high bioavailability.

Highlights • Doctors (surgeons) have lower baseline hand hygiene compliance than nurses. • Light-guided nudging and data-driven performance feedback improve compliance. • Individual performance feedback might be more effective than group feedback. • The Sani nudge system detects more opportunities than using manual observations. • Nurses and doctors disinfect hands more often after rather than before patient contact., Graphical Abstract Image, graphical abstract, Background Evidence-based practices to increase hand hygiene compliance (HHC) among health care workers are warranted. We aimed to investigate the effect of a multimodal strategy on HHC. Methods During this 14-month prospective, observational study, an automated monitoring system was implemented in a 29-bed surgical ward. Hand hygiene opportunities and alcohol-based hand rubbing events were measured in patient and working rooms (medication, utility, storerooms, toilets). We compared baseline HHC of health care workers across periods with light-guided nudging from sensors on dispensers and data-driven performance feedback (multimodal strategy) using the Student's t test. Results The doctors (n = 10) significantly increased their HHC in patient rooms (16% vs 42%, P< .0001) and working rooms (24% vs 78%, P= .0006) when using the multimodal strategy. The nurses (n = 26) also increased their HHC significantly from baseline in both patient rooms (27% vs 43%, P = .0005) and working rooms (39% vs 64%, P< .0001). The nurses (n = 9), who subsequently received individual performance feedback, further increased HHC, compared with the period when they received group performance feedback (patient rooms: 43% vs 55%, P< .0001 and working rooms: 64% vs 80%, P< .0001). Conclusions HHC of doctors and nurses can be significantly improved with light-guided nudging and data-driven performance feedback using an automated hand hygiene system.