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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 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.

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.

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).

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.

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.

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.

Purpose To determine the prevalence of SARS-CoV-2 at a Danish tertiary referral otorhinolaryngology clinic during the first wave of the COVID-19 pandemic among patients with suspected acute upper airway infection (UAI) and patients operated for head and neck cancer (HNC), respectively. To monitor changes in the number of patient encounters for acute UAI and the number of referrals for the workup of HNC. Trial registration: NCT-04356560 (Clinicaltrials.gov). Methods Prospective enrolled case series of all patients with suspected acute UAI (n = 88) and of patients undergoing surgery for HNC (n = 96), respectively, from March 23rd to May 5th, 2020, at a public tertiary referral otorhinolaryngology clinic in Denmark. SARS-CoV-2 was diagnosed with nasopharyngeal and oropharyngeal swabbing. Patients with suspected acute UAI had symptoms and definitive diagnoses registered in a database. Trends in the number of referrals and patient encounters were retrieved from an electronic patient journal system and analyzed retrospectively. Results Eighty-eight patients with acute UAI were enrolled including 55 men and 34 women, median age of 31 years (range: 10 months to 82 years). One patient (1.1%) tested positive. Among 96 patients operated for HNC, zero tested positive. The number of referrals for HNC workup, and patient encounters for peritonsillar abscesses, decreased markedly in the first 3 weeks. Conclusion The prevalence of SARS-CoV-2 during the first 6 weeks of the first wave was minimal among patients with acute UAI and zero among patients operated for HNC. The decrease in referrals for the workup of HNC may increase time to treatment initiation and patient morbidity. Supplementary Information The online version contains supplementary material available at 10.1007/s00405-020-06514-6.

Importance Otorhinolaryngology is considered one of the medical specialties with a high risk for exposure to corona disease 2019 (COVID-19). Uncontrolled transmission in a hospital department poses a risk to both healthcare workers (HCWs) and patients. Objective To monitor SARS-CoV-2 incidence, transmission, and antibody development among HCWs to identify high risk procedures, pathways, and work areas within the department. Methods Prospective cohort study of HCWs using repetitive oro- and nasopharygeal swab samples, antibody tests, and self-reported symptoms questionnaires at a tertiary referral center in Copenhagen, Denmark. Results 347/361 (96%) HCWs participated. Seven (1.9%) were positive on swab tests and none had symptoms. Fifteen (4.2%) developed antibodies. Only one case of potential transmission between HCWs was identified. Infection rates were low and no procedures or areas within the department were identified as exposing HCWs to a higher risk. Conclusions and relevance Adherence to the surveillance program was high. The low incidence among HCW during the first wave of the COVID-19 pandemic may reflect local transmission and infection control precautions, as well as a low infectious burden in the Danish society.

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 P 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.

Background Mecillinam (amdinocillin) is active against Gram-negative bacteria. Clinical data on the efficacy of IV mecillinam for severe urinary tract infections is sparse. Objectives To assess the effectiveness of targeted IV mecillinam compared with other β-lactams for bacteraemia with Escherichia coli and Klebsiella spp. and a urinary tract focus. Patients and methods We performed a retrospective cohort study at five university hospitals in the Capital Region of Denmark from 1 January 2012 to 31 December 2017. We used Cox proportional hazard regression to compare the primary composite endpoint (all-cause mortality or bacteraemia recurrence within 30 days) between patients treated with mecillinam versus ampicillin, cefuroxime, piperacillin/tazobactam and meropenem. Results We included 1129 patients in the primary analysis, of which 146 were given IV mecillinam as targeted treatment. We found no significant difference in the primary endpoint between patients treated with mecillinam versus ampicillin and cefuroxime, but found a higher risk for the primary endpoint in the piperacillin/tazobactam and meropenem groups, with adjusted HRs of 2.22 (95% CI 1.24–3.97, P Conclusions The results of this study suggest that IV mecillinam may be a suitable targeted treatment for bacteraemia with a urinary tract focus. However, these results need confirmation by randomized controlled studies.

Background Infected walled-off pancreatic necrosis (WON) is associated with increased morbidity and mortality. Systemic antibiotics are the main treatment, but are associated with adverse reactions and risk of superinfections. This study evaluates the efficacy of local instillation of antibiotics into WON. Methods We performed a retrospective cohort study of all consecutive patients with infected WON, who were treated with endoscopic transmural drainage and necrosectomy (ETDN) at a tertiary referral hospital between 2012 and 2016. A total of 91 patients were included. Patients often received concomitant intravenous and local antibiotics. Local antibiotics were added to the irrigation fluid depending on microbiological findings. A beneficial response was defined as the eradication of a microbe on subsequent culturing. Univariable and multivariable logistic regression analyses were used to evaluate antimicrobial efficacy. Results At the first drainage 81 (86%) patients had infected and 10 sterile WON. Among patients with bacterial infections, neither local nor systemic antibiotics were associated with the eradication of microbes between first and second culture. Between the second and third culture, the use of local antibiotics was associated with the eradication of microbes (OR, 2.54; 95% CI, 1.25–5.18; p = 0.01), but not systemic antibiotics (OR, 0.75; 95% CI, 0.38–1.38; p = 0.33). Twelve patients had fungal infections treated with local amphotericin B between first and second culture. The fungus was eradicated in all 12 patients. Conclusion Local instillation of antibiotics may be a promising supplement to systemic administration.

Purpose: The pharmacokinetic properties of mecillinam (MEC) for urinary tract infections are excellent, and the resistance rate in Enterobacteriaceae is low compared to other recommended antibiotics. The oral prodrug pivmecillinam (P-MEC) has been used successfully as first choice for cystitis in the Nordic countries for many years. Norwegian and Danish guidelines also recommend P-MEC for acute uncomplicated pyelonephritis (AUP) and intravenous (IV) MEC for suspected urosepsis (only in Denmark). Here, we wish to present an updated investigation on the clinical data behind these recommendations together with sparse but more current clinical data. Methods: Prospective clinical trials evaluating MEC as monotherapy or in polytherapy with one other beta-lactam (mostly ampicillin [AMP]) for pyelonephritis or bacteremia were reviewed. Outcomes of primary interest were clinical and bacteriological success and relapse, respectively. Search databases used were PubMed, Cochrane Library, and Embase. Results: Twelve clinical studies (1979-2015) were included in this integrated literature review. Clinical success was seen in 38/51 (75%) patients treated with MEC as monotherapy and in 152/164 (93%) patients treated with MEC and one other beta-lactam. Bacteriological success was seen in 35/47 (74%) and 117/167 (70%) patients treated with MEC alone and with one other beta-lactam, respectively. In complicated infections, bacteriological success was much lower. Clinical relapse rate was not well described. Several uropathogenic bacteremia cases were treated successfully with MEC alone (ie, 10/15 [67%] and 13/15 [87%] for clinical and bacteriological success, respectively) or with one other beta-lactam (ie, 57/65 [88%] and 53/63 [84%] for clinical and bacteriological success, respectively). However, data on bacteremia are very sparse. Adverse reactions were few and mild (73/406 [18%]) and primarily seen when AMP was co-administered (69/73 [95%]). No serious adverse reactions were reported. Conclusion: IV MEC or oral P-MEC for 14 days may be suitable for the treatment of AUP and pediatric pyelonephritis. Randomized controlled trials using a single standardized dose of P-MEC compared to other current recommendations are warranted. Similarly, more evidence is required before MEC should be recommended for bacteremia or sepsis due to Enterobacteriaceae.

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.

Aim We investigated the consequences of applying different imaging guidelines for urological anomalies after first pyelonephritis in children with normal routine antenatal ultrasounds. Methods The cohort comprised 472 children treated for their first culture positive pyelonephritis and investigated with ultrasound and renal scintigraphy. We excluded patients with known urological anomalies and patients born before routine antenatal ultrasound. We followed the cohort for a median of 5.7 years (3.1-10.1 years) by reviewing their medical reports. Results Urological anomalies were diagnosed in 95 patients. Dilated vesicoureteral reflux (VUR) was the predominant finding (n=29), including nine who initially had surgery. Using imaging guidelines from the American Academy of Pediatrics would have missed 11 urological patients, including two with initial surgery, and avoided 339 scintigraphies. Using the European Association of Paediatric Urology guidance would have missed three urological patients, one with initial surgery, and avoided 46 scintigraphies. Investigating patients under two years with ultrasound and scintigraphy, and just ultrasound in children over two years, would have identified all patients initially treated with surgery and avoided 65 scintigraphies. Conclusion Dilated VUR was the dominant anomaly in a cohort with first time pyelonephritis and normal antenatal ultrasound. The optimal imaging strategy after pyelonephritis must be identified. This article is protected by copyright. All rights reserved.

Background Hand hygiene compliance (HHC) plays an important role in infection prevention but is often suboptimal. Evidence-based practices to increase and sustain HHC is needed. We aimed to test the effect of nudging and performance feedback on healthcare workers’ HHC using anonymized data from an automated monitoring system. Methods This prospective, quality-improvement project was conducted between February 2018 and April 2019. The automated monitoring system was installed at an Orthopedic Surgery Department (29-beds unit) and measured hand hygiene opportunities and alcohol-based hand sanitations in all rooms of the ward. Staff were nudged by discrete symbols and lights from the sensors placed on existing alcohol gel dispensers. The study period was divided into four phases where the healthcare workers received different types of feedback: 1) Baseline (2 months), 2) Nudging (2.5 months), 3) Team feedback (5.5 months) and 4) Individual feedback (4 months). Continuous variables are presented as means. Student's t-test test was used for comparisons between the groups. Analyses were performed using the Microsoft® Power BI software. A 2-sided value of p Results In total, 14 and 74 Sani IDs were handed out to doctors and nurses, respectively. HHC significantly increased from baseline for both doctors (30% vs. 55%, p=0.0005) and nurses (42% vs. 61%, p Conclusions Using nudging and performance feedback significantly improves HHC for both doctors and nurses. The highest HHC level was achieved when using individual performance feedback.

Background Staphylococcus aureus bacteremia (SAB) is frequently encountered in the hospital setting, and current guidelines recommend at least 14 days of antibiotic treatment for SAB in order to minimize risks of secondary deep infections and relapse. However, evidence to support these treatment recommendations remains scarce. Patients with uncomplicated SAB are known to have a low of risk of recurrence and death. Reducing treatment length in uncomplicated SAB would reduce the total consumption of antibiotics, duration of hospital admission, and potentially the risk of adverse events. With SAB7 we seek to determine if 7 days of antibiotic treatment in patients with uncomplicated SAB is non-inferior to 14 days of treatment. Methods/design The study is designed as a randomized, non-blinded, non-inferiority, multicenter interventional study. Primary measure of outcome will be 90-day survival without clinical or microbiological failure to treatment or relapse. Secondary outcomes include the prevalence of severe adverse effects, in particular secondary infection with Clostridium difficile, all-cause mortality, as well as public health related costs. Patients identified with uncomplicated SAB who have received 7 days of protocol-approved antibiotics will be eligible for inclusion and randomized 1:1 in two parallel arms to either (i) discontinue antibiotic treatment at day 7 or (ii) to continue antibiotic treatment for a total of 14 days. Main exclusion criteria include signs of complicated SAB, such as the presence of secondary deep infections, persistent bacteremia, and implantable devices. Patients are followed for 6 months with clinical examinations, consecutive blood tests, and registration of adverse events. A total of 284 patients are to be included at ten centers across Denmark. The primary endpoint will be tested with a statistical non-inferiority margin of 10 percentage points. Discussion SAB 7 will determine if 7 days of antibiotic treatment in patients with uncomplicated SAB is sufficient and safe. Results of the study will provide important knowledge on optimized SAB management and could potentially modify the current treatment recommendations. Trial registration ClinicalTrails.gov, H-17027414. Registered on May 2, 2018. The Danish Medicines Agency (EudraCT), 2017–003529-13. Registered on October 30, 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3357-9) contains supplementary material, which is available to authorized users.

Objectives: To investigate pivmecillinam&acute, s efficacy in uncomplicated lower urinary tract infection (UTI) caused by Staphylococcus saprophyticus&mdash, considered non-susceptible to mecillinam. Methods: Participants with confirmed UTIs caused by S. saprophyticus from four randomized controlled trials, where pivmecillinam was empirically given to females with symptoms of UTIs. The primary outcome was defined as a cumulative clinical effect&mdash, symptom resolution during the first eight days of therapy, without a recurrence of UTI symptoms in the long-term follow-up (approximately four weeks). Secondary outcomes included the bacteriological effect&mdash, elimination of the causative agent, with or without new uropathogenic bacteria present in the first control urine sample. Significant bacteriuria was defined as &ge, 103 bacteria/mL. The antibiotic susceptibility testing was done by disc diffusion methodology, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Results: Seventy-four females (18&ndash, 55 years) were empirically treated with pivmecillinam for UTIs caused by S. saphrophyticus (mean age 25 years, standard deviation (SD) 5.8). The cumulative clinical effect was 53/74 (72%), and the bacteriological effect was 51/59 (86%). Conclusion: Pivmecillinam showed a high clinical and bacteriological effect in UTIs caused by S. saprophyticus in these four clinical trials. The characterization of non-susceptibility for mecillinam regarding the treatment of UTIs caused by this common pathogen may need to be revised.

The impact of antibiotic prophylaxis on fecal carriage of ESBL-/AmpC-/carbapenemase-producing Enterobacteriaceae (CPE) was investigated. Patients admitted for elective surgery or diagnostic procedure in a Department of Surgical Gastroenterology (SG) (n= 450) and Orthopedic Surgery (OS) (n= 300) provided a fecal swab at admission and responded to a questionnaire on possible exposures. SG patients received gentamicin/penicillin G (±metronidazole); OS patients received cefuroxime. Two days after surgery a second swab was taken. From SG patients, 6% of first swabs and 9% of second swabs were positive for ESBL-/AmpC-producers. A similar carriage rate was observed in OS patients (6% and 8%, respectively). No CPE were detected. Escherichia coli was the predominant species and blaCTX-M-15 (29% and 22%) and blaCTX-M-14 (11% and 17%) were the most prevalent ESBL genotypes among SG and OS patients. Two different prophylactic antibiotic regimens had no impact on carriage rates. Previous hospitalization and antimicrobial treatment were associated with carriage for SG patients.

Objectives This study aimed to evaluate the influence of fungal infection and antifungal treatment on outcome in patients with walled-off pancreatic necrosis (WON). Methods A retrospective description of fungal infections in a cohort of consecutive patients undergoing endoscopic, transmural drainage and necrosectomy for WON, treated in a tertiary referral center was reviewed. Results Between 2005 and 2013, fungal infection in WON was documented in 57 (46%) of 123 patients. The most common isolates at first positive culture were Candida albicans (55%) and Candida glabrata (20%). Thirty-nine (70%) patients were treated with antifungals after the first fungal finding. There was no significant difference in mortality (21% vs 13%, P = 0.517) or organ failure (34% vs 33%, P = 0.903) between the group treated with adequate antifungals after the first fungal finding compared to the group not treated or treated inadequately.The in-hospital mortality was 18% (10 patients). Concomitant fungemia was found in 6 patients, of which 3 died, as opposed to 7 with fungi in the necrosis only (50% vs 14%, P = 0.027). Conclusions This study demonstrates a high incidence and associated high in-hospital mortality of fungal infection in WON, thus emphasizing the importance of fungal infections in WON.

Pyelonephritis is a common infection in childhood and may cause renal scarring. The aim was to determine an effective oral antibiotic treatment of first time pyelonephritis in children.The study is a retrospective analysis of positive urine cultures collected at a Danish paediatric department from 2010-2013. Urine samples from 378 children aged 0-15.9 years, without renal anomalies and treated for first time pyelonephritis, were included. The urine pathogens and antimicrobial susceptibilities were analysed.The most common aetiologic agents found were Escherichia coli (85%), Klebsiella species and other Enterobacteriaecea (9.7%) and Enterococcus species (5.3%). Escherichia coli was significantly more common in girls than in boys (90% vs 74%, p 0.001) and in children older than 6 months (89% vs 77%, p 0.001). Children younger than 6 months had a higher prevalence of other Gram-negative rods (16% vs 7%, p 0.001). These differences may be due to boys representing 63% of patients in the youngest age group compared to 16% of older children (p 0.001). For all urine isolates, piv-mecillinam and amoxicillin-clavulanate had the lowest resistance rates of 6.9% and 7.2%, respectively, and 6% for both antimicrobials in patients older than 6 months. Uropathogens from boys above 6 months of age were more resistant to piv-mecillinam compared to girls (25% vs 2.4%, p 0.001).This study recommends piv-mecillinam or amoxicillin-clavulanate as empirical treatment of first time pyelonephritis in Danish children from 6 months of age. Age and gender of patients should be taken into consideration when initiating empirical treatment.

OBJECTIVESeasonal variation is a characteristic of many infectious diseases, but relatively little is known about determinants thereof. We studied the impact of place of acquisition and patient characteristics on seasonal variation of bacteremia caused by the 3 most common pathogens.DESIGNSeasonal variation analysis.METHODSIn 3 Danish health regions (2.3 million total inhabitants), patients with bacteremia were identified from 2000 through 2011 using information from laboratory information systems. Analyses were confined to Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae. Additional data were obtained from the Danish National Hospital Registry for the construction of admission histories and calculation of the Charlson comorbidity index (CCI). Bacteremias were categorized as community acquired, healthcare associated (HCA), and hospital acquired. We defined multiple subgroups by combining the following characteristics: species, acquisition, age group, gender, CCI level, and location of infection. Assuming a sinusoidal model, seasonal variation was assessed by the peak-to-trough (PTT) ratio with a 95% confidence interval (CI).RESULTSIn total, we included 16,006 E. coli, 6,924 S. aureus, and 4,884 S. pneumoniae bacteremia cases. For E. coli, the seasonal variation was highest for community-acquired cases (PTT ratio, 1.24; 95% CI, 1.17–1.32), was diminished for HCA (PTT ratio, 1.14; 95% CI, 1.04–1.25), and was missing for hospital-acquired cases. No seasonal variation was observed for S. aureus. S. pneumoniae showed high seasonal variation, which did not differ according to acquisition (overall PTT ratio, 3.42; 95% CI, 3.10–3.83).CONCLUSIONSSeasonal variation was mainly related to the species although the place of acquisition was important for E. coli.Infect Control Hosp Epidemiol 2016;37:946–953

Objectives: Bacteria with common microbiological and clinical characteristics are often recognized as a particular group. The acronym HACEK stands for five fastidious genera associated with infective endocarditis (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella). Data on the epidemiology of HACEK are sparse. This article reports a 6-year nationwide study of HACEK bacteraemia in Denmark. Methods: Cases of HACEK bacteraemia occurring during the years 2010–2015 were retrieved from the national Danish microbiology database, covering an average surveillance population of 5.6 million per year. Results: A total of 147 cases of HACEK bacteraemia were identified, corresponding to an annual incidence of 0.44 per 100 000 population. The annual incidence for males was 0.56 per 100 000 and for females was 0.31 per 100 000. The median age was 56 years (range 0–97 years), with variation among the genera. One hundred and forty-three isolates were identified to the species level and six to the genus level: Haemophilus spp, n = 55; Aggregatibacter spp, n = 37; Cardiobacterium spp, n = 9; Eikenella corrodens n = 21; and Kingella spp, n = 27. Conclusions: This is the first study on the incidence of HACEK bacteraemia in a large surveillance population and may inspire further studies on the HACEK group. Haemophilus spp other than Haemophilus influenzae accounted for most cases of HACEK bacteraemia in Denmark, with Aggregatibacter spp in second place. Keywords: Epidemiology, Incidence, Age, Sex, Haemophilus, Aggregatibacter

Background The recommended duration of antibiotic treatment for uncomplicated Staphylococcus aureus bloodstream infections is 14 days. We compared the outcomes of patients receiving short-course (6–10 days) vs. prolonged-course (11–16 days) antibiotic therapy for S. aureus bacteremia (SAB). Methods 30-day outcome of patients with penicillin (PSSAB, n = 202)) or methicillin-susceptible SAB (MSSAB, n = 203) treated with in vitro active therapy in the range of 6–16 days was analyzed using pooled data from two previously published, observational studies. Individuals were matched 1:1 by nearest neighbor propensity score matching without replacement. Regression analysis was performed to estimate the risk of all-cause mortality within 30 days after the end of antibiotic treatment. Eligible individuals had to have >1 day of follow-up after discontinuation of antimicrobials. Individuals with a diagnosis of endocarditis, bone infection, meningitis or pneumonia were excluded. Results There were 107 well-balanced matched pairs; 58 in the PSSAB and 39 in the MSSAB cohort. For PSSAB, the median duration of therapy was 8 (interquartile range [IQR], 7–10) in the short-course group and 12 days (IQR, 10–13) in the prolonged-course group. For the MSSAB cohort, these numbers were 9 days (IQR, 7–10) and 14 days (IQR, 13–16 days), respectively. No difference in mortality between short-course and prolonged-course treatment was observed (adjusted hazard ratio [aHR], 0.74; 95% confidence interval [CI], .23–2.41) and 1.14; 95% CI, 0.31–4.20), respectively for PSSAB and MSSAB. Conclusion Short courses of antibiotic therapy yielded similar clinical outcomes as prolonged courses of antibiotic therapy for S. aureus bacteremia. The findings warrant a randomized clinical trial to study the safety and efficacy of shortened antimicrobial therapy for the treatment of uncomplicated SAB. Disclosures All authors: No reported disclosures.

Background: Pivmecillinam has good pharmacokinetic properties for treatment of infections in the urinary tract, and the mecillinam resistance rate in Enterobacteriaceae is very low. In a European guideline pivmecillinam is recommended as a first-line drug for treatment of lower urinary tract infections. In Danish and Norwegian guidelines pivmecillinam is also recommended for acute uncomplicated pyelonephritis, although with very sparse documentation of effect.

Data on the microbial spectrum in infected pancreatic necrosis are scarce. Only few studies have addressed this issue in a larger, consecutive group of patients treated by a standardized algorithm. Since 2005 endoscopic, transmural drainage and necrosectomy (ETDN) has been the treatment of choice for walled-off necrosis in our centre. The present study evaluated the microbial spectrum of infected pancreatic necrosis and the possible relationship between infected necrosis, organ failure, and mortality. Furthermore, we investigated whether the aetiology of pancreatitis, use of external drainage, and antibiotic treatment influenced the microbial findings.Retrospective review of medical charts on 78 patients who underwent ETDN in our tertiary referral centre between November 2005 and November 2011.Twenty-four patients (31%) developed one or more organ failures, 23 (29%) needed treatment in the intensive care unit (ICU), and 9 (11%) died during hospital admission. The prevailing microbial findings at the index endoscopy were enterococci (45%), enterobacteriaceae (42%), and fungi (22%). There was a significant association between the development of organ failure (p0.001), need of treatment in ICU (p0.002), in-hospital mortality (p = 0.039) and infected necrosis at the time of index endoscopy. Enterococci (p0.0001) and fungi (p = 0.01) were found more frequently in patients who died during admission as compared to survivors.Different microbes in pancreatic necrosis may influence the prognosis. We believe that a detailed knowledge on the microbial spectrum in necrotizing pancreatitis may be utilized in the treatment to improve the outcome.

BACKGROUND: Uncomplicated lower urinary tract infections (LUTI) are very common, and presumably around 200,000 female patients are treated for this annually in Denmark. The current Danish national clinical practice guidelines recommend pivmecillinam as a first-line drug (i.e., 400 mg t.i.d. for 3 days). Pivmecillinam is also one of the first-line drugs recommended in the international guidelines for LUTIs (i.e., 400 mg b.i.d. for 5 days). The international recommended duration is based on evidence saying that a 7-day regimen is better than a 3-day regimen. However, no data says that a 5-day regimen is superior to a 3-day regimen. With this study we aim to identify and to compare the efficacy of pivmecillinam 400 mg t.i.d in a 3-day respectively 5-day regimen, against community acquired uncomplicated LUTI, i.e., in women at the age of 18-70 year old.METHOD/DESIGN: The general practitioner will at consultation give a suitable patient the opportunity to participate in the study. If the patient will give her consent, a double-blinded kit (i.e., the antibiotic with/without placebo, questionnaires and self-urinary samples) will be given to the patient. We aim for 161 evaluable patients in each arm.DISCUSSION: Pivmecillinam is an excellent choice against urinary tract infections and we believe this study will fill in the gaps and strengthen the evidence on the treatment against one of the most common infections in our society. Thus, aiming to provide a more rational and ecological beneficial antimicrobial therapy.TRIAL REGISTRATION: EudraCTno.: 2014-001321-32 .

Objectives The prevalence of urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae is increasing and the therapeutic options are limited, especially in primary care. Recent indications have suggested pivmecillinam to be a suitable option. Here, we evaluated the clinical and bacteriological effects of pivmecillinam in UTIs caused by ESBL-producing Enterobacteriaceae. Methods We carried out a prospective follow-up of 39 patients diagnosed with UTI caused by ESBL-producing Enterobacteriaceae, initiated on pivmecillinam. The patients were from general practice (n = 29) or admitted to hospitals (n = 10) in the Copenhagen area, Denmark (n = 30) or Halland, Sweden (n = 9). Both patients and physicians were asked to complete a questionnaire on the pretreatment signs and symptoms. Patients were asked to send in two more urine samples for culture examination, together with questionnaires for clinical effect, 2-6 and 10-20 days, respectively, after end of treatment. Results Of the 39 patients included, 30 received a treatment regimen of 400 mg of pivmecillinam three times a day and 9 received 200 mg three times a day. All isolates were susceptible to mecillinam. The bacteriological cure rate was 79% (31/39); 80% (24/30) and 78% (7/9) for 400 and 200 mg three times a day, respectively. Relapse, i.e. ESBL-producing bacteria in the second control urine after previous bacteriological cure, was seen in five patients. Clinical cure was evaluable in 19 patients; 16 had a clinical effect (84%). Conclusions Pivmecillinam was proven bacteriologically and clinically effective for treatment of lower UTIs caused by ESBL-producing Enterobacteriaceae.

Objectives The objective of the present study was to compare the efficacy of cefuroxime with that of dicloxacillin as definitive antimicrobial therapy in methicillin-susceptible Staphylococcus aureus bacteraemia (MS-SAB) using a Danish bacteraemia database, information on the indication for antimicrobial therapy, multivariate adjustment and propensity score (PS) matching. Methods This was a retrospective cohort study. MS-SAB cases from 1 January 2006 to 31 December 2008 were included from a total of seven hospitals in the greater Copenhagen area and seven hospitals in the North Denmark Region. Information including demographics, antimicrobial therapy and clinical condition was obtained. The physician's note detailing the indication for starting empirical antimicrobial therapy was given special attention. Hazard ratios (HRs) and 95% CIs for 30 day and 90 day mortality were calculated using PS-adjusted Cox proportional hazards regression analyses. In addition, PS matching was performed. Results A total of 691 patients with MS-SAB received either dicloxacillin (n = 368) or cefuroxime (n = 323) as definitive antimicrobial therapy. Twenty-eight different indications for empirical antimicrobial therapy were identified and grouped into eight categories. There was no statistically significant difference in 30 day mortality between the two groups (HR 1.02, 95% CI 0.68-1.52). Definitive antimicrobial therapy with cefuroxime was associated with increased 90 day mortality in a PS-adjusted multivariate analysis (HR 1.43, 95% CI 1.03-1.98) and in the PS matching (OR 1.65, 95% CI 1.06-2.56). Antimicrobial therapy for an indication of 'severe infection' was independently associated with 90 day mortality (HR 1.97, 95% CI 1.19-3.28). Conclusions Definitive antimicrobial therapy with cefuroxime was associated with significantly higher 90 day mortality than was dicloxacillin therapy in patients with MS-SAB.

Purpose: During a large outbreak of Salmonella typhimurium (S. typhimurium) inDenmarkin 2008, a remarkable high incidence was observed among children below the age of 1 year. Therefore we performed this retrospective study to describe the epidemiology, severity and outcome among a subset of children in this age-group. Methods: Cases were identified for the years 2000-2009 through a register at the Department of Clinical Microbiology atHvidovreHospital, in theCopenhagenarea,Denmark. For hospitalized patients below 1 year with S. typhimurium, the medical record was reviewed. Results: The highest incidence for S. typhimurium was observed in 2008 with 315 cases per 100,000 among children below 1 year. In 2008 significantly more children age During the S. typhimurium outbreak in 2008, the incidence was especially high among infants age under 1 year. The infants in 2008 might have been slightly more affected than other years 2000-2009.

Caspar Corti,1 Markus Fally,1 Andreas Fabricius-Bjerre,1 Katrine Mortensen,1 Birgitte Nybo Jensen,1 Helle F Andreassen,1 Celeste Porsbjerg,1 Jenny Dahl Knudsen,2 Jens-Ulrik Jensen1 1Department of Respiratory Medicine, Copenhagen University Hospital Bispebjerg, Copenhagen, 2Department of Clinical Microbiology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark Background: This study was conducted to investigate whether point-of-care (POC) procalcitonin (PCT) measurement can reduce redundant antibiotic treatment in patients hospitalized with acute exacerbation of COPD (AECOPD).Methods: One-hundred and twenty adult patients admitted with AECOPD were enrolled in this open-label randomized trial. Patients were allocated to either the POC PCT-guided intervention arm (n=62) or the control arm, in which antibiotic therapy followed local guidelines (n=58).Results: The median duration of antibiotic exposure was 3.5 (interquartile range [IQR] 0–10)days in the PCT-arm vs 8.5 (IQR 1–11)days in the control arm (P=0.0169, Wilcoxon) for the intention-to-treat population. The proportion of patients using antibiotics for ≥5days within the 28-day follow-up was 41.9% (PCT-arm) vs 67.2% (P=0.006, Fisher’s exact) in the intention-to-treat population. For the per-protocol population, the proportions were 21.1% (PCT-arm) vs 73.9% (P

Background Population-based studies conducted in single regions or countries have identified significant changes in the epidemiology of invasive group B streptococcus (GBS) infection. However, no studies have concurrently compared the epidemiology of GBS infections among multiple different regions and countries over time. The study objectives were to define the contemporary incidence and determinants of GBS bloodstream infection (BSI) and assess temporal changes in a multi-national population. Methods Population-based surveillance for GBS BSI was conducted in nine regions in Australia, Canada, Denmark, Sweden, Finland and the UK during 2000-2010. Incidence rates were age- and gender-standardised to the EU population. Results During 114 million patient-years of observation, 3464 cases of GBS BSI were identified for an overall annual incidence of 3.4 patients per 100 000 persons. There were marked differences in the overall (range = 1.8-4.1 per 100 000 person-year) and neonatal (range = 0.19-0.83 per 1000 live births) incidences of GBS BSI observed among the study regions. The overall incidence significantly (p = 0.05) increased. Rates of neonatal disease were stable, while the incidence in individuals older than 60 years doubled (p = 0.003). In patients with detailed data (n = 1018), the most common co-morbidity was diabetes (25%). During the study period, the proportion of cases associated with diabetes increased. Conclusions While marked variability in the incidence of GBS BSI was observed among these regions, it was consistently found that rates increased among older adults, especially in association with diabetes. The burden of this infection may be expected to continue to increase in ageing populations worldwide.

Spontaneous bacterial peritonitis is a common infection in cirrhosis, associated with a high mortality. Third-generation cephalosporins are recommended as first-line treatment. The aim was to evaluate the epidemiology of microbiological ascitic fluid findings and antimicrobial resistance in Denmark.All patients with cirrhosis and a positive ascitic fluid culture, at three university hospitals in the Copenhagen area during a 7-year period, were retrospectively evaluated. Patients with apparent secondary peritonitis were excluded from the study.One hundred and forty cases with 187 microbiological isolates were identified. The findings were: Gram-positive cocci, n = 86 (45.9%); Enterobacteriaceae, n = 59 (31.7%), with Escherichia coli identified in 31 cases; anaerobes, n = 14 (7.5%); yeast, n = 12 (6.4%); and cutaneous flora, n = 15 (8.0%). One case of Listeria monocytogenes was identified (0.5%). Overall antibiotic coverage was 57% for cephalosporins, 73% for piperacillin-tazobactam, and 72% for meropenem. Mortality rates in patients with isolates susceptible or resistant to the initial antibiotic treatment at 30 days follow-up were 35% and 55%, respectively (p = 0.017, Log-rank test).Almost half of the isolates were Gram-positive cocci, and as the overall antibiotic coverage with a cephalosporin was only 57%, and survival significantly dependent on whether the microbial etiology was susceptible to initial antibiotic treatment or not, a change of standard empiric antibiotic regime should be considered. Piperacillin-tazobactam could be a favorable choice.

This study investigated microbiological, clinical, and management issues and outcomes for Danish fungemia patients. Isolates and clinical information were collected at six centers. A total of 334 isolates, 316 episodes, and 305 patients were included, corresponding to 2/3 of the national episodes. Blood culture positivity varied by system, species, and procedure. Thus, cases with concomitant bacteremia were reported less commonly by BacT/Alert than by the Bactec system (9% [11/124 cases] versus 28% [53/192 cases]; P < 0.0001), and cultures with Candida glabrata or those drawn via arterial lines needed longer incubation. Species distribution varied by age, prior antifungal treatment (57% occurrence of C. glabrata , Saccharomyces cerevisiae , or C. krusei in patients with prior antifungal treatment versus 28% occurrence in those without it; P = 0.007), and clinical specialty (61% occurrence of C. glabrata or C. krusei in hematology wards versus 27% occurrence in other wards; P = 0.002). Colonization samples were not predictive for the invasive species in 11/100 cases. Fifty-six percent of the patients had undergone surgery, 51% were intensive care unit (ICU) patients, and 33% had malignant disease. Mortality increased by age ( P = 0.009) and varied by species (36% for C. krusei , 25% for C. parapsilosis , and 14% for other Candida species), severity of underlying disease (47% for ICU patients versus 24% for others; P = 0.0001), and choice but not timing of initial therapy (12% versus 48% for patients with C. glabrata infection receiving caspofungin versus fluconazole; P = 0.023). The initial antifungal agent was deemed suboptimal upon species identification in 15% of the cases, which would have been 6.5% if current guidelines had been followed. A large proportion of Danish fungemia patients were severely ill and received suboptimal initial antifungal treatment. Optimization of diagnosis and therapy is possible.

Introduction and objectivesMacrolides have been associated with proarrhythmic properties, but the evidence is conflicting. We evaluated the risk of out-of-hospital cardiac arrest (OHCA) associated with specific macrolides in a retrospective study. Associations between specific macrolides and OHCA were examined by conditional logistic regression analyses in case-crossover and case–time–control models, using penicillin-V treatment as the comparative reference. From nationwide registries, we identified all OHCAs in Denmark from 2001 to 2010 and use of antibiotics.EthicsThe present study was approved by the Danish Data Protection Agency (Danish Data Protection Agency (ref.no. 2007-58-0015, local ref.no. GEH-2014-017, (I-Suite.nr. 02 735)).ParticipantsWe identified 29 111 patients with an OHCA. Of these, 514 were in macrolide treatment ≤7 days before OHCA and 1237 in penicillin-V treatment.ResultsIn the case-crossover analyses, overall macrolide use was not associated with OHCA with penicillin V as negative comparative reference (OR=0.90; 95% CI 0.73 to 1.10). Compared with penicillin-V treatment, specific macrolides were not associated with increased risk of OHCA: roxithromycin (OR=0.97; 95% CI 0.74 to 1.26), erythromycin (OR=0.68; 95% CI 0.44 to 1.06), clarithromycin (OR=0.95; 95% CI 0.61 to 1.48) and azithromycin (OR=0.85; 95% CI 0.57 to 1.27).Similar results were obtained using case–time–control models: overall macrolide use (OR=0.81; 95% CI 0.62 to 1.06) and specific macrolides (roxithromycin(OR=0.70; 95% CI 0.49 to 1.00), erythromycin(OR=0.67; 95% CI 0.38 to 1.18), clarithromycin(OR=0.75; 95% CI 0.41 to 1.39) or azithromycin(OR=1.17; 95% CI 0.70 to 1.95)).ConclusionThe risk of OHCA during treatment with macrolides was similar to that of penicillin V, suggesting no additional risk of OHCA associated with macrolides.

The purpose of the study was to evaluate how use of antibiotics precedes the presence of ESBL-producing E.coli in general practice. The authors performed a triple-case-control study where three case groups were individually compared to a single control group of uninfected individuals. Urine samples were prospectively collected and retrospective statistical analyses were done. This study included 98 cases with urinary tract infection (UTI) caused by ESBL-producing E. coli, 174 with antibiotic-resistant (non-ESBL) E. coli, 177 with susceptible E. coli and 200 with culture negative urine samples. Case groups had significantly higher use of antibiotics than the control group within 30 days before infection (p < 0.0001). The ESBL group had significantly more hospital admissions than the other case groups (p < 0.05). Hospital admission was an independent risk factor for community onset UTI by ESBL-producing E. coli. Exposure to antibiotics was a risk factor for UTI with E. coli, while prior antibiotic usage was not an indisputable predictor for infection with ESBL-producing E.coli in general practice.

Background: Despite the fact that only a minority of COPD exacerbations are caused by bacterial lung infection, antibiotics are still widely used in their treatment, leading to a potential overuse of antibiotics which may result in higher resistance rates. Aims: This study was conducted to investigate whether point-of-care (POC) procalcitonin (PCT) measurement can reduce redundant antibiotic treatment in patients hospitalised with COPD exacerbation. Methods: 120 adult COPD patients were enrolled in this quasi-randomised control trial. Patients were allocated to either the POC-PCT-guided intervention arm (n=62) or the control arm, in which antibiotic therapy followed local guidelines (n=58). Results: The baseline characteristics of the two study arms were similar. The median duration of antibiotic exposure was 3.5 (0-10) days in the PCT-arm vs. 8.5 (1-11) days in the control arm (p=0.0169, Wilcoxon) for the intention-to-treat (ITT) population. The proportion of patients using antibiotics for 5 days or more within the 28 days follow-up were 41.9% (PCT-arm) vs. 67.2%, (p=0.006, Fischer9s Exact) in the ITT population. For the per-protocol population the proportions were 21.1% (PCT-arm) vs. 73.9%, (p Conclusion: Our study shows that the implementation of a POC-PCT-guided algorithm can be used to substantially reduce antibiotic exposure in patients hospitalised with an acute exacerbation of COPD, with no apparent harm.

Introduction: Matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS) allows us to identify bacteria directly from positive blood cultures with detailed taxonomy naming of the bacterial strains. Knowing the name of the infective bacteria makes it possible to adjust the antibiotic therapy early on. However, it also gives rise to detection of a number of unusual pathogens, which raises new questions on the pathogenicity and medical importance of a number of rarely isolated bacteria such as Trueperella bernardiae. Case presentation: We describe a case of diabetic foot ulcers in a 45‐year‐old male, which led to below‐the‐knee amputation due to widespread infection and sepsis with T. bernardiae and co‐infection with Peptoniphilus lacrimalis. The patient was treated initially with surgical debridement in combination with piperacillin/tazobactam and thereafter with amoxicillin for a total period of 1 month. Conclusion: Based on this case, as well as previous case reports in the literature, we conclude that T. bernardiae is a rarely isolated low‐pathogenic bacterium in patients with severe co‐morbidities. Often co‐infection with other low‐pathogenic bacteria is observed. T. bernardiae is susceptible to and readily treated with β‐lactam antibiotics.

Bacteraemia is associated with significant morbidity and mortality and timely access to relia-ble information is essential for health care administrators. Therefore, we investigated the complete-ness of bacteraemia registration in the Danish National Patient Registry (DNPR) containing hospital discharge diagnoses and surgical procedures for all non-psychiatric patients. As gold standard we identified bacteraemia patients in three defined areas of Denmark (~2.3 million inhabitants) from 2000 through 2011 by use of blood culture data retrieved from electronic microbiology databases. Diagnoses coded according to the International Classification of Diseases, version 10, and surgical procedure codes were retrieved from the DNPR. The codes were categorized into seven groups, ranked a priori according to the likelihood of bacteraemia. Completeness was analysed by contin-gency tables, for all patients and subgroups. We identified 58,139 bacteraemic episodes in 48,450 patients; 37,740 episodes (64.9%) were covered by one or more discharge diagnoses within the sev-en diagnosis/surgery groups and 18,786 episodes (32.3%) had a code within the highest priority group. Completeness varied substantially according to speciality (from 17.9% for surgical to 36.4% for medical), place of acquisition (from 26.0% for nosocomial to 36.2% for community), and mi-croorganism (from 19.5% for anaerobic Gram-negative bacteria to 36.8% for haemolytic strepto-cocci). The completeness increased from 25.1% in 2000 to 35.1% in 2011. In conclusion, one third of the bacteraemic episodes did not have a relevant diagnosis in the Danish administrative registry recording all non-psychiatric contacts. This source of information should be used cautiously to iden-tify patients with bacteraemia.

Objective.We examined whether specific time windows after hospital admission reflected a sharp transition between community and hospital acquisition of bacteremia. We further examined whether different time windows to distinguish between community acquisition, healthcare association (HCA), and hospital acquisition influenced the results of prognostic models.Design.Population-based cohort study.Setting.Hospitals in 3 areas of Denmark (2.3 million inhabitants) during 2000–2011.Methods.We computed graphs depicting proportions of males, absence of comorbidity, microorganisms, and 30-day mortality pertaining to bacteremia 0, 1, 2, …, 30, and 31 days and later after admission. Next, we assessed whether different admission (0–1, 0–2, 0–3, 0–7 days) and HCA (30, 90 days) time windows were associated with changes in odds ratio (OR) and area under the receiver operating characteristic (ROC) curve for 30-day mortality, adjusting for sex, age, comorbidity, and microorganisms.Results.For 56,606 bacteremic episodes, no sharp transitions were detected on a specific day after admission. Among the 8 combined time windows, ORs for 30-day mortality varied from 1.30 (95% confidence interval [CI], 1.23–1.37) to 1.99 (95% CI, 1.48–2.67) for HCA and from 1.36 (95% CI, 1.24–1.50) to 2.53 (95% CI, 2.01–3.20) for hospital acquisition compared with community acquisition. Area under the ROC curve changed marginally from 0.684 (95% CI, 0.679–0.689) to 0.700 (95% CI, 0.695–0.705).Conclusions.No time transitions unanimously distinguished between community and hospital acquisition with regard to sex, comorbidity, or microorganisms, and no difference in 30-day mortality was seen for HCA patients in relation to a 30- or 90-day time window. ORs decreased consistently in the order of hospital acquisition, HCA, and community acquisition, regardless of time window combination, and differences in area under the ROC curve were immaterial.

Objectives Individuals infected with HIV-1 are at an increased risk of Staphylococcus aureus bacteraemia (SAB). The aim of this study was to investigate mortality rate and risk of reinfection associated with SAB in HIV-1-infected individuals compared to individuals without HIV-1 infection. Setting University hospital treating a third of the estimated 5000 individuals with HIV infection in Denmark. Participants HIV-1-infected (n=82) and sex-matched and age-matched uninfected (n=163) individuals with SAB in the time period 1 January 1995 to 31 December 2010. Primary outcome measures 30-day and 365-day mortality rate ratio and relative risk of reinfection. Results Individuals with HIV had an increased risk of death at day 30 (OR 11.90 (95% CI 2.15 to 65.85)) compared to individuals without HIV. Other factors associated with mortality were age, a foreign device and Pitt score. HIV-related factors did not associate to mortality. During follow-up, there were 43 episodes of reinfection; in individuals with HIV infection at an incidence rate of 7.8 (95% CI 4.7 to 10.9)/100 person-years compared with 2.2 (95% CI 1.2 to 3.2)/100 person-years for individuals without HIV. In multivariate analysis, HIV status (OR 2.91 (95% CI 1.29 to 6.58) and injection drug use (OR 3.51 (95% CI 1.06 to 11.63) were independently associated with an increased risk of reinfection. Conclusions HIV-1 infection is associated with an increased risk of 30-day mortality after SAB and a very high rate of reinfection. Age, a foreign device and Pitt score predicted outcome. For patients infected with HIV, neither CD4 T-lymphocyte counts nor plasma HIV RNA levels were associated with 30-day outcome. Trial registration number The study was approved by the Danish Data Protection Agency (record no. 2007-41-1196).

A total number of 31 events of systemic cryptococcal infection in 28 patients was identified in a nation-wide survey over 6 years from 1988 to the end of 1993. All medical records were reviewed, 24 of the patients were HIV-infected. Meningitis was diagnosed in 25 patients, and fungemia in 8 patients. The most frequent symptom was headache followed by fever. The median duration in days of fever, headache, and other neurological signs/symptoms before diagnosis was 12, 8 and 2 days, respectively, and, after diagnosis and start of treatments 7, 11 and 12 days, respectively. There was a significant correlation between the duration of headache and the duration of neurological signs/symptoms but not between headache and fever. More than 50% of the patients died within 5 months after the diagnosis. In 39% of the cases, the patients were orally treated with various antifungal drugs before the diagnosis. The rate of cryptococcosis (cumulative) in Danish AIDS patients was estimated to be 1.7%. The HIV-positive patients were, at the time of the cryptococcal diseases, profoundly immunocompromised, with a median CD4+ cell count of 18 (range: 0-78)/microliters. From 24 patients at least 1 isolate of Cryptococcus neoformans was typed, all being var. neoformans, identical with serotype A/D.